227 research outputs found
Study Analyzing the Perspectives of National Board Certified Media Specialists
The purpose of this study was to examine the perceptions of ESLMS\u27s (Expert School Library Media Specialists) as total educators (Fullan & Hargreaves, 1996), including the SLMSs (School Library Media Specialist) purpose, the ESLMS as a person, the organizational context and the culture of the SLMS\u27s school. The hypothesis was that ESLMSs role and development as experts in their field was directly related to their purpose and motivations, their view of themselves as persons including their beliefs and values, and the culture and organizational context of the specific school in which they work. Three SLMS\u27s currently employed in Georgia public high schools whom have earned National Board Certification in Library Media were selected for this study. Qualitative research methodology, including questionnaires and interviews, analysis of state and federal reports, an examination of collected artifacts, and an analysis of an online discussion forum, was utilized to create case studies of these three ESLMS\u27s. This research indicated that in order to excel in the media field all four aspects of the total educator must be addressed. The overall results indicate that 1) SLMSs must understand their purpose and goals and those purposes and goals must align with those of the schools in which they work in order to excel in their profession; 2) SLMSs must be aware of themselves as persons in order to grow and develop as professionals and 1 educators; 3) The organizational context of the SLMSs school must allow them control of aspects of their media program in order to implement an exemplary media program; and 4) The culture in which the SLMS\u27s works must provide administrative and staff support for the media program in order for them to implement an exemplary media program. Recommendations include the need to further the leadership roles of SLMSs within their schools; the call for SLMSs to augment their leadership role within their field; the need to increase the understanding and support of administrators for SLMSs; the obligation that SLMSs have to link their role within a school to student achievement; and the necessity to enhance the incentives for accomplishing National Board Certification
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Decreased soluble guanylate cyclase contributes to cardiac dysfunction induced by chronic doxorubicin treatment in mice
Aims: The use of doxorubicin, a potent chemotherapeutic agent, is limited by cardiotoxicity. We tested the hypothesis that decreased soluble guanylate cyclase (sGC) enzyme activity contributes to the development of doxorubicin-induced cardiotoxicity. Results: Doxorubicin administration (20 mg/kg, intraperitoneally [IP]) reduced cardiac sGC activity in wild-type (WT) mice. To investigate whether decreased sGC activity contributes to doxorubicin-induced cardiotoxicity, we studied mice with cardiomyocyte-specific deficiency of the sGC alpha 1-subunit (mice with cardiomyocyte-specific deletion of exon 6 of the sGC alpha 1 allele [sGC alpha 1(-/-CM)]). After 12 weeks of doxorubicin administration (2 mg/kg/week IP), left ventricular (LV) systolic dysfunction was greater in sGC alpha 1(-/-CM) than WT mice. To further assess whether reduced sGC activity plays a pathogenic role in doxorubicin-induced cardiotoxicity, we studied a mouse model in which decreased cardiac sGC activity was induced by cardiomyocyte-specific expression of a dominant negative sGC alpha 1 mutant (DNsGC alpha 1) upon doxycycline removal (Tet-off). After 8 weeks of doxorubicin administration, DNsGC alpha 1(tg/+), but not WT, mice displayed LV systolic dysfunction and dilatation. The difference in cardiac function and remodeling between DNsGC alpha 1(tg/+) and WT mice was even more pronounced after 12 weeks of treatment. Further impairment of cardiac function was attenuated when DNsGC alpha 1 gene expression was inhibited (beginning at 8 weeks of doxorubicin treatment) by administering doxycycline. Furthermore, doxorubicin-associated reactive oxygen species generation was higher in sGC alpha 1-deficient than WT hearts. Innovation and Conclusion: These data demonstrate that a reduction in cardiac sGC activity worsens doxorubicin-induced cardiotoxicity in mice and identify sGC as a potential therapeutic target. Various pharmacological sGC agonists are in clinical development or use and may represent a promising approach to limit doxorubicin-associated cardiotoxicity
Learning to Apply Mindfulness to Pain (LAMP): Design for a Pragmatic Clinical Trial of Two Mindfulness-Based Interventions for Chronic Pain
Background: Mindfulness-based interventions (MBIs) are evidence-based nonpharmacological treatments for treating chronic pain. However, the predominant MBI, mindfulness-based stress reduction, has features that pose significant implementation barriers.
