Cost-Effective Control of Infectious Disease Outbreaks Accounting for Societal Reaction

Background Studies of cost-effective disease prevention have typically focused on the tradeoff between the cost of disease transmission and the cost of applying control measures. We present a novel approach that also accounts for the cost of social disruptions resulting from the spread of disease. These disruptions, which we call social response, can include heightened anxiety, strain on healthcare infrastructure, economic losses, or violence. Methodology The spread of disease and social response are simulated under several different intervention strategies. The modeled social response depends upon the perceived risk of the disease, the extent of disease spread, and the media involvement. Using Monte Carlo simulation, we estimate the total number of infections and total social response for each strategy. We then identify the strategy that minimizes the expected total cost of the disease, which includes the cost of the disease itself, the cost of control measures, and the cost of social response. Conclusions The model-based simulations suggest that the least-cost disease control strategy depends upon the perceived risk of the disease, as well as media intervention. The most cost-effective solution for diseases with low perceived risk was to implement moderate control measures. For diseases with higher perceived severity, such as SARS or Ebola, the most cost-effective strategy shifted toward intervening earlier in the outbreak, with greater resources. When intervention elicited increased media involvement, it remained important to control high severity diseases quickly. For moderate severity diseases, however, it became most cost-effective to implement no intervention and allow the disease to run its course. Our simulation results imply that, when diseases are perceived as severe, the costs of social response have a significant influence on selecting the most cost-effective strategy.United States. Defense Threat Reduction Agency (Contract HDTRA1-12-C-0061

Repositioning of Verrucosidin, a purported inhibitor of chaperone protein GRP78, as an inhibitor of mitochondrial electron transport chain complex I.

Verrucosidin (VCD) belongs to a group of fungal metabolites that were identified in screening programs to detect molecules that preferentially kill cancer cells under glucose-deprived conditions. Its mode of action was proposed to involve inhibition of increased GRP78 (glucose regulated protein 78) expression during hypoglycemia. Because GRP78 plays an important role in tumorigenesis, inhibitors such as VCD might harbor cancer therapeutic potential. We therefore sought to characterize VCD's anticancer activity in vitro. Triple-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468 were treated with VCD under different conditions known to trigger increased expression of GRP78, and a variety of cellular processes were analyzed. We show that VCD was highly cytotoxic only under hypoglycemic conditions, but not in the presence of normal glucose levels, and VCD blocked GRP78 expression only when glycolysis was impaired (due to hypoglycemia or the presence of the glycolysis inhibitor 2-deoxyglucose), but not when GRP78 was induced by other means (hypoxia, thapsigargin, tunicamycin). However, VCD's strictly hypoglycemia-specific toxicity was not due to the inhibition of GRP78. Rather, VCD blocked mitochondrial energy production via inhibition of complex I of the electron transport chain. As a result, cellular ATP levels were quickly depleted under hypoglycemic conditions, and common cellular functions, including general protein synthesis, deteriorated and resulted in cell death. Altogether, our study identifies mitochondria as the primary target of VCD. The possibility that other purported GRP78 inhibitors (arctigenin, biguanides, deoxyverrucosidin, efrapeptin, JBIR, piericidin, prunustatin, pyrvinium, rottlerin, valinomycin, versipelostatin) might act in a similar GRP78-independent fashion will be discussed

Walker use, but not falls, is associated with lower physical functioning and health of residents in an assisted-living environment

The relationship between perceived health and walker use has seldom been addressed. Concerns over falls and falls risk are precursors to walker use. We compared the SF-36 scores of 26 women and 14 men, mean age 86.8 ± 6.0 years based on walker use and faller status. An analysis of covariance (ANCOVA) with age as the covariate, compared groups for the SF-36 constructs and totals score. Significant differences were noted between walker users and nonusers in physical functioning, role limitations due to physical problems, general health, and the total SF-36 score. Pairwise comparisons favored nonusers, while no differences were seen due to faller status. Walker use is associated with lower self-perceptions of physical functioning, role limitations due to physical problems, and general health in assisted-living residents. Faller status is not associated with self-perceived health status. Although walker use aids mobility and lowers the probability of falls, further research is needed to determine if the prescription of assistive devices has a more negative impact on self-perceived health than does falling. This possibility could be explained, in part, by the greater activity levels of those individuals who do not depend on walkers

