European multidecadal solar variability badly captured in all centennial reanalyses except CERA20C

Long-term historic climate datasets are valuable tools to investigate climate variability, validate climate models and contextualize anticipated climate change. Surface solar radiation is one particularly relevant variable, with implications on policy decisions (e.g., performance of solar panels) and fundamental questions in climate science (e.g., regarding the energy budget). While all current twentieth century reanalyses provide surface solar radiation, we demonstrate that most of them fail to capture multidecadal surface radiation variability in Europe. To this end, we systematically compare the reanalyses 20CRv2c, 20CRv3, ERA20C and CERA20C and the free model run ERA20CM. We show that only CERA20C captures dimming (1949 - 1979) and brightening (1979 -2009) in line with station observations, satellite-era reanalyses and established theory. The lack of multidecadal surface radiation variability in 20CRv2c/v3 is plausible given the use of constant aerosols. In contrast, ERA20CM, ERA20C and CERA20C are forced with time-varying aerosols. Despite this common forcing, ERA20CM and ERA20C surprisingly show no trends in clear-sky fluxes over the dimming and brightening periods while CERA20C shows significant trends. We discuss different potential explanations for this discrepancy (model versions, ocean coupling and ensemble size) and conclude that none of them provides a convincing explanation. Our results therefore imply that only CERA20C is suitable for assessments of surface solar radiation variability on multi-decadal timescales. This particularly applies to impact studies, for example, on long-term potentials of solar power generation

Single-cell proteomics defines the cellular heterogeneity of localized prostate cancer

Localized prostate cancer exhibits multiple genomic alterations and heterogeneity at the proteomic level. Single-cell technologies capture important cell-to-cell variability responsible for heterogeneity in biomarker expression that may be overlooked when molecular alterations are based on bulk tissue samples. This study aims to identify prognostic biomarkers and describe the heterogeneity of prostate cancer and the associated microenvironment by simultaneously quantifying 36 proteins using single-cell mass cytometry analysis of over 1.6 million cells from 58 men with localized prostate cancer. We perform this task, using a high-dimensional clustering pipeline named Franken to describe subpopulations of immune, stromal, and prostate cells, including changes occurring in tumor tissues and high-grade disease that provide insights into the coordinated progression of prostate cancer. Our results further indicate that men with localized disease already harbor rare subpopulations that typically occur in castration-resistant and metastatic disease

Revisiting Solid-solid Phase Transitions in Sodium and Potassium Tetrafluoroborate for Thermal Energy Storage

In situ synchrotron powder x-ray diffraction (PXRD) study was conducted on sodium and potassium tetrafluoroborate (NaBF4 and KBF4) to elucidate structural changes across solid-solid phase transitions over multiple heating-cooling cycles. The phase transition temperatures from diffraction measurements are consistent with the differential scanning calorimetry data (~240 °C for NaBF4 and ~290 °C for KBF4). The crystal structure of the high-temperature (HT) NaBF4 phase has been determined from synchrotron PXRD data. The HT disordered phase of NaBF4 crystallizes in the hexagonal, space group P63/mmc (No. 194) with a = 4.98936(2) Å, c = 7.73464(4) Å, V = 166.748(2) Å3, and Z = 2 at 250 °C. Density functional theory molecular dynamics (MD) calculations imply that the P63/mmc is indeed a stable structure for rotational NaBF4. MD simulations reproduce experimental phase sequence upon heating and indicates that F atoms are markedly more mobile than K and B atoms in the disordered state. Thermal expansion coefficients for both phases were determined from high precision lattice parameters at elevated temperatures, as obtained from Rietveld refinement of PXRD data. Interestingly for the HT-phase of NaBF4, the structure (upon heating) contracts slightly in the a-b plane but expands in the c direction such that overall thermal expansion is positive. Thermal conductivity at room temperature were measured and the values are 0.8-1.0 W.m-1K-1 for NaBF4 and 0.55-0.65 W.m-1K-1 for KBF4. The thermal conductivity and diffusivity showed a gradual decrease up to the transition temperature and then rose slightly. Both materials show good thermal and structural stabilities over multiple heating/cooling cycles.<br/

Incidence of type 2 diabetes in people with a history of hospitalisation for major mental illness in Scotland 2001-2015: a retrospective cohort study

