Angular dependence of the Wigner time delay upon tunnel ionization of H2H_{2}

More than 100 years after its discovery and its explanation in the energy domain, the duration of the photoelectric effect is still heavily studied. The emission time of a photoelectron can be quantified by the Wigner time delay. Experiments addressing this time delay for single-photon ionization became feasible during the last 10 years. A missing piece, which has not been studied, so far, is the Wigner time delay for strong-field ionization of molecules. Here we show experimental data on the Wigner time delay for tunnel ionization of $H_{2}$ molecules and demonstrate its dependence on the emission direction of the electron with respect to the molecular axis. We find, that the observed changes in the Wigner time delay can be quantitatively explained by elongated/shortened travel paths of the electrons that are due to spatial shifts of the electron's birth position after tunneling. This introduces an intuitive perspective towards the Wigner time delay in strong-field ionization.Comment: 17 pages, 6 figure

Reducing the impact of physical inactivity: evidence to support the case for targeting people with chronic mental and physical conditions

Background : Recent evidence suggests that small increases in the physical activity of those considered least active can have a bigger health impact than raising levels of those already achieving or close to achieving recommendations. Profiling the characteristics of those who are least active allows for appropriate targeting of interventions. This study therefore examined the characteristics of people in the lowest physical activity bracket. Methods : Data were taken from the Collaboration for Leadership in Applied Health Research and Care (CLAHRC) funded ‘South Yorkshire Cohort’, a longitudinal observational dataset of residents of South Yorkshire, England. Five separate outcomes based on a shortened version of the GPPAQ were used to represent the lowest levels of physical activity. Potential predictors examined were age, sex, body mass index, ethnicity, chronic conditions, current employment and deprivation. Descriptive statistics and logistic regression were conducted. Results : Individuals with chronic mental and physical conditions (fatigue, insomnia, anxiety, depression, diabetes, breathing problems, high blood pressure, heart disease, stroke and cancer) were more likely to report the lowest levels of physical activity across all five outcomes. Demographic variations were also observed. Conclusions : Targeting people with chronic mental and physical conditions has the potential to reduce the impact of physical inactivity.</p

Understanding Dwarf Galaxies in order to Understand Dark Matter

Much progress has been made in recent years by the galaxy simulation community in making realistic galaxies, mostly by more accurately capturing the effects of baryons on the structural evolution of dark matter halos at high resolutions. This progress has altered theoretical expectations for galaxy evolution within a Cold Dark Matter (CDM) model, reconciling many earlier discrepancies between theory and observations. Despite this reconciliation, CDM may not be an accurate model for our Universe. Much more work must be done to understand the predictions for galaxy formation within alternative dark matter models.Comment: Refereed contribution to the Proceedings of the Simons Symposium on Illuminating Dark Matter, to be published by Springe

Interaction of developmental factors and ordinary stressful life events on brain structure in adults

An interplay of early environmental and genetic risk factors with recent stressful life events (SLEs) in adulthood increases the risk for adverse mental health outcomes. The interaction of early risk and current SLEs on brain structure has hardly been investigated. Whole brain voxel-based morphometry analysis was performed in N = 786 (64.6% female, mean age = 33.39) healthy subjects to identify correlations of brain clusters with commonplace recent SLEs. Genetic and early environmental risk factors, operationalized as those for severe psychopathology (i.e., polygenic scores for neuroticism, childhood maltreatment, urban upbringing and paternal age) were assessed as modulators of the impact of SLEs on the brain. SLEs were negatively correlated with grey matter volume in the left medial orbitofrontal cortex (mOFC, FWE p = 0.003). This association was present for both, positive and negative, life events. Cognitive-emotional variables, i.e., neuroticism, perceived stress, trait anxiety, intelligence, and current depressive symptoms did not account for the SLE-mOFC association. Further, genetic and environmental risk factors were not correlated with grey matter volume in the left mOFC cluster and did not affect the association between SLEs and left mOFC grey matter volume. The orbitofrontal cortex has been implicated in stress-related psychopathology, particularly major depression in previous studies. We find that SLEs are associated with this area. Important early life risk factors do not interact with current SLEs on brain morphology in healthy subjects

