Developement of real time diagnostics and feedback algorithms for JET in view of the next step

Real time control of many plasma parameters will be an essential aspect in the development of reliable high performance operation of Next Step Tokamaks. The main prerequisites for any feedback scheme are the precise real-time determination of the quantities to be controlled, requiring top quality and highly reliable diagnostics, and the availability of robust control algorithms. A new set of real time diagnostics was recently implemented on JET to prove the feasibility of determining, with high accuracy and time resolution, the most important plasma quantities. With regard to feedback algorithms, new model–based controllers were developed to allow a more robust control of several plasma parameters. Both diagnostics and algorithms were successfully used in several experiments, ranging from H-mode plasmas to configuration with ITBs. Since elaboration of computationally heavy measurements is often required, significant attention was devoted to non-algorithmic methods like Digital or Cellular Neural/Nonlinear Networks. The real time hardware and software adopted architectures are also described with particular attention to their relevance to ITER.Comment: 12th International Congress on Plasma Physics, 25-29 October 2004, Nice (France

A Historical Writing Apprenticeship for Adolescents: Integrating Disciplinary Learning With Cognitive Strategies

This study explored the extent to which an 18â day history and writing curriculum intervention, taught over the course of one year, helped culturally and academically diverse adolescents achieve important disciplinary literacy learning in history. Teachers used a cognitive apprenticeship form of instruction for the integration of historical reading and writing strategies and content learning with the goal of improving students’ historical argument writing. The intervention had positive and significant results for each writing outcome. After controlling for variables associated with students’ incoming abilities, the researchers found moderate to large effects for all participants. Relative to basic readers in the control condition, those participating in the intervention scored higher in historical writing and writing quality and wrote longer essays; these results translate into effect sizes of .45 on basic readers’ historical writing, .32 on their overall writing quality, and .60 on the length of their papers. Teachers implemented the reading and writing curriculum intervention with high levels of implementation fidelity, leading the researchers to explore additional factors that contributed to students’ success after accounting for teacher effectiveness. The results indicate further benefits dependent on the degree to which students completed the curriculum.Chineseæ ¬ç  ç©¶æ ¨å ¨æ ¢è®¨ä¸ ä¸ªå å ²ä¸ å ä½ è¯¾ç¨ å¹²é¢ æ å­¦ç æ è ½,è¯¥å¹²é¢ æ 学为æ 18天å å¸ å ¨ä¸ æ ´å­¦å¹´ç è¯¾ç¨ ä¸­è¿ è¡ ,å ¶ç ®ç æ ¯å¸®å ©æ å ä¸ å å å­¦ä¸ æ ç»©ä¸ å ç é å° å¹´å­¦ä¹ å¾ å °å å ²ç§ ä¸­é è¦ ç å­¦ç§ è¯»å æ è ½,æ è ½ç ç¡®å® æ ¯å ºäº å ¨å¤ å¤§ç¨ åº¦ä¸ è¿ å¹²é¢ æ å­¦è ½è¾¾è ³å ¶ç ®ç ã æ å¸ ä½¿ç ¨è®¤ç ¥å­¦å¾ æ¨¡å¼ ç æ å­¦æ ¹æ³ ,ä»¥æ ´å å å ²é 读å å ä½ ç­ ç ¥ä»¥å å å ²å å®¹ç ¥è¯ ç 学习,ç ®ç æ ¯æ é« å­¦ç ç å å ²ç§ è®®è®ºæ å ä½ æ è ½ã å¹²é¢ æ å­¦ä¸ºæ¯ é¡¹å ä½ å­¦ä¹ æ æ å¸¦æ ¥äº æ­£é ¢å æ ¾è ç ç» æ ã å ¨æ §å ¶äº ä¸ å­¦ç å ¨å¹²é¢ å å·²æ è ½å ç ¸å ³ç å é å ,ç  ç©¶äººå å ç °æ æ å ä¸ è é ½å¾ å °ä¸­è ³é« æ åº å ¼ã ç ¸å¯¹äº å ¨æ §å ¶ç» ä¸­ç å ºæ ¬é 读è ,å ¨å¹²é¢ ç» ä¸­ç å­¦ç ,å å ¨å å ²å ä½ å å ä½ è´¨é ä¸ ç å¾ å è¾ é« è æ ç« å å å¾ è¾ é ¿;è¿ äº ç» æ ç æ åº å ¼å å «æ ¯:å ºæ ¬é 读è ç å å ²å ä½ æ ¯.45,æ »ä½ å ä½ è´¨é æ ¯.32,æ ç« é ¿åº¦æ ¯.60ã æ å¸ å® æ ½ç é 读å å ä½ è¯¾ç¨ å¹²é¢ ,å ·æ é« åº¦ç å® æ ½ä¿ ç 度,æ ä»¥ç  ç©¶äººå å ¨æ §å ¶äº æ å¸ æ è ½å è¦ æ ¢è®¨å ¶ä» å¯¼è ´å­¦ç æ å ç å  ç´ ã æ ¬ç  ç©¶ç» æ æ ¾ç¤º,å­¦ç è¿ ä¸ æ­¥ç å¾ ç ,æ ¯å å ³äº ä» ä»¬å·²å® æ è¿ è¯¾ç¨ ç ç¨ åº¦ã SpanishEste estudio exploró hasta qué punto una intervención de 18 días en el currículo de historia y escritura, enseñado en el curso de un año, ayudó a adolescentes de diversas culturas y capacidades académicas lograr un aprendizaje importante en la disciplina de la historia. Los maestros usaron una forma de instrucción cognitiva de aprendizaje para integrar las lecturas históricas y las estrategias de escritura y el aprendizaje del contenido con la meta de mejorar la