Objectives: This study will test two approaches to delivering MBIs for improving Veterans' chronic pain and mental health comorbidities. These two approaches address key implementation barriers.
Methods: We will conduct a four-site, three-arm pragmatic randomized controlled trial, Learning to Apply Mindfulness to Pain (LAMP), to test the effectiveness of two MBIs at improving pain and mental health comorbidities. Mobile+Group LAMP consists of prerecorded modules presented by a mindfulness instructor that are viewed in an online group setting and interspersed with discussions led by a facilitator. Mobile LAMP consists of the same prerecorded modules but does not include a group component. We will test whether either of these MBIs will be more effective than usual care at improving chronic pain and whether the Mobile+Group LAMP will be more effective than Mobile LAMP at improving chronic pain. Comparisons for the primary hypotheses will be conducted with continuous outcomes (Brief Pain Inventory interference score) repeated at 10 weeks, 6 months, and 12 months. The secondary hypotheses are that Mobile+Group LAMP and Mobile LAMP will be more effective than usual care at improving secondary outcomes (e.g., post-traumatic stress disorder, depression). We will also confirm the comparisons for the primary and secondary hypotheses in gender-specific strata.
Implications: This trial is expected to result in two approaches for delivering MBIs that will optimize engagement, adherence, and sustainability and be able to reach large numbers of Veterans
Platform adaptive trial of novel antivirals for early treatment of COVID-19 In the community (PANORAMIC): protocol for a randomised, controlled, open-label, adaptive platform trial of community novel antiviral treatment of COVID-19 in people at increased risk of more severe disease
Introduction: There is an urgent need to determine the safety, effectiveness and cost-effectiveness of novel antiviral treatments for COVID-19 in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19.
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Methods and analysis: PANORAMIC is a UK-wide, open-label, prospective, adaptive, multiarm platform, randomised clinical trial that evaluates antiviral treatments for COVID-19 in the community. A master protocol governs the addition of new antiviral treatments as they become available, and the introduction and cessation of existing interventions via interim analyses. The first two interventions to be evaluated are molnupiravir (Lagevrio) and nirmatrelvir/ritonavir (Paxlovid). Eligibility criteria: community-dwelling within 5âdays of onset of symptomatic COVID-19 (confirmed by PCR or lateral flow test), and either (1) aged 50 years and over, or (2) aged 18â49 years with qualifying comorbidities. Registration occurs via the trial website and by telephone. Recruitment occurs remotely through the central trial team, or in person through clinical sites. Participants are randomised to receive either usual care or a trial drug plus usual care. Outcomes are collected via a participant-completed daily electronic symptom diary for 28 days post randomisation. Participants and/or their Trial Partner are contacted by the research team after days 7, 14 and 28 if the diary is not completed, or if the participant is unable to access the diary. The primary efficacy endpoint is all-cause, non-elective hospitalisation and/or death within 28 days of randomisation. Multiple prespecified interim analyses allow interventions to be stopped for futility or superiority based on prespecified decision criteria. A prospective economic evaluation is embedded within the trial.
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Ethics and dissemination: Ethical approval granted by South CentralâBerkshire REC number: 21/SC/0393; IRAS project ID: 1004274. Results will be presented to policymakers and at conferences, and published in peer-reviewed journals.
