Development of a social studies unit on westward expansion in the United States at a beginning 3rd grade level

This paper is a curriculum packet for teaching of the westward expansion in the United States for a third grade level

The Global academic research organization network: Data sharing to cure diseases and enable learning health systems.

Introduction:Global data sharing is essential. This is the premise of the Academic Research Organization (ARO) Council, which was initiated in Japan in 2013 and has since been expanding throughout Asia and into Europe and the United States. The volume of data is growing exponentially, providing not only challenges but also the clear opportunity to understand and treat diseases in ways not previously considered. Harnessing the knowledge within the data in a successful way can provide researchers and clinicians with new ideas for therapies while avoiding repeats of failed experiments. This knowledge transfer from research into clinical care is at the heart of a learning health system. Methods:The ARO Council wishes to form a worldwide complementary system for the benefit of all patients and investigators, catalyzing more efficient and innovative medical research processes. Thus, they have organized Global ARO Network Workshops to bring interested parties together, focusing on the aspects necessary to make such a global effort successful. One such workshop was held in Austin, Texas, in November 2017. Representatives from Japan, Taiwan, Singapore, Europe, and the United States reported on their efforts to encourage data sharing and to use research to inform care through learning health systems. Results:This experience report summarizes presentations and discussions at the Global ARO Network Workshop held in November 2017 in Austin, TX, with representatives from Japan, Korea, Singapore, Taiwan, Europe, and the United States. Themes and recommendations to progress their efforts are explored. Standardization and harmonization are at the heart of these discussions to enable data sharing. In addition, the transformation of clinical research processes through disruptive innovation, while ensuring integrity and ethics, will be key to achieving the ARO Council goal to overcome diseases such that people not only live longer but also are healthier and happier as they age. Conclusions:The achievement of global learning health systems will require further exploration, consensus-building, funding aligned with incentives for data sharing, standardization, harmonization, and actions that support global interests for the benefit of patients

Novel in vitro and mathematical models for the prediction of chemical toxicity

The focus of much scientific and medical research is directed towards understanding the disease process and defining therapeutic intervention strategies. Whilst the scientific basis of drug safety has received relatively little attention, despite the fact that adverse drug reactions (ADRs) are a major health concern and a serious impediment to development of new medicines. Toxicity issues account for ~21% drug attrition during drug development and safety testing strategies require considerable animal use. Mechanistic relationships between drug plasma levels and molecular/cellular events that culminate in whole organ toxicity underpins development of novel safety assessment strategies. Current in vitro test systems are poorly predictive of toxicity of chemicals entering the systemic circulation, particularly to the liver. Such systems fall short because of 1) the physiological gap between cells currently used & human hepatocytes existing in their native state, 2) the lack of physiological integration with other cells/systems within organs, required to amplify the initial toxicological lesion into overt toxicity, 3) the inability to assess how low level cell damage induced by chemicals may develop into overt organ toxicity in a minority of patients, 4) lack of consideration of systemic effects. Reproduction of centrilobular & periportal hepatocyte phenotypes in in vitro culture is crucial for sensitive detection of cellular stress. Hepatocyte metabolism/phenotype is dependent on cell position along the liver lobule, with corresponding differences in exposure to substrate, oxygen & hormone gradients. Application of bioartificial liver (BAL) technology can encompass in vitro predictive toxicity testing with enhanced sensitivity and improved mechanistic understanding. Combining this technology with mechanistic mathematical models describing intracellular metabolism, fluid-­‐flow, substrate, hormone and nutrient distribution provides the opportunity to design the BAL specifically to mimic the in vivo scenario. Such mathematical models enable theoretical hypothesis testing, will inform the design of in vitro experiments, and will enable both refinement and reduction of in vivo animal trials. In this way, development of novel mathematical modelling tools will help to focus and direct in vitro and in vivo research, and can be used as a framework for other areas of drug safety science

FAST Heroes : Results of Cross-Country Implementation of a Global School-Based Stroke Education Campaign

