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Sleep and circadian timing shifts later during adolescence, conflicting with early school start times, and resulting in circadian misalignment. Although circadian misalignment has been linked to depression, substance use, and altered reward function, a paucity of experimental studies precludes the determination of causality. Here we tested, for the first time, whether experimentally-imposed circadian misalignment alters the neural response to monetary reward and/or response inhibition.
Healthy adolescents (n = 25, ages 13–17) completed two in-lab sleep schedules in counterbalanced order: An ‘aligned’ condition based on typical summer sleep-wake times (0000–0930) and a ‘misaligned’ condition mimicking earlier school year sleep-wake times (2000–0530). Participants completed morning and afternoon functional magnetic resonance imaging scans during each condition, including monetary reward (morning only) and response inhibition (morning and afternoon) tasks. Total sleep time and circadian phase were assessed via actigraphy and salivary melatonin, respectively.
Bilateral ventral striatal (VS) activation during reward outcome was lower during the Misaligned condition after accounting for the prior night's total sleep time. Bilateral VS activation during reward anticipation was lower during the Misaligned condition, including after accounting for covariates, but did not survive correction for multiple comparisons. Right inferior frontal gyrus activation during response inhibition was lower during the Misaligned condition, before and after accounting for total sleep time and vigilant attention, but only during the morning scan.
Our findings provide novel experimental evidence that circadian misalignment analogous to that resulting from school schedules may have measurable impacts on healthy adolescents' reward processing and inhibition of prepotent responses.
Evidence is limited on how to synthesize and incorporate the views of stakeholders into a multisite pragmatic trial and how much academic teams change study design and protocol in response to stakeholder input. This qualitative study describes how stakeholders contributed to the design, conduct, and dissemination of findings of a multisite pragmatic clinical trial, the COMprehensive Post-Acute Stroke Services (COMPASS) Study. We engaged stakeholders as integral research partners by embedding them in study committees and community resource networks that supported local sites. Data stemmed from formal focus groups and continuous participation in working groups. Guided by Grounded Theory, we extracted themes from focus group and meeting notes. These were discussed as a team and with other stakeholder groups for feasibility. A consensus approach was used. Stakeholder input changed many aspects of the study including: the care model that treated stroke as a chronic condition after hospital discharge, training for hospital-based providers who often lacked awareness of the barriers to recovery that patients face, support for caregivers who were essential for stroke patients’ recovery, and for community-based health and social service providers whose services can support recovery yet often go underutilized. Stakeholders brought value to both pragmatic research and health service delivery. Future studies should test the impact of elements of study implementation informed by stakeholders vs those that are not.
We examined the item properties of the Two Peas Questionnaire (TPQ) among a sample of same-sex twin pairs from the Washington State Twin Registry. With the exception of the ‘two peas’ item, three of the mistakenness items showed differential item functioning. Results showed that the monozygotic (MZ) and dizygotic (DZ) pairs may differ in their responses on these items, even among those with similar latent traits of similarity and confusability. Upon comparing three classification methods to determine the zygosity of same-sex twins, the overall classification accuracy rate was over 90% using the unit-weighted pair zygosity sum score, providing an efficient and sufficiently accurate zygosity classification. Given the inherent nature of twin-pair similarity, the TPQ is more accurate in the identification of MZ than DZ pairs. We conclude that the TPQ is a generally accurate, but by no means infallible, method of determining zygosity in twins who have not been genotyped.
Older adults often have atypical presentation of illness and are particularly vulnerable to influenza and its sequelae, making the validity of influenza case definitions particularly relevant. We sought to assess the performance of influenza-like illness (ILI) and severe acute respiratory illness (SARI) criteria in hospitalized older adults.
Prospective cohort study.
The Serious Outcomes Surveillance Network of the Canadian Immunization Research Network undertakes active surveillance for influenza among hospitalized adults.
Data were pooled from 3 influenza seasons: 2011/12, 2012/13, and 2013/14. The ILI and SARI criteria were defined clinically, and influenza was laboratory confirmed. Frailty was measured using a validated frailty index.
Of 11,379 adult inpatients (7,254 aged ≥65 years), 4,942 (2,948 aged ≥65 years) had laboratory-confirmed influenza. Their median age was 72 years (interquartile range [IQR], 58–82) and 52.6% were women. The sensitivity of ILI criteria was 51.1% (95% confidence interval [CI], 49.6–52.6) for younger adults versus 44.6% (95% CI, 43.6–45.8) for older adults. SARI criteria were met by 64.1% (95% CI, 62.7–65.6) of younger adults versus 57.1% (95% CI, 55.9–58.2) of older adults with laboratory-confirmed influenza. Patients with influenza who were prefrail or frail were less likely to meet ILI and SARI case definitions.
A substantial proportion of older adults, particularly those who are frail, are missed by standard ILI and SARI case definitions. Surveillance using these case definitions is biased toward identifying younger cases, and does not capture the true burden of influenza. Because of the substantial fraction of cases missed, surveillance definitions should not be used to guide diagnosis and clinical management of influenza.
Research Electronic Data Capture (REDCap) is a secure, web-based electronic data capture application for building and managing surveys and databases. It can also be used for study management, data transfer, and data export into a variety of statistical programs. REDcap was developed and supported by the National Center for Advancing Translational Sciences Program and is used in over 3700 institutions worldwide. It can also be used to track and measure stakeholder engagement, an integral element of research funded by the Patient-Centered Outcomes Research Institute (PCORI). Continuously and accurately tracking and reporting on stakeholder engagement activities throughout the life of a PCORI-funded trial can be challenging, particularly in complex trials with multiple types of engagement.
In this paper, we show our approach for collecting and capturing stakeholder engagement activities using a shareable REDCap tool in one of the PCORI’s first large pragmatic clinical trials (the Comprehensive Post-Acute Stroke Services) to inform other investigators planning cluster-randomized pragmatic trials. Benefits and challenges are highlighted for researchers seeking to consistently monitor and measure stakeholder engagement.
We describe how REDCap can provide a time-saving approach to capturing how stakeholders engage in a PCORI-funded study and reporting how stakeholders influenced the study in progress reports back to PCORI.
When open-cut mines are eventually abandoned, they leave a large hole with sloping sides. The hole fills with rain water, and there is also contaminated run-off from surrounding land, that moves through the rock and eventually through the sloping sides of the abandoned mine. This paper considers a two-dimensional unsteady model motivated by this leaching flow through the rock and into the rain-water reservoir. The stability of the interface between the two fluids is analysed in the inviscid limit. A viscous Boussinesq model is also presented, and a closed-form solution is presented to this problem, after it has been linearized in a manner consistent with Boussinesq theory. That solution suggests that the interfacial zone is effectively neutrally stable as it evolves in time. However, an asymptotic theory in the interfacial region shows the interface to be unstable. In addition, the nonlinear Boussinesq model is solved using a spectral method. Interfacial travelling waves and roll-up are observed and discussed, and compared against the predictions of asymptotic Boussinesq theory.
Cognitive behavioural therapy (CBT) for problematic hoarding is an effective treatment, but further research in diverse, naturalistic settings is needed to see whether this treatment is effective across settings and in smaller doses. The current study investigated the outcome of a 12-session group CBT for hoarding offered in an outpatient hospital setting. Sixty-four participants completed therapy, and 38 participants completed posttreatment assessments. Results demonstrated statistically significant improvements in hoarding symptom severity, saving cognitions, and self-reported distress tolerance. Effect sizes for changes in saving cognitions were generally large. However, effect sizes were modest for most other outcome variables, and only 4 of 38 participants achieved clinically significant change in hoarding symptom severity. These results suggest that 12 sessions of group CBT for hoarding is associated with significant change in saving cognitions, but less meaningful change in other indicators of symptom severity.
While hot-water drilling is a well-established technique used to access the subsurface of ice masses, drilling into high-elevation (≳ 4000 m a.s.l.) debris-covered glaciers faces specific challenges. First, restricted transport capacity limits individual equipment items to a volume and mass that can be slung by small helicopters. Second, low atmospheric oxygen and pressure reduces the effectiveness of combustion, limiting a system's ability to pump and heat water. Third, thick supraglacial debris, which is both highly uneven and unstable, inhibits direct access to the ice surface, hinders the manoeuvring of equipment and limits secure sites for equipment placement. Fourth, englacial debris can slow the drilling rate such that continued drilling becomes impracticable and/or boreholes deviate substantially from vertical. Because of these challenges, field-based englacial and subglacial data required to calibrate numerical models of high-elevation debris-covered glaciers are scarce or absent. Here, we summarise our experiences of hot-water drilling over two field seasons (2017–2018) at the debris-covered Khumbu Glacier, Nepal, where we melted 27 boreholes up to 192 m length, at elevations between 4900 and 5200 m a.s.l. We describe the drilling equipment and operation, evaluate the effectiveness of our approach and suggest equipment and methodological adaptations for future use.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
It has been over 5 years since the last special issue of Twin Research and Human Genetics on ‘Twin Registries Worldwide: An Important Resource for Scientific Research’ was published. Much progress has been made in the broad field of twin research since that time, and the current special issue is a follow-up to update the scientific community about twin registries around the globe. The present article builds upon our 2013 Registry description by summarizing current information on the Washington State Twin Registry (WSTR), including history and construction methods, member characteristics, available data, and major research goals. We also provide a section with brief summaries of recently completed studies and discuss the future research directions of the WSTR. The Registry has grown in terms of size and scope since 2013; highlights include recruitment of youth pairs under 18 years of age, extensive geocoding work to develop environmental exposures that can be linked to survey and administrative health data such as death records, and expansion of a biobank with specimens collected for genotyping, DNA methylation, and microbiome based-studies.
Introduction: Cardioactive steroid poisoning occurs worldwide with the use of pharmaceutical digoxin and botanical cardiac glycosides. The wholesale price of the antidote, digoxin immune fab, has increased over 300% from 2010 to 2015. Our objective was to identify gaps in the existing literature with respect to the use of digoxin immune fab in cardioactive steroid toxicity in acute care settings. Methods: We used scoping study methodology, as described by Arksey and O'Malley, to assess the range and scope of empiric research and will report: 1) sources of cardioactive steroid toxicity in acute settings; 2) doses of digoxin immune fab used in treatment; and, 3) intervention outcomes of acute cardioactive steroid toxicity following the administration of digoxin immune fab as first or second-line therapy. We collaborated with a library scientist to devise search strategies for PubMed, CINAHL, EMBASE, CENTRAL and Toxnet. We sought unpublished literature through the Canadian Electronic Library, Proquest, and Scopus and searched reference lists of included studies. We hand searched relevant conference proceedings and applicable guidelines. Two reviewers independently reviewed titles and abstracts using predetermined criteria. Using a structured data abstraction form, two reviewers independently extracted data. All discrepancies were resolved through consensus. Results: Our search strategy yielded 3458 results. After screening titles and abstracts 384 underwent full text screening. We included 147 studies and are currently extracting data from 12 French studies and 135 English studies. To date we have extracted data from 90 case reports and case series. Conclusion: Given concerns over rising costs, our findings will shed light on the extent of the evidence for use of digoxin immune fab in acute care settings.
Malthus was severely critical of the old poor law, especially when the payments paid to recipients were made in conformity to the principles adopted by the local magistrates in Speenhamland in 1795. He considered that it encouraged early and improvident marriage with unfortunate consequences. There have been a number of attempts to determine whether Malthus was justified in supposing that the old poor law had this effect, some concluding that he was correct in his assumption, others that he was mistaken. The information contained in the first four English censuses did not include a breakdown of the population by age, sex, and marital status, and therefore did not provide a basis for a definitive test of Malthus's assertion before the repeal of the old poor law in 1834. The 1851 census, however, did provide this breakdown for five-year age groups which makes it possible to compare marriage patterns in counties in which a large proportion of the male workforce were ‘peasants’ (Malthus's term for agricultural labourers), and the Speenhamland provisions were widely adopted, with other counties. The results show that Malthus was mistaken.
