Integration Process for the Habitat Demonstration Unit

The Habitat Demonstration Unit (HDU) is an experimental exploration habitat technology and architecture test platform designed for analog demonstration activities. The HDU previously served as a test bed for testing technologies and sub-systems in a terrestrial surface environment. in 2010 in the Pressurized Excursion Module (PEM) configuration. Due to the amount of work involved to make the HDU project successful, the HDU project has required a team to integrate a variety of contributions from NASA centers and outside collaborators The size of the team and number of systems involved With the HDU makes Integration a complicated process. However, because the HDU shell manufacturing is complete, the team has a head start on FY--11 integration activities and can focus on integrating upgrades to existing systems as well as integrating new additions. To complete the development of the FY-11 HDU from conception to rollout for operations in July 2011, a cohesive integration strategy has been developed to integrate the various systems of HDU and the payloads. The highlighted HDU work for FY-11 will focus on performing upgrades to the PEM configuration, adding the X-Hab as a second level, adding a new porch providing the astronauts a larger work area outside the HDU for EVA preparations, and adding a Hygiene module. Together these upgrades result in a prototype configuration of the Deep Space Habitat (DSH), an element under evaluation by NASA's Human Exploration Framework Team (HEFT) Scheduled activates include early fit-checks and the utilization of a Habitat avionics test bed prior to installation into HDU. A coordinated effort to utilize modeling and simulation systems has aided in design and integration concept development. Modeling tools have been effective in hardware systems layout, cable routing, sub-system interface length estimation and human factors analysis. Decision processes on integration and use of all new subsystems will be defined early in the project to maximize the efficiency of both integration and field operations. In addition a series of tailored design reviews are utilized to quickly define the systems and their integration into the DSH configuration. These processes are necessary to ensure activities, such as partially reversing integration of the X-Hab second story of the HDU and deploying and stowing the new work porch for transportation to the JSC Rock Yard and to the Arizona Black Point Lava Flow Site are performed with minimal or no complications. In addition, incremental test operations leading up to an Integrated systems test allows for an orderly systems test program. For FY-11 activities, the HDU DSH will act as a laboratory utilizing a new X-Hab inflatable second floor with crew habitation features. In addition to the day to day operations involving maintenance of the HDU and exploring the surrounding terrain, testing and optimizing the use of the new X-Hab, work porch, Hygiene Module, and other sub-system enhancements will be the focus of the FY-11 test objectives. The HDU team requires a successful integration strategy using a variety of tools and approaches to prepare the DSH for these test objectives. In a challenging environment where the prototyping influences the system design, as well as Vice versa, results of the HDU DSH field tests will influence future designs of habitat systems

Sr-Nd isotope geochemistry of the early Precambrian sub-alkaline mafic igneous rocks from the southern Bastar craton, Central India

Sr–Nd isotope data are reported for the early Precambrian sub-alkaline mafic igneous rocks of the southern Bastar craton, central India. These mafic rocks are mostly dykes but there are a few volcanic exposures. Field relationships together with the petrological and geochemical characteristics of these mafic dykes divide them into two groups; Meso-Neoarchaean sub-alkaline mafic dykes (BD1) and Paleoproterozoic (1.88 Ga) sub-alkaline mafic dykes (BD2). The mafic volcanics are Neoarchaean in age and have very close geochemical relationships with the BD1 type. The two groups have distinctly different concentrations of high-field strength (HFSE) and rare earth elements (REE). The BD2 dykes have higher concentrations of HFSE and REE than the BD1 dykes and associated volcanics and both groups have very distinctive petrogenetic histories. These rocks display a limited range of initial 143Nd/144Nd but a wide range of apparent initial 87Sr/86Sr. Initial 143Nd/144Nd values in the BD1 dykes and associated volcanics vary between 0.509149 and 0.509466 and in the BD2 dykes the variation is between 0.510303 and 0.510511. All samples have positive εNd values the BD1 dykes and associated volcanics have εNd values between +0.3 and +6.5 and the BD2 dykes between +1.9 to +6.0. Trace element and Nd isotope data do not suggest severe crustal contamination during the emplacement of the studied rocks. The positive εNd values suggest their derivation from a depleted mantle source. Overlapping positive εNd values suggest that a similar mantle source tapped by variable melt fractions at different times was responsible for the genesis of BD1 (and associated volcanics) and BD2 mafic dykes. The Rb–Sr system is susceptible to alteration and resetting during post-magmatic alteration and metamorphism. Many of the samples studied have anomalous apparent initial 87Sr/86Sr suggesting post-magmatic changes of the Rb–Sr system which severely restricts the use of Rb–Sr for petrogenetic interpretation

