Ensuring Payload Safety in Missions with Special Partnerships

The National Aeronautics and Space Administration (NASA) Expendable Launch Vehicle (ELV) payload space flight missions involve cooperative work between NASA and partners including spacecraft (or payload) contractors, universities, nonprofit research centers, Agency payload organization, Range Safety organization, Agency launch service organizations, and launch vehicle contractors. The role of NASA's Safety and Mission Assurance (SMA) Directorate is typically fairly straightforward, but when a mission's partnerships become more complex, to realize cost and science benefits (e.g., multi-agency payload(s) or cooperative international missions), the task of ensuring payload safety becomes much more challenging. This paper discusses lessons learned from NASA safety professionals working multiple-agency missions and offers suggestions to help fellow safety professionals working multiple-agency missions

Determining Effective Methadone Doses for Individual Opioid-Dependent Patients

BACKGROUND: Randomized clinical trials of methadone maintenance have found that on average high daily doses are more effective for reducing heroin use, and clinical practice guidelines recommend 60 mg/d as a minimum dosage. Nevertheless, many clinicians report that some patients can be stably maintained on lower methadone dosages to optimal effect, and clinic dosing practices vary substantially. Studies of individual responses to methadone treatment may be more easily translated into clinical practice. METHODS AND FINDINGS: A volunteer sample of 222 opioid-dependent US veterans initiating methadone treatment was prospectively observed over the year after treatment entry. In the 168 who achieved at least 1 mo of heroin abstinence, methadone dosages on which patients maintained heroin-free urine samples ranged from 1.5 mg to 191.2 mg (median = 69 mg). Among patients who achieved heroin abstinence, higher methadone dosages were predicted by having a diagnosis of posttraumatic stress disorder or depression, having a greater number of previous opioid detoxifications, living in a region with lower average heroin purity, attending a clinic where counselors discourage dosage reductions, and staying in treatment longer. These factors predicted 42% of the variance in dosage associated with heroin abstinence. CONCLUSIONS: Effective and ineffective methadone dosages overlap substantially. Dosing guidelines should focus more heavily on appropriate processes of dosage determination rather than solely specifying recommended dosages. To optimize therapy, methadone dosages must be titrated until heroin abstinence is achieved

General Anesthetics Predicted to Block the GLIC Pore with Micromolar Affinity

Although general anesthetics are known to modulate the activity of ligand-gated ion channels in the Cys-loop superfamily, there is at present neither consensus on the underlying mechanisms, nor predictive models of this modulation. Viable models need to offer quantitative assessment of the relative importance of several identified anesthetic binding sites. However, to date, precise affinity data for individual sites has been challenging to obtain by biophysical means. Here, the likely role of pore block inhibition by the general anesthetics isoflurane and propofol of the prokaryotic pentameric channel GLIC is investigated by molecular simulations. Microscopic affinities are calculated for both single and double occupancy binding of isoflurane and propofol to the GLIC pore. Computations are carried out for an open-pore conformation in which the pore is restrained to crystallographic radius, and a closed-pore conformation that results from unrestrained molecular dynamics equilibration of the structure. The GLIC pore is predicted to be blocked at the micromolar concentrations for which inhibition by isofluorane and propofol is observed experimentally. Calculated affinities suggest that pore block by propofol occurs at signifcantly lower concentrations than those for which inhibition is observed: we argue that this discrepancy may result from binding of propofol to an allosteric site recently identified by X-ray crystallography, which may cause a competing gain-of-function effect. Affinities of isoflurane and propofol to the allosteric site are also calculated, and shown to be 3 mM for isoflurane and for propofol; both anesthetics have a lower affinity for the allosteric site than for the unoccupied pore

Lentiviral-Mediated Transgene Expression Can Potentiate Intestinal Mesenchymal-Epithelial Signaling

