In the absence of pharmaceutical interventions, social distancing is being used worldwide to curb the spread of COVID-19. The impact of these measures has been inconsistent, with some regions rapidly ...nearing disease elimination and others seeing delayed peaks or nearly flat epidemic curves. Here we build a stochastic epidemic model to examine the effects of COVID-19 clinical progression and transmission network structure on the outcomes of social distancing interventions. Our simulations show that long delays between the adoption of control measures and observed declines in cases, hospitalizations, and deaths occur in many scenarios. We find that the strength of within-household transmission is a critical determinant of success, governing the timing and size of the epidemic peak, the rate of decline, individual risks of infection, and the success of partial relaxation measures. The structure of residual external connections, driven by workforce participation and essential businesses, interacts to determine outcomes. We suggest limited conditions under which the formation of household "bubbles" can be safe. These findings can improve future predictions of the timescale and efficacy of interventions needed to control second waves of COVID-19 as well as other similar outbreaks, and highlight the need for better quantification and control of household transmission.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Anthocyanins are of interest due to their anti-oxidative and vasodilatory properties. Earlier reviews have shown that berries and other anthocyanin rich foods or extracts can improve vascular health, ...however the effect of anthocyanins on vascular function has not yet been reviewed. To address this gap in the literature, we conducted a systematic review and meta-analysis of randomised-controlled trials examining anthocyanin-rich foods or extracts on measures of vascular reactivity and/or stiffness in adults. Data from 24 studies were pooled as standardized mean difference (SMD) with 95% confidence intervals (CI). Anthocyanin consumption significantly improved flow-mediated dilation (FMD) following acute (SMD: 3.92%, 95% CI: 1.47, 6.38,
= 0.002; I² = 91.8%) and chronic supplementation (SMD: 0.84%, 95% CI: 0.55, 1.12,
= 0.000;
² = 62.5%). Pulse wave velocity was improved following acute supplementation only (SMD: -1.27 m/s, 95% CI: -1.96, -0.58,
= 0.000;
² = 17.8%). These results support the findings of previous reviews that anthocyanin rich foods or extracts may indeed improve vascular health, particularly with respect to vascular reactivity measured by FMD. More research is required to determine the optimal dosage, and the long-term effects of consumption.
The emergence of drug resistance during antimicrobial therapy is a major global health problem, especially for chronic infections like human immunodeficiency virus, hepatitis B and C, and ...tuberculosis. Sub-optimal adherence to long-term treatment is an important contributor to resistance risk. New long-acting drugs are being developed for weekly, monthly or less frequent dosing to improve adherence, but may lead to long-term exposure to intermediate drug levels. In this study, we analyse the effect of dosing frequency on the risk of resistance evolving during time-varying drug levels. We find that long-acting therapies can increase, decrease or have little effect on resistance, depending on the source (pre-existing or de novo) and degree of resistance, and rates of drug absorption and clearance. Long-acting therapies with rapid drug absorption, slow clearance and strong wild-type inhibition tend to reduce resistance caused by partially resistant strains in the early stages of treatment even if they do not improve adherence. However, if subpopulations of microbes persist and can reactivate during sub-optimal treatment, longer-acting therapies may substantially increase the resistance risk. Our results show that drug kinetics affect selection for resistance in a complicated manner, and that pathogen-specific models are needed to evaluate the benefits of new long-acting therapies.
Antibiotic-resistant infections are a growing threat to human health, but basic features of the eco-evolutionary dynamics remain unexplained. Most prominently, there is no clear mechanism for the ...long-term coexistence of both drug-sensitive and resistant strains at intermediate levels, a ubiquitous pattern seen in surveillance data. Here we show that accounting for structured or spatially-heterogeneous host populations and variability in antibiotic consumption can lead to persistent coexistence over a wide range of treatment coverages, drug efficacies, costs of resistance, and mixing patterns. Moreover, this mechanism can explain other puzzling spatiotemporal features of drug-resistance epidemiology that have received less attention, such as large differences in the prevalence of resistance between geographical regions with similar antibiotic consumption or that neighbor one another. We find that the same amount of antibiotic use can lead to very different levels of resistance depending on how treatment is distributed in a transmission network. We also identify parameter regimes in which population structure alone cannot support coexistence, suggesting the need for other mechanisms to explain the epidemiology of antibiotic resistance. Our analysis identifies key features of host population structure that can be used to assess resistance risk and highlights the need to include spatial or demographic heterogeneity in models to guide resistance management.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Massive research efforts are now underway to develop a cure for HIV infection, allowing patients to discontinue lifelong combination antiretroviral therapy (ART). New latency-reversing agents (LRAs) ...may be able to purge the persistent reservoir of latent virus in resting memory CD4⁺ T cells, but the degree of reservoir reduction needed for cure remains unknown. Here we use a stochastic model of infection dynamics to estimate the efficacy of LRA needed to prevent viral rebound after ART interruption. We incorporate clinical data to estimate population-level parameter distributions and outcomes. Our findings suggest that ~2,000-fold reductions are required to permit a majority of patients to interrupt ART for 1 y without rebound and that rebound may occur suddenly after multiple years. Greater than 10,000-fold reductions may be required to prevent rebound altogether. Our results predict large variation in rebound times following LRA therapy, which will complicate clinical management. This model provides benchmarks for moving LRAs from the laboratory to the clinic and can aid in the design and interpretation of clinical trials. These results also apply to other interventions to reduce the latent reservoir and can explain the observed return of viremia after months of apparent cure in recent bone marrow transplant recipients and an immediately-treated neonate.
