A Composite Genome Approach to Identify Phylogenetically Informative Data from Next-Generation Sequencing

We have developed a novel method to rapidly obtain homologous genomic data for phylogenetics directly from next-generation sequencing reads without the use of a reference genome. This software, called SISRS, avoids the time consuming steps of de novo whole genome assembly, genome-genome alignment, and annotation. For simulations SISRS is able to identify large numbers of loci containing variable sites with phylogenetic signal. For genomic data from apes, SISRS identified thousands of variable sites, from which we produced an accurate phylogeny. Finally, we used SISRS to identify phylogenetic markers that we used to estimate the phylogeny of placental mammals. We recovered phylogenies from multiple datasets that were consistent with previous conflicting estimates of the relationships among mammals. SISRS is open source and freely available at https://github.com/rachelss/SISRS.Comment: 12 pages plus36 figures, 1 supplementary table, 3 supplementary figure

Influences of Provider-Patient Communication on Health Literacy and Public Policy Relevant Outcomes

Several artifacts of federal policy address the connection between health literacy of patients and health outcomes. These laws include The Plain Writing Act, Health Information Technology for Economic and Clinical Health, and the Health Insurance Portability and Accountability Act. Even with this policy structure, little is known about how nurses\u27 knowledge of health literacy may influence patient understanding of medical information and health outcomes. Using Knowles\u27 principles of effective communication, the purpose of this mixed-methods study was to concurrently examine the relationship between nurse knowledge of health literacy and communication techniques used by nurses to identify any causal relationships in the provider-patient-interaction linking health literacy and health outcomes. Quantitative and qualitative data were gathered from 47 registered nurses in south Florida using an online survey. These data were analyzed using descriptive statistics and a content analysis procedure. Descriptive statistics revealed that there is a lack of health literacy knowledge among nurses and nurses rarely or never use Knowles\u27 communication techniques to relay health information to patients. By contrast, content analysis of qualitative data revealed that nurses have a basic understanding of the complexities of health literacy. No correlation existed between a nurse\u27s knowledge of health literacy and the use of appropriate and varied communication techniques when the data sets were merged. This finding suggests that there may be another root cause of low health literacy that requires additional research to fully explore. The positive social change implications stemming from this study include recommendations to policy makers to encourages changes to existing law and policy that supports patient communication training to nurses in order to improve health outcomes for patients

Estimating error models for whole genome sequencing using mixtures of Dirichlet-multinomial distributions

Motivation: Accurate identification of genotypes is an essential part of the analysis of genomic data, including in identification of sequence polymorphisms, linking mutations with disease and determining mutation rates. Biological and technical processes that adversely affect genotyping include copy-number-variation, paralogous sequences, library preparation, sequencing error and reference-mapping biases, among others. Results: We modeled the read depth for all data as a mixture of Dirichlet-multinomial distributions, resulting in significant improvements over previously used models. In most cases the best model was comprised of two distributions. The major-component distribution is similar to a binomial distribution with low error and low reference bias. The minor-component distribution is overdispersed with higher error and reference bias. We also found that sites fitting the minor component are enriched for copy number variants and low complexity regions, which can produce erroneous genotype calls. By removing sites that do not fit the major component, we can improve the accuracy of genotype calls. Availability and Implementation: Methods and data files are available at https://github.com/ CartwrightLab/WuEtAl2017/ (doi:10.5281/zenodo.256858). Contact: [email protected] Supplementary information: Supplementary data is available at Bioinformatics online

Depressive Symptoms and Marital Satisfaction in the Context of Chronic Disease: A Longitudinal Dyadic Analysis

These analyses examined the longitudinal relationships between depressive symptoms and marital satisfaction over a 2-year period as experienced by 315 patients with end-stage renal disease and their spouses. Using multilevel modeling, the authors examined both individual and cross-partner effects of depressive symptoms and marital satisfaction on patients and spouses, testing bidirectional causality. Results indicate that mean and time-varying depressive symptoms of both patients and spouses were associated with their own marital satisfaction. Although mean marital satisfaction was associated with own depressive symptoms for both patients and spouses, time-varying marital satisfaction did not affect depressive symptoms for either patients or spouses. Significant cross-partner effects reveal that both mean enduring and time-varying depressive symptoms of the spouse affected marital satisfaction of the patient. Findings highlight the complex nature of the relationship between depressive symptoms and marital satisfaction in late-life couples

Expression of voltage-dependent potassium channels in first trimester human placentae

Potassium channel α-subunits encoded by KCNQ1-5 genes form voltage-dependent channels (Kv7), modulated by KCNE1-5 encoded accessory proteins. The aim was to determine KCNQ and KCNE mRNA expression and assess protein expression/localisation of the KCNQ3 and KCNE5 isoforms in first trimester placental tissue. Placentae were obtained from women undergoing elective surgical termination of pregnancy (TOP) at 10 weeks’ (mid TOP) gestations. KCNQ1-5 expression was unchanged during the first trimester. KCNE5 expression increased in mid TOP vs. early TOP samples (P=0.022). This novel study reports mRNA and protein expression of Kv7 channels in first trimester placentae

Effects of Caregiver Burden and Satisfaction on Affect of Older End-Stage Renal Disease Patients and Their Spouses