Mesenchymal-epithelial signaling is essential for the development of many organs and is often disrupted in disease. In this study, we demonstrate the use of lentiviral-mediated transgene delivery as an effective approach for ectopic transgene expression and an alternative to generation of transgenic animals. One benefit to this approach is that it can be used independently or in conjunction with established transgenic or knockout animals for studying modulation of mesenchymal-epithelial interactions. To display the power of this approach, we explored ectopic expression of a Wnt ligand in the mouse intestinal mesenchyme and demonstrate its functional influence on the adjacent epithelium. Our findings highlight the efficient use of lentiviral-mediated transgene expression for modulating mesenchymal-epithelial interactions in vivo

Strategies to facilitate integrated care for people with alcohol and other drug problems: a systematic review

Background: There is a growing body of research highlighting the potential benefits of integrated care as a way of addressing the needs of people with alcohol and other drug (AOD) problems, given the broad range of other issues clients often experience. However, there has been little academic attention on the strategies that treatment systems, agencies and clinicians could implement to facilitate integrated care. Methods: We synthesised the existing evidence on strategies to improve integrated care in an AOD treatment context by conducting a systematic review of the literature. We searched major academic databases for peer-reviewed articles that evaluated strategies that contribute to integrated care in an AOD context between 1990 and 2014. Over 2600 articles were identified, of which 14 met the study inclusion criteria of reporting on an empirical study to evaluate the implementation of integrated care strategies. The types of strategies utilised in included articles were then synthesised. Results: We identified a number of interconnected strategies at the funding, organisational, service delivery and clinical levels. Ensuring that integrated care is included within service specifications of commissioning bodies and is adequately funded was found to be critical in effective integration. Cultivating positive inter-agency relationships underpinned and enabled the implementation of most strategies identified. Staff training in identifying and responding to needs beyond clinicians' primary area of expertise was considered important at a service level. However, some studies highlight the need to move beyond discrete training events and towards longer term coaching-type activities focussed on implementation and capacity building. Sharing of client information (subject to informed consent) was critical for most integrated care strategies. Case-management was found to be a particularly good approach to responding to the needs of clients with multiple and complex needs. At the clinical level, screening in areas beyond a clinician's primary area of practice was a common strategy for facilitating referral and integrated care, as was joint care planning. Conclusion: Despite considerable limitations and gaps in the literature in terms of the evaluation of integrated care strategies, particularly between AOD services, our review highlights several strategies that could be useful at multiple levels. Given the interconnectedness of integrated care strategies identified, implementation of multi-level strategies rather than single strategies is likely to be preferable

Alcohol Consumption and Dietary Patterns: The FinDrink Study

The aim of this population-based study was to investigate differences in dietary patterns in relation to the level of alcohol consumption among Finnish adults. This study was part of the FinDrink project, an epidemiologic study on alcohol use among Finnish population. It utilized data from the Kuopio Ischaemic Heart Disease Risk Factor Study. A total of 1720 subjects comprising of 816 men and 904 women aged 53–73 years were included in the study in 1998–2001. Food intake was collected via a 4-day food diary method. Self-reported alcohol consumption was assessed with quantity-frequency method based on the Nordic Alcohol Consumption Inventory. Weekly alcohol consumption was categorized into three groups: non-drinkers (<12 grams), moderate drinkers (12–167.9 grams for men, 12–83.9 grams for women) and heavy drinkers (≥168 grams for men, ≥84 grams for women). Data were analyzed for men and women separately using multiple linear regression models, adjusted for age, occupational status, marital status, smoking, body mass index and leisure time physical activity. In women, moderate/heavy drinkers had lower fibre intake and moderate drinkers had higher vitamin D intake than non-drinkers. Male heavy drinkers had lower fibre, retinol, calcium and iron intake, and moderate/heavy drinkers had higher vitamin D intake than non-drinkers. Fish intake was higher among women moderate drinkers and men moderate/heavy drinkers than non-drinkers. In men, moderate drinkers had lower fruit intake and heavy drinkers had lower milk intake than non-drinkers. Moderate drinkers had higher energy intake from total fats and monosaturated fatty acids than non-drinkers. In contrast, energy intake from carbohydrates was lower among moderate/heavy drinkers than non-drinkers. In conclusion, especially male heavy drinkers had less favorable nutritional intake than moderate and non-drinkers. Further studies on the relationship between alcohol consumption and dietary habits are needed to plan a comprehensive dietary intervention programs in future

