Experiences and perceptions of Spring Lane Sure Start Children's Centre

Spring Lane Sure Start Children’s Centre was designated in September 2007, and ‘officially opened’ in February 2009. The Centre is housed in refurbished premises within a nursery/school complex in the heart of Northampton and offers diverse health, childcare, early education and support services delivered by a multi-professional team. These services and activities are available to children aged 0-5 years old, and their parents/carers, residing within a catchment area comprising eight ‘Super Output Areas’ in the Castle and St. James ward of Northampton. In April 2009, the Centre for Children and Youth (CCY) – a research centre based at The University of Northampton – was commissioned by Spring Lane Sure Start Children’s Centre to collate and gather evaluative data regarding experiences and perceptions of the Children’s Centre during its first year of activitie

Discordance between the predictors of clinical and imaging remission in patients with early rheumatoid arthritis in clinical practice: implications for the use of ultrasound within a treatment to target strategy

Objective: To assess the prevalence, relationship between and predictors of clinical and imaging remission in early rheumatoid arthritis (RA), achieved with treat-to-target management in clinical practice. Methods: A prospective observational study was conducted in patients with new-onset RA. The treatment target was remission by disease activity score (DAS28-CRP<2.6). Twelve month outcomes included DAS28-CRP remission, DAS44-CRP remission, ACR/EULAR Boolean remission (BR) and absent or absent/minimal power Doppler activity (PDA) on ultrasound (US) of 26 joints (total PDA score=0 or ≤1, respectively). Logistic regression was conducted to identify baseline predictors of these outcomes. Results: Of 105 patients with complete 12-month data, the rate of DAS28-CRP remission was 43%, DAS44-CRP remission was 39%, BR was 14%, absent PDA was 40% and absent/minimal PDA was 57%. Amongst patients achieving clinical remission defined by DAS28-CRP, DAS44-CRP or BR, absence of PDA was observed in 42%, 44% and 40%, respectively; absent/minimal PDA was detected in 62%, 66% and 67%, respectively. On multivariable analysis, shorter symptom duration, male gender, fewer tender joints and lower disability were associated with the clinical remission definitions. Lack of osteoarthritis predicted absence of PDA and lower total baseline PDA predicted absent/minimal PDA. Conclusion: DAS28-CRP remission and absence of PDA were observed in almost half of patients, but less than a quarter achieved both. Achievement of BR was rare. The low agreement between any of the clinical and imaging outcomes and differences in their predictors highlight the complex interaction between symptoms and synovitis, with implications for treat-to-target management. Long-term follow-up should determine the most appropriate target

Modern foraminifera, δ\u3csup\u3e13\u3c/sup\u3eC, and bulk geochemistry of central Oregon tidal marshes and their application in paleoseismology

We assessed the utility of δ13C and bulk geochemistry (total organic content and C:N) to reconstruct relative sea-level changes on the Cascadia subduction zone through comparison with an established sea-level indicator (benthic foraminifera). Four modern transects collected from three tidal environments at Siletz Bay, Oregon, USA, produced three elevation-dependent groups in both the foraminiferal and δ13C/bulk geochemistry datasets. Foraminiferal samples from the tidal flat and low marsh are identified by Miliammina fusca abundances of \u3e 45%, middle and high marsh by M. fusca abundances of \u3c 45% and the highest marsh by Trochamminita irregularis abundances \u3e 25%. The δ13C values from the groups defined with δ13C/bulk geochemistry analyses decrease with an increasing elevation; − 24.1 ± 1.7‰ in the tidal flat and low marsh; − 27.3 ± 1.4‰ in the middle and high marsh; and − 29.6 ± 0.8‰ in the highest marsh samples. We applied the modern foraminiferal and δ13C distributions to a core that contained a stratigraphic contact marking the great Cascadia earthquake of AD 1700. Both techniques gave similar values for coseismic subsidence across the contact (0.88 ± 0.39 m and 0.71 ± 0.56 m) suggesting that δ13C has potential for identifying amounts of relative sea-level change due to tectonics

Antigenic and genetic characterization of a divergent African virus, Ikoma lyssavirus

