Ion Pair-Directed Regiocontrol in Transition-Metal Catalysis: A Meta-Selective C-H Borylation of Aromatic Quaternary Ammonium Salts

The use of noncovalent interactions to direct transition-metal catalysis is a potentially powerful yet relatively underexplored strategy, with most investigations thus far focusing on using hydrogen bonds as the controlling element. We have developed an ion pair-directed approach to controlling regioselectivity in the iridium-catalyzed borylation of two classes of aromatic quaternary ammonium salts, leading to versatile meta-borylated products. By examining a range of substituted substrates, this provides complex, functionalized aromatic scaffolds amenable to rapid diversification and more broadly demonstrates the viability of ion-pairing for control of regiochemistry in transition-metal catalysis.Engineering and Physical Sciences Research Council and Pfizer (CASE studentship), AstraZeneca (AZ-Cambridge Ph.D. Program studentship), Royal Society (University Research Fellowship), Engineering and Physical Sciences Research Council and Engineering and Physical Sciences Research Council U.K. National Mass Spectrometry Facility (Swansea University

Early diagnosis and treatment of HIV infection: magnitude of benefit on short-term mortality is greatest in older adults.

BACKGROUND: the number and proportion of adults diagnosed with HIV infection aged 50 years and older has risen. This study compares the effect of CD4 counts and anti-retroviral therapy (ART) on mortality rates among adults diagnosed aged ≥50 with those diagnosed at a younger age. METHODS: retrospective cohort analysis of national surveillance reports of HIV-diagnosed adults (15 years and older) in England, Wales and Northern Ireland. The relative impacts of age, CD4 count at diagnosis and ART on mortality were determined in Cox proportional hazards models. RESULTS: among 63,805 adults diagnosed with HIV between 2000 and 2009, 9% (5,683) were aged ≥50 years; older persons were more likely to be white, heterosexual and present with a CD4 count <200 cells/mm(3) (48 versus 32% P < 0.01) and AIDS at diagnosis (19 versus 9%, P < 0.01). One-year mortality was higher in older adults (10 versus 3%, P < 0.01) and especially in those diagnosed with a CD4 <200 cells/mm(3) left untreated (46 versus 15%, P < 0.01). While the relative mortality risk reduction from ART initiation at CD <200 cells/mm(3) was similar in both age groups, the absolute risk difference was higher among older adults (40 versus 12% fewer deaths) such that the number needed to treat older adults to prevent one death was two compared with eight among younger adults. CONCLUSIONS: the magnitude of benefit from ART is greater in older adults than younger adults. Older persons should be considered as a target for HIV testing. Coupled with prompt treatment, earlier diagnosis is likely to reduce substantially deaths in this group

Montreal Cognitive Assessment for the diagnosis of Alzheimer's disease and other dementias.

BACKGROUND: Dementia is a progressive syndrome of global cognitive impairment with significant health and social care costs. Global prevalence is projected to increase, particularly in resource-limited settings. Recent policy changes in Western countries to increase detection mandates a careful examination of the diagnostic accuracy of neuropsychological tests for dementia. OBJECTIVES: To determine the diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) at various thresholds for dementia and its subtypes. SEARCH METHODS: We searched MEDLINE, EMBASE, BIOSIS Previews, Science Citation Index, PsycINFO and LILACS databases to August 2012. In addition, we searched specialised sources containing diagnostic studies and reviews, including MEDION (Meta-analyses van Diagnostisch Onderzoek), DARE (Database of Abstracts of Reviews of Effects), HTA (Health Technology Assessment Database), ARIF (Aggressive Research Intelligence Facility) and C-EBLM (International Federation of Clinical Chemistry and Laboratory Medicine Committee for Evidence-based Laboratory Medicine) databases. We also searched ALOIS (Cochrane Dementia and Cognitive Improvement Group specialized register of diagnostic and intervention studies). We identified further relevant studies from the PubMed 'related articles' feature and by tracking key studies in Science Citation Index and Scopus. We also searched for relevant grey literature from the Web of Science Core Collection, including Science Citation Index and Conference Proceedings Citation Index (Thomson Reuters Web of Science), PhD theses and contacted researchers with potential relevant data. SELECTION CRITERIA: Cross-sectional designs where all participants were recruited from the same sample were sought; case-control studies were excluded due to high chance of bias. We searched for studies from memory clinics, hospital clinics, primary care and community populations. We excluded studies of early onset dementia, dementia from a secondary cause, or studies where participants were selected on the basis of a specific disease type such as Parkinson's disease or specific settings such as nursing homes. DATA COLLECTION AND ANALYSIS: We extracted dementia study prevalence and dichotomised test positive/test negative results with thresholds used to diagnose dementia. This allowed calculation of sensitivity and specificity if not already reported in the study. Study authors were contacted where there was insufficient information to complete the 2x2 tables. We performed quality assessment according to the QUADAS-2 criteria.Methodological variation in selected studies precluded quantitative meta-analysis, therefore results from individual studies were presented with a narrative synthesis. MAIN RESULTS: Seven studies were selected: three in memory clinics, two in hospital clinics, none in primary care and two in population-derived samples. There were 9422 participants in total, but most of studies recruited only small samples, with only one having more than 350 participants. The prevalence of dementia was 22% to 54% in the clinic-based studies, and 5% to 10% in population samples. In the four studies that used the recommended threshold score of 26 or over indicating normal cognition, the MoCA had high sensitivity of 0.94 or more but low specificity of 0.60 or less. AUTHORS' CONCLUSIONS: The overall quality and quantity of information is insufficient to make recommendations on the clinical utility of MoCA for detecting dementia in different settings. Further studies that do not recruit participants based on diagnoses already present (case-control design) but apply diagnostic tests and reference standards prospectively are required. Methodological clarity could be improved in subsequent DTA studies of MoCA by reporting findings using recommended guidelines (e.g. STARDdem). Thresholds lower than 26 are likely to be more useful for optimal diagnostic accuracy of MoCA in dementia, but this requires confirmation in further studies.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/14651858.CD010775.pub

Moving from evidence-based medicine to evidence-based health.

