Water quality effects following establishment of the invasive Dreissena polymorpha (Pallas) in a shallow eutrophic lake: implications for pollution mitigation measures

This study investigates whether ecosystem alteration occurred in a shallow, lowland lake following establishment of the alien zebra mussel, Dreissena polymorpha (Pallas). Measurements of total phosphorus (TP) loads, lake TP concentrations, phytoplankton (chlorophyll a) and transparency levels for the period 1990-2008 were examined to determine the water quality effects of D. polymorpha. The period of time also included the implementation of catchment measures aimed at reducing phosphorus (P) loading to the lake. A range of loading-response models was also tested to explore changes in the net sedimentation rate for P. Results show that while high TP loads from the catchment were reduced, TP concentrations in the lake remained high after D. polymorpha invasion. Decoupling of the previous chlorophyll a –TP relationship also occurred. Results from a TP loading-response model that closely simulated observed concentrations in the lake prior to establishment of D. polymorpha indicated that measured TP post establishment was statistically higher than predicted for the same conditions but without the presence of D. polymorpha. Data presented in the paper highlight the need to consider the potential impacts of invasive species in evaluations of the effectiveness of measures aimed at mitigating aquatic pollution

Temporal inabilities and decision-making capacity in depression

We report on an interview-based study of decision-making capacity in two classes of patients suffering from depression. Developing a method of second-person hermeneutic phenomenology, we articulate the distinctive combination of temporal agility and temporal inability characteristic of the experience of severely depressed patients. We argue that a cluster of decision-specific temporal abilities is a critical element of decision-making capacity, and we show that loss of these abilities is a risk factor distinguishing severely depressed patients from mildly/moderately depressed patients. We explore the legal and clinical consequences of this result

Testing Multiple Hypotheses through IMP weighted FDR Based on a Genetic Functional Network with Application to a New Zebrafish Transcriptome Study

In genome-wide studies, hundreds of thousands of hypothesis tests are performed simultaneously. Bonferroni correction and False Discovery Rate (FDR) can effectively control type I error but often yield a high false negative rate. We aim to develop a more powerful method to detect differentially expressed genes. We present a Weighted False Discovery Rate (WFDR) method that incorporate biological knowledge from genetic networks. We first identify weights using Integrative Multi-species Prediction (IMP) and then apply the weights in WFDR to identify differentially expressed genes through an IMP-WFDR algorithm. We performed a gene expression experiment to identify zebrafish genes that change expression in the presence of arsenic during a systemic Pseudomonas aeruginosa infection. Zebrafish were exposed to arsenic at 10 parts per billion and/or infected with P. aeruginosa. Appropriate controls were included. We then applied IMP-WFDR during the analysis of differentially expressed genes. We compared the mRNA expression for each group and found over 200 differentially expressed genes and several enriched pathways including defense response pathways, arsenic response pathways, and the Notch signaling pathway

Compendium-Wide Analysis of Pseudomonas aeruginosa Core and Accessory Genes Reveals Transcriptional Patterns across Strains PAO1 and PA14.

Pseudomonas aeruginosa is an opportunistic pathogen that causes difficult-to-treat infections. Two well-studied divergent P. aeruginosa strain types, PAO1 and PA14, have significant genomic heterogeneity, including diverse accessory genes present in only some strains. Genome content comparisons find core genes that are conserved across both PAO1 and PA14 strains and accessory genes that are present in only a subset of PAO1 and PA14 strains. Here, we use recently assembled transcriptome compendia of publicly available P. aeruginosa RNA sequencing (RNA-seq) samples to create two smaller compendia consisting of only strain PAO1 or strain PA14 samples with each aligned to their cognate reference genome. We confirmed strain annotations and identified other samples for inclusion by assessing each sample\u27s median expression of PAO1-only or PA14-only accessory genes. We then compared the patterns of core gene expression in each strain. To do so, we developed a method by which we analyzed genes in terms of which genes showed similar expression patterns across strain types. We found that some core genes had consistent correlated expression patterns across both compendia, while others were less stable in an interstrain comparison. For each accessory gene, we also determined core genes with correlated expression patterns. We found that stable core genes had fewer coexpressed neighbors that were accessory genes. Overall, this approach for analyzing expression patterns across strain types can be extended to other groups of genes, like phage genes, or applied for analyzing patterns beyond groups of strains, such as samples with different traits, to reveal a deeper understanding of regulation

