Randomised Controlled Trial of Lactobacillus Rhamnosus (LGG) Versus Placebo in Children Presenting to the Emergency Department with Acute Gastroenteritis: the PECARN Probiotic Study Protocol.

INTRODUCTION: Acute gastroenteritis (AGE) is a common and burdensome condition that affects millions of children worldwide each year. Currently available strategies are limited to symptomatic management, treatment and prevention of dehydration and infection control; no disease-modifying interventions exist. Probiotics, defined as live microorganisms beneficial to the host, have shown promise in improving AGE outcomes, but existing studies have sufficient limitations such that the use of probiotics cannot currently be recommended with confidence. Here we present the methods of a large, rigorous, randomised, double-blind placebo-controlled study to assess the effectiveness and side effect profile of Lactobacillus rhamnosus GG (LGG) (ATCC 53103) in children with AGE. METHODS AND ANALYSIS: The study is being conducted in 10 US paediatric emergency departments (EDs) within the federally funded Pediatric Emergency Care Applied Research Network, in accordance with current SPIRIT and CONSORT statement recommendations. We will randomise 970 children presenting to participating EDs with AGE to either 5 days of treatment with LGG (10(10)colony-forming unit twice a day) or placebo between July 2014 to December 2017. The main outcome is the occurrence of moderate-to-severe disease over time, as defined by the Modified Vesikari Scale. We also record adverse events and side effects related to the intervention. We will conduct intention-to-treat analyses and use an enrichment design to restore the statistical power in case the presence of a subpopulation with a substantially low treatment effect is identified. ETHICS AND DISSEMINATION: Institutional review board approval has been obtained at all sites, and data and material use agreements have been established between the participating sites. The results of the trial will be published in peer-reviewed journals. A deidentified public data set will be made available after the completion of all study procedures. TRIAL REGISTRATION NUMBER: NCT01773967

Variables Associated with Intravenous Rehydration and Hospitalization in Children with Acute Gastroenteritis: A Secondary Analysis of 2 Randomized Clinical Trials

Importance: Despite guidelines endorsing oral rehydration therapy, intravenous fluids are commonly administered to children with acute gastroenteritis in high-income countries. Objective: To identify factors associated with intravenous fluid administration and hospitalization in children with acute gastroenteritis. Design, Setting, and Participants: This study is a planned secondary analysis of the Pediatric Emergency Research Canada (PERC) and Pediatric Emergency Care Applied Research Network (PECARN) probiotic trials. Participants include children aged 3 to 48 months with 3 or more watery stools in 24 hours between November 5, 2013, and April 7, 2017, for the PERC study and July 8, 2014, and June 23, 2017, for the PECARN Study. Children were from 16 pediatric emergency departments throughout Canada (6) and the US (10). Data were analyzed from November 2, 2018, to March 16, 2021. Exposures: Sex, age, preceding health care visit, distance between home and hospital, country (US vs Canada), frequency and duration of vomiting and diarrhea, presence of fever, Clinical Dehydration Scale score, oral ondansetron followed by oral rehydration therapy, and infectious agent. Main Outcomes and Measures: Intravenous fluid administration and hospitalization. Results: This secondary analysis of 2 randomized clinical trials included 1846 children (mean [SD] age, 19.1 [11.4] months; 1007 boys [54.6%]), of whom 534 of 1846 (28.9%) received oral ondansetron, 240 of 1846 (13.0%) received intravenous rehydration, and 67 of 1846 (3.6%) were hospitalized. The following were independently associated with intravenous rehydration: higher Clinical Dehydration Scale score (mild to moderate vs none, odds ratio [OR], 8.73; 95% CI, 5.81-13.13; and severe vs none, OR, 34.15; 95% CI, 13.45-86.73); country (US vs Canada, OR, 6.76; 95% CI, 3.15-14.49); prior health care visit with intravenous fluids (OR, 4.55; 95% CI, 1.32-15.72); and frequency of vomiting (per 5 episodes, OR, 1.66; 95% CI, 1.39-1.99). The following were independently associated with hospitalization: higher Clinical Dehydration Scale score (mild to moderate vs none, OR, 11.10; 95% CI, 5.05-24.38; and severe vs none, OR, 23.55; 95% CI, 7.09-78.25) and country (US vs Canada, OR, 3.37; 95% CI, 1.36-8.40). Oral ondansetron was associated with reduced odds of intravenous rehydration (OR, 0.21; 95% CI, 0.13-0.32) and hospitalization (OR, 0.44; 95% CI, 0.21-0.89). Conclusions and Relevance: Intravenous rehydration and hospitalization were associated with clinical evidence of dehydration and lack of an oral ondansetron-supported oral rehydration period. Strategies focusing on oral ondansetron administration followed by oral rehydration therapy in children with dehydration may reduce the reliance on intravenous rehydration and hospitalization. Trial Registration: ClinicalTrials.gov Identifiers: NCT01853124 (PERC) and NCT01773967 (PECARN)