Funding Information: This study received funding from Boehringer Ingelheim (Grant Number 395479, 2019). The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. Publisher Copyright: Copyright © 2022 Tsakpounidou, van der Merwe, Klinke, Webb, Ouriques Martins and Proios.Background: Educating the at-risk population about stroke symptoms and requirement of calling an ambulance when stroke strikes is challenging. This exploratory cross-country study provides insights to the FAST Heroes educational campaign and outcomes hitherto achieved. Aims: The primary aim of the study was to measure the transfer of stroke-related knowledge to parents after a global school-based FAST Heroes educational campaign for 5- to 9-year-old children in 14 different countries. The secondary aim was to evaluate parents and teachers' acceptability toward the program. Methods: The duration of the program was 5 h; 1 h per week, joining face-to-face educational sessions with workbooks, cartoons, web-based learning, and other fun activities. Outcomes were measured before implementation (t1), after implementation (t2), and at 6-month follow-up (t3). Program acceptability and stroke knowledge were evaluated by feedback surveys for teachers and parents. Results: Worldwide, 4,202 parents completed the program with their children and answered surveys at t1 and t2. They increased their knowledge of three stroke symptoms from 48 to 83% (p < 0.001). All three surveys were completed by 86 parents, who improved their knowledge of stroke symptoms, 55% (t1), 79% (t2), and 94% (t3) (p < 0.001). Overall, the educational messages were successfully passed onward. Conclusions: Findings confirm the primary aim of the study that is knowledge about stroke transfer well from children to their families through the FAST Heroes program. Second, parents and teachers globally consider the program feasible and worthwhile. The results will inform further rollout of the campaign.Peer reviewe

Orbital Decay in M82 X-2

© 2022. The Author(s). Published by the American Astronomical Society. This is an open access article distributed under the Creative Commons Attribution License, to view a copy of the license, https://creativecommons.org/licenses/by/4.0/M82 X-2 is the first pulsating ultraluminous X-ray source discovered. The luminosity of these extreme pulsars, if isotropic, implies an extreme mass transfer rate. An alternative is to assume a much lower mass transfer rate, but with an apparent luminosity boosted by geometrical beaming. Only an independent measurement of the mass transfer rate can help discriminate between these two scenarios. In this paper, we follow the orbit of the neutron star for 7 yr, measure the decay of the orbit ( Ṗorb/Porb≈−8·10−6yr−1 ), and argue that this orbital decay is driven by extreme mass transfer of more than 150 times the mass transfer limit set by the Eddington luminosity. If this is true, the mass available to the accretor is more than enough to justify its luminosity, with no need for beaming. This also strongly favors models where the accretor is a highly magnetized neutron star.Peer reviewe

A population of gamma-ray emitting globular clusters seen with the Fermi Large Area Telescope

Globular clusters with their large populations of millisecond pulsars (MSPs) are believed to be potential emitters of high-energy gamma-ray emission. Our goal is to constrain the millisecond pulsar populations in globular clusters from analysis of gamma-ray observations. We use 546 days of continuous sky-survey observations obtained with the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope to study the gamma-ray emission towards 13 globular clusters. Steady point-like high-energy gamma-ray emission has been significantly detected towards 8 globular clusters. Five of them (47 Tucanae, Omega Cen, NGC 6388, Terzan 5, and M 28) show hard spectral power indices $(0.7 < \Gamma <1.4)$ and clear evidence for an exponential cut-off in the range 1.0-2.6 GeV, which is the characteristic signature of magnetospheric emission from MSPs. Three of them (M 62, NGC 6440 and NGC 6652) also show hard spectral indices $(1.0 < \Gamma < 1.7)$, however the presence of an exponential cut-off can not be unambiguously established. Three of them (Omega Cen, NGC 6388, NGC 6652) have no known radio or X-ray MSPs yet still exhibit MSP spectral properties. From the observed gamma-ray luminosities, we estimate the total number of MSPs that is expected to be present in these globular clusters. We show that our estimates of the MSP population correlate with the stellar encounter rate and we estimate 2600-4700 MSPs in Galactic globular clusters, commensurate with previous estimates. The observation of high-energy gamma-ray emission from a globular cluster thus provides a reliable independent method to assess their millisecond pulsar populations that can be used to make constraints on the original neutron star X-ray binary population, essential for understanding the importance of binary systems in slowing the inevitable core collapse of globular clusters.Comment: Accepted for publication in A&A. Corresponding authors: J. Kn\"odlseder, N. Webb, B. Pancraz

Severe male infertility after failed ICSI treatment-a phenomenological study of men's experiences

