Payload crew interface design criteria and techniques. Task 1: Inflight operations and training for payloads

Guidelines are developed for use in control and display panel design for payload operations performed on the aft flight deck of the orbiter. Preliminary payload procedures are defined. Crew operational concepts are developed. Payloads selected for operational simulations were the shuttle UV optical telescope (SUOT), the deep sky UV survey telescope (DUST), and the shuttle UV stellar spectrograph (SUSS). The advanced technology laboratory payload consisting of 11 experiments was selected for a detailed evaluation because of the availability of operational data and its operational complexity

Examination of the effect of acute levodopa administration on the loudness dependence of auditory evoked potentials (LDAEP) in humans

Rationale: The loudness dependence of the auditory evoked potential (LDAEP) is considered a noninvasive in vivo marker of central serotonergic functioning in humans. Nevertheless, results of genetic association studies point towards a modulation of this biomarker by dopaminergic neurotransmission. Objective: We examined the effect of dopaminergic modulation on the LDAEP using L-3,4-dihydroxyphenylalanine (levodopa)/benserazide (Madopar®) as a challenge agent in healthy volunteers. Methods: A double-blind placebo-controlled challenge design was chosen. Forty-two healthy participants (21 females and 21 males) underwent two LDAEP measurements, following a baseline LDAEP measurement either placebo or levodopa (levodopa 200mg/benserazide 50mg) were given orally. Changes in the amplitude and dipole source activity of the N1/P2 intensities (60, 70, 80, 90, and 100dB) were analyzed. Results: The participants of neither the levodopa nor the placebo group showed any significant LDAEP alterations compared to the baseline measurement. The test-retest reliability (Cronbachs Alpha) between baseline and intervention was 0.966 in the verum group and 0.759 in the placebo group, respectively. Conclusions: The administration of levodopa showed no effect on the LDAEP. These findings are in line with other trials using dopamine receptor agonist

Team functioning across different tumour types: Insights from a Swiss cancer center using qualitative and quantitative methods.

BACKGROUND: Multidisciplinary care is pivotal in cancer centres and the interaction of all cancer disease specialists in decision making processes is state-of-the-art. AIM: To describe differences of MDTMs by tumour type. METHODS: Twelve multidisciplinary team meetings (MDTMs) with participation of different cancer disease specialists at a tertiary hospital were assessed by an exploratory sequential mixed method approach with interviews, observations and a survey to address the following five topics: organisational structure and supporting technology; leadership; teamwork; decision-making, perceived value and motivation. Thirteen persons with different tumour specialities and levels of seniority were interviewed. The 12 MDTMs were observed twice by uninvolved persons and evaluated by the participating physicians with a survey. RESULTS: There were no systematic differences between MDTMs for different tumour types with the exception of the non-disease specific type MDTM, which was the only one for which the organisational structure was not driven by an electronic tool. However, several factors could be identified that generally influenced the functioning of the MDTMs. In particular, the quality of decision-making was highly dependent on the availability of case-based information and the presence of relevant cancer disease specialists. Leadership and teamwork were rated as important and were comparable across the MDTM. Team participants' motivation and perceived value of MDTMs was high across all meetings. CONCLUSION: MDTM at a single institution did not demonstrate disease specific characteristics. An effective MDTM, irrespective of the tumour type, can be successfully structured by technical means and a chairperson coordinating the interaction of cancer disease specialists to improve the decision-making process

Viability Conditions for a Compartmentalized Protometabolic System: A Semi-Empirical Approach

In this work we attempt to find out the extent to which realistic prebiotic compartments, such as fatty acid vesicles, would constrain the chemical network dynamics that could have sustained a minimal form of metabolism. We combine experimental and simulation results to establish the conditions under which a reaction network with a catalytically closed organization (more specifically, an ()-system) would overcome the potential problem of self-suffocation that arises from the limited accessibility of nutrients to its internal reaction domain. The relationship between the permeability of the membrane, the lifetime of the key catalysts and their efficiency (reaction rate enhancement) turns out to be critical. In particular, we show how permeability values constrain the characteristic time scale of the bounded protometabolic processes. From this concrete and illustrative example we finally extend the discussion to a wider evolutionary context

Global-scale climate impact functions: the relationship between climate forcing and impact

Although there is a strong policy interest in the impacts of climate change corresponding to different degrees of climate change, there is so far little consistent empirical evidence of the relationship between climate forcing and impact. This is because the vast majority of impact assessments use emissions-based scenarios with associated socio-economic assumptions, and it is not feasible to infer impacts at other temperature changes by interpolation. This paper presents an assessment of the global-scale impacts of climate change in 2050 corresponding to defined increases in global mean temperature, using spatially-explicit impacts models representing impacts in the water resources, river flooding, coastal, agriculture, ecosystem and built environment sectors. Pattern-scaling is used to construct climate scenarios associated with specific changes in global mean surface temperature, and a relationship between temperature and sea level used to construct sea level rise scenarios. Climate scenarios are constructed from 21 climate models to give an indication of the uncertainty between forcing and response. The analysis shows that there is considerable uncertainty in the impacts associated with a given increase in global mean temperature, due largely to uncertainty in the projected regional change in precipitation. This has important policy implications. There is evidence for some sectors of a non-linear relationship between global mean temperature change and impact, due to the changing relative importance of temperature and precipitation change. In the socio-economic sectors considered here, the relationships are reasonably consistent between socio-economic scenarios if impacts are expressed in proportional terms, but there can be large differences in absolute terms. There are a number of caveats with the approach, including the use of pattern-scaling to construct scenarios, the use of one impacts model per sector, and the sensitivity of the shape of the relationships between forcing and response to the definition of the impact indicator

Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries

RATIONALE: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. OBJECTIVE: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. METHODS AND RESULTS: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10-10, OR=0.69 per C allele). SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10-5). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A, which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart. CONCLUSIONS: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A. Genomic and functional data support a causal role of WNT5A at the locus