Formation and relaxation of K-2 and K-2V double-core-hole states in n-butane.

Using a magnetic bottle multi-electron time-of-flight spectrometer in combination with synchrotron radiation, double-core-hole pre-edge and continuum states involving the K-shell of the carbon atoms in n-butane (n-C4H10) have been identified, where the ejected core electron(s) and the emitted Auger electrons from the decay of such states have been detected in coincidence. An assignment of the main observed spectral features is based on the results of multi-configurational self-consistent field (MCSCF) calculations for the excitation energies and static exchange (STEX) calculations for energies and intensities. MCSCF results have been analyzed in terms of static and dynamic electron relaxation as well as electron correlation contributions to double-core-hole state ionization potentials. The analysis of applicability of the STEX method, which implements the one-particle picture toward the complete basis set limit, is motivated by the fact that it scales well toward large species. We find that combining the MCSCF and STEX techniques is a viable approach to analyze double-core-hole spectra.

Role of Rare Genetic Variants Found in Families With Intracranial Aneurysms in the General Dutch and UK Population.

[Figure: see text].

Functional Neuroimaging of Adult-to-Adult Romantic Attachment Separation, Rejection, and Loss: A Systematic Review.

Romantic attachment rejection (RAR) is a highly prevalent phenomenon among young adults. Rejection by a romantic attachment figure can be a painful and incapacitating experience with lasting negative mental health sequelae, yet the underlying neurobiology of RAR is not well characterized. We systematically reviewed functional neuroimaging studies of adult RAR. Four functional magnetic resonance imaging (fMRI) studies that measured participants' responses to real or imagined RAR and met inclusion criteria were evaluated. These included studies were published between 2004 and 2018. Brain activity in adult participants with an RAR appears to be influenced by the stimulus used to elicit a reaction as well as by attachment styles. Brain regions that show a significant change in activation following a rejection stimulus include cortical regions (cingulate, insular, orbitofrontal, and prefrontal), and subcortical regions (angular gyrus, hippocampus, striatum, tegmental area, and temporal pole) and correspond to (i) pain, distress, and memory retrieval; (ii) reward, romantic love, and dopaminergic circuits; and (iii) emotion regulation and behavioural adaptation. Further neuroimaging studies of adult RAR, as moderated by stimulus and attachment style, are needed to better understand the underlying neurobiology of RAR.

Correction: Mitochondrial oxodicarboxylate carrier deficiency is associated with mitochondrial DNA depletion and spinal muscular atrophy-like disease.

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Relative extent of triple Auger decay in CO and CO2.

Systematic measurements on single and triple Auger decay in CO and CO2 after the creation of a C 1s or a O 1s core vacancy show that the percentage of triple Auger decay is on the order of 10-2 of the single Auger decay in these molecules. The fractions of triple Auger decay are compared with triple Auger fractions for carbon atoms and some noble gas atoms, and are found to follow a linear trend correlated to the number of valence electrons on the atom with the initial core vacancy and on its closest neighbours. This linear trend for the percentage of triple Auger decay is represented by a predictive equation TA = 0.13·Nve - 0.5.

Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus.

Influenza A virus-specific B lymphocytes and the antibodies they produce protect against infection. However, the outcome of interactions between an influenza haemagglutinin-specific B cell via its receptor (BCR) and virus is unclear. Through somatic cell nuclear transfer we generated mice that harbour B cells with a BCR specific for the haemagglutinin of influenza A/WSN/33 virus (FluBI mice). Their B cells secrete an immunoglobulin gamma 2b that neutralizes infectious virus. Whereas B cells from FluBI and control mice bind equivalent amounts of virus through interaction of haemagglutinin with surface-disposed sialic acids, the A/WSN/33 virus infects only the haemagglutinin-specific B cells. Mere binding of virus is not sufficient for infection of B cells: this requires interactions of the BCR with haemagglutinin, causing both disruption of antibody secretion and FluBI B-cell death within 18 h. In mice infected with A/WSN/33, lung-resident FluBI B cells are infected by the virus, thus delaying the onset of protective antibody release into the lungs, whereas FluBI cells in the draining lymph node are not infected and proliferate. We propose that influenza targets and kills influenza-specific B cells in the lung, thus allowing the virus to gain purchase before the initiation of an effective adaptive response.

Clinical characteristics of women captured by extending the definition of severe postpartum haemorrhage with 'refractoriness to treatment': a cohort study.

