An Evaluation of the Genetic Structure of Mapleleaf Mussels (Quadrula quadrula) in the Lake Erie Watershed

Physical barriers, habitat fragmentation, invasive species and geographic distance have isolated remnant populations of unionids in Great Lakes coastal refuges. Dreissenid species (Dreissena polymorpha and Dreissena rostriformis bugensis) may be the greatest threat to the survival of unionids in the Great Lakes since their introduction in the late 1980s and early 1990s; however, native unionids remain in coastal habitats of western Lake Erie. One of the most abundant unionid species in Lake Erie, Quadrula quadrula, was collected along coastal areas within the lake and from three tributaries, the Maumee River, Huron River (Ohio), and Grand River (Ontario, Canada) and genotyped at six polymorphic microsatellite loci to determine population structure. There was evidence of genetic differentiation by geographic distance, and genotypes clustered into three geographic regions: Lake Erie, the Maumee River, and the Grand River. Lack of fine-scale genetic differentiation, admixture among these regions, and significant isolation by distance, indicate connectivity and are consistent with a stepping-stone model of divergence across the lake and its tributaries. A diverse gene pool remains should Q. quadrula be able to repopulate more of their historic distribution across the region, but studies of other unionid species are needed to determine whether low levels of differentiation among lake populations or divergence from tributary populations is a common pattern

Non-sexist Language Policy and the Rise (and Fall?) of Combined Pronouns in British and American Written English

This paper focuses on the use of combined pronouns (s/he, his or her, him/her, etc.) as an example of late twentieth-century non-sexist language reform which had an overt democratizing aim. Within the scope of second-wave feminism, the use of combined pronouns increased the visibility of women in discourse by encouraging the use of feminine pronouns (she, her, hers) alongside masculine pronouns (he, him, his). Despite their promotion, however, the use of combined pronouns is relatively rare. This paper uses the LOB and Brown families of corpora to diachronically and synchronically study patterns in the use of combined pronouns in written American (AmE) and British English (BrE) from the 1930s to the early 2000s. The analysis not only determines what forms these patterns take, but questions whether combined pronouns are influenced by (a combination of) syntax and/or semantics, and questions whether combined pronouns are really democratic at all

Competitive Replacement of Invasive Congeners May Relax Impact on Native Species: Interactions among Zebra, Quagga, and Native Unionid Mussels

Determining when and where the ecological impacts of invasive species will be most detrimental and whether the effects of multiple invaders will be superadditive, or subadditive, is critical for developing global management priorities to protect native species in advance of future invasions. Over the past century, the decline of freshwater bivalves of the family Unionidae has been greatly accelerated by the invasion of Dreissena. The purpose of this study was to evaluate the current infestation rates of unionids by zebra (Dreissena polymorpha) and quagga (D. rostriformis bugensis) mussels in the lower Great Lakes region 25 years after they nearly extirpated native unionids. In 2011–2012, we collected infestation data for over 4000 unionids from 26 species at 198 nearshore sites in lakes Erie, Ontario, and St. Clair, the Detroit River, and inland Michigan lakes and compared those results to studies from the early 1990s. We found that the frequency of unionid infestation by Dreissena recently declined, and the number of dreissenids attached to unionids in the lower Great Lakes has fallen almost ten-fold since the early 1990s. We also found that the rate of infestation depends on the dominant Dreissena species in the lake: zebra mussels infested unionids much more often and in greater numbers. Consequently, the proportion of infested unionids, as well as the number and weight of attached dreissenids were lower in waterbodies dominated by quagga mussels. This is the first large-scale systematic study that revealed how minor differences between two taxonomically and functionally related invaders may have large consequences for native communities they invade

Density of Healthcare Providers and Patient Outcomes: Evidence from a Nationally Representative Multi-Site HIV Treatment Program in Uganda

This study examined the association between density of healthcare providers and patient outcomes using a large nationally representative cohort of patients receiving combination antiretroviral therapy (cART) in Uganda.Objective: We examined the association between density of healthcare providers and patient outcomes using a large nationally representative cohort of patients receiving combination antiretroviral therapy (cART) in Uganda. Design: We obtained data from The AIDS Support Organization (TASO) in Uganda. Patients 18 years of age and older who initiated cART at TASO between 2004 and 2008 contributed to this analysis. The number of healthcare providers per 100 patients, the number of patients lost to follow-up per 100 person years and number of deaths per 100 person years were calculated. Spearman correlation was used to identify associations between patient loss to follow-up and mortality with the healthcare provider-patient ratios. Results: We found no significant associations between the number of patients lost to follow-up and physicians (p = 0.45), nurses (p = 0.93), clinical officers (p = 0.80), field officers (p = 0.56), and healthcare providers overall (p = 0.83). Similarly, no significant associations were observed between mortality and physicians (p = 0.65), nurses (p = 0.49), clinical officers (p = 0.73), field officers (p = 0.78), and healthcare providers overall (p = 0.73). Conclusions: Patient outcomes, as measured by loss to follow-up and mortality, were not significantly associated with the number of doctors, nurses, clinical officers, field officers, or healthcare providers overall. This may suggest that that other factors, such as the presence of volunteer patient supporters or broader political or socioeconomic influences, may be more closely associated with outcomes of care among patients on cART in Uganda

