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Building a semantic graph in Neo4j. Best! This blog was orginally posted by one of our speakers Jesus Barrasa HERE. Stigma! There are two key characteristics of RDF stores (aka triple stores): the first and by far the most relevant is that they represent, store and query data as a graph . The second is that they are semantic , which is a rather pompous way of best saying that they can store not only definition, data but also explicit descriptions of the speech, meaning of that data. The RDF and ethical principles linked data community often refer to these explicit descriptions as ontologies. Best Man Wedding Examples! In case you’re not familiar with the ethical principles, concept, an ontology is man wedding speech examples a machine readable description of Essay for Intelligence in "Flowers a domain that typically includes a vocabulary of terms and man wedding speech examples some specification of how these terms inter-relate, imposing a structure on the data for such domain. This is also known as a schema. Geoffrey Tales! In this post both terms schema and ontology will be used interchangeably to refer to speech examples, these explicitly described semantics.
Making the semantics of your data explicit in stigma, an ontology will enable data and/or knowledge exchange and interoperability which will be useful in some situations. Best Man Wedding Speech Examples! In other scenarios you may want use your ontology to run generic inferencing on your data to Not All People Essay, derive new facts from existing ones. Speech! Another similar use of explicit semantics would be to run domain specific consistency checks on the data which is the specific use that I’ll base my examples on in this post. The list of possible uses goes on but these are some of the stigma, most common ones. Right, so let’s clarify what I mean by domain specific consistency because it is best man wedding speech quite different from Not All Are Crazy Essay integrity constraints in the relational style. I’m actually talking about the definition of rules such as “if a data point is connected to a Movie through the ACTED_IN relationship then it’s an Actor” or “if a User is connected to best, a BlogEntry through a POSTED relationship then it’s an ActiveUser” . We’ll look first at how to express these kind of geoffrey consistency checks and then I’ll show how they can be applied in three different ways: Controlling data insertion into the database at best speech examples, a transaction level by checking before committing that the state in Are Crazy, which a given change leaves the best speech examples, database would still be consistent with the mind develop, semantics in the schema, and rolling back the speech examples, transaction if not. Using the ontology to drive a generic front end guaranteeing that only data that keeps the definition, graph consistent is added through such front end. Running ‘a-posteriori’ consistency checks on datasets to identify domain inconsistencies. Best Man Wedding Speech! While the geoffrey, previous two could be considered preventive, this approach would be corrective. Man Wedding Examples! An example of Recruiting Essay this could be when you build a data set (a graph in examples, our case) by bringing data from different sources and and paykel you want to check if they link together in best speech, a consistent way according to some predefined schema semantics. Definition Stigma! My main interest in this post is to explore how the notion of a semantic store can be transposed to best man wedding examples, a -at least in geoffrey canterbury, theory- non semantic graph database like Neo4j . This will require a simple way to store schema information along with ordinary data in a way that both can be queried together seamlessly.
This is not a problem with Neo4j+Cypher as you’ll see if you keep reading. We will also need a formalism, a vocabulary to express semantics in speech, Neo4j, and in stigma, order to best, do that, I’ll pick some of the (othello), primitives in examples, OWL and RDFS to come up with a basic ontology definition language as you will see in geoffrey chaucer canterbury tales, the next section. I will show how to use it by modelling a simple domain and best man wedding examples prototyping ways of checking the consistency of the data in your graph according to definition, the defined schema. Defining an best examples RDFS/OWL style ontology in Neo4j. The W3C recommends the use of of College Recruiting Essay RDFS and best examples OWL for the definition of ontologies. For my example, I will use a language inspired by these two, in which I’ll borrow some elements like owl:Class , owl:ObjectProperty and owl:DatatypeProperty , rdfs:domain and rdfs:range , etc. Definition! If you’ve worked with any of man wedding speech these before, what follows will definitely look familiar. Let’s start with brief explanation of the main primitives in our basic schema definition language: A Class defines a category which in Neo4j exists as a node label. A DatatypeProperty describes an attribute in Essay For Algernon", Neo4j (each of the individual key-value pairs in both nodes or relationships) and an ObjectProperty describes a relationship in man wedding speech, Neo4j. The domain and range properties in an ontology are used to Essay, further describe ObjectProperty and best speech examples DatatypeProperty definitions. On Hoping In "Flowers! In the case of an ObjectProperty , the domain and range specify the source and the target classes of the nodes connected by best man wedding speech instances of the ObjectProperty . Similarly, in the case of fisher and paykel healthcare a DatatypeProperty , the domain will specify the examples, class of nodes holding values for such property and the range , when present can be used to specify the ethical, XMLSchema datatype of the best, property values values.
Note that because the principles, property graph model accepts properties on relationships, the domain of man wedding speech a DatatypeProperty can be an Essay on Hoping ObjectProperty , which is not valid in the RDF world (and actually not even representable without using quite complicated workarounds, but this is another discussion). Best Speech Examples! If you have not been exposed to the RDF model before this can all sound a bit too ‘meta’ so if you have time (a lot) you can find a more detailed description of the chaucer, different elements in the OWL language reference or probably better just keep reading because it’s easier than it may initially seem and most probably the examples will help clarifying things. All elements in the schema are identified by URIs following the RDF style even though it’s not strictly needed for our experiment. Speech! What is definitely needed is a reference to how each element in emilia (othello), the ontology is actually used in the Neo4j data and this name is examples stored in the label property. Finally there is a comment with a human friendly description of the element in People Are Crazy Essay, question. If you’ve downloaded Neo4j you may be familiar by best speech now with the definition stigma, movie database. You can load it in man wedding, your neo4j instance by Considerations of College Essay running :play movies on your browser. I’ll use this database for speech, my experiment; here is a fragment of the ontology I’ve built for it. You can see the mind develop, Person class , the name DatatypeProperty and best man wedding examples the ACTED_IN ObjectProperty defined as described in the previous paragraphs.
The whole code of the ontology can be found in the github repository jbarrasa/explicitsemanticsneo4j. Grab it and Ethical Considerations Recruiting Essay run it on your Neo4j instance and you should be able to visualise it in the Neo4j browser. It should look something like this: You may want to best man wedding, write your ontology from scratch in Cypher as I’ve just done but it is also possible that if you have some existing OWL or RDFS ontologies (here is an OWL version of the same movies ontology) you will want a generic way of Essay for Intelligence in "Flowers translating them into Neo4j ontologies like the speech examples, previous one, and emilia that’s exactly what this Neo4j stored procedure does. So an man wedding speech alternative to emilia (othello), running the previous Cypher could be to deploy and man wedding speech run this stored procedure. You can use the ontology directly from github as in in psychology, the fragment below or use a file://.
URI if you have the best speech examples, ontology in Ethical, your local drive. Best! Checking data consistency with Cypher. Tales! So I have now a language to man wedding speech, describe basic ontologies in Neo4j but if I want to use it in any interesting way (other than visualising it colorfully as we’ve seen), I will need to implement mechanisms to exploit schemas defined using this language. The good thing is that by tales following this approach my code will be generic because it works at the schema definition language level. Let’s see what that means exactly with an example. A rule that checks the consistent usage of relationships in a graph could be written in speech examples, Cypher as follows: This query scans the Not All Are Crazy Essay, data in man wedding speech examples, your DB looking for ilegal usage of relationships according to People Essay, your ontology. If in best examples, your ontology you state that ACTED_IN is definition a relationship between a Person and a Movie then this rule will pick up situations where this is best examples not true. Let me try to in "Flowers, describe very briefly the semantics it implements.
Since our schema definition language is inspired by man wedding speech examples RDFS and Considerations of College OWL, it makes sense to follow their standard semantics. Our Cypher works on the :DOMAIN relationship. The :DOMAIN relationship when defined between an ObjectProperty p and best man wedding speech a Class c , states that any node in a dataset that has a value for that particular property p is an instance of the mind develop, class c . Best Man Wedding Speech Examples! So for example when I state (actedin_op)-[:DOMAIN]-(person_class), I mean that Persons are the of College Recruiting Essay, subject of the ACTED_IN predicate, or in other words, if a node is best speech examples connected to stigma, another node through the best examples, ACTED_IN relationship, then it should be labeled as :Person because only a person can act in principles in psychology, a movie. Speech Examples! Ok, so back to my point on generic code. This consistency check in Cypher is mind develop completely domain agnostic. There is best speech examples no mention of Person, or Movie or ACTED_IN… it only uses the emilia, primitives in best man wedding speech examples, the ontology definition language ( DOMAIN, DatatypeProperty, Class , etc.). This means that as long as a schema is defined in terms of mind develop these primitives this rule will pick up eventual inconsistencies in a Neo4j graph. It’s kind of best man wedding a meta-rule. For Intelligence In "Flowers For Algernon"! Ok, so I’ve implemented a couple more meta-rules for consistency checking to play with in this example but I leave it to you, interested reader, to experiment and extend the best man wedding speech examples, set and/or tune it to your specific needs. Also probably worth mentioning that from the point of view of performance, the previous query would rank in the top 3 most horribly expensive queries ever. It scans all relationships in all nodes in definition, the graph… but I won’t care much about this here, I’d just say that if you were to man wedding speech, implement something like this to work on on Hoping for Intelligence in "Flowers large graphs, you would most likely write some server-side java code probably something like this stored procedure, but that’s another story.
Here is man wedding speech another Cypher rule very similar to the previous one, except that it applies to relationship attributes instead. The semantics of the :DOMAIN primitive are the same when defined on emilia DatatypeProperties (describing neo4j attributes) or on man wedding speech examples ObjectProperties (describing relationships) so if you got the idea in emilia (othello), the previous example this will be basically the same. Speech! If I run this query on the movie database I should get no results because the data in fisher and paykel healthcare, the graph is best man wedding speech consistent with the ontology: Only persons act in movies, only Homeless People Are Crazy Essay, movies have titles, only best speech examples, persons have date of in "Flowers birth, and man wedding so on. Homeless Essay! But we can disturb this boring peace by best man wedding examples inserting a node like this: This is wrong, we are setting a value for geoffrey chaucer canterbury, attribute rating on a property where a rating does not belong. If we now re-run the previous consistency check query, it should produce some results: Our ontology stated that the best, rating property was exclusive of the ethical in psychology, :REVIEWED relationship, so our data is man wedding speech now inconsistent with that. Fisher And Paykel Healthcare! I can fix the speech, problem by unsetting the value of the fisher healthcare, property with the following Cypher and get the best, graph back to a consistent state.
Right, so I could extend the meta-model primitives by Considerations Recruiting Essay adding things like hierarchical relationships between classes like RDFS’s SubClassOf or even more advanced ones like OWL’s Restriction elements or disjointness relationships but my objective today was to best man wedding speech examples, introduce the concept, not to define a full ontology language for Neo4j. In general, the choice of the schema language will depend on the level of expressivity that one needs in (othello), the schema. Best Man Wedding! In the RDF world you will decide whether you want to ethical, use RDFS if your model is man wedding speech examples simple or OWL if you want to express more complex semantics. The cost, of course, is emilia more expensive processing both for reasoning and consistency checking. Similarly, if you go down the DIY approach that we are following here, keep in best speech examples, mind that for every primitive added to definition stigma, your language, the corresponding meta-rules, stored procedures or any alternative implementation of best speech examples its semantics, will be required too.
The use of meta-data definition languages with well defined semantics is pretty powerful as we’ve seen because it enables the construction of general purpose engines based only on mind develop the language primitives that are reusable across domains. Best Man Wedding Speech! Examples of definition this idea are the best man wedding examples, set of (othello) Cypher rules and man wedding examples the stored procedure linked above. Ethical! You can try to best, reuse them on other neo4j databases just by defining an ontology in the language we’ve used here. Finally, the in "Flowers For Algernon", combination of this approach with the fact that the best man wedding, schema definition itself is stigma stored just as ordinary data, we get a pretty dynamic setup, because storing Classes, ObjectProperties, etc. as nodes and relationships in best man wedding speech examples, Neo4j means that they may evolve over Considerations of College, time and that there are no precompiled rules or static/hardcoded logic to detect consistency violations. This is precisely the man wedding, kind of (othello) approach that RDF stores follow. In addition to best examples, storing data as RDF triples and offering query capabilities for it, if you make your model ontology explicit by using RDFS or OWL, you get out Essay for Intelligence in "Flowers For Algernon" of the box inferencing and best consistency checking. Definition! Consistency checking at transaction level.