Objective: To determine the incidence of type 2 diabetes in people with a history of hospitalization for major mental illness versus no mental illness in Scotland by time period and sociodemographics. Research Design and Methods: We used national Scottish population-based records to create cohorts with a hospital record of schizophrenia, bipolar disorder, or depression or no mental illness and to ascertain diabetes incidence. We used quasi-Poisson regression models including age, sex, time period, and area-based deprivation to estimate incidence and relative risks (RRs) of diabetes by mental illness status. Estimates are illustrated for people aged 60 years and in the middle deprivation quintile in 2015. Results: We identified 254,136 diabetes cases during 2001–2015. Diabetes incidence in 2015 was 1.5- to 2.5-fold higher in people with versus without a major mental disorder, with the gap having slightly increased over time. RRs of diabetes incidence were greater among women than men for schizophrenia (RR 2.40 [95% CI 2.01, 2.85] and 1.63 [1.38, 1.94]), respectively) and depression (RR 2.10 [1.86, 2.36] and 1.62 [1.43, 1.82]) but similar for bipolar disorder (RR 1.65 [1.35, 2.02] and 1.50 [1.22, 1.84]). Absolute and relative differences in diabetes incidence associated with mental illness increased with increasing deprivation. Conclusions: Disparities in diabetes incidence between people with and without major mental illness appear to be widening. Major mental illness has a greater effect on diabetes risk in women and people living in more deprived areas, which has implications for intervention strategies to reduce diabetes risk in this vulnerable population

Ultra-deep sequencing confirms immunohistochemistry as a highly sensitive and specific method for detecting BRAF (V600E) mutations in colorectal carcinoma

The activating BRAF (V600) mutation is a well-established negative prognostic biomarker in metastatic colorectal carcinoma (CRC). A recently developed monoclonal mouse antibody (clone VE1) has been shown to detect reliably BRAF (V600E) mutated protein by immunohistochemistry (IHC). In this study, we aimed to compare the detection of BRAF (V600E) mutations by IHC, Sanger sequencing (SaS), and ultra-deep sequencing (UDS) in CRC. VE1-IHC was established in a cohort of 68 KRAS wild-type CRCs. The VE1-IHC was only positive in the three patients with a known BRAF (V600E) mutation as assessed by SaS and UDS. The test cohort consisted of 265 non-selected, consecutive CRC samples. Thirty-nine out of 265 cases (14.7 %) were positive by VE1-IHC. SaS of 20 randomly selected IHC negative tumors showed BRAF wild-type (20/20). Twenty-four IHC-positive cases were confirmed by SaS (24/39; 61.5 %) and 15 IHC-positive cases (15/39; 38.5 %) showed a BRAF wild-type by SaS. UDS detected a BRAF (V600E) mutation in 13 of these 15 discordant cases. In one tumor, the mutation frequency was below our threshold for UDS positivity, while in another case, UDS could not be performed due to low DNA amount. Statistical analysis showed sensitivities of 100 % and 63 % and specificities of 95 and 100 % for VE1-IHC and SaS, respectively, compared to combined results of SaS and UDS. Our data suggests that there is high concordance between UDS and IHC using the anti-BRAF(V600E) (VE1) antibody. Thus, VE1 immunohistochemistry is a highly sensitive and specific method in detecting BRAF (V600E) mutations in colorectal carcinoma

Safety and Feasibility of Research Lumbar Puncture in Huntington’s Disease: The HDClarity Cohort and Bioresource

Background: Biomarkers are needed to monitor disease progression, target engagement and efficacy in Huntington’s disease (HD). Cerebrospinal fluid (CSF) is an ideal medium to research such biomarkers due to its proximity to the brain. Objective: To investigate the safety and feasibility of research lumbar punctures (LP) in HD. Methods: HDClarity is an ongoing international biofluid collection initiative built on the Enroll-HD platform, where clinical assessments are recorded. It aims to recruit 1,200 participants. Biosamples are collected following an overnight fast: blood via venipuncture and CSF via LP. Participants are healthy controls and HD gene expansion carriers across the disease spectrum. We report on monitored data from February 2016 to September 2019. Results: Of 448 participants screened, 398 underwent at least 1 sampling visit, of which 98.24% were successful (i.e., CSF was collected), amounting to 10,610 mL of CSF and 8,200 mL of plasma. In the total 572 sampling visits, adverse events were reported in 24.13%, and headaches of any kind and post-LP headaches in 14.86% and 12.24%, respectively. Frequencies were less in manifest HD; gender, age, body mass index and disease burden score were not associated with the occurrence of the events in gene expansion carriers. Headaches and back pain were the most frequent adverse events. Conclusion: HDClarity is the largest CSF collection initiative to support scientific research into HD and is now stablished as a leading resource for HD research. Our data confirm that research LP in HD are feasible and acceptable to the community, and have a manageable safety profile

Unfavourable birth outcomes of the Roma women in the Czech Republic and the potential explanations: a population-based study

BACKGROUND: Data on the health status of the Roma people in Central and Eastern Europe are sparse and the reasons for their poor health are not clear. The objective of this study was to quantify the differences in birth outcomes between Roma and non-Roma mothers in the Czech Republic and to investigate the potential causes of such differences. METHOD: A population-based study recruited 8938 non-Roma and 1388 Roma hospitalised singleton births that occurred in two Czech districts (Teplice and Prachatice) between 1995 and 2004. During their stay in hospital, mothers completed a questionnaire on their demographic and socioeconomic characteristics and maternal smoking and alcohol consumption. Data on maternal height and weight and on infants' birth weight and gestational age were taken from hospital records. RESULTS: Birth weight and gestational age of Roma infants was 373 (SE 15) g and 0.92 (0.05) weeks, respectively, lower than in non-Roma infants. Controlling for demographic, socioeconomic and behavioural factors reduced these differences to 133 (18) g and 0.57 (0.06) weeks, respectively (all p-values < 0.001). In terms of binary outcomes, the Roma vs. non-Roma odds ratios were 4.5 (95% CI 3.7–5.4) for low birth weight (< 2500 g), 2.8 (2.2–3.4) for preterm birth (< 37 weeks of gestation), and 2.9 (2.5–3.4) for intrauterine grown retardation (<10(th )percentile of birth weight for gestational age); controlling for all covariates reduced these odds ratios to 1.7 (1.3–2.2), 1.5 (1.1–2.0) and 1.3 (1.0–1.6), respectively. Maternal education made the largest contribution to the ethnic differences; the role of health behaviours was relatively modest. CONCLUSION: There are striking differences in birth outcomes between Roma and non-Roma mothers. The causes of these differences are complex but largely socioeconomic

Prognostic Significance of POLE Proofreading Mutations in Endometrial Cancer

Background: Current risk stratification in endometrial cancer (EC) results in frequent over- and underuse of adjuvant therapy, and may be improved by novel biomarkers. We examined whether POLE proofreading mutations, recently reported in about 7% of ECs, predict prognosis. Methods: We performed targeted POLE sequencing in ECs from the PORTEC-1 and -2 trials (n = 788), and analyzed clinical outcome according to POLE status. We combined these results with those from three additional series (n = 628) by meta-analysis to generate multivariable-adjusted, pooled hazard ratios (HRs) for recurrence-free survival (RFS) and cancer-specific survival (CSS) of POLE-mutant ECs. All statistical tests were two-sided. Results: POLE mutations were detected in 48 of 788 (6.1%) ECs from PORTEC-1 and-2 and were associated with high tumor grade (P < .001). Women with POLE-mutant ECs had fewer recurrences (6.2% vs 14.1%) and EC deaths (2.3% vs 9.7%), though, in the total PORTEC cohort, differences in RFS and CSS were not statistically significant (multivariable-adjusted HR = 0.43, 95% CI = 0.13 to 1.37, P = .15; HR = 0.19, 95% CI = 0.03 to 1.44, P = .11 respectively). However, of 109 grade 3 tumors, 0 of 15 POLE-mutant ECs recurred, compared with 29 of 94 (30.9%) POLE wild-type cancers; reflected in statistically significantly greater RFS (multivariable-adjusted HR = 0.11, 95% CI = 0.001 to 0.84, P = .03). In the additional series, there were no EC-related events in any of 33 POLE-mutant ECs, resulting in a multivariable-adjusted, pooled HR of 0.33 for RFS (95% CI = 0.12 to 0.91, P = .03) and 0.26 for CSS (95% CI = 0.06 to 1.08, P = .06). Conclusion: POLE proofreading mutations predict favorable EC prognosis, independently of other clinicopathological variables, with the greatest effect seen in high-grade tumors. This novel biomarker may help to reduce overtreatment in E

Serological and virological characterization of clinically diagnosed cases of measles in suburban Khartoum

Measles continues to be a major childhood disease in terms of global morbidity and mortality. In the main areas of its endemicity the only available means of diagnosis are based on clinical criteria: the presence of a maculopapular rash and fever accompanied by cough, coryza, and/or conjunctivitis. We have studied 38 clinically diagnosed cases of measles in Khartoum, Sudan, by means of serology, reverse transcriptase PCR (RT-PCR) on throat swabs and virus isolation from lymphocytes. On the basis of serology, 28 patients were diagnosed as having an acute measles virus (MV) infection, while in 10 cases the clinical symptoms proved to have other causes. It was shown that in cases with low serum immunoglobulin M (IgM) levels, an additional measurement of IgG or virus-neutralizing antibodies was necessary to discriminate between patients with an acute MV infection sampled during an early stage of the disease and patients who had experienced an MV infection in the more distant past. The serological laboratory diagnosis was validated by an MV-specific RT-PCR: for all confirmed measles cases tested a fragment of the correct size which hybridized with a third MV-specific primer could be amplified, while all serologically negative cases were also RT-PCR negative. MV could be isolated from 17 out of 23 of the serologically confirmed cases, demonstrating that virus isolation is less reliable as a diagnostic tool than serology or RT-PCR. This study stresses the urgent need for a rapid diagnostic field test for measles