To develop an archive of self-report questions assessing sleep disturbance and sleep-related impairments (SRI), to develop item banks from this archive, and to validate and calibrate the item banks ...using classic validation techniques and item response theory analyses in a sample of clinical and community participants.
Cross-sectional self-report study.
Academic medical center and participant homes.
One thousand nine hundred ninety-three adults recruited from an Internet polling sample and 259 adults recruited from medical, psychiatric, and sleep clinics.
None.
This study was part of PROMIS (Patient-Reported Outcomes Information System), a National Institutes of Health Roadmap initiative. Self-report item banks were developed through an iterative process of literature searches, collecting and sorting items, expert content review, qualitative patient research, and pilot testing. Internal consistency, convergent validity, and exploratory and confirmatory factor analysis were examined in the resulting item banks. Factor analyses identified 2 preliminary item banks, sleep disturbance and SRI. Item response theory analyses and expert content review narrowed the item banks to 27 and 16 items, respectively. Validity of the item banks was supported by moderate to high correlations with existing scales and by significant differences in sleep disturbance and SRI scores between participants with and without sleep disorders.
The PROMIS sleep disturbance and SRI item banks have excellent measurement properties and may prove to be useful for assessing general aspects of sleep and SRI with various groups of patients and interventions.
Latent class analysis (LCA) identifies distinct groups within a heterogeneous population, but its application to accelerometry-assessed physical activity and sedentary behavior has not been ...systematically explored. We conducted a systematic scoping review to describe the application of LCA to accelerometry.
Comprehensive searches in PubMed, Web of Science, CINHAL, SPORTDiscus, and Embase identified studies published through December 31, 2021. Using Covidence, two researchers independently evaluated inclusion criteria and discrepancies were resolved by consensus. Studies with LCA applied to accelerometry or combined accelerometry/self-reported measures were selected. Data extracted included study characteristics and both accelerometry and LCA methods.
Of 2555 papers found, 66 full-text papers were screened, and 12 papers (11 cross-sectional, 1 cohort) from 8 unique studies were included. Study sample sizes ranged from 217-7931 (mean 2249, standard deviation 2780). Across 8 unique studies, latent class variables included measures of physical activity (100%) and sedentary behavior (75%). About two-thirds (63%) of the studies used accelerometry only and 38% combined accelerometry and self-report to derive latent classes. The accelerometer-based variables in the LCA model included measures by day of the week (38%), weekday vs. weekend (13%), weekly average (13%), dichotomized minutes/day (13%), sex specific z-scores (13%), and hour-by-hour (13%). The criteria to guide the selection of the final number of classes and model fit varied across studies, including Bayesian Information Criterion (63%), substantive knowledge (63%), entropy (50%), Akaike information criterion (50%), sample size (50%), Bootstrap likelihood ratio test (38%), and visual inspection (38%). The studies explored up to 5 (25%), 6 (38%), or 7+ (38%) classes, ending with 3 (50%), 4 (13%), or 5 (38%) final classes.
This review explored the application of LCA to physical activity and sedentary behavior and identified areas of improvement for future studies leveraging LCA. LCA was used to identify unique groupings as a data reduction tool, to combine self-report and accelerometry, and to combine different physical activity intensities and sedentary behavior in one LCA model or separate models.
Dilated cardiomyopathy is characterized by substantial locus, allelic, and clinical heterogeneity that necessitates testing of many genes across clinically overlapping diseases. Few studies have ...sequenced sufficient individuals; thus, the contributions of individual genes and the pathogenic variant spectrum are still poorly defined. We analyzed 766 dilated cardiomyopathy patients tested over 5 years in our molecular diagnostics laboratory.
Patients were tested using gene panels of increasing size from 5 to 46 genes, including 121 cases tested with a multiple-cardiomyopathy next-generation panel covering 46 genes. All variants were reassessed using our current clinical-grade scoring system to eliminate false-positive disease associations that afflict many older analyses.
Up to 37% of dilated cardiomyopathy cases carry a clinically relevant variant in one of 20 genes, titin (TTN) being the largest contributor (up to 14%). Desmoplakin (DSP), an arrhythmogenic right ventricular cardiomyopathy gene, contributed 2.4%, illustrating the utility of multidisease testing. The clinical sensitivity increased from 10 to 37% as gene panel sizes increased. However, the number of inconclusive cases also increased from 4.6 to 51%.
Our data illustrate the utility of broad gene panels for genetically and clinically heterogeneous diseases but also highlight challenges as molecular diagnostics moves toward genome-wide testing.
