Investigation of advanced navigation and guidance system concepts for all-weather rotorcraft operations

Results are presented of a survey conducted of active helicopter operators to determine the extent to which they wish to operate in IMC conditions, the visibility limits under which they would operate, the revenue benefits to be gained, and the percent of aircraft cost they would pay for such increased capability. Candidate systems were examined for capability to meet the requirements of a mission model constructed to represent the modes of flight normally encountered in low visibility conditions. Recommendations are made for development of high resolution radar, simulation of the control display system for steep approaches, and for development of an obstacle sensing system for detecting wires. A cost feasibility analysis is included

The Health Impacts of Eviction: Evidence from the National Longitudinal Study of Adolescent to Adult Health

Eviction represents an urgent social and economic issue in the United States, with nearly two million evictions occurring annually in the U.S. Still, the population health impacts of evictions, as well as the pathways linking eviction to health, are not well documented or understood, particularly among young adults. Using nationally-representative, longitudinal data from the National Longitudinal Study of Adolescent to Adult Health (1994-2008) (n=9,029), the present study uses a combination of analytic methods—including prospective lagged dependent variable regression models, inverse probabilities of treatment weighting, longitudinal first difference models, causal mediation techniques—to comprehensively assess whether and how evictions relate to depressive risk and self-rated health across early adulthood, paying particular attention to the stress-related pathways linking eviction and health. Results provide robust evidence of positive longitudinal associations between eviction and depressive risk, in particular. In the prospective regression models, young adults who experienced recent eviction had more depressive symptoms and worse self-rated health than those who were not evicted, net a host of background characteristics. Using treatment weighting techniques, results showed that young adults who experienced eviction had more depressive symptoms than those who were not evicted (5.921 vs. 4.998 depressive symptoms, p=0.003). Perceived social stress mediated nearly 18 percent of the associations between eviction and the depressive symptoms (p\u3c0.001). In the first difference models, young people who experienced eviction between survey waves experienced greater increases in depressive symptoms over time compared to those who were not evicted, net of changes in other indicators of socioeconomic status and residential instability. Taken together, our results suggest that the recent surges in evictions in the U.S. serve as a potent threat to population health during the emerging adult period, with especially devastating consequences for low-income individuals and communities of color

“Toxic” Schools? How School Exposures During Adolescence Influence Trajectories of Health Through Young Adulthood

© 2020 The Author(s) A large body of research identifies the critical role of early-life social contexts such as neighborhoods and households in shaping life course trajectories of health. Less is known about whether and how school characteristics affect individual health and contribute to population health inequality. However, recent scholarship argues that some school environments are so stressful due to high levels of violence, disorder, and poverty that they may be “toxic” to student health, but this hypothesis has not been tested using population data. Integrating insights from the life course perspective and stress process model, we use rich longitudinal data from the National Longitudinal Study of Adolescent to Adult Health (n = 11,382), diverse markers of physiological functioning and psychological well-being, and multilevel regression models to examine whether and how school characteristics shape trajectories of physiological dysregulation and depressive risk from adolescence through early adulthood. Findings reveal that, across multiple measures of physiological functioning and psychological well-being, the social and structural characteristics of schools play an essential role in shaping health risk from adolescence through young adulthood—long after students left school. In particular, indicators of school-level violence and perceptions of safety and school social disconnectedness had especially strong associations with health risk in both the short- and long-term. School socioeconomic composition was also strongly associated with physiological dysregulation in young adulthood, net of individual and neighborhood socioeconomic exposures. Together, findings from this study suggest that school environments can serve as early-life stressors in the lives of young people that unequally shape health trajectories and contribute to broader patterns of health inequality

Biodegradable nano-films for capture and non-invasive release of circulating tumor cells

Selective isolation and purification of circulating tumor cells (CTCs) from whole blood is an important capability for both clinical medicine and biological research. Current techniques to perform this task place the isolated cells under excessive stresses that reduce cell viability, and potentially induce phenotype change, therefore losing valuable information about the isolated cells. We present a biodegradable nano-film coating on the surface of a microfluidic chip, which can be used to effectively capture as well as non-invasively release cancer cell lines such as PC-3, LNCaP, DU 145, H1650 and H1975. We have applied layer-by-layer (LbL) assembly to create a library of ultrathin coatings using a broad range of materials through complementary interactions. By developing an LbL nano-film coating with an affinity-based cell-capture surface that is capable of selectively isolating cancer cells from whole blood, and that can be rapidly degraded on command, we are able to gently isolate cancer cells and recover them without compromising cell viability or proliferative potential. Our approach has the capability to overcome practical hurdles and provide viable cancer cells for downstream analyses, such as live cell imaging, single cell genomics, and invitro cell culture of recovered cells. Furthermore, CTCs from cancer patients were also captured, identified, and successfully released using the LbL-modified microchips

Epigenetics in the primary and secondary prevention of cardiovascular disease: influence of exercise and nutrition

