Supersonic transport grid generation, validation, and optimization

The ever present demand for reduced flight times has renewed interest in High Speed Civil Transports (HSCT). The need for an HSCT becomes especially apparent when the long distance, over-sea, high growth Pacific rim routes are considered. Crucial to any successful HSCT design are minimal environmental impact and economic viability. Vital is the transport's aerodynamic efficiency, ultimately effecting both the environmental impact and the operating cost. Optimization, including numerical optimization, coupled with the use of computational fluid dynamics (CFD) technology, has and will offer a significant improvement beyond traditional methods

Hydroxycobalamin reveals the involvement of hydrogen sulfide in the hypoxic responses of rat carotid body chemoreceptor cells

Producción CientíficaCarotid body (CB) chemoreceptor cells sense arterial blood PO2, generating a neurosecretory response proportional to the intensity of hypoxia. Hydrogen sulfide (H2S) is a physiological gaseous messenger that is proposed to act as an oxygen sensor in CBs, although this concept remains controversial. In the present study we have used the H2S scavenger and vitamin B12 analog hydroxycobalamin (Cbl) as a new tool to investigate the involvement of endogenous H2S in CB oxygen sensing. We observed that the slow-release sulfide donor GYY4137 elicited catecholamine release from isolated whole carotid bodies, and that Cbl prevented this response. Cbl also abolished the rise in [Ca2+]i evoked by 50 µM NaHS in enzymatically dispersed CB glomus cells. Moreover, Cbl markedly inhibited the catecholamine release and [Ca2+]i rise caused by hypoxia in isolated CBs and dispersed glomus cells, respectively, whereas it did not alter these responses when they were evoked by high [K+]e. The L-type Ca2+ channel blocker nifedipine slightly inhibited the rise in CB chemoreceptor cells [Ca2+]i elicited by sulfide, whilst causing a somewhat larger attenuation of the hypoxia-induced Ca2+ signal. We conclude that Cbl is a useful and specific tool for studying the function of H2S in cells. Based on its effects on the CB chemoreceptor cells we propose that endogenous H2S is an amplifier of the hypoxic transduction cascade which acts mainly by stimulating non-L-type Ca2+ channels.Ministerio de Economía, Industria y Competitividad - Fondo Europeo de Desarrollo Regional (project BFU2015-70616-R)Junta de Castilla y León (project VA106G18)Centro de Investigación Biomédica en Red de Enfermedades Respiratorias . Instituto de Salud Carlos III (project CIBER CB06/06/0050

Can Medication Free, Treatment-Resistant, Depressed Patients Who Initially Respond to TMS Be Maintained Off Medications? A Prospective, 12-Month Multisite Randomized Pilot Study

AbstractBackgroundRepetitive transcranial magnetic stimulation (TMS) is efficacious for acute treatment of resistant major depressive disorder (MDD), but there is little information on maintenance TMS after acute response.Objective/hypothesisThis pilot feasibility study investigated 12-month outcomes comparing two maintenance TMS approaches – a scheduled, single TMS session delivered monthly (SCH) vs. observation only (OBS).MethodsAntidepressant-free patients with unipolar, non-psychotic, treatment-resistant MDD participated in a randomized, open-label, multisite trial. Patients meeting protocol-defined criteria for improvement after six weeks of acute TMS were randomized to SCH or OBS regimens. TMS reintroduction was available for symptomatic worsening; all patients remained antidepressant-free during the trial.ResultsSixty-seven patients enrolled in the acute phase, and 49 (73%) met randomization criteria. Groups were matched, although more patients in the SCH group had failed ≥2 antidepressants (p = .035). There were no significant group differences on any outcome measure. SCH patients had nonsignificantly longer time to first TMS reintroduction, 91 ± 66 days, vs. OBS, 77 ± 52 days; OBS patients were nonsignificantly more likely to need reintroduction (odds ratio = 1.21, 95% CI .38–3.89). Reintroduction lasted 14.3 ± 17.8 days (SCH) and 16.9 ± 18.9 days (OBS); 14/18 (78%) SCH and 17/27 (63%) OBS responded to reintroduction. Sixteen patients (32.7%) completed all 53 weeks of the study.ConclusionsMaintaining treatment-resistant depressed patients off medications with periodic TMS appears feasible in some cases. There was no statistical advantage of SCH vs. OBS, although SCH was associated with a nonsignificantly longer time to relapse. Those who initially respond to TMS have a strong chance of re-responding if relapse occurs

Hydroxycobalamin Reveals the Involvement of Hydrogen Sulfide in the Hypoxic Responses of Rat Carotid Body Chemoreceptor Cells