Metabolite profiles of medulloblastoma for rapid and non-invasive detection of molecular disease groups

\ua9 2024 The AuthorsBackground: The malignant childhood brain tumour, medulloblastoma, is classified clinically into molecular groups which guide therapy. DNA-methylation profiling is the current classification ‘gold-standard’, typically delivered 3–4 weeks post-surgery. Pre-surgery non-invasive diagnostics thus offer significant potential to improve early diagnosis and clinical management. Here, we determine tumour metabolite profiles of the four medulloblastoma groups, assess their diagnostic utility using tumour tissue and potential for non-invasive diagnosis using in vivo magnetic resonance spectroscopy (MRS). Methods: Metabolite profiles were acquired by high-resolution magic-angle spinning NMR spectroscopy (MAS) from 86 medulloblastomas (from 59 male and 27 female patients), previously classified by DNA-methylation array (WNT (n = 9), SHH (n = 22), Group3 (n = 21), Group4 (n = 34)); RNA-seq data was available for sixty. Unsupervised class-discovery was performed and a support vector machine (SVM) constructed to assess diagnostic performance. The SVM classifier was adapted to use only metabolites (n = 10) routinely quantified from in vivo MRS data, and re-tested. Glutamate was assessed as a predictor of overall survival. Findings: Group-specific metabolite profiles were identified; tumours clustered with good concordance to their reference molecular group (93%). GABA was only detected in WNT, taurine was low in SHH and lipids were high in Group3. The tissue-based metabolite SVM classifier had a cross-validated accuracy of 89% (100% for WNT) and, adapted to use metabolites routinely quantified in vivo, gave a combined classification accuracy of 90% for SHH, Group3 and Group4. Glutamate predicted survival after incorporating known risk-factors (HR = 3.39, 95% CI 1.4–8.1, p = 0.025). Interpretation: Tissue metabolite profiles characterise medulloblastoma molecular groups. Their combination with machine learning can aid rapid diagnosis from tissue and potentially in vivo. Specific metabolites provide important information; GABA identifying WNT and glutamate conferring poor prognosis. Funding: Children with Cancer UK, Cancer Research UK, Children\u27s Cancer North and a Newcastle University PhD studentship

The northern hemisphere circumglobal teleconnection in a seasonal forecast model and its relationship to European summer forecast skill

Forecasting seasonal variations in European summer weather represents a considerable challenge. Here, we assess the performance of a seasonal forecasting model at representing a major mode of northern hemisphere summer climate variability, the circumglobal teleconnection (CGT), and the implications of errors in its representation on seasonal forecasts for the European summer (June, July, August). Using seasonal hindcasts initialised at the start of May, we find that the model skill for forecasting the interannual variability of 500 hPa geopotential height is poor, particularly over Europe and several other “centres of action” of the CGT. The model also has a weaker CGT pattern than is observed, particularly in August, when the observed CGT wavetrain is strongest. We investigate several potential causes of this poor skill. First, model variance in geopotential height in west-central Asia (an important region for the maintenance of the CGT) is lower than observed in July and August, associated with a poor representation of the link between this region and Indian monsoon precipitation. Second, analysis of the Rossby wave source shows that the source associated with monsoon heating is both too strong and displaced to the northeast in the model. This is related to errors in monsoon precipitation over the Bay of Bengal and Arabian Sea, where the model has more precipitation than is observed. Third, the model jet is systematically shifted northwards by several degrees latitude over large parts of the northern hemisphere, which may affect the propagation characteristics of Rossby waves in the model

Predicting the outcome of grade II glioma treated with temozolomide using proton magnetic resonance spectroscopy

