Preindustrial 14CH4 indicates greater anthropogenic fossil CH4 emissions.

Atmospheric methane (CH4) is a potent greenhouse gas, and its mole fraction has more than doubled since the preindustrial era1. Fossil fuel extraction and use are among the largest anthropogenic sources of CH4 emissions, but the precise magnitude of these contributions is a subject of debate2,3. Carbon-14 in CH4 (14CH4) can be used to distinguish between fossil (14C-free) CH4 emissions and contemporaneous biogenic sources; however, poorly constrained direct 14CH4 emissions from nuclear reactors have complicated this approach since the middle of the 20th century4,5. Moreover, the partitioning of total fossil CH4 emissions (presently 172 to 195 teragrams CH4 per year)2,3 between anthropogenic and natural geological sources (such as seeps and mud volcanoes) is under debate; emission inventories suggest that the latter account for about 40 to 60 teragrams CH4 per year6,7. Geological emissions were less than 15.4 teragrams CH4 per year at the end of the Pleistocene, about 11,600 years ago8, but that period is an imperfect analogue for present-day emissions owing to the large terrestrial ice sheet cover, lower sea level and extensive permafrost. Here we use preindustrial-era ice core 14CH4 measurements to show that natural geological CH4 emissions to the atmosphere were about 1.6 teragrams CH4 per year, with a maximum of 5.4 teragrams CH4 per year (95 per cent confidence limit)-an order of magnitude lower than the currently used estimates. This result indicates that anthropogenic fossil CH4 emissions are underestimated by about 38 to 58 teragrams CH4 per year, or about 25 to 40 per cent of recent estimates. Our record highlights the human impact on the atmosphere and climate, provides a firm target for inventories of the global CH4 budget, and will help to inform strategies for targeted emission reductions9,10.

Source-based morphometry reveals structural brain pattern abnormalities in 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11DS) is the most frequently occurring microdeletion in humans. It is associated with a significant impact on brain structure, including prominent reductions in gray matter volume (GMV), and neuropsychiatric manifestations, including cognitive impairment and psychosis. It is unclear whether GMV alterations in 22q11DS occur according to distinct structural patterns. Then, 783 participants (470 with 22q11DS: 51% females, mean age [SD] 18.2 [9.2]; and 313 typically developing [TD] controls: 46% females, mean age 18.0 [8.6]) from 13 datasets were included in the present study. We segmented structural T1-weighted brain MRI scans and extracted GMV images, which were then utilized in a novel source-based morphometry (SBM) pipeline (SS-Detect) to generate structural brain patterns (SBPs) that capture co-varying GMV. We investigated the impact of the 22q11.2 deletion, deletion size, intelligence quotient, and psychosis on the SBPs. Seventeen GMV-SBPs were derived, which provided spatial patterns of GMV covariance associated with a quantitative metric (i.e., loading score) for analysis. Patterns of topographically widespread differences in GMV covariance, including the cerebellum, discriminated individuals with 22q11DS from healthy controls. The spatial extents of the SBPs that revealed disparities between individuals with 22q11DS and controls were consistent with the findings of the univariate voxel-based morphometry analysis. Larger deletion size was associated with significantly lower GMV in frontal and occipital SBPs; however, history of psychosis did not show a strong relationship with these covariance patterns. 22q11DS is associated with distinct structural abnormalities captured by topographical GMV covariance patterns that include the cerebellum. Findings indicate that structural anomalies in 22q11DS manifest in a nonrandom manner and in distinct covarying anatomical patterns, rather than a diffuse global process. These SBP abnormalities converge with previously reported cortical surface area abnormalities, suggesting disturbances of early neurodevelopment as the most likely underlying mechanism.

The Eczema Area and Severity Index: An update of progress and challenges in its measurement of atopic dermatitis after 20 years of use.