While evidence-based medicine (EBM) has advanced medical practice, the health care system has been inconsistent in translating EBM into improvements in health. Disparities in health and health care play out through patients' limited ability to incorporate the advances of EBM into their daily lives. Assisting patients to self-manage their chronic conditions and paying attention to unhealthy community factors could be added to EBM to create a broader paradigm of evidence-based health. A perspective of evidence-based health may encourage physicians to consider their role in upstream efforts to combat socially patterned chronic disease

Musical preferences and technologies: Contemporary material and symbolic distinctions criticised

Today how individuals interact with various cultural items is not perfectly consistent with theoretical frameworks of influential scholars on cultural consumption, such as Bourdieu (1984), Gans (1999), and Peterson and Simkus (1992). One such variation is in the ever increasing variety of technological modes to acquire and listen to music (Pinch and Bijsterveld, 2004). However, as a consequence of digital divides (van Dijk, 2006), technological items may not be distributed equally among social groups. At present, the value of status-making through a preference for different genres of music extends itself to different forms of consumption and ways of experiencing music. We are yet to fully understand the power these practices have on generating status. This article is therefore motivated by the need to integrate within quantitative frameworks of taste and cultural consumption, an analysis of individuals’ technological engagement. These two dimensions, integrated as components of musical practices, enhance our understanding of cultural boundaries across different social groups.The objective is to bridge a gap detected in the literature, addressing the following questions: Are technological modes to listen to music related to musical tastes

Retrograde semaphorin-plexin signalling drives homeostatic synaptic plasticity.

Homeostatic signalling systems ensure stable but flexible neural activity and animal behaviour. Presynaptic homeostatic plasticity is a conserved form of neuronal homeostatic signalling that is observed in organisms ranging from Drosophila to human. Defining the underlying molecular mechanisms of neuronal homeostatic signalling will be essential in order to establish clear connections to the causes and progression of neurological disease. During neural development, semaphorin-plexin signalling instructs axon guidance and neuronal morphogenesis. However, semaphorins and plexins are also expressed in the adult brain. Here we show that semaphorin 2b (Sema2b) is a target-derived signal that acts upon presynaptic plexin B (PlexB) receptors to mediate the retrograde, homeostatic control of presynaptic neurotransmitter release at the neuromuscular junction in Drosophila. Further, we show that Sema2b-PlexB signalling regulates presynaptic homeostatic plasticity through the cytoplasmic protein Mical and the oxoreductase-dependent control of presynaptic actin. We propose that semaphorin-plexin signalling is an essential platform for the stabilization of synaptic transmission throughout the developing and mature nervous system. These findings may be relevant to the aetiology and treatment of diverse neurological and psychiatric diseases that are characterized by altered or inappropriate neural function and behaviour

A qualitative exploration of the effect of visual field loss on daily life in home-dwelling stroke survivors

Objective: To explore the effect of visual field loss on the daily life of community-dwelling stroke survivors. Design: A qualitative interview study. Participants: Adult stroke survivors with visual field loss of at least six months’ duration. Methods: Semi-structured interviews were conducted with a non-purposive sample of 12 stroke survivors in their own homes. These were recorded, transcribed verbatim and analyzed with the framework method, using an inductive approach. Results: Two key analytical themes emerged. ‘Perception, experience and knowledge’ describes participant’s conflicted experience of having knowledge of their impaired vision but lacking perception of that visual field loss and operating under the assumption that they were viewing an intact visual scene when engaged in activities. Inability to recognize and deal with visual difficulties, and experiencing the consequences, contributed to their fear and loss of self-confidence. ‘Avoidance and adaptation’ were two typologies of participant response to visual field loss. Initially, all participants consciously avoided activities. Some later adapted to vision loss using self-directed head and eye scanning techniques. Conclusions: Visual field loss has a marked impact on stroke survivors. Stroke survivors lack perception of their visual loss in everyday life, resulting in fear and loss of confidence. Activity avoidance is a common response, but in some, it is replaced by self-initiated adaptive techniques

Delineation of individual human chromosomes in metaphase and interphase cells by in situ suppression hybridization using recombinant DNA libraries

A method of in situ hybridization for visualizing individual human chromosomes from pter to qter, both in metaphase spreads and interphase nuclei, is reported. DNA inserts from a single chromosomal library are labeled with biotin and partially preannealed with a titrated amount of total human genomic DNA prior to hybridization with cellular or chromosomal preparations. The cross-hybridization of repetitive sequences to nontargeted chromosomes can be markedly suppressed under appropriate preannealing conditions. The remaining single-stranded DNA is hybridized to specimens of interest and detected with fluorescent or enzymelabeled avidin conjugates following post-hybridization washes. DNA inserts from recombinant libraries for chromosomes 1, 4, 7, 8, 13, 14, 18, 20, 21, 22, and X were assessed for their ability to decorate specifically their cognate chromosome; most libraries proved to be highly specific. Quantitative densitometric analyses indicated that the ratio of specific to nonspecific hybridization signal under optimal preannealing conditions was at least 8:1. Interphase nuclei showed a cohesive territorial organization of chromosomal domains, and laserscanning confocal fluorescence microscopy was used to aid the 3-D visualization of these domains. This method should be useful for both karyotypic studies and for the analysis of chromosome topography in interphase cells