Gamma and Beta Oscillations in Human MEG Encode the Contents of Vibrotactile Working Memory

Ample evidence suggests that oscillations in the beta band represent quantitative information about somatosensory features during stimulus retention. Visual and auditory working memory (WM) research, on the other hand, has indicated a predominant role of gamma oscillations for active WM processing. Here we reconciled these findings by recording whole-head magnetoencephalography during a vibrotactile frequency comparison task. A Braille stimulator presented healthy subjects with a vibration to the left fingertip that was retained in WM for comparison with a second stimulus presented after a short delay. During this retention interval spectral power in the beta band from the right intraparietal sulcus and inferior frontal gyrus (IFG) monotonically increased with the to-be-remembered vibrotactile frequency. In contrast, induced gamma power showed the inverse of this pattern and decreased with higher stimulus frequency in the right IFG. Together, these results expand the previously established role of beta oscillations for somatosensory WM to the gamma band and give further evidence that quantitative information may be processed in a fronto-parietal network

Embedding physical activity in the heart of the NHS: the need for a whole-system approach

Solutions to the global challenge of physical inactivity have tended to focus on interventions at an individual level, when evidence shows that wider factors, including the social and physical environment, play a major part in influencing health-related behaviour. A multidisciplinary perspective is needed to rewrite the research agenda on physical activity if population-level public health benefits are to be demonstrated. This article explores the questions that this raises regarding the particular role that the UK National Health Service (NHS) plays in the system. The National Centre for Sport and Exercise Medicine in Sheffield is put forward as a case study to discuss some of the ways in which health systems can work in collaboration with other partners to develop environments and systems that promote active lives for patients and staff

Personalized diagnosis in suspected myocardial infarction

Background: In suspected myocardial infarction (MI), guidelines recommend using high-sensitivity cardiac troponin (hscTn)- based approaches. These require fixed assay-specific thresholds and timepoints, without directly integrating clinical information. Using machine-learning techniques including hs-cTn and clinical routine variables, we aimed to build a digital tool to directly estimate the individual probability of MI, allowing for numerous hs-cTn assays. Methods: In 2,575 patients presenting to the emergency department with suspected MI, two ensembles of machine-learning models using single or serial concentrations of six different hs-cTn assays were derived to estimate the individual MI probability ( ARTEMIS model). Discriminative performance of the models was assessed using area under the receiver operating characteristic curve (AUC) and logLoss. Model performance was validated in an external cohort with 1688 patients and tested for global generalizability in 13 international cohorts with 23,411 patients. Results: Eleven routinely available variables including age, sex, cardiovascular risk factors, electrocardiography, and hs-cTn were included in the ARTEMIS models. In the validation and generalization cohorts, excellent discriminative performance was confirmed, superior to hs-cTn only. For the serial hs-cTn measurement model, AUC ranged from 0.92 to 0.98. Good calibration was observed. Using a single hs-cTn measurement, the ARTEMIS model allowed direct rule-out of MI with very high and similar safety but up to tripled efficiency compared to the guideline- recommended strategy. Conclusion We developed and validated diagnostic models to accurately estimate the individual probability of MI, which allow for variable hs-cTn use and flexible timing of resampling. Their digital application may provide rapid, safe and efficient personalized patient care

Accelerating cryoprotectant diffusion kinetics improves cryopreservation of pancreatic islets

