Supported nickel-rhenium catalysts for selective hydrogenation of methyl esters to alcohols

The addition of Re to Ni on TiO2 yields efficient catalysts for the hydrogenation of acids and esters to alcohols under mild conditions. Rhenium promotes the formation of atomically dispersed and sub-nanometre-sized bimetallic species interacting strongly with the oxide support

Clinician-centric diagnosis of rare genetic diseases: performance of a gene pertinence metric in decision support for clinicians

Background In diagnosis of rare genetic diseases we face a decision as to the degree to which the sequencing lab offers one or more diagnoses based on clinical input provided by the clinician, or the clinician reaches a diagnosis based on the complete set of variants provided by the lab. We tested a software approach to assist the clinician in making the diagnosis based on clinical findings and an annotated genomic variant table, using cases already solved using less automated processes. Results For the 81 cases studied (involving 216 individuals), 70 had genetic abnormalities with phenotypes previously described in the literature, and 11 were not described in the literature at the time of analysis (“discovery genes”). These included cases beyond a trio, including ones with different variants in the same gene. In 100% of cases the abnormality was recognized. Of the 70, the abnormality was ranked #1 in 94% of cases, with an average rank 1.1 for all cases. Large CNVs could be analyzed in an integrated analysis, performed in 24 of the cases. The process is rapid enough to allow for periodic reanalysis of unsolved cases. Conclusions A clinician-friendly environment for clinical correlation can be provided to clinicians who are best positioned to have the clinical information needed for this interpretation

Vitamin D composition of Australian foods

Australia needs accurate vitamin D food composition data to support public health initiatives. Previously, limitations in analytical methodology have precluded development of a comprehensive database. We used liquid chromatography with triple quadrupole mass spectrometry (LC-QQQ) to analyse 149 composite samples representing 98 foods (primary samples n = 896) in duplicate for vitamin D3, 25-hydroxyvitamin D3 (25(OH)D3), vitamin D2, 25(OH)D2. The greatest concentrations of vitamin D3 were found in canned salmon and a malted chocolate drink powder (fortified); chicken eggs and chicken leg meat contained the most 25(OH)D3. Margarine (fortified) and chocolate contained the greatest concentrations of vitamin D2, with smaller amounts found in various meat products. 25(OH)D2 was detected in various foods, including meats, and was quantitated in lamb liver. These data advance knowledge of dietary vitamin D in Australia and highlight the importance of analysis of these four forms of vitamin D to accurately represent the vitamin D content of food

Detecting and Quantifying Lewisite Degradation Products in Environmental Samples Using Arsenic Speciation

This report describes a unique method for identifying and quantifying lewisite degradation products using arsenic (III) and arsenic (IV) speciation in solids and in solutions. Gas chromatographic methods, as well as high-performance liquid chromatographic methods are described for separation of arsenic species. Inductively coupled plasma-mass spectrographic methods are presented for the detection of arsenic

Age-associated changes in 4D flow CMR derived tricuspid valvular flow and right ventricular blood flow kinetic energy

Assessment of right ventricular (RV) diastolic function is not routinely carried out. This is due to standard two-dimensional imaging techniques being unreliable. Four-dimensional flow (4D flow) derived right ventricular blood flow kinetic energy assessment could circumvent the issues of the current imaging modalities. It also remains unknown whether there is an association between right ventricular blood flow kinetic energy (KE) and healthy ageing. We hypothesise that healthy ageing requires maintaining normal RV intra-cavity blood flow as quantified using KE method. The main objective of this study was to investigate the effect of healthy ageing on tricuspid through-plane flow and right ventricular blood flow kinetic energy. In this study, fifty-three healthy participants received a 4D flow cardiovascular magnetic resonance (CMR) scan on 1.5 T Philips Ingenia. Cine segmentation and 4D flow analysis were performed using dedicated software. Standard statistical methods were carried out to investigate the associations. Both RV E-wave KEiEDV (r = −0.3, P = 0.04) and A-wave KEiEDV (r = 0.42, P < 0.01) showed an association with healthy ageing. Additionally, the right ventricular blood flow KEiEDV E/A ratio demonstrated the strongest association with healthy ageing (r = −0.53, P < 0.01) when compared to all RV functional and haemodynamic parameters. Furthermore, in a multivariate regression model, KEiEDV E/A ratio and 4D flow derived tricuspid valve stroke volume demonstrated independent association to healthy ageing (beta −0.02 and 0.68 respectively, P < 0.01). Ageing is independently associated with 4D flow derived tricuspid stroke volume and RV blood flow KE E/A ratio. These novel 4D flow CMR derived imaging markers have future potential for RV diastolic assessment

Exploring the disparity between inflammation and disability in the 10-year outcomes of people with rheumatoid arthritis

Objectives: To identify groups of people with rheumatoid arthritis (RA) with different disability trajectories over ten years, despite comparable levels of inflammation.Methods: Data for this analysis came from three European prospective cohort studies of people with RA (Norfolk Arthritis Register [NOAR], Early Rheumatoid Arthritis Network [ERAN], Étude et Suivi des Polyarthrites Indifférenciées Récentes [ESPOIR]). Participants were assessed regularly over 8 (ERAN) to 10 (NOAR/ESPOIR) years. Inclusion criteria were: recruited after 1/1/2000, <24 months baseline symptom duration, and disability (Health Assessment Questionnaire [HAQ]) and inflammation (two-component disease activity score [DAS28-2C]) recorded at baseline and one other follow-up. People in each cohort also completed patient reported outcome measures at each assessment (pain, fatigue, depression). Group-based trajectory models (GBTM) were used to identify distinct groups of people with similar HAQ and DAS28-2C trajectories over follow-up.Results: This analysis included 2500 people with RA (NOAR: 1000, ESPOIR: 766, ERAN: 734). People in ESPOIR were younger and included more women (mean [standard deviation] age: NOAR: 57.1 [14.6], ESPOIR: 47.6 [12.5], ERAN: 56.8 [13.8]; women: NOAR: 63.9%, ESPOIR: 76.9%, ERAN: 69.1%). Within each cohort, two pairs of trajectories that followed the hypothesised pattern (comparable DAS28-2C but different HAQ) were identified. Higher pain, fatigue and depression were associated with increased odds of being in the high HAQ trajectories. Conclusion: Excess disability is persistent in RA. Controlling inflammation may not be sufficient to alleviate disability in all people with RA, and effective pain, fatigue and mood management may be needed in some groups to improve long-term function

The Scottish Early Rheumatoid Arthritis (SERA) Study:an inception cohort and biobank

Background: The Scottish Early Rheumatoid Arthritis (SERA) study is an inception cohort of rheumatoid (RA) and undifferentiated arthritis (UA) patients that aims to provide a contemporary description of phenotype and outcome and facilitate discovery of phenotypic and prognostic biomarkers Methods: Demographic and clinical outcome data are collected from newly diagnosed RA/UA patients every 6 months from around Scotland. Health service utilization data is acquired from Information Services Division, NHS National Services Scotland. Plain radiographs of hands and feet are collected at baseline and 12 months. Additional samples of whole blood, plasma, serum and filtered urine are collected at baseline, 6 and 12 months Results: Results are available for 1073 patients; at baseline, 76 % were classified as RA and 24 % as UA. Median time from onset to first review was 163 days (IQR97-323). Methotrexate was first-line DMARD for 75 % patients. Disease activity, functional ability and health-related quality of life improved significantly between baseline and 24 months, however the proportion in any employment fell (51 to 38 %, p = 0.0005). 24 % patients reported symptoms of anxiety and/or depression at baseline. 35/391 (9 %) patients exhibited rapid radiographic progression after 12 months. The SERA Biobank has accrued 60,612 samples Conclusions: In routine care, newly diagnosed RA/UA patients experience significant improvements in disease activity, functional ability and health-related quality of life but have high rates of psychiatric symptoms and declining employment rates. The co-existence of a multi-domain description of phenotype and a comprehensive biobank will facilitate multi-platform translational research to identify predictive markers of phenotype and prognosis

Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren’s syndrome

Sjögren’s syndrome is a common autoimmune disease (~0.7% of European Americans) typically presenting as keratoconjunctivitis sicca and xerostomia. In addition to strong association within the HLA region at 6p21 (Pmeta=7.65×10−114), we establish associations with IRF5-TNPO3 (Pmeta=2.73×10−19), STAT4 (Pmeta=6.80×10−15), IL12A (Pmeta =1.17×10−10), FAM167A-BLK (Pmeta=4.97×10−10), DDX6-CXCR5 (Pmeta=1.10×10−8), and TNIP1 (Pmeta=3.30×10−8). Suggestive associations with Pmeta<5×10−5 were observed with 29 regions including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2, and PHIP amongst others. These results highlight the importance of genes involved in both innate and adaptive immunity in Sjögren’s syndrome

Diagnosis of pulmonary hypertension with cardiac MRI: Derivation and validation of regression models

Purpose: To derive and test multiparametric cardiac MRI models for the diagnosis of pulmonary hypertension (PH). Materials and Methods: Images and patient data from consecutive patients suspected of having PH who underwent cardiac MRI and right-sided heart catheterization (RHC) between 2012 and 2016 were retrospectively reviewed. Of 2437 MR images identified, 603 fit the inclusion criteria. The mean patient age was 61 years (range, 18-88 years; mean age of women, 60 years [range, 18-84 years]; mean age of men, 62 years [range, 22-88 years]). In the first 300 patients (derivation cohort), cardiac MRI metrics that showed correlation with mean pulmonary arterial pressure (mPAP) were used to create a regression algorithm. The performance of the model was assessed in the 303-patient validation cohort by using receiver operating characteristic (ROC) and x² analysis. Results: In the derivation cohort, cardiac MRI mPAP model 1 (right ventricle and black blood) was defined as follows: 2179 + loge interventricular septal angle × 42.7 + log10 ventricular mass index (right ventricular mass/left ventricular mass) × 7.57 + black blood slow flow score × 3.39. In the validation cohort, cardiac MRI mPAP model 1 had strong agreement with RHC-measured mPAP, an intraclass coefficient of 0.78, and high diagnostic accuracy (area under the ROC curve = 0.95; 95% confidence interval [CI]: 0.93, 0.98). The threshold of at least 25 mm Hg had a sensitivity of 93% (95% CI: 89%, 96%), specificity of 79% (95% CI: 65%, 89%), positive predictive value of 96% (95% CI: 93%, 98%), and negative predictive value of 67% (95% CI: 53%, 78%) in the validation cohort. A second model, cardiac MRI mPAP model 2 (right ventricle pulmonary artery), which excludes the black blood flow score, had equivalent diagnostic accuracy (ROC difference: P = .24). Conclusion: Multiparametric cardiac MRI models have high diagnostic accuracy in patients suspected of having pulmonary hypertension

Nocturia, Sleep-Disordered Breathing, and Cardiovascular Morbidity in a Community-Based Cohort

Background: Nocturia has been independently associated with cardiovascular morbidity and all-cause mortality, but such studies did not adjust for sleep-disordered breathing (SDB), which may have mediated such a relationship. Our aims were to determine whether an association between nocturia and cardiovascular morbidity exists that is independent of SDB. We also determined whether nocturia is independently associated with SDB. Methodology/Principal Findings: In order to accomplish these aims we performed a cross-sectional analysis of the Sleep Heart Health Study that contained information regarding SDB, nocturia, and cardiovascular morbidity in a middle-age to elderly community-based population. In 6342 participants (age 63±11 [SD] years, 53% women), after adjusting for known confounders such as age, body mass index, diuretic use, diabetes mellitus, alpha-blocker use, nocturia was independently associated with SDB (measured as Apnea Hypopnea index >15 per hour; OR 1.3; 95%CI, 1.2-1.5). After adjusting for SDB and other known confounders, nocturia was independently associated with prevalent hypertension (OR 1.23; 95%CI 1.08-1.40; P = 0.002), cardiovascular disease (OR 1.26; 95%CI 1.05-1.52; P = 0.02) and stroke (OR 1.62; 95%CI 1.14-2.30; P = 0.007). Moreover, nocturia was also associated with adverse objective alterations of sleep as measured by polysomnography and self-reported excessive daytime sleepiness (P<0.05). Conclusions/Significance: Nocturia is independently associated with sleep-disordered breathing. After adjusting for SDB, there remained an association between nocturia and cardiovascular morbidity. Such results support screening for SDB in patients with nocturia, but the mechanisms underlying the relationship between nocturia and cardiovascular morbidity requires further study. MeSH terms: Nocturia, sleep-disordered breathing, obstructive sleep apnea, sleep apnea, polysomnography, hypertension