Addressing Occupational Deprivation in Refugees: A Scoping Review

In 2015, over 21 million refugees were displaced worldwide. A significant issue faced by this population is occupational deprivation – being deprived of engagement in meaningful activities. Despite this being a global problem, information on interventions that address occupational deprivation has not been synthesized. To bridge this gap, we conducted a scoping review to examine interventions that can be used when working with refugees who face this issue. For our methods, we used a five-step framework and reviewed interventions using the following databases: PubMed, CINAHL, PsycINFO, and Google Scholar. Initial searches yielded 191 studies, 7 of which were retained. Community-based rehabilitation, familiar activities from native countries, projective techniques allowing for emotional expression, mastery of practical skills allowing for navigation in new environments, and activities that promote social participation can be used with refugees who face occupational deprivation. These interventions may help promote refugees’ engagement in activities that hold personal, social, and cultural meaning

Oral rehydration versus intravenous therapy for treating dehydration due to gastroenteritis in children: a meta-analysis of randomised controlled trials

BACKGROUND: Despite treatment recommendations from various organizations, oral rehydration therapy (ORT) continues to be underused, particularly by physicians in high-income countries. We conducted a systematic review of randomised controlled trials (RCTs) to compare ORT and intravenous therapy (IVT) for the treatment of dehydration secondary to acute gastroenteritis in children. METHODS: RCTs were identified through MEDLINE, EMBASE, CENTRAL, authors and references of included trials, pharmaceutical companies, and relevant organizations. Screening and inclusion were performed independently by two reviewers in order to identify randomised or quasi-randomised controlled trials comparing ORT and IVT in children with acute diarrhea and dehydration. Two reviewers independently assessed study quality using the Jadad scale and allocation concealment. Data were extracted by one reviewer and checked by a second. The primary outcome measure was failure of rehydration. We analyzed data using standard meta-analytic techniques. RESULTS: The quality of the 14 included trials ranged from 0 to 3 (Jadad score); allocation concealment was unclear in all but one study. Using a random effects model, there was no significant difference in treatment failures (risk difference [RD] 3%; 95% confidence intervals [CI]: 0, 6). The Mantel-Haenzsel fixed effects model gave a significant difference between treatment groups (RD 4%; 95% CI: 2, 5) favoring IVT. Based on the four studies that reported deaths, there were six in the IVT groups and two in ORT. There were no significant differences in total fluid intake at six and 24 hours, weight gain, duration of diarrhea, or hypo/hypernatremia. Length of stay was significantly shorter for the ORT group (weighted mean difference [WMD] -1.2 days; 95% CI: -2.4,-0.02). Phlebitis occurred significantly more often with IVT (number needed to treat [NNT] 33; 95% CI: 25,100); paralytic ileus occurred more often with ORT (NNT 33; 95% CI: 20,100). These results may not be generalizable to children with persistent vomiting. CONCLUSION: There were no clinically important differences between ORT and IVT in terms of efficacy and safety. For every 25 children (95% CI: 20, 50) treated with ORT, one would fail and require IVT. The results support existing practice guidelines recommending ORT as the first course of treatment in appropriate children with dehydration secondary to gastroenteritis

Classecol: classifiers to understand public opinions of nature

1) Human perceptions of nature, once the domain of the social sciences, are now an important part of environmental research. However, the data and tools to tackle this research are lacking or are difficult to apply. 2) Here, we present a collection of text classifier models to identify text relevant to the broad topics of hunting and nature, describing whether opinions are pro- or against-hunting, or show interest, concern, or dislike of nature. The methods also include a biographical classification – describing whether the author of the text is a person, nature expert, nature organisation, or ‘Other’. The classifiers were developed using an extensive social media dataset, and are designed to support qualitative analysis of big data (especially from Twitter). 3) The classifiers accurately identified biographies, text related to hunting and nature, and the stance towards hunting and nature (weighted F-scores: 0.79 - 0.99; 1 indicates perfect accuracy). 4) These classifiers, alongside an array of other text processing and analysis functions, are presented in the form of an R package classecol. classecol also acts as a proof of concept that nature related text classifiers can be developed with high accuracy

Longitudinal Impact of Childhood Adversity on Early Adolescent Mental Health During the COVID-19 Pandemic in the ABCD Study Cohort: Does Race or Ethnicity Moderate Findings?

Background During the COVID-19 pandemic in the United States, mental health among youth has been negatively affected. Youth with a history of adverse childhood experiences (ACEs), as well as youth from minoritized racial-ethnic backgrounds, may be especially vulnerable to experiencing COVID-19–related distress. The aims of this study are to examine whether exposure to pre-pandemic ACEs predicts mental health during the COVID-19 pandemic in youth and whether racial-ethnic background moderates these effects. Methods From May to August 2020, 7983 youths (mean age, 12.5 years; range, 10.6–14.6 years) in the Adolescent Brain Cognitive Development (ABCD) Study completed at least one of three online surveys measuring the impact of the pandemic on their mental health. Data were evaluated in relation to youths\u27 pre-pandemic mental health and ACEs. Results Pre-pandemic ACE history significantly predicted poorer mental health across all outcomes and greater COVID-19–related stress and impact of fears on well-being. Youths reported improved mental health during the pandemic (from May to August 2020). While reporting similar levels of mental health, youths from minoritized racial-ethnic backgrounds had elevated COVID-19–related worry, stress, and impact on well-being. Race and ethnicity generally did not moderate ACE effects. Older youths, girls, and those with greater pre-pandemic internalizing symptoms also reported greater mental health symptoms. Conclusions Youths who experienced greater childhood adversity reported greater negative affect and COVID-19–related distress during the pandemic. Although they reported generally better mood, Asian American, Black, and multiracial youths reported greater COVID-19–related distress and experienced COVID-19–related discrimination compared with non-Hispanic White youths, highlighting potential health disparities

