The value of a spaceflight clinical decision support system for earth-independent medical operations.

As NASA prepares for crewed lunar missions over the next several years, plans are also underway to journey farther into deep space. Deep space exploration will require a paradigm shift in astronaut medical support toward progressively earth-independent medical operations (EIMO). The Exploration Medical Capability (ExMC) element of NASA's Human Research Program (HRP) is investigating the feasibility and value of advanced capabilities to promote and enhance EIMO. Currently, astronauts rely on real-time communication with ground-based medical providers. However, as the distance from Earth increases, so do communication delays and disruptions. Moreover, resupply and evacuation will become increasingly complex, if not impossible, on deep space missions. In contrast to today's missions in low earth orbit (LEO), where most medical expertise and decision-making are ground-based, an exploration crew will need to autonomously detect, diagnose, treat, and prevent medical events. Due to the sheer amount of pre-mission training required to execute a human spaceflight mission, there is often little time to devote exclusively to medical training. One potential solution is to augment the long duration exploration crew's knowledge, skills, and abilities with a clinical decision support system (CDSS). An analysis of preliminary data indicates the potential benefits of a CDSS to mission outcomes when augmenting cognitive and procedural performance of an autonomous crew performing medical operations, and we provide an illustrative scenario of how such a CDSS might function.

Advances in the Synthesis of Preceramic Polymers for the Formation of Silicon-Based and Ultrahigh-Temperature Non-Oxide Ceramics.

Preceramic polymers (PCPs) are a group of specialty macromolecules that serve as precursors for generating inorganics, including ceramic carbides, nitrides, and borides. PCPs represent interesting synthetic challenges for chemists due to the elements incorporated into their structure. This group of polymers is also of interest to engineers as PCPs enable the processing of polymer-derived ceramic products including high-performance ceramic fibers and composites. These finished ceramic materials are of growing significance for applications that experience extreme operating environments (e.g., aerospace propulsion and high-speed atmospheric flight). This Review provides an overview of advances in the synthesis and postpolymerization modification of macromolecules forming nonoxide ceramics. These PCPs include polycarbosilanes, polysilanes, polysilazanes, and precursors for ultrahigh-temperature ceramics. Following our review of PCP synthetic chemistry, we provide examples of the application and processing of these polymers, including their use in fiber spinning, composite fabrication, and additive manufacturing. The principal objective of this Review is to provide a resource that bridges the disciplines of synthetic chemistry and ceramic engineering while providing both insights and inspiration for future collaborative work that will ultimately drive the PCP field forward.

NCCN Virtual Patient Advocacy Summit: Cancer Across the Lifespan.

Patients with cancer have widely divergent experiences throughout their care from screening through survivorship. Differences in care delivery and outcomes may be due to varying patient preferences, patient needs according to stage of life, access to care, and implicit or explicit bias in care according to patient age. NCCN convened a series of stakeholder meetings with patients, caregivers, and patient advocacy groups to discuss the complex challenges and robust opportunities in this space. These meetings informed the NCCN Virtual Patient Advocacy Summit: Cancer Across the Lifespan held on December 10, 2020, which featured a keynote presentation, multidisciplinary panels, and presentations from patient advocacy organizations. This article encapsulates and expounds upon the findings from the stakeholder meetings and discussions during the summit.

The biogeographic differentiation of algal microbiomes in the upper ocean from pole to pole.

Eukaryotic phytoplankton are responsible for at least 20% of annual global carbon fixation. Their diversity and activity are shaped by interactions with prokaryotes as part of complex microbiomes. Although differences in their local species diversity have been estimated, we still have a limited understanding of environmental conditions responsible for compositional differences between local species communities on a large scale from pole to pole. Here, we show, based on pole-to-pole phytoplankton metatranscriptomes and microbial rDNA sequencing, that environmental differences between polar and non-polar upper oceans most strongly impact the large-scale spatial pattern of biodiversity and gene activity in algal microbiomes. The geographic differentiation of co-occurring microbes in algal microbiomes can be well explained by the latitudinal temperature gradient and associated break points in their beta diversity, with an average breakpoint at 14 °C ± 4.3, separating cold and warm upper oceans. As global warming impacts upper ocean temperatures, we project that break points of beta diversity move markedly pole-wards. Hence, abrupt regime shifts in algal microbiomes could be caused by anthropogenic climate change.