The Eczema Area and Severity Index is an investigator-assessed instrument reporting clinical signs of atopic dermatitis. The instrument is extensively validated in both adult and paediatric populations and recommended as a core outcome measure to assess clinical signs by the Harmonising Outcome Measures for Eczema initiative in clinical trials and was recently recommended as an option to measure signs in clinical practice. Here, we review the validation of the instrument using standard assessment criteria, explore controversies and challenges to its universal applicability and highlight future electronic adaptations. We find that the instrument demonstrates adequate performance in the measurement properties recommended by the COnsensus-based Standards for the selection of health Measurement INstruments initiative for instruments reporting clinical signs, is clinically interpretable, and is suitable for all atopic dermatitis severities. Some validation gaps remain. Information reporting on its performance in diverse populations, with emphasis on deeply pigmented skin, is promising though limited. Technological adaptations are demonstrating promising initial validation results and may facilitate remote and/or automated assessments assisting clinical care and decentralized clinical trials in the future. We find no strong evidence limiting its use in trials or clinical practice although questions pertaining to the effect of investigator training remain. We recommend that the Eczema Area and Severity Index be used in all interventional atopic dermatitis trials and be considered alongside other recommended clinical practice severity instruments.

Brain Growth Charts for Quantitative Analysis of Pediatric Clinical Brain MRI Scans with Limited Imaging Pathology.

Background Clinically acquired brain MRI scans represent a valuable but underused resource for investigating neurodevelopment due to their technical heterogeneity and lack of appropriate controls. These barriers have curtailed retrospective studies of clinical brain MRI scans compared with more costly prospectively acquired research-quality brain MRI scans. Purpose To provide a benchmark for neuroanatomic variability in clinically acquired brain MRI scans with limited imaging pathology (SLIPs) and to evaluate if growth charts from curated clinical MRI scans differed from research-quality MRI scans or were influenced by clinical indication for the scan. Materials and Methods In this secondary analysis of preexisting data, clinical brain MRI SLIPs from an urban pediatric health care system (individuals aged ≤22 years) were scanned across nine 3.0-T MRI scanners. The curation process included manual review of signed radiology reports and automated and manual quality review of images without gross pathology. Global and regional volumetric imaging phenotypes were measured using two image segmentation pipelines, and clinical brain growth charts were quantitatively compared with charts derived from a large set of research controls in the same age range by means of Pearson correlation and age at peak volume. Results The curated clinical data set included 532 patients (277 male; median age, 10 years [IQR, 5-14 years]; age range, 28 days after birth to 22 years) scanned between 2005 and 2020. Clinical brain growth charts were highly correlated with growth charts derived from research data sets (22 studies, 8346 individuals [4947 male]; age range, 152 days after birth to 22 years) in terms of normative developmental trajectories predicted by the models (median r = 0.979). Conclusion The clinical indication of the scans did not significantly bias the output of clinical brain charts. Brain growth charts derived from clinical controls with limited imaging pathology were highly correlated with brain charts from research controls, suggesting the potential of curated clinical MRI scans to supplement research data sets. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Ertl-Wagner and Pai in this issue.

ß

For the first time, the (d,^{2}He) reaction was successfully used in inverse kinematics to extract the Gamow-Teller transition strength in the ß^{+} direction from an unstable nucleus. The new technique was made possible by the use of an active-target time-projection chamber and a magnetic spectrometer, and opens a path to addressing a range of scientific challenges, including in astrophysics and neutrino physics. In this Letter, the nucleus studied was ^{14}O, and the Gamow-Teller transition strength to ^{14}N was extracted up to an excitation energy of 22 MeV. The data were compared to shell-model and state-of-the-art coupled-cluster calculations. Shell-model calculations reproduce the measured Gamow-Teller strength distribution up to about 15 MeV reasonably well, after the application of a phenomenological quenching factor. In a significant step forward to better understand this quenching, the coupled-cluster calculation reproduces the full strength distribution well without such quenching, owing to the large model space, the inclusion of strong correlations, and the coupling of the weak interaction to two nucleons through two-body currents.

Genetic and Environmental Variation in Continuous Phenotypes in the ABCD Study®.

