Attacks on quantum key distribution protocols that employ non-ITS authentication

We demonstrate how adversaries with unbounded computing resources can break Quantum Key Distribution (QKD) protocols which employ a particular message authentication code suggested previously. This authentication code, featuring low key consumption, is not Information-Theoretically Secure (ITS) since for each message the eavesdropper has intercepted she is able to send a different message from a set of messages that she can calculate by finding collisions of a cryptographic hash function. However, when this authentication code was introduced it was shown to prevent straightforward Man-In-The-Middle (MITM) attacks against QKD protocols. In this paper, we prove that the set of messages that collide with any given message under this authentication code contains with high probability a message that has small Hamming distance to any other given message. Based on this fact we present extended MITM attacks against different versions of BB84 QKD protocols using the addressed authentication code; for three protocols we describe every single action taken by the adversary. For all protocols the adversary can obtain complete knowledge of the key, and for most protocols her success probability in doing so approaches unity. Since the attacks work against all authentication methods which allow to calculate colliding messages, the underlying building blocks of the presented attacks expose the potential pitfalls arising as a consequence of non-ITS authentication in QKD-postprocessing. We propose countermeasures, increasing the eavesdroppers demand for computational power, and also prove necessary and sufficient conditions for upgrading the discussed authentication code to the ITS level.Comment: 34 page

Genome-wide analysis of the human Alu Yb-lineage.

The Alu Yb-lineage is a \u27young\u27 primarily human-specific group of short interspersed element (SINE) subfamilies that have integrated throughout the human genome. In this study, we have computationally screened the draft sequence of the human genome for Alu Yb-lineage subfamily members present on autosomal chromosomes. A total of 1,733 Yb Alu subfamily members have integrated into human autosomes. The average ages of Yb-lineage subfamilies, Yb7, Yb8 and Yb9, are estimated as 4.81, 2.39 and 2.32 million years, respectively. In order to determine the contribution of the Alu Yb-lineage to human genomic diversity, 1,202 loci were analysed using polymerase chain reaction (PCR)-based assays, which amplify the genomic regions containing individual Yb-lineage subfamily members. Approximately 20 percent of the Yb-lineage Alu elements are polymorphic for insertion presence/absence in the human genome. Fewer than 0.5 percent of the Yb loci also demonstrate insertions at orthologous positions in non-human primate genomes. Genomic sequencing of these unusual loci demonstrates that each of the orthologous loci from non-human primate genomes contains older Y, Sg and Sx Alu family members that have been altered, through various mechanisms, into Yb8 sequences. These data suggest that Alu Yb-lineage subfamily members are largely restricted to the human genome. The high copy number, level of insertion polymorphism and estimated age indicate that members of the Alu Yb elements will be useful in a wide range of genetic analyses

Distribution of health care expenditures for HIV-infected patients

BACKGROUND: Health care expenditures for persons infected with human immunodeficiency virus (HIV) in the United State determined on the basis of actual health care use have not been reported in the era of highly active antiretroviral therapy. METHODS: Patients receiving primary care at the University of Alabama at Birmingham HIV clinic were included in the study. All encounters (except emergency room visits) that occurred within the University of Alabama at Birmingham Hospital System from 1 March 2000 to 1 March 2001 were analyzed. Medication expenditures were determined on the basis of 2001 average wholesale price. Hospitalization expenditures were determined on the basis of 2001 Medicare diagnostic related group reimbursement rates. Clinic expenditures were determined on the basis of 2001 Medicare current procedural terminology reimbursement rates. RESULTS: Among the 635 patients, total annual expenditures for patients with CD4+ cell counts \u3c50 cells/microL (36,533 dollars per patient) were 2.6-times greater than total annual expenditures for patients with CD4+ cell counts \u3e or =350 cells/microL (13,885 dollars per patient), primarily because of increased expenditures for nonantiretroviral medication and hospitalization. Expenditures for highly active antiretroviral therapy were relatively constant at approximately 10,500 dollars per patient per year across CD4+ cell count strata. Outpatient expenditures were 1558 dollars per patient per year; however, the clinic and physician component of these expenditures represented only 359 dollars per patient per year, or 2% of annual expenses. Health care expenditures for patients with HIV infection increased substantially for those with more-advanced disease and were driven predominantly by medication costs (which accounted for 71%-84% of annual expenses). CONCLUSIONS: Physician reimbursements, even with 100% billing and collections, are inadequate to support the activities of most clinics providing HIV care. These findings have important implications for the continued support of HIV treatment programs in the United States