Biomorphic Ceramics: Synthesis and Characterization of Preceramic Polymer-Modified Melanin.

Recent efforts have demonstrated that the morphology of ceramics can be manipulated to control both their deformation mechanism and mechanical performance. However, precise control of the ceramic nanostructure is still difficult to achieve. Biotemplating, leading to biomorphic materials, provides a facile route to manipulate the nanostructure of the resulting materials, and the use of melanin as a coating provides a new route to biotemplated materials. Melanin is underutilized for structural materials partly due to the cost of procuring it from natural sources and the inability to control the shape and sizes of melanin particles. Taking a combined synthetic biology and chemical synthesis approach, we report the melanization of Escherichia coli and its subsequent silanization and functionalization with preceramic polymers to make novel biomorphic silicon-based ceramic materials. Graft-to and graft-from reactions were used to append preceramic polymers to the melanin, followed by pyrolysis under argon. Samples were analyzed by FTIR, XRD, XPS, and TEM and found to retain the shape and size of the original cells with high fidelity. The homogeneity of coverage and yield of the resulting ceramic materials depended on the type of grafting reaction. This work provides a promising proof-of-concept that bacterial-templated ceramics can be readily made and opens a host of possibilities for further studies and applications.

Accelerating Advances in Cancer Care Research: A Lookback at the 21st Century Cures Act in 2020.

The 21st Century Cures Act (Cures Act), signed into law in 2016, was designed to advance new therapies by modernizing clinical trials, funding research initiatives, and accelerating the development and use of health information technology. To analyze the current issues in cancer care related to the implementation and impact of the Cures Act, NCCN convened a multistakeholder working group. Participants discussed the legislation's impact on the oncology community since enactment and identified the remaining gaps and challenges as experienced by stakeholders. In June 2020, the policy recommendations of the working group were presented at the virtual NCCN Policy Summit: Accelerating Advances in Cancer Care Research: A Lookback at the 21st Century Cures Act in 2020. The summit consisted of informative discussions and a multistakeholder panel to explore the recommendations and the future of the Cures Act. This article explores identified policy recommendations from the NCCN Working Group and the NCCN Policy Summit, and analyzes opportunities to advance innovative cancer care and patient access to data.

NCCN Policy Summit: Defining, Measuring, and Applying Quality in an Evolving Health Policy Landscape and the Implications for Cancer Care.

Quality measurement is a critical component of advancing a health system that pays for performance over volume. Although there has been significant attention paid to quality measurement within health systems in recent years, significant challenges to meaningful measurement of quality care outcomes remain. Defining cost can be challenging, but is arguably not as elusive as quality, which lacks standard measurement methods and units. To identify industry standards and recommendations for the future, NCCN recently hosted the NCCN Oncology Policy Summit: Defining, Measuring, and Applying Quality in an Evolving Health Policy Landscape and the Implications for Cancer Care. Key stakeholders including physicians, payers, policymakers, patient advocates, and technology partners reviewed current quality measurement programs to identify success and challenges, including the Oncology Care Model. Speakers and panelists identified gaps in quality measurement and provided insights and suggestions for further advancing quality measurement in oncology. This article provides insights and recommendations; however, the goal of this program was to highlight key issues and not to obtain consensus.

The State of Cancer Care in America: Impact of State Policy on Access to High-Quality Cancer Care.

Health policy in America has shifted rapidly over the last decade, and states are increasingly exercising greater authority over health policy decision-making. This localization and regionalization of healthcare policy poses significant challenges for patients with cancer, providers, advocates, and policymakers. To identify the challenges and opportunities that lay ahead of stakeholders, NCCN hosted the 2019 Policy Summit: The State of Cancer Care in America on June 27, 2019, in Washington, DC. The summit featured multidisciplinary panel discussions to explore the implications for access to quality cancer care within a shifting health policy landscape from a patient, provider, and lawmaker perspective. This article encapsulates the discussion from this NCCN Policy Summit.