BACKGROUND: The absence of a uniform and clinically relevant definition of severe postpartum haemorrhage hampers comparative studies and optimization of clinical management. The concept of persistent postpartum haemorrhage, based on refractoriness to initial first-line treatment, was proposed as an alternative to common definitions that are either based on estimations of blood loss or transfused units of packed red blood cells (RBC). We compared characteristics and outcomes of women with severe postpartum haemorrhage captured by these three types of definitions. METHODS: In this large retrospective cohort study in 61 hospitals in the Netherlands we included 1391 consecutive women with postpartum haemorrhage who received either ≥4 units of RBC or a multicomponent transfusion. Clinical characteristics and outcomes of women with severe postpartum haemorrhage defined as persistent postpartum haemorrhage were compared to definitions based on estimated blood loss or transfused units of RBC within 24 h following birth. Adverse maternal outcome was a composite of maternal mortality, hysterectomy, arterial embolisation and intensive care unit admission. RESULTS: One thousand two hundred sixty out of 1391 women (90.6%) with postpartum haemorrhage fulfilled the definition of persistent postpartum haemorrhage. The majority, 820/1260 (65.1%), fulfilled this definition within 1 h following birth, compared to 819/1391 (58.7%) applying the definition of ≥1 L blood loss and 37/845 (4.4%) applying the definition of ≥4 units of RBC. The definition persistent postpartum haemorrhage captured 430/471 adverse maternal outcomes (91.3%), compared to 471/471 (100%) for ≥1 L blood loss and 383/471 (81.3%) for ≥4 units of RBC. Persistent postpartum haemorrhage did not capture all adverse outcomes because of missing data on timing of initial, first-line treatment. CONCLUSION: The definition persistent postpartum haemorrhage identified women with severe postpartum haemorrhage at an early stage of haemorrhage, unlike definitions based on blood transfusion. It also captured a large majority of adverse maternal outcomes, almost as large as the definition of ≥1 L blood loss, which is commonly applied as a definition of postpartum haemorrhage rather than severe haemorrhage.

Interrelationship of the rs7903146 TCF7L2 gene variant with measures of glucose metabolism and adiposity: The NEO study.

BACKGROUND AND AIMS: We investigated the interrelationship of rs7903146-T in TCF7L2 with measures of glucose metabolism and measures of adiposity. METHODS AND RESULTS: This cross-sectional analysis was conducted in 5744 middle-aged participants (mean (standard deviation [SD]) age is 55.9 (6.0) years) from the Netherlands Epidemiology of Obesity (NEO) Study. Associations between rs7903146-T and Type 2 diabetes mellitus (T2D) were assessed with logistic regression. Additive (per-allele) associations with measures of glucose metabolism (e.g., fasting insulin) and adiposity (e.g., body mass index [BMI]) were examined with multivariable linear regression. In the total study population, rs7903146-T was associated with a higher risk of T2D (additive odds ratio: 1.42; 95% confidence interval: 1.17; 1.72), and specifically with T2D treated with insulin analogs (2.31 [1.19; 4.46]). After exclusion of participants treated with glucose-lowering medication, rs7903146-T was associated with lower mean insulin concentration (additive mean difference: -0.07 SD [-0.14; 0.00]), but not with higher mean glucose concentration (0.03 SD [-0.01; 0.07]). Furthermore, rs7903146-T was associated with, among other measures of adiposity, a lower mean BMI (-0.04 SD [-0.09; -0.00]), and a lower mean total body fat (-0.04 SD [-0.08; -0.00]). The association between rs7903146-T and T2D increased after adjustment for BMI (odds ratio: 1.51 [1.24; 1.86]); the association between rs7903146-T and fasting insulin diminished after adjustment (-0.05 SD [-0.11; 0.02]). CONCLUSION: rs7903146-T is associated with a decreased insulin concentration and increased risk of T2D with opposing effects of adjustment for adiposity.

Dissociations of water ions after valence and inner-valence ionization.

Energy selected and mass-resolved electron-ion coincidence spectra of heavy water have been recorded for ionization energies from 18 to 35 eV. Dissociation from the B2B2 state produces both O+ and D2 + at energies near their thermodynamic thresholds in addition to the known products D+ and OD+. The relative yields of O+, OD+, and D+ in the B2B2 state breakdown diagram are modulated by the vibrational structure of the B-state population, implying incomplete energy equilibration before fragmentation. Decay from the C-state produces OD+ in addition to the known O+ and D+. The fragment kinetic energies suggest that O+ and D+ from the C state are the products of full atomization of the molecule.

Discrepancy in prevalence of Huntington's disease in two Swedish regions.

BACKGROUND: Huntington's disease (HD) is a neurodegenerative disease with an autosomal dominant pattern of inheritance. The prevalence varies between different geographical regions with an estimated average in Europe of about 6/100 000. Parts of northern Sweden are known to have an accumulation of HD, but no prevalence studies have been undertaken for 50 years. OBJECT: The aim of this study was to estimate the prevalence of HD in the two different Swedish counties of Jämtland and Uppsala and compare them with the reported prevalence in Europe. METHOD: Patients registered with the diagnosis of HD were identified through medical records in each county. Presymptomatic patients were excluded. We also compared the annual number of individuals with HD registered in the database of the National Board of Health and Welfare in these regions, with all of Sweden. RESULTS: The prevalence of HD was found to be 22.1/100 000 in Jämtland and 4.9/100 000 in Uppsala county. The mean age was 62.2 years and 61.8 years, respectively. The annual average of patients with HD registered at inpatient care was 1.5/100 000 in Jämtland, 0.44/100 000 in Uppsala county, and 0.56/100 000 in all of Sweden. CONCLUSION: The prevalence of patients with the diagnosis of HD is four times higher in the county of Jämtland than in the county of Uppsala, where the prevalence is more similar to the average in Europe. Our results support earlier findings of regional variations of HD prevalence with an accumulation in certain parts of northern Sweden.

Association of meteorological and geographical factors and risk of initial Pