Mortality Reduction Associated with HIV/AIDS Care and Antiretroviral Treatment in Rural Malawi: Evidence from Registers, Coffin Sales and Funerals

BACKGROUND: To report on the trend in all-cause mortality in a rural district of Malawi that has successfully scaled-up HIV/AIDS care including antiretroviral treatment (ART) to its population, through corroborative evidence from a) registered deaths at traditional authorities (TAs), b) coffin sales and c) church funerals. METHODS AND FINDINGS: Retrospective study in 5 of 12 TAs (covering approximately 50% of the population) during the period 2000-2007. A total of 210 villages, 24 coffin workshops and 23 churches were included. There were a total of 18,473 registered deaths at TAs, 15781 coffins sold, and 2762 church funerals. Between 2000 and 2007, there was a highly significant linear downward trend in death rates, sale of coffins and church funerals (X(2) for linear trend: 338.4 P<0.0001, 989 P<0.0001 and 197, P<0.0001 respectively). Using data from TAs as the most reliable source of data on deaths, overall death rate reduction was 37% (95% CI:33-40) for the period. The mean annual incremental death rate reduction was 0.52/1000/year. Death rates decreased over time as the percentage of people living with HIV/AIDS enrolled into care and ART increased. Extrapolating these data to the entire district population, an estimated 10,156 (95% CI: 9786-10259) deaths would have been averted during the 8-year period. CONCLUSIONS: Registered deaths at traditional authorities, the sale of coffins and church funerals showed a significant downward trend over a 8-year period which we believe was associated with the scaling up HIV/AIDS care and ART

Structure of Complement Component C2a: Implications for Convertase Formation and Substrate Binding

SummaryC2a provides the catalytic center to the convertase complexes of the classical and lectin-binding pathways of complement activation. We determined two crystal structures of full-length C2a, with and without a pseudo ligand bound. Both structures reveal a near-active conformation of the catalytic center of the serine protease domains, while the von Willebrand factor A-type domains display an intermediate activation state of helix α7 with an open, activated metal-ion-dependent adhesion site. The open adhesion site likely serves to enhance the affinity for the ligand C4b, similar to “inside-out” signaling in integrins. Surprisingly, the N-terminal residues of C2a are buried in a crevice near helix α7, indicative of a structural switch between C2 and C2a. Extended loops on the protease domain possibly envelop the protruding anaphylatoxin domain of the substrate C3. Together with a putative substrate-induced completion of the oxyanion hole, this may contribute to the high substrate specificity of the convertases

Protracted timescales of lower crustal growth at the fast-spreading East Pacific Rise

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Geoscience 5 (2012): 275-278, doi:10.1038/ngeo1378.Formation of the oceanic crust at mid-ocean ridges is a fundamental component of plate tectonics. A majority of the crust at many ridges is composed of plutonic rocks that form by crystallization of mantle-derived magmas within the crust. Recent application of U/Pb dating to samples from in-situ oceanic crust has begun to provide exciting new insight into the timing, duration and distribution of magmatism during formation of the plutonic crust1-4. Previous studies have focused on samples from slow-spreading ridges, however, the time scales and processes of crustal growth are expected to vary with plate spreading rate. Here we present the first high-precision dates from plutonic crust formed at the fast-spreading East Pacific Rise (EPR). Individual zircon minerals yielded dates from 1.420–1.271 million years ago, with uncertainties of ± 0.006–0.081 million years. Within individual samples, zircons record a range of dates of up to ~0.124 million years, consistent with protracted crystallization or assimilation of older zircons from adjacent rocks. The variability in dates is comparable to data from the Vema lithospheric section on the Mid-Atlantic Ridge (MAR)3, suggesting that time scales of magmatic processes in the lower crust may be similar at slow- and fast-spreading ridges.This research was partially funded by NSF grant OCE-0727914 (SAB), a Cardiff University International Collaboration Award (CJL) and NERC grant NE/C509023/1 (CJM).2012-07-2

Use of Self-Selected Postures to Regulate Multi-Joint Stiffness During Unconstrained Tasks