Approximately 12% of U.S. adults have type 2 diabetes (T2D). Diagnosed T2D is caused by a combination of genetic and environmental factors including age and lifestyle. In adults 45 years and older, the Discordant Twin (DISCOTWIN) consortium of twin registries from Europe and Australia showed a moderate-to-high contribution of genetic factors of T2D with a pooled heritability of 72%. The purpose of this study was to investigate the contributions of genetic and environmental factors of T2D in twins 45 years and older in a U.S. twin cohort (Washington State Twin Registry, WSTR) and compare the estimates to the DISCOTWIN consortium. We also compared these estimates with twins under the age of 45. Data were obtained from 2692 monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs over 45 and 4217 twin pairs under 45 who responded to the question ‘Has a doctor ever diagnosed you with (type 2) diabetes?’ Twin similarity was analyzed using both tetrachoric correlations and structural equation modeling. Overall, 9.4% of MZ and 14.7% of DZ twins over the age of 45 were discordant for T2D in the WSTR, compared to 5.1% of MZ and 8% of DZ twins in the DISCOTWIN consortium. Unlike the DISCOTWIN consortium in which heritability was 72%, heritability was only 52% in the WSTR. In twins under the age of 45, heritability did not contribute to the variance in T2D. In a U.S. sample of adult twins, environmental factors appear to be increasingly important in the development of T2D.
We consider the linearized form of the regularized 13-moment equations (R13) to model the slow, steady gas dynamics surrounding a rigid, heat-conducting sphere when a uniform temperature gradient is imposed far from the sphere and the gas is in a state of rarefaction. Under these conditions, the phenomenon of thermophoresis, characterized by forces on the solid surfaces, occurs. The R13 equations, derived from the Boltzmann equation using the moment method, provide closure to the mass, momentum and energy conservation laws in the form of constitutive, transport equations for the stress and heat flux that extend the Navier–Stokes–Fourier model to include non-equilibrium effects. We obtain analytical solutions for the field variables that characterize the gas dynamics and a closed-form expression for the thermophoretic force on the sphere. We also consider the slow, streaming flow of gas past a sphere using the same model resulting in a drag force on the body. The thermophoretic velocity of the sphere is then determined from the balance between thermophoretic force and drag. The thermophoretic force is compared with predictions from other theories, including Grad’s 13-moment equations (G13), variants of the Boltzmann equation commonly used in kinetic theory, and with recently published experimental data. The new results from R13 agree well with results from kinetic theory up to a Knudsen number (based on the sphere’s radius) of approximately 0.1 for the values of solid-to-gas heat conductivity ratios considered. However, in this range of Knudsen numbers, where for a very high thermal conductivity of the solid the experiments show reversed thermophoretic forces, the R13 solution, which does result in a reversal of the force, as well as the other theories predict significantly smaller forces than the experimental values. For Knudsen numbers between 0.1 and 1 approximately, the R13 model of thermophoretic force qualitatively shows the trend exhibited by the measurements and, among the various models considered, results in the least discrepancy.
The theoretical framework developed by Rayleigh and Plateau in the 19th century has been remarkably accurate in describing macroscale experiments of liquid cylinder instability. Here we re-evaluate and revise the Rayleigh–Plateau instability for the nanoscale, where molecular dynamics experiments demonstrate its inadequacy. A new framework based on the stochastic lubrication equation is developed that captures nanoscale flow features and highlights the critical role of thermal fluctuations at small scales. Remarkably, the model indicates that classically stable (i.e. ‘fat’) liquid cylinders can be broken at the nanoscale, and this is confirmed by molecular dynamics.