Short Excited-State Lifetimes Enable Photo-Oxidatively Stable Rubrene Derivatives.

A series of rubrene derivatives were synthesized and the influence of the side group in enhancing photo-oxidative stability was evaluated. Photo-oxidation half-lives were determined via UV-vis absorption spectroscopy, which revealed thiophene containing derivatives to be the most stable species. The electron affinity of the compounds did not correlate with stability as previously reported in literature. Our work shows that shorter excited-state lifetimes result in increased photo-oxidative stability in these rubrene derivatives. These results confirm that faster relaxation kinetics out-compete the formation of reactive oxygen species that ultimately degrade linear oligoacenes. This report highlights the importance of using molecular design to tune excited-state lifetimes in order to generate more stable oligoacenes.

The Use of Optimal Treatment for DLBCL Is Improving in All Age Groups and Is a Key Factor in Overall Survival, but Non-Clinical Factors Influence Treatment.

INTRODUCTION: Diffuse large B cell lymphoma (DLBCL) is an aggressive form of non-Hodgkin lymphoma for which a cure is usually the therapeutic goal of optimal treatment. Using a large population-based cohort we sought to examine the factors associated with optimal DLBCL treatment and survival. METHODS: DLBCL cases were identified through the population-based Victorian Cancer Registry, capturing new diagnoses for two time periods: 2008-2009 and 2012-2013. Treatment was pre-emptively classified as 'optimal' or 'suboptimal', according to compliance with current treatment guidelines. Univariable and multivariable logistic regression models were fitted to determine factors associated with treatment and survival. RESULTS: Altogether, 1442 DLBCL cases were included. Based on multivariable analysis, delivery of optimal treatment was less likely for those aged ≥80 years (p < 0.001), women (p = 0.012), those with medical comorbidity (p < 0.001), those treated in a non-metropolitan hospital (p = 0.02) and those who were ex-smokers (p = 0.02). Delivery of optimal treatment increased between 2008-2009 and the 2012-2013 (from 60% to 79%, p < 0.001). Delivery of optimal treatment was independently associated with a lower risk of death (hazard ratio (HR) = 0.60 (95% confidence interval (CI) 0.45-0.81), p = 0.001). CONCLUSION: Delivery of optimal treatment for DLBCL is associated with hospital location and category, highlighting possible demographic variation in treatment patterns. Together with an increase in the proportion of patients receiving optimal treatment in the more recent time period, this suggests that treatment decisions in DLBCL may be subject to non-clinical influences, which may have implications when evaluating equity of treatment access. The positive association with survival emphasizes the importance of delivering optimal treatment in DLBCL.

Childhood health motivation and adult cardiometabolic health in the Childhood Determinants of Adult Health (CDAH) study.

OBJECTIVE: This research examined if childhood health motivation was associated with adult health behaviors and objectively measured health outcomes. METHOD: Data were from the Childhood Determinants of Adult Health study. Children aged 9 to 15 years in 1985 completed a questionnaire with health motivation items. In 2004-2006, when aged 26 to 36, participants completed assessments of health behaviors (smoking, diet, alcohol consumption, and physical activity) and cardiometabolic outcomes (body mass index, carotid intima-media thickness from ultrasound, and HOMA insulin resistance from fasting blood samples). Structural path regression analyses examined pathways from health motivation in childhood to adult cardiometabolic outcomes, mediated via adult health behaviors measured concurrently, controlling for age, sex and socioeconomic position. RESULTS: There were 6,230 (49% female) children with data on health motivation. There were two latent constructs: health motivation (4 items: visiting a dentist, visiting a doctor, knowing about your body, and eating a good diet) and risk motivation (3 items: not being a smoker, not being fat, and not drinking alcohol). Greater health motivation was directly associated with nonsmoking, lower carotid intima-media thickness, and lower body mass index in adulthood. Greater risk motivation was directly associated with smoking, higher alcohol consumption, and poorer diets in adulthood. It was also indirectly associated with higher carotid intima-media thickness and higher HOMA insulin resistance via poorer health behaviors. CONCLUSIONS: Health motivation during childhood appears important to maintain health across the life course. It could be a target for interventions to improve cardiovascular health in children and adults. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Gait initiation time is associated with the risk of multiple falls-A population-based study.