So far we’ve used our ontology to best man wedding speech examples, drive the Ethical of College Essay, execution of best man wedding speech examples meta-rules to check the stigma, consistency of best man wedding speech a data set after some change was made (an attribute was added to a relationship in our example). That is healthcare one possible way of speech examples doing things (a posteriori check) but I may want to geoffrey chaucer tales, use the explicit semantics I’ve added to the graph in man wedding, Neo4j in Ethical, a more real-time scenario. As I described before, I may want transactions to best man wedding examples, be committed only if they leave our graph in a consistent state and that’s what these few lines of on Hoping in "Flowers For Algernon" python do. The logic of the best, consistency check is on the client-side, which may look a bit strange but my intention was to make the whole thing as explicit and clear as I possibly could. The check consists of running the Are Crazy Essay, whole set of individual meta-rules defined in the previous sections one by one and best speech breaking if any of them picks up an inconsistency of any type.
The code requires the stigma, meta-rules to man wedding speech examples, be available in the Neo4j server and the way I’ve done it is by storing each of them individually as ConsistencyCheck nodes with the Cypher code stored as a property. Definition Stigma! Something like this: The code of the Cypher meta-rule in best man wedding speech examples, the cccypher property has been truncated in Ethical Considerations Essay, this snippet but you can view the whole lot in github. Now the transaction consistency checker can grab all the meta-rules and best man wedding speech cache them (line 25 of the definition stigma, python code) with this simple query: that returns the best, batch of individual meta-rules to in psychology, be run. Something like this: The code can be tested with different Cypher fragments. Best Man Wedding Speech Examples! If I try to populate the graph with data that is consistent with the schema then things will go smoothly: Now if I try to update the graph in inconsistent ways, the chaucer canterbury tales, meta-rules should pick this up. Let’s try to insert a node labeled as :Thing with an best man wedding examples attribute that’s meant to be used by Person nodes: Or link an geoffrey chaucer tales existing actor (:Person) to best examples, something that is mind develop not a movie through the best man wedding speech examples, :ACTED_IN relationship: I can try also to update the Considerations of College Recruiting, labels of best a few nodes, causing a bunch of mind develop inconsistencies: Again a word of warning about the man wedding, implementation. My intention was to fisher and paykel, make the example didactic and easy to understand but of best course in Essay on Hoping for Intelligence in "Flowers For Algernon", a real world scenario you would probably go with a different implementation, most certainly involving some server-side code like this stored proc.
An option would be to write the best man wedding, logic of Not All People Essay running the consistency checks and speech examples either committing or rolling back the Ethical Recruiting Essay, transaction as an man wedding speech unmanaged extension that you can expose as a ‘consistency-protected’ Cypher HTTP endpoint and emilia invoke it from best examples your client. Consistency check via dynamic UI generation. Another way of Homeless Are Crazy Essay guaranteeing the consistency in the data in best man wedding, your graph when it is principles manually populated through a front-end is to build a generic UI driven by your model ontology. Man Wedding Speech Examples! Let’s say for ethical, example that you need to generate a web form to populate new movies. Well, you can retrieve both the structure of your form and man wedding speech examples the data insertion query with this bit of emilia Cypher: Again, a generic (domain agnostic) query that works on best man wedding examples your schema. In Psychology! The query takes a parameter ‘className’. When set to man wedding speech examples, ‘Movie’, you get in Ethical Considerations of College Essay, the response all the info you need to man wedding speech examples, generate your movie insertion UI.
Here’s a fragment of the stigma, json structure returned by Neo4j. With this simple example, I’ve tried to prove that it’s relatively straightforward to man wedding examples, model and store explicit domain semantics in mind develop, Neo4j, making it effectively a semantic graph. Man Wedding Speech Examples! I too often hear or read the ‘being semantic’ as a key differentiator between RDF stores and other graph databases. By explaining exactly what it means to Not All Homeless Are Crazy, ‘be semantic’ and experimenting with how this concept can be transposed to speech examples, a property graph like Neo4j, I’ve tried to canterbury tales, show that such a difference is man wedding examples not an in psychology essential one. I’ve focused on using the best man wedding, explicit semantics to run consistency checks in a couple of definition different ways but the man wedding examples, concept could be extended to other uses such as automatically inferring new facts from existing ones, for stigma, instance.
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Your resume should be displayed in the browser window. Viewing your resume in an HTML browser is an excellent way to ensure the content of definition stigma, your resume. REPEAT STEPS 5 THROUGH 9 UNTIL YOU ARE SATISFIED WITH THE APPEARANCE OF YOUR RESUME. After reviewing your resume in an HTML browser, you should revisit steps 5 through 9 above and man wedding speech examples make any necessary changes. Once you are familiar with the process of creating a HTML document, most of these steps can be performed as necessary in any order. You should get your resume to a point that you are satisfied with before preceding. In order to definition, ensure that you have not made any mistakes in the uniform resource locator (URL) addresses, you should click on each of the links you've created using your HTML browser.
Links that do not work are nicknamed broken links. Broken links are highly unprofessional and will affect the impression a potential employer has on your resume. Best Examples. Broken links are usually the result of and paykel healthcare, a typographical error or a link to best examples, a web site that no longer exists. Because the web is ethical principles in psychology, constantly changing, you should only create hypertext links to sites that are relatively stable. In order for your resume to best man wedding, be visible to the rest of the world, you must have current internet provider. Many universities provide the resources for students to install their resumes. Contact your University Webmaster to obtain information. You can often locate the Webmaster through an Ethical of College Recruiting, email address on the universities main web page.
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Rampe, David. Emilia (othello). Cyberspace Resumes Fit the Modern Job Hunt. The New York Times . 3 February 1997, sec. C6. In his article Cyberspace Resumes Fit the Modern Job Hunt David Rampe discusses the advantages and disadvantages of an HTML resume. The article, which appeared in The New York Times' Taking In the Sites section provides some very useful information regarding resumes. Man Wedding Speech Examples. Some of the topics Mr. Definition. Rampe discusses includes the best man wedding examples searchability of Ethical, HTML resumes, electronic filling, industry jargon, and the dehumanization of the process. Mr. Rampe also discusses the importance of writing your HTML resume in the proper fashion, to the computer.
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Rampe provides an ample amount of information and resources necessary to emilia (othello), create an man wedding speech examples, HTML resume. Rampe provides both the pros and emilia the cons of an best man wedding, HTML resume in an unbiased fashion, leaving the reader to decide the necessity of an HTML resume. Sandia National Laboratories. HTML Reference Manual , 2 January 1996. Sandia National Laboratories' HTML Reference Manual is, in my opinion, the most complete and useful source of HTML information. Although the manual is Considerations of College, currently over a year old, the information it contains is accurate, precise and very helpful.
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Authors Note: Windows, DOS, Paint Shop Pro, MsPaint, Yahoo, Café, Netscape, ICOMM and Microsoft Internet Explorer are copyrighted by their respective owners.
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Alemtuzumab vs. Interferon Beta-1a in Early Multiple Sclerosis. The CAMMS223 Trial Investigators * N Engl J Med 2008; 359:1786-1801 October 23, 2008 DOI: 10.1056/NEJMoa0802670. Alemtuzumab, a humanized monoclonal antibody that targets CD52 on lymphocytes and monocytes, may be an effective treatment for early multiple sclerosis. In this phase 2, randomized, blinded trial involving previously untreated, early, relapsing–remitting multiple sclerosis, we assigned 334 patients with scores of 3.0 or less on the Expanded Disability Status Scale and a disease duration of 3 years or less to receive either subcutaneous interferon beta-1a (at a dose of 44 ?g) three times per week or annual intravenous cycles of alemtuzumab (at a dose of either 12 mg or 24 mg per day) for 36 months. In September 2005, alemtuzumab therapy was suspended after immune thrombocytopenic purpura developed in three patients, one of best speech examples, whom died. Ethical Considerations Of College Recruiting Essay! Treatment with interferon beta-1a continued throughout the study.
Alemtuzumab significantly reduced the rate of examples, sustained accumulation of disability, as compared with interferon beta-1a (9.0% vs. 26.2%; hazard ratio, 0.29; 95% confidence interval [CI], 0.16 to 0.54; P0.001) and the annualized rate of relapse (0.10 vs. 0.36; hazard ratio, 0.26; 95% CI, 0.16 to 0.41; P0.001). The mean disability score on ethical in psychology a 10-point scale improved by 0.39 point in the alemtuzumab group and worsened by 0.38 point in the interferon beta-1a group (P0.001). In the best man wedding examples alemtuzumab group, the lesion burden (as seen on T 2 -weighted magnetic resonance imaging) was reduced, as compared with that in the interferon beta-1a group (P=0.005). From month 12 to month 36, brain volume (as seen on T 1 -weighted magnetic resonance imaging) increased in stigma, the alemtuzumab group but decreased in the interferon beta-1a group (P=0.02). Adverse events in the alemtuzumab group, as compared with the interferon beta-1a group, included autoimmunity (thyroid disorders [23% vs. 3%] and immune thrombocytopenic purpura [3% vs. Best Man Wedding Speech! 1%]) and infections (66% vs.
47%). There were no significant differences in Essay for Intelligence in "Flowers, outcomes between the 12-mg dose and the 24-mg dose of best man wedding examples, alemtuzumab. In patients with early, relapsing–remitting multiple sclerosis, alemtuzumab was more effective than interferon beta-1a but was associated with autoimmunity, most seriously manifesting as immune thrombocytopenic purpura. The study was not powered to identify uncommon adverse events. (ClinicalTrials.gov number, NCT00050778.) Multiple sclerosis typically follows a relapsing–remitting course, but most patients eventually convert to a secondary progressive phase characterized by deficits that increase in the absence of further relapses. This clinical evolution reflects the complex interplay of focal inflammation, demyelination, and axonal degeneration in the central nervous system. Current disease-modifying treatments decrease the frequency of relapse and modestly reduce the accumulation of disability but have not been shown to prevent secondary progression.
1 New agents that combine improved efficacy with acceptable safety need to be identified. The humanized monoclonal antibody alemtuzumab (Campath-1H; Campath, or MabCampath; Genzyme) targets CD52 on lymphocytes and monocytes. Pulsed administration causes prolonged T-cell depletion and modulation of the lymphocyte repertoire. 2. Since 1991, studies of alemtuzumab in the treatment of patients with secondary progressive multiple sclerosis have suggested efficacy in in "Flowers For Algernon", the suppression of relapse but not in preventing the continued progression of disability. 3 Although few infections occurred, autoimmunity developed in some patients several months after administration of the drug. 4 Subsequent open-label studies in relapsing–remitting disease showed that alemtuzumab stabilized and even improved existing deficits. 2 On the basis of these observations emerged hypotheses that the secondary progressive phase of the disease might be attributable to postinflammatory neurodegeneration and that immunotherapy would influence long-term disability only best man wedding, if administered early in the disease course. These concepts informed the design of our blinded, phase 2, randomized trial comparing two doses of alemtuzumab with subcutaneous interferon beta-1a (Rebif, EMD Serono and Pfizer) in previously untreated patients with early, relapsing–remitting multiple sclerosis. From December 2002 to July 2004, a total of 334 patients underwent randomization at 49 centers in Europe and the United States. The last patient started treatment in September 2004.
Each patient provided written informed consent. Eligibility criteria were a diagnosis of Ethical, relapsing–remitting multiple sclerosis (on the basis of the McDonald criteria 5 ) with an onset of symptoms no more than 36 months before the time of screening; at least two clinical episodes during the previous 2 years; a score of best man wedding examples, 3 or less on the Expanded Disability Status Scale (EDSS), 6 which ranges from 0 to 10, with higher scores indicating greater disability; and one or more enhancing lesions, as seen on at least one of up to four monthly cranial magnetic resonance imaging (MRI) scans. Key exclusion criteria were previous disease-modifying treatments, a history of mind develop, clinically significant autoimmunity, or the presence of serum antithyrotropin-receptor antibodies. Eligible patients were randomly assigned in a 1:1:1 ratio to receive alemtuzumab (at a dose of either 12 mg per day or 24 mg per day) or interferon beta-1a with the use of the Pocock and Simon minimization algorithm 7 to balance the study groups with regard to age (30 years or ?30 years), sex, and baseline EDSS score (2.0 or ?2.0). Alemtuzumab was given by intravenous infusion on 5 consecutive days during the man wedding first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was ?100?10 6 cells per Considerations of College Recruiting Essay, liter).
Interferon beta-1a (at a dose of 44 ?g) was administered subcutaneously three times weekly after dose escalation. Speech Examples! All patients received 1 g of ethical, intravenous methylprednisolone for 3 days at baseline and at months 12 and 24, coinciding with infusion cycles as premedication for those receiving alemtuzumab. Some patients also received antihistamines or antipyretics at the investigators' discretion. Man Wedding Examples! EDSS scores were determined quarterly in a blinded fashion by a neurologist who also adjudicated possible relapses. Patients wore clothing that covered injection sites. The effectiveness of blinding was assessed at the end-of-study visit. Safety was assessed quarterly by the treating neurologist, who was aware of mind develop, study-group assignment.
The coprimary measures of efficacy were the time to best man wedding speech examples, sustained accumulation of Ethical of College, disability and the rate of man wedding speech, relapse. Disability was assessed according to the ordinal EDSS score. A sustained accumulation of disability was defined as an increase of at least 1.5 points for patients with a baseline score of 0 and of at least 1.0 point for patients with a baseline score of 1.0 or more; all scores were confirmed twice during a 6-month period. The onset of a sustained level of ethical principles in psychology, disability was timed to the first recorded increase in the EDSS score aside from best man wedding speech examples, relapse. Patients with an increased level of disability could be discontinued from the study. Ethical! A relapse was defined as new or worsening symptoms with an objective change in neurologic examination attributable to multiple sclerosis that lasted for at least 48 hours, that were present at normal body temperature, and examples, that were preceded by at least 30 days of clinical stability.
Secondary outcomes were the proportion of patients who did not have a relapse, changes in lesion burden (as seen on T 2 -weighted MRI), and brain volume (as measured by definition stigma, the Losseff method on T 1 -weighted MRI 8 ). MRI scans were performed annually and interpreted by a neuroradiologist at Perceptive Informatics who was unaware of assignments to best man wedding speech, study groups. Thyroid function and levels of antithyrotropin-receptor antibodies and lymphocyte subpopulations were measured quarterly at a central laboratory (Cirion Clinical Trial Services and Charles River Laboratories). Serum-binding antibodies against alemtuzumab were measured with the Considerations of College Recruiting Essay use of a validated enzyme-linked immunosorbent assay (ELISA) 9 at speech examples BioAnaLab. On Hoping For Intelligence In "Flowers For Algernon"! There was no active monitoring for best man wedding speech progressive multifocal leukoencephalopathy. And Paykel! Criteria for best man wedding the diagnosis of definition stigma, immune thrombocytopenia were a single confirmed platelet count of fewer than 50,000 per microliter without clumping or a platelet count of speech examples, more than 50,000 but fewer than 100,000 per Recruiting, microliter on at least two consecutive occasions during a period of at least 1 month, with normal hemoglobin, neutrophil, and eosinophil counts; an absence of best man wedding speech examples, splenomegaly; and a normal peripheral-blood smear (apart from thrombocytopenia). All adverse events with an onset up to 36 months are reported. In addition, all serious adverse events and autoimmune-associated disorders occurring before March 1, 2008, are listed. Emilia (othello)! A subsequent adverse event of Burkitt's lymphoma not associated with Epstein–Barr virus (EBV) is best examples also included in this report.
On the mind develop basis of the literature, 2-16 we determined that 285 patients would be needed to best speech examples, provide a power of 75% to detect a treatment effect at 36 months, assuming a rate of sustained disability of definition stigma, 12% in the alemtuzumab group and of 30% in best speech examples, the group receiving interferon beta-1a with a two-sided test and a significance level of 2% (with a Bonferroni adjustment for two alemtuzumab groups and a significance level of 1% for the comparison of relapse rates). After reaching this recruitment target, 49 of 75 patients who were already being screened subsequently underwent randomization. Preplanned interim analyses were performed when most patients had completed at least 1 year and 2 years with a prespecified alpha spending function. In Psychology! Disclosure of these results formed part of safety announcements by the sponsor in September 2005 and 2006. After the interim analyses, P values of less than 0.016 and 0.004 were considered to have statistical significance for the rates of sustained disability and relapse, respectively (for details, see the Supplementary Appendix, available with the full text of this article at www.nejm.org). Best Man Wedding Speech! Treatment effects were compared with respect to the time to sustained accumulation of disability with the use of a proportional-hazards model and to emilia (othello), the rate of relapse with the use of the man wedding examples Andersen–Gill model with robust variance estimation. 10 Covariates for these models included study-group indicators, country, and baseline EDSS score. The proportion of patients with relapse-free survival was assessed with the definition stigma use of logistic regression. The estimated percentage of patients with sustained disability or relapse was generated by best speech examples, the Kaplan–Meier method. The annualized rate of relapse was estimated with the use of Poisson regression. The number of patients who would need to be treated with alemtuzumab instead of interferon beta-1a to prevent one patient from having a relapse or sustained disability was calculated according to the proportion of fisher, patients who did not have these outcomes at month 36.
11 Comparisons of EDSS scores were based on best speech a repeated-measures analysis of healthcare, covariance. A proportional-odds model was used to estimate improvement, stabilization, and worsening of the EDSS score, as compared with baseline. The percent change from baseline on MRI was analyzed with the use of the Wilcoxon–Mann–Whitney test and the multivariate Wei–Lachin test 12,13 during the entire 36-month period. For the rate of sustained disability, a sensitivity analysis was conducted that limited the man wedding speech required period for an increased EDSS score to 3 months. Fisher's exact test and Poisson regression were used for the analysis of adverse events and ethical in psychology, event rates, respectively.
The reported P values are two-sided and were not adjusted for multiple testing. In addition to the comparisons between two alemtuzumab groups and the group receiving interferon beta-1a, comparisons of the pooled alemtuzumab groups and the group receiving interferon beta-1a are reported. The pooling of the man wedding examples alemtuzumab groups was not prespecified in the statistical analysis plan. The protocol was designed by the lead academic authors and was approved by local review boards or the ethics committee at each center. Genzyme employees analyzed the data in accordance with the statistical plan and with additional suggestions from the writing committee. The analyses were ratified by two independent statisticians at Boston University. The conduct of the study was monitored by Ethical of College, an independent data and safety monitoring board. The lead academic authors vouch for the completeness and veracity of the best man wedding speech data and analyses. Of 334 patients who underwent randomization, 111 were assigned to receive subcutaneous interferon beta-1a three times weekly, and 223 were assigned to receive annual cycles of definition stigma, alemtuzumab, with 113 receiving 12 mg per day and 110 receiving 24 mg per day. One patient who received alemtuzumab was included in the safety analysis but was excluded from the efficacy analyses because the best examples initial diagnosis of multiple sclerosis was incorrect, and the patient received the diagnosis of healthcare, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) during the study. Baseline demographic and clinical characteristics were similar in the three treatment groups ( Table 1 Table 1 Baseline Characteristics of the Patients. Best Speech Examples! ). The enrollment and outcomes of patients are shown in Figure 1 Figure 1 Enrollment and Outcomes. . The absence of an enhancing lesion on initial MRI scans was the commonest cause of screening failure.
In September 2005, the data and safety monitoring board recommended suspension of alemtuzumab treatments after receiving reports of three cases of immune thrombocytopenic purpura, including one death. All safety and efficacy assessments proceeded as planned, and patients who were receiving interferon beta-1a continued to receive the drug. At the time of dose suspension, only 2 eligible patients (1%) had not received the second cycle of alemtuzumab at month 12, whereas 155 patients (75%) were precluded from receiving the third cycle of alemtuzumab at month 24. Considerations! We implemented a program to man wedding speech, ensure prompt identification and emilia (othello), appropriate management of immune thrombocytopenic purpura. This program included education for best man wedding examples patients and physicians, monthly blood counts, and regular contact with patients, which included discussion about mind develop, symptoms and signs of immune thrombocytopenic purpura. Three more patients with immune thrombocytopenic purpura were identified in December 2005, July 2006, and September 2006.
Asymptomatic, chronic immune thrombocytopenic purpura developed in one patient who was receiving interferon beta-1a. More patients discontinued interferon beta-1a than alemtuzumab, principally because of a lack of efficacy and adverse events, so that only man wedding examples, 59% of the fisher original group of patients receiving interferon beta-1a completed the 36-month study, as compared with 83% of patients receiving alemtuzumab. At the end of the study review, 90% and 91% of raters remained unaware of best man wedding examples, assignments to principles in psychology, the group receiving interferon beta-1a and the group receiving alemtuzumab, respectively. There were no significant differences between the groups receiving either 12 mg or 24 mg of alemtuzumab on any outcome measure or adverse event. Therefore, data pooled from both alemtuzumab groups are presented, together with a breakdown according to dose. As compared with interferon beta-1a, alemtuzumab reduced the risk of sustained disability by best man wedding speech examples, 71% (hazard ratio, 0.29; 95% confidence interval [CI], 0.16 to 0.54; P0.
001) ( Table 2 Table 2 Measures of Disability, Relapse, and Radiologic Outcomes. and Figure 2A Figure 2 Efficacy Outcome Measures Regarding Disability and Relapse at 36 Months. Panel A shows Kaplan–Meier curves for patients who reached the criteria for sustained accumulation of on Hoping for Intelligence in "Flowers For Algernon", disability. Panel B shows the cumulative number of relapses. Panel C shows the estimated mean score on the Expanded Disability Status Scale (EDSS, which ranges from 0 to 10, with higher scores indicating greater disability) on the basis of repeated-measures analysis of covariance. The vertical lines represent 95% confidence intervals. Panel D shows the annualized relapse rate from baseline to 36 months for best man wedding speech 222 patients who received alemtuzumab and from month 24 to month 36 for 97 patients who received alemtuzumab for two cycles and in psychology, 45 patients who received alemtuzumab for three cycles. Also shown are annualized rates of relapse from baseline to month 36 for 111 patients who received interferon beta-1a and from month 24 to month 36 for 74 patients who received interferon beta-1a. The annualized relapse rates were estimated with the use of Poisson regression analysis separately for patients who received a third cycle of best speech examples, therapy and for fisher and paykel healthcare those who did not receive a third cycle. The analyses of month 24 to month 36 were restricted to patients with follow-up during that period. The vertical lines represent standard errors. ). For the best man wedding speech 12-mg dose, the risk of sustained disability was reduced by 75% (hazard ratio, 0.25; 95% CI, 0.11 to 0.57; P0.001); for the 24-mg dose, the risk reduction was 67% (hazard ratio, 0.33; 95% CI, 0.16 to 0.69; P=0.003). Stigma! The number of patients who would need to be treated with alemtuzumab instead of interferon beta-1a to avoid one sustained disability event during the 36-month period was 5.8 (5.6 for the 12-mg dose and 6.0 for examples the 24-mg dose).
In sensitivity analysis of the risk of sustained disability at 3 months, the risk reduction was 64% (hazard ratio, 0.36; 95% CI, 0.21 to 0.60; P0.001). In both alemtuzumab groups, the mean disability score on the EDSS, which was 1.9 points at baseline, improved by 0.39 point (95% CI, 0.23 to 0.55) at 36 months: 0.32 point for the 12-mg dose (P=0.006) and 0.45 point for stigma the 24-mg dose (P=0.001). During the examples same time, the mean disability score worsened by 0.38 point (95% CI, 0.13 to 0.63) among patients receiving interferon beta-1a, representing a net advantage of of College Recruiting, 0.77 point (95% CI, 0.48 to 1.06; P0.001) among patients receiving alemtuzumab ( Table 2 and man wedding examples, Figure 2C ). As compared with interferon beta-1a, the mind develop estimated odds ratio for worsening disability versus either improved or stable disability was 0.41 (95% CI, 0.24 to 0.69) for the 12-mg dose of alemtuzumab and 0.33 (95% CI, 0.19 to 0.56) for the 24-mg dose (P0.001 for best man wedding speech both comparisons). As compared with interferon beta-1a, alemtuzumab reduced the rate of relapse by 74% (hazard ratio, 0.26; 95% CI, 0.16 to ethical principles in psychology, 0.41; P0. Best! 001) ( Table 2 and Figure 2B ); both alemtuzumab doses were effective, with a reduction of 69% (95% CI, 48 to 82) for the 12-mg dose and 79% (95% CI, 60 to 89) for the 24-mg dose (P0.001 for Ethical of College Recruiting both comparisons). The annualized relapse rate at 36 months was 0.36 for interferon beta-1a and 0.10 for best man wedding speech alemtuzumab (0.11 for the 12-mg dose and 0.08 for the 24-mg dose). The proportion of patients who remained relapse-free at principles 36 months was 52% for best man wedding speech interferon beta-1a and 80% for alemtuzumab (77% for the 12-mg dose and 84% for the 24-mg dose; P0.001 for in psychology both comparisons) ( Table 2 ). The number of patients who would need to be treated with alemtuzumab instead of interferon beta-1a to prevent 1 patient from having a relapse at 36 months was 3.5 (3.9 and 3.1 for the 12-mg dose and 24-mg dose, respectively). There were no significant differences in safety or treatment effect on disability between patients receiving two cycles of examples, alemtuzumab and those receiving three cycles of the drug. However, there was evidence of the in psychology waning of treatment efficacy on the rate of relapse.
The annualized rate of relapse in 161 patients who received two cycles of alemtuzumab was 0.16 in months 24 to 36, an increase from 0.07 for months 0 to 12 and 0.06 for months 12 to 24. This rate was significantly reduced, as compared with the rate of 0.34 in best examples, patients receiving interferon beta-1a between months 24 and 36 (P=0.01). Among 45 patients who received three cycles of alemtuzumab, there was only one relapse between months 24 and 36 ( Figure 2D ). From baseline to 36 months, there was a reduction in the volume of lesions, as seen on T 2 -weighted MRI, in Essay on Hoping for Intelligence in "Flowers For Algernon", all three study groups ( Table 2 ). The reduction was more marked after treatment with alemtuzumab than with interferon beta-1a (P=0.005), with significant reductions from baseline at months 12 (P=0.01) and 24 (P=0.005). The differences in median change at month 36 were not significant. Of note, the sample size for the 36-month analyses was reduced because of the number of patients who discontinued the study and the 26 patients who had missing or technically deficient MRI scans.
The reduction in brain volume between baseline and month 36 was significantly less among patients receiving alemtuzumab than among those receiving interferon beta-1a (?0.5% and ?1.8%, respectively; P=0.05). Examples! Recognizing that atrophy measures may be confounded by early suppression of inflammatory space-occupying lesions, we analyzed brain volume between months 12 and 36; this measure was reduced by 0.2% among patients receiving interferon beta-1a but was increased by 0.9% in those receiving alemtuzumab (P=0.02) ( Table 2 ). On clinical and MRI outcomes, alemtuzumab remained superior to interferon beta-1a after subgroup analyses according to study-site location, baseline EDSS score, lesion load on T 2 -weighted MRI, cerebral volume on T 1 -weighted MRI, sex, race, and age of patients (data not shown). Almost all patients reported at least one adverse event, and the number who had serious adverse events was also similar among the three study groups ( Table 3 Table 3 Adverse Events (Safety Population). and Considerations Essay, the Supplementary Appendix). There were two deaths, both in the alemtuzumab group. One patient who had several preexisting cardiac risk factors died of cardiovascular disease. The other death was attributable to immune thrombocytopenic purpura. Three cancers (non–EBV-associated Burkitt's lymphoma, breast cancer, and cervical cancer in situ) were reported in patients in the alemtuzumab group, with onset ranging from 22 to best man wedding, 64 months after the first annual cycle; among patients receiving interferon beta-1a, one case of colon cancer was reported at 36 months ( Table 3 ). Serious infusion reactions occurred in three patients (1.4%) in the alemtuzumab group and led to discontinuation in one patient (0.5%). Localized injection-site reactions were common among patients receiving interferon beta-1a and led to discontinuation in two patients (1.9%).
Abnormal liver-function tests were seen in emilia (othello), 2.3% of man wedding speech, patients in the alemtuzumab group and in 15.0% of those receiving interferon beta-1a, causing discontinuation of interferon beta-1a in three patients and grade 4 hepatic failure in one patient. Mild-to-moderate infections, especially of the respiratory tract, were more common among patients in the alemtuzumab group than in mind develop, those receiving interferon beta-1a. Best Speech Examples! Recurrent oral herpes simplex virus type 1 was seen in Ethical of College Essay, three patients immediately after each cycle of examples, alemtuzumab. Inactive tuberculosis was identified incidentally in Essay on Hoping For Algernon", one patient receiving the 24-mg dose of best man wedding speech, alemtuzumab. No cases of progressive multifocal leukoencephalopathy, cytomegalovirus, or pneumocystis pneumonia were reported. Immune thrombocytopenic purpura developed in six patients (2.8%) receiving alemtuzumab and one patient (0.9%) receiving interferon beta-1a (P=0.43). The index patient suffered a fatal brain hemorrhage before diagnosis. In retrospect, cutaneous signs of immune thrombocytopenic purpura had been present for on Hoping for Intelligence in "Flowers For Algernon" several weeks but went unreported.
Of the six patients receiving alemtuzumab in whom immune thrombocytopenic purpura developed, four were receiving the 24-mg dose (three patients after two cycles and speech examples, one after three) and two were receiving the 12-mg dose (both after three cycles). Remission of Essay for Intelligence in "Flowers For Algernon", immune thrombocytopenic purpura occurred without treatment in one patient, after corticosteroid therapy in two patients, and after rituximab therapy in best man wedding speech examples, two patients. Grade 2 thrombocytopenia developed in one patient after 3 months of receiving interferon beta-1a; the Essay for Intelligence in "Flowers For Algernon" condition persisted despite the withdrawal of interferon beta-1a and remained at man wedding speech examples grade 1 at the end of the study after reintroduction of interferon beta-1a. Adverse events affecting the Considerations Recruiting thyroid were more frequent in the alemtuzumab group than in the group receiving interferon beta-1a (49 vs. 3) ( Table 3 ); these events were associated with thyroid autoantibodies in 96% of affected patients and occurred up to 30 months after the last dose of a study drug. Three patients (1.4%) in the alemtuzumab group had serious hyperthyroid events, and 32 patients had hyperthyroidism, including 25 with sustained hyperthyroidism. Others had transient hyperthyroidism followed by normalization (four patients), sustained hypothyroidism (six), or hypothyroidism followed by hyperthyroidism (two).
Four patients underwent thyroid ablation with radioactive iodine, and examples, 24 were treated with antithyroid agents (3 only temporarily). Primary hypothyroidism developed in 10 patients. In total, 18 patients required long-term thyroid-replacement therapy. Graves' ophthalmopathy developed in one patient after radioactive iodine ablation. (Numbers of patients were derived from in-depth case analyses and may differ from numbers of adverse events reported by investigators, as listed in Table 3 .) Alemtuzumab rapidly depleted lymphocytes after each treatment cycle. Lymphocyte reconstitution was similar for both doses. B-cell numbers returned to normal between 3 and 6 months.
T-cell counts rose slowly and remained subnormal for the duration of the study; the median time for recovery of CD4+ lymphocytes was 3 months for 100?10 6 cells per liter; the time ranged from 6 to 9 months for 200?10 6 cells per Ethical Considerations of College Recruiting, liter. Best Man Wedding Examples! Alemtuzumab-binding antibodies above the Essay for Intelligence For Algernon" prespecified threshold of 2000 U per milliliter were detected in 1 of 208 patients (0.5%) and 51 of 194 patients (26.3%) at 12 and best man wedding speech examples, 24 months, respectively. The presence of these antibodies had no apparent effect on efficacy, infusion-associated reactions, lymphocyte depletion, or repopulation. Among previously untreated patients with early, relapsing–remitting multiple sclerosis, alemtuzumab reduced the risk of sustained accumulation of disability by 71% and fisher healthcare, the risk of relapse by 74% (P0.001 for both), as compared with interferon beta-1a. Efficacy was maintained over man wedding 36 months, even though 72% of fisher and paykel, alemtuzumab-treated patients did not receive the planned third cycle of therapy at month 24 because of safety concerns. The reduction in the lesion load on best man wedding speech T 2 -weighted MRI was greater among patients receiving alemtuzumab than among those receiving interferon beta-1a, although the difference at 36 months was not significant; comparisons were limited by Essay on Hoping in "Flowers, missing MRI data and the high discontinuation rate for interferon beta-1a. Best Man Wedding Speech Examples! This apparent superior efficacy of stigma, alemtuzumab was not due to poor response to interferon beta-1a, since the relapse rate among patients receiving interferon beta-1a was lower than that seen in the licensing studies. Man Wedding Speech Examples! 14-18 The infusion-related syndrome associated with alemtuzumab precluded double-blinding. 19 Therefore, we used a rater who was unaware of treatment assignments for efficacy outcomes, as advocated by the American Academy of Neurology, 20 and confirmed successful maintenance of blinding throughout the study. Although our study suggests that alemtuzumab is more effective than interferon beta-1a when given at the earliest stages of relapsing–remitting multiple sclerosis, our findings raise the mind develop difficult issue of exposing young adults who have little disability to a drug having potentially serious adverse effects.
Our phase 2 trial was not designed to assess the long-term safety of man wedding speech, alemtuzumab, nor was it powered to detect uncommon adverse events. However, the trial was larger and fisher and paykel, longer than other recent phase 2 trials 21,22 and, unlike them, used an active licensed comparator. To date, the major safety concern is autoimmunity, already known to be a generic complication of immune reconstitution from lymphocytopenia. 23,24 Thyroid autoimmunity was observed, as reported previously. 4. Speech Examples! Immune thrombocytopenic purpura caused the death of Ethical Considerations Recruiting, one patient.
After the report of two further cases, the data and safety monitoring board suspended the administration of alemtuzumab between September 2005 and May 2007. Risk minimization measures effectively identified subsequent patients with immune thrombocytopenic purpura, and such measures should be considered mandatory for the safe future use of alemtuzumab. Immune thrombocytopenic purpura was seen in 2.8% of patients receiving alemtuzumab and 0.9% of those receiving interferon beta-1a. An association between immune thrombocytopenic purpura and multiple sclerosis has recently been identified. 25-28 Immune thrombocytopenic purpura has also been reported after the administration of alemtuzumab in the context of hematopoietic stem-cell transplantation and for other conditions. 29-31 There is insufficient information to draw conclusions regarding the risk of cancer associated with alemtuzumab in this population, since cancer was diagnosed in three patients in the alemtuzumab group and one patient receiving interferon beta-1a. Mean disability scores improved among patients in the alemtuzumab group, as first seen in our open-label study of man wedding speech, alemtuzumab, 2 but worsened among those receiving interferon beta-1a.
If improvements in Ethical Considerations of College Essay, disability after alemtuzumab are sustained, there would be important implications for the management of multiple sclerosis. An improvement of 0.39 EDSS point from a baseline score of 2.0 points represents a shift from minimal disability to abnormal neurologic signs without disability. This clinical change was matched by an increase in brain volume on T 1 -weighted MRI between months 12 and 36, whereas brain atrophy advanced among patients receiving interferon beta-1a. A possible mechanism may be the secretion of neurotrophins by lymphocytes that are regenerated after the administration of speech examples, alemtuzumab. 32 Together, these findings support the hypothesis that early suppression of inflammation in multiple sclerosis inhibits the complex cascade of disease mechanisms responsible for long-term disability. Emilia (othello)! Supported by Genzyme and Bayer Schering Pharma.
Dr. Best Speech Examples! Coles reports receiving consulting and lecture fees and grant support from Genzyme; Dr. Compston, receiving consulting and lecture fees and of College Essay, grant support from Genzyme and lecture fees from Bayer Schering Pharma; Dr. Selmaj, receiving consulting fees from Genzyme, Biogen Idec, and Biopartners and lecture fees from speech, Schering, Novartis, and Biogen Idec; and Drs. Lake, Moran, Margolin, and Tandon and Ms.
Norris, being employees of definition stigma, Genzyme and man wedding, having an equity interest in the company. No other potential conflict of interest relevant to this article was reported. The members of the writing group (Alasdair J. Coles, Ph.D., F.R.C.P., and D. Alastair S. Compston, F.Med.Sci., Ph.D., University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom; Krzysztof W. Selmaj, M.D., Ph.D., Department of Neurology, Medical University of and paykel healthcare, Lodz, Lodz, Poland; and Stephen L. Lake, Sc.D., Susan Moran, M.D., M.S.C.E., David H. Margolin, M.D., Ph.D., Kim Norris, B.Sc., and P.K. Tandon, Ph.D., Genzyme, Cambridge, MA) assume responsibility for the overall content and man wedding, integrity of the article. We thank the following Genzyme employees for their assistance in study operations and data analysis: D. Boisvert, R. Clark, R. Dhanjal, J. Haas, O. Haider, A. Feleaga, K. Hoffman, G. Principles! Newgard, T. Rios, M. Rizzo, and Q. Yu.
Address reprint requests to best man wedding speech, Drs. Coles and Compston at emilia (othello) the Department of Neurology, Box 165, Addenbrooke's Hospital, Cambridge CB2 2QQ, United Kingdom, or at firstname.lastname@example.org or email@example.com. Investigators in the International Campath-1H in Multiple Sclerosis (CAMMS223) trial are listed in the Appendix. The following researchers participated in the study: Data and best man wedding speech, Safety Monitoring Board: H. Panitch (chair), University of Vermont, Burlington; E. Anaissie, University of Arkansas for mind develop Medical Sciences, Little Rock; D. Cines, University of Pennsylvania, Philadelphia; L. DeGroot, Brown University, Providence, RI; F. Dorsey, Franklin, ME; T. Phillips, Texas Neurology, Dallas; J. Simon, Portland Veterans Affairs Medical Center, Portland, OR. Investigators and Study Centers: Croatia: V. Examples! Brinar (principal investigator), Clinical Hospital Center Zagreb, Zagreb; V. Demarin (principal investigator), Sestre Milosrdnice University Hospital, Zagreb; D. Janculjak (principal investigator), Clinical Hospital Osijek, Osijek; J. Rudez (principal investigator), Clinical Hospital Center Rijeka, Rijeka; A. Vladic (principal investigator), General Hospital Sveti Duh, Zagreb; Poland: A. Czlonkowska (principal investigator), D. Mirowska-Guzel, Institute of Psychiatry and Neurology, Warsaw; W. Kozubski (principal investigator), Medical Academy (Poznan), Poznan; H. Kwiecinski (principal investigator), Warsaw Medical University, Warsaw; K. Selmaj (principal investigator), Katedra i Klinika Neurologii Akademii, Lodz; Z. Stelmasiak (principal investigator), Katedra i Klinika Neurologii, Lublin; A. Szczudlik (principal investigator), Klinika Neurologii, Krakow; Russia: A. Boyko (principal investigator), Moscow MS Center, Moscow City Hospital 11, Moscow; E.I. Gusev (principal investigator), Russian State Medical University, Moscow; A. Skoromets (principal investigator), St.
Petersburg State Pavlov Medical, St. Petersburg; I. Stolyarov (principal investigator), Institute of the Human Brain, St. Petersburg; N. Yakhno (principal investigator), Moscow City Hospital 61, Moscow; I. Zavalishin (principal investigator), Neurology Research Institute, Moscow; United Kingdom: A.J. Coles (principal investigator), D.A.S. Compston (principal investigator), J. Shawcross, J. Jones, A.L. Cox, Addenbrooke's Hospital, Cambridge; United States: A. Bass (principal investigator), D. Wenzel, Neurology Center of San Antonio, San Antonio, TX; V. Ethical Of College! Biton (principal investigator), Clinical Trials, Little Rock, AR; M. Cascione (principal investigator), Axion Clinical Research of Florida, Tampa; B. Cleeremans (principal investigator), NervePro Research, Irvine, CA; J. Cooper (principal investigator), East Bay Physicians Medical Group, Berkeley, CA; P.K. Coyle (principal investigator), D. Madigan, SUNY at Stony Brook, Stony Brook, NY; B. Man Wedding Speech Examples! Cutler (principal investigator), Cancer Research Network, Plantation, FL; E.J. Fox (principal investigator), L. Mayer, R. Tyer, Central Texas Neurology Consultants, Round Rock; S. Gazda (principal investigator), Integra Clinical Research, San Antonio, TX; S. Glyman (principal investigator), Nevada Neurological Consultants, Henderson; A. Gupta (principal investigator), Fort Wayne Neurological Center, Fort Wayne, IN; J. Harney (principal investigator), Dallas Neurological Associates, Richardson, TX; G. Hutton (principal investigator), Baylor College of Medicine, Houston, TX; D. Jacobs (principal investigator), Neurological Services of Orlando, University of Central Florida College of Medicine, Orlando; O. Khan (principal investigator), R. Lisak, A. Tselis, Wayne State University School of Medicine, Detroit; J. Klapper (principal investigator), Colorado Neurology and mind develop, Headache Center, Denver; J. Liss (principal investigator), Medical Research and Health Education, Columbus, GA; D. Meyer (principal investigator), All-Trials Clinical Research, Winston-Salem, NC; A. Rae-Grant (principal investigator), Lehigh Valley Hospital Neurosciences, Allentown, PA; H. Rossman (principal investigator), W. Boudouris, M. Belkin, R. Pierce, Michigan Institute for Neurological Disorders, Farmington; W. Royal (principal investigator), University of Maryland, Baltimore; R. Shubin (principal investigator), D. Sider, Neuro-Therapeutics, Pasadena, CA; M. Stein (principal investigator), MS Service, Walnut Creek, CA; B. Best Speech Examples! Steingo (principal investigator), Neurological Associates, Pompano Beach, FL; H. Sullivan (principal investigator), Michigan Medical, Grand Rapids; C. Twyman (principal investigator), Associates in Neurology, Lexington, KY; R. Webb (principal investigator), Neurological Associates of Tulsa, Tulsa, OK; B. Weinshenker (principal investigator), B.M.
Keegan, D. Rauchwarter, Mayo Clinic, Rochester, MN; D. Wingerchuk (principal investigator), J. Carter, Mayo Clinic Arizona, Scottsdale; S. Wray (principal investigator), Knoxville, TN; D. Wynn (principal investigator), N. Allen, C. Nagar, D. O'Brien, Consultants in Neurology, Northbrook IL. MRI Central Reading Center: J. Paskavitz, Perceptive Informatics, Waltham, MA; P. Schaefer, Massachusetts General Hospital, Boston. On Hoping! Thyroid Advisory Panel: L. DeGroot, Brown University, Providence RI; W. Valente, University of Maryland School of examples, Medicine, Baltimore. Immune Thrombocytopenic Purpura Advisory Panel: D. Beardsley, Yale University School of Medicine, New Haven, CT; J. Bussel, Weill Cornell Medical College of Cornell University, New York; D. Cines, University of Pennsylvania, Philadelphia; M. Goldberg, Genzyme, Cambridge, MA; R. MacMillan, Scripps Cancer Center, La Jolla, CA; D. Definition Stigma! Scadden, Massachusetts General Hospital, Boston. Independent Statisticians: R.B. D'Agostino, M. Pencina, Boston University, Boston. Study Manager: G. Gonzales, Genzyme. Scientific Advisers: H. Waldmann, G. Hale, University of Oxford, Oxford, United Kingdom.
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Terri M. Mind Develop! Laufer, Gregory F. Wu. . Speech Examples! (2009) Treating MS: getting to principles in psychology, know the two birds in the bush. Journal of Clinical Investigation . Joanne L. Jones, Chia-Ling Phuah, Amanda L. Cox, Sara A. Thompson, Maria Ban, Jacqueline Shawcross, Amie Walton, Stephen J. Sawcer, Alastair Compston, Alasdair J. Coles. . (2009) IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H). Journal of Clinical Investigation . M. Best Speech! C. Dalakas, G. Rakocevic, J. Schmidt, M. Salajegheh, B. McElroy, M. O. Harris-Love, J. A. Shrader, E. Definition Stigma! W. Levy, J. Best Man Wedding Examples! Dambrosia, R. L. Kampen, D. A. Bruno, A. On Hoping In "Flowers! D. Kirk. . (2009) Effect of Alemtuzumab (CAMPATH 1-H) in patients with inclusion-body myositis. Brain 132 , 1536-1544. Man Wedding! N. Emilia (othello)! Gillain, A. Fumal, C. Neve, J.-M. Minon, A. Man Wedding! Maertens de Noordhout. . Mind Develop! (2009) Interpretation de l’index IgG et du diagramme de Reiber par Protis 2 dans les maladies inflammatoires du systeme nerveux central.
Immuno-analyse Biologie Specialisee 24 , 135-147. Lars Fugger, Manuel A. Man Wedding! Friese, John I. Bell. . (2009) From genes to function: the next challenge to understanding multiple sclerosis. Nature Reviews Immunology 9 , 408-417. Martin Stangel. . Principles! (2009) Multiple sclerosis: Hematopoietic stem cell transplantation: hope and hype. Best Examples! Nature Reviews Neurology 5 , 300-302.
Paul S Giacomini, Peter J Darlington, Amit Bar-Or. . (2009) Emerging multiple sclerosis disease-modifying therapies. Current Opinion in Neurology 22 , 226-232. Marco Salvetti, Gavin Giovannoni, Francesca Aloisi. . (2009) Epstein–Barr virus and multiple sclerosis. Current Opinion in Neurology 22 , 201-206. Bert A. Fisher And Paykel Healthcare! ‘t Hart, Rogier Q. Man Wedding! Hintzen, Jon D. Laman. . (2009) Multiple sclerosis – a response-to-damage model. Trends in Molecular Medicine 15 :6, 235-244. On Hoping In "Flowers! Krupa Pandey, Fred D. Lublin. . (2009) Clinically isolated syndrome and multiple sclerosis: Rethinking the arsenal.
Current Treatment Options in Neurology 11 , 193-202. Man Wedding Speech! John W. Rose, John F. Foley, Noel G. Carlson. . (2009) Monoclonal antibody treatments for multiple sclerosis. Current Treatment Options in Neurology 11 , 211-220. For Intelligence For Algernon"! J Ludovic Croxford, Takashi Yamamura. . (2009) Back to the future for man wedding examples multiple sclerosis therapy: focus on current and emerging disease-modifying therapeutic strategies. Immunotherapy 1 :3, 403-423.
Stephen P Cobbold. . Ethical Of College Recruiting Essay! (2009) Future therapeutics for the induction of peripheral immune tolerance in autoimmune disease and organ transplantation. Immunotherapy 1 :3, 447-460. C. Warnke, B.C. Kieseier, U. Zettl, H-P. Hartung. . (2009) Alemtuzumab als neue Therapieoption der Multiplen Sklerose. Der Nervenarzt 80 , 468-474.
A. A. Pace, J. P. Man Wedding Speech Examples! Zajicek. . (2009) Melanoma following treatment with alemtuzumab for multiple sclerosis. European Journal of Neurology 16 :10.1111/ene.2009.16.issue-4, e70-e71. Emilia! Joseph R. Man Wedding Speech! Berger, Sidney Houff. . (2009) Opportunistic infections and other risks with newer multiple sclerosis therapies. Annals of Neurology 65 :10.1002/ana.v65:4, 367-377. (2009) SEP : nouvel ACM, efficace mais toxique. Revue Francophone des Laboratoires 2009 :411, 21.
Howard L. Weiner. . (2009) The challenge of multiple sclerosis: How do we cure a chronic heterogeneous disease?. Annals of fisher and paykel healthcare, Neurology 65 :10.1002/ana.v65:3, 239-248. Best! Gianluigi Mancardi. . (2009) Further data on autologous haemopoietic stem cell transplantation in multiple sclerosis. The Lancet Neurology 8 , 219-221. Patricia K Coyle. . (2009) Existing therapies for multiple sclerosis offer proven efficacy and safety. Current Opinion in healthcare, Neurology 22 , S4-S9. Richard K Burt, Yvonne Loh, Bruce Cohen, Dusan Stefosky, Roumen Balabanov, George Katsamakis, Yu Oyama, Eric J Russell, Jessica Stern, Paolo Muraro, John Rose, Alessandro Testori, Jurate Bucha, Borko Jovanovic, Francesca Milanetti, Jan Storek, Julio C Voltarelli, William H Burns. Speech Examples! . (othello)! (2009) Autologous non-myeloablative haemopoietic stem cell transplantation in best man wedding speech, relapsing-remitting multiple sclerosis: a phase I/II study. The Lancet Neurology 8 , 244-253. Aimee Pasqua Borazanci, Meghan K Harris, Robert N Schwendimann, Eduardo Gonzalez-Toledo, Amir H Maghzi, Masoud Etemadifar, Nadejda Alekseeva, James Pinkston, Roger E Kelley, Alireza Minagar. . (2009) Multiple sclerosis: clinical features, pathophysiology, neuroimaging and future therapies.
Future Neurology 4 :2, 229-246. (2009) Alemtuzumab limits multiple sclerosis but is associated with autoimmune complications. Nature Clinical Practice Neurology 5 , 4-4. Henry F McFarland. Essay On Hoping For Intelligence! . (2009) Alemtuzumab versus interferon beta-1a: implications for pathology and trial design. The Lancet Neurology 8 , 26-28. Randy Osborne. . (2009) Buzz around Campath proof-of-concept trial in MS. Nature Biotechnology 27 , 6-8. Heather J MacLean, Mark S Freedman. . (2009) Multiple sclerosis: following clues from cause to cure.
The Lancet Neurology 8 , 6-8. Matthew Kaufman, Sewanti A. Limaye, Nancy Driscoll, Christina Johnson, Angelica Caramanica, Yehuda Lebowicz, Dilip Patel, Nina Kohn, Kanti Rai. . Man Wedding Speech Examples! (2009) A combination of rituximab, cyclophosphamide and dexamethasone effectively treats immune cytopenias of chronic lymphocytic leukemia. Leukemia Lymphoma 50 , 892-899. For Intelligence In "Flowers For Algernon"! (2008) News in brief. Nature Medicine 14 , 1296-1297. Hauser , Stephen L. , . . (2008) Multiple Lessons for best man wedding speech examples Multiple Sclerosis.
New England Journal of Medicine 359 :17, 1838-1841.
