Mature Religiosity Scale: Validity of a New Questionnaire

In order to validate a new questionnaire, the Mature Religiosity Scale (MRS), it was presented to a sample of 336 persons, of which 171 were parishioners and 165 outpatients of Christian mental health clinics. A first version of this questionnaire was designed by studying both psychi- atric/psychological and theological literature. Validity and reliability were studied by including other questionnaires, among them the Spiritual Well-Being Scale (SWBS), the Duke Religion Index, the Religious/Spiritual Coping (RCoPE) and the State-Trait Anxiety Inventory (STAI). The results indicate that 16 items of the 19-item questionnaire make up one factor with good internal consistency, which is measured by Cronbach’s alpha. This factor was used as the Mature Religiosity Scale in this study. out of correlations with other validated scales and correlations with characteristics of known groups this scale proved to have good validity. The Mature Re- ligiosity Scale is suitable for use in both mental healthcare and pastoral care. It is designed and validated for these two groups, giving direction to professional communication about faith and meaning of life

Overcommitment to work is associated with changes in cardiac sympathetic regulation.

Objective: Work stress is associated with an increased risk for cardiovascular disease (CVD). Exaggerated cardiovascular reactivity to work-related stressors or incomplete recovery after work is a proposed mechanism underlying this increase in risk. This study examined the effects of work stress on 24-hour profiles of the pre-ejection period (PEP), a measure of cardiac sympathetic activity, obtained from ambulatory measurement of the impedance cardiogram. Methods: A total of 67 male white-collar workers (age 47.1 ± 5.2) underwent ambulatory monitoring on 2 workdays and 1 non-workday. Work stress was defined according to Siegrist's model as 1) a combination of high effort and low reward at work (high imbalance) or 2) an exhaustive work-related coping style (high overcommitment). Results: High overcommitment was associated with shorter absolute PEP levels during all periods on all 3 measurement days, reduced wake-to-sleep PEP differences and reduced PEP variability, as indexed by the SD. Conclusions: Overcommitment to work was associated with an increase in basal sympathetic drive and a reduction in the dynamic range of cardiac sympathetic regulation. Both findings are compatible with the hypothesis that overcommitment induces β-receptor down-regulation

Minimizing the risk of inappropriately administering thrombolytic therapy (Thrombolysis and Angioplasty in Myocardial Infarction [TAMI] study group)

Despite the proven benefits of thrombolytic therapy in acute myocardial infarction, concern for its complications, especially in patients misdiagnosed with myocardial infarction, has led to hesitancy in its use. Historical, clinical and electrocardiographic criteria were developed for enrolling patients with suspected acute myocardial infarction into thrombolytic trials by noncardiovascular specialists. The incidence of misdiagnosis of myocardial infarction and the clinical outcomes when these criteria were used were evaluated for 1,387 consecutive patients given thrombolytic therapy. Twenty-five community hospitals and 7 interventional centers were the sites of enrollment. Most patients (63%) were enrolled from community hospitals. Criteria for thrombolytic therapy included: symptoms of acute myocardial infarction 20 minutes, and not relieved by nitroglycerin; and ST-segment elevation >=1 mm in 2 contiguous leads or ST-segment depression of posterior myocardial infarction. Exclusion criteria reflecting increased risk of bleeding were used. A final diagnosis of myocardial infarction was based on creatinine kinase-MB, electrocardiographic and ventriculographic evaluation. Acute myocardial infarction was misdiagnosed in 20 patients (1.4%; 95% confidence interval 0.8-2.0%). These patients were demographically similar to those with acute myocardial infarction. All misdiagnosed patients survived; no significant adverse events occurred. Thus, in several clinical settings, a simple algorithm with specific criteria was used for diagnosing acute myocardial infarction and administering thrombolytic therapy. The inclusion criteria used in this study led to a low rate of misdiagnosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30893/1/0000562.pd

