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The possibility of exploiting motile microorganisms as tiny propellers represents a fascinating strategy for the transport of colloidal cargoes. However, delivery on target sites usually requires external control fields to steer propellers and trigger cargo release. The need for a constant feedback mechanism prevents the design of compact devices where biopropellers could perform their tasks autonomously. Here we show that properly designed three-dimensional (3D) microstructures can define accumulation areas where bacteria spontaneously and efficiently store colloidal beads. The process is stochastic in nature and results from the rectifying action of an asymmetric energy landscape over the fluctuating forces arising from collisions with swimming bacteria. As a result, the concentration of colloids over target areas can be strongly increased or depleted according to the topography of the underlying structures. Besides the significance to technological applications, our experiments pose some important questions regarding the structure of stationary probability distributions in non-equilibrium systems. Transport of colloidal cargoes to target sites can be done by controlling active carriers, like self-propelled bacteria, under external stimuli. Koumakis et al. show that bacteria can autonomously achieve the same goal when moving over pre-designed asymmetric microstructures.

Active granular particles can harness unbiased mechanical vibrations in the environment to generate directed motion. We provide a theoretical framework that connects the geometrical shape of a three dimensional object to its self-propulsion characteristics over a vertically vibrated plate. We find that a maximally efficient propulsion is achieved for structures having tilted flexible legs forming a characteristic angle with the vertical. Our predictions are verified by experimental observations on a class of 3D printed structures with smoothly varying geometrical features.

BackgroundTachykinins have been implicated in the pathophysiology of IBS with diarrhoea (IBS-D). Our aim was to study the efficacy and safety of ibodutant, a selective neurokinin-2 (NK2) receptor antagonist, in patients with IBS-D.MethodsThis multinational double-blind, placebo-controlled study recruited 559 patients with IBS-D according to Rome III criteria. After a 2-week treatment-free run-in, patients were randomised to ibodutant 1 mg, 3 mg, 10 mg or placebo once daily for eight consecutive weeks. Responders were those with a combined response of satisfactory relief (weekly binary question yes/no) of overall IBS symptoms and abdominal pain/discomfort on ≥75% weeks (primary end point). Secondary end points included abdominal pain and stool pattern. Data were also analysed according to US Food and Drug Administration (FDA)-approved interim end points (improvement of pain and stool consistency). Safety was assessed by monitoring adverse events and laboratory tests. Prespecified statistical analysis involved the whole group as well as gender subgroups.ResultsDemographics and baseline characteristics were comparable for all treatment arms. In the overall population, responsiveness tended to increase with escalating ibodutant doses. In the prespecified analysis by gender, ibodutant 10 mg demonstrated significant superiority over placebo in females (p=0.003), while no significant effect occurred in males. This was confirmed for secondary end points and for the responder analysis according to FDA-approved end points. The tolerability and safety of ibodutant was excellent at all doses.ConclusionsIbodutant showed dose-dependent efficacy response in IBS-D, reaching statistical significance at the 10 mg dose in female patients. The safety and tolerability profile of ibodutant was similar to placebo.Trial registration numberNCT01303224.