In 2009, a novel lyssavirus (subsequently named Ikoma lyssavirus, IKOV) was detected in the brain of an African civet (Civettictis civetta) with clinical rabies in the Serengeti National Park of Tanzania. The degree of nucleotide divergence between the genome of IKOV and those of other lyssaviruses predicted antigenic distinction from, and lack of protection provided by, available rabies vaccines. In addition, the index case was considered likely to be an incidental spillover event, and therefore the true reservoir of IKOV remained to be identified. The advent of sensitive molecular techniques has led to a rapid increase in the discovery of novel viruses. Detecting viral sequence alone, however, only allows for prediction of phenotypic characteristics and not their measurement. In the present study we describe the in vitro and in vivo characterization of IKOV, demonstrating that it is (1) pathogenic by peripheral inoculation in an animal model, (2) antigenically distinct from current rabies vaccine strains and (3) poorly neutralized by sera from humans and animals immunized against rabies. In a laboratory mouse model, no protection was elicited by a licensed rabies vaccine. We also investigated the role of bats as reservoirs of IKOV. We found no evidence for infection among 483 individuals of at least 13 bat species sampled across sites in the Serengeti and Southern Kenya

Atypical Case Of Wolfram Syndrome Revealed Through Targeted Exome Sequencing In A Patient With Suspected Mitochondrial Disease

Background: Mitochondrial diseases comprise a diverse set of clinical disorders that affect multiple organ systems with varying severity and age of onset. Due to their clinical and genetic heterogeneity, these diseases are difficult to diagnose. We have developed a targeted exome sequencing approach to improve our ability to properly diagnose mitochondrial diseases and apply it here to an individual patient. Our method targets mitochondrial DNA (mtDNA) and the exons of 1,600 nuclear genes involved in mitochondrial biology or Mendelian disorders with multi-system phenotypes, thereby allowing for simultaneous evaluation of multiple disease loci. Case Presentation: Targeted exome sequencing was performed on a patient initially suspected to have a mitochondrial disorder. The patient presented with diabetes mellitus, diffuse brain atrophy, autonomic neuropathy, optic nerve atrophy, and a severe amnestic syndrome. Further work-up revealed multiple heteroplasmic mtDNA deletions as well as profound thiamine deficiency without a clear nutritional cause. Targeted exome sequencing revealed a homozygous c.1672C > T (p.R558C) missense mutation in exon 8 of WFS1 that has previously been reported in a patient with Wolfram syndrome. Conclusion: This case demonstrates how clinical application of next-generation sequencing technology can enhance the diagnosis of patients suspected to have rare genetic disorders. Furthermore, the finding of unexplained thiamine deficiency in a patient with Wolfram syndrome suggests a potential link between WFS1 biology and thiamine metabolism that has implications for the clinical management of Wolfram syndrome patients

An Ethical Framework for Library Publishing: Version 0.5 (Draft for Comment)

Background: At the Library Publishing Coalition (LPC) Membership Meeting at the 2017 Library Publishing Forum in Baltimore, Maryland, the community discussed how the LPC can respond to the current political climate. The discussion was wide-ranging, but kept coming back to the importance of library values and our responsibility as library publishers to center our publishing practice around them. A number of those present offered to devise a way for the conversation to continue beyond the Forum. That group included Marilyn Billings, Jason Boczar, Rebel Cummings-Sauls, Harrison W. Inefuku, Joshua Neds-Fox, Matt Ruen, Emily Stenberg, and Monica Westin, who proposed a task force to tackle the issues raised. This task force was charged with creating an Ethical Framework for Library Publishing . From July of 2017 to June of 2018, the task force members (listed on the title page as authors of this document) identified the topics to be covered in the framework, and then worked in subgroups to review the literature on those topics and identify existing resources of particular relevance to the community of library publishers. The subgroups then drafted the sections you see in this document. Throughout this process, they worked iteratively to devise a structure and format for the framework—a challenging task, and one for which there were many inspirations, but no clear models. In the end, they decided that the most effective structure for the document would break each section into an introduction , a scope statement , a review of existing resources , and a set of recommendations for library publishers. Some sections also include a note about new resources that are needed and/or further readings on the topic. Context: library publishing and ethics: Academic libraries have entered the publishing space due to changes in ways of disseminating information and in response to faculty members’ desire to control their own publishing destiny. This work has been enabled by the emergence of open source or low-cost technologies for publishing, but the motivations for it are broad and deep—for example, library publishers are also deeply engaged with emerging forms of scholarship (and emerging disciplines) that do not yet have a voice within the traditional publishing environment. These motivations often include a desire for increased openness and sustainability in the scholarly communication landscape. Unlike commercial publishers and traditional presses, the work of library publishers is largely funded through existing library budgets without a profit motive. The goal is instead to increase the impact of scholarship created by faculty and students affiliated with an institution and to disseminate that scholarship as broadly as possible, by emphasizing open access as a means of distribution. Because these publishing activities for academic libraries are a relatively recent endeavor, education and training for librarians as publishers is not fully established and thus one of the objectives for preparing this guide. Publishing as a role for librarians is increasing in importance for all academic libraries and is not limited to just research libraries, but also includes community colleges and four-year undergraduate institutions. Library publishers are also uniquely positioned to look beyond traditional prestige publishing priorities to partner with faculty, students, and organizations in order provide services such as data preservation and engage in publishing as pedagogy. As relative newcomers to the world of publishing, libraries are able to draw on a wealth of resources and expertise developed by more established players. To avoid reinventing the wheel, this document is structured primarily around existing resources. The framework pulls together existing publishing codes of ethics (many of which are included in the Publishing Practice section), along with resources from librarianship and other related fields, and contextualizes them for library publishers. The recommendations in each section attempt to distill a wealth of knowledge and guidance into a small set of actionable steps meant to answer the question, “But how do I get started?” They are by no means the only steps to be taken in these areas, but they may help library publishers begin to incorporate these important ethical considerations into their work. Future plans for the framework From the beginning of this project, the taskforce designed An Ethical Framework for Library Publishing to be an iterative document, more formal than a wiki but less so than a monograph or white paper. The founding group of authors worked on the framework with an understanding that every topic could not be covered, especially with a goal to create a document in less than a year. This framework was always envisioned as a starting place. In light of an iterative approach, we have decided to call this version 1 from the outset. The definitive version of An Ethical Framework for Library Publishing will always be the most current version. Versioning the document will also help make visible the historical transition. Version 2, the taskforce hopes, can be started by a new group of library publishing professionals with new views and ideas. In this way, we hope, An Ethical Framework for Library Publishing will never be a static, antiquated document created only from the viewpoint of a small group of people. It can, and should, be a community project

