Efficacy of recommended drugs against soil transmitted helminths: systematic review and network meta-analysis

Objective To evaluate efficacies of anthelmintic drugs against soil transmitted helminths in terms of cure rates and egg reduction rates.Design Systematic review and network meta-analysis.Data Sources PubMed, ISI Web of Science, Embase, ScienceDirect, the Cochrane Central Register of Clinical Trials, and the World Health Organization library database from 1960 until 31 December 2016.Study selection Randomised controlled trials evaluating the efficacy of a single dose regimen of albendazole, mebendazole, levamisole, and pyrantel pamoate against Ascaris lumbricoides, hookworm (Necator americanus and Ancylostoma duodenale) and Trichuris trichiura. The primary outcomes included cure rates analysed by network meta-analysis with mixed logistic regression models and egg reduction rates with mixed linear models.Results 55 and 46 randomised controlled trials were included in the analysis of cure rates and egg reduction rates, respectively. All drugs were highly efficacious against A lumbricoides Albendazole showed the highest efficacy against hookworm infections with a cure rate of 79.5% (95% confidence interval 71.5% to 85.6%) and an egg reduction rate of 89.6% (81.9% to 97.3%). All drugs had low efficacy against T trichiura, with mebendazole showing the highest cure rate of 42.1% (25.9% to 60.2%) and egg reduction rate of 66.0% (54.6% to 77.3%). Estimates for the years 1995 and 2015 showed significant reductions in efficacy of albendazole against T trichiura: by 2015 the egg reduction rates fell from 72.6% (53.7% to 91.5%) to 43.4% (23.5% to 63.3%; P=0.049) and the cure rates fell from 38.6% (26.2% to 52.7%) to 16.4 (7.7% to 31.3%; P=0.027).Conclusions All four currently recommended drugs show limitations in their efficacy profile. While only albendazole showed good efficacy against hookworm infection, all drugs had low efficacy against T trichiura The decrease in efficacy of albendazole against T trichiura over the past two decades is of concern. The findings indicate the need for strengthening efforts to develop new drug treatments, with a particular focus on drugs against T trichiura

A perfusion culture system for assessing bone marrow stromal cell differentiation on PLGA scaffolds for bone repair

Biomaterials development for bone repair is currently hindered by the lack of physiologically relevant in vitro testing systems. Here we describe the novel use of a bi-directional perfusion bioreactor to support the long term culture of human bone marrow stromal cells (BMSCs) differentiated on polylactic co-glycolic acid (PLGA). Primary human BMSCs were seeded onto porous PLGA scaffolds and cultured in static vs. perfusion culture conditions for 21 days in osteogenic vs. control media. PLGA scaffolds were osteoconductive, supporting a mature osteogenic phenotype as shown by the upregulation of Runx2 and the early osteocyte marker E11. Perfusion culture enhanced the expression of osteogenic genes Osteocalcin and Osteopontin. Extracellular matrix deposition and mineralisation were spatially regulated within PLGA scaffolds in a donor dependant manner. This, together with the observed upregulation of Collagen type X suggested an environment permissive for the study of differentiation pathways associated with both intramembranous and endochondral ossification routes of bone healing. This culture system offers a platform to assess BMSC behavior on candidate biomaterials under physiologically relevant conditions. Use of this system may improve our understanding of the environmental cues orchestrating BMSC differentiation and enable fine tuning of biomaterial design as we develop tissue-engineered strategies for bone regeneration

U.S. Army Corps of Engineers Freshwater Harmful Algal Bloom Research & Development Initiative

Freshwater Harmful Algal Blooms (HABs) are particularly impactful to the U.S. Army Corps of Engineers (USACE), which manages vast freshwater resources and waterways that provide a variety of services including navigation, flood risk reduction, recreation, fish and wildlife management, as well as potable water supply. The Water Resources Development Act of 2018 (WRDA 2018) authorized the U.S. Army Engineer Research Development Center (USACE-ERDC) to implement a 5-year technology demonstration program to deliver scalable technologies for HAB prevention, detection and management that will reduce HAB frequency and effects to our nation’s freshwater resources across scales (e.g. small waterbodies to river reaches), ecoregions (e.g. subtropical Florida to temperate Ohio and New York), and system types (e.g. reservoirs, riverine, lakes). The USACE-ERDC HAB Research & Development (R&D) portfolio features a range of HAB-combatting methods, models, and technologies that may be used alone or in combination to effectively reduce HAB frequency and impacts to water resource development projects across the nation. An overview of USACE-ERDC sponsored HAB R&D projects will highlight the range of HAB methods, models, and technologies in development, and will provide an opportunity to engage with federal, state, local, and university partners