The isotope dependence of plasma transport will have a significant impact on the performance of future D-T experiments in JET and ITER and eventually on the fusion gain and economics of future reactors. In preparation for future D-T operation on JET, dedicated experiments and comprehensive transport analyses were performed in H, D and H-D mixed plasmas. The analysis of the data has demonstrated an unexpectedly strong and favourable dependence of the global confinement of energy, momentum and particles in ELMy H-mode plasmas on the atomic mass of the main ion species, the energy confinement time scaling as ${\\tau _E}\\sim {A^{0.5}}$ (Maggi et al., Plasma Phys. Control. Fusion, vol. 60, 2018, 014045; JET Team, Nucl. Fusion, vol. 39, 1999, pp. 1227–1244), i.e. opposite to the expectations based only on local gyro-Bohm (GB) scaling, ${\\tau _E}\\sim {A^{ - 0.5}}$, and stronger than in the commonly used H-mode scaling for the energy confinement (Saibene et al., Nucl. Fusion, vol. 39, 1999, 1133; ITER Physics Basis, Nucl. Fusion, vol. 39, 1999, 2175). The scaling of momentum transport and particle confinement with isotope mass is very similar to that of energy transport. Nonlinear local GENE gyrokinetic analysis shows that the observed anti-GB heat flux is accounted for if collisions, E × B shear and plasma dilution with low-Z impurities (9Be) are included in the analysis (E and B are, respectively the electric and magnetic fields). For L-mode plasmas a weaker positive isotope scaling ${\\tau _E}\\sim {A^{0.14}}$ has been found in JET (Maggi et al., Plasma Phys. Control. Fusion, vol. 60, 2018, 014045), similar to ITER97-L scaling (Kaye et al., Nucl. Fusion, vol. 37, 1997, 1303). Flux-driven quasi-linear gyrofluid calculations using JETTO-TGLF in L-mode show that local GB scaling is not followed when stiff transport (as is generally the case for ion temperature gradient modes) is combined with an imposed boundary condition taken from the experiment, in this case predicting no isotope dependence. A dimensionless identity plasma pair in hydrogen and deuterium L-mode plasmas has demonstrated scale invariance, confirming that core transport physics is governed, as expected, by the 4 dimensionless parameters ρ*, ν*, β, q (normalised ion Larmor radius, collisionality, plasma pressure and safety factor) consistently with global quasi-linear gyrokinetic TGLF calculations (Maggi et al., Nucl. Fusion, vol. 59, 2019, 076028). We compare findings in JET with those in different devices and discuss the possible reasons for the different isotope scalings reported from different devices. The diversity of observations suggests that the differences may result not only from differences affecting the core, e.g. heating schemes, but are to a large part due to differences in device-specific edge and wall conditions, pointing to the importance of better understanding and controlling pedestal and edge processes.

Studies are increasingly examining the relationship between the neighborhood environment and cognitive decline; yet, few have investigated associations between multiple neighborhood features and Alzheimer's disease and related dementias (ADRD). We investigated the relationship between neighborhood features and ADRD cumulative incidence from 2010 to 2014 in the South Carolina Alzheimer's Disease Registry (SCADR). Diagnosed ADRD cases of age were ascertained from the SCADR by ZIP code and census tract. Neighborhood features from multiple secondary sources included poverty, air pollution [particulate matter with a diameter of 2.5 micrometers or less ( )], and rurality at the census-tract level and access to healthy food, recreation facilities, and diabetes screening at the county level. In addition to using Poisson generalized linear regression to estimate ADRD incident rate ratios (IRR) with 95% confidence intervals (CIs), we applied integrated nested Laplace approximations and stochastic partial differential equations (INLA-SPDE) to address disparate spatial scales. We estimated associations between neighborhood features and ADRD cumulative incidence. The average annual ADRD cumulative incidence was 690 per 100,000 people per census tract (95% CI: 660, 710). The analysis was limited to 98% of census tracts with a population old (i.e., 1,081 of 1,103). The average percent of families living below the federal poverty line per census tract was 18.8%, and of census tracts were considered rural. The average percent of households with limited access to healthy food was 6.4%. In adjusted models, every ) increase of was associated with 65% higher ADRD cumulative incidence ( ; 95% CI: 1.30, 2.09), where at or below is considered healthy. Compared to large urban census tracts, rural and small urban tracts had 10% ( ; 95% CI: 1.00, 1.23) and 5% ( ; 95% CI: 0.96, 1.16) higher ADRD, respectively. For every percent increase of the county population with limited access to healthy food, ADRD was 2% higher ( ; 95% CI: 1.01, 1.04). Neighborhood environment features, such as higher air pollution levels, were associated with higher neighborhood ADRD incidence. The INLA-SPDE method could have broad applicability to data collected across disparate spatial scales. https://doi.org/10.1289/EHP13183.

Background: Cardiovascular disease (CVD) significantly impacts Alzheimer’s Disease and Related Dementia (AD/ADRD) mortality. South Carolina has a high incidence of CVD and dementia mortality. The aim of this study, therefore, was to examine the neurological causes of death and the leading causes of death in the South Carolina Alzheimer’s Disease Registry (SCADR). Method: Data from 2005–2018 were extracted from the SCADR using ICD-9 and ICD-10 codes. The top 10 leading causes of death (LCOD) were identified using death certificates. Some neurological causes of death were operationalized by combining related ICD codes, such as CVD_C (I219, I251, I500, I64) and chronic obstructive pulmonary disease (COP_C), (J449, C349), and χ2 was used to compare socio-demographic characteristics and mortality. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) were estimated using extended Cox Proportional Hazard modeling, adjusting for socio-demographic factors. Results: A total of 207,093 registry cases were included in the analysis. About 70% of cases had Alzheimer’s Disease (AD) diagnosis, and 40% of all cases were 85 years and older. The LCOD was CVD_C (13.4%). The risk of death among cases with vascular dementia (VaD) was 1.17 times the risk of death among those with AD (aHR: 1.172, 95% CI: 1.148–1.196). Among all deaths, cases with COP_C had a significantly higher likelihood of death compared to those with CVD_C (aHR: 1.06, 95% CI: 1.025–1.090). Conclusions: The study highlights CVD_C as the LCOD in frequency, with survival analysis indicating COP_C risk of death as significantly higher compared to CVD_C deaths. There is a need to prioritize CVD and lung-related comorbidity prevention, assessment, and management programs for individuals living with ADRD.