Integration of priority population, health and nutrition interventions into health systems: systematic review

Objective of the study was to assess the effects of strategies to integrate targeted priority population, health and nutrition interventions into health systems on patient health outcomes and health system effectiveness and thus to compare integrated and non-integrated health programmes. Systematic review using Cochrane methodology of analysing randomised trials, controlled before-and-after and interrupted time series studies. We defined specific strategies to search PubMed, CENTRAL and the Cochrane Effective Practice and Organisation of Care Group register, considered studies published from January 1998 until September 2008, and tracked references and citations. Two reviewers independently agreed on eligibility, with an additional arbiter as needed, and extracted information on outcomes: primary (improved health, financial protection, and user satisfaction) and secondary (improved population coverage, access to health services, efficiency, and quality) using standardised, pre-piloted forms. Two reviewers in the final stage of selection jointly assessed quality of all selected studies using the GRADE criteria. Of 8,274 citations identified 12 studies met inclusion criteria. Four studies compared the benefits of Integrated Management of Childhood Illnesses in Tanzania and Bangladesh, showing improved care management and higher utilisation of health facilities at no additional cost. Eight studies focused on integrated delivery of mental health and substance abuse services in the United Kingdom and United States of America. Integrated service delivery resulted in better clinical outcomes and greater reduction of substance abuse in specific sub-groups of patients, with no significant difference found overall. Quality of care, patient satisfaction, and treatment engagement were higher in integrated delivery models. Targeted priority population health interventions we identified led to improved health outcomes, quality of care, patient satisfaction and access to care. Limited evidence with inconsistent findings across varied interventions in different settings means no general conclusions can be drawn on the benefits or disadvantages of integrated service delivery

Patient Complexity: More Than Comorbidity. The Vector Model of Complexity

BACKGROUND: The conceptualization of patient complexity is just beginning in clinical medicine. OBJECTIVES: This study aims (1) to propose a conceptual approach to complex patients; (2) to demonstrate how this approach promotes achieving congruence between patient and provider, a critical step in the development of maximally effective treatment plans; and (3) to examine availability of evidence to guide trade-off decisions and assess healthcare quality for complex patients. METHODS/RESULTS: The Vector Model of Complexity portrays interactions between biological, socioeconomic, cultural, environmental and behavioral forces as health determinants. These forces are not easily discerned but exert profound influences on processes and outcomes of care for chronic medical conditions. Achieving congruence between patient, physician, and healthcare system is essential for effective, patient-centered care; requires assessment of all axes of the Vector Model; and, frequently, requires trade-off decisions to develop a tailored treatment plan. Most evidence-based guidelines rarely provide guidance for trade-off decisions. Quality measures often exclude complex patients and are not designed explicitly to assess their overall healthcare. CONCLUSIONS/RECOMMENDATIONS: We urgently need to expand the evidence base to inform the care of complex patients of all kinds, especially for the clinical trade-off decisions that are central to tailoring care. We offer long- and short-term strategies to begin to incorporate complexity into quality measurement and performance profiling, guided by the Vector Model. Interdisciplinary research should lay the foundation for a deeper understanding of the multiple sources of patient complexity and their interactions, and how provision of healthcare should be harmonized with complexity to optimize health

Loess plateau storage of northeastern Tibetan plateau-derived Yellow River sediment

Marine accumulations of terrigenous sediment are widely assumed to accurately record climatic- and tectonic-controlled mountain denudation and play an important role in understanding late Cenozoic mountain uplift and global cooling. Underpinning this is the assumption that the majority of sediment eroded from hinterland orogenic belts is transported to and ultimately stored in marine basins with little lag between erosion and deposition. Here we use a detailed and multi-technique sedimentary provenance dataset from the Yellow River to show that substantial amounts of sediment eroded from Northeast Tibet and carried by the river’s upper reach are stored in the Chinese Loess Plateau and the western Mu Us desert. This finding revises our understanding of the origin of the Chinese Loess Plateau and provides a potential solution for mismatches between late Cenozoic terrestrial sedimentation and marine geochemistry records, as well as between global CO2 and erosion records