Twin studies yield valuable insights into the sources of variation, covariation and causation in human traits. The ABCD Study® (abcdstudy.org) was designed to take advantage of four universities known for their twin research, neuroimaging, population-based sampling, and expertise in genetic epidemiology so that representative twin studies could be performed. In this paper we use the twin data to: (i) provide initial estimates of heritability for the wide range of phenotypes assessed in the ABCD Study using a consistent direct variance estimation approach, assuring that both data and methodology are sound; and (ii) provide an online resource for researchers that can serve as a reference point for future behavior genetic studies of this publicly available dataset. Data were analyzed from 772 pairs of twins aged 9-10 years at study inception, with zygosity determined using genotypic data, recruited and assessed at four twin hub sites. The online tool provides twin correlations and both standardized and unstandardized estimates of additive genetic, and environmental variation for 14,500 continuously distributed phenotypic features, including: structural and functional neuroimaging, neurocognition, personality, psychopathology, substance use propensity, physical, and environmental trait variables. The estimates were obtained using an unconstrained variance approach, so they can be incorporated directly into meta-analyses without upwardly biasing aggregate estimates. The results indicated broad consistency with prior literature where available and provided novel estimates for phenotypes without prior twin studies or those assessed at different ages. Effects of site, self-identified race/ethnicity, age and sex were statistically controlled. Results from genetic modeling of all 53,172 continuous variables, including 38,672 functional MRI variables, will be accessible via the user-friendly open-access web interface we have established, and will be updated as new data are released from the ABCD Study. This paper provides an overview of the initial results from the twin study embedded within the ABCD Study, an introduction to the primary research domains in the ABCD study and twin methodology, and an evaluation of the initial findings with a focus on data quality and suitability for future behavior genetic studies using the ABCD dataset. The broad introductory material is provided in recognition of the multidisciplinary appeal of the ABCD Study. While this paper focuses on univariate analyses, we emphasize the opportunities for multivariate, developmental and causal analyses, as well as those evaluating heterogeneity by key moderators such as sex, demographic factors and genetic background.

Genetic Influences on Longitudinal Trajectories of Cortical Thickness and Surface Area during the First 2 Years of Life.

Genetic influences on cortical thickness (CT) and surface area (SA) are known to vary across the life span. Little is known about the extent to which genetic factors influence CT and SA in infancy and toddlerhood. We performed the first longitudinal assessment of genetic influences on variation in CT and SA in 501 twins who were aged 0-2 years. We observed substantial additive genetic influences on both average CT (0.48 in neonates, 0.37 in 1-year-olds, and 0.44 in 2-year-olds) and total SA (0.59 in neonates, 0.74 in 1-year-olds, and 0.73 in 2-year-olds). In addition, we found strong heritability of the change in average CT (0.49) from neonates to 1-year-olds, but not from 1- to 2-year-olds. Moreover, we found strong genetic correlations for average CT (rG = 0.92) between 1- and 2-year-olds and strong genetic correlations for total SA across all timepoints (rG = 0.96 between neonates and 1-year-olds, rG = 1 between 1- and 2-year-olds). In addition, we found CT and SA are strongly genetic correlated at birth, but weaken over time. Overall, results suggest a dynamic genetic relationship between CT and SA during first 2 years of life and provide novel insights into how genetic influences shape the cortical structure during early brain development.

Exploring the overlap between alopecia areata and major depressive disorder: Epidemiological and genetic perspectives.

BACKGROUND: Research suggests that Alopecia areata (AA) and Major Depressive Disorder (MDD) show substantial comorbidity. To date, no study has investigated the hypothesis that this is attributable to shared genetic aetiology. OBJECTIVES: To investigate AA-MDD comorbidity on the epidemiological and molecular genetic levels. METHODS: First, epidemiological analyses were performed using data from a cohort of adult German health insurance beneficiaries (n = 1.855 million) to determine the population-based prevalence of AA-MDD comorbidity. Second, analyses were performed to determine the prevalence of MDD in a clinical AA case-control sample with data on psychiatric phenotypes, stratifying for demographic factors to identify possible contributing factors to AA-MDD comorbidity. Third, the genetic overlap between AA and MDD was investigated using a polygenic risk score (PRS) approach and linkage disequilibrium score (LDSC) regression. For PRS, summary statistics from a large MDD GWAS meta-analysis (PGC-MD2) were used as the training sample, while a Central European AA cohort, including the above-mentioned AA patients, and an independent replication US-AA cohort were used as target samples. LDSC was performed using summary statistics of PGC-MD2 and the largest AA meta-analysis to date. RESULTS: High levels of AA-MDD comorbidity were reported in the population-based (MDD in 24% of AA patients), and clinical samples (MDD in 44% of AA patients). MDD-PRS explained a modest proportion of variance in AA case-control status (R2  = 1%). This signal was limited to the major histocompatibility complex (MHC) region on chromosome 6. LDSC regression (excluding MHC) revealed no significant genetic correlation between AA and MDD. CONCLUSIONS: As in previous research, AA patients showed an increased prevalence of MDD. The present analyses suggest that genetic overlap may be confined to the MHC region, which is implicated in immune function. More detailed investigation is required to refine understanding of how the MHC is involved in the development of AA and MDD comorbidity.