escritura de argumentos históricos de los estudiantes. La intervención tuvo resultados positivos e importantes para cada uno de los resultados de escritura. Habiendo controlado los variables asociados con las habilidades de los estudiantes al comenzar el estudio, los investigadores encontraron efectos desde moderados a importantes en todos los participantes. En relación a los lectores básicos del grupo de control, los que participaron en la intervención sacaron mejores notas en la escritura histórica y la calidad de la escritura, y escribieron ensayos más largos; estos resultados se traducen en una magnitud de efectos de .45 en la escritura histórica de lectores básicos, .32 en la calidad total de su escritura, y .60 en la extensión de sus ensayos. Los maestros implementaron la intervención curricular de lectura y escritura con altos niveles de fidelidad, llevando a los investigadores a explorar factores adicionales que contribuyeron al éxito de los estudiantes después de tomar en consideración la eficacia del maestro. Los resultados indican más posibles beneficios dependiendo del grado al cual los estudiantes completaron el currículo.Arabicتبحث ٠ذ٠ا٠دراسة إ٠٠أ٠٠د٠ساعد تدخ٠ا Ù Ù 18 ٠٠٠ا ٠٠دراسة ا٠تار٠خ ٠٠٠٠ج ا٠٠تابة Ø Ù Ø¯Ù Ø±Ù Ù Ø³Ù ØªÙ Ø¹Ù Ù Ù Ø¯Ø§Ø± س٠ة Ù Ø§Ø­Ø¯Ø©Ø Ø«Ù Ø§Ù Ù Ø§ ٠أ٠اد٠٠٠ا ا٠٠را٠٠٠٠٠٠خ٠٠٠ات ٠خت٠٠ة تح٠٠٠تع٠٠ا٠ضباط٠٠ا٠٠٠٠جا٠ا٠٠تابة ا٠تار٠خة. استخدا٠ا٠٠ع٠٠٠٠٠س٠٠ة ا٠٠عر٠ة ا٠٠٠٠٠ة ٠٠أج٠إد٠اج استرات٠ج٠ات ا٠٠راءة ٠ا٠٠تابة ا٠تار٠خ٠ة ٠٠حت٠٠ا٠ع٠٠٠٠ط٠اب ب٠د٠تحس٠٠ا٠٠تابة ا٠بر٠ا٠٠ة ٠٠ادة ا٠تار٠خ. ٠٠ا٠٠٠تدخ٠٠تائج إ٠جاب٠ة ٠٠ا٠ة ٠٠٠٠٠ا٠س ا٠٠تابة. بعد ا٠أخذ بع٠٠ا٠إعتبار ا٠٠تغ٠رات ا٠٠رتبطة ب٠درات ا٠ط٠اب Ø§Ù Ù Ø¨Ø¯Ø¦Ù Ø©Ø Ù Ø¬Ø¯ ا٠باحث٠٠تأث٠رات ٠عتد٠ة إ٠٠٠ب٠رة ٠د٠ج٠٠ع ا٠٠شار٠٠٠. با٠٠سبة ٠٠٠راء ٠٠ا٠٠ج٠٠عة Ø§Ù Ø¶Ø§Ø¨Ø·Ø©Ø Ø§Ù Ù Ø´Ø§Ø±Ù Ù Ù Ù Ù Ø§Ù ØªØ¯Ø®Ù Ø³Ø¬Ù Ù Ø§ ع٠ا٠ات أع٠٠٠٠ا٠٠تابة ا٠تار٠خ٠ة ٠ج٠دة ا٠٠تابة ٠٠تب٠ا ٠٠ا٠ات أط٠٠. ت٠ت٠ر٠ج٠٠٠ذ٠ا٠٠تائج إ٠٠تأث٠ر 0.45 ٠٠٠راء ا٠٠تابة Ø§Ù ØªØ§Ø±Ù Ø®Ù Ø©Ø 0.32 ع٠٠ج٠دة ا٠٠تابة Ø§Ù Ø¹Ø§Ù Ø©Ø Ù 0.60 ع٠٠ط٠٠أ٠را٠٠٠. طب٠ا٠٠ع٠٠٠٠٠٠ا٠ج ا٠تدخ٠٠٠٠راءة ٠٠٠٠تابة ا٠دراس٠ة ٠ع ٠ست٠٠ات عا٠٠ة ٠٠د٠ة Ø§Ù ØªÙ Ù Ù Ø°Ø Ù Ù Ø§ أبد٠با٠باحث٠٠٠است٠شا٠ا٠ع٠ا٠٠ا٠إضا٠٠ة ا٠ت٠سا٠٠ت ٠٠٠جاح ا٠ط٠اب بعد ا٠أخذ بع٠٠ا٠إعتبار ٠٠عا٠٠ة ا٠٠ع٠٠. ٠تش٠ر ا٠٠تائج إ٠٠٠ز٠د ٠٠ا٠٠٠ائد ٠ا٠ت٠تعت٠د ع٠٠ا٠٠أ٠٠د٠أت٠ا٠ط٠اب ا٠٠٠٠ج ا٠دراس٠.RussianÐ Ñ Ñ Ð»ÐµÐ´Ð¾Ð²Ð°Ñ ÐµÐ»Ð¸ Ð²Ñ Ñ Ñ Ð½Ð¸Ð»Ð¸, каким Ð¾Ð±Ñ Ð°Ð·Ð¾Ð¼ в Ñ ÐµÐ·Ñ Ð»Ñ Ñ Ð°Ñ Ðµ 18â дневного â но Ñ Ð°Ñ Ñ Ñ Ð½Ñ Ñ Ð¾Ð³Ð¾ на Ñ ÐµÐ»Ñ Ð¹ Ð°ÐºÐ°Ð´ÐµÐ¼Ð¸Ñ ÐµÑ ÐºÐ¸Ð¹ год â Ð²Ð¼ÐµÑ Ð°Ñ ÐµÐ»Ñ Ñ Ñ Ð²Ð° в Ñ Ñ ÐµÐ±Ð½Ñ Ð¹ план по Ð¸Ñ Ñ Ð¾Ñ Ð¸Ð¸ и Ð¿Ð¸Ñ Ñ Ð¼Ñ Ð¿Ð¾Ð´Ñ Ð¾Ñ Ñ ÐºÐ¸ Ñ Ð°Ð·Ð½Ð¾Ð³Ð¾ Ñ Ñ Ð½Ð¸Ñ ÐµÑ ÐºÐ¾Ð³Ð¾ Ð¿Ñ Ð¾Ð¸Ñ Ñ Ð¾Ð¶Ð´ÐµÐ½Ð¸Ñ Ð¸ Ñ Ñ Ð¾Ð²Ð½Ñ Ñ Ñ Ð¿ÐµÐ²Ð°ÐµÐ¼Ð¾Ñ Ñ Ð¸ Ð´Ð¾Ð±Ð¸Ð»Ð¸Ñ Ñ Ñ Ñ Ð¿ÐµÑ Ð¾Ð² в Ð¾Ð±Ð»Ð°Ñ Ñ Ð¸ Ð¸Ñ Ñ Ð¾Ñ Ð¸Ñ ÐµÑ ÐºÐ¾Ð¹ Ð³Ñ Ð°Ð¼Ð¾Ñ Ð½Ð¾Ñ Ñ Ð¸. Ð£Ñ Ð¸Ñ ÐµÐ»Ñ Ð¸Ñ Ð¿Ð¾Ð»Ñ Ð·Ð¾Ð²Ð°Ð»Ð¸ Ð¼ÐµÑ Ð¾Ð´ â Ð¿Ð¾Ð·Ð½Ð°Ð²Ð°Ñ ÐµÐ»Ñ Ð½Ð¾Ð³Ð¾ Ñ Ñ ÐµÐ½Ð¸Ñ ÐµÑ Ñ Ð²Ð°â Ð´Ð»Ñ Ð¸Ð½Ñ ÐµÐ³Ñ Ð°Ñ Ð¸Ð¸ Ñ Ñ ÐµÐ½Ð¸Ñ Ð¸Ñ Ñ Ð¾Ñ Ð¸Ñ ÐµÑ ÐºÐ¸Ñ Ñ ÐµÐºÑ Ñ Ð¾Ð², Ñ Ñ Ñ Ð°Ñ ÐµÐ³Ð¸Ð¹ Ñ Ð¾Ð·Ð´Ð°Ð½Ð¸Ñ Ð¿Ð¸Ñ Ñ Ð¼ÐµÐ½Ð½Ð¾Ð³Ð¾ Ñ ÐµÐºÑ Ñ Ð° и Ñ Ñ Ð²Ð¾ÐµÐ½Ð¸Ñ Ñ Ð¾Ð´ÐµÑ Ð¶Ð°Ð½Ð¸Ñ . Ð Ñ Ñ ÐµÐ»Ñ Ñ Ð±Ñ Ð»Ð¾ Ð¿Ð¾Ð²Ñ Ñ Ð¸Ñ Ñ ÐºÐ°Ñ ÐµÑ Ñ Ð²Ð¾ Ð°Ñ Ð³Ñ Ð¼ÐµÐ½Ñ Ð¸Ñ Ð¾Ð²Ð°Ð½Ð½Ñ Ñ Ñ Ñ Ñ Ðµ на Ð¸Ñ Ñ Ð¾Ñ Ð¸Ñ ÐµÑ ÐºÐ¸Ðµ Ñ ÐµÐ¼Ñ . Ранное Ð²Ð¼ÐµÑ Ð°Ñ ÐµÐ»Ñ Ñ Ñ Ð²Ð¾ Ð¿Ñ Ð¸Ð²ÐµÐ»Ð¾ к Ñ Ñ Ñ ÐµÑ Ñ Ð²ÐµÐ½Ð½Ñ Ð¼ Ð¿Ð¾Ð»Ð¾Ð¶Ð¸Ñ ÐµÐ»Ñ Ð½Ñ Ð¼ Ñ ÐµÐ·Ñ Ð»Ñ Ñ Ð°Ñ Ð°Ð¼ Ð´Ð»Ñ Ð²Ñ ÐµÑ Ð¿Ð°Ñ Ð°Ð¼ÐµÑ Ñ Ð¾Ð² Ð¿Ð¸Ñ Ñ Ð¼Ð°. Ð£Ñ Ð¸Ñ Ñ Ð²Ð°Ñ Ð¿ÐµÑ ÐµÐ¼ÐµÐ½Ð½Ñ Ðµ, Ñ Ð²Ñ Ð·Ð°Ð½Ð½Ñ Ðµ Ñ Ð¾ Ñ Ð¿Ð¾Ñ Ð¾Ð±Ð½Ð¾Ñ Ñ Ñ Ð¼Ð¸ Ñ Ñ Ð°Ñ Ð¸Ñ Ñ Ñ Ð¸ Ð¸Ñ Ñ Ð¼ÐµÐ½Ð¸Ñ Ð¼Ð¸ на Ð²Ñ Ð¾Ð´Ðµ в Ñ ÐºÑ Ð¿ÐµÑ Ð¸Ð¼ÐµÐ½Ñ , Ð¸Ñ Ñ Ð»ÐµÐ´Ð¾Ð²Ð°Ñ ÐµÐ»Ð¸ Ð¾Ñ Ð¼ÐµÑ Ð¸Ð»Ð¸ Ñ Ð¼ÐµÑ ÐµÐ½Ð½Ñ Ð¹ или Ð·Ð½Ð°Ñ Ð¸Ñ ÐµÐ»Ñ Ð½Ñ Ð¹ Ð¿Ð¾Ð»Ð¾Ð¶Ð¸Ñ ÐµÐ»Ñ Ð½Ñ Ð¹ Ñ Ñ Ñ ÐµÐºÑ Ñ Ð²Ñ ÐµÑ Ð±ÐµÐ· Ð¸Ñ ÐºÐ»Ñ Ñ ÐµÐ½Ð¸Ñ . Ð£Ñ Ð°Ñ Ñ Ð½Ð¸ÐºÐ¸ Ñ ÐºÑ Ð¿ÐµÑ Ð¸Ð¼ÐµÐ½Ñ Ð° Ð¿Ñ ÐµÐ²Ð·Ð¾Ñ Ð»Ð¸ ÐºÐ¾Ð½Ñ Ñ Ð¾Ð»Ñ Ð½Ñ Ñ Ð³Ñ Ñ Ð¿Ð¿Ñ Ð² понимании Ð¸Ñ Ñ Ð¾Ñ Ð¸Ð¸ и длине и Ñ Ñ Ð¾Ð²Ð½Ðµ Ð½Ð°Ð¿Ð¸Ñ Ð°Ð½Ð½Ñ Ñ Ð¸Ð¼Ð¸ Ñ Ñ Ñ Ðµ: знание Ð¸Ñ Ñ Ð¾Ñ Ð¸Ð¸ Ð¾ÐºÐ°Ð·Ð°Ð»Ð¾Ñ Ñ Ð½Ð° 45%, ÐºÐ°Ñ ÐµÑ Ñ Ð²Ð¾ Ð¿Ð¸Ñ Ñ Ð¼Ð° на 33,2% и длина Ñ Ñ Ñ Ðµ на 60% Ð²Ñ Ñ Ðµ, Ñ ÐµÐ¼ Ñ Ð¸Ñ Ñ Ð²ÐµÑ Ñ Ñ Ð½Ð¸ÐºÐ¾Ð² из ÐºÐ¾Ð½Ñ Ñ Ð¾Ð»Ñ Ð½Ð¾Ð¹ Ð³Ñ Ñ Ð¿Ð¿Ñ . Ð£Ñ Ð¸Ñ ÐµÐ»Ñ Ð¾Ñ Ñ Ñ ÐµÑ Ñ Ð²Ð¸Ð»Ð¸ Ð¿Ñ ÐµÐ´Ð»Ð¾Ð¶ÐµÐ½Ð½Ð¾Ðµ Ð²Ð¼ÐµÑ Ð°Ñ ÐµÐ»Ñ Ñ Ñ Ð²Ð¾ в Ñ Ñ ÐµÐ±Ð½Ñ Ð¹ план ÐºÑ Ð°Ð¹Ð½Ðµ Ñ Ñ Ð°Ñ ÐµÐ»Ñ Ð½Ð¾, Ð·Ð°Ñ Ñ Ð°Ð²Ð¸Ð² Ð¸Ñ Ñ Ð»ÐµÐ´Ð¾Ð²Ð°Ñ ÐµÐ»ÐµÐ¹ Ð¿Ñ Ð¾Ð°Ð½Ð°Ð»Ð¸Ð·Ð¸Ñ Ð¾Ð²Ð°Ñ Ñ â помимо Ñ Ñ Ñ ÐµÐºÑ Ð¸Ð²Ð½Ð¾Ñ Ñ Ð¸ Ñ Ð°Ð±Ð¾Ñ Ñ Ñ Ñ Ð¸Ñ ÐµÐ»Ñ â Ð´Ð¾Ð¿Ð¾Ð»Ð½Ð¸Ñ ÐµÐ»Ñ Ð½Ñ Ðµ Ñ Ð°ÐºÑ Ð¾Ñ Ñ , ÐºÐ¾Ñ Ð¾Ñ Ñ Ðµ Ñ Ð¿Ð¾Ñ Ð¾Ð±Ñ Ñ Ð²Ð¾Ð²Ð°Ð»Ð¸ Ñ Ñ Ð¿ÐµÑ Ñ Ñ Ñ ÐµÐ½Ð¸ÐºÐ¾Ð². Ð Ð¾Ð»Ñ Ñ ÐµÐ½Ñ Ð´Ð°Ð½Ð½Ñ Ðµ о Ð¼Ð½Ð¾Ð³Ð¸Ñ Ð¿Ð¾Ð·Ð¸Ñ Ð¸Ð²Ð½Ñ Ñ Ñ ÐµÐ·Ñ Ð»Ñ Ñ Ð°Ñ Ð°Ñ Ð² Ð¿Ñ Ð¾Ñ ÐµÑ Ñ Ðµ Ñ Ñ Ð²Ð¾ÐµÐ½Ð¸Ñ Ð²Ñ ÐµÑ Ñ Ð°Ð·Ð´ÐµÐ»Ð¾Ð² Ñ Ñ ÐµÐ±Ð½Ð¾Ð³Ð¾ плана.FrenchCette recherche étudie dans quelle mesure une intervention de 18 jours du programme d’histoire et dâ écriture, entreprise pendant une durée d’un an, aide sur le plan culturel et académique des adolescents diversifiés à permet un important apprentissage de littératie en histoire. Les enseignants ont mis en Å uvre une forme cognitive d’enseignement d’intégration de la lecture de l’histoire et de stratégies dâ écriture avec l’apprentissage du contenu afin de développer lâ écriture argumentative en histoire des élèves. Cette intervention a conduit à des résultats positifs et significatifs dans tous les types dâ écriture de l’histoire. Après contrôle des variables associées aux compétences de départ des élèves, les chercheurs ont trouvé des effets moyens ou grands chez tous les participants. Par rapport aux lecteurs de base du groupe contrôle, ceux qui ont participé à l’intervention ont obtenu de meilleurs résultats en écriture historique et qualité de lâ écriture et ils ont écrit des textes plus longs ; ces résultats traduisent des effets de la taille de .45 par rapport aux lecteurs de base en écriture historique, de .32 dans la qualité de dâ écriture en général, et de .60 dans la longueur de leurs écrits. Les enseignants ont mis en place l’intervention du programme de lectureâ écriture avec de hauts niveaux de fidélité dans la mise en place ; ce qui a conduit les chercheurs à explorer d’autres facteurs qui ont contribué à la réussite des élèves après prise en compte de l’efficacité du maître. Les résultats indiquent des progrès ultérieurs variables selon le degré auquel les élèves ont suivi le programme.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135405/1/rrq147-sup-0002-AppendixB.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135405/2/rrq147_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135405/3/rrq147-sup-0001-AppendixA.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135405/4/rrq147.pd