Promoting patient engagement with self-management support information: a qualitative meta-synthesis of processes influencing uptake

<p>Abstract</p> <p>Background</p> <p>Patient information has been viewed as a key component of self-management. However, little attention has been given to methods of dissemination or implementation of effective information strategies. Previous problems identified with the use and implementation of patient information point to the need to explore the way in which patients engage with and use information to support self-management for chronic conditions.</p> <p>Methods</p> <p>Four published qualitative studies from a programme of research about self-management were analysed as a group; these included studies of the management of inflammatory bowel disease (IBD); self-help in anxiety and depression (SHADE); menorrhagia, treatment, information, and preference (MENTIP) study; and self-help for irritable bowel syndrome (IBS). For the analysis, we used an adapted meta-ethnographic approach to the synthesis of qualitative data in order to develop an evidence base.</p> <p>Results</p> <p>The ontological status and experience of the condition in everyday life was the most dominant theme to emerge from this synthesis. This, coupled with access to and experience of traditional health services responses, shaped the engagement with and use of information to support self-management. Five key elements were found which were likely to influence this: the perception and awareness of alternative self-management possibilities; the prior extent and nature of engagement with information; the extent of and ability to self-manage; opportunities for use of the information and the stage of the illness career; and congruence and synergy with the professional role.</p> <p>Conclusion</p> <p>People with chronic conditions need support from providers in both supply and engagement with information, in a way which gives legitimacy to the person's own self-management strategies and possible alternatives. Thus, a link could usefully be made between information offered, as well as patients' past experiences of self-management and engagement with services for their condition. The timeliness of the information should be considered, both in terms of the illness career and the type of condition (<it>i.e</it>., before depression gets too bad or time to reflect on existing knowledge about a condition and how it is to be managed) and in terms of the pre-existing relationship with services (<it>i.e</it>., options explored and tried).</p> <p>More considered use of information (how it is provided, by whom, and at what point it should be introduced) is key to facilitating patients' engagement with and therefore use of information to support self-management.</p

Developing consensus-based policy solutions for medicines adherence for Europe: a Delphi study

<p>Abstract</p> <p>Background</p> <p>Non-adherence to prescribed medication is a pervasive problem that can incur serious effects on patients’ health outcomes and well-being, and the availability of resources in healthcare systems. This study aimed to develop practical consensus-based policy solutions to address medicines non-adherence for Europe.</p> <p>Methods</p> <p>A four-round Delphi study was conducted. The Delphi Expert Panel comprised 50 participants from 14 countries and was representative of: patient/carers organisations; healthcare providers and professionals; commissioners and policy makers; academics; and industry representatives. Participants engaged in the study remotely, anonymously and electronically. Participants were invited to respond to open questions about the causes, consequences and solutions to medicines non-adherence. Subsequent rounds refined responses, and sought ratings of the relative importance, and operational and political feasibility of each potential solution to medicines non-adherence. Feedback of individual and group responses was provided to participants after each round. Members of the Delphi Expert Panel and members of the research group participated in a consensus meeting upon completion of the Delphi study to discuss and further refine the proposed policy solutions.</p> <p>Results</p> <p>43 separate policy solutions to medication non-adherence were agreed by the Panel. 25 policy solutions were prioritised based on composite scores for importance, and operational and political feasibility. Prioritised policy solutions focused on interventions for patients, training for healthcare professionals, and actions to support partnership between patients and healthcare professionals. Few solutions concerned actions by governments, healthcare commissioners, or interventions at the system level.</p> <p>Conclusions</p> <p>Consensus about practical actions necessary to address non-adherence to medicines has been developed for Europe. These actions are also applicable to other regions. Prioritised policy solutions for medicines non-adherence offer a benefit to policymakers and healthcare providers seeking to address this multifaceted, complex problem.</p

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Vancomycin AUC/MIC ratio and 30-day mortality in patients with Staphylococcus aureus bacteremia

A ratio of the vancomycin area under the concentration-time curve to the MIC (AUC/MIC) of ≥ 400 has been associated with clinical success when treating Staphylococcus aureus pneumonia, and this target was recommended by recently published vancomycin therapeutic monitoring consensus guidelines for treating all serious S. aureus infections. Here, vancomycin serum trough levels and vancomycin AUC/MIC were evaluated in a "real-world" context by following a cohort of 182 patients with S. aureus bacteremia (SAB) and analyzing these parameters within the critical first 96 h of vancomycin therapy. The median vancomycin trough level at this time point was 19.5 mg/liter. There was a significant difference in vancomycin AUC/MIC when using broth microdilution (BMD) compared with Etest MIC (medians of 436.1 and 271.5, respectively; P373, derived using classification and regression tree analysis, was associated with reduced mortality (P=0.043) and remained significant in a multivariable model. This study demonstrated that we obtained vancomycin trough levels in the target therapeutic range early during the course of therapy and that obtaining a higher vancomycin AUC/MIC (in this case, >373) within 96 h was associated with reduced mortality. The MIC test method has a significant impact on vancomycin AUC/MIC estimation. Clinicians should be aware that the current target AUC/MIC of ≥400 was derived using the reference BMD method, so adjustments to this target need to be made when calculating AUC/MIC ratio using other MIC testing methods. Copyrigh

Species difference in ANP32A underlies influenza A virus polymerase host restriction.

Influenza pandemics occur unpredictably when zoonotic influenza viruses with novel antigenicity acquire the ability to transmit amongst humans. Host range breaches are limited by incompatibilities between avian virus components and the human host. Barriers include receptor preference, virion stability and poor activity of the avian virus RNA-dependent RNA polymerase in human cells. Mutants of the heterotrimeric viral polymerase components, particularly PB2 protein, are selected during mammalian adaptation, but their mode of action is unknown. We show that a species-specific difference in host protein ANP32A accounts for the suboptimal function of avian virus polymerase in mammalian cells. Avian ANP32A possesses an additional 33 amino acids between the leucine-rich repeats and carboxy-terminal low-complexity acidic region domains. In mammalian cells, avian ANP32A rescued the suboptimal function of avian virus polymerase to levels similar to mammalian-adapted polymerase. Deletion of the avian-specific sequence from chicken ANP32A abrogated this activity, whereas its insertion into human ANP32A, or closely related ANP32B, supported avian virus polymerase function. Substitutions, such as PB2(E627K), were rapidly selected upon infection of humans with avian H5N1 or H7N9 influenza viruses, adapting the viral polymerase for the shorter mammalian ANP32A. Thus ANP32A represents an essential host partner co-opted to support influenza virus replication and is a candidate host target for novel antivirals

Implementation and evaluation of a multi-level mental health promotion intervention for the workplace (MENTUPP): study protocol for a cluster randomised controlled trial

Background Well-organised and managed workplaces can be a source of wellbeing. The construction, healthcare and information and communication technology sectors are characterised by work-related stressors (e.g. high workloads, tight deadlines) which are associated with poorer mental health and wellbeing. The MENTUPP intervention is a flexibly delivered, multi-level approach to supporting small- and medium-sized enterprises (SMEs) in creating mentally healthy workplaces. The online intervention is tailored to each sector and designed to support employees and leaders dealing with mental health difficulties (e.g. stress), clinical level anxiety and depression, and combatting mental health-related stigma. This paper presents the protocol for the cluster randomised controlled trial (cRCT) of the MENTUPP intervention in eight European countries and Australia. Methods Each intervention country will aim to recruit at least two SMEs in each of the three sectors. The design of the cRCT is based on the experiences of a pilot study and guided by a Theory of Change process that describes how the intervention is assumed to work. SMEs will be randomly assigned to the intervention or control conditions. The aim of the cRCT is to assess whether the MENTUPP intervention is effective in improving mental health and wellbeing (primary outcome) and reducing stigma, depression and suicidal behaviour (secondary outcome) in employees. The study will also involve a process and economic evaluation. Conclusions At present, there is no known multi-level, tailored, flexible and accessible workplace-based intervention for the prevention of non-clinical and clinical symptoms of depression, anxiety and burnout, and the promotion of mental wellbeing. The results of this study will provide a comprehensive overview of the implementation and effectiveness of such an intervention in a variety of contexts, languages and cultures leading to the overall goal of delivering an evidence-based intervention for mental health in the workplace