Safety and Efficacy of Teduglutide in Pediatric Patients With Intestinal Failure due to Short Bowel Syndrome : A 24-Week, Phase III Study

Background This study evaluated the safety and efficacy of teduglutide in pediatric patients with short bowel syndrome-associated intestinal failure (SBS-IF). Methods A 24-week, phase III trial with 2 randomized, double-blind teduglutide dose groups and a nonblinded standard of care (SOC) arm was used; patients received 0.025 mg/kg or 0.05 mg/kg teduglutide once daily. Safety end points included treatment-emergent adverse events (TEAEs) and growth parameters. The primary efficacy/pharmacodynamic end point was the number of patients who achieved a >= 20% reduction in parenteral support (PS) from baseline at week 24. Results All 59 enrolled patients completed the study (0.025 mg/kg, n = 24; 0.05 mg/kg, n = 26; SOC, n = 9). Baseline demographics and disease characteristics were comparable among groups. TEAEs were reported by 98% and 100% of patients in the teduglutide and SOC groups, respectively. The most common TEAEs in the teduglutide-treated groups were pyrexia and vomiting. The primary end point was achieved by 13 (54.2%), 18 (69.2%), and 1 (11.1%) patients who received 0.025 mg/kg teduglutide, 0.05 mg/kg teduglutide, and SOC, respectively (P <0.05 vs SOC). Both 0.025-mg/kg and 0.05-mg/kg teduglutide groups showed clinically significant reductions in PS volume (P <0.05 vs SOC), PS calories, days per week and hours per day of PS infusions, and increases in enteral nutrition and plasma citrulline at week 24 compared with baseline. Two (8.3%, 0.025 mg/kg teduglutide) and 3 patients (11.5%, 0.05 mg/kg teduglutide) achieved enteral autonomy. Conclusion The safety profile of teduglutide was similar to that reported previously in children and adults. Treatment with teduglutide was associated with significant reductions in PS for pediatric patients with SBS-IF over 24 weeks.Peer reviewe

Safety Findings in Pediatric Patients During Long-Term Treatment With Teduglutide for Short-Bowel Syndrome-Associated Intestinal Failure : Pooled Analysis of 4 Clinical Studies

Background This analysis assessed combined safety data from 4 clinical studies of teduglutide in pediatric patients with short-bowel syndrome-associated intestinal failure (SBS-IF). Methods Safety data from teduglutide-treated patients in 4 clinical trials were pooled. The completed 12-week and 24-week phase 3 core studies (NCT01952080/EudraCT 2013-004588-30 and NCT02682381/EudraCT 2015-002252-27) enrolled children aged 1-17 years with SBS-IF. Patients could elect to enroll in ongoing open-label extensions (NCT02949362/EudraCT 2016-000863-17 and NCT02954458/EudraCT 2016-000849-30). Interim data from ongoing studies were included. Results Safety data are reported for 89 pediatric patients treated with teduglutide for a median (range) of 51.7 (5.0-94.7) weeks. Adverse events (AEs) were reported in all patients; the most common were vomiting (51.7%), pyrexia (43.8%), upper respiratory tract infection (41.6%), and cough (33.7%). Thirty-five patients (39.3%) had AEs considered related to teduglutide treatment; abdominal pain and vomiting were most frequent (5.6% each). Three serious AEs in 3 patients (3.4%) were considered related to teduglutide treatment: ileus, d-lactic acidosis, and gastrointestinal obstruction due to hard stools. All 3 events resolved. One cecal polyp was detected, which was not biopsied or found on repeat colonoscopy. No cases of neoplasia occurred. Conclusion Based on integrated data from 4 clinical studies, including long-term follow-up forPeer reviewe