International audienceBACKGROUND: This study was designed to evaluate proton magnetic resonance spectroscopy ((1)H-MRS) for monitoring the WHO grade II glioma (low-grade glioma (LGG)) treated with temozolomide (TMZ).METHODS: This prospective study included adult patients with progressive LGG that was confirmed by magnetic resonance imaging (MRI). Temozolomide was administered at every 28 days. Response to TMZ was evaluated by monthly MRI examinations that included MRI with volumetric calculations and (1)H-MRS for assessing Cho/Cr and Cho/NAA ratios. Univariate, multivariate and receiver-operating characteristic statistical analyses were performed on the results.RESULTS: A total of 21 LGGs from 31 patients were included in the study, and followed for at least n=14 months during treatment. A total of 18 (86%) patients experienced a decrease in tumour volume with a greater decrease of metabolic ratios. Subsequently, five (28%) of these tumours resumed growth despite the continuation of TMZ administration with an earlier increase of metabolic ratios of 2 months. Three (14%) patients did not show any volume or metabolic change. The evolutions of the metabolic ratios, mean(Cho/Cr)(n) and mean(Cho/NAA)(n), were significantly correlated over time (Spearman ρ=+0.95) and followed a logarithmic regression (P>0.001). The evolutions over time of metabolic ratios, mean(Cho/Cr)(n) and mean(Cho/NAA)(n), were significantly correlated with the evolution of the mean relative decrease of tumour volume, mean(ΔV(n)/V(o)), according to a linear regression (P<0.001) in the 'response/no relapse' patient group, and with the evolution of the mean tumour volume (meanV(n)), according to an exponential regression (P<0.001) in the 'response/relapse' patient group. The mean relative decrease of metabolic ratio, mean(Δ(Cho/Cr)(n)/(Cho/Cr)(o)), at n=3 months was predictive of tumour response over the 14 months of follow-up. The mean relative change between metabolic ratios, mean((Cho/NAA)(n)-(Cho/Cr)(n))/(Cho/NAA)(n), at n=4 months was predictive of tumour relapse with a significant cutoff of 0.046, a sensitivity of 60% and a specificity of 100% (P=0.004).CONCLUSIONS: The (1)H-MRS profile changes more widely and rapidly than tumour volume during the response and relapse phases, and represents an early predictive factor of outcome over 14 months of follow-up. Thus, (1)H-MRS may be a promising, non-invasive tool for predicting and monitoring the clinical response to TMZ

Possible Race and Gender Divergence in Association of Genetic Variations with Plasma von Willebrand Factor: A Study of ARIC and 1000 Genome Cohorts

The synthesis, secretion and clearance of von Willebrand factor (VWF) are regulated by genetic variations in coding and promoter regions of the VWF gene. We have previously identified 19 single nucleotide polymorphisms (SNPs), primarily in introns that are associated with VWF antigen levels in subjects of European descent. In this study, we conducted race by gender analyses to compare the association of VWF SNPs with VWF antigen among 10,434 healthy Americans of European (EA) or African (AA) descent from the Atherosclerosis Risk in Communities (ARIC) study. Among 75 SNPs analyzed, 13 and 10 SNPs were associated with VWF antigen levels in EA male and EA female subjects, respectively. However, only one SNP (RS1063857) was significantly associated with VWF antigen in AA females and none was in AA males. Haplotype analysis of the ARIC samples and studying racial diversities in the VWF gene from the 1000 genomes database suggest a greater degree of variations in the VWF gene in AA subjects as compared to EA subjects. Together, these data suggest potential race and gender divergence in regulating VWF expression by genetic variations

Development and preliminary validation of Brace Questionnaire (BrQ): a new instrument for measuring quality of life of brace treated scoliotics

BACKGROUND: The quality of life among children with idiopathic scoliosis during their adolescence has been reported to be affected by the brace itself. However, a controversy exists whether brace treated scoliotics experience a poor quality of life, thus there is a need for the development of a brace-oriented instrument, as the now-existing questionnaires that are commonly used, such as the SRS -22, take into consideration the effects of both the conservative and the surgical treatment on quality of life of scoliotic children. The aim of the present study is to assess the validity and reliability of Brace Questionnaire (BrQ), a new instrument for measuring quality of life of scoliotic adolescents who are treated conservatively with a brace. MATERIAL-METHOD: Methodology of development involved literature review, patient and health care professionals' in-depth interviews and content validity analysis on patients. A validation study was performed on 28 brace treated scoliotic children aged between 9 and 18 years old. BrQ was assessed for the following psychometric properties: item convergent validity, floor and ceiling effects, internal consistency reliability, clinical validity and responsiveness to change. RESULTS: BrQ is self administrated and developmentally appropriate for ages 9 to 18 years old and is consisted of 34 Likert-scale items associated with eight domains: general health perception, physical functioning, emotional functioning, self esteem and aesthetics, vitality, school activity, bodily pain and social functioning of scoliotic children treated conservatively with a brace. The subscales of these eight dimensions can be combined to produce a total score. Higher scores mean a better quality of life. An item convergent validity ≥ 0.40 was satisfied by all items in the present study. A satisfactory internal consistency reliability for the BrQ was recorded (Cronbach's alpha coefficient was 0.82). There were no floor or ceiling effects. The correlation between BrQ overall scores and mild and moderate scoliosis was statistically significant (p < 0.001), revealing high clinical validity. An increase in effect sizes for the patient with improved scoliotic curves indicates that the BrQ is responsive to change in health status. CONCLUSION: BrQ is reliable, valid and responsive to change in adolescents with IS who are treated conservatively with a brace

