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The gut microbiome is impacted by certain types of dietary fibre. However, the type, duration and dose needed to elicit gut microbial changes and whether these changes also influence microbial metabolites remain unclear. This study investigated the effects of supplementing healthy participants with two types of non-digestible carbohydrates (resistant starch (RS) and polydextrose (PD)) on the stool microbiota and microbial metabolite concentrations in plasma, stool and urine, as secondary outcomes in the Dietary Intervention Stem Cells and Colorectal Cancer (DISC) Study. The DISC study was a double-blind, randomised controlled trial that supplemented healthy participants with RS and/or PD or placebo for 50 d in a 2 × 2 factorial design. DNA was extracted from stool samples collected pre- and post-intervention, and V4 16S rRNA gene sequencing was used to profile the gut microbiota. Metabolite concentrations were measured in stool, plasma and urine by high-performance liquid chromatography. A total of fifty-eight participants with paired samples available were included. After 50 d, no effects of RS or PD were detected on composition of the gut microbiota diversity (alpha- and beta-diversity), on genus relative abundance or on metabolite concentrations. However, Drichlet’s multinomial mixture clustering-based approach suggests that some participants changed microbial enterotype post-intervention. The gut microbiota and fecal, plasma and urinary microbial metabolites were stable in response to a 50-d fibre intervention in middle-aged adults. Larger and longer studies, including those which explore the effects of specific fibre sub-types, may be required to determine the relationships between fibre intake, the gut microbiome and host health.
To measure SARS-CoV-2 anti-nucleocapsid (anti-N) antibody seropositivity among healthcare personnel (HCP) without a history of COVID-19 and to identify HCP characteristics associated with seropositivity.
Design:
Prospective cohort study from September 22, 2020, to March 3, 2022.
Setting:
A tertiary care academic medical center.
Participants:
727 HCP without prior positive SARS-CoV-2 PCR testing were enrolled; 559 HCP successfully completed follow-up.
Methods:
At enrollment and follow-up 1–6 months later, HCP underwent SARS-CoV-2 anti-N testing and were surveyed on demographics, employment information, vaccination status, and COVID-19 symptoms and exposures.
Results:
Of 727 HCP enrolled, 27 (3.7%) had a positive SARS-CoV-2 anti-N test at enrollment. Seropositive HCPs were more likely to have a household exposure to COVID-19 in the past 30 days (OR 7.92, 95% CI 2.44–25.73), to have had an illness thought to be COVID-19 (4.31, 1.94–9.57), or to work with COVID-19 patients more than half the time (2.09, 0.94–4.77). Among 559 HCP who followed-up, 52 (9.3%) had a positive SARS-CoV-2 anti-N antibody test result. Seropositivity at follow-up was associated with community/household exposures to COVID-19 within the past 30 days (9.50, 5.02–17.96; 2.90, 1.31–6.44), having an illness thought to be COVID-19 (8.24, 4.44–15.29), and working with COVID-19 patients more than half the time (1.50, 0.80–2.78).
Conclusions:
Among HCP without prior positive SARS-CoV-2 testing, SARS-CoV-2 anti-N seropositivity was comparable to that of the general population and was associated with COVID-19 symptomatology and both occupational and non-occupational exposures to COVID-19.
The Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Cross-Trial Statistics Group gathered lessons learned from statisticians responsible for the design and analysis of the 11 ACTIV therapeutic master protocols to inform contemporary trial design as well as preparation for a future pandemic. The ACTIV master protocols were designed to rapidly assess what treatments might save lives, keep people out of the hospital, and help them feel better faster. Study teams initially worked without knowledge of the natural history of disease and thus without key information for design decisions. Moreover, the science of platform trial design was in its infancy. Here, we discuss the statistical design choices made and the adaptations forced by the changing pandemic context. Lessons around critical aspects of trial design are summarized, and recommendations are made for the organization of master protocols in the future.
Depression is an independent risk factor for cardiovascular disease (CVD), but it is unknown if successful depression treatment reduces CVD risk.
Methods
Using eIMPACT trial data, we examined the effect of modernized collaborative care for depression on indicators of CVD risk. A total of 216 primary care patients with depression and elevated CVD risk were randomized to 12 months of the eIMPACT intervention (internet cognitive-behavioral therapy [CBT], telephonic CBT, and select antidepressant medications) or usual primary care. CVD-relevant health behaviors (self-reported CVD prevention medication adherence, sedentary behavior, and sleep quality) and traditional CVD risk factors (blood pressure and lipid fractions) were assessed over 12 months. Incident CVD events were tracked over four years using a statewide health information exchange.
