79 research outputs found
The role of gender in the processing of dating scripts
The issues under investigation were gender differences in either content or memory discrimination of dating scripts and general examination for differences in memory of typical and atypical events using the script pointer plus tag (SP+T) hypothesis. A total of 52 female and 54 male undergraduates participated. Subjects were enrolled in introductory psychology classes at a large midwest university and were primarily Caucasian, single, and between the ages of 18-21 years. In Phase 1 and Phase 2 of the study, items that would possibly occur in 4 different dating scenarios were generated and then rated for typicality. Males and females both generated and rated items similarly in the first 2 phases. In Phase 3, the taped dating stories were presented along with a single-item recognition test which included many of these typical and atypical events. Analyses showed that memory discrimination varied significantly with gender, F(1, 51) = 4.07, p \u3c .05, and typicality, F(1, 51) = 395.80, p \u3c .0001, and a significant gender x typicality interaction was found, F(1, 51) = 7.17, p \u3c .01. Females displayed better memory discrimination overall, especially on atypical items. It was concluded that further investigation on possible gender differences in role, meaning, attention, and social norm affectation of dating scripts may explain differences in memory discrimination
Benefits and challenges of electronic prescribing for general practitioners and pharmacists in regional Australia
Objective: To explore the benefits and challenges of electronic prescribing (e-prescribing) for general practitioners (GPs) and pharmacists in regional New South Wales (NSW). Methods: This qualitative study utilised semistructured interviews conducted virtually or in-person between July and September 2021. Setting and Participants: General practitioners and pharmacists practising in Bathurst NSW. Main Outcomes: Self-reported perceived and experienced benefits and challenges of e-prescribing. Results: Two GPs and four pharmacists participated in the study. Reported benefits of e-prescribing included improvement in the prescribing and dispensing process, patient adherence, and prescription safety and security. The increased convenience for the patients was appreciated particularly during the COVID-19 pandemic. Challenges discussed were how the system was perceived to be unsafe and insecure, costs of messaging and updating general practice software, utilisation of new systems and patient awareness. Pharmacists reported the need for education to patients and staff to minimise the impact of inexperience with the novel technology on workflow efficacy. Conclusion: This study provided first insight and information on the perspectives of GPs and pharmacists 12 months after the implementation of e-prescribing. Further nationwide studies are required to consolidate these findings; provide comparisons with the system's progress since conception; determine whether metropolitan and rural health care professionals share similar perspectives; and shed light on where additional government support may be required
Glycan shifting on hepatitis C virus (HCV) E2 glycoprotein is a mechanism for escape from broadly neutralizing antibodies
Hepatitis C virus (HCV) infection is a major cause of liver disease and hepatocellular carcinoma. Glycan shielding has been proposed to be a mechanism by which HCV masks broadly neutralizing epitopes on its viral glycoproteins. However, the role of altered glycosylation in HCV resistance to broadly neutralizing antibodies is not fully understood. Here, we have generated potent HCV neutralizing antibodies hu5B3.v3 and MRCT10.v362 that, similar to the previously described AP33 and HCV1, bind to a highly conserved linear epitope on E2. We utilize a combination of in vitro resistance selections using the cell culture infectious HCV and structural analyses to identify mechanisms of HCV resistance to hu5B3.v3 and MRCT10.v362. Ultra deep sequencing from in vitro HCV resistance selection studies identified resistance mutations at asparagine N417 (N417S, N417T and N417G) as early as 5 days post treatment. Comparison of the glycosylation status of soluble versions of the E2 glycoprotein containing the respective resistance mutations revealed a glycosylation shift from N417 to N415 in the N417S and N417T E2 proteins. The N417G E2 variant was glycosylated neither at residue 415 nor at residue 417 and remained sensitive to MRCT10.v362. Structural analyses of the E2 epitope bound to hu5B3.v3 Fab and MRCT10.v362 Fab using X-ray crystallography confirmed that residue N415 is buried within the antibody–peptide interface. Thus, in addition to previously described mutations at N415 that abrogate the β-hairpin structure of this E2 linear epitope, we identify a second escape mechanism, termed glycan shifting, that decreases the efficacy of broadly neutralizing HCV antibodies
Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver
miR-122, an abundant liver-specific microRNA (miRNA), regulates cholesterol metabolism and promotes hepatitis C virus (HCV) replication. Reduced miR-122 expression in hepatocellular carcinoma (HCC) correlates with metastasis and poor prognosis. Nevertheless, the consequences of sustained loss of function of miR-122 in vivo have not been determined. Here, we demonstrate that deletion of mouse Mir122 resulted in hepatosteatosis, hepatitis, and the development of tumors resembling HCC. These pathologic manifestations were associated with hyperactivity of oncogenic pathways and hepatic infiltration of inflammatory cells that produce pro-tumorigenic cytokines, including IL-6 and TNF. Moreover, delivery of miR-122 to a MYC-driven mouse model of HCC strongly inhibited tumorigenesis, further supporting the tumor suppressor activity of this miRNA. These findings reveal critical functions for miR-122 in the maintenance of liver homeostasis and have important therapeutic implications, including the potential utility of miR-122 delivery for selected patients with HCC and the need for careful monitoring of patients receiving miR-122 inhibition therapy for HCV.This work was supported, in part, by NIH grants CA122694 (to K. Ghoshal), DK088076 (to K. Ghoshal), CA086978 (to K. Ghoshal and S.T. Jacob), Pelotonia Idea Grant (to J. Yu and K. Ghoshal), CA120185 (to J.T. Mendell), CA134292 (to J.T. Mendell), and the Cancer Prevention and Research Institute of Texas (to J.T. Men- dell). Bo Wang is supported by a Pelotonia graduate fellowship
Estimating genetic diversity across the neutral genome with the use of dense marker maps
<p>Abstract</p> <p>Background</p> <p>With the advent of high throughput DNA typing, dense marker maps have become available to investigate genetic diversity on specific regions of the genome. The aim of this paper was to compare two marker based estimates of the genetic diversity in specific genomic regions lying in between markers: IBD-based genetic diversity and heterozygosity.</p> <p>Methods</p> <p>A computer simulated population was set up with individuals containing a single 1-Morgan chromosome and 1665 SNP markers and from this one, an additional population was produced with a lower marker density i.e. 166 SNP markers. For each marker interval based on adjacent markers, the genetic diversity was estimated either by IBD probabilities or heterozygosity. Estimates were compared to each other and to the true genetic diversity. The latter was calculated for a marker in the middle of each marker interval that was not used to estimate genetic diversity.</p> <p>Results</p> <p>The simulated population had an average minor allele frequency of 0.28 and an LD (r<sup>2</sup>) of 0.26, comparable to those of real livestock populations. Genetic diversities estimated by IBD probabilities and by heterozygosity were positively correlated, and correlations with the true genetic diversity were quite similar for the simulated population with a high marker density, both for specific regions (r = 0.19-0.20) and large regions (r = 0.61-0.64) over the genome. For the population with a lower marker density, the correlation with the true genetic diversity turned out to be higher for the IBD-based genetic diversity.</p> <p>Conclusions</p> <p>Genetic diversities of ungenotyped regions of the genome (i.e. between markers) estimated by IBD-based methods and heterozygosity give similar results for the simulated population with a high marker density. However, for a population with a lower marker density, the IBD-based method gives a better prediction, since variation and recombination between markers are missed with heterozygosity.</p
The Atacama Cosmology Telescope: Cosmological parameters from three seasons of data
We present constraints on cosmological and astrophysical parameters from
high-resolution microwave background maps at 148 GHz and 218 GHz made by the
Atacama Cosmology Telescope (ACT) in three seasons of observations from 2008 to
2010. A model of primary cosmological and secondary foreground parameters is
fit to the map power spectra and lensing deflection power spectrum, including
contributions from both the thermal Sunyaev-Zeldovich (tSZ) effect and the
kinematic Sunyaev-Zeldovich (kSZ) effect, Poisson and correlated anisotropy
from unresolved infrared sources, radio sources, and the correlation between
the tSZ effect and infrared sources. The power ell^2 C_ell/2pi of the thermal
SZ power spectrum at 148 GHz is measured to be 3.4 +\- 1.4 muK^2 at ell=3000,
while the corresponding amplitude of the kinematic SZ power spectrum has a 95%
