971 research outputs found
Rural land mobile radio market assessment and satellite and terrestrial system concepts
Market potential exists; the nature of the market in terms of service needs, usage characteristics, service requirements, and forecasting the demand to the year 2000; alternative system cncepts that show promise in addressing the identified needs, in a cost effective manner; and advanced technology requirements associated with these concepts are considered
Spacecraft design sensitivity for a disaster warning satellite system
A disaster warning satellite (DWS) is described for warning the general public of impending natural catastrophes. The concept is responsive to NOAA requirements and maximizes the use of ATS-6 technology. Upon completion of concept development, the study was extended to establishing the sensitivity of the DWSS spacecraft power, weight, and cost to variations in both warning and conventional communications functions. The results of this sensitivity analysis are presented
Prospects for the rapid detection of mealiness in apples by nondestructive NMR relaxometry
The potential of nuclear magnetic resonance (NMR) relaxometry for quantitative evaluation of apple mealiness has been investigated. The degree of "mealiness" was defined by several mechanical techniques, including penetration, compression and shear rupture as well as by the BRIX (soluble solids) and juiciness levels. These data were correlated with both magnetic resonance imaging (MRI) and NMR water proton transverse relaxation time measurements on a fruit-by-fruit basis. It was found that increasing mealiness caused a systematic increase in the transverse relaxation rate. The potential for rapid, on-line NMR/MRI detection of apple mealiness is discussed
Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I
Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism presenting with striatal lesions anatomically and symptomatically similar to Huntington disease. Affected children commonly suffer acute brain injury in the context of a catabolic state associated with nonspecific illness. The mechanisms underlying injury and age-dependent susceptibility have been unknown, and lack of a diagnostic marker heralding brain injury has impeded intervention efforts. Using a mouse model of GA-I, we show that pathologic events began in the neuronal compartment while enhanced lysine accumulation in the immature brain allowed increased glutaric acid production resulting in age-dependent injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance (1H NMR) spectroscopy as a diagnostic marker. Blocking brain lysine uptake reduced glutaric acid levels and brain injury. These findings provide what we believe are new monitoring and treatment strategies that may translate for use in human GA-I
Social representations and the politics of participation
Recent work has called for the integration of different perspectives into the field of political psychology (Haste, 2012). This chapter suggests that one possible direction that such efforts can take is studying the role that social representations theory (SRT) can play in understanding political participation and social change. Social representations are systems of common-sense knowledge and social practice; they provide the lens through which to view and create social and political realities, mediate people's relations with these sociopolitical worlds and defend cultural and political identities. Social representations are therefore key for conceptualising participation as the activity that locates individuals and social groups in their sociopolitical world. Political participation is generally seen as conditional to membership of sociopolitical groups and therefore is often linked to citizenship. To be a citizen of a society or a member of any social group one has to participate as such. Often political participation is defined as the ability to communicate one's views to the political elite or to the political establishment (Uhlaner, 2001), or simply explicit involvement in politics and electoral processes (Milbrath, 1965). However, following scholars on ideology (Eagleton, 1991; Thompson, 1990) and social knowledge (Jovchelovitch, 2007), we extend our understanding of political participation to all social relations and also develop a more agentic model where individuals and groups construct, develop and resist their own views, ideas and beliefs. We thus adopt a broader approach to participation in comparison to other political-psychological approaches, such as personality approaches (e.g. Mondak and Halperin, 2008) and cognitive approaches or, more recently, neuropsychological approaches (Hatemi and McDermott, 2012). We move away from a focus on the individual's political behaviour and its antecedents and outline an approach that focuses on the interaction between psychological and political phenomena (Deutsch and Kinnvall, 2002) through examining the politics of social knowledge
Phosphodiesterase 5 inhibitors lower both portal and pulmonary pressure in portopulmonary hypertension: a case report