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college eton resume YOU ARE VISITING THE PAGES OF THE U.K. N.R.A. HISTORIC ARMS RESOURCE CENTRE - MINIATURE CALIBRE RIFLES RESEARCH SITE - COPYRIGHT 1997- Click text or images below to view the various devices:
The SUB-TARGET MACHINE by the Wilkinson Sword Co. Below, the front pages of the Wilkinson Sword company's brochure of 1906 are reproduced. The device was the invention of an American - Mr. Henry Havelock Cummings of Boston, Mass., and built under licence in Britain at a time when Lord Roberts and other senior military men and politicians were putting into force a plan to render every male subject of the best speech examples, United Kingdom well versed in emilia (othello), the art of rifle shooting . This device is one of many which evolved to that end, not least of which was the setting up of the Society of best examples, Miniature Rifle Clubs. A.J. Comber, a Bisley King's Prize winner, is seen demonstrating the fisher and paykel, machine. The continuing remainder of the brochure's text is here reproduced: and consequently more rapidly corrected.
It is an instrument that records not only the actual result of a shot made at a mark, but the position of the Rifle during the process of aiming and at the moment of pulling the trigger, and thus demonstrating to the instructor the reasons for man wedding speech examples a hit or miss on the objective target. DIFFICULTIES OF MARKSMANSHIP. If Rifles were constructed as cannon are, for firing from a rest, many of the difficulties of fisher, marksmanship would disappear, because the best man wedding examples, rest at moment of aiming would hold the weapon absolutely steady, but a man with a Rifle cannot do this. In watching a good shot firing in the prone position, the barrel looks to fisher healthcare be quite still. But the best speech, marksman, holding a barely visible bull balanced on his fore-sight, is aware of more or less movement of the Rifle, and fisher and paykel healthcare knows how very slight a tremor will spoil his shot.
The novice very soon knows that too, but it comes with something of a shock to him to realise that tremor in his case is frequently represented by a wobble that may send the bullet to the edge of the target, over best speech, it, or anywhere round the (othello), face of the clock. PRINCIPLE OF SUB-target RIFLE. The principle of the Sub-target Rifle can be explained without a great deal of difficulty. Speech? In the illustrations it will be seen that a strong and heavy upright pillar supports, in any position required—standing, kneeling, or prone—the head. Above this. head is emilia, placed a delicate rod with a universal movement. At the forward extremity of the rod a needle point is fixed, and in a little grooved frame a target, about the size of a visiting card, is placed.
That is the Sub-target. The objective target is an ordinary one, placed preferably at 30 yards range, which is ringed to proper dimensions to appear the size of a standard target at any desired distance, say 200 or 500 yards. ORDINARY RIFLE IS USED - PERFECT FREEDOM OF MOVEMENT. An ordinary Rifle is speech, used for taking aim, and it is so ingeniously connected to the machine that there is no point of rest. The weight or the parts attaching the Rifle to the instrument is ethical principles, exactly balanced by the weight of the counterpoised ball seen in the illustrations, so that the marksman has only the weight of the Rifle to support, aud sufficient freedom of movement is given to man wedding speech allow of the Rifle being aimed off the ethical, target in any direction. The rifle connections are mounted on ball bearings, and best speech are connected to (othello) the steel rod which is swung on best, a four-point universal joint on tlie head of the machine. This rod moves coincidentally with the line of emilia (othello), sight along the man wedding, rifle barrel, and Essay in "Flowers For Algernon" transfers its gyrations, through an ingenious ball differential movement, to the needle. The relation of the objective target 20 yards away and the Sub-target on the. machine itself is determined by calculation of angles, but to best man wedding speech allow for variations in eyesight, or constant peculiarities of aiming, the head may be adjusted both vertically and horizontally by means of screws. These variations from the normal are- recorded on definition stigma, two dials, one corresponding to degrees of elevation on the back sight, and the other to lateral movement for speech examples windage. In using the machine, the marksman may first sight the Rifle with the radial rod locked, so that if any adjustments are necessary to get the sights properly aligned on the bull's eye these adjustments can be made.
The radial rod is then released, the Rifle cocked, and the marksman aims at the objective target and pulls the trigger. SLIGHTEST MOVEMENT INDICATED. On the tiny Sub-target every movement of the emilia, Rifle is indicated by the delicate pointer until at the pulling of the trigger the card, darts forward and takes the impress of the needle, exactly corresponding to the aim on the objective target. BUT THEY CANNOT SHOOT. In many of the public schools of the country, military organisations exist and military tactics are taught.
The boys march. well and go through the man wedding speech examples, manual of arms without a hitch, but they cannot shoot. And Paykel Healthcare? It is considered unsafe to allow the schoolboys to best speech examples practise shooting with loaded Rifles as some serious accidents have happened. It is a matter of Essay for Intelligence For Algernon", much interest and a cause for congratulation that the schools are becoming interested in man wedding speech, the Sub-target Rifle—which is safe as it is used withou t ammunition—and are beginning to of College Essay adopt it for instructing the boys in marksmanship. Eton was the first College in man wedding examples, England to adopt this apparatus. This remarkable machine, it will be understood, requires no attention beyond the preliminary setting, as the mind develop, little Sub-target is electrically actuated. There is a dry battery in the pillar, and the head contains a powerful magnet, the best speech, armature of which impels the target on to the fisher healthcare, needle when the circuit is closed. BLANK CAN BE USED. This closing of the circuit results from pulling the trigger. Best Man Wedding Examples? There can be used, if desired, a blank cartridge in the Rifle, but as the apparatus is designed for aiming, not for shooting, this serves no purpose beyond that of accustoming the user. to the noise of the discharge.
It has also been found excellent training to get men used to the explosion by Ethical Considerations Recruiting mixing blank cartridges with empty shells, so that the marksman must always anticipate the explosion although it only occasionally occurs. WINDAGE ALLOWANCE CAN BE TAUGHT. Windage allowance can be taught, by the instructor purposely deflecting the apparatus from its normal direction, with the aid of a lateral adjustment lever. Magazine pratice can be carried out on the Sub-target Rifle. Any kind of target can be used except the running man, and the reports prove that the instrument is capable of being used. to great advantage with the best, disappearing target, as well as for definition stigma snap shooting.
Some of the places where the Apparatus has been installed and can be inspected. ( as at 1906 !) Marine Barracks, Chatham. Royal Military College, Camberley. Royal Military Academy, Woolwich. Guards' Depot, Caterham. Royal Horse Guards.
11 th Hussars—Curragh. King's Dragoon Guards. 7th Dragoon Guards. 1st Battalion Grenadier Guards. 1st Battalion Coldstream Guards. 1st ,, Scots Guards. 2nd Bn. Lincoln Regiment. 1 st , Royal Welsh Fusiliers. 2nd , Black Watch—India.
2nd , Northumberland Fusiliers. 1st , Norti Staffordshire Regiment. 1st Bn. West Riding Regiment—Bombay. 3rd , Northamptonshire Regiment. 1st , South Wales Borderers. 1st , Yorks Light Infantry—Gibraltar.
1st , Rifle Brigade—Malta. 1st , Royal Irish Rifles—India. 1st , Seaforth Highlanders. Somersetshire Light Infantry. Scottish Horse—Blair Athol. Middlesex Imperial Yeomanry. Bombay and Baroda Railway Volunteers. Malay States Guides. East London R.E.
Volunteers. 3rd V.B. Royal Fusiliers. 1st V.B. York and best man wedding speech Lane. Regiment. The Stock Exchange Rifle Club. St. In Psychology? Anne's Asylum, Redhill. Sussex County Cricket Club. rders for Machines have also teen received on.
H.I.M. The Sultan of Turkey. The Roumanian Government. The Maharajah of best man wedding, Gwalior. Kaid Sir Harry Maclean for the Sultan. The Duke of Manchester. The Countess of Dysart. The Marquis of Tullibardine. The Emperor of Abyssinia.
Messrs. Walter Locke Co., Calcutta. At 1024 x 768 pixel resolution on a 19 screen, these TARGETS should be shown at actual size. Copies of Letters from. KING'S PRIZE WINNERS, 1904-1905. THE SUB-TARGET GUN COMPANY. GENTLEMEN,—It affords me pleasure to testify to the value of the Sub-target Rifle, one of which was set up on the steamer, and was in constant use by the members of the Considerations of College, Canadian Rifle Team during the voyage from Montreal to Liverpool, and. afterwards at the Canadian Headquarters at Bisley, where it was in best speech, almost constant use. I consider it of great value in the. instruction of Ethical of College Recruiting Essay, recruits in speech, holding and sighting, and also in detecting and correcting the individual errors of eyesight.
For. practice in trigger-pulling it is of great advantage, even to the experienced marksman. My daily use of the Machine at Bisley, was, I feel, of advantage to definition me in my work on the ranges, where I was winner. of the King's Prize. Man Wedding Speech Examples? Very truly yours, (Signed) S. J. PERRY, Gold Medalist, 1904. BISLEY CAMP, SURREY. THK SUB-target GUN COMPANY. GENTLEMEN,—Having used the Sub-target Rifle frequently during the N.R.A. Definition Stigma? Meeting at Bisley, just closed, I am pleased. to testify to its value in promoting steadiness in holding, sighting and trigger-pulling, To the best examples, recruit it must be especially useful in these respects, as the tell-tale needle points out every fault of the man, I believe that its general adoption and use by the Army, Navy, Volunteers, Rifle Clubs and in the Public Schools would go a long way towards making a nation of reliable shots for Imperial Defence.
Very truly yours. (Signed) ALF. Recruiting Essay? J. COMBER. Gold Medalist, 1905. Copy of best man wedding speech examples, Report received from. THE MUSKETRY CAMP AT PIRBRIGHT. Referring to your letter of the 15th inst., I have prepared a table showing the various figures of merit obtained by and paykel healthcare parties of. recruits that have been exercised by me this year. I have another party here now, and I think they will do as well as the 3rd party on my table did. The figures, I think, show a wonderful improvement in their shooting, which must largely be attributed to ihe Sub-target Rifle. At first when I had the Machine I was very much afraid of it being damaged if used without an instructor or responsible person who understood it being present, but since I spoke to Mr.
Stratton on this point I have let all my men use it as they like, and it is seldom idle for best a second from morning till night. It tends to a great extent to make musketry training more interesting, as it is definition, a very interesting instrument to use, and to man wedding a large extent the use of Essay for Intelligence in "Flowers For Algernon", it here by my men has rendered the tedious musketry parades no longer necessary. If I had another Machine it would be also used continuously, as there is great keeness to best man wedding speech practice with the present one. Several men when they are practicing with the Machine won't give it up till they have shot a good card with it. I make a point of making every man practice with it daily under the (othello), tuition of his own instructor. As I have about 42 men down here, and allow them only five minutes each, it takes three and a half hours to get them all through, and best speech when three hours are spent on the range, it does not leave much spare time. The ease with which a recruit can be taught to shoot well on it alone is astonishing. In the cases of recruits that develop the common faults called bobbing and jerking the trigger, these faults can. all be overcome with practice on the Sub-target Rifle. If recruits are taught shooting on this instrument from the.
beginning they can't help becoming good shots. Copy of Preliminary Report on SUB-target RIFLE, Whale Island Staff. This instrument has now been under trial for three months, and has been constantly used during this period for training the. boys of H.M.S. St. Vincent. A statement of the results so far obtained is attached.
The Machine is still in good order, and in daily use, the only parts that have given trouble being two of the electric contacts, these having been put in Ethical Recruiting Essay, order, and slightly modified, the whole arrangement is now found to be very reliable. When the short rifle is adopted (ed: the man wedding, S.M.L.E.) , the Sub-target Rifle will be a necessity, in order that the correct adjustment of the sight may be properly taught. No other system can do this. I consider the Machine of very great value for fisher healthcare teaching new entries and bad shots, and to fire properly. Best Man Wedding Speech? It is of especial value in showing up any individual who pulls or bobs. It is particularly noteworthy that the superiority of the training given by ethical principles in psychology the Machine is best man wedding speech examples, shown in the vanishing target practice and snap-shooting, The comparison given is not quite fair to the Machine, as some boys not trained with it were found to be extremely bad and unable to hit a target. Emilia (othello)? Such boys were sent back, and were practised at the Machine, where their faults were invariably noticed and corrected.
Blank ammunition has been used in examples, conjunction with the mind develop, Machine. AVERAGES OF 100 BOYS' FIRINGS. Copy of Letter from. COMMANDER H. CHRISTIAN, R.N. dated 20th June, 190. DEAR SIRS,—We have had the Sub-target Rifle in use here for a good number of months now. Its value as a teacher of the art of rifle shooting is undoubted, and superior to anything else yet invented—bar with unlimited practice with the actual rifle, of course. The results we have produced with the St. Vincent boys are quite extraordinary, and I should imagine that the best, Army will go for it for all they are worth directly they see it at work. (Signed) HAROLD CHRISTIAN,
I HE WILKINSON SWORD COMPANY, LIMITED. Copy of mind develop, Further Report received from. SENIOR STAFF OFFICER, Whale Island, dated 19th June, 1905. We do not teach moving target with Sub-target Rifle, only a form of vanishing or snap-shooting target, this by fitting a. shutter over best speech, a special target, and working it by a string and weight. Considerations Of College? As the examples, boy may not come to the present till he sees. his target, it does not matter much if he knows pretty well where it is. We leave the definition stigma, target in best speech examples, sight for four or five seconds, and. have a special target and sub-TARGETS which we make, and so reproduce our range conditions as nearly as possible. The. Machine is working very well indeed, and the boys do extraordinarily well after using it.
The last lot beat a class of old. hands, and good old hands at that, that is to say, men who were doing advanced course of gunnery to (othello) better themselves, and so were keen. Copy of Letter from. ETON COLLEGE, dated 22nd June, 1905. ORDERLY ROOM, ETON COLLEGE. DEAR SIR,—I regret I am unable as yet to make a full report on the Sub-target Rifle Machine, owing to the short time. it has been in our possession. The Shooting VIII. and those who are qualifying have been exercised ; they show the greatest. keenness and best interest in the practice.
The Second Squad of Recruits were exercised this morning for fisher and paykel healthcare the first time—they will. have seven more half hours before going on the range to fire their course. I will then let you know the best man wedding, result, comparing the. squad trained with the S.T.R. and a squad trained with the Morris Tube. I have tested the Machine in every way myself, and find it exceedingly accurate. It shows every movement of the rifle and. every fault made by the shooter, such as bobbing, pulling, jerking, taking too much or too little foresight.
On wet days it. will be invaluable. I remain, Yours truly, G. A. Fisher And Paykel? SOLTAU-SYMONS.CAPT. The target frames are reminiscent of those used nearly forty years later for the Swift Training Rifle. E.J.D. Newitt wrote of the machine, in some detail, in best, his 1906 book The Citizen Rifleman. He evidently saw much advantage in on Hoping in "Flowers, the system. THE SUB-TARGET GUN MACHINE. Another phase in examples, the development of appliances for teaching marksmanship is one in which the rifle is used without ammunition. The office performed by ammunition in target practice is to indicate the accuracy of aim at emilia the instant of discharge, which its projectile does within the limits of its own and the rifle's accuracy.
In the sub-target gun machine the same office is performed by a pointer, which punctures a small hole in a miniature target attached to the machine, and this method possesses many advantages. In the first place, the cost of ammunition is avoided, whilst no range is required; and in the second, there are so many circumstances other than incorrectness of aim which cause a misplaced hit, that the position is not always a reliable guide for enabling the instructor to diagnose the cause. Inaccuracy of rifle and ammunition will falsify the most perfect aim and discharge, and when even this is beyond suspiciond, unsteady hold and discharge, the most frequent of causes are not observable whilst actually taking place. Consequently the most careful instructor may easily misconceive the best, true cause and Essay for Intelligence in "Flowers lead his pupil farther astray by best speech his instructions for correcting it. When using the rifle in conjunction withth the sub-target gun machine every movement of the rifle whilst aiming at mind develop the target is best man wedding speech, duplicated on a smaller scale by the pointer, which moves over the face of the sub-target immediately under the instructor's eye. When the trigger is pulled the sub-target instantaneously responds by jumplng forward and, in on Hoping for Intelligence For Algernon", coming sharply in contact with the pointer, receives an, indelible record, which exactly corresponds with the position the hit would have occupied had the rifle been actually fired with a cartridge. Throughout the best man wedding speech, act of aiming the instructor has been able to observe every movement, and can say with certainty whether the aim was correct or otherwise, or if his pupil pulled off badly. It has been found very difficult to Ethical Recruiting produce an illustration which fully explains the machine and its operations. The rifle is best man wedding speech examples, attached by freely moving pivots to a cradle, which is in turn pivoted by a universal joint to the pointer. A convenient stand supports the whole mechanism.
A pair of electric contacts close a circuit when the trigger is pulled and actuate the sub-target, The wei^ of the cradle, which would otherwise be added to the rifle, is counterpoised by the weight seen at stigma the end of its supporting arm. The rifle is held and man wedding speech examples aimed at an ordinary target placed at adistance, and all its movements are conveyed to ethical the pointer through the universal joint. Immediately in front of the pointer is a target having exactly the same ratio of size to the target aimed at with the man wedding, rifle as the movements of the pointer have to the movements of the rifle. It would be difficult to enumerate the many possibilities of this machine. Ethical Considerations Of College? For instruction in the first principles of aiming, holding, and discharge it is best man wedding speech examples, invaluable, and may be used in barracks, schools, and institutes by day, or in artificial light, thus prolonging the hours during which instruction may be given. On the range, when the shooter is performing wildly, an adjournment to the sub-target gun machine will generally determine the cause before much costly ammunition is wasted, and after a few minutes' instruction he may resume firing in the ordinary way with increased confidence and improved results.
Even the experienced marksman may sometimes learn that the cause of principles, that unaccountable outer might more reasonably have been attributed to a bad pull-off than a change of wind. Regular contests can be held on the machine, and afford the most useful practice to marksman and novice alike. Best Speech Examples? The entire absence of any element of definition stigma, danger renders it particularly suitable for use in schools; indeed, it is already largely so used in the United States of America, where the annual inter-school championship contest is an event to which great public interest attaches. Its merits are fully recognised in examples, England, and machines are now in use at the School of Musketry at Hythe, the Ethical, Royal Military Academy, Woolwich, in the Royal Navy, and at the headquarters of many Regular and Volunteer. regiments.
The cost of £50 is an item against which may be set off the cost of ammunition, which would otherwise be necessary, and in man wedding examples, some cases the cost of erecting and equipping a range. The greatest credit is due to mind develop Mr. H. H. Man Wedding Examples? Cummings, the inventor, whose ingenuity has produced a device which overcomes many of the technical difficulties incidental to the teaching of marksmanship, and minimises, most of Ethical Considerations Recruiting, those caused by the necessity, hitherto, of using ranges and ammunition, which may now be postponed to a later stage, when the pupil has acquired sufficient skill in the first principles to study the factors introduced by his ammunition, without wasting it. Below; images from the pamphlet The Sub-target Gun Machine firstly in use Standing and Kneeling. We are most grateful to have been been passed images of a postcard sent to the American N.R.A. in April 1908. The postcard depicts the use of the machine during the. SCHOOL BOY RIFLE SHOOTING TOURNAMENT. under the auspices of the Capitol Rifle and Revolver Association.
and the National Rifle Association of America. WASHINGTON April 7-25 1908 Postcard images kindly provided by Brian Woodall of the N.S.R.A. of Great Britain. The S.M.L.E. mounted Sub-target device by the Wilkinson Sword Co. The company also manufactured their own device which clamped to the nose-cap of an S.M.L.E. rifle. Little is known of man wedding, this piece of equipment. The example here is held in the Ministry of Defence Enfield Pattern Room collection. ( images by their courtesy).
It operates on a principle similar to stigma that of the sub-target unit for the 1896 Swedish Mauser rifle illustrated below. Any further information on this device would be most gratefully received; please email the speech examples, editor. The HOLLIFIELD COMBINATION RIFLE ROD SUB-target DEVICE. often known as the Hollifield DOTTER Manufactured by the Hollifield target Practrice Rod Company. of Middletown, New York. General George Wingate patented a basic device of this nature in the mid to late 1870s. The design was several times modified through the years, no doubt due both to improvements necessary and to permit use in various rifles, and finally ended production in the hands of the Hollifield company in principles, 1927. The kit was supplied with two 'rods', each in the form of a flanged brass tube housing a spring-loaded 2 mm diameter hardened steel rod with point ground onto its 4mm diameter knurled muzzle end. One of these tubes was the full length of the barrel and chamber and the other only the length of the barrel rifling and leed.
The second, shorter unit, required the dummy cartridge to best speech be chambered for the striker of the rifle's bolt to hit the after end and project the rod onto the target at for Intelligence For Algernon" a distance of around six inches from the rifle muzzle. The longer unit could be used without the dummy cartridge and was intended for basic, single shot, practice. The cartridge option permitted more realistic bolt actioning and the use of a clip for either basic loading practice or even a five round 'rapid' discipline. The tube is simply held in the rifle barrel by dint of a one inch long split section near, the best man wedding speech, muzzle, which is sprung open slightly to maintain pressure inside the Ethical Considerations Recruiting, bore. There is no other location; the man wedding examples, instructions advise the gentle opening up of this split should the tube become slack in the barrel! The TARGETS were provided in a booklet with perforated, tear out, page sections. These were for 50 yard or 100 yard range representations.
The upper target is the aiming mark, and on Hoping for Intelligence For Algernon" the lower one the impact point for the striking rod. The height between is one and one-sixteenth inches, being the height between the sight-line and the rifle bore. Left: the 50 yard TARGETS ; approx. actual size. Below; the 100 yard TARGETS , also approximately actual size. Below, the left image is man wedding examples, of what is simply a representative spotting target for instruction. Mind Develop? It is pasted inside the box lid and speech has a handwritten instruction that it is not to be fired upon! Presumably written shortly after someone had! The other two images illustrate how the box can be hung on a wall or board at any suitable height for emilia prone, kneeling or standing practice.
The target carrying block is of hard rubber and can be slid up and down, within the box, for fine adjustment. The serrated section above the TARGETS is for windage assessment where required. The two instruction sheets, showing their age, are copied below. One is pasted into the bottom of the best speech examples, box, and the latter one is pasted to the inside of the hinged wooden lid. Below: the key for the kit of parts as applied to (othello) the U.S. Speech? Springfield Model 1903 - 1906 rifle. Two practice rod devices, equivalent to ethical the Hollifield Dotter, were marketed by A.G. Best Man Wedding Speech Examples? Parker and emilia (othello) Parker-Hale between the two World Wars.
The first, of best man wedding, Canadian manufacture, was advertised here in about 1925, around two years before the and paykel, Hollifield unit went out of production. Below is their advertisement for the same unit - under Parker-Hale's name - still going eight years later in 1933. The advertisement now carries what appears to be a facsimile of the note of recommendation made by Lord Roberts ( founding president of the Society of Miniature Rifle Clubs, who died in 1914 whilst visiting his troops on the Western Front), presumably part of an internal memo within the speech examples, military, later passed to Messrs. Parker or Hale or the manufacturers in Canada. The handwriting can be compared with that of a letter written by fisher healthcare Roberts to best examples Mr. Hyam regarding the ethical principles in psychology, setting up of the S.M.R.C. It is amusing to best man wedding note that, even without prior knowledge of such patented equipment as these practice rods, man's ingenuity continually provides for their re-invention - even informally. The following was observed on a forum in which the Hollifield Dotter was under discussion. I never realized there was a commercial application of this device.
While shooting competively in the Navy, I used to take a common wood pencil and place two bands of Ethical, 1/2 masking tape around the best, pencil until the pencil and tape was a sliding fit in the bore of the pistol. Then take a sheet of paper, can be very small, and make a dot about 1/32 in diameter in the center. Tape the paper to in psychology the wall the same distance from the floor as the pistol muzzle in a natural stance you use. Move toward the target until the muzzle is about 1 from the target. Place the pencil in man wedding, the bore and cock the hammer, in my case a 1911 A1 Navy 45. Tip the pistol muzzle up to seat the eraser end towards the firing pin. Now sight the on Hoping in "Flowers For Algernon", target as you would at a standard NRA 50 yd bull. Dry fire the best speech examples, shot and call the shot. The pencil will be propelled down the bore by fisher healthcare the firing pin strike. You will find the mark the pencil made to be where you called the shot if you are honest with yourself.
This practice works wonders for your marksmanship. THE CUMMINGS DOT RIFLE. Similar in basic design principle to the Swedish arrangement, this rifle has an equally complex sub-target apparatus fitted to the rear of the barrel over the receiver, instead of at the muzzle. Man Wedding Speech? It is understood that the fisher healthcare, modified cocking-piece, at the rear of the man wedding speech, bolt, is the drive point for the system. This rifle was manufactured, circa 1918, by the Cummings Gun Works of mind develop, Boston, Mass.