Presynchronization with prostaglandin F2α and gonadotropin-releasing hormone simultaneously improved first-service pregnancy per artificial insemination in lactating Holstein cows compared with Presynch-14 when combined with detection of estrus.

This study aimed to determine the effect of 2 simple breeding strategies combining artificial insemination (AI) after detection of estrus (AIED) and timed AI (TAI) on first-service fertility in lactating Holstein cows. Weekly, lactating Holstein cows (n = l,049) between 40 and 46 d in milk (DIM) were randomly assigned to initiate 1 of 2 breeding strategies for first service: Presynch-14 and PG+G. Presynch-14 is a presynchronization strategy with 2 PGF2α treatments 14 d apart with the last PGF2α 14 d before the initiation of the Ovsynch protocol. Cows treated with PG+G receive a simpler presynchronization program that uses PGF2α and GnRH simultaneously 7 d before Ovsynch. In both treatments, cows detected in standing estrus by tail chalk at any time ≥55 DIM were inseminated, and treatment was discontinued (n = 525). Cows completing treatment received TAI from 78 to 84 DIM (n = 526). In a subgroup of cows that received TAI, blood was collected (n = 163) to assess circulating concentrations of progesterone, and ultrasonographic evaluations of ovaries were performed on the day of first GnRH of Ovsynch (n = 162) and PGF2α of Ovsynch (n = 122). The proportion of cows that received TAI was greater for PG+G compared with Presynch-14 (63.5 vs. 31.9%), which increased DIM at first service for cows treated with PG+G compared with Presynch-14 (75.5 ± 0.4 vs. 68.7 ± 0.4). For cows receiving TAI, the ovulatory response to first GnRH of Ovsynch (73.8 vs. 48.8%) and the proportion of cows with functional corpora lutea (92.6 vs. 73.1%) were greater for PG+G than Presynch-14. Cows treated with PG+G had greater overall pregnancy per AI (P/AI) 42 ± 7 d after AI (40.2 vs. 33.6%) and calving per AI (32.1 vs. 25.2%) than Presynch-14. For cows receiving AIED, treatment did not affect P/AI 42 ± 7 d after AI. However, for cows receiving TAI, PG+G increased P/AI compared with Presynch-14 (44.6 vs. 35.2%). Overall, cows receiving TAI had greater P/AI 42 ± 7 d after AI (42.5 vs. 31.5%) and calving per AI (34.1 vs. 23.7%) and decreased pregnancy loss (16.8 vs. 25.2%) than cows receiving AIED. In summary, PG+G increased the proportion of cows receiving TAI and the DIM at first service, P/AI, and calving per AI compared with Presynch-14 when both TAI programs were combined with AIED.

Are patients benefiting from participation in the German skin cancer screening programme? A large cohort study based on administrative data.