Association of the SULT1A1 R213H polymorphism with colorectal cancer

1. Sulphotransferases are a superfamily of enzymes involved in both detoxification and bioactivation of endogenous and exogenous compounds. The arylsulphotransferase SULT1A1 has been implicated in a decreased activity and thermostability when the wild-type arginine at position 213 of the coding sequence is substituted by a histidine. SULT1A1 is the isoform primarily associated with the conversion of dietary N -OH arylamines to DNA binding adducts and is therefore of interest to determine whether this polymorphism is linked to colorectal cancer. 2. Genotyping, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, was performed using DNA samples of healthy control subjects (n = 402) and patients with histologically proven colorectal cancer (n = 383). Both control and test populations possessed similar frequencies for the mutant allele (32.1 and 31%, respectively; P = 0.935). Results were not altered when age and gender were considered as potential confounders in a logistic regression analysis. 3. Examination of the sulphonating ability of the two allozymes with respect to the substrates p -nitrophenol and paracetamol showed that the affinity and rate of sulphonation was unaffected by substitution of arginine to histidine at position 213 of the amino acid sequence. 4. From this study, we conclude that the SULT1A1 R213H polymorphism is not linked with colorectal cancer in this elderly Australian population

Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction (HARP-2) trial : study protocol for a randomized controlled trial

Acute lung injury (ALI) is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI

Interpretation and application of carbon isotope ratios in freshwater diatom silica