Soldier operational performance is determined by their fitness, nutritional status, quality of rest/recovery, and remaining injury/illness free. Understanding large fluctuations in nutritional status during operations is critical to safeguarding health and well-being. There are limited data world-wide describing the effect of extreme climate change on nutrient profiles. This study investigated the effect of hot-dry deployments on vitamin D status (assessed from 25-hydroxyvitamin D (25(OH)D) concentration) of young, male, military volunteers. Two data sets are presented (pilot study, n 37; main study, n 98), examining serum 25(OH)D concentrations before and during 6-month summer operational deployments to Afghanistan (March to October/November). Body mass, percentage of body fat, dietary intake and serum 25(OH)D concentrations were measured. In addition, parathyroid hormone (PTH), adjusted Ca and albumin concentrations were measured in the main study to better understand 25(OH)D fluctuations. Body mass and fat mass (FM) losses were greater for early (pre- to mid-) deployment compared with late (mid- to post-) deployment (P<0·05). Dietary intake was well-maintained despite high rates of energy expenditure. A pronounced increase in 25(OH)D was observed between pre- (March) and mid-deployment (June) (pilot study: 51 (sd 20) v. 212 (sd 85) nmol/l, P<0·05; main study: 55 (sd 22) v. 167 (sd 71) nmol/l, P<0·05) and remained elevated post-deployment (October/November). In contrast, PTH was highest pre-deployment, decreasing thereafter (main study: 4·45 (sd 2·20) v. 3·79 (sd 1·50) pmol/l, P<0·05). The typical seasonal cycling of vitamin D appeared exaggerated in this active male population undertaking an arduous summer deployment. Further research is warranted, where such large seasonal vitamin D fluctuations may be detrimental to bone health in the longer-term.
This article proposes a new reading of a late first-century c.e. inscribed dedication from Todi (Umbria) as an accusation of witchcraft, a rhetorical text aimed at propagating a particular story among the local community. Historical and anthropological studies of witchcraft accusations in other societies have emphasised how they can reveal tensions and anxieties that are normally not visible to the observer. By drawing on these studies and close examination of the language and content of the inscription, this article analyses an historical agent's experience of the social structure of early imperial Italy. The accusation is read as a freedman's response to his ambiguous position in a slave society, the ambivalent power of writing in Roman culture and the religious claims of Flavian imperial discourse.
Background: Patients suffering from traumatic brain injury (TBI) are at increased risk of venous thromboembolism (VTE). However, initiation of pharmacological venous thromboprophylaxis (VTEp) may cause further intracranial hemorrhage. We reviewed the literature to determine the postinjury time interval at which VTEp can be administered without risk of TBI evolution and hematoma expansion. Methods: MEDLINE and EMBASE databases were searched. Inclusion criteria were studies investigating timing and safety of VTEp in TBI patients not previously on oral anticoagulation. Two investigators extracted data and graded the papers’ levels of evidence. Randomized controlled trials were assessed for bias according to the Cochrane Collaboration Tool and Cohort studies were evaluated for bias using the Newcastle-Ottawa Scale. We performed univariate meta-regression analysis in an attempt to identify a relationship between VTEp timing and hemorrhagic progression and assess study heterogeneity using an I2 statistic. Results: Twenty-one studies were included in the systematic review. Eighteen total studies demonstrated that VTEp postinjury in patients with stable head computed tomography scan does not lead to TBI progression. Fourteen studies demonstrated that VTEp administration 24 to 72 hours postinjury is safe in patients with stable injury. Four studies suggested that administering VTEp within 24 hours of injury in patients with stable TBI does not lead to progressive intracranial hemorrhage. Overall, meta-regression analysis demonstrated that there was no relationship between rate of hemorrhagic progression and VTEp timing. Conclusions: Literature suggests that administering VTEp 24 to 48 hours postinjury may be safe for patients with low-hemorrhagic-risk TBIs and stable injury on repeat imaging.