Characterization of CDK(5) Inhibitor, 20-223 (aka CP668863) for Colorectal Cancer Therapy

Colorectal cancer (CRC) remains one of the leading causes of cancer related deaths in the United States. Currently, there are limited therapeutic options for patients suffering from CRC, none of which focus on the cell signaling mechanisms controlled by the popular kinase family, cyclin dependent kinases (CDKs). Here we evaluate a Pfizer developed compound, CP668863, that inhibits cyclin-dependent kinase 5 (CDK5) in neurodegenerative disorders. CDK5 has been implicated in a number of cancers, most recently as an oncogene in colorectal cancers. Our lab synthesized and characterized CP668863 – now called 20-223. In our established colorectal cancer xenograft model, 20-223 reduced tumor growth and tumor weight indicating its value as a potential anti-CRC agent. We subjected 20-223 to a series of cell-free and cell-based studies to understand the mechanism of its anti-tumor effects. In our hands, in vitro 20-223 is most potent against CDK2 and CDK5. The clinically used CDK inhibitor AT7519 and 20-223 share the aminopyrazole core and we used it to benchmark the 20-223 potency. In CDK5 and CDK2 kinase assays, 20-223 was ~3.5-fold and ~65.3-fold more potent than known clinically used CDK inhibitor, AT7519, respectively. Cell-based studies examining phosphorylation of downstream substrates revealed 20-223 inhibits the kinase activity of CDK5 and CDK2 in multiple CRC cell lines. Consistent with CDK5 inhibition, 20-223 inhibited migration of CRC cells in a wound-healing assay. Profiling a panel of CRC cell lines for growth inhibitory effects showed that 20-223 has nanomolar potency across multiple CRC cell lines and was on an average \u3e2-fold more potent than AT7519. Cell cycle analyses in CRC cells revealed that 20-223 phenocopied the effects associated with AT7519. Collectively, these findings suggest that 20-223 exerts anti-tumor effects against CRC by targeting CDK 2/5 and inducing cell cycle arrest. Our studies also indicate that 20-223 is a suitable lead compound for colorectal cancer therapy

Outcomes from a 12-Week, Open-Label, Multicenter Clinical Trial of Teduglutide in Pediatric Short Bowel Syndrome

Objective To determine safety and pharmacodynamics/efficacy of teduglutide in children with intestinal failure associated with short bowel syndrome (SBS-IF). Study design This 12-week, open-label study enrolled patients aged 1-17 years with SBS-IF who required parenteral nutrition (PN) and showed minimal or no advance in enteral nutrition (EN) feeds. Patients enrolled sequentially into 3 teduglutide cohorts (0.0125 mg/kg/d [n = 8], 0.025 mg/kg/d [n = 14], 0.05 mg/kg/d [n = 15]) or received standard of care (SOC, n = 5). Descriptive summary statistics were used. Results All patients experienced ≥1 treatment-emergent adverse event; most were mild or moderate. No serious teduglutide-related treatment-emergent adverse events occurred. Between baseline and week 12, prescribed PN volume and calories (kcal/kg/d) changed by a median of −41% and −45%, respectively, with 0.025 mg/kg/d teduglutide and by −25% and −52% with 0.05 mg/kg/d teduglutide. In contrast, PN volume and calories changed by 0% and −6%, respectively, with 0.0125 mg/kg/d teduglutide and by 0% and −1% with SOC. Per patient diary data, EN volume increased by a median of 22%, 32%, and 40% in the 0.0125, 0.025, and 0.05 mg/kg/d cohorts, respectively, and by 11% with SOC. Four patients achieved independence from PN, 3 in the 0.05 mg/kg/d cohort and 1 in the 0.025 mg/kg/d cohort. Study limitations included its short-term, open-label design, and small sample size. Conclusions Teduglutide was well tolerated in pediatric patients with SBS-IF. Teduglutide 0.025 or 0.05 mg/kg/d was associated with trends toward reductions in PN requirements and advancements in EN feeding in children with SBS-IF