Projecting the future distributions of commercially and ecologically important species has become a critical approach for ecosystem managers to strategically anticipate change, but large ...uncertainties in projections limit climate adaptation planning. Although distribution projections are primarily used to understand the scope of potential change—rather than accurately predict specific outcomes—it is nonetheless essential to understand where and why projections can give implausible results and to identify which processes contribute to uncertainty. Here, we use a series of simulated species distributions, an ensemble of 252 species distribution models, and an ensemble of three regional ocean climate projections, to isolate the influences of uncertainty from earth system model spread and from ecological modeling. The simulations encompass marine species with different functional traits and ecological preferences to more broadly address resource manager and fishery stakeholder needs, and provide a simulated true state with which to evaluate projections. We present our results relative to the degree of environmental extrapolation from historical conditions, which helps facilitate interpretation by ecological modelers working in diverse systems. We found uncertainty associated with species distribution models can exceed uncertainty generated from diverging earth system models (up to 70% of total uncertainty by 2100), and that this result was consistent across species traits. Species distribution model uncertainty increased through time and was primarily related to the degree to which models extrapolated into novel environmental conditions but moderated by how well models captured the underlying dynamics driving species distributions. The predictive power of simulated species distribution models remained relatively high in the first 30 years of projections, in alignment with the time period in which stakeholders make strategic decisions based on climate information. By understanding sources of uncertainty, and how they change at different forecast horizons, we provide recommendations for projecting species distribution models under global climate change.
Projecting the future distributions of species has become critical for climate adaption planning, but we don't have a precise understanding of how accurate projections can be without waiting decades for validation. Here, we model simulated species responses under climate change to quantify and understand sources of uncertainty, and how they change at different forecast horizons. We provide recommendations for projecting species distribution models under global climate change.
The utility of poly(ε-caprolactone) (PCL) as a shape memory polymer (SMP) may be improved by accelerating its degradation. Recently, we have reported novel semi-interpenetrating networks (semi-IPNs) ...composed of cross-linked PCL diacrylate (PCL-DA) and thermoplastic poly(l-lactic acid) (PLLA) that exhibited SMP behavior, accelerated degradation, and enhanced moduli versus the PCL-DA control. Herein, we systematically varied the thermoplastic component of the PCL-based semi-IPNs, incorporating homo- and copolymers based on lactic acid of different
, hydrophilicity, and crystallinity. Specifically, semicrystalline PLLAs of different
s (7.5, 15, 30, and 120 kDa) were explored as the thermoplastics in the semi-IPNs. Additionally, to probe crystallinity and hydrophilicity, amorphous (or nearly amorphous) thermoplastics of different hydrophilicities (PDLLA and PLGAs 85:15, 70:30, and 50:50, l-lactide:glycolide mole % ratio) were employed. For all semi-IPNs, the wt % ratio of the cross-linked PCL-DA to thermoplastic was 75:25. The nature of the thermoplastics was linked to semi-IPN miscibility and the trends in accelerated degradation rates.
Both increases in temperature and changes in precipitation may limit future tree growth, but rising atmospheric CO
2
could offset some of these stressors through increased plant Water Use Efficiency ...(WUE). The net balance between the negative impacts of climate change and positive effects of CO
2
on tree growth is crucial for ecotones, where increased climate stress could drive mortality and shifts in range. Here, we quantify the effects of climate, stand structure, and rising CO
2
on both annual tree-ring growth increment and intrinsic WUE (iWUE) at a savanna-forest boundary in the Upper Midwest United States. Taking a Bayesian hierarchical modelling approach, we find that plant iWUE increased by ~ 16–23% over the course of the twentieth century, but on average, tree-ring growth increments do not significantly increase. Consistent with higher iWUE under increased CO
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and recent wetting, we observe a decrease in sensitivity of tree growth to annual precipitation, leading to ~ 35–41% higher growth under dry conditions compared to trees of similar size in the past. However, an emerging interaction between summer maximum temperatures and annual precipitation diminishes the water-savings benefit under hot and dry conditions. This decrease in precipitation sensitivity, and the interaction between temperature and precipitation are strongest in open canopy microclimates, suggesting that stand structure may modulate response to future changes. Overall, while higher iWUE may provide some water savings benefits to growth under normal drought conditions, near-term future temperature increases combined with drought events could drive growth declines of about 50%.
Lack of longitudinal research hinders causal inference on the association between the built environment and walking. In the present study, we used data from 6,027 adults in the Multi-Ethnic Study of ...Atherosclerosis who were 45-84 years of age at baseline to investigate the association of neighborhood built environment with trends in the amount of walking between 2000 and 2012. Walking for transportation and walking for leisure were assessed at baseline and at 3 follow-up visits (median follow-up = 9.15 years). Time-varying built environment measures (measures of population density, land use, number of destinations, bus access, and street connectivity) were created using geographic information systems. We used linear mixed models to estimate the associations between baseline levels of and a change in each built environment feature and a change in the frequency of walking. After adjustment for potential confounders, we found that higher baseline levels of population density, area zoned for retail, social destinations, walking destinations, and street connectivity were associated with greater increases in walking for transportation over time. Higher baseline levels of land zoned for residential use and distance to buses were associated with less pronounced increases (or decreases) in walking for transportation over time. Increases in the number of social destinations, the number of walking destinations, and street connectivity over time were associated with greater increases in walking for transportation. Higher baseline levels of both land zoned for retail and walking destinations were associated with greater increases in leisure walking, but no changes in built environment features were associated with leisure walking. The creation of mixed-use, dense developments may encourage adults to incorporate walking for transportation into their everyday lives.