Symptom burden and health-related quality of life in chronic kidney disease:A global systematic review and meta-analysis

BACKGROUND: The importance of patient-reported outcome measurement in chronic kidney disease (CKD) populations has been established. However, there remains a lack of research that has synthesised data around CKD-specific symptom and health-related quality of life (HRQOL) burden globally, to inform focused measurement of the most relevant patient-important information in a way that minimises patient burden. The aim of this review was to synthesise symptom prevalence/severity and HRQOL data across the following CKD clinical groups globally: (1) stage 1-5 and not on renal replacement therapy (RRT), (2) receiving dialysis, or (3) in receipt of a kidney transplant.METHODS AND FINDINGS: MEDLINE, PsycINFO, and CINAHL were searched for English-language cross-sectional/longitudinal studies reporting prevalence and/or severity of symptoms and/or HRQOL in CKD, published between January 2000 and September 2021, including adult patients with CKD, and measuring symptom prevalence/severity and/or HRQOL using a patient-reported outcome measure (PROM). Random effects meta-analyses were used to pool data, stratified by CKD group: not on RRT, receiving dialysis, or in receipt of a kidney transplant. Methodological quality of included studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data, and an exploration of publication bias performed. The search identified 1,529 studies, of which 449, with 199,147 participants from 62 countries, were included in the analysis. Studies used 67 different symptom and HRQOL outcome measures, which provided data on 68 reported symptoms. Random effects meta-analyses highlighted the considerable symptom and HRQOL burden associated with CKD, with fatigue particularly prevalent, both in patients not on RRT (14 studies, 4,139 participants: 70%, 95% CI 60%-79%) and those receiving dialysis (21 studies, 2,943 participants: 70%, 95% CI 64%-76%). A number of symptoms were significantly (p &lt; 0.05 after adjustment for multiple testing) less prevalent and/or less severe within the post-transplantation population, which may suggest attribution to CKD (fatigue, depression, itching, poor mobility, poor sleep, and dry mouth). Quality of life was commonly lower in patients on dialysis (36-Item Short Form Health Survey [SF-36] Mental Component Summary [MCS] 45.7 [95% CI 45.5-45.8]; SF-36 Physical Component Summary [PCS] 35.5 [95% CI 35.3-35.6]; 91 studies, 32,105 participants for MCS and PCS) than in other CKD populations (patients not on RRT: SF-36 MCS 66.6 [95% CI 66.5-66.6], p = 0.002; PCS 66.3 [95% CI 66.2-66.4], p = 0.002; 39 studies, 24,600 participants; transplant: MCS 50.0 [95% CI 49.9-50.1], p = 0.002; PCS 48.0 [95% CI 47.9-48.1], p = 0.002; 39 studies, 9,664 participants). Limitations of the analysis are the relatively few studies contributing to symptom severity estimates and inconsistent use of PROMs (different measures and time points) across the included literature, which hindered interpretation.CONCLUSIONS: The main findings highlight the considerable symptom and HRQOL burden associated with CKD. The synthesis provides a detailed overview of the symptom/HRQOL profile across clinical groups, which may support healthcare professionals when discussing, measuring, and managing the potential treatment burden associated with CKD.PROTOCOL REGISTRATION: PROSPERO CRD42020164737.</p