<p>Abstract</p> <p>Background</p> <p>Portopulmonary hypertension (PPHTN) is a severe complication in liver cirrhosis. PDE5 inhibitors lower pulmonary arterial pressure (PAP) in PPHTN. However, their effect on portal hypertension has not yet been investigated.</p> <p>Case presentation</p> <p>A 55 year old male patient presented with PPHTN and alcoholic liver cirrhosis. 10 mg of Tadalafil, a PDE5 inhibitor with a long half-life, was administered orally under continuous monitoring of pulmonary and portal hemodynamics. For maintenance therapy the patient received Sildenafil 20 mg bid.</p> <p>Tadalafil lowered mean PAP from 45 to 39 mmHg within 60 minutes. Cardiac output (CO) increased from 6.8 to 7.9 l/min. Central venous pressure (CVP) remained stable at 3 mmHg. Systolic and diastolic blood pressure was lowered from 167/89 to 159/86 mmHg. Pulse rate increased from 75 to 87 per min. Wedged hepatic vein pressure (WHVP) decreased from 21 to 18 mm Hg, hepatovenous pressure gradient (HVPG) decreased from 10 to 7 mmHg. Hemodynamic monitoring after 6 months of Sildenafil therapy revealed a sustained lowering of mean PAP. HVPG remained constant at 10 mmHg. Cardiac and pulmonary performance had further improved.</p> <p>Conclusion</p> <p>This case report shows for the first time, that phosphodiesterase 5 inhibitors lower both portal and pulmonary pressure in portopulmonary hypertension.</p
Elevated Pontine and Putamenal GABA Levels in Mild-Moderate Parkinson Disease Detected by 7 Tesla Proton MRS
Background: Parkinson disease (PD) is characterized by the degeneration of nigrostriatal dopaminergic neurons. However, postmortem evidence indicates that the pathology of lower brainstem regions, such as the pons and medulla, precedes nigral involvement. Consistently, pontomedullary damage was implicated by structural and PET imaging in early PD. Neurochemical correlates of this early pathological involvement in PD are unknown. Methodology/Principal Finding: To map biochemical alterations in the brains of individuals with mild-moderate PD we quantified neurochemical profiles of the pons, putamen and substantia nigra by 7 tesla (T) proton magnetic resonance spectroscopy. Thirteen individuals with idiopathic PD (Hoehn & Yahr stage 2) and 12 age- and gender-matched healthy volunteers participated in the study. c-Aminobutyric acid (GABA) concentrations in the pons and putamen were significantly higher in patients (N = 11, off medications) than controls (N = 11, p,0.001 for pons and p,0.05 for putamen). The GABA elevation was more pronounced in the pons (64%) than in the putamen (32%). No other neurochemical differences were observed between patients and controls. Conclusion/Significance: The GABA elevation in the putamen is consistent with prior postmortem findings in patients with PD, as well as with in vivo observations in a rodent model of PD, while the GABA finding in the pons is novel. The more significant GABA elevation in the pons relative to the putamen is consistent with earlier pathological involvement of th
Reconceptualizing conservation
Early definitions of conservation focused largely on the end goals of protection or restoration of nature, and the various disciplinary domains that contribute to these ends. Conservation science and practice has evolved beyond being focused on just issues of scarcity and biodiversity decline. To better recognize the inherent links between human behaviour and conservation, “success” in conservation is now being defined in terms that include human rights and needs. We also know that who engages in conservation, and how, dictates the likelihood that conservation science will be embraced and applied to yield conservation gains. Here we present ideas for reconceptualizing conservation. We emphasize the HOW in an attempt to reorient and repurpose the term in ways that better reflect what contemporary conservation is or might aspire to be. To do so, we developed an acrostic using the letters in the term “CONSERVATION” with each serving as an adjective where C = co-produced, O = open, N = nimble, S = solutions-oriented, E = empowering, R = relational, V = values-based, A = actionable, T = transdisciplinary, I = inclusive, O = optimistic, and N = nurturing. For each adjective, we briefly describe our reasoning for its selection and describe how it contributes to our vision of conservation. By reconceptualizing conservation we have the potential to center how we do conservation in ways that are more likely to result in outcomes that benefit biodiversity while also being just, equitable, inclusive, and respectful of diverse rights holders, knowledge holders, and other actors. We hope that this acrostic will be widely adopted in training to help the next generation of conservation researchers and practitioners keep in mind what it will take to make their contributions effective and salient
Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial
Background:
Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma.
Methods:
In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete.
Findings:
Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p<0·0001). In patients with a homologous recombination deficient carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 [0·24–0·42]; p<0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 [0·30–0·45]; p<0·0001). Treatment-emergent adverse events of grade 3 or higher in the safety population (372 [99%] patients in the rucaparib group vs 189 [100%] in the placebo group) were reported in 209 (56%) patients in the rucaparib group versus 28 (15%) in the placebo group, the most common of which were anaemia or decreased haemoglobin concentration (70 [19%] vs one [1%]) and increased alanine or aspartate aminotransferase concentration (39 [10%] vs none).
Interpretation:
Across all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy.
Funding:
Clovis Oncology
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