Space Solar Power Aids Space Settlement

The Grand Prize for the 2011 NASA Ames Space Settlement Contest went to a team of 7 students (11-12 grades) from Punjab, India for creating the Hyperion Space Settlement. This year the contest received 355 submissions from 1078 students sponsored by 114 teachers. Entries came from 14 countries: Australia, Bulgaria, Canada, China, India, Ireland, Japan, Pakistan, Romania, Singapore, Turkey, Ukraine, United Arab Emirates, and the United States. The prize was conferred on the students during the International Space Development Conference 2011 (ISDC 2011) held in Huntsville, Alabama, USA. Advisors: The teachers of Spring Dale Senior School in Amritsar, India. Stephen Buchanan of Ohio University served as a Space Journal Liaiso

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Effectiveness of brief cognitive-behavioral therapy for schizophrenia delivered by mental health nurses: relapse and recovery at 24 months

Background: evidence of the efficacy of cognitive-behavioral therapy (CBT) for schizophrenia is increasing. There are very few studies of effectiveness, especially in the medium term.Objective: to evaluate the durability of the effect of brief CBT provided by mental health nurses in community-based patients with schizophrenia (diagnosed according to ICD-10 research criteria), using time to relapse as primary outcome and days hospitalized and occupational recovery as secondary outcomes at 24-month follow-up.Method: a 2:1 randomized trial, conducted from 1999 to 2003, was performed to evaluate the effects of brief CBT delivered by mental health nurses trained over 10 days with ongoing supervision compared to treatment as usual (TAU), with measurement performed by raters blind to treatment allocation.Results: 205 (79.8%) of 257 CBT patients and 125 (75.8%) of 165 TAU patients could be followed up at 24 months. Of 205 patients in the CBT group, 64 (31.2%) relapsed, versus 57 (45.6%) of 125 patients in the TAU group (p = .02). Patients rehospitalized from the CBT group spent a total of 6710 days in hospital (mean=32.7 days), while those from the TAU group were inpatients for 6114 days (mean = 48.9 days) (p &lt;.05). Twenty-one (10.2%) of 205 patients made an occupational recovery in the CBT group, and 17 (13.6%) of 125, in the TAU group (chi2 test not significant). Mean time to relapse was 356.8 days (SD = 241.9 days) for the CBT group and 296.1 days (SD = 215.7 days) for the TAU group (OR =1.592, 95% CI = 1.038 to 2.441, p =.033).Conclusion: beneficial effects on relapse and rehospitalization following brief CBT delivered by mental health nurses in community-based patients with schizophrenia are maintained at 24-month follow-up. Occupational recovery is not improved by brief CBT.<br/

Hexokinase 2 is dispensable for T cell-dependent immunity

Abstract Background T cells and cancer cells utilize glycolysis for proliferation. The hexokinase (1–4) family of enzymes catalyze the first step of glycolysis. Hexokinase 2 (HK2) is one of the most highly upregulated metabolic enzymes in both cancer and activated T cells. HK2 is required for the development and/or growth of cancer in several cancer models, but the necessity of HK2 in T cells is not fully understood. The clinical applicability of HK2 inhibition in cancer may be significantly limited by any potential negative effects of HK2 inhibition on T cells. Therefore, we investigated the necessity of HK2 for T cell function. In order to identify additional therapeutic cancer targets, we performed RNA-seq to compare in vivo proliferating T cells to T cell leukemia. Methods HK2 was genetically ablated in mouse T cells using a floxed Hk2 allele crossed to CD4-Cre. CD4+ and CD8+ cells from mice were characterized metabolically and tested in vitro. T cell function in vivo was tested in a mouse model of colitis, Th2-mediated lung inflammation, and viral infection. Treg function was tested by crossing Hk2-floxed mice to FoxP3-Cre mice. Hematopoietic function was tested by deleting HK2 from bone marrow with Vav1-iCre. RNA-seq was used to compare T cells proliferating in response to virus with primary T-ALL leukemia induced with mutant Notch1 expression. Results We unexpectedly report that HK2 is largely dispensable for in vitro T cell activation, proliferation, and differentiation. Loss of HK2 does not impair in vivo viral immunity and causes only a small impairment in the development of pathological inflammation. HK2 is not required for Treg function or hematopoiesis in vivo. One hundred sixty-seven metabolic genes were identified as being differentially expressed between T cells and leukemia. Conclusions HK2 is a highly upregulated enzyme in cancer and in T cells. The requirement for HK2 in various cancer models has been described previously. Our finding that T cells are able to withstand the loss of HK2 indicates that HK2 may be a promising candidate for cancer therapy. Furthermore, we identify several other potential metabolic targets in T-ALL leukemia that could spare T cell function