Carotid body (CB) chemoreceptor cells sense arterial blood PO2, generating a neurosecretory response proportional to the intensity of hypoxia. Hydrogen sulfide (H2S) is a physiological gaseous messenger that is proposed to act as an oxygen sensor in CBs, although this concept remains controversial. In the present study we have used the H2S scavenger and vitamin B12 analog hydroxycobalamin (Cbl) as a new tool to investigate the involvement of endogenous H2S in CB oxygen sensing. We observed that the slow-release sulfide donor GYY4137 elicited catecholamine release from isolated whole carotid bodies, and that Cbl prevented this response. Cbl also abolished the rise in [Ca2+]i evoked by 50 µM NaHS in enzymatically dispersed CB glomus cells. Moreover, Cbl markedly inhibited the catecholamine release and [Ca2+]i rise caused by hypoxia in isolated CBs and dispersed glomus cells, respectively, whereas it did not alter these responses when they were evoked by high [K+]e. The L-type Ca2+ channel blocker nifedipine slightly inhibited the rise in CB chemoreceptor cells [Ca2+]i elicited by sulfide, whilst causing a somewhat larger attenuation of the hypoxia-induced Ca2+ signal. We conclude that Cbl is a useful and specific tool for studying the function of H2S in cells. Based on its effects on the CB chemoreceptor cells we propose that endogenous H2S is an amplifier of the hypoxic transduction cascade which acts mainly by stimulating non-L-type Ca2+ channels

Integrated Colours of Milky Way Globular Clusters and Horizontal Branch Morphology

Broadband colours are often used as metallicity proxies in the study of extragalactic globular clusters. A common concern is the effect of variations in horizontal branch (HB) morphology--the second-parameter effect--on such colours. We have used UBVI, Washington, and DDO photometry for a compilation of over 80 Milky Way globular clusters to address this question. Our method is to fit linear relations between colour and [Fe/H], and study the correlations between the residuals about these fits and two quantitative measures of HB morphology. While there is a significant HB effect seen in U-B, for the commonly used colours B-V, V-I, and C-T_1, the deviations from the baseline colour-[Fe/H] relations are less strongly related to HB morphology. There may be weak signatures in B-V and C-T_1, but these are at the limit of observational uncertainties. The results may favour the use of B-I in studies of extragalactic globular clusters, especially when its high [Fe/H]-sensitivity is considered.Comment: 19 pages, including 26 figures. AN in press. Figure 9 stubbornly resists attempts to correct i

Role of SRC-Family Kinases in Hypoxic Vasoconstriction of Rat Pulmonary Artery

Aims: We investigated the role of src-family kinases (srcFKs) in hypoxic pulmonary vasoconstriction (HPV) and how this relates to Rho-kinase-mediated Ca(2+) sensitization and changes in intracellular Ca(2+) concentration ([Ca(2+)](i)). Methods and results: Intra-pulmonary arteries (IPAs) were obtained from male Wistar rats. HPV was induced in myograph-mounted IPAs. Auto-phosphorylation of srcFKs and phosphorylation of the regulatory subunit of myosin phosphatase (MYPT-1) and myosin light-chain (MLC(20)) in response to hypoxia were determined by western blotting. Translocation of Rho-kinase and effects of siRNA knockdown of src and fyn were examined in cultured pulmonary artery smooth muscle cells (PASMCs). [Ca(2+)](i) was estimated in Fura-PE3-loaded IPA. HPV was inhibited by two blockers of srcFKs, SU6656 and PP2. Hypoxia enhanced phosphorylation of three srcFK proteins at Tyr-416 (60, 59, and 54 kDa, corresponding to src, fyn, and yes, respectively) and enhanced srcFK-dependent tyrosine phosphorylation of multiple target proteins. Hypoxia caused a complex, time-dependent enhancement of MYPT-1 and MLC(20) phosphorylation, both in the absence and presence of pre-constriction. The sustained component of this enhancement was blocked by SU6656 and the Rho-kinase inhibitor Y27632. In PASMCs, hypoxia caused translocation of Rho-kinase from the nucleus to the cytoplasm, and this was prevented by anti-src siRNA and to a lesser extent by anti-fyn siRNA. The biphasic increases in [Ca(2+)](i) that accompany HPV were also inhibited by PP2. Conclusion: Hypoxia activates srcFKs and triggers protein tyrosine phosphorylation in IPA. Hypoxia-mediated Rho-kinase activation, Ca(2+) sensitization, and [Ca(2+)](i) responses are depressed by srcFK inhibitors and/or siRNA knockdown, suggesting a central role of srcFKs in HPV