Carbon incorporated into diatom frustule walls is protected from degradation enabling analysis for carbon isotope composition (δ13Cdiatom). This presents potential for tracing carbon cycles via a single photosynthetic host with well-constrained ecophysiology. Improved understanding of environmental processes controlling carbon delivery and assimilation is essential to interpret changes in freshwater δ13Cdiatom. Here relationships between water chemistry and δ13Cdiatom from contemporary regional data sets are investigated. Modern diatom and water samples were collected from river catchments within England and lake sediments from across Europe. The data suggest dissolved, biogenically produced carbon supplied proportionately to catchment productivity was critical in the rivers and soft water lakes. However, dissolved carbon from calcareous geology overwhelmed the carbon signature in hard water catchments. Both results demonstrate carbon source characteristics were the most important control on δ13Cdiatom, with a greater impact than productivity. Application of these principles was made to a sediment record from Lake Tanganyika. δ13Cdiatom co-varied with δ13Cbulk through the last glacial and Holocene. This suggests carbon supply was again dominant and exceeded authigenic demand. This first systematic evaluation of contemporary δ13Cdiatom controls demonstrates that diatoms have the potential to supply a record of carbon cycling through lake catchments from sediment records over millennial timescales

Alcohol and HIV Disease Progression: Weighing the Evidence

Heavy alcohol use is commonplace among HIV-infected individuals; however, the extent that alcohol use adversely impacts HIV disease progression has not been fully elucidated. Fairly strong evidence suggests that heavy alcohol consumption results in behavioral and biological processes that likely increase HIV disease progression, and experimental evidence of the biological effect of heavy alcohol on simian immunodeficiency virus in macaques is quite suggestive. However, several observational studies of the effect of heavy alcohol consumption on HIV progression conducted in the 1990s found no association of heavy alcohol consumption with time to AIDS diagnosis, while some more recent studies showed associations of heavy alcohol consumption with declines of CD4 cell counts and nonsuppression of HIV viral load. We discuss several plausible biological and behavioral mechanisms by which alcohol may cause HIV disease progression, evidence from prospective observational human studies, and suggest future research to further illuminate this important issue

Design of experiments to study the impact of process parameters on droplet size and development of non-invasive imaging techniques in tablet coating

Atomisation of an aqueous solution for tablet film coating is a complex process with multiple factors determining droplet formation and properties. The importance of droplet size for an efficient process and a high quality final product has been noted in the literature, with smaller droplets reported to produce smoother, more homogenous coatings whilst simultaneously avoiding the risk of damage through over-wetting of the tablet core. In this work the effect of droplet size on tablet film coat characteristics was investigated using X-ray microcomputed tomography (XμCT) and confocal laser scanning microscopy (CLSM). A quality by design approach utilising design of experiments (DOE) was used to optimise the conditions necessary for production of droplets at a small (20 μm) and large (70 μm) droplet size. Droplet size distribution was measured using real-time laser diffraction and the volume median diameter taken as a response. DOE yielded information on the relationship three critical process parameters: pump rate, atomisation pressure and coating-polymer concentration, had upon droplet size. The model generated was robust, scoring highly for model fit (R2 = 0.977), predictability (Q2 = 0.837), validity and reproducibility. Modelling confirmed that all parameters had either a linear or quadratic effect on droplet size and revealed an interaction between pump rate and atomisation pressure. Fluidised bed coating of tablet cores was performed with either small or large droplets followed by CLSM and XμCT imaging. Addition of commonly used contrast materials to the coating solution improved visualisation of the coating by XμCT, showing the coat as a discrete section of the overall tablet. Imaging provided qualitative and quantitative evidence revealing that smaller droplets formed thinner, more uniform and less porous film coats

High rates of burnout among maternal health staff at a referral hospital in Malawi: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Burnout among maternal healthcare workers in sub-Saharan Africa may have a negative effect on services provided and efforts to mitigate high maternal mortality rates. In Malawi, research on burnout is limited and no empirical research has been conducted specifically among maternal health staff. Therefore, the aims of the study were to examine the prevalence and degree of burnout reported by healthcare workers who provide antenatal, intrapartum, and postnatal services in a district referral hospital in Malawi; and, to explore factors that may influence the level of burnout healthcare workers experience.</p> <p>Methods</p> <p>In the current cross-sectional study, levels of burnout among staff working in obstetrics and gynaecology at a referral hospital in Malawi were examined, in addition to individual and job characteristics that may be associated with burnout.</p> <p>Results</p> <p>In terms of the three dimensions of burnout, of the 101 participants, nearly three quarters (72%) reported emotional exhaustion, over one third (43%) reported depersonalization while almost three quarters (74%) experienced reduced personal accomplishment.</p> <p>Conclusions</p> <p>Based on these findings, burnout appears to be common among participating maternal health staff and they experienced more burnout than their colleagues working in other medical settings and countries. Further research is needed to identify factors specific to Malawi that contribute to burnout in order to inform the development of prevention and treatment within the maternal health setting.</p