Multi-dimensional predictors of first drinking initiation and regular drinking onset in adolescence: A prospective longitudinal study

Early adolescent drinking onset is linked to myriad negative consequences. Using the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) baseline to year 8 data, this study (1) leveraged best subsets selection and Cox Proportional Hazards regressions to identify the most robust predictors of adolescent first and regular drinking onset, and (2) examined the clinical utility of drinking onset in forecasting later binge drinking and withdrawal effects. Baseline predictors included youth psychodevelopmental characteristics, cognition, brain structure, family, peer, and neighborhood domains. Participants (N=538) were alcohol-naïve at baseline. The strongest predictors of first and regular drinking onset were positive alcohol expectancies (Hazard Ratios [HRs]=1.67-1.87), easy home alcohol access (HRs=1.62-1.67), more parental solicitation (e.g., inquiring about activities; HRs=1.72-1.76), and less parental control and knowledge (HRs=.72-.73). Robust linear regressions showed earlier first and regular drinking onset predicted earlier transition into binge and regular binge drinking (βs=0.57-0.95). Zero-inflated Poisson regressions revealed that delayed first and regular drinking increased the likelihood (Incidence Rate Ratios [IRR]=1.62 and IRR=1.29, respectively) of never experiencing withdrawal. Findings identified behavioral and environmental factors predicting temporal paths to youthful drinking, dissociated first from regular drinking initiation, and revealed adverse sequelae of younger drinking initiation, supporting efforts to delay drinking onset

Adapting a Program to Inform African American and Hispanic American Women About Cancer Clinical Trials

The dearth of evidence-based clinical trial education programs may contribute to the underrepresentation of African American and Hispanic American women in cancer research studies. This study used focus group-derived data from 80 women distributed among eight Spanish- and English-language focus groups. These data guided the researchers’ adaptation and refinement of the National Cancer Institute’s various clinical trials education programs into a program that was specifically focused on meeting the information needs of minority women and addressing the barriers to study participation that they perceived. A “sisterhood” theme was adopted and woven throughout the presentation

JWST/NIRCam Transmission Spectroscopy of the Nearby Sub-Earth GJ 341b

We present a JWST/NIRCam transmission spectrum from $3.9-5.0$ $\mu$m of the recently-validated sub-Earth GJ 341b ($\mathrm{R_P} = 0.92$ $\mathrm{R_{\oplus}}$, $\mathrm{T_{eq}} = 540$ K) orbiting a nearby bright M1 star ($\mathrm{d} = 10.4$ pc, $\mathrm{K_{mag}}=5.6$). We use three independent pipelines to reduce the data from the three JWST visits and perform several tests to check for the significance of an atmosphere. Overall, our analysis does not uncover evidence of an atmosphere. Our null hypothesis tests find that none of our pipelines' transmission spectra can rule out a flat line, although there is weak evidence for a Gaussian feature in two spectra from different pipelines (at 2.3 and $2.9\sigma$). However, the candidate features are seen at different wavelengths (4.3 $\mu$m vs 4.7 $\mu$m), and our retrieval analysis finds that different gas species can explain these features in the two reductions (CO$_2$ at $3.1\sigma$ compared to O$_3$ at $2.9\sigma$), suggesting that they are not real astrophysical signals. Our forward model analysis rules out a low mean molecular weight atmosphere ($< 350\times$ solar metallicity) to at least $3\sigma$, and disfavors CH$_4$-dominated atmospheres at $1-3\sigma$, depending on the reduction. Instead, the forward models find our transmission spectra are consistent with no atmosphere, a hazy atmosphere, or an atmosphere containing a species that does not have prominent molecular bands across the NIRCam/F444W bandpass, such as a water-dominated atmosphere. Our results demonstrate the unequivocal need for two or more transit observations analyzed with multiple reduction pipelines, alongside rigorous statistical tests, to determine the robustness of molecular detections for small exoplanet atmospheres.Comment: 25 pages, 18 figures, 6 tables. Accepted for publication in A