Comparing pediatric gastroenteritis emergency department care in Canada and the United States

BACKGROUND: Between-country variation in health care resource use and its impact on outcomes in acute care settings have been challenging to disentangle from illness severity by using administrative data. METHODS: We conducted a preplanned analysis employing patient-level emergency department (ED) data from children enrolled in 2 previously conducted clinical trials. Participants aged 3 to,48 months with,72 hours of gastroenteritis were recruited in pediatric EDs in the United States (N = 10 sites; 588 participants) and Canada (N = 6 sites; 827 participants). The primary outcome was an unscheduled health care provider visit within 7 days; the secondary outcomes were intravenous fluid administration and hospitalization at or within 7 days of the index visit. RESULTS: In adjusted analysis, unscheduled revisits within 7 days did not differ (adjusted odds ratio [aOR]: 0.72; 95% confidence interval (CI): 0.50 to 1.02). At the index ED visit, although participants in Canada were assessed as being more dehydrated, intravenous fluids were administered more frequently in the United States (aOR: 4.6; 95% CI: 2.9 to 7.1). Intravenous fluid administration rates did not differ after enrollment (aOR: 1.4; 95% CI: 0.7 to 2.8; US cohort with Canadian as referent). Overall, intravenous rehydration was higher in the United States (aOR: 3.8; 95% CI: 2.5 to 5.7). Although hospitalization rates during the 7 days after enrollment (aOR: 1.1; 95% CI: 0.4 to 2.6) did not differ, hospitalization at the index visit was more common in the United States (3.9% vs 2.3%; aOR: 3.2; 95% CI: 1.6 to 6.8). CONCLUSIONS: Among children with gastroenteritis and similar disease severity, revisit rates were similar in our 2 study cohorts, despite lower rates of intravenous rehydration and hospitalization in Canadian-based EDs

A Pilot Study of Lay Health Worker Outreach and Colorectal Cancer Screening Among Chinese Americans

The research team recruited eight Chinese American (seven females, one male) lay health workers (LHWs). They received 12 h of training about colorectal cancer (CRC), its screening, and basic health education techniques. Each LHW were asked to recruit ten participants and conduct two educational sessions. Of the 81 participants recruited, 73 had not received colorectal cancer screening. Their mean age was 63.0 years, and 72.6% were women. Knowledge of colorectal cancer, its causes, and its screening increased significantly. Receipt of first colorectal cancer screening test increased from 0.0% at baseline to 55.7% for fecal occult blood tests, 7.1% for sigmoidoscopy, and 7.1% for colonoscopy. LHW outreach is feasible and may be effective in promoting CRC screening among Chinese Americans

What's in a copy?