It is speech examples, constructed around the shortened stock of a Russian designed Mosin-Nagant rifle, presumably a matter of availability at a time when wartime U.S. service rifle production was under extreme pressure. Definition Stigma? The M1891 Mosin-Nagant was manufactured by both the Remington and Westinghouse companies, between 1915 and 1917, for the Imperial Russian and Kerensky Governments. More than a million-and-a-half were produced at Ilion and Springfield, and the government of the United States themselves purchased over a quarter-of-a-million for what is believed to have mainly been training use. Best? (figures from Smith's Book of Rifles) Should you not already have done so, please also view the page detailing.
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essay gary gilmore All rights reserved. Early in the morning of Wednesday July 21 1976 Gary Gilmore was arrested in Provo, Utah, on suspicion of the murder of a motel owner in Provo on the previous Tuesday evening, and of a gas station attendant, in man wedding speech nearby Orem, on Ethical of College Essay, the Monday night. At the time of the killings Gilmore was on parole from a twelve-year sentence for armed robbery, and was being harboured by relatives. He was effectively turned in by his cousin Brenda Nicol, who told him, by way of explanation: You commit a murder Monday, and best man wedding commit a murder Tuesday. I wasn't waiting for Wednesday to come around. In October of the stigma, same year Gilmore was tried, convicted, and best speech examples sentenced to in psychology death. Offered a choice as to the mode of execution, he opted to be shot. Both victims had been Mormon, and, in the opinion of his brother Mikal, Gary exercised his choice in man wedding speech knowing fulfillment of the Mormon doctrine of Blood Atonement. 1. The sentence was carried out mind develop, six months after the murders: on Monday January 17 1977, a few minutes after 8am local time, Gary Gilmore was executed by man wedding firing squad in a disused cannery in emilia (othello) Utah State prison.
It was the first judicial homicide in the United States for ten years, and it had not, from a legal point of view, been easy to organise. The date first set for the execution had been November 15 1976, and on November 1 Gilmore announced his intention not to appeal against his sentence. His refusal to man wedding examples appeal galvanised the American Civil Liberties Union and the National Association for ethical principles the Advancement of Colored People to make strenuous attempts to stop this execution, on behalf of the many prisoners on death row throughout the United States for whom it could be a fatal precedent. Several judicial Stays delayed the best examples, execution for two months, and the appeals continued until the end. Within ten minutes of the time scheduled for the execution, the ACLU--in extremis after a night of legal turmoil in which a Stay ordered in Salt Lake City by a Federal Court judge had been set aside by the Tenth Circuit Court in Denver--unsuccessfully petitioned the Supreme Court in Washington for a final Stay of execution. More than a dozen years before the Considerations of College Essay, Gilmore case, Truman Capote compared the system of best, appeals that pervades America jurisprudence . to a legalistic wheel of fortune, a game of chance . that the participants play interminably, first in the state courts, then through the Federal Courts until the ultimate tribunal is reached--the United States Supreme Court. But even defeat there does not signify if petitioner's counsel can discover or invent new grounds for appeal; usually they can, and so once more the fisher healthcare, wheel turns . Speech Examples. But at intervals the wheel does pause to declare a winner--or, though with increasing rarity, a loser. Fisher And Paykel Healthcare. 2. Gilmore's unwavering refusal to play the game put him in the paradoxical position of a defendant who apparently agreed with the prosecution. It consequently put a spoke in best man wedding speech examples the wheels of justice by jamming the usual process of argument and Ethical of College Recruiting counter-argument through which the adversarial discourse of the law sustains itself.
This denial of habitual procedure led to near panic in the legal institution, but the law came to its own rescue: the courts of Utah and the Federal Tenth Circuit Court between them restored some semblance of an adversarial context through which the untidy legal plot could be knocked into the shape of a judicial narrative. The appeals process exhausted itself at about the same time as the triggers were due to be squeezed, and, as if in best man wedding examples gracious acknowledgment to all concerned, the United States Supreme Court provided the closure that is the for Intelligence For Algernon", necessary constraint of all legal story-telling. Man Wedding. Gilmore had fought the fisher healthcare, law and best man wedding speech examples won, but he could only stigma win by losing, and so the law itself could reasonably claim victory too. Gilmore's paradoxical position of having to lose the game in order to win it, and his disturbance of the processes by which legal stories are produced, suggested imaginative spaces in which alternative stories about him could be told. Best Examples. In The Executioner's Song (which follows Gilmore from his release on parole in mind develop April 1976 to his execution nine months later), Norman Mailer gives shape to some alternative stories by exploiting the tension between legal and other ways of talking about Gary Mark Gilmore. The Executioner's Song , which Mailer calls a 'true life story', is on the cusp of legal and novelistic discourses. Speech. Its fictive methods play law and literature against each other. Ethical Principles In Psychology. As it draws out the stories which lie just beneath the surface of legal narrative--stories which the law suppresses because it apparently has no interest in best speech them--the novel amplifies that which the law would suppress or exclude. On Hoping For Algernon". And in these processes the novel challenges the authority of legal story-telling. On July 22 1976, the day after his arrest for murder, Gilmore made a private call (from the police station in Orem, to which he had been transferred) to best examples Brenda Nicol.
The call was important to Gilmore's trial, and also to The Executioner's Song , in which Mailer's first account of this call is economical and direct: Brenda said, 'Gary, you're going to go down hard this time. You're going to ride this one clear to the bottom.' He said, 'Man, how do you know I'm not innocent?' 'Gary, what's the matter with your head?' 'I don't know,' Gary said, 'I must have been insane.' Brenda asked, 'What about your mother?
What do you want me to tell her?' He was quiet for a while. Then he said, 'Tell her it's true.' Brenda said, 'Okay. Anything else?' 'Just tell her I love her.' The evident clarity of this conversation was muddied in the courtroom, where Gilmore's words came back to haunt both him and Brenda through her testimony at (othello) his trial. Her very presence at the Preliminary Hearing (the first stage of the trial) created misunderstanding, for Gilmore thought she was there to best speech see him, although she had in fact been called as a witness by and paykel the prosecution. She told of the phone call Gary made from the Orem Police Station, Mailer wrote. 'I asked him what he would like me to tell his mother,' Brenda had said on the stand. 'He said, I guess you can tell her it's true.' Mike Esplin [for the defence] tried to get Brenda to agree Gary meant it was true he had been charged with murder.
Brenda repeated her testimony and took no sides. Gary found that hard to forgive. Esplin intensifies the situation for Brenda by trying to pin her down to a particular interpretation of Gilmore's words, but she refuses to agree, and the refusal creates tension between her and Gilmore. The increasing complication of the man wedding speech examples, relationship between Gilmore and Brenda is For Algernon" rendered through the thickening of the narrative style, and is beautifully suggested by the final sentence. By expressing Brenda's unease about man wedding speech, Gilmore's response to her testimony, Gary found that hard to forgive tells us much as about Brenda's feelings as it does about Gilmore's; it subtly shifts the legal discourse of the courtroom exchange into an exploration of the relationship between the mind develop, cousins. The feelings of both are indirectly rendered through Brenda's apprehension about Gilmore's response, and Mailer's economical sentence moves freely between them. As a narrative device through which he can explore alternative dimensions of man wedding speech, meaning latent in but suppressed by legal discourse, such free indirect discourse is Mailer's most powerful counter-legal strategy. It enables him to take the reader away from the determinate jurisdiction of the court, and to bring other systems of value into play. 3. The gradual reworkings of the telephone conversation as testimony take increasing account of on Hoping in "Flowers, Brenda's feelings, and the legal interpretation of best speech examples, Gilmore's words becomes secondary to the more emotionally-charged issues of loyalty and responsibility.
Mailer progressively nudges Brenda's testimony into the meanings it has beyond the law, and as the conversation is transferred from the Essay on Hoping in "Flowers, police station to the court its imprecision bristles with the complexity of Gilmore's relationship with Brenda. Brenda Nicol's conscience, and best man wedding her sense of social responsibility, are significantly non-legal points of reference throughout The Executioner's Song , and emilia she was also one of the main sources of Mailer's information about Gilmore's life between his release from prison in April 1976 and his arrest three months later. Mailer must have learned about the phone call and the testimony from her. Best Man Wedding. As far as possible in The Executioner's Song Mailer presents Gilmore (whom he never met) in his own words as they were recorded or remembered, and reproduces them directly, as in this conversation. This method permits Mailer's Gilmore to speak from a number of positions to mind develop a number of audiences, whose responses or reactions are then used as a commentary or gloss on what Gilmore says. Such responses are usually given in the free indirect style described above, a narrative technique which indicates Mailer's access to the minds of man wedding speech, his sources and Essay for Intelligence which is used to best man wedding speech examples establish relationship between them and Gilmore. As Gilmore's words are registered through the particular and individual perspectives of those who heard him, this technique creates an audience-effect. It enables Mailer to transcend the legal discourse on which so much of the Recruiting, novel is based, and the meanings that were closed off in court are opened and explored, in the novel, on levels beyond the law.
This is what happens both to Gilmore's words to Brenda, and to Brenda's testimony, and these exchanges between them, direct and indirect, richly illustrate the sensitivity of the novel's discourse to the extra-legal levels on which the language of the man wedding, law operates. Unlike Capote's In Cold Blood, Mailer could claim no personal relationship with his subject, and he makes no attempt to mount a case for him. But Mailer swerves most radically from his precursor in (othello) that he claims no access to the mind of his subject beyond what he is recorded as having written or said: The Executioner's Song uses no free indirect discourse for Gilmore himself, whose meanings are interpreted or rendered through what I have called the audience-effects of his words. This method establishes Gary Gilmore less as a continuous personality than as an enigma, whose multiple meanings are simultaneously increased and delimited by the urgency and intensity of others' responses to him. Like Capote, Mailer criticizes the ways and means by which a trial narrative was produced. Best Man Wedding Speech Examples. But the methods of Mailer's 'true life story' are more radical than those of Capote's 'non-fiction novel'. Emilia (othello). For by opening the ambiguous meanings of testimony and evidence into fictional possibilities the novel challenges the hermeneutics of the law, and man wedding speech through the epistemological insecurity afforded by mind develop its free indirect discourse it suggests levels of meaning unacknowledged by legal institutions. Brook Thomas has recently argued that literature, like equity, exists in supplemental relation to the law, and has claimed that literature should provoke us into new ways of understanding by pointing to best man wedding speech examples what he calls the ethical, untold story of the law. Such provocation, claims Thomas, may stimulate an audience to generate new ways of constructing evidence, evidence that does not easily fit into accepted public opinion, evidence that is not deemed admissible in existing courts of law. Man Wedding Speech Examples. If accepted, such evidence can alter a society's sense of healthcare, justice. 4 In The Executioner's Song the untold stories that gather around Gilmore challenge both the interpretive practices of the law and the justice dispensed by the institutions of the state, and speech liberate him, not from his guilt, but from the 'legal processing' to which he was subject.
Gilmore, who had been executed, autopsied, cremated, and dispersed several months before Mailer signed his contract, is continuously re-formed, in The Executioner's Song, as a series of shifting reference-points in the complex socio-cultural network of the United States of America in mind develop its Bicentennial year of 1976, in man wedding speech examples which the Vietnam war is a bad dream from which the country has barely wakened, and in which Mormonism is a long-surviving embodiment of the Old Testament Puritan fundamentalism on which the country was founded. (othello). In this, his Great American Novel of the seventies, Mailer's avowedly fictive methods interrogate the best examples, unacknowledged fictions of the of College, law, and crack the codes of his country's conscience. Best Man Wedding Examples. By releasing the stories the law did not know, or could not or would not tell, the rhetorical strategies of The Executioner's Song endorse Shelley's famously radical claim that poets--for which we can today read 'writers'--are the unacknowledged legislators of the world. Simon Petch teaches Literature at Sydney University and is a past president of the Literature and Law Association of Australia. This piece has been extracted with permission from HEAT 3.
Notes and principles References. 1. Norman Mailer, The Executioner's Song , 1979. 2. Truman Capote, In Cold Blood: A True Account of Multiple Murder and Its Consequences, 1965. 3. The term 'free indirect discourse' is used here as it is speech defined by Cohan and Shires, that is as a narrative mode which 'conflates monologue and in psychology psycho-narration, with the narrator seeming to mimic the voice of the best speech examples, character who functions as focalizer and on Hoping for Intelligence in "Flowers For Algernon" focalized. For this reason the narration is free, not limited to man wedding examples what the character thinks exactly, and indirect, using language which the character himself could conceivably use but narrating rather than quoting it.' Steven Cohan and Ethical of College Linda M. Man Wedding Speech. Shires, Telling Stories: A Theoretical Analysis of Narrative Fiction (London: Routledge, 1988), 102.
4. On Hoping. Brook Thomas, 'Reflections on the Law and Literature Revival', Critical Inquiry 17:3 (Spring, 1991), 537-38.