Laboratory Factors Associated with Symptomatic Hemorrhagic Conversion of Acute Stroke after Systemic Thrombolysis

BACKGROUND: Laboratory factors associated with hemorrhagic conversion (HC) after Intravenous thrombolysis with rtPA (IVT) for Acute Ischemic Stroke (AIS) remain nebulous despite advances in our knowledge of AIS. This study aimed to investigate the laboratory factors predisposing to HC in AIS patients receiving IVT. METHODS: We retrospectively reviewed the medical records of patients who received IV tPA for AIS at our comprehensive stroke center over a 9.6-year period. Besides age, gender, NIHSS, history of diabetes mellitus (DM), history of atrial fibrillation (Afib), we gathered their laboratory data including International Normalized Ratio (INR), lipid panel, serum albumin, serum creatinine, hemoglobin A1c (HbA1c), and admission blood glucose. Post-thrombolysis brain imagings were reviewed to evaluate for symptomatic ICH (sICH). The mean values of above mentioned laboratory data were compared between the group with sICH and patients with no sICH. Univariate and multivariate logistic regression were performed to evaluate the association of the laboratory findings with presence of sICH. sICH was defined as ICH causing an increase in NIHSS ≥4. RESULTS: Of the 794 subjects in this study 51 (6.4%) had sICH. In the univariate analysis, patients who developed sICH had significantly higher NIHSS on admission (14.2 ± 5.4 vs 11.2 ± 6.5, p \u3c .001), LDL-cholesterol (113.3 mg/dl ±36.9 vs. 101.8 mg/dl ± 38.2, p = .032), HbA1c (6.9% ± 2.3 vs. 6.1 ± 1.3, p = .003) and lower levels of Albumin (3.5 g/dl ±0.4 vs. 3.9 g/dl ± 0.5, p \u3c .001). Furthermore, a higher prevalence of history of DM (45% vs. 21.6%, p = .020) and Afib (25.4% vs. 10.4%, p = .028) was found in subjects who developed sICH. There were no significant group differences regarding age, sex, total cholesterol, blood glucose on admission, serum creatinine or INR levels (p \u3e .05). After adjusting for multiple covariates, lower Albumin level and and higher HbA1c were significantly associated with an increased risk for sICH development (p \u3c .05). Chances of sICH increased by 33% for every 1 g/dl below a normal albumin level of 4.0 g/dl (p \u3c .05). CONCLUSION: Lower endogenous albumin level and higher HbA1c have shown to predispose to a higher risk of sICH after IVT for AIS and might be good predictors of sICH post IVT

Effect of endobronchial coils vs usual care on exercise tolerance in patients with severe emphysema the RENEW randomized clinical trial

