Ambulatory sleep scoring using accelerometers—distinguishing between nonwear and sleep/wake states

Background. Differentiating nonwear time from sleep and wake times is essential forthe estimation of sleep duration based on actigraphy data. To efficiently analyze large-scale data sets, an automatic method of identifying these three different states is re-quired. Therefore, we developed a classification algorithm to determine nonwear, sleepand wake periods from accelerometer data. Our work aimed to (I) develop a new patternrecognition algorithm for identifying nonwear periods from actigraphy data based onthe influence of respiration rate on the power spectrum of the acceleration signal andimplement it in an automatic classification algorithm for nonwear/sleep/wake states;(II) address motion artifacts that occur during nonwear periods and are known to causemisclassification of these periods; (III) adjust the algorithm depending on the sensorposition (wrist, chest); and (IV) validate the algorithm on both healthy individuals andpatients with sleep disorders. Methods. The study involved 98 participants who wore wrist and chest accelerationsensors for one day of measurements. They spent one night in the sleep laboratoryand continued to wear the sensors outside of the laboratory for the remainder of theday. The results of the classification algorithm were compared to those of the referencesource: polysomnography for wake/sleep and manual annotations for nonwear/wearclassification. Results. The median kappa values for the two locations were 0.83 (wrist) and 0.84(chest). The level of agreement did not vary significantly by sleep health (good sleepersvs. subjects with sleep disorders) (p=0.348,p=0.118) or by sex (p=0.442,p=0.456).The intraclass correlation coefficients of nonwear total time between the referenceand the algorithm were 0.92 and 0.97 with the outliers and 0.95 and 0.98 after theoutliers were removed for the wrist and chest, respectively. There was no evidence of anassociation between the mean difference (and 95% limits of agreement) and the meanof the two methods for either sensor position (wrist p=0.110, chest p=0.164), and themean differences (algorithm minus reference) were 5.11 [95% LoA−15.4–25.7] and1.32 [95% LoA−9.59–12.24] min/day, respectively, after the outliers were removed. Discussion. We studied the influence of the respiration wave on the power spectrum ofthe acceleration signal for the differentiation of nonwear periods from sleep and wakeperiods. The algorithm combined both spectral analysis of the acceleration signal and rescoring. Based on the Bland-Altman analysis, the chest-worn accelerometer showed better results than the wrist-worn accelerometer

First-trimester prediction of preterm prelabour rupture of membranes incorporating cervical length measurement

Objectives: To examine early pregnancy risk factors for preterm prelabour rupture of membranes (PPROM) and develop a predictive model. Study design: Retrospective analysis of a cohort of mixed-risk singleton pregnancies screened in the first and second trimesters in three Danish tertiary fetal medicine centres, including a cervical length measurement at 11–14 weeks, at 19–21 weeks and at 23–24 weeks of gestation. Univariable and multivariable logistic regression analyses were employed to identify predictive maternal characteristics, biochemical and sonographic factors. Receiver operating characteristic (ROC) curve analysis was used to determine predictors for the most accurate model. Results: Of 3477 screened women, 77 (2.2%) had PPROM. Maternal factors predictive of PPROM in univariable analysis were nulliparity (OR 2.0 (95% CI 1.2–3.3)), PAPP-A < 0.5 MoM (OR 2.6 (1.1–6.2)), previous preterm birth (OR 4.2 (1.9–8.9)), previous cervical conization (OR 3.6 (2.0–6.4)) and cervical length ≤ 25 mm on transvaginal imaging (first-trimester OR 15.9 (4.3–59.3)). These factors all remained statistically significant in a multivariable adjusted model with an AUC of 0.72 in the most discriminatory first-trimester model. The detection rate using this model would be approximately 30% at a false-positive rate of 10%. Potential predictors such as bleeding in early pregnancy and pre-existing diabetes mellitus affected very few cases and could not be formally assessed. Conclusions: Several maternal characteristics, placental biochemical and sonographic features are predictive of PPROM with moderate discrimination. Larger numbers are required to validate this algorithm and additional biomarkers, not currently used for first-trimester screening, may improve model performance

Associations between fruit and vegetable intake, leisure-time physical activity, sitting time and self-rated health among older adults : cross-sectional data from the WELL study