Monitoring fever treatment behaviour and equitable access to effective medicines in the context of initiatives to improve ACT access: baseline results and implications for programming in six African countries

BACKGROUND: Access to artemisinin-based combination therapy (ACT) remains limited in high malaria-burden countries, and there are concerns that the poorest people are particularly disadvantaged. This paper presents new evidence on household treatment-seeking behaviour in six African countries. These data provide a baseline for monitoring interventions to increase ACT coverage, such as the Affordable Medicines Facility for malaria (AMFm). METHODS: Nationally representative household surveys were conducted in Benin, the Democratic Republic of Congo (DRC), Madagascar, Nigeria, Uganda and Zambia between 2008 and 2010. Caregivers responded to questions about management of recent fevers in children under five. Treatment indicators were tabulated across countries, and differences in case management provided by the public versus private sector were examined using chi-square tests. Logistic regression was used to test for association between socioeconomic status and 1) malaria blood testing, and 2) ACT treatment. RESULTS: Fever treatment with an ACT is low in Benin (10%), the DRC (5%), Madagascar (3%) and Nigeria (5%), but higher in Uganda (21%) and Zambia (21%). The wealthiest children are significantly more likely to receive ACT compared to the poorest children in Benin (OR = 2.68, 95% CI = 1.12-6.42); the DRC (OR = 2.18, 95% CI = 1.12-4.24); Madagascar (OR = 5.37, 95% CI = 1.58-18.24); and Nigeria (OR = 6.59, 95% CI = 2.73-15.89). Most caregivers seek treatment outside of the home, and private sector outlets are commonly the sole external source of treatment (except in Zambia). However, children treated in the public sector are significantly more likely to receive ACT treatment than those treated in the private sector (except in Madagascar). Nonetheless, levels of testing and ACT treatment in the public sector are low. Few caregivers name the national first-line drug as most effective for treating malaria in Madagascar (2%), the DRC (2%), Nigeria (4%) and Benin (10%). Awareness is higher in Zambia (49%) and Uganda (33%). CONCLUSIONS: Levels of effective fever treatment are low and inequitable in many contexts. The private sector is frequently accessed however case management practices are relatively poor in comparison with the public sector. Supporting interventions to inform caregiver demand for ACT and to improve provider behaviour in both the public and private sectors are needed to achieve maximum gains in the context of improved access to effective treatment

RNA Silencing of Mcl-1 Enhances ABT-737-Mediated Apoptosis in Melanoma: Role for a Caspase-8-Dependent Pathway

BACKGROUND: Malignant melanoma is resistant to almost all conventional forms of chemotherapy. Recent evidence suggests that anti-apoptotic proteins of the Bcl-2 family are overexpressed in melanoma and may contribute to melanoma's striking resistance to apoptosis. ABT-737, a small-molecule inhibitor of Bcl-2, Bcl-xl and Bcl-w, has demonstrated efficacy in several forms of leukemia, lymphoma as well as solid tumors. However, overexpression of Mcl-1, a frequent observance in melanoma, is known to confer ABT-737 resistance. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that knockdown of Mcl-1 greatly reduces cell viability in combination with ABT-737 in six different melanoma cell lines. We demonstrate that the cytotoxic effect of this combination treatment is due to apoptotic cell death involving not only caspase-9 activation but also activation of caspase-8, caspase-10 and Bid, which are normally associated with the extrinsic pathway of apoptosis. Caspase-8 (and caspase-10) activation is abrogated by inhibition of caspase-9 but not by inhibitors of the death receptor pathways. Furthermore, while caspase-8/-10 activity is required for the full induction of cell death with treatment, the death receptor pathways are not. Finally, we demonstrate that basal levels of caspase-8 and Bid correlate with treatment sensitivity. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that the combination of ABT-737 and Mcl-1 knockdown represents a promising, new treatment strategy for malignant melanoma. We also report a death receptor-independent role for extrinsic pathway proteins in treatment response and suggest that caspase-8 and Bid may represent potential markers of treatment sensitivity