ABSTRACTI will answer the question “What’s in a copy?” by considering three sets of related issues: the importance of copies in academia; in cultural life; and in the economic world. In academia the current capability of making copies is challenging pedagogical practices and the trust of its members, plagiarism being the most immediate problem. The notion of authorship is also undergoing changes provoked by a proliferation of authors and new possibilities opened up by cyberspace. In cultural life, imitation and mimesis have long been fundamental engines of socialization. Our enhanced capacity of copying problematizes, with new intensity, the relationships between homogeneity and heterogeneity, between the genuine and the spurious. In the economic world, the digital era is threatening some of the fundamental tenets of capitalism, especially of its variant called the “knowledge society”, regarding the control of intellectual property rights. The gap between normativity and social practices is widening. The many dilemmas and tensions identified in the text are understood as symptoms of two major characteristics of the current times: hyperfetishism and hyperanimism. ________________________________________________________________________________ RESUMOResponderei à pergunta “O que existe em uma cópia?” considerando três conjuntos de questões relacionadas: a importância das cópias na academia, na vida cultural, no mundo econômico. Na academia a presente capacidade de fazer cópias está desafiando práticas pedagógicas e a confiança dos seus membros, o plágio sendo o problema mais imediato. A noção de autoria também está sofrendo mudanças provocadas por uma proliferação de autores e novas possibilidades abertas pelo ciberespaço. Na vida cultural, a imitação e a mimese de há muito são importantes motores de socialização. A nossa capacidade ampliada de fazer cópias problematiza, com nova intensidade, as relações entre homogeneidade e heterogeneidade, entre o genuíno e o espúrio. No mundo econômico, a era digital ameaça algumas das premissas fundamentais do capitalismo, especialmente da sua variante “sociedade do conhecimento”, no tocante aos direitos de propriedade intelectual. Cresce a distância entre normatividade e práticas sociais. Os muitos dilemas e tensões identificados no texto são compreendidos como sintomas de duas grandes características do presente: o hiperfetichismo e o hiperanimismo

Childhood in Sociology and Society: The US Perspective

The field of childhood studies in the US is comprised of cross-disciplinary researchers who theorize and conduct research on both children and youth. US sociologists who study childhood largely draw on the childhood literature published in English. This article focuses on American sociological contributions, but notes relevant contributions from non-American scholars published in English that have shaped and fueled American research. This article also profiles the institutional support of childhood research in the US, specifically outlining the activities of the ‘Children and Youth’ Section of the American Sociological Association (ASA), and assesses the contributions of this area of study for sociology as well as the implications for an interdisciplinary field.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1.

With resistance to most antimalarials increasing, it is imperative that new drugs are developed. We previously identified an aryl acetamide compound, MMV006833 (M-833), that inhibited the ring-stage development of newly invaded merozoites. Here, we select parasites resistant to M-833 and identify mutations in the START lipid transfer protein (PF3D7_0104200, PfSTART1). Introducing PfSTART1 mutations into wildtype parasites reproduces resistance to M-833 as well as to more potent analogues. PfSTART1 binding to the analogues is validated using organic solvent-based Proteome Integral Solubility Alteration (Solvent PISA) assays. Imaging of invading merozoites shows the inhibitors prevent the development of ring-stage parasites potentially by inhibiting the expansion of the encasing parasitophorous vacuole membrane. The PfSTART1-targeting compounds also block transmission to mosquitoes and with multiple stages of the parasite's lifecycle being affected, PfSTART1 represents a drug target with a new mechanism of action

Man and the Last Great Wilderness: Human Impact on the Deep Sea

The deep sea, the largest ecosystem on Earth and one of the least studied, harbours high biodiversity and provides a wealth of resources. Although humans have used the oceans for millennia, technological developments now allow exploitation of fisheries resources, hydrocarbons and minerals below 2000 m depth. The remoteness of the deep seafloor has promoted the disposal of residues and litter. Ocean acidification and climate change now bring a new dimension of global effects. Thus the challenges facing the deep sea are large and accelerating, providing a new imperative for the science community, industry and national and international organizations to work together to develop successful exploitation management and conservation of the deep-sea ecosystem. This paper provides scientific expert judgement and a semi-quantitative analysis of past, present and future impacts of human-related activities on global deep-sea habitats within three categories: disposal, exploitation and climate change. The analysis is the result of a Census of Marine Life – SYNDEEP workshop (September 2008). A detailed review of known impacts and their effects is provided. The analysis shows how, in recent decades, the most significant anthropogenic activities that affect the deep sea have evolved from mainly disposal (past) to exploitation (present). We predict that from now and into the future, increases in atmospheric CO2 and facets and consequences of climate change will have the most impact on deep-sea habitats and their fauna. Synergies between different anthropogenic pressures and associated effects are discussed, indicating that most synergies are related to increased atmospheric CO2 and climate change effects. We identify deep-sea ecosystems we believe are at higher risk from human impacts in the near future: benthic communities on sedimentary upper slopes, cold-water corals, canyon benthic communities and seamount pelagic and benthic communities. We finalise this review with a short discussion on protection and management methods