BackgroundLifestyle behaviours, such as healthy diet, physical activity and sedentary behaviour, are key elements of healthy ageing and important modifiable risk factors in the prevention of chronic diseases. Little is known about the relationship between these behaviours in older adults. The purpose of this study was to explore the relationship between fruit and vegetable (F&amp;V) intake, leisure-time physical activity (LTPA) and sitting time (ST), and their association with self-rated health in older adults.MethodsThis cross-sectional study comprised 3,644 older adults (48% men) aged 55-65 years, who participated in the Wellbeing, Eating and Exercise for a Long Life (&quot;WELL&quot;) study. Respondents completed a postal survey about their health and their eating and physical activity behaviours in 2010 (38% response rate). Spearman\u27s coefficient (rho) was used to evaluate the relationship between F&amp;V intake, LTPA and ST. Their individual and shared associations with self-rated health were examined using ordinal logistic regression models, stratified by sex and adjusted for confounders (BMI, smoking, long-term illness and socio-demographic characteristics).ResultsThe correlations between F&amp;V intake, LTPA and ST were low. F&amp;V intake and LTPA were positively associated with self-rated health. Each additional serving of F&amp;V or MET-hour of LTPA were associated with approximately 10% higher likelihood of reporting health as good or better among women and men. The association between ST and self-rated health was not significant in the multivariate analysis. A significant interaction was found (ST*F&amp;V intake). The effect of F&amp;V intake on self-rated health increased with increasing ST in women, whereas the effect decreased with increasing ST in men.ConclusionThis study contributes to the scarce literature related to lifestyle behaviours and their association with health indicators among older adults. The findings suggest that a modest increase in F&amp;V intake, or LTPA could have a marked effect on the health of older adults. Further research is needed to fully understand the correlates and determinants of lifestyle behaviours, particularly sitting time, in this age group

A tumor cord model for Doxorubicin delivery and dose optimization in solid tumors

<p>Abstract</p> <p>Background</p> <p>Doxorubicin is a common anticancer agent used in the treatment of a number of neoplasms, with the lifetime dose limited due to the potential for cardiotoxocity. This has motivated efforts to develop optimal dosage regimes that maximize anti-tumor activity while minimizing cardiac toxicity, which is correlated with peak plasma concentration. Doxorubicin is characterized by poor penetration from tumoral vessels into the tumor mass, due to the highly irregular tumor vasculature. I model the delivery of a soluble drug from the vasculature to a solid tumor using a tumor cord model and examine the penetration of doxorubicin under different dosage regimes and tumor microenvironments.</p> <p>Methods</p> <p>A coupled ODE-PDE model is employed where drug is transported from the vasculature into a tumor cord domain according to the principle of solute transport. Within the tumor cord, extracellular drug diffuses and saturable pharmacokinetics govern uptake and efflux by cancer cells. Cancer cell death is also determined as a function of peak intracellular drug concentration.</p> <p>Results</p> <p>The model predicts that transport to the tumor cord from the vasculature is dominated by diffusive transport of free drug during the initial plasma drug distribution phase. I characterize the effect of all parameters describing the tumor microenvironment on drug delivery, and large intercapillary distance is predicted to be a major barrier to drug delivery. Comparing continuous drug infusion with bolus injection shows that the optimum infusion time depends upon the drug dose, with bolus injection best for low-dose therapy but short infusions better for high doses. Simulations of multiple treatments suggest that additional treatments have similar efficacy in terms of cell mortality, but drug penetration is limited. Moreover, fractionating a single large dose into several smaller doses slightly improves anti-tumor efficacy.</p> <p>Conclusion</p> <p>Drug infusion time has a significant effect on the spatial profile of cell mortality within tumor cord systems. Therefore, extending infusion times (up to 2 hours) and fractionating large doses are two strategies that may preserve or increase anti-tumor activity and reduce cardiotoxicity by decreasing peak plasma concentration. However, even under optimal conditions, doxorubicin may have limited delivery into advanced solid tumors.</p

Functional characterization of the YmcB and YqeV tRNA methylthiotransferases of Bacillus subtilis