Funder: W. D. Armstrong Fund (School of Technology, University of Cambridge)Abstract: Cryopreservation offers the potential to increase the availability of pancreatic islets for treatment of diabetic patients. However, current protocols, which use dimethyl sulfoxide (DMSO), lead to poor cryosurvival of islets. We demonstrate that equilibration of mouse islets with small molecules in aqueous solutions can be accelerated from > 24 to 6 h by increasing incubation temperature to 37 °C. We utilize this finding to demonstrate that current viability staining protocols are inaccurate and to develop a novel cryopreservation method combining DMSO with trehalose pre-incubation to achieve improved cryosurvival. This protocol resulted in improved ATP/ADP ratios and peptide secretion from β-cells, preserved cAMP response, and a gene expression profile consistent with improved cryoprotection. Our findings have potential to increase the availability of islets for transplantation and to inform the design of cryopreservation protocols for other multicellular aggregates, including organoids and bioengineered tissues

Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia

Developmental dyslexia (DD) is one of the most prevalent learning disorders, with high impact on school and psychosocial development and high comorbidity with conditions like attention-deficit hyperactivity disorder (ADHD), depression, and anxiety. DD is characterized by deficits in different cognitive skills, including word reading, spelling, rapid naming, and phonology. To investigate the genetic basis of DD, we conducted a genome-wide association study (GWAS) of these skills within one of the largest studies available, including nine cohorts of reading-impaired and typically developing children of European ancestry (N = 2562-3468). We observed a genome-wide significant effect (p <1 x 10(-8)) on rapid automatized naming of letters (RANlet) for variants on 18q12.2, within MIR924HG (micro-RNA 924 host gene; rs17663182 p = 4.73 x 10(-9)), and a suggestive association on 8q12.3 within NKAIN3 (encoding a cation transporter; rs16928927, p = 2.25 x 10(-8)). rs17663182 (18q12.2) also showed genome-wide significant multivariate associations with RAN measures (p = 1.15 x 10(-8)) and with all the cognitive traits tested (p = 3.07 x 10(-8)), suggesting (relational) pleiotropic effects of this variant. A polygenic risk score (PRS) analysis revealed significant genetic overlaps of some of the DD-related traits with educational attainment (EDUyears) and ADHD. Reading and spelling abilities were positively associated with EDUyears (p similar to [10(-5)-10(-7)]) and negatively associated with ADHD PRS (p similar to [10(-8)-10(-17)]). This corroborates a long-standing hypothesis on the partly shared genetic etiology of DD and ADHD, at the genome-wide level. Our findings suggest new candidate DD susceptibility genes and provide new insights into the genetics of dyslexia and its comorbities.Peer reviewe

Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia

Developmental dyslexia (DD) is one of the most prevalent learning disorders, with high impact on school and psychosocial development and high comorbidity with conditions like attention-deficit hyperactivity disorder (ADHD), depression, and anxiety. DD is characterized by deficits in different cognitive skills, including word reading, spelling, rapid naming, and phonology. To investigate the genetic basis of DD, we conducted a genome-wide association study (GWAS) of these skills within one of the largest studies available, including nine cohorts of reading-impaired and typically developing children of European ancestry (N = 2562-3468). We observed a genome-wide significant effect (p < 1 x 10(-8)) on rapid automatized naming of letters (RANlet) for variants on 18q12.2, within MIR924HG (micro-RNA 924 host gene;rs17663182 p = 4.73 x 10(-9)), and a suggestive association on 8q12.3 within NKAIN3 (encoding a cation transporter;rs16928927, p = 2.25 x 10(-8)). rs17663182 (18q12.2) also showed genome-wide significant multivariate associations with RAN measures (p = 1.15 x 10(-8)) and with all the cognitive traits tested (p = 3.07 x 10(-8)), suggesting (relational) pleiotropic effects of this variant. A polygenic risk score (PRS) analysis revealed significant genetic overlaps of some of the DD-related traits with educational attainment (EDUyears) and ADHD. Reading and spelling abilities were positively associated with EDUyears (p similar to [10(-5)-10(-7)]) and negatively associated with ADHD PRS (p similar to [10(-8)-10(-17)]). This corroborates a long-standing hypothesis on the partly shared genetic etiology of DD and ADHD, at the genome-wide level. Our findings suggest new candidate DD susceptibility genes and provide new insights into the genetics of dyslexia and its comorbities