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Trial registration number: ISRCTN30448031; EudraCT number: 2021-005748-31
Are men universally more dismissing than women? Gender differences in romantic attachment across 62 cultural regions
The authors thank Susan Sprecher (USA), Del
Paulhus (Canada), Glenn D. Wilson (England), Qazi
Rahman (England), Alois Angleitner (Germany),
Angelika Hofhansl (Austria), Tamio Imagawa
(Japan), Minoru Wada (Japan), Junichi Taniguchi
(Japan), and Yuji Kanemasa (Japan) for helping with
data collection and contributing significantly to the
samples used in this study.Gender differences in the dismissing form of adult romantic attachment were investigated as part of the International Sexuality Description Projectâa survey study of 17,804 people from 62 cultural regions. Contrary to research findings previously reported in Western cultures, we found that men were not significantly more dismissing than women across all cultural regions. Gender differences in dismissing romantic attachment were evident in most cultures, but were typically only small to moderate in magnitude. Looking across cultures, the degree of gender differentiation in dismissing romantic attachment was predictably associated with sociocultural indicators. Generally, these associations supported evolutionary theories of romantic attachment, with smaller gender differences evident in cultures with highâstress and highâfertility reproductive environments. Social role theories of human sexuality received less support in that more progressive sexârole ideologies and national gender equity indexes were not crossâculturally linked as expected to smaller gender differences in dismissing romantic attachment.peer-reviewe
Effects of smoking on the genetic risk of obesity: the population architecture using genomics and epidemiology study
Abstract Background Although smoking behavior is known to affect body mass index (BMI), the potential for smoking to influence genetic associations with BMI is largely unexplored. Methods As part of the âPopulation Architecture using Genomics and Epidemiology (PAGE)â Consortium, we investigated interaction between genetic risk factors associated with BMI and smoking for 10 single nucleotide polymorphisms (SNPs) previously identified in genome-wide association studies. We included 6 studies with a total of 56,466 subjects (16,750 African Americans (AA) and 39,716 European Americans (EA)). We assessed effect modification by testing an interaction term for each SNP and smoking (current vs. former/never) in the linear regression and by stratified analyses. Results We did not observe strong evidence for interactions and only observed two interactions with p-values <0.1: for rs6548238/TMEM18, the risk allele (C) was associated with BMI only among AA females who were former/never smokers (ÎČ = 0.018, p = 0.002), vs. current smokers (ÎČ = 0.001, p = 0.95, pinteraction = 0.10). For rs9939609/FTO, the A allele was more strongly associated with BMI among current smoker EA females (ÎČ = 0.017, p = 3.5x10-5), vs. former/never smokers (ÎČ = 0.006, p = 0.05, pinteraction = 0.08). Conclusions These analyses provide limited evidence that smoking status may modify genetic effects of previously identified genetic risk factors for BMI. Larger studies are needed to follow up our results. Clinical Trial Registration NCT0000061
Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes
Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.NovartisEli Lilly and CompanyAstraZenecaAbbViePfizer UKCelgeneEisaiGenentechMerck Sharp and DohmeRocheCancer Research UKGovernment of CanadaArray BioPharmaGenome CanadaNational Institutes of HealthEuropean CommissionMinistĂšre de l'Ăconomie, de lâInnovation et des Exportations du QuĂ©becSeventh Framework ProgrammeCanadian Institutes of Health Researc
The Science Performance of JWST as Characterized in Commissioning
This paper characterizes the actual science performance of the James Webb
Space Telescope (JWST), as determined from the six month commissioning period.
We summarize the performance of the spacecraft, telescope, science instruments,
and ground system, with an emphasis on differences from pre-launch
expectations. Commissioning has made clear that JWST is fully capable of
achieving the discoveries for which it was built. Moreover, almost across the
board, the science performance of JWST is better than expected; in most cases,
JWST will go deeper faster than expected. The telescope and instrument suite
have demonstrated the sensitivity, stability, image quality, and spectral range
that are necessary to transform our understanding of the cosmos through
observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures;
https://iopscience.iop.org/article/10.1088/1538-3873/acb29
The James Webb Space Telescope Mission
Twenty-six years ago a small committee report, building on earlier studies,
expounded a compelling and poetic vision for the future of astronomy, calling
for an infrared-optimized space telescope with an aperture of at least .
With the support of their governments in the US, Europe, and Canada, 20,000
people realized that vision as the James Webb Space Telescope. A
generation of astronomers will celebrate their accomplishments for the life of
the mission, potentially as long as 20 years, and beyond. This report and the
scientific discoveries that follow are extended thank-you notes to the 20,000
team members. The telescope is working perfectly, with much better image
quality than expected. In this and accompanying papers, we give a brief
history, describe the observatory, outline its objectives and current observing
program, and discuss the inventions and people who made it possible. We cite
detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space
Telescope Overview, 29 pages, 4 figure
Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease
We identified rare coding variants associated with Alzheimerâs disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1Ă10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5Ă10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38Ă10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56Ă10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55Ă10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development
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