BACKGROUND: The German programme for skin cancer screening was established in 2008 with the aim of reducing skin cancer mortality. However, the effectiveness and risk-benefit ratio of the programme remain unclear. OBJECTIVES: To compare the mortality rates of patients with melanoma who participate in a screening programme to those who do not. METHODS: A retrospective cohort study, based on pseudonymized health insurance data of 1 431 327 individuals from Saxony, Germany, was conducted for the period 2010-2016. Patients with prevalent and incident melanoma were defined based on diagnosis, medical procedures and prescriptions. Patients who underwent screening and had a first diagnosis of melanoma within 2 years of screening were assigned to the intervention group. Relative survival and Cox regression were used to assess potential differences in mortality. RESULTS: We identified 4552 individuals with prevalent and 2475 individuals with incident melanoma. The percentage of screening participants (n = 1801) who had locoregional (4·2% vs. 13·5%) and/or distant metastases (4·3% vs. 8·0%), or who were treated with systemic anticancer therapies (11·6% vs. 21·8%) was lower vs. nonparticipants (n = 674). Screening participants had significantly better survival rates. The unadjusted Cox model gave a hazard ratio (HR) of 0·37 [95% confidence interval (CI) 0·30-0·46]. After adjusting for named confounders, the effect remained (HR 0·62, 95% CI 0·48-0·80). CONCLUSIONS: Patients who participated in the screening programme had lower mortality than those who had not undergone screening. However, these findings may result from a healthy screen bias and/or overdiagnosis associated with screening, and not from the screening itself.

Evaluation of Potential Cumulative Risk of Multiple 1.5-T MRI Examinations in Patients With Cardiac Implanted Electronic Devices.

Although professional societies now support MRI in patients with nonconditional (legacy) cardiac implanted electronic devices (CIEDs), concern remains regarding potential cumulative effects of serial examinations. We evaluated 481 patients with CIEDs who underwent 599 1.5-T MRI examinations (44.6% cardiac examinations), including 68 patients who underwent multiple examinations (maximum, seven examinations). No major events occurred. The minor adverse event rate was 5.7%. Multiple statistical evaluations showed no increase in adverse event rate with increasing number of previous examinations.

The Heritability of Cortical Folding: Evidence from the Human Connectome Project.

The mechanisms underlying cortical folding are incompletely understood. Prior studies have suggested that individual differences in sulcal depth are genetically mediated, with deeper and ontologically older sulci more heritable than others. In this study, we examine FreeSurfer-derived estimates of average convexity and mean curvature as proxy measures of cortical folding patterns using a large (N = 1096) genetically informative young adult subsample of the Human Connectome Project. Both measures were significantly heritable near major sulci and primary fissures, where approximately half of individual differences could be attributed to genetic factors. Genetic influences near higher order gyri and sulci were substantially lower and largely nonsignificant. Spatial permutation analysis found that heritability patterns were significantly anticorrelated to maps of evolutionary and neurodevelopmental expansion. We also found strong phenotypic correlations between average convexity, curvature, and several common surface metrics (cortical thickness, surface area, and cortical myelination). However, quantitative genetic models suggest that correlations between these metrics are largely driven by nongenetic factors. These findings not only further our understanding of the neurobiology of gyrification, but have pragmatic implications for the interpretation of heritability maps based on automated surface-based measurements.

Lifetime prevalence and determinants of hand eczema in an adolescent population in Germany: 15-year follow-up of the LISA cohort study.

BACKGROUND: Hand eczema is a common inflammatory skin disorder in both adolescence and adulthood. OBJECTIVES: We sought to assess the lifetime prevalence of hand eczema and associated exogenous and endogenous risk factors among adolescents in Germany. METHODS: This was a cross-sectional study embedded into a prospective population-based birth cohort in four regions of Germany, which recruited healthy neonates born between November 1997 and January 1999. We included 1736 participants who had completed the 15-year follow-up from birth cohort and 84.6% (1468/1736) had clearly reported whether they have ever had hand eczema. All the data were based on questionnaires and blood tests (immunoglobulin E). Multivariable logistic regression analysis was used to examine endogenous and exogenous factors in relation to the lifetime prevalence of hand eczema among adolescents. RESULTS: One thousand four hundred and sixty-eight adolescents (715 girls, 48.7%) were included in the final analysis. The lifetime prevalence of hand eczema among adolescents at the age of 15 was 10.4% (95% confidence interval [CI]: 8.9%-12.1%), with a significantly higher lifetime prevalence among girls than boys (12.7% vs. 8.2%, P = 0.005). Multivariable logistic regression analysis indicated statistically significant associations between the lifetime prevalence of hand eczema and having ever been diagnosed with atopic dermatitis (aOR = 1.8, 95% CI: 1.1-2.8) or having ever had dry skin (aOR = 1.9, 95% CI: 1.1-3.1), respectively. No statistically significant independent associations were found between asthma, hay fever, allergy-related clinical symptoms, immunoglobulin E positivity and other exogenous factors in relation to hand eczema. CONCLUSION: Our study fills a research gap on the epidemiological burden of hand eczema among adolescents. One out of ten ever suffered from hand eczema until age 15 years indicating that hand eczema constitutes a significant burden in paediatric populations. The role of atopic dermatitis in hand eczema reinforces previous findings. Exogenous risk factors warrant further investigation.