Bleeding and thrombotic risk in pregnant women with Fontan physiology

Background/objectives Pregnancy may potentiate the inherent hypercoagulability of the Fontan circulation, thereby amplifying adverse events. This study sought to evaluate thrombosis and bleeding risk in pregnant women with a Fontan.  Methods We performed a retrospective observational cohort study across 13 international centres and recorded data on thrombotic and bleeding events, antithrombotic therapies and pre-pregnancy thrombotic risk factors.  Results We analysed 84 women with Fontan physiology undergoing 108 pregnancies, average gestation 33 +/- 5 weeks. The most common antithrombotic therapy in pregnancy was aspirin (ASA, 47 pregnancies (43.5%)). Heparin (unfractionated (UFH) or low molecular weight (LMWH)) was prescribed in 32 pregnancies (30%) and vitamin K antagonist (VKA) in 10 pregnancies (9%). Three pregnancies were complicated by thrombotic events (2.8%). Thirty-eight pregnancies (35%) were complicated by bleeding, of which 5 (13%) were severe. Most bleeds were obstetric, occurring antepartum (45%) and postpartum (42%). The use of therapeutic heparin (OR 15.6, 95% CI 1.88 to 129, p=0.006), VKA (OR 11.7, 95% CI 1.06 to 130, p=0.032) or any combination of anticoagulation medication (OR 13.0, 95% CI 1.13 to 150, p=0.032) were significantly associated with bleeding events, while ASA (OR 5.41, 95% CI 0.73 to 40.4, p=0.067) and prophylactic heparin were not (OR 4.68, 95% CI 0.488 to 44.9, p=0.096). Conclusions Current antithrombotic strategies appear effective at attenuating thrombotic risk in pregnant women with a Fontan. However, this comes with high (>30%) bleeding risk, of which 13% are life threatening. Achieving haemostatic balance is challenging in pregnant women with a Fontan, necessitating individualised risk-adjusted counselling and therapeutic approaches that are monitored during the course of pregnancy

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation

Objectives To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks.Design The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF).Participants Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk.Results The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64–0.67), 0.64 (0.61–0.66) and 0.64 (0.61–0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74).Conclusions Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks.</div

Development and validation of a targeted gene sequencing panel for application to disparate cancers

Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy

Mechanical design of the optical modules intended for IceCube-Gen2

IceCube-Gen2 is an expansion of the IceCube neutrino observatory at the South Pole that aims to increase the sensitivity to high-energy neutrinos by an order of magnitude. To this end, about 10,000 new optical modules will be installed, instrumenting a fiducial volume of about 8 km3. Two newly developed optical module types increase IceCube’s current sensitivity per module by a factor of three by integrating 16 and 18 newly developed four-inch PMTs in specially designed 12.5-inch diameter pressure vessels. Both designs use conical silicone gel pads to optically couple the PMTs to the pressure vessel to increase photon collection efficiency. The outside portion of gel pads are pre-cast onto each PMT prior to integration, while the interiors are filled and cast after the PMT assemblies are installed in the pressure vessel via a pushing mechanism. This paper presents both the mechanical design, as well as the performance of prototype modules at high pressure (70 MPa) and low temperature (−40∘C), characteristic of the environment inside the South Pole ice

The next generation neutrino telescope: IceCube-Gen2

The IceCube Neutrino Observatory, a cubic-kilometer-scale neutrino detector at the geographic South Pole, has reached a number of milestones in the field of neutrino astrophysics: the discovery of a high-energy astrophysical neutrino flux, the temporal and directional correlation of neutrinos with a flaring blazar, and a steady emission of neutrinos from the direction of an active galaxy of a Seyfert II type and the Milky Way. The next generation neutrino telescope, IceCube-Gen2, currently under development, will consist of three essential components: an array of about 10,000 optical sensors, embedded within approximately 8 cubic kilometers of ice, for detecting neutrinos with energies of TeV and above, with a sensitivity five times greater than that of IceCube; a surface array with scintillation panels and radio antennas targeting air showers; and buried radio antennas distributed over an area of more than 400 square kilometers to significantly enhance the sensitivity of detecting neutrino sources beyond EeV. This contribution describes the design and status of IceCube-Gen2 and discusses the expected sensitivity from the simulations of the optical, surface, and radio components

Sensitivity of IceCube-Gen2 to measure flavor composition of Astrophysical neutrinos

The observation of an astrophysical neutrino flux in IceCube and its detection capability to separate between the different neutrino flavors has led IceCube to constraint the flavor content of this flux. IceCube-Gen2 is the planned extension of the current IceCube detector, which will be about 8 times larger than the current instrumented volume. In this work, we study the sensitivity of IceCube-Gen2 to the astrophysical neutrino flavor composition and investigate its tau neutrino identification capabilities. We apply the IceCube analysis on a simulated IceCube-Gen2 dataset that mimics the High Energy Starting Event (HESE) classification. Reconstructions are performed using sensors that have 3 times higher quantum efficiency and isotropic angular acceptance compared to the current IceCube optical modules. We present the projected sensitivity for 10 years of data on constraining the flavor ratio of the astrophysical neutrino flux at Earth by IceCube-Gen2