The pen as mighty as the microscope : ethical issues in science and medical journalism

Science is difficult for even its researchers to understand. Science journalists must understand scientific discoveries well enough to write clear, accurate explanations of scientific discoveries for laypeople. A sense of ethical judgment will help journalists ensure that their accounts are reliable and appropriate. Responsible science journalists will maintain a working knowledge of statistics so they can accurately present the statistical aspects of scientific studies. Also, the traditional emphasis on fairness and balance in news coverage may backfire in science reporting, when equal coverage for unreliable “sides” of an issue would in fact be inaccurate. Not all sources are equally reliable; information from peer-reviewed journals, researchers and press officers, while all useful, should be treated with different degrees of caution. These principles of responsible science journalism are shown in three case studies of pharmaceutical debates in the mass media over the past twenty years: the question of whether the MMR vaccine causes autism, the benefits and risks of postmenopausal hormone replacement therapy, and the hazards of the fen-phen diet drug

Development and initial testing of the self‐care of chronic illness inventory

Aim The aim was to develop and psychometrically test the self‐care of chronic illness Inventory, a generic measure of self‐care. Background Existing measures of self‐care are disease‐specific or behaviour‐specific; no generic measure of self‐care exists. Design Cross‐sectional survey. Methods We developed a 20‐item self‐report instrument based on the Middle Range Theory of Self‐Care of Chronic Illness, with three separate scales measuring Self‐Care Maintenance, Self‐Care Monitoring, and Self‐Care Management. Each of the three scales is scored separately and standardized 0–100 with higher scores indicating better self‐care. After demonstrating content validity, psychometric testing was conducted in a convenience sample of 407 adults (enrolled from inpatient and outpatient settings at five sites in the United States and ResearchMatch.org). Dimensionality testing with confirmatory factor analysis preceded reliability testing. Results The Self‐Care Maintenance scale (eight items, two dimensions: illness‐related and health‐promoting behaviour) fit well when tested with a two‐factor confirmatory model. The Self‐Care Monitoring scale (five items, single factor) fitted well. The Self‐Care Management scale (seven items, two factors: autonomous and consulting behaviour), when tested with a two‐factor confirmatory model, fitted adequately. A simultaneous confirmatory factor analysis on the combined set of items supported the more general model. Conclusion The self‐care of chronic illness inventory is adequate in reliability and validity. We suggest further testing in diverse populations of patients with chronic illnesses

Quantitative Methods in Contexts of Everyday Violence

The analysis of violence from an individual or household perspective is arguably one of the most challenging research areas in social science. Outbreaks of violence affect the core of human relations and social norms. They occur in non?linear cycles, and co?exist at different levels of social interaction within the family, the community or the state. Analysis of this complexity cannot be restricted to one social science discipline or method of analysis. This article reflects on an innovative methodology adopted to capture the experience of living with violence in communities in Brazil, Jamaica, Mexico and Nigeria. The methodology confronted disciplinary boundaries by encouraging close dialogue between quantitative and qualitative researchers in violent settings, and creating processes for learning and sharing. This article describes the methodology, presents the main results of the quantitative analysis and reflects on the challenges and lessons

Genetic diversity of human RNase 8

<p>Abstract</p> <p>Background</p> <p>Ribonuclease 8 is a member of the RNase A family of secretory ribonucleases; orthologs of this gene have been found only in primate genomes. RNase 8 is a divergent paralog of RNase 7, which is lysine-enriched, highly conserved, has prominent antimicrobial activity, and is expressed in both normal and diseased skin; in contrast, the physiologic function of RNase 8 remains uncertain. Here, we examine the genetic diversity of human RNase 8, a subject of significant interest given the existence of functional pseudogenes (coding sequences that are otherwise intact but with mutations in elements crucial for ribonucleolytic activity) in non-human primate genomes.</p> <p>Results</p> <p>RNase 8 expression was detected in adult human lung, spleen and testis tissue by quantitative reverse-transcription PCR. Only two single-nucleotide polymorphisms and four unique alleles were identified within the RNase 8 coding sequence; nucleotide sequence diversity (π = 0.00122 ± 0.00009 per site) was unremarkable for a human nuclear gene. We isolated transcripts encoding RNase 8 via rapid amplification of cDNA ends (RACE) and RT-PCR which included a distal potential translational start site followed by sequence encoding an additional 30 amino acids that are conserved in the genomes of several higher primates. The distal translational start site is functional and promotes RNase 8 synthesis in transfected COS-7 cells.</p> <p>Conclusions</p> <p>These results suggest that RNase 8 may diverge considerably from typical RNase A family ribonucleases and may likewise exhibit unique function. This finding prompts a reconsideration of what we have previously termed functional pseudogenes, as RNase 8 may be responding to constraints that promote significant functional divergence from the canonical structure and enzymatic activity characteristic of the RNase A family.</p