Atopic dermatitis: disease characteristics and comorbidities in smoking and non-smoking patients from the TREATgermany registry.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease with a multifactorial genesis including genetic predispositions and environmental risk and trigger factors. One of the latter possibly is smoking, indicated by an increased prevalence of AD in adults and children that are actively or passively exposed to cigarette smoke. OBJECTIVES: In this study, AD characteristics and its atopic comorbidities are compared in smoking and non-smoking AD patients. METHODS: TREATgermany is a non-interventional clinical registry which includes patients with moderate to severe AD in Germany. Baseline data of patients included in TREATgermany from inception in June 2016 to April 2020 in 39 sites across Germany was analysed comparing AD disease characteristics and comorbidities in smokers vs. non-smokers. RESULTS: Of 921 patients, 908 (male: 58.7%) with a mean age of 41.9 ± 14.4 reported their smoking status. The objective Scoring of Atopic Dermatitis (oSCORAD) did not differ between smokers (n = 352; 38.8%) and non-smokers, however, lesions' intensity of oozing/crusts and excoriations as well as patient global assessment scores (PGA) of AD severity were higher in smoking as opposed to non-smoking patients. Smokers reported a lower number of weeks with well-controlled AD and more severe pruritus than non-smokers. Total IgE levels were more elevated in smokers and they displayed a younger age at the initial diagnosis of bronchial asthma. After adjustment for potential confounders, the increased intensity of oozing/crusts, the reduced number of weeks with well-controlled AD and the greater pruritus remained different in smokers compared to non-smokers. In addition, smoking patients with adult-onset AD showed a 2.5 times higher chance of involvement of the feet. CONCLUSIONS: German registry data indicate that AD patients who smoke have a higher disease burden with a different distribution pattern of lesions in adult-onset AD.

[Evolution of histocompatibility methods in organ transplantation: an update in 2022]. / Évolution des méthodes d'histocompatibilité dans la greffe d'organe : le point en 2022.

The evaluation of anti-HLA immunization in organ transplantation has evolved dramatically since the first lymphocytotoxic crossmatch between donor and recipient was described. The same is true for HLA typing, which can now be performed by high-resolution sequencing. Nevertheless, the transplantation of a totally compatible organ remains an exception and the appearance of anti-HLA antibodies during the transplantation is inevitable, which conditions the long-term survival of the graft. New computer tools are currently being developed to evaluate and quantify the degree of incompatibility between donor and recipient, with a view to predicting the risk of rejection and adapting immunosuppressive therapy in a targeted manner for each patient.

L'évaluation de l'immunisation anti-HLA dans la transplantation d'organe a évolué de façon spectaculaire depuis la description des premiers crossmatchs par lymphocytotoxicité entre donneur et receveur. Il en est de même pour le typage HLA, qui peut maintenant être réalisé par séquençage en haute résolution. Néanmoins, la greffe d'organe totalement compatible reste une exception et l'apparition d'anticorps anti-HLA dans le décours de la greffe est inévitable, ce qui conditionne la survie du greffon à long terme. De nouveaux outils informatiques sont actuellement développés pour évaluer et quantifier le degré d'incompatibilité entre donneur et receveur, dans la perspective de prédire le risque de rejet et adapter la thérapie immunosuppressive de façon ciblée pour chaque patient.