High Levels of Relatedness between Brown-Headed Cowbird (Molothrus ater) Nestmates in a Heavily Parasitized Host Community

Multiple parasitism of host nests by generalist brood parasites reflects the decisions of laying females and may influence the development and behavior of parasitic young. We used microsatellite and mtDNA control-region haplotype data to examine the relatedness of Brown-headed Cowbird (Molothrus ater) offspring in multiply parasitized nests sampled from a heavily parasitized host community in northeastern Kansas. We also examined how host nest availability influenced the degree of multiple parasitism, and used community-wide parasitism data to explore whether female cowbirds were constrained in their laying decisions. Relatedness estimates for all suitable pairwise comparisons (n = 94 from 41 multiply parasitized nests) found that the mean likelihood than an individual cowbird in a multiply parasitized nest shared its nest with a full sibling was 40.4% (95% confidence interval: 28.4–52.4%), indicating that many cowbird offspring were reared with full siblings. Extensive community-wide parasitism data revealed that most cowbird offspring shared the nest with ≥1 other conspecific. Additionally, we found that the proportion of available host nests increased steeply at the start of the breeding season and remained high for most of the breeding season, but that the degree of multiple parasitism was unrelated to the number of new nests. We found evidence that laying decisions of female cowbirds were constrained, which suggests that heavy parasitism levels were due to a high degree of competition for host nests. This intense competition for host nests, in turn, results in cowbird offspring often competing with conspecifics in our population, including full siblings, for host parental care.Keywords: Molothrus ater, Brown-headed Cowbird, nestmate relatedness, kinship, generalist brood parasite, laying patter

Case report: response to the ERK1/2 inhibitor ulixertinib in BRAF D594G cutaneous melanoma.

Melanoma is characterized by oncogenic mutations in pathways regulating cell growth, proliferation, and metabolism. Greater than 80% of primary melanoma cases harbor aberrant activation of the mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase (MEK/ERK) pathway, with oncogenic mutations in BRAF, most notably BRAF V600E, being the most common. Significant progress has been made in BRAF-mutant melanoma using BRAF and MEK inhibitors; however, non-V600 BRAF mutations remain a challenge with limited treatment options. We report the case of an individual diagnosed with stage III BRAF D594G-mutant melanoma who experienced an extraordinary response to the ERK1/2 inhibitor ulixertinib as fourth-line therapy. Ulixertinib was obtained via an intermediate expanded access protocol with unique flexibility to permit both single-agent and combination treatments, dose adjustments, breaks in treatment to undergo surgery, and long-term preventive treatment following surgical resection offering this patient the potential for curative treatment

The impact of albendazole treatment on the incidence of viral- and bacterial-induced diarrhea in school children in southern Vietnam: study protocol for a randomized controlled trial

Anthelmintics are one of the more commonly available classes of drugs to treat infections by parasitic helminths (especially nematodes) in the human intestinal tract. As a result of their cost-effectiveness, mass school-based deworming programs are becoming routine practice in developing countries. However, experimental and clinical evidence suggests that anthelmintic treatments may increase susceptibility to other gastrointestinal infections caused by bacteria, viruses, or protozoa. Hypothesizing that anthelmintics may increase diarrheal infections in treated children, we aim to evaluate the impact of anthelmintics on the incidence of diarrheal disease caused by viral and bacterial pathogens in school children in southern Vietnam.This is a randomized, double-blinded, placebo-controlled trial to investigate the effects of albendazole treatment versus placebo on the incidence of viral- and bacterial-induced diarrhea in 350 helminth-infected and 350 helminth-uninfected Vietnamese school children aged 6-15 years. Four hundred milligrams of albendazole, or placebo treatment will be administered once every 3 months for 12 months. At the end of 12 months, all participants will receive albendazole treatment. The primary endpoint of this study is the incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance. Secondary endpoints include the prevalence and intensities of helminth, viral, and bacterial infections, alterations in host immunity and the gut microbiota with helminth and pathogen clearance, changes in mean z scores of body weight indices over time, and the number and severity of adverse events.In order to reduce helminth burdens, anthelmintics are being routinely administered to children in developing countries. However, the effects of anthelmintic treatment on susceptibility to other diseases, including diarrheal pathogens, remain unknown. It is important to monitor for unintended consequences of drug treatments in co-infected populations. In this trial, we will examine how anthelmintic treatment impacts host susceptibility to diarrheal infections, with the aim of informing deworming programs of any indirect effects of mass anthelmintic administrations on co-infecting enteric pathogens.ClinicalTrials.gov: NCT02597556 . Registered on 3 November 2015