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The article evaluates the HY4 electric aircraft powered by liquid hydrogen from H2FLY.

ABSTRACTVentricular dysfunction is common among patients with repaired cyanotic congenital heart disease. To date, no pharmacologic intervention has been demonstrated to be beneficial in this setting. To begin addressing this knowledge gap, we conducted a single-center prospective, randomized, open-label pilot study to investigate the effects of eplerenone on serologic markers of collagen turnover and inflammation, 6-minute walk distance, and quality of life in patients with tetralogy of Fallot (TOF) or transposition of the great arteries with a systemic right ventricle (transposition of the great arteries [TGA]). Patients were randomized to a 3-month drug-free period at the beginning of the treatment period or at the end. All patients received 12 months of eplerenone therapy during the treatment period. Twenty-six patients were enrolled in the trial; 17 completed the study protocol: 8 with TOF and 9 with TGV. Eplerenone had no effect on serum levels of procollagen 1 N-terminal peptide (PINP), procollagen 3 N-terminal peptide (PIIINP), or galectin-3 (G3). Similarly, eplerenone had no effect on 6-minute walk distance or quality of life. In conclusion, PINP and PIIINP levels are as high as or higher in patients with TOF and TGA than in patients with normal cardiac anatomy and heart failure, whereas G3 levels are lower. Eplerenone is well tolerated by adults born with congenital heart disease.

IMPORTANCE: Many studies that found improved quality of life (QOL) after radiotherapy of bone metastases have small sample sizes and do not use specific questionnaires. How soon after radiotherapy one can expect an improvement in QOL is unknown. OBJECTIVE: To investigate QOL at days 10 and 42 after radiotherapy with a bone metastases–specific QOL tool. DESIGN, SETTING, AND PARTICIPANTS: In this secondary analysis of the NCIC Clinical Trials Group Symptom Control Trial SC.23, a double-blind randomized clinical trial that investigated dexamethasone for the prophylaxis of pain flare after radiotherapy, patients were accrued from 23 Canadian centers from May 30, 2011, to December 11, 2014, and were followed up for 42 days after treatment. Participants referred for radiotherapy for bone metastases were required to have a pain score at the site(s) of treatment of at least 2 (range, 0-10). INTERVENTIONS: Patients were treated with a single 8-Gy radiotherapy dose for 1 or 2 bone metastases. MAIN OUTCOMES AND MEASURES: Patients reported their worst pain score and analgesic intake at baseline and days 10 and 42 after treatment. Pain response was assessed with International Bone Metastases Consensus Endpoint Definitions. Self-reported QOL was completed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Bone Metastases Module (QLQ-BM22) and the European Organisation for Research and Treatment of Cancer Quality of Life Core 15 Palliative (QLQ-C15-PAL) at the same time points. RESULTS: A total of 298 patients were accrued (median age, 68.8 [range, 32-94] years at day 10 and 68.0 [range, 34-90] years at day 42). A total of 122 patients (40.9%) responded to radiotherapy at day 10 and 116 patients (38.9%) at day 42. At day 10, compared with nonresponders, patients with a pain response had a greater reduction in pain (mean reduction, 17.0 vs 1.8; P = .002) and pain characteristics (mean reduction, 12.8 vs 1.1; P = .002), as well as greater improvements in functional interference (mean increase, 11.6 vs 3.6; P = .01) and psychosocial aspects (mean increase, 1.2 points in responders vs mean decrease of 2.2 points in nonresponders, P = .04). Comparing changes in QOL from baseline to day 42, responders had significantly greater improvements in the physical (mean increase, 6.2 vs −9.0; P < .001), emotional (mean increase, 12.3 vs −5.5; P < .001), and global domains (mean increase, 10.3 vs −4.5; P < .001) of the QLQ-C15-PAL compared with nonresponders. CONCLUSIONS AND RELEVANCE: Forty percent of patients experienced pain reduction and better QOL at day 10 after radiotherapy with further improvements in QOL at day 42 in responders. A single 8-Gy radiotherapy dose for bone metastases should be offered to all patients, even those with poor survival. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01248585

Aim:The present study aimed to determine the prognostic survival value of pretreatment health-related quality of life (HRQOL) and changes in HRQOL following whole-brain radiation treatment in patients with brain metastases. Methods:Patients who were treated with whole-brain radiation treatment and completed HRQOL questionnaires were included. Univariate and multivariate Cox proportional hazard models of overall survival (OS) were conducted for overall HRQOL and domain scores. Results & conclusion:Patients with lower HRQOL at baseline, especially lower physical functioning and motor dysfunction domains, were more likely to have poorer survival. Changes in overall HRQOL and its domains were not significantly related to OS. Pretreatment HRQOL, especially physical functioning and motor dysfunction, has added prognostic value in patients with brain metastases.