Full text
Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
This paper presents a case study of long-term post-retraction citation to falsified clinical trial data (Matsuyama et al. in Chest 128(6):3817–3827, 2005.
https://doi.org/10.1378/chest.128.6.3817
), ...demonstrating problems with how the current digital library environment communicates retraction status. Eleven years after its retraction, the paper continues to be cited positively and uncritically to support a medical nutrition intervention, without mention of its 2008 retraction for falsifying data. To date no high quality clinical trials reporting on the efficacy of omega-3 fatty acids on reducing inflammatory markers have been published. Our paper uses network analysis, citation context analysis, and retraction status visibility analysis to illustrate the potential for extended propagation of misinformation over a citation network, updating and extending a case study of the first 6 years of post-retraction citation (Fulton et al. in Publications 3(1):7–26, 2015.
https://doi.org/10.3390/publications3010017
). The current study covers 148 direct citations from 2006 through 2019 and their 2542 second-generation citations and assesses retraction status visibility of the case study paper and its retraction notice on 12 digital platforms as of 2020. The retraction is not mentioned in 96% (107/112) of direct post-retraction citations for which we were able to conduct citation context analysis. Over 41% (44/107) of direct post-retraction citations that do not mention the retraction describe the case study paper in detail, giving a risk of diffusing misinformation from the case paper. We analyze 152 second-generation citations to the most recent 35 direct citations (2010–2019) that do not mention the retraction but do mention methods or results of the case paper, finding 23 possible diffusions of misinformation from these non-direct citations to the case paper. Link resolving errors from databases show a significant challenge in a reader reaching the retraction notice via a database search. Only 1/8 databases (and 1/9 database records) consistently resolved the retraction notice to its full-text correctly in our tests. Although limited to evaluation of a single case (
N
= 1), this work demonstrates how retracted research can continue to spread and how the current information environment contributes to this problem.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Inconsistent findings regarding sex differences in cognition have been found in people with autism spectrum disorder (ASD). This study evaluated sex differences in cognitive-developmental functioning ...in a large clinical sample of young children diagnosed with ASD. The sample included children 18–68 months of age who received the Mullen Scales of Early Learning (MSEL) through Autism Treatment Network (ATN) sites from 2007 to 2013 (N = 1587, 16.7% female). In this large clinically referred sample of young children with ASD in the United States, no significant differences were found between the sexes for the MSEL Early Learning Composite (ELC) standard score, domain T Scores or age equivalents. These findings persisted when examining different age ranges, cognitive levels and domain profiles.
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, ODKLJ, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
The efficacy of antiretroviral therapy is significantly compromised by medication non-adherence. Long-acting enteral systems that can ease the burden of daily adherence have not yet been developed. ...Here we describe an oral dosage form composed of distinct drug-polymer matrices which achieved week-long systemic drug levels of the antiretrovirals dolutegravir, rilpivirine and cabotegravir in a pig. Simulations of viral dynamics and patient adherence patterns indicate that such systems would significantly reduce therapeutic failures and epidemiological modelling suggests that using such an intervention prophylactically could avert hundreds of thousands of new HIV cases. In sum, weekly administration of long-acting antiretrovirals via a novel oral dosage form is a promising intervention to help control the HIV epidemic worldwide.
Bed bug outbreaks pose a major challenge in urban environments and cause significant strain on public resources. Few studies have systematically analyzed this insect epidemic or the potential effects ...of policies to combat bed bugs. Here we use three sources of administrative data to characterize the spatial-temporal trends of bed bug inquiries, complaints, and reports in New York City. Bed bug complaints have significantly decreased (p < 0.01) from 2014-2020, the absolute number of complaints per month dropping by half (875 average complaints per month to 440 average complaints per month); conversely, complaints for other insects including cockroaches and flies did not decrease over the same period. Despite the decrease of bed bug complaints, areas with reported high bed bug infestation tend to remain infested, highlighting the persistence of these pests. There are limitations to the datasets; still the evidence available suggests that interventions employed by New York City residents and lawmakers are stemming the bed bug epidemic and may serve as a model for other large cities.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