New

The discrepancy between observations from γ-ray astronomy of the ^{60}Fe/^{26}Al γ-ray flux ratio and recent calculations is an unresolved puzzle in nuclear astrophysics. The stellar ß-decay rate of ^{59}Fe is one of the major nuclear uncertainties impeding us from a precise prediction. The important Gamow-Teller strengths from the low-lying states in ^{59}Fe to the ^{59}Co ground state are measured for the first time using the exclusive measurement of the ^{59}Co(t,^{3}He+γ)^{59}Fe charge-exchange reaction. The new stellar decay rate of ^{59}Fe is a factor of 3.5±1.1 larger than the currently adopted rate at T=1.2 GK. Stellar evolution calculations show that the ^{60}Fe production yield of an 18 solar mass star is decreased significantly by 40% when using the new rate. Our result eliminates one of the major nuclear uncertainties in the predicted yield of ^{60}Fe and alleviates the existing discrepancy of the ^{60}Fe/^{26}Al ratio.

eCross-cultural adaptation of the spine oncology-specific SOSGOQ2.0 questionnaire to German language and the assessment of its validity and reliability in the clinical setting.

BACKGROUND: The recently developed Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ2.0) was proven a valid and reliable instrument measuring health-related quality of life (HRQOL) for patients with spinal malignancies. A German version was not available. OBJECTIVE: A cross-cultural adaptation of the SOSGOQ2.0 to the German language and its multicenter evaluation. METHODS: In a multistep process, a cross-cultural adaptation of the SOSGOQ2.0 was conducted. Subsequently, a multicenter, prospective observational cohort study was initiated to assess the reliability and validity of the German adaptation. To assess external construct validity of the cross-cultural adapted questionnaire, a comparison to the established questionnaire QLQ-C30 from the European Organisation for Research and Treatment of Cancer was conducted. Mean-difference plots were used to measure the agreement between the questionnaires in total score and by domain (deviation from mean up to 10% allowed). Further reliability and validity tests were carried out. Change to baseline was analysed 3-16 weeks later after different interventions occurred. Clinically relevant thresholds in comparison to the EORTC QLQ-C30 questionnaire were evaluated by ROC curve analysis. RESULTS: We could enroll 113 patients from four different university hospitals (58 females, 55 males). Mean age was 64.11 years (sd 11.9). 80 patients had an ECOG performance status of 2 or higher at baseline. External construct validity in comparison to the EORTC QLQ-C30 questionnaire in total score and by domain was confirmed (range of deviation 4.4 to 9.0%). Good responsiveness for the domains Physical Functioning (P < .001) and Pain (P < .001) could be shown. The group mean values also displayed a difference in the domains of Social Functioning (P = .331) and Mental Health (P = .130), but not significant. The minimum clinically relevant threshold values for the questionnaire ranged from 4.0 to 7.5 points. CONCLUSIONS: According to our results, the cross-cultural adapted questionnaire is a reliable and valid tool to measure HRQOL in German speaking patients with spinal malignancies. Especially the domains Physical Functioning and Pain showed overall good psychometric characteristics. In this way, a generic questionnaire, such as the EORTC QLQ-C30, can be usefully supplemented by spine-specific questions to increase the overall accuracy measuring HRQOL in patients with spinal malignancies.

Altered white matter microstructure in 22q11.2 deletion syndrome: a multisite diffusion tensor imaging study.

22q11.2 deletion syndrome (22q11DS)-a neurodevelopmental condition caused by a hemizygous deletion on chromosome 22-is associated with an elevated risk of psychosis and other developmental brain disorders. Prior single-site diffusion magnetic resonance imaging (dMRI) studies have reported altered white matter (WM) microstructure in 22q11DS, but small samples and variable methods have led to contradictory results. Here we present the largest study ever conducted of dMRI-derived measures of WM microstructure in 22q11DS (334 22q11.2 deletion carriers and 260 healthy age- and sex-matched controls; age range 6-52 years). Using harmonization protocols developed by the ENIGMA-DTI working group, we identified widespread reductions in mean, axial and radial diffusivities in 22q11DS, most pronounced in regions with major cortico-cortical and cortico-thalamic fibers: the corona radiata, corpus callosum, superior longitudinal fasciculus, posterior thalamic radiations, and sagittal stratum (Cohen's d's ranging from -0.9 to -1.3). Only the posterior limb of the internal capsule (IC), comprised primarily of corticofugal fibers, showed higher axial diffusivity in 22q11DS. 22q11DS patients showed higher mean fractional anisotropy (FA) in callosal and projection fibers (IC and corona radiata) relative to controls, but lower FA than controls in regions with predominantly association fibers. Psychotic illness in 22q11DS was associated with more substantial diffusivity reductions in multiple regions. Overall, these findings indicate large effects of the 22q11.2 deletion on WM microstructure, especially in major cortico-cortical connections. Taken together with findings from animal models, this pattern of abnormalities may reflect disrupted neurogenesis of projection neurons in outer cortical layers.