BAE Systems Radiation Hardened SpaceWire ASIC and Roadmap

An Application Specific Integrated Circuit (ASIC) that implements the SpaceWire protocol has been developed in a radiation hardened 0.25 micron CMOS, technology. This effort began in March 2003 as a joint development between the NASA Goddard Space Flight Center (GSFC) and BAE Systems. The BAE Systems SpaceWire ASlC is comprised entirely of reusable core elements, many of which are already flight-proven. It incorporates a 4-port SpaceWire router with two local ports, dual PC1 bus interfaces, a microcontroller, 32KB of internal memory, -and a memory controller for additional external memory use. The SpaceWire ASlC is planned for use on both the Geostationary Operational Environmental Satellites (GOES)-R and the Lunar Reconnaissance Orbiter (LRO). Engineering parts have already been delivered to both programs. This paper discusses the SpaceWire protocol and those elements of it that have been built into the current SpaceWire reusable core. There are features within the core that go beyond the current standard that can be enabled or disabled by the user and these will be described. The adaptation of SpaceWire to BAE Systems' On Chip Bus (OCB) for compatibility with the other reusable cores will be discussed. Optional configurations within user systems will be shown. The physical imp!ementation of the design will be described and test results from the hardware will be discussed. Finally, the BAE Systems roadmap for SpaceWire developments will be discussed, including some products already in design as well as longer term plans

ASSOCIATION BETWEEN FUNCTIONAL CAPACITY AND HANDGRIP STRENGTH IN PEOPLE WITH DIABETES MELLITUS

Objective: to investigate the association between handgrip strength and functional capacity in people with diabetes.Method: observational cross-sectional study with 168 participants seen at an outpatient clinic in Curitiba, Brazil, in 2019. Clinical, sociodemographic, and socioeconomic data were collected, and the following protocols were applied: World Health Organization Disability Assessment Schedule; Timed Up and Go; and dynamometry. For the analysis, multiple linear regression models were adjusted for the dependent variables related to functional capacity.Results: we observed mild disability, borderline functional mobility, and higher correlation between functional mobility scale and handgrip strength (r=-0.384; p < 0.01). Handgrip strength with other covariates explained less than 30% of the functional variability.Conclusion: these results contribute to the problem-solving of clinical practice in that they show that muscle strength and functional capacity should be considered in the evaluation of the patient in combination, making it clearer and more comprehensive.

Families With Violence Exposure and the Intergenerational Transmission of Somatization

Introduction: Adults who have histories of childhood trauma have been noted to display greater somatization, dissociative symptoms and affect dysregulation. What happens in the parent-child relationship when those traumatized children become parents? A potential link to somatization in the child has been suggested by several prior studies. Children who have early attachment disturbances had more physical complaints if their mothers displayed less maternal sensitivity during observed parent-child interactions. Yet, the intergenerational link between maternal and child somatization has not been sufficiently explored in a longitudinal study in order to understand the potential impact of maternal trauma history and related psychopathology on subsequent child somatization and psychopathology. Methods: This paper examined prospective, longitudinal data of 64 mother-toddler dyads (mean age = 2.4 years, SD = 0.7) who were later studied when children had a mean age of 7 years. Mothers with and without histories of interpersonal violence (IPV; physical/sexual abuse and/or family violence exposure) were included. Mothers with IPV histories were oversampled. Linear and Poisson regression models were used to test the associations between maternal IPV-related post-traumatic stress disorder (PTSD) with maternal somatization severity when children were toddlers, and between maternal somatization and maternal interactive behaviors with child somatization by maternal report and clinician-rated assessment at school-age. Results: Maternal PTSD severity was significantly associated with increased maternal somatization severity (p = 0.031). Maternal somatization severity during the child's early childhood predicted both maternal report of child somatization (p = 0.011) as well as child thought problems (p = 0.007) when children were school-aged. No association was found between maternal somatization and child-reported psychopathology. The study did not find that maternal alexithymia, caregiving behaviors or child exposure to violence contributed significantly to the model examining the association between maternal and child somatization. Conclusion: The results are in line with the hypothesis of intergenerational transmission of somatization in the context of IPV and related maternal PTSD during formative early development. We interpret this as an expression of psychological distress from mother to child, as maternal trauma and pathology affect the caregiving environment and, thus, the parent-child relationship. The authors conclude with a discussion of implications for parent-infant and early childhood intervention