AIMS: In a population-based study of older people to examine whether 1) overall gait initiation (GI) time or its components are associated with falls and 2) GI under dual-task is a stronger predictor of falls risk than under single-task. METHODS: Participants aged 60-85 years were randomly selected from the electoral roll. GI was obtained with a force platform under both single and dual-task conditions. Falls were ascertained prospectively over a 12-month period. Log multinomial regression was used to examine the association between GI time (total and its components) and risk of single and multiple falls. Age, sex and physiological and cognitive falls risk factors were considered as confounders. RESULTS: The mean age of the sample (n=124) was 71.0 (SD 6.8) years and 58.9% (n=73) were male. Over 12 months 21.8% (n=27) of participants reported a single fall and 16.1% (n=20) reported multiple falls. Slower overall GI time under both single (RR all per 100ms 1.28, 95%CI 1.03, 1.58) and dual-task (RR 1.14, 95%CI 1.02, 1.27) was associated with increased risk of multiple, but not single falls (p<0.05). Multiple falls were also associated with slower time to first lateral movement under single-task (RR 1.90 95%CI 0.59, 1.51) and swing time under dual-task condition (RR 1.44 95%CI 1.08, 1.94). CONCLUSION: Slower GI time is associated with the risk of multiple falls independent of other risk factors, suggesting it could be used as part of a comprehensive falls assessment. Time to the first lateral movement under single-task may be the best measures of this risk.

Evaluation of rodent spaceflight in the NASA animal enclosure module for an extended operational period (up to 35 days).

The National Aeronautics and Space Administration Animal Enclosure Module (AEM) was developed as a self-contained rodent habitat for shuttle flight missions that provides inhabitants with living space, food, water, ventilation, and lighting, and this study reports whether, after minimal hardware modification, the AEM could support an extended term up to 35 days for Sprague-Dawley rats and C57BL/6 female mice for use on the International Space Station. Success was evaluated based on comparison of AEM housed animals to that of vivarium housed and to normal biological ranges through various measures of animal health and well-being, including animal health evaluations, animal growth and body masses, organ masses, rodent food bar consumption, water consumption, and analysis of blood contents. The results of this study confirmed that the AEMs could support 12 adult female C57BL/6 mice for up to 35 days with self-contained RFB and water, and the AEMs could also support 5 adult male Sprague-Dawley rats for 35 days with external replenishment of diet and water. This study has demonstrated the capability and flexibility of the AEM to operate for up to 35 days with minor hardware modification. Therefore, with modifications, it is possible to utilize this hardware on the International Space Station or other operational platforms to extend the space life science research use of mice and rats.

Cancers in Australia in 2010 attributable to tobacco smoke.

OBJECTIVES: To estimate the population attributable fraction (PAF) and numbers of cancers occurring in Australia in 2010 attributable to tobacco smoking, both personal and by a partner. METHODS: We used a modified Peto-Lopez approach to calculate the difference between the number of lung cancer cases observed and the number expected assuming the entire population developed lung cancer at the same rate as never smokers. For cancers other than lung, we applied the standard PAF formula using relative risks from a large cohort and derived notional smoking prevalence. To estimate the PAF for partners' smoking, we used the standard formula incorporating the proportion of non-smoking Australians living with an ever-smoking partner and relative risks associated with partner smoking. RESULTS: An estimated 15,525 (13%) cancers in Australia in 2010 were attributable to tobacco smoke, including 8,324 (81%) lung, 1,973 (59%) oral cavity and pharynx, 855 (60%) oesophagus and 951 (6%) colorectal cancers. Of these, 136 lung cancers in non-smokers were attributable to partner tobacco smoke. CONCLUSIONS: More than one in eight cancers in Australia is attributable to tobacco smoking and would be avoided if nobody smoked. IMPLICATIONS: Strategies to reduce the prevalence of smoking remain a high priority for cancer control.

Air pollution events from forest fires and emergency department attendances in Sydney, Australia 1996-2007: a case-crossover analysis.

BACKGROUND: Severe air pollution generated by forest fires is becoming an increasingly frequent public health management problem. We measured the association between forest fire smoke events and hospital emergency department (ED) attendances in Sydney from 1996-2007. METHODS: A smoke event occurred when forest fires caused the daily citywide average concentration of particulate matter (PM10 or PM2.5) to exceed the 99th percentile of the entire study period. We used a time-stratified case-crossover design and conditional logistic regression models adjusted for meteorology, influenza epidemics, and holidays to estimate odds ratios (OR) and 95% confidence intervals (CI) for ED attendances on event days compared with non-event days for all non-trauma ED attendances and selected cardiorespiratory conditions. RESULTS: The 46 validated fire smoke event days during the study period were associated with same day increases in ED attendances for all non-trauma conditions (1.03, 95% CI 1.02, 1.04), respiratory conditions (OR 1.07, 95% CI 1.04, 1.10), asthma (OR 1.23, 95% CI 1.15, 1.30), and chronic obstructive pulmonary disease (OR 1.12, 95% CI 1.02, 1.24). Positive associations persisted for one to three days after the event. Ischaemic heart disease ED attendances were increased at a lag of two days (OR 1.07, 95% CI 1.01, 1.15) while arrhythmias had an inverse association at a lag of two days (OR 0.91, 95% CI 0.83, 0.99). In age-specific analyses, no associations present in children less than 15 years of age for any outcome, although a non-significant trend towards a positive association was seen with childhood asthma. A further association between smoke event and heart failure attendances was present for the 15-65 year age group, but not older adults at a lag of two days (OR 1.37 95% CI 1.05, 1.78). CONCLUSION: Smoke events were associated with an immediate increase in presentations for respiratory conditions and a lagged increase in attendances for ischaemic heart disease and heart failure. Respiratory impacts were either absent or considerably attenuated in those <15 years. Similar to previous studies we found inconsistent associations between fire smoke and cardiovascular diseases. Better characterisation of the spectrum of population health risks is needed to guide public heath responses to severe smoke events as this exposure becomes increasingly common with global climate change.

Impact of a pedometer program on nurses working in a health-promoting hospital.

The aim of this research was to describe the impact of a pedometer-based activity program on a subset of nurses in a university-affiliated, multisite health care center in Canada. This study used a longitudinal design with preintervention-postintervention (8 weeks) and follow-up (6 months). At baseline, 60 nurses participated; 51 (85%) remained for the postprogram assessment and 33 (55%) also completed the follow-up questionnaire. Data were collected through self-administered questionnaires (weight, height, fatigue, insomnia, stress and step data) and blood tests (total cholesterol and low-density lipoprotein and high-density lipoprotein cholesterol). At postprogram, participants reported 12 thinsp;912 steps on average per day. At follow-up, 79% of participants indicated that they maintained their physical activity after the pedometer program. A significant decrease in insomnia was evident in postprogram scores compared with baseline scores, and this decrease was maintained at follow-up. A significant decrease in minutes spent sitting per week was also observed from baseline to postprogram and also maintained at follow-up. Participants' stress and low-density lipoprotein cholesterol levels decreased from baseline to postprogram (marginally significant). Finally, their weight decreased from baseline to follow-up (marginally significant). The pedometer program generated some positive outcomes for nurses after 6 months.

Determinants and benefits of physical activity maintenance in hospital employees.