Results
The intervention group exhibited greater improvement in depressive symptoms (p < 0.01) and sleep quality (p < 0.01) than the usual care group, but there was no intervention effect on systolic blood pressure (p = 0.36), low-density lipoprotein cholesterol (p = 0.38), high-density lipoprotein cholesterol (p = 0.79), triglycerides (p = 0.76), CVD prevention medication adherence (p = 0.64), or sedentary behavior (p = 0.57). There was an intervention effect on diastolic blood pressure that favored the usual care group (p = 0.02). The likelihood of an incident CVD event did not differ between the intervention (13/107, 12.1%) and usual care (9/109, 8.3%) groups (p = 0.39).
Conclusions
Successful depression treatment alone is not sufficient to lower the heightened CVD risk of people with depression. Alternative approaches are needed.
To determine the prevalence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) IgG nucleocapsid (N) antibodies among healthcare personnel (HCP) with no prior history of COVID-19 and to identify factors associated with seropositivity.
Design:
Prospective cohort study.
Setting:
An academic, tertiary-care hospital in St. Louis, Missouri.
Participants:
The study included 400 HCP aged ≥18 years who potentially worked with coronavirus disease 2019 (COVID-19) patients and had no known history of COVID-19; 309 of these HCP also completed a follow-up visit 70–160 days after enrollment. Enrollment visits took place between September and December 2020. Follow-up visits took place between December 2020 and April 2021.
Methods:
At each study visit, participants underwent SARS-CoV-2 IgG N-antibody testing using the Abbott SARS-CoV-2 IgG assay and completed a survey providing information about demographics, job characteristics, comorbidities, symptoms, and potential SARS-CoV-2 exposures.
Results:
Participants were predominately women (64%) and white (79%), with median age of 34.5 years (interquartile range [IQR], 30–45). Among the 400 HCP, 18 (4.5%) were seropositive for IgG N-antibodies at enrollment. Also, 34 (11.0%) of 309 were seropositive at follow-up. HCP who reported having a household contact with COVID-19 had greater likelihood of seropositivity at both enrollment and at follow-up.
Conclusions:
In this cohort of HCP during the first wave of the COVID-19 pandemic, ∼1 in 20 had serological evidence of prior, undocumented SARS-CoV-2 infection at enrollment. Having a household contact with COVID-19 was associated with seropositivity.
White kidney bean extract (WKBE) is a nutraceutical often advocated as an anti-obesity agent. The main proposed mechanism for these effects is alpha-amylase inhibition, thereby slowing carbohydrate digestion and absorption. Thus, it is possible that WKBE could impact the gut microbiota and modulate gut health. We investigated the effects of supplementing 20 healthy adults with WKBE for 1 week in a randomised, placebo-controlled crossover trial on the composition of the gut microbiota, gastrointestinal (GI) inflammation (faecal calprotectin), GI symptoms, and stool habits. We conducted in vitro experiments and used a gut model system to explore potential inhibition of alpha-amylase. We gained qualitative insight into participant experiences of using WKBE via focus groups. WKBE supplementation decreased the relative abundance of Bacteroidetes and increased that of Firmicutes, however, there were no significant differences in post-intervention gut microbiota measurements between the WKBE and control. There were no significant effects on GI inflammation or symptoms related to constipation, or stool consistency or frequency. Our in vitro and gut model system analyses showed no effects of WKBE on alpha-amylase activity. Our findings suggest that WKBE may modulate the gut microbiota in healthy adults, however, the underlying mechanism is unlikely due to active site inhibition of alpha-amylase.
Using capture-recapture analysis we estimate the effective size of the active Amazon Mechanical Turk (MTurk) population that a typical laboratory can access to be about 7,300 workers. We also estimate that the time taken for half of the workers to leave the MTurk pool and be replaced is about 7 months. Each laboratory has its own population pool which overlaps, often extensively, with the hundreds of other laboratories using MTurk. Our estimate is based on a sample of 114,460 completed sessions from 33,408 unique participants and 689 sessions across seven laboratories in the US, Europe, and Australia from January 2012 to March 2015.
In the summer of 1986 a mass grave was discovered along the bank of the river Tryggevælde Å where it empties into Køge Bugt, the bay south of modern Copenhagen, Denmark. The human remains, dating to the late Mesolithic Ertebølle culture, consisted of eight individuals of multiple ages, ranging c. 35–45 years old to newborn children. Four were arranged on one side of the grave, with four on the other, placed head to foot. How they were related and what befell them is a mystery. Herein, we present a bioarchaeological assessment of these individuals for the first time and apply an acid etch-based analysis of dimorphic sex chromosome-linked tooth enamel peptides to confirm their biological sex. Our results allow a direct connection between engendered grave treatment and biological sex in non-adult individuals as young as c. 4 years of age. We conclude with a discussion of the possible circumstances of their deaths and their possible relationships to one another.