N=2 Heterotic Superstring and its Dual Theory in Five Dimensions

We study quantum effects in five dimensions in heterotic superstring theory compactified on K_3 x S_1 and analyze the conjecture that its dual effective theory is eleven-dimensional supergravity compactified on a Calabi-Yau threefold. This theory is also equivalent to type II superstring theory compactified on the same Calabi-Yau manifold, in an appropriate large volume limit. In this limit the conifold singularity disappears and is replaced by a singularity associated to enhanced gauge symmetries, as naively expected from the heterotic description. Furthermore, we exhibit the existence of additional massless states which appear in the strong coupling regime of the heterotic theory and are related to a different type of singular points on Calabi-Yau threefolds.Comment: 26 pages, LaTe

Probing the embedded YSOs of the R CrA region through VLT-ISAAC spectroscopy

Near IR spectra obtained with ISAAC at VLT, have been used to pose constraints on the evolutionary state and accretion properties of a sample of five embedded YSOs located in the R CrA core. This sample includes three Class I sources (HH100 IR, IRS2 and IRS5), and two sources with NIR excesses (IRS6 and IRS3). Absorption lines have been detected in the medium resolution spectra of all the observed targets, together with emission lines likely originating in the disk-star-wind connected regions. We derived spectral types, veiling and stellar luminosity of the five observed sources, which in turn have been used to infer their mass and age adopting pre-main sequence evolutionary tracks. We find that in HH100 IR and IRS2 most of the bolometric luminosity is due to accretion, while the other three investigated sources, including the Class I object IRS5a, present a low accretion activity (L_{acc}/L_{bol} < 0.2). We observe a general correlation between the accretion luminosity, the IR veiling and the emission line activity of the sources. A correlation between the accretion activity and the spectral energy distribution slope is recognizable but with the notable exception of IRS5a. Our analysis therefore shows how the definition of the evolutionary stage of deeply embedded YSOs by means of IR colors needs to be more carefully refined.Comment: 17 pages, 13 figures, accepted on A&

‘We Need to Deploy Them Very Thoughtfully and Carefully’: Perceptions of Analytical Treatment Interruptions in HIV Cure Research in the United States – A Qualitative Inquiry

Strategies to control HIV in the absence of antiretroviral therapy are needed to cure HIV. However, such strategies will require analytical treatment interruptions (ATIs) to determine their efficacy. We investigated how U.S. stakeholders involved in HIV cure research perceive ATIs. We conducted 36 in-depth interviews with three groups of stakeholders: 12 people living with HIV, 11 clinician-researchers, and 13 policy-makers/bioethicists. Qualitative data revealed several themes. First, there was little consensus on when ATIs would be ethically warranted. Second, the most frequent perceived hypothetical motivators for participating in research on ATIs were advancing science and contributing to society. Third, risks related to viral rebound were the most prevalent concerns related to ATIs. Stakeholders suggested ways to minimize the risks of ATIs in HIV cure research. Increased cooperation between scientists and local communities may be useful for minimizing risk. Further ethics research is necessary

Willingness to Participate in HIV Cure Research: Survey Results from 400 People Living with HIV in the United States

Introduction Participation in early-phase HIV cure studies includes clinical risks with little to no likelihood of clinical benefit. Examining the willingness of people living with HIV to participate is important to guide study design and informed consent. Our study examined the overall willingness of people living with HIV to participate in HIV cure research in the US, focusing on perceived risks and benefits of participation. Methods We undertook an online survey of adults living with HIV in the US. Survey questions were developed based on previous research and a scoping review of the literature. We quantitatively assessed individuals’ perceived risks and benefits of HIV cure-related research and respondents’ willingness to participate in different modalities of HIV cure studies. Results We recruited 409 study participants of whom 400 were eligible for the study and were included in the analysis (nine were not eligible due to self-declared HIV-negative status). We found >50% willingness to participate in 14 different types of HIV cure studies. Perceived clinical benefits and social benefits were important motivators, while personal clinical risks appeared to deter potential participation. Roughly two-thirds of survey respondents (68%) indicated that they were somewhat willing to stop treatment as part of HIV cure research. In the bivariate models, females, African Americans/blacks, Hispanics, individuals in the lowest income bracket, people living with HIV for longer periods of their lives, and people who were self-perceived ‘very healthy’ were less willing to participate in certain types of HIV cure studies than others. Multivariate results showed the perceived benefits (adjusted odds ratios >1) and perceived risks (adjusted odds ratios <1) acted as potential motivators and deterrents to participation, respectively. Conclusion Our study is the first attempt to quantify potential motivators and deterrents of participation in HIV cure research in the US using perceived risks and benefits. The results offer guidance to HIV cure researchers and developers of interventions about the beneficial and detrimental characteristics of HIV cure strategies that are most meaningful to people living with HIV. The study also highlights new potential lines of inquiry for further social science and ethics research

Perceptions of Equipoise, Risk/Benefit Ratios, and ‘Otherwise Healthy Volunteers’ in the Context of Early-Phase HIV Cure Research in the United States – A Qualitative Inquiry

Early-phase HIV cure research is conducted against a background of highly effective antiretroviral therapy, and involves risky interventions in individuals who enjoy an almost normal life expectancy. To explore perceptions of three ethical topics in the context of HIV cure research—(a) equipoise, (b) risk–benefit ratios, and (c) “otherwise healthy volunteers”—we conducted 36 in-depth interviews (IDIs) with three groups of purposively selected key informants: clinician-researchers (n = 11), policy-makers and bioethicists (n = 13), and people living with HIV (PLWHIV; n = 12). Our analysis revealed variability in perceptions of equipoise. Second, most key informants believed there was no clear measure of risk–benefit ratios in HIV cure research, due in part to the complexity of weighing (sometimes unknown) risks to participants and (sometimes speculative) benefits to science and society. Third, most clinician-researchers and policy-makers/bioethicists viewed potential HIV cure study participants as “otherwise healthy volunteers,” but this perception was not shared among PLWHIV in our study

Antiemetic use among pregnant women in the United States: the escalating use of ondansetron

PURPOSE: To examine ondansetron use in pregnancy in the context of other antiemetic use among a large insured United States population of women delivering live births. METHODS: We assessed ondansetron and other antiemetic use among pregnant women delivering live births between 2001 and 2015 in 15 data partners contributing data to the Mini-Sentinel Distributed Database. We identified live birth pregnancies using a validated algorithm, and all forms of ondansetron and other available antiemetics were identified using National Drug Codes or procedure codes. We assessed the prevalence of antiemetic use by trimester, calendar year, and formulation. RESULTS: In over 2.3 million pregnancies, the prevalence of ondansetron, promethazine, metoclopramide, or doxylamine/pyridoxine use anytime in pregnancy was 15.2, 10.3, 4.0, and 0.4%, respectively. Ondansetron use increased from \u3c1% of pregnancies in 2001 to 22.2% in 2014, with much of the increase attributable to oral ondansetron beginning in 2006. Promethazine and metoclopramide use increased modestly between 2001 (13.8%, 3.2%) and 2006 (16.0%, 6.0%) but decreased annually through 2014 (8.0%, 3.2%). Doxylamine/pyridoxine, approved for management of nausea and vomiting in pregnancy in 2013, was used in 1.8% of pregnancies in 2014. For all antiemetics, use was highest in the first trimester. CONCLUSIONS: We observed a marked increase in ondansetron use by study year, prescribed to nearly one-quarter of insured pregnant women in 2014, occurring in conjunction with decreased use of promethazine and metoclopramide. Given the widespread use of ondansetron in pregnancy, data establishing product efficacy and methodologically rigorous evaluation of post-marketing safety are needed