Large-scale mapping of cortical alterations in 22q11.2 deletion syndrome: Convergence with idiopathic psychosis and effects of deletion size.

The 22q11.2 deletion (22q11DS) is a common chromosomal microdeletion and a potent risk factor for psychotic illness. Prior studies reported widespread cortical changes in 22q11DS, but were generally underpowered to characterize neuroanatomic abnormalities associated with psychosis in 22q11DS, and/or neuroanatomic effects of variability in deletion size. To address these issues, we developed the ENIGMA (Enhancing Neuro Imaging Genetics Through Meta-Analysis) 22q11.2 Working Group, representing the largest analysis of brain structural alterations in 22q11DS to date. The imaging data were collected from 10 centers worldwide, including 474 subjects with 22q11DS (age = 18.2 ± 8.6; 46.9% female) and 315 typically developing, matched controls (age = 18.0 ± 9.2; 45.9% female). Compared to controls, 22q11DS individuals showed thicker cortical gray matter overall (left/right hemispheres: Cohen's d = 0.61/0.65), but focal thickness reduction in temporal and cingulate cortex. Cortical surface area (SA), however, showed pervasive reductions in 22q11DS (left/right hemispheres: d = -1.01/-1.02). 22q11DS cases vs. controls were classified with 93.8% accuracy based on these neuroanatomic patterns. Comparison of 22q11DS-psychosis to idiopathic schizophrenia (ENIGMA-Schizophrenia Working Group) revealed significant convergence of affected brain regions, particularly in fronto-temporal cortex. Finally, cortical SA was significantly greater in 22q11DS cases with smaller 1.5 Mb deletions, relative to those with typical 3 Mb deletions. We found a robust neuroanatomic signature of 22q11DS, and the first evidence that deletion size impacts brain structure. Psychotic illness in this highly penetrant deletion was associated with similar neuroanatomic abnormalities to idiopathic schizophrenia. These consistent cross-site findings highlight the homogeneity of this single genetic etiology, and support the suitability of 22q11DS as a biological model of schizophrenia.

Outcomes for Pressure Ulcer Trials (OUTPUTs) project: review and classification of outcomes reported in pressure ulcer prevention research.

In order to overcome inconsistencies in the reporting of outcomes in clinical trials, core outcome sets (COSs) have been developed in many clinical areas and the awareness of this concept is growing steadily. The Outcomes for Pressure Ulcer Trials (OUTPUTs) project aims to improve the quality of evidence from pressure ulcer prevention trials by developing a COS. As an initial step in the COS process we aimed to identify and classify both outcomes and concepts that represent potential outcomes for future trials that have been reported in pressure ulcer prevention research. A review was conducted in 12 major databases covering the literature indexed until 2016. Outcomes and relevant concepts reported in primary studies and/or reviews on pressure ulcer prevention in adult patients were extracted as presented in the articles, and afterwards inductively grouped into outcome domains. The domains were then categorized according to the outcome domain taxonomy recently proposed by the COMET group. In total 332 studies were included and 68 outcome domains were identified, covering multiple aspects of pressure ulcer prevention. Pressure ulcer occurrence was reported in 71% of all included studies, representing the most frequent outcome, followed by costs (22% of all studies) and acceptability of intervention and comfort (18% of all studies). A plethora of different outcomes are applied in pressure ulcer prevention research and substantial variations in definitions and reporting of similar outcomes were observed. A COS for pressure ulcer prevention trials is needed to overcome the noncomparability of outcomes.