<p>Abstract</p> <p>Background</p> <p>Male-factor infertility underlies approximately 30% of infertility in couples seeking treatment; of which 10% is due to azoospermia. The development of assisted reproductive technology (ART), enabling the use of epididymal or testicular sperm for fertilization of the partner's oocytes, has made biological fatherhood possible for men with obstructive azoospermia. There is limited knowledge of men's experience of their own infertility. The aim of this study was to describe men's experiences of obstructive azoospermia infertility.</p> <p>Methods</p> <p>Eight men with obstructive azoospermia, who had terminated Swedish public health system ART treatment two years previously without subsequent childbirth, were interviewed using a descriptive phenomenological method.</p> <p>Results</p> <p>The essence of the phenomenon is expressed with a metaphor: climbing a mountain step by step with the aim of reaching the top, i.e. having a child and thus a family with a child. Four constituents are included (1) inadequacy followed by a feeling of redress (2) marginalisation, (3) chivalry (4) extension of life and starting a family as driving forces.</p> <p>Conclusions</p> <p>Knowledge of men's experiences of their own infertility is important as a supporting measure to increase the quality of care of infertile couples. By adopting this facet of gender perspective in fertility treatment guidelines, care can hopefully be optimized.</p

The Role of Intestinal Microbiota in the Development and Severity of Chemotherapy-Induced Mucositis

Mucositis, also referred to as mucosal barrier injury, is one of the most debilitating side effects of radiotherapy and chemotherapy treatment. Clinically, mucositis is associated with pain, bacteremia, and malnutrition. Furthermore, mucositis is a frequent reason to postpone chemotherapy treatment, ultimately leading towards a higher mortality in cancer patients. According to the model introduced by Sonis, both inflammation and apoptosis of the mucosal barrier result in its discontinuity, thereby promoting bacterial translocation. According to this five-phase model, the intestinal microbiota plays no role in the pathophysiology of mucositis. However, research has implicated a prominent role for the commensal intestinal microbiota in the development of several inflammatory diseases like inflammatory bowel disease, pouchitis, and radiotherapy-induced diarrhea. Furthermore, chemotherapeutics have a detrimental effect on the intestinal microbial composition (strongly decreasing the numbers of anaerobic bacteria), coinciding in time with the development of chemotherapy-induced mucositis. We hypothesize that the commensal intestinal microbiota might play a pivotal role in chemotherapy-induced mucositis. In this review, we propose and discuss five pathways in the development of mucositis that are potentially influenced by the commensal intestinal microbiota: 1) the inflammatory process and oxidative stress, 2) intestinal permeability, 3) the composition of the mucus layer, 4) the resistance to harmful stimuli and epithelial repair mechanisms, and 5) the activation and release of immune effector molecules. Via these pathways, the commensal intestinal microbiota might influence all phases in the Sonis model of the pathogenesis of mucositis. Further research is needed to show the clinical relevance of restoring dysbiosis, thereby possibly decreasing the degree of intestinal mucositis

Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder

Individual response to stress is correlated with neuroticism and is an important predictor of both neuroticism and the onset of major depressive disorder (MDD). Identification of the genetics underpinning individual differences in response to negative events (stress-sensitivity) may improve our understanding of the molecular pathways involved, and its association with stress-related illnesses. We sought to generate a proxy for stress-sensitivity through modelling the interaction between SNP allele and MDD status on neuroticism score in order to identify genetic variants that contribute to the higher neuroticism seen in individuals with a lifetime diagnosis of depression compared to unaffected individuals. Meta-analysis of genome-wide interaction studies (GWIS) in UK Biobank (N = 23,092) and Generation Scotland: Scottish Family Health Study (N = 7,155) identified no genome-wide significance SNP interactions. However, gene-based tests identified a genome-wide significant gene, ZNF366, a negative regulator of glucocorticoid receptor function implicated in alcohol dependence (p = 1.48x10-7; Bonferroni-corrected significance threshold p < 2.79x10-6). Using summary statistics from the stress-sensitivity term of the GWIS, SNP heritability for stress-sensitivity was estimated at 5.0%. In models fitting polygenic risk scores of both MDD and neuroticism derived from independent GWAS, we show that polygenic risk scores derived from the UK Biobank stress-sensitivity GWIS significantly improved the prediction of MDD in Generation Scotland. This study may improve interpretation of larger genome-wide association studies of MDD and other stress-related illnesses, and the understanding of the etiological mechanisms underpinning stress-sensitivity