confidence level upper limit of 8.6 muK^2. Combining ACT power spectra with the
WMAP 7-year temperature and polarization power spectra, we find excellent
consistency with the LCDM model. We constrain the number of effective
relativistic degrees of freedom in the early universe to be Neff=2.79 +\- 0.56,
in agreement with the canonical value of Neff=3.046 for three massless
neutrinos. We constrain the sum of the neutrino masses to be Sigma m_nu < 0.39
eV at 95% confidence when combining ACT and WMAP 7-year data with BAO and
Hubble constant measurements. We constrain the amount of primordial helium to
be Yp = 0.225 +\- 0.034, and measure no variation in the fine structure
constant alpha since recombination, with alpha/alpha0 = 1.004 +/- 0.005. We
also find no evidence for any running of the scalar spectral index, dns/dlnk =
-0.004 +\- 0.012.Comment: 26 pages, 22 figures. This paper is a companion to Das et al. (2013)
and Dunkley et al. (2013). Matches published JCAP versio
Advancing the Field of Pediatric Exercise Oncology: Research and Innovation Needs
The field of pediatric exercise oncology explores the relationships between physical activity (PA), including exercise, and a range of outcomes among children and adolescents affected by cancer. Although PA is safe and beneficial for this population, several important gaps in knowledge and practice remain. In this article, we describe research and innovation needs that were developed with a team of international experts and relevant literature, a series of online surveys, and an in-person meeting. Addressing these needs will contribute valuable knowledge and practice outputs to advance this field, ultimately enabling a greater number of children and adolescents affected by cancer to realize the benefits of moving more
Robotic Table Tennis: A Case Study into a High Speed Learning System
We present a deep-dive into a real-world robotic learning system that, in
previous work, was shown to be capable of hundreds of table tennis rallies with
a human and has the ability to precisely return the ball to desired targets.
This system puts together a highly optimized perception subsystem, a high-speed
low-latency robot controller, a simulation paradigm that can prevent damage in
the real world and also train policies for zero-shot transfer, and automated
real world environment resets that enable autonomous training and evaluation on
physical robots. We complement a complete system description, including
numerous design decisions that are typically not widely disseminated, with a
collection of studies that clarify the importance of mitigating various sources
of latency, accounting for training and deployment distribution shifts,
robustness of the perception system, sensitivity to policy hyper-parameters,
and choice of action space. A video demonstrating the components of the system
and details of experimental results can be found at
https://youtu.be/uFcnWjB42I0.Comment: Published and presented at Robotics: Science and Systems (RSS2023
The international Pediatric Oncology Exercise Guidelines (iPOEG)
Physical activity (PA) and exercise are safe and beneficial for children and adolescents affected by cancer. Yet, this population is not active enough to receive benefits. PA guideline and recommendation statements can support individual behavior and practice change. The purpose of this project was to develop the international Pediatric Oncology Exercise Guidelines (iPOEG), comprised of guideline and recommendation statements, to promote PA among children and adolescents affected by cancer. Guideline development procedures, stakeholder engagement strategies, and the Delphi technique were used. Four online surveys were distributed to the iPOEG network (n = 9 core team members, n = 122 expert consensus committee members). Surveys included closed- and open-ended items informed by a literature synthesis and an in-person meeting. Responses were analyzed using descriptive statistics and content analysis. Consensus was defined as >= 80% agreement. Response rates to online surveys ranged from 82% to 91%. The iPOEG network agreed on four guideline and five recommendation statements, which highlight that movement is important for all children and adolescents affected by cancer. These statements are generic in nature as more research is still required to provide specific guidance on the frequency, intensity, time, and type of PA for this population. Nevertheless, the iPOEG statements represent available evidence and expert opinion, collectively suggesting that it is time for children and adolescents affected by cancer to move more.</p
Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019
Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens
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