Methylthiotransferases (MTTases) are a closely related family of proteins that perform both radical-S-adenosylmethionine (SAM) mediated sulfur insertion and SAM-dependent methylation to modify nucleic acid or protein targets with a methyl thioether group (–SCH3). Members of two of the four known subgroups of MTTases have been characterized, typified by MiaB, which modifies N6-isopentenyladenosine (i6A) to 2-methylthio-N6-isopentenyladenosine (ms2i6A) in tRNA, and RimO, which modifies a specific aspartate residue in ribosomal protein S12. In this work, we have characterized the two MTTases encoded by Bacillus subtilis 168 and find that, consistent with bioinformatic predictions, ymcB is required for ms2i6A formation (MiaB activity), and yqeV is required for modification of N6-threonylcarbamoyladenosine (t6A) to 2-methylthio-N6-threonylcarbamoyladenosine (ms2t6A) in tRNA. The enzyme responsible for the latter activity belongs to a third MTTase subgroup, no member of which has previously been characterized. We performed domain-swapping experiments between YmcB and YqeV to narrow down the protein domain(s) responsible for distinguishing i6A from t6A and found that the C-terminal TRAM domain, putatively involved with RNA binding, is likely not involved with this discrimination. Finally, we performed a computational analysis to identify candidate residues outside the TRAM domain that may be involved with substrate recognition. These residues represent interesting targets for further analysis

Functional characterization of the YmcB and YqeV tRNA methylthiotransferases of Bacillus subtilis

Methylthiotransferases (MTTases) are a closely related family of proteins that perform both radical-S-adenosylmethionine (SAM) mediated sulfur insertion and SAM-dependent methylation to modify nucleic acid or protein targets with a methyl thioether group (–SCH3). Members of two of the four known subgroups of MTTases have been characterized, typified by MiaB, which modifies N6-isopentenyladenosine (i6A) to 2-methylthio-N6-isopentenyladenosine (ms2i6A) in tRNA, and RimO, which modifies a specific aspartate residue in ribosomal protein S12. In this work, we have characterized the two MTTases encoded by Bacillus subtilis 168 and find that, consistent with bioinformatic predictions, ymcB is required for ms2i6A formation (MiaB activity), and yqeV is required for modification of N6-threonylcarbamoyladenosine (t6A) to 2-methylthio-N6-threonylcarbamoyladenosine (ms2t6A) in tRNA. The enzyme responsible for the latter activity belongs to a third MTTase subgroup, no member of which has previously been characterized. We performed domain-swapping experiments between YmcB and YqeV to narrow down the protein domain(s) responsible for distinguishing i6A from t6A and found that the C-terminal TRAM domain, putatively involved with RNA binding, is likely not involved with this discrimination. Finally, we performed a computational analysis to identify candidate residues outside the TRAM domain that may be involved with substrate recognition. These residues represent interesting targets for further analysis

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Democratic research: Setting up a research commons for a qualitative, comparative, longitudinal interview study during the COVID-19 pandemic

The sudden and dramatic advent of the COVID-19 pandemic led to urgent demands for timely, relevant, yet rigorous research. This paper discusses the origin, design, and execution of the SolPan research commons, a large-scale, international, comparative, qualitative research project that sought to respond to the need for knowledge among researchers and policymakers in times of crisis. The form of organization as a research commons is characterized by an underlying solidaristic attitude of its members and its intrinsic organizational features in which research data and knowledge in the study is shared and jointly owned. As such, the project is peer-governed, rooted in (idealist) social values of academia, and aims at providing tools and benefits for its members. In this paper, we discuss challenges and solutions for qualitative studies that seek to operate as research commons

Fish, Mercury, Selenium and Cardiovascular Risk: Current Evidence and Unanswered Questions

Controversy has arisen among the public and in the media regarding the health effects of fish intake in adults. Substantial evidence indicates that fish consumption reduces coronary heart disease mortality, the leading cause of death in developed and most developing nations. Conversely, concerns have grown regarding potential effects of exposure to mercury found in some fish. Seafood species are also rich in selenium, an essential trace element that may protect against both cardiovascular disease and toxic effects of mercury. Such protective effects would have direct implications for recommendations regarding optimal selenium intake and for assessing the potential impact of mercury exposure from fish intake in different populations. Because fish consumption appears to have important health benefits in adults, elucidating the relationships between fish intake, mercury and selenium exposure, and health risk is of considerable scientific and public health relevance. The evidence for health effects of fish consumption in adults is reviewed, focusing on the strength and consistency of evidence and relative magnitudes of effects of omega-3 fatty acids, mercury, and selenium. Given the preponderance of evidence, the focus is on cardiovascular effects, but other potential health effects, as well as potential effects of polychlorinated biphenyls and dioxins in fish, are also briefly reviewed. The relevant current unanswered questions and directions of further research are summarized