We examined the extent to which a 2-factor model of affect explains how the burdens and satisfactions experienced by caregivers influence their own well-being and that of the spouses for whom they provide care. Using data from 315 older patients with end-stage renal disease and their spouses, we extended tests of Lawton et al.\u27s (1991) 2-factor model both longitudinally and dyadically. Multilevel modeling analyses partially support the 2-factor model. Consistent with the model, mean caregiver burden has a stronger effect on both caregiver and patient negative affect than does mean caregiver satisfaction. Contrary to the model, mean caregiver satisfaction has an effect on caregiver positive affect that is similar to that of mean caregiver burden, and it has no effect on patient positive affect. Time-varying effects of caregiver burden are consistent with the 2-factor model for caregiver but not patient negative affect. Time-varying effects of caregiver satisfaction are not consistent with the 2-factor model for either patients or caregivers. Results highlight the powerful role of caregiver burden for both caregivers and patients and suggest important new directions for conducting health-related research with late-life marital dyads

Altering the availability of healthier vs. less healthy items in UK hospital vending machines: a multiple treatment reversal design

Abstract: Background: Altering the availability of healthier or less-healthy products may increase healthier purchases, but evidence is currently limited. The current study aimed to investigate the impact of altering the absolute-and-relative availability of healthier and less-healthy products – i.e. simultaneously altering the number of options available and the proportion of healthier options – in hospital vending machines. Methods: An adapted multiple treatment reversal design was used, altering products available in ten vending machines serving snack foods and/or cold drinks in one English hospital. Machines were randomised to one of two sequences for the seven 4-week study periods: ABCADEA or ADEABCA. In Condition A (study periods 1, 4 and 7) the proportions of healthier products were standardised across all machines, so that 25% of all snack slots and 75% of drink slots were healthier. In Condition B, 20% of vending machine slots were emptied by removing less-healthy products. In Condition C, the empty slots created in Condition B were filled with healthier products. Conditions D and E were operationalised in the same way as B and C, except healthier products were removed in D, and then less-healthy products added in E. Sales data were obtained from machine restocking records. Separate linear mixed models were conducted to examine the impact of altering availability on energy purchased (kcal) from (i) snacks or (ii) drinks each week, with random effects for vending machine. Results: The energy purchased from drinks was reduced when the number of slots containing less-healthy drinks was decreased, compared to standardised levels (− 52.6%; 95%CI: − 69.3,-26.9). Findings were inconclusive for energy purchased from snacks when less-healthy snack slots were reduced (− 17.2%; 95%CI: − 47.4,30.5). Results for altering the number of slots for healthier drinks or snacks were similarly inconclusive, with no statistically significant impact on energy purchased. Conclusions: Reducing the availability of less-healthy drinks could reduce the energy purchased from drinks in vending machines. Further studies are needed to establish whether any effects might be smaller for snacks, or found with higher baseline proportions of healthier options

Recovery-focused care planning and coordination in England and Wales: a cross-national mixed methods comparative case study

Background In the UK, concerns about safety and fragmented community mental health care led to the development of the care programme approach in England and care and treatment planning in Wales. These systems require service users to have a care coordinator, written care plan and regular reviews of their care. Processes are required to be collaborative, recovery-focused and personalised but have rarely been researched. We aimed to obtain the views and experiences of stakeholders involved in community mental health care and identify factors that facilitate or act as barriers to personalised, collaborative, recovery-focused care. Methods We conducted a cross-national comparative study employing a concurrent transformative mixed-methods approach with embedded case studies across six service provider sites in England and Wales. The study included a survey of views on recovery, empowerment and therapeutic relationships in service users (n = 448) and recovery in care coordinators (n = 201); embedded case studies involving interviews with service providers, service users and carers (n = 117) and a review of care plans (n = 33). Quantitative and qualitative data were analysed within and across sites using inferential statistics, correlations and framework method. Results Significant differences were found across sites for scores on therapeutic relationships. Variation within sites and participant groups was reported in experiences of care planning and understandings of recovery and personalisation. Care plans were described as administratively burdensome and were rarely consulted. Carers reported varying levels of involvement. Risk assessments were central to clinical concerns but were rarely discussed with service users. Service users valued therapeutic relationships with care coordinators and others, and saw these as central to recovery. Conclusions Administrative elements of care coordination reduce opportunities for recovery-focused and personalised work. There were few common understandings of recovery which may limit shared goals. Conversations on risk appeared to be neglected and assessments kept from service users. A reluctance to engage in dialogue about risk management may work against opportunities for positive risk-taking as part of recovery-focused work. Research to investigate innovative approaches to maximise staff contact time with service users and carers, shared decision-making in risk assessments, and training designed to enable personalised, recovery-focused care coordination is indicated

Myeloma cells down‐regulate adiponectin in bone marrow adipocytes via TNF‐alpha

Multiple myeloma is caused by abnormal plasma cells that accumulate in the bone marrow and interact with resident cells of the bone microenvironment to drive disease progression and development of an osteolytic bone disease. Bone marrow adipocytes (BMAds) are emerging as having important endocrine functions that can support myeloma cell growth and survival. However, how BMAds respond to infiltrating tumor cells remains poorly understood. Using the C57BL/KaLwRij murine model of myeloma, bone marrow adiposity was found to be increased in early stage myeloma with BMAds localizing along the tumor‐bone interface at later stages of disease. Myeloma cells were found to uptake BMAd‐derived lipids in vitro and in vivo, although lipid uptake was not associated with the ability of BMAds to promote myeloma cell growth and survival. However, BMAd‐derived factors were found to increase myeloma cell migration, viability, and the evasion of apoptosis. BMAds are a major source of adiponectin, which is known to be myeloma‐suppressive. Myeloma cells were found to downregulate adiponectin specifically in a model of BMAds but not in white adipocytes. The ability of myeloma cells to downregulate adiponectin was dependent at least in part on TNF‐α. Collectively our data support the link between increased bone marrow adiposity and myeloma progression. By demonstrating how TNF‐α downregulates BMAd‐derived adiponectin, we reveal a new mechanism by which myeloma cells alter the bone microenvironment to support disease progression. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research