Importance Preliminary clinical trials have demonstrated that endobronchial coils compress emphysematous lung tissue and may improve lung function, exercise tolerance, and symptoms in patients with emphysema and severe lung hyperinflation. Objective To determine the effectiveness and safety of endobronchial coil treatment. Design, Setting, and Participants Randomized clinical trial conducted among 315 patients with emphysema and severe air trapping recruited from 21 North American and 5 European sites from December 2012 through November 2015. Interventions Participants were randomly assigned to continue usual care alone (guideline based, including pulmonary rehabilitation and bronchodilators; n = 157) vs usual care plus bilateral coil treatment (n = 158) involving 2 sequential procedures 4 months apart in which 10 to 14 coils were bronchoscopically placed in a single lobe of each lung. Main Outcomes and Measures The primary effectiveness outcome was difference in absolute change in 6-minute-walk distance between baseline and 12 months (minimal clinically important difference [MCID], 25 m). Secondary end points included the difference between groups in 6-minute walk distance responder rate, absolute change in quality of life using the St George’s Respiratory Questionnaire (MCID, 4) and change in forced expiratory volume in the first second (FEV1; MCID, 10%). The primary safety analysis compared the proportion of participants experiencing at least 1 of 7 prespecified major complications. Results Among 315 participants (mean age, 64 years; 52% women), 90% completed the 12-month follow-up. Median change in 6-minute walk distance at 12 months was 10.3 m with coil treatment vs −7.6 m with usual care, with a between-group difference of 14.6 m (Hodges-Lehmann 97.5% CI, 0.4 m to ∞; 1-sided P = .02). Improvement of at least 25 m occurred in 40.0% of patients in the coil group vs 26.9% with usual care (odds ratio, 1.8 [97.5% CI, 1.1 to ∞]; unadjusted between-group difference, 11.8% [97.5% CI, 1.0% to ∞]; 1-sided P = .01). The between-group difference in median change in FEV1 was 7.0% (97.5% CI, 3.4% to ∞; 1-sided P < .001), and the between-group St George’s Respiratory Questionnaire score improved −8.9 points (97.5% CI, −∞ to −6.3 points; 1-sided P < .001), each favoring the coil group. Major complications (including pneumonia requiring hospitalization and other potentially life-threatening or fatal events) occurred in 34.8% of coil participants vs 19.1% of usual care (P = .002). Other serious adverse events including pneumonia (20% coil vs 4.5% usual care) and pneumothorax (9.7% vs 0.6%, respectively) occurred more frequently in the coil group. Conclusions and Relevance Among patients with emphysema and severe hyperinflation treated for 12 months, the use of endobronchial coils compared with usual care resulted in an improvement in median exercise tolerance that was modest and of uncertain clinical importance, with a higher likelihood of major complications. Further follow-up is needed to assess long-term effects on health outcomes. Trial Registration clinicaltrials.gov Identifier: NCT0160849

The IBV Valve trial: a multicenter, randomized, double-blind trial of endobronchial therapy for severe emphysema.

BACKGROUND: Lung volume reduction surgery improves quality of life, exercise capacity, and survival in selected patients but is accompanied by significant morbidity. Bronchoscopic approaches may provide similar benefits with less morbidity. METHODS: In a randomized, sham procedure controlled, double-blind trial, 277 subjects were enrolled at 36 centers. Patients had emphysema, airflow obstruction, hyperinflation, and severe dyspnea. The primary effectiveness measure was a significant improvement in disease-related quality of life (St. George\u27s Respiratory Questionnaire) and changes in lobar lung volumes. The primary safety measure was a comparison of serious adverse events. RESULTS: There were 6/121 (5.0%) responders in the treatment group at 6 months, significantly \u3e1/134 (0.7%) in the control group [Bayesian credible intervals (BCI), 0.05%, 9.21%]. Lobar volume changes were significantly different with an average decrease in the treated lobes of -224 mL compared with -17 mL for the control group (BCI, -272, -143). The proportion of responders in St. George\u27s Respiratory Questionnaire was not greater in the treatment group. There were significantly more subjects with a serious adverse event in the treatment group (n=20 or 14.1%) compared with the control group (n=5 or 3.7%) (BCI, 4.0, 17.1), but most were neither procedure nor device related. CONCLUSIONS: This trial had technical and statistical success but partial-bilateral endobronchial valve occlusion did not obtain clinically meaningful results. Safety results were acceptable and compare favorably to lung volume reduction surgery and other bronchial valve studies. Further studies need to focus on improved patient selection and a different treatment algorithm. TRIAL REGISTRY: ClinicalTrials.gov NCT00475007