Assessing the Factorial Validity of the Attitudes and Belief Scale 2-Abbreviated Version: A Call for the Development a Gold Standard Method of Measuring Rational and Irrational Beliefs

Rational Emotive Behaviour Therapy (REBT) does not possess a measure of rational and irrational beliefs that meets internationally recognised standards for acceptable psychometric properties. Without such a measure the theory/practice of REBT cannot be rigorously evaluated, thus undermining its scientific veracity. The current study investigates the validity and reliability of a recently developed measure of rational and irrational beliefs: the Attitudes and Belief Scale 2-Abbreviated Version (ABS-2-AV). University students from three countries completed the ABS-2-AV (N = 397). An alternative models framework using confirmatory factor analysis indicated that a theoretically consistent eight-factor model of the ABS-2-AV provided the best fit of the data. A number of post-hoc modifications were required in order to achieve acceptable model fit results, and these modifications revealed important methodological limitations with the ABS-2-AV. Results indicated that the validity of the ABS-2-AV was undermined due to items measuring both the psychological process of interest (rational and irrational beliefs) and the context in which these beliefs processes are presented. This is a serious methodological limitation of the ABS-2 and all questionnaires derived from it, including the ABS-2-AV. This methodological limitation resulted in the ABS-2-AV possessing poor internal reliability. These limitations are discussed in relation to the broader REBT literature and the impact such problems have on research and practice. A call is made for REBT researchers to come together to develop a “gold standard” method of assessing rational and irrational beliefs that meets international standard for psychometric excellence

Towards a cancer mission in Horizon Europe: recommendations.

A comprehensive translational cancer research approach focused on personalized and precision medicine, and covering the entire cancer research-care-prevention continuum has the potential to achieve in 2030 a 10-year cancer-specific survival for 75% of patients diagnosed in European Union (EU) member states with a well-developed healthcare system. Concerted actions across this continuum that spans from basic and preclinical research through clinical and prevention research to outcomes research, along with the establishment of interconnected high-quality infrastructures for translational research, clinical and prevention trials and outcomes research, will ensure that science-driven and social innovations benefit patients and individuals at risk across the EU. European infrastructures involving comprehensive cancer centres (CCCs) and CCC-like entities will provide researchers with access to the required critical mass of patients, biological materials and technological resources and can bridge research with healthcare systems. Here, we prioritize research areas to ensure a balanced research portfolio and provide recommendations for achieving key targets. Meeting these targets will require harmonization of EU and national priorities and policies, improved research coordination at the national, regional and EU level and increasingly efficient and flexible funding mechanisms. Long-term support by the EU and commitment of Member States to specialized schemes are also needed for the establishment and sustainability of trans-border infrastructures and networks. In addition to effectively engaging policymakers, all relevant stakeholders within the entire continuum should consensually inform policy through evidence-based advice

Effects of a 105 hours psychological training program on attitudes, communication skills and occupational stress in oncology: a randomised study

There is today a wide consensus regarding the need to improve communication skills (CS) of health-care professionals (HCPs) dealing with cancer patients. Psychological training programs (PTPs) may be useful to acquire the needed CS. Testing the efficacy of PTP will allow to define their optimal content. The present study was designed to assess the impact of a PTP on HCP stress, attitudes and CS, and on HCP and patients' satisfaction with HCP communication skills in a randomised study. A total of 115 oncology nurses were randomly assigned to a 105-h PTP or to a waiting list. Stress was assessed with the Nursing Stress Scale, attitudes with a Semantic Differential Questionnaire, CS used during one simulated and one actual patient interview with the Cancer Research Campaign Workshop Evaluation Manual, and satisfaction with the nurses' CS with a questionnaire completed by the patients and the nurses. Trained (TG) and control (CG) groups were compared at baseline, after 3 months (just following training for TG) and after 6 months (3 months after the end of training for TG). Compared to controls, trained nurses reported positive changes on their stress levels (P</=0.05) and on their attitudes (P</=0.05). Positive training effects were found on CS used during the simulated interview: a significant increase in facilitative behaviours (open questions: P</=0.001; evaluative functions: P</=0.05) and a significant decrease in inhibitory behaviours (inappropriate information: P</=0.01; false reassurance: P</=0.05). Less positive training effects were found regarding interviews with a cancer patient: a significant increase in educated guesses (P</=0.001) was noticed. No training effect was observed on nurses' satisfaction levels, but a positive training effect was found on patients' satisfaction levels (P</=0.01). Although results outline PTP efficacy, they indicate the need to design PTP, amplifying the transfer of learned CS to clinical practice.info:eu-repo/semantics/publishe