The human motor system is highly redundant, having more kinematic degrees of freedom than necessary to complete a given task. Understanding how kinematic redundancies are utilized in different tasks remains a fundamental question in motor control. One possibility is that they can be used to tune the mechanical properties of a limb to the specific requirements of a task. For example, many tasks such as tool usage compromise arm stability along specific directions. These tasks only can be completed if the nervous system adapts the mechanical properties of the arm such that the arm, coupled to the tool, remains stable. The purpose of this study was to determine if posture selection is a critical component of endpoint stiffness regulation during unconstrained tasks.Three-dimensional (3D) estimates of endpoint stiffness were used to quantify limb mechanics. Most previous studies examining endpoint stiffness adaptation were completed in 2D using constrained postures to maintain a non-redundant mapping between joint angles and hand location. Our hypothesis was that during unconstrained conditions, subjects would select arm postures that matched endpoint stiffness to the functional requirements of the task. The hypothesis was tested during endpoint tracking tasks in which subjects interacted with unstable haptic environments, simulated using a 3D robotic manipulator. We found that arm posture had a significant effect on endpoint tracking accuracy and that subjects selected postures that improved tracking performance. For environments in which arm posture had a large effect on tracking accuracy, the self-selected postures oriented the direction of maximal endpoint stiffness towards the direction of the unstable haptic environment.These results demonstrate how changes in arm posture can have a dramatic effect on task performance and suggest that postural selection is a fundamental mechanism by which kinematic redundancies can be exploited to regulate arm stiffness in unconstrained tasks

Resectability and Ablatability Criteria for the Treatment of Liver Only Colorectal Metastases:Multidisciplinary Consensus Document from the COLLISION Trial Group

The guidelines for metastatic colorectal cancer crudely state that the best local treatment should be selected from a 'toolbox' of techniques according to patient- and treatment-related factors. We created an interdisciplinary, consensus-based algorithm with specific resectability and ablatability criteria for the treatment of colorectal liver metastases (CRLM). To pursue consensus, members of the multidisciplinary COLLISION and COLDFIRE trial expert panel employed the RAND appropriateness method (RAM). Statements regarding patient, disease, tumor and treatment characteristics were categorized as appropriate, equipoise or inappropriate. Patients with ECOG≤2, ASA≤3 and Charlson comorbidity index ≤8 should be considered fit for curative-intent local therapy. When easily resectable and/or ablatable (stage IVa), (neo)adjuvant systemic therapy is not indicated. When requiring major hepatectomy (stage IVb), neo-adjuvant systemic therapy is appropriate for early metachronous disease and to reduce procedural risk. To downstage patients (stage IVc), downsizing induction systemic therapy and/or future remnant augmentation is advised. Disease can only be deemed permanently unsuitable for local therapy if downstaging failed (stage IVd). Liver resection remains the gold standard. Thermal ablation is reserved for unresectable CRLM, deep-seated resectable CRLM and can be considered when patients are in poor health. Irreversible electroporation and stereotactic body radiotherapy can be considered for unresectable perihilar and perivascular CRLM 0-5cm. This consensus document provides per-patient and per-tumor resectability and ablatability criteria for the treatment of CRLM. These criteria are intended to aid tumor board discussions, improve consistency when designing prospective trials and advance intersociety communications. Areas where consensus is lacking warrant future comparative studies.</p

Diversity arrays technology (DArT) markers in apple for genetic linkage maps

Diversity Arrays Technology (DArT) provides a high-throughput whole-genome genotyping platform for the detection and scoring of hundreds of polymorphic loci without any need for prior sequence information. The work presented here details the development and performance of a DArT genotyping array for apple. This is the first paper on DArT in horticultural trees. Genetic mapping of DArT markers in two mapping populations and their integration with other marker types showed that DArT is a powerful high-throughput method for obtaining accurate and reproducible marker data, despite the low cost per data point. This method appears to be suitable for aligning the genetic maps of different segregating populations. The standard complexity reduction method, based on the methylation-sensitive PstI restriction enzyme, resulted in a high frequency of markers, although there was 52–54% redundancy due to the repeated sampling of highly similar sequences. Sequencing of the marker clones showed that they are significantly enriched for low-copy, genic regions. The genome coverage using the standard method was 55–76%. For improved genome coverage, an alternative complexity reduction method was examined, which resulted in less redundancy and additional segregating markers. The DArT markers proved to be of high quality and were very suitable for genetic mapping at low cost for the apple, providing moderate genome coverage

Resolving identity ambiguity through transcending fandom

Identity construction involves accumulating cultural, social, and symbolic capital, with initial endowments being accrued through socialization into one’s habitus. This research explores the experiences of individuals that feel a lack of capital, which leads to ambiguity regarding their identities and places in the world. Through in-depth interviews, this interpretive research shows that such individuals may turn to fandom for gaining status and belonging. Fandoms are consumption fields with clear, limited forms of cultural capital. Through serial fandom and engagement with fandom in different ways, individuals were able to learn the skill of identifying and accruing relevant cultural capital. The skill became decontextualized and recontextualized, allowing individuals to transcend fandom and accrue general forms of cultural capital. Learning the skill aids individuals in dealing with the simultaneously debilitating and empowering freedom of contemporary consumer culture. Moreover, gaining cultural capital could be altogether developing into the form of the process we describe