This study investigated whether the positive behavioral and anthropometric outcomes of a pedometer-based physical activity 8-week challenge were maintained 6 months after the end of the program. It further investigated the motivational profile of those who maintained their physical activity levels in the months following the end of the program and of those who did not. Hospital employees from a university-affiliated multisite health care center in Canada participated using a questionnaire. Of the 235 participants who completed the 8-week challenge, 157 questionnaires were returned 6 months later. Paired-samples t tests were conducted between the baseline and follow-up scores as well as between the postprogram and follow-up scores to detect significant differences between the measurement points. This study shows that the pedometer-based physical activity helped hospital employees maintain a high level of physical activity as well as maintain a healthy body mass index after 6 months. The results demonstrated that during maintenance the high physical activity group obtained higher scores for identified regulation and intrinsic regulation compared with the other groups. The results of the study revealed that identified and intrinsic regulations are important contributors to maintaining physical activity among hospital employees.

Formoterol, a long-acting ß2 adrenergic agonist, improves cognitive function and promotes dendritic complexity in a mouse model of Down syndrome.

BACKGROUND: Down syndrome is associated with significant failure in cognitive function. Our previous investigation revealed age-dependent degeneration of locus coeruleus, a major player in contextual learning, in the Ts65Dn mouse model of Down syndrome. We studied whether drugs already available for use in humans can be used to improve cognitive function in these mice. METHODS: We studied the status of ß adrenergic signaling in the dentate gyrus of the Ts65Dn mouse model of Down syndrome. Furthermore, we used fear conditioning to study learning and memory in these mice. Postmortem analyses included the analysis of synaptic density, dendritic arborization, and neurogenesis. RESULTS: We found significant atrophy of dentate gyrus and failure of ß adrenergic signaling in the hippocampus of Ts65Dn mice. Our behavioral analyses revealed that formoterol, a long-acting ß2 adrenergic receptor agonist, caused significant improvement in the cognitive function in Ts65Dn mice. Postmortem analyses revealed that the use of formoterol was associated with a significant improvement in the synaptic density and increased complexity of newly born dentate granule neurons in the hippocampus of Ts65Dn mice. CONCLUSIONS: Our data suggest that targeting ß2 adrenergic receptors is an effective strategy for restoring synaptic plasticity and cognitive function in these mice. Considering its widespread use in humans and positive effects on cognition in Ts65Dn mice, formoterol or similar ß2 adrenergic receptor agonists with ability to cross the blood brain barrier might be attractive candidates for clinical trials to improve cognitive function in individuals with Down syndrome.

Air pollution from bushfires and their association with hospital admissions in Sydney, Newcastle and Wollongong, Australia 1994-2007.

OBJECTIVE: We examined the association between validated bushfire smoke pollution events and hospital admissions in three eastern Australian cities from 1994 to 2007. METHODS: Smoke events were defined as days on which bushfire smoke caused the 24-hour citywide average concentration of airborne particles to exceed the 99(th) percentile of the daily distribution for the study period. We used a time-stratified case-crossover design to assess the association between smoke events and hospital admissions. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for cardiovascular and respiratory conditions on event days compared with non-event days. Models were adjusted for daily meteorology, influenza epidemics and holidays. RESULTS: Smoke events occurred on 58 days in Sydney (population: 3,862,000), 33 days in Wollongong (population: 406,000) and 50 days in Newcastle (population: 278,000). In Sydney, events were associated with a 6% (OR=1.06, 95%CI=1.02-1.09) same day increase in respiratory hospital admissions. Same day chronic obstructive pulmonary disease admissions increased 13% (OR=1.13, 95%CI=1.05-1.22) and asthma admissions by 12% (OR=1.12, 95%CI=1.05-1.19). Events were also associated with increased admissions for respiratory conditions in Newcastle and Wollongong. CONCLUSIONS: Smoke events were associated with increased hospital admissions for respiratory but not cardiovascular conditions. Large populations are needed to assess the impacts of brief exposures. Implications : Public health impacts from bushfire pollution events are likely to increase in association with a warming climate and more frequent severe fire weather.