Neoadjuvant or adjuvant therapy for resectable esophageal cancer: a systematic review and meta-analysis

BACKGROUND: Carcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. The large and growing number of patients affected, the high mortality rates, the worldwide geographic variation in practice, and the large body of good quality research warrants a systematic review with meta-analysis. METHODS: A systematic review and meta-analysis investigating the impact of neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer to inform evidence-based practice was produced. MEDLINE, CANCERLIT, Cochrane Library, EMBASE, and abstracts from the American Society of Clinical Oncology and the American Society for Therapeutic Radiology and Oncology were searched for trial reports. Included were randomized trials or meta-analyses of neoadjuvant or adjuvant treatments compared with surgery alone or other treatments in patients with resectable thoracic esophageal cancer. Outcomes of interest were survival, adverse effects, and quality of life. Either one- or three-year mortality data were pooled and reported as relative risk ratios. RESULTS: Thirty-four randomized controlled trials and six meta-analyses were obtained and grouped into 13 basic treatment approaches. Single randomized controlled trials detected no differences in mortality between treatments for the following comparisons: - Preoperative radiotherapy versus postoperative radiotherapy. - Preoperative and postoperative radiotherapy versus postoperative radiotherapy. Preoperative and postoperative radiotherapy was associated with a significantly higher mortality rate. - Postoperative chemotherapy versus postoperative radiotherapy. - Postoperative radiotherapy versus postoperative radiotherapy plus protein-bound polysaccharide versus chemoradiation versus chemoradiation plus protein-bound polysaccharide. Pooling one-year mortality detected no statistically significant differences in mortality between treatments for the following comparisons: - Preoperative radiotherapy compared with surgery alone (five randomized trials). - Postoperative radiotherapy compared with surgery alone (five randomized trials). - Preoperative chemotherapy versus surgery alone (six randomized trials). - Preoperative and postoperative chemotherapy versus surgery alone (two randomized trials). - Preoperative chemoradiation therapy versus surgery alone (six randomized trials). Single randomized controlled trials detected differences in mortality between treatments for the following comparison: - Preoperative hyperthermia and chemoradiotherapy versus preoperative chemoradiotherapy in favour of hyperthermia. Pooling three-year mortality detected no statistically significant difference in mortality between treatments for the following comparison: - Postoperative chemotherapy compared with surgery alone (two randomized trials). Pooling three-year mortality detected statistically significant differences between treatments for the following comparisons: - Preoperative chemoradiation therapy versus surgery alone (six randomized trials) in favour of preoperative chemoradiation with surgery. - Preoperative chemotherapy compared with preoperative radiotherapy (one randomized trial) in favour of preoperative radiotherapy. CONCLUSION: For adult patients with resectable thoracic esophageal cancer for whom surgery is considered appropriate, surgery alone (i.e., without neoadjuvant or adjuvant therapy) is recommended as the standard practice

Identifying causes of Western Pacific ITCZ drift in ECMWF System 4 hindcasts

The development of systematic biases in climate models used in operational seasonal forecasting adversely affects the quality of forecasts they produce. In this study, we examine the initial evolution of systematic biases in the ECMWF System 4 forecast model, and isolate aspects of the model simulations that lead to the development of these biases. We focus on the tendency of the simulated intertropical convergence zone in the western equatorial Pacific to drift northwards by between 0.5° and 3° of latitude depending on season. Comparing observations with both fully coupled atmosphere–ocean hindcasts and atmosphere-only hindcasts (driven by observed sea-surface temperatures), we show that the northward drift is caused by a cooling of the sea-surface temperature on the Equator. The cooling is associated with anomalous easterly wind stress and excessive evaporation during the first twenty days of hindcast, both of which occur whether air-sea interactions are permitted or not. The easterly wind bias develops immediately after initialisation throughout the lower troposphere; a westerly bias develops in the upper troposphere after about ten days of hindcast. At this point, the baroclinic structure of the wind bias suggests coupling with errors in convective heating, although the initial wind bias is barotropic in structure and appears to have an alternative origin