Infants younger than 6 months of age are at high risk for complications of coronavirus disease 2019 (Covid-19) and are not eligible for vaccination. Transplacental transfer of antibodies against ...severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after maternal Covid-19 vaccination may confer protection against Covid-19 in infants.
We used a case-control test-negative design to assess the effectiveness of maternal vaccination during pregnancy against hospitalization for Covid-19 among infants younger than 6 months of age. Between July 1, 2021, and March 8, 2022, we enrolled infants hospitalized for Covid-19 (case infants) and infants hospitalized without Covid-19 (control infants) at 30 hospitals in 22 states. We estimated vaccine effectiveness by comparing the odds of full maternal vaccination (two doses of mRNA vaccine) among case infants and control infants during circulation of the B.1.617.2 (delta) variant (July 1, 2021, to December 18, 2021) and the B.1.1.259 (omicron) variant (December 19, 2021, to March 8, 2022).
A total of 537 case infants (181 of whom had been admitted to a hospital during the delta period and 356 during the omicron period; median age, 2 months) and 512 control infants were enrolled and included in the analyses; 16% of the case infants and 29% of the control infants had been born to mothers who had been fully vaccinated against Covid-19 during pregnancy. Among the case infants, 113 (21%) received intensive care (64 12% received mechanical ventilation or vasoactive infusions). Two case infants died from Covid-19; neither infant's mother had been vaccinated during pregnancy. The effectiveness of maternal vaccination against hospitalization for Covid-19 among infants was 52% (95% confidence interval CI, 33 to 65) overall, 80% (95% CI, 60 to 90) during the delta period, and 38% (95% CI, 8 to 58) during the omicron period. Effectiveness was 69% (95% CI, 50 to 80) when maternal vaccination occurred after 20 weeks of pregnancy and 38% (95% CI, 3 to 60) during the first 20 weeks of pregnancy.
Maternal vaccination with two doses of mRNA vaccine was associated with a reduced risk of hospitalization for Covid-19, including for critical illness, among infants younger than 6 months of age. (Funded by the Centers for Disease Control and Prevention.).
As vaccination coverage against SARS-CoV-2 increases amidst the emergence and spread of more infectious and potentially more deadly viral variants, decisions on timing and extent of relaxing ...effective, but unsustainable, non-pharmaceutical interventions (NPIs) need to be made.
An individual-based transmission model of SARS-CoV-2 dynamics, OpenCOVID, was developed to compare the impact of various vaccination and NPI strategies on the COVID-19 epidemic in Switzerland. OpenCOVID uses the Oxford Containment Health Index (OCHI) to quantify the stringency of NPIs.
Even if NPIs in place in March 2021 were to be maintained and the vaccine campaigns rollout rapidly scaled-up, a ‘third wave’ was predicted. However, we find a cautious phased relaxation can substantially reduce population-level morbidity and mortality. We find that a faster vaccination campaign can offset the size of such a wave, allowing more flexibility for NPIs to be relaxed sooner. Model outcomes were most sensitive to the level of infectiousness of variants of concern observed in Switzerland.
A rapid vaccination rollout can allow the sooner relaxation of NPIs, however ongoing surveillance of - and swift responses to - emerging viral variants is of utmost importance for epidemic control.
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While plaques comprised of fibrillar Aβ aggregates are hallmarks of Alzheimer's disease, soluble Aβ oligomers present higher neurotoxicity. Thus, one therapeutic approach is to prevent the formation ...of Aβ oligomers and reduce their associated harmful effects. We have proposed a peptoid mimic of the Aβ hydrophobic KLVFF core as an ideal candidate aggregation inhibitor due to its ability to evade proteolytic degradation via repositioning of the side chain from the α‐carbon to the amide nitrogen. This peptoid, JPT1, utilizes chiral sidechains to achieve a helical structure, while C‐terminal addition of two phenylalanine residues places aromatic groups on two sides of the helix with spacing designed to facilitate interaction with amyloid β‐sheet structure. We have previously shown that JPT1 modulates Aβ fibril formation. Here, we demonstrate that JPT1 also modulates Aβ oligomerization, and we explore the role of the charge on the linker between the KLVFF mimic and the extended aromatic residues. Additionally, we demonstrate that peptoid‐induced changes in Aβ oligomerization correlate with attenuation of oligomer‐induced nuclear factor‐κB activation in SH‐SY5Y human neuroblastoma cells. These findings support the therapeutic potential of peptoids to target early stages of Aβ aggregation and impact the associated Aβ‐induced cellular response.
When SH‐SY5Y human neuroblastoma cells were incubated with 4 μM Aβ1‐42 oligomers (Control), increased nuclear factor‐κB (NF‐κB) activation was visualized. However, when the cells incubated with 4 μM Aβ1‐42 oligomers formed in the presence of peptoids that modulate oligomer formation (JPT1, JPT1_I6K, or JPT1_I6E), significant attenuation of NF‐κB activation was observed.
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