Increasing evidence links changes in epigenetic systems, such as DNA methylation, histone modification, and non-coding RNA expression, to the occurrence of cardiovascular disease (CVD). These epigenetic modifications can change genetic function under influence of exogenous stimuli and can be transferred to next generations, providing a potential mechanism for inheritance of behavioural intervention effects. The benefits of exercise and nutritional interventions in the primary and secondary prevention of CVD are well established, but the mechanisms are not completely understood. In this review, we describe the acute and chronic epigenetic effects of physical activity and dietary changes. We propose exercise and nutrition as potential triggers of epigenetic signals, promoting the reshaping of transcriptional programmes with effects on CVD phenotypes. Finally, we highlight recent developments in epigenetic therapeutics with implications for primary and secondary CVD prevention

Impact of culture towards disaster risk reduction

Number of natural disasters has risen sharply worldwide making the risk of disasters a global concern. These disasters have created significant losses and damages to humans, economy and society. Despite the losses and damages created by disasters, some individuals and communities do not attached much significance to natural disasters. Risk perception towards a disaster not only depends on the danger it could create but also the behaviour of the communities and individuals that is governed by their culture. Within this context, this study examines the relationship between culture and disaster risk reduction (DRR). A comprehensive literature review is used for the study to evaluate culture, its components and to analyse a series of case studies related to disaster risk. It was evident from the study that in some situations, culture has become a factor for the survival of the communities from disasters where as in some situations culture has acted as a barrier for effective DRR activities. The study suggests community based DRR activities as a mechanism to integrate with culture to effectively manage disaster risk

First administration to man of Org 25435, an intravenous anaesthetic: A Phase 1 Clinical Trial

BACKGROUND: Org 25435 is a new water-soluble alpha-amino acid ester intravenous anaesthetic which proved satisfactory in animal studies. This study aimed to assess the safety, tolerability and efficacy of Org 25435 and to obtain preliminary pharmacodynamic and pharmacokinetic data. METHODS: In the Short Infusion study 8 healthy male volunteers received a 1 minute infusion of 0.25, 0.5, 1.0, or 2.0 mg/kg (n = 2 per group); a further 10 received 3.0 mg/kg (n = 5) or 4.0 mg/kg (n = 5). Following preliminary pharmacokinetic modelling 7 subjects received a titrated 30 minute Target Controlled Infusion (TCI), total dose 5.8-20 mg/kg. RESULTS: Within the Short Infusion study, all subjects were successfully anaesthetised at 3 and 4 mg/kg. Within the TCI study 5 subjects were anaesthetised and 2 showed signs of sedation. Org 25435 caused hypotension and tachycardia at doses over 2 mg/kg. Recovery from anaesthesia after a 30 min administration of Org 25435 was slow (13.7 min). Pharmacokinetic modelling suggests that the context sensitive half-time of Org 25435 is slightly shorter than that of propofol in infusions up to 20 minutes but progressively longer thereafter. CONCLUSIONS: Org 25435 is an effective intravenous anaesthetic in man at doses of 3 and 4 mg/kg given over 1 minute. Longer infusions can maintain anaesthesia but recovery is slow. Hypotension and tachycardia during anaesthesia and slow recovery of consciousness after cessation of drug administration suggest this compound has no advantages over currently available intravenous anaesthetics

Epigenetics in the primary and secondary prevention of cardiovascular disease: influence of exercise and nutrition

Increasing evidence links changes in epigenetic systems, such as DNA methylation, histone modification, and non-coding RNA expression, to the occurrence of cardiovascular disease (CVD). These epigenetic modifications can change genetic function under influence of exogenous stimuli and can be transferred to next generations, providing a potential mechanism for inheritance of behavioural intervention effects. The benefits of exercise and nutritional interventions in the primary and secondary prevention of CVD are well established, but the mechanisms are not completely understood. In this review, we describe the acute and chronic epigenetic effects of physical activity and dietary changes. We propose exercise and nutrition as potential triggers of epigenetic signals, promoting the reshaping of transcriptional programmes with effects on CVD phenotypes. Finally, we highlight recent developments in epigenetic therapeutics with implications for primary and secondary CVD prevention

A mutation update for the FLNC gene in myopathies and cardiomyopathies

Filamin C (FLNC) variants are associated with cardiac and muscular phenotypes. Originally, FLNC variants were described in myofibrillar myopathy (MFM) patients. Later, high-throughput screening in cardiomyopathy cohorts determined a prominent role for FLNC in isolated hypertrophic and dilated cardiomyopathies (HCM and DCM). FLNC variants are now among the more prevalent causes of genetic DCM. FLNC-associated DCM is associated with a malignant clinical course and a high risk of sudden cardiac death. The clinical spectrum of FLNC suggests different pathomechanisms related to variant types and their location in the gene. The appropriate functioning of FLNC is crucial for structural integrity and cell signaling of the sarcomere. The secondary protein structure of FLNC is critical to ensure this function. Truncating variants with subsequent haploinsufficiency are associated with DCM and cardiac arrhythmias. Interference with the dimerization and folding of the protein leads to aggregate formation detrimental for muscle function, as found in HCM and MFM. Variants associated with HCM are predominantly missense variants, which cluster in the ROD2 domain. This domain is important for binding to the sarcomere and to ensure appropriate cell signaling. We here review FLNC genotype–phenotype correlations based on available evidence