Introduction: Stereotactic body radiation therapy allows for the precise delivery of high-dose radiation to disease sites and is becoming increasingly used to treat nonspine bone metastases. Previous studies have shown that remineralization of lytic bone metastases follows after conventional radiotherapy. The objective of this study was to investigate changes in bone density in nonspine bone metastases following stereotactic body radiation therapy.Methods: A retrospective review was conducted for all patients treated with stereotactic body radiation therapy to nonspine bone metastases between May 2011 and April 2014. A minimum of 1 pretreatment and 1 posttreatment computed tomography scan was required. An independent musculoskeletal radiologist contoured the lesions on the most representative computed tomography slices. Density was measured in Hounsfield units and analyzed using pretreatment and posttreatment ratios.Results: Forty sites were treated (55% lytic, 30% sclerotic, and 15% mixed). The median follow-up duration was 7 months. Lytic osseous metastases from renal cell carcinoma progressed during initial follow-up imaging and then returned to baseline. Of 9 lytic lesions not from renal cell carcinoma, 6 showed an immediate increase in density and 2 remained stable. Six of 7 sclerotic lesions from prostate cancer showed decreased density throughout all follow-ups.Conclusion: Stereotactic body radiation therapy is efficacious in the remineralization of lytic and demineralization of sclerotic nonspine bone metastases.

Aims:To assess the ability of the Brain Metastases Symptom and Impact Questionnaire (BASIQ) in evaluating symptoms and impact on daily life. Patients & methods:Patients with brain metastases completed BASIQ, Functional Assessment of Cancer Therapy-General, FACT-Brain at baseline and at 1, 2 and 3 months follow-ups. Results:Thirty-six patients completed all follow-ups. BASIQ correlated well (r ≥ 0.40) with FACT subscales, except for social/family and emotional wellbeing. Linear regression analysis found no significant changes in quality of life (QOL) over time in both the BASIQ and FACT scales. Therefore, the two questionnaires coincide as both detected nonchanges. Conclusion:The ability of the BASIQ in evaluating symptoms and impact on over longer assessment periods was supported by the FACT questionnaires.

•Social norms are fundamental to interaction, culture, language and social life.•Two kinds of norms matter: what people do, and what they are expectedto do.•The prejudice that people report is almost exactly what prejudice norms say they shouldfeel.•Norms strongly influence energy use, although people are unaware of their influence.•Experiencing conflicting norms polarizes; it can both motivate and stymie behavior.

AbstractObjectiveThe objective of the study was to identify incidence, aetiology, and outcomes of extubation failure in infants with shunt-dependent pulmonary blood flow at a single tertiary care, academic children's hospital. The second objective of this study was to determine the haemodynamic effects of transition of positive pressure ventilation to spontaneous breathing in infants with extubation failure.Patients and methodsExtubation failure for our study was defined as the need for positive pressure ventilation within 96 hours after extubation. We collected demographics, pre-operative, intra-operative, post-operative, and peri-extubation data in a retrospective, observational format in patients who underwent a modified Blalock–Taussig shunt between January, 2005 and March, 2011. Infants undergoing Norwood operation or Damus–Kaye–Stansel with modified Blalock–Taussig shunt were excluded from the study. The cardiorespiratory variables collected before extubation and immediately after extubation included heart rate, respiratory rate, mean arterial blood pressure, central venous pressures, near infrared spectroscopy, oxygen saturations, and lactate levels. Clinical outcomes evaluated included the success or failure of extubation, cardiovascular intensive care unit length of stay, hospital length of stay, and mortality. Descriptive and univariate statistics were utilised to compare groups with extubation failure and extubation success.ResultsOf the 55 eligible patients during the study period, extubation failure occurred in 27% (15/55) of the patients. Of the 15 patients with extubation failure, 10 patients needed reintubation and five patients received continuous positive pressure ventilation without getting reintubated. There were three patients who had extubation failure in the first 2 hours after extubation, nine patients in the 2–24-hour period, and three patients in the 24–96-hour period. In all, eight patients were extubated in the second attempt after the first extubation failure, with a median duration of mechanical ventilation of 2 days (1 day, 6 days). The median age of patients at extubation was 19 days (12 days, 22 days) and median weight of patients was 3.6 kg (3.02 kg, 4.26 kg). In all, 38% (21/55) of the patients were intubated before surgery. The most common risk factors for failed extubation were lung disease in 46% (7/15), cardiac dysfunction in 26% (4/15), diaphragmatic paralysis in 13% (2/15), airway oedema in 6% (1/15), and vocal cord paralysis in 6% (1/15). The median duration of mechanical ventilation was 4 days (1 day, 10.5 days), median cardiovascular intensive care unit length of stay was 11 days (6.5 days, 23.5 days), and the median hospital length of stay was 30 days (14 days, 48 days). The overall mortality at the time of hospital discharge was 7%.ConclusionsExtubation failure in infants with shunt-dependent pulmonary blood flow and univentricular physiology is high and aetiology is diverse. Cardiopulmonary effects of removal of positive pressure ventilation are more pronounced in children with extubation failure and include escalation in the need for oxygen requirement and increase in mean arterial blood pressure. The majority of extubation failures in this select patient population occurs in the first 24 hours. Extubation failure in these patients is not associated with increased hospital length of stay or mortality.