A Review of Discourse Analysis in Literacy Research: Equitable Access

This review represents research employing discourse analysis conducted by scholars interested in literacy issues in education across the age span—preschool to adult—during the last 10 years. Drawing from more than 300 studies, we discerned that a common theme was understanding how the literacy education of all students can be successfully accomplished. We organized the review into two complementary sections. The first section highlights discourse analytic approaches taken to investigate: Whose literacies count? Which literacies count? The second section explains the contributions the studies made organized according to five questions: What are literate identities, how are they constructed, and by whom? How are disciplinary knowledges, discourses, and identities constructed? How can schools provide students with access to school‐based literacies? What are the shifting roles of literacy teachers and learners within and outside of school? How does discourse analysis research address movement within and across literacy sites and practices in a contemporary, globalized, and increasingly digitally influenced world? تلخيص البحث: تمثل هذه المراجعة الأبحاث التي يوجد فيها تحليل الخطاب الذي قام به الباحثون المهتمون بشؤون تعلم القراءة والكتابة في التعليم عبر الأعمار—من الروضة حتى بالغ سن الرشد—في السنوات العشرة الماضية. لقد حددنا موضوعاً مشتركاً من استجماع أكثر من 300 دراسة وهو الطريقة التي قد يتم فيها تعليم القراءة والكتابة لجميع الطلاب بالنجاح. وقد نظمنا المراجعة في قسمين متكاملين الأول يسلط الضوء على طرق الخطاب التحليلية المأخوذة للتحقيق في: لمن معارف القراءة والكتابة التي نحتاج إلى أخذها بعين الاعتبار؟ وأية معارف من هذه يجب الأخذ في الحسبان؟ والقسم الثاني يشرح مساهمات الدراسات المندرجة تحت الأصناف المبنية على خمسة أسئلة: ما هي هويات معرفة القراءة والكتابة وكيف يتم تشكيلها ومن يشكلها؟ وكيف يتم تشكيل المعارف الدراسية والخطابية والهوية؟ وكيف تستطيع المدارس أن توفر الطلاب بوسيلة للمعارف القائمة في المدرسة؟ ما هي الأدوار المتغيرة لمعلمي القراءة والكتابة وطلابهم داخل المدرسة وخارجها؟ وكيف يعالج التحليل الخطابي الحركات في مواقع القراءة والكتابة وعبرها وكذلك الممارسات التي تتم في عالم معاصر عولمي فيه يزداد التأثير الرقمي؟ 本文旨在阐述过去10年期间，学者致力于不同学龄（由学前以至成人）的读写教育问题研究时所使用的语篇分析方法。作者从300多个研究里整理出一个共通的主题，就是去理解如何使到所有学生的读写教育取得成功。本文献综述是由两个互补的章节组成。第一节重点介绍研究调查所采用的两个语篇分析的处理方法：是谁的读写文化有重要意义？哪些读写文化有重要意义？第二节根据五个问题来阐釋这些研究的贡献：1.有读写文化的人的身份认同，所指的是什么？是怎样建构而成的？由谁所建构而成的？2.各种学科知识、话语及身份认同是如何建构而成的？3.学校如何为学生提供获取校本读写文化知识的门路？4.读写教学教师与学生在校内及校外在角色上有什么转移？5.在当前全球化和日益受数码化影响的世界中，语篇分析研究如何处理流动于各种写文化网站以内及之间的文化信息及各种文化实践的问题？ Cet état de la question présente l'analyse du discours dans les recherches des chercheurs qui s'intéressent aux questions de littératie en éducation— du niveau préscolaire à l'adulte — au cours des dix dernières années. En nous basant sur plus de 300 études, une préoccupation commune nous est apparue qui est de comprendre comment l'enseignement de la littératie peut permettre à tous les élèves de réussir. Nous avons organisé l'état de la question en deux parties complémentaires. La première partie s'intéresse au discours des approches analytiques réalisées pour étudier les questions suivantes: prendre en compte les littératies de qui ? prendre en compte quelles littératies? La seconde partie explique ce qu'ont apporté les études effectuées en réponse à cinq questions: que sont les identités lettrées ? comment sont‐elles construites, et par qui ? Comment sont construits les avoirs disciplinaires, les discours, et les identités ? Comment les écoles fournissent‐elles aux élèves un accès aux littératies basées sur l'école ? Quels sont les changements de rôles des professeurs de littératie et des apprenants dans l'école et hors de celle‐ci ? Comment le discours de la recherche analysé prend‐il en compte le mouvement au sein et au travers des sites de littératie et des pratiques dans un monde contemporain globalisé et de plus en plus influencé par l'informatique. В