This Special Issue of the International Journal of Molecular Sciences collects the latest research on different biological processes and molecular mechanisms that cause diabetes [...].This Special Issue of the International Journal of Molecular Sciences collects the latest research on different biological processes and molecular mechanisms that cause diabetes [...].

While studies have documented the influence of caregiver and care recipient factors on caregiver health, it is important to address the potential impact of neighborhood contexts. This study estimated the cross-sectional associations between neighborhood characteristics and mental health among caregivers cohabiting with Alzheimer’s disease care recipients that were experiencing severe or non-severe neuropsychiatric symptoms (NPSs) (e.g., aggression/anxiety). We obtained data collected in 2010 on caregivers and care recipients (n = 212) from a subset of South Carolina’s Alzheimer’s Disease Registry. Neighborhood measures (within 1 mile of the residence) came from the American Community Survey and the Rural-Urban Commuting Area Code. We categorized the neighborhood median household income into tertiles, namely, “low” (< $31,000), “medium” ($ 31,000–40,758), and “high” (>$40,758), and rurality as “large urban,” “small urban,” and “rural.” We used negative binomial regression to estimate the prevalence ratios (PRs) and 95% confidence intervals (CIs) for caregiver mental health using neighborhood characteristics. The mean age was 58 ± 10.3 years, 85% were women, and 55% were non-Hispanic Black. Among the caregivers cohabiting with a recipient experiencing severe NPS, higher distress was experienced by caregivers living in low- (PR = 1.61 (95% CI = 1.26–2.04)) and medium- (PR = 1.45 (95% CI = 1.17–1.78)) vs. high-income neighborhoods after an adjustment. These results suggest that neighborhood characteristics may amplify other social stressors experienced by caregivers.

Background Serum cell-free DNA (cfDNA) holds promise as a non-invasive cancer biomarker. The objective of this study was to evaluate the association of cfDNA concentration with clinicopathologic variables of poor prognosis and overall survival among women with uterine cancer compared to benign cancer-free controls. Methods cfDNA was extracted from the serum of 91 women with multiple uterine cancer histologies and 22 post-menopausal controls without cancer. Low molecular weight (LMW) cfDNA was separated from contaminating genomic high molecular weight cfDNA using paramagnetic bead purification and its concentration was measured using fluorometric quantification. Clinicopathologic data was abstracted from the electronic medical record. The association between serum cfDNA concentration, clinicopathologic variables, and overall survival was assessed using linear regression modelling, Cox proportional hazards modelling, and the Kaplan–Meier method. Results Median total serum cfDNA concentration for the cohort was 69.2 ng/mL (IQR 37.4, 132.3) and median LMW cfDNA concentration was 23.8 ng/mL (IQR 14.9, 44.4). There were no significant differences in total serum cfDNA concentration with any clinicopathologic variables. However, LMW cfDNA concentration was significantly higher in serum of women with cancer (25.8 ng/mL IQR 16.0, 49.6) compared to benign controls (15.5 ng/mL IQR 9.3, 25.8 ng/mL) (p < 0.01). It is also significantly higher among women with early stage cancer than benign controls (p < 0.01). There were also significant associations between LMW cfDNA concentration and stage of cancer (p = 0.01) and histology (p = 0.02). Patients with leiomyosarcoma and carcinosarcoma had higher cfDNA concentrations than those with endometrioid cancer. Over a median follow-up of 51.9 months, 75th percentile for overall survival for women with cancer was 24.0 months. Higher LMW cfDNA concentrations is associated with lower survival among women with cancer (p < 0.01). Conclusions Serum LMW cfDNA concentration is associated with overall survival in women with uterine cancer, and it is higher among women with uterine cancer compared to those of controls.