Sustained hypoxia is a neurocognitive depressant, which has been shown to impair respiratory load sensation. Hypoxia has also been shown to impair arousal in animal models, but the effects of sustained hypoxia on arousal in humans have not been studied. The aim of this study was to assess the effects of sustained hypoxia on arousal from sleep in normal subjects.

BackgroundWhen performed inappropriately cardiopulmonary resuscitation (CPR) can prevent those with irreversible illness having a peaceful death. In people approaching the end of life, making decisions about whether to attempt CPR is integral to good care.AimAudit clinical practice around CPR decision–making and communication with patient‘s, those important to them and other healthcare professionals (HCPs) against regional standards.Use audit outcomes to update regional standards and guidelines.MethodsSystematic literature review examining education for HCPs, communication with patients and those important to them and dissemination of decisionsSurvey of HCPs working in specialist palliative careMulti–centre retrospective case note review of patients with a do not attempt cardiopulmonary resuscitation (DNACPR) decision receiving specialist palliative care in hospital, hospice or community settings. Results73 HCP’s participated in the survey and 87% had discussions about CPR. In HCPs having conversations about CPR 75% rated their confidence in doing so as 8/10 or higher.187 case notes were reviewed. While DNACPR forms indicated whether the decision had been discussed with the patient in 87% only 72% had a record of this in the written notes. 68% of case notes had a record of discussions or reasons for non-discussion with those important to the patient.34% of patients moved care setting after the DNACPR decision, of these 64% transferred with a unified DNACPR form.ConclusionThis audit shows ongoing challenges in communicating with patients and those important to them about CPR. Improvement is required in disseminating DNACPR decisions when patients transfer care settings.

BackgroundHypercalcemia of malignancy (HCM) is a common and significant cause of morbidity and mortality. Treatment includes clinically assisted hydration and bisphosphonates. Denosumab has been used in some centres. Clinical management of hypercalcaemia varies across settings and many recommendations are based on expert opinion.AimWithin a Regional Palliative Care Clinical Network in the North West of England, we aimed to:Evaluate the management of HCM in community, hospice and hospital settingsDevelop new standards and guidelinesMethodSystematic literature review.Six-month retrospective case note analysis of the management of HCM in community, hospice and hospital patients.Multi-professional questionnaire survey of palliative care professionals.ResultsA systematic literature identified 32 articles to inform development of the regional standards and guidelines. Data for 79 patients was recorded from hospital (n=53, 67%), hospice (n=25, 32%) and community (n=1, 1%) settings. Patients reported high symptomatic burden: fatigue (n=41, 52%), weakness (n=38, 48%), drowsiness (n=32, 41%) and constipation (n=26, 37%). Intravenous fluids were administered in 72 (91%) patients; 0.9% saline was most used (n=67, 85%) within 24 hours of diagnosis (n=64, 81%). Bisphosphonates were used in 55 (70%): zoledronic acid (n=28, 35%) and pamidronate (n=24, 30%) were most common. Two (3%) received denosumab and one (1%) calcitonin. Thirty-four (43%) had a previous episode of HCM, 20 (25%) had an episode in previous 4 weeks of which 12 (60%) achieved normocalcaemia following bisphosphonates.Plans for monitoring serum calcium were not documented in 33 (43%) cases. Many healthcare professionals considered treatment inappropriate in dying patients (n=51/66, 77%) and 8 (12%) had used denosumab previously for HCM.ConclusionThis analysis provides quantitative data about management of HCM across a variety of settings and has informed development of standards and guidelines. Further study is needed to determine the role of denosumab in management of HCM.

Introduction: Volumetric and density parameters measured from computed tomography scans were investigated for evaluating treatment response of nonspine bone lesions following stereotactic body radiation therapy.Methods: Twenty-three patients treated with stereotactic body radiation therapy to nonspine bone metastases with pre- and post-treatment radiological follow-up with computed tomography imaging were identified in a retrospective review. An expert radiologist classified 26 lesions by type (lytic, sclerotic) and by response. Two independent radiation oncologists created separate contours of the bone and soft tissue lesion volumes. Density and volume were assessed relative to baseline values.Results: For bone-only lesions, all lesions designated as local control decreased in volume or remained within 20% of baseline volumes. Lytic lesions classified as progressive disease exhibited much larger volume increases. Lytic bone lesions showed indications of remineralization with some exhibiting immediate increases in density (1-6 months) and others decreasing initially then increasing back toward baseline between 7 and 12 months. The majority of sclerotic lesions, all classified as local control, decreased slightly in both volume and density. Lesions with both soft tissue and boney involvement resulted in contradictory results when employing both radiological and size parameters for assessing treatment response. Classification was dominated by changes in soft tissue volume, despite associated volume or density changes in the corresponding boney lesion. In contrast, when soft tissue volume changes were minimal (<20% increase), classification appeared to be related primarily to density changes and not bone volume.Conclusions: Volume and density changes show promise as quantitative parameters for classifying treatment responses of nonspine osseous lesions. Further work is required for clarifying how these metrics can be applied to lesions with both boney and soft tissue components.