этом обзоре представлены исследования, проведенные на протяжении последних десяти лет с помощью дискурс‐анализа и посвященные проблемам развития грамотности людей разного возраста – от дошкольников до взрослых. Общая тема для более чем трехсот рассмотренных авторами источников: как добиться успеха в становлении грамотности? Обзор состоит из двух взаимодополняющих разделов. В первом описаны подходы к анализу дискурса, которые помогают понять, что принимается за образцы грамотности и кто может им соответствовать. Во втором разделе результаты исследований рассмотрены согласно пяти категориям: Как человек осознает себя в плане грамотности, на чем и кем строится эта идентичность? Как конструируется предметное или дисциплинарное знание, дискурс и идентичность? Как может школа дать учащимся доступ к школьной академической грамотности? В чем состоят и как меняются роли преподавателей грамотности и учащихся в стенах школы и за ее пределами? Как исследования дискурс‐анализа отражают перемещения участников дискурса в реальном и виртуальном пространстве в современном глобализированном мире? Este repaso presenta investigación que ha sido llevada a cabo usando análisis del discurso por estudiosos interesados en cuestiones de alfabetización en la educación a todas las edades—preescolar hasta adulto—en los últimos diez años. Al examinar más de 300 estudios, vimos que un tema común es el de entender cómo lograr exitosamente la educación de competencias de todos los estudiantes. Organizamos el repaso en dos secciones complementarias. Enfocamos la primera en los acercamientos analíticos del discurso que se han usado para investigar: ¿Cuáles competencias cuentan o valen? ¿Las competencias de quiénes cuentan o valen? La segunda sección explica las contribuciones que hicieron los estudios organizadas de acuerdo a cinco temas: ¿Qué son identidades competentes, cómo se construyen, y por quiénes? ¿Cómo se construyen el conocimiento, el discurso y las identidades de las disciplinas? ¿Cómo pueden las escuelas darles acceso a los estudiantes a las competencias basadas en la escuela? ¿Cuáles son los papeles cambiantes de los maestros y los estudiantes de competencias dentro y fuera de la escuela? ¿Cómo plantea la investigación del análisis del discurso el movimiento dentro y a través de los sitios de competencias y prácticas en este mundo contemporáneo, globalizado y digital?Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88086/1/RRQ.45.1.5.pd

Regional and cellular gene expression changes in human Huntington's disease brain

Huntington's disease (HD) pathology is well understood at a histological level but a comprehensive molecular analysis of the effect of the disease in the human brain has not previously been available. To elucidate the molecular phenotype of HD on a genome-wide scale, we compared mRNA profiles from 44 human HD brains with those from 36 unaffected controls using microarray analysis. Four brain regions were analyzed: caudate nucleus, cerebellum, prefrontal association cortex [Brodmann's area 9 (BA9)] and motor cortex [Brodmann's area 4 (BA4)]. The greatest number and magnitude of differentially expressed mRNAs were detected in the caudate nucleus, followed by motor cortex, then cerebellum. Thus, the molecular phenotype of HD generally parallels established neuropathology. Surprisingly, no mRNA changes were detected in prefrontal association cortex, thereby revealing subtleties of pathology not previously disclosed by histological methods. To establish that the observed changes were not simply the result of cell loss, we examined mRNA levels in laser-capture microdissected neurons from Grade 1 HD caudate compared to control. These analyses confirmed changes in expression seen in tissue homogenates; we thus conclude that mRNA changes are not attributable to cell loss alone. These data from bona fide HD brains comprise an important reference for hypotheses related to HD and other neurodegenerative disease