In this prospective, longitudinal study, we examined the risk factors for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among a cohort of chronic hemodialysis (HD) patients and healthcare personnel (HCPs) over a 6-month period. The risk of SARS-CoV-2 infection among HD patients and HCPs was consistently associated with a household member having SARS-CoV-2 infection.
In a prospective cohort of healthcare personnel (HCP), we measured severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) nucleocapsid IgG antibodies after SARS-CoV-2 infection. Among 79 HCP, 68 (86%) were seropositive 14–28 days after their positive PCR test, and 54 (77%) of 70 were seropositive at the 70–180-day follow-up. Many seropositive HCP (95%) experienced an antibody decline by the second visit.
As clinical trials were rapidly initiated in response to the COVID-19 pandemic, Data and Safety Monitoring Boards (DSMBs) faced unique challenges overseeing trials of therapies never tested in a disease not yet characterized. Traditionally, individual DSMBs do not interact or have the benefit of seeing data from other accruing trials for an aggregated analysis to meaningfully interpret safety signals of similar therapeutics. In response, we developed a compliant DSMB Coordination (DSMBc) framework to allow the DSMB from one study investigating the use of SARS-CoV-2 convalescent plasma to treat COVID-19 to review data from similar ongoing studies for the purpose of safety monitoring.
Methods:
The DSMBc process included engagement of DSMB chairs and board members, execution of contractual agreements, secure data acquisition, generation of harmonized reports utilizing statistical graphics, and secure report sharing with DSMB members. Detailed process maps, a secure portal for managing DSMB reports, and templates for data sharing and confidentiality agreements were developed.
Results:
Four trials participated. Data from one trial were successfully harmonized with that of an ongoing trial. Harmonized reports allowing for visualization and drill down into the data were presented to the ongoing trial’s DSMB. While DSMB deliberations are confidential, the Chair confirmed successful review of the harmonized report.
Conclusion:
It is feasible to coordinate DSMB reviews of multiple independent studies of a similar therapeutic in similar patient cohorts. The materials presented mitigate challenges to DSMBc and will help expand these initiatives so DSMBs may make more informed decisions with all available information.
Dialysis patients may not have access to conventional renal replacement therapy (RRT) following disasters. We hypothesized that improvised renal replacement therapy (ImpRRT) would be comparable to continuous renal replacement therapy (CRRT) in a porcine acute kidney injury model.
Methods:
Following bilateral nephrectomies and 2 hours of caudal aortic occlusion, 12 pigs were randomized to 4 hours of ImpRRT or CRRT. In the ImpRRT group, blood was circulated through a dialysis filter using a rapid infuser to collect the ultrafiltrate. Improvised replacement fluid, made with stock solutions, was infused pre-pump. In the CRRT group, commercial replacement fluid was used. During RRT, animals received isotonic crystalloids and norepinephrine.
Results:
There were no differences in serum creatinine, calcium, magnesium, or phosphorus concentrations. While there was a difference between groups in serum potassium concentration over time (P < 0.001), significance was lost in pairwise comparison at specific time points. Replacement fluids or ultrafiltrate flows did not differ between groups. There were no differences in lactate concentration, isotonic crystalloid requirement, or norepinephrine doses. No difference was found in electrolyte concentrations between the commercial and improvised replacement solutions.
Conclusion:
The ImpRRT system achieved similar performance to CRRT and may represent a potential option for temporary RRT following disasters.
Good education requires student experiences that deliver lessons about practice as well as theory and that encourage students to work for the public good—especially in the operation of democratic institutions (Dewey 1923; Dewy 1938). We report on an evaluation of the pedagogical value of a research project involving 23 colleges and universities across the country. Faculty trained and supervised students who observed polling places in the 2016 General Election. Our findings indicate that this was a valuable learning experience in both the short and long terms. Students found their experiences to be valuable and reported learning generally and specifically related to course material. Postelection, they also felt more knowledgeable about election science topics, voting behavior, and research methods. Students reported interest in participating in similar research in the future, would recommend other students to do so, and expressed interest in more learning and research about the topics central to their experience. Our results suggest that participants appreciated the importance of elections and their study. Collectively, the participating students are engaged and efficacious—essential qualities of citizens in a democracy.
Edited by
Susanna Pietropaolo, Centre National de la Recherche Scientifique (CNRS), Paris,Frans Sluyter, University of Portsmouth,Wim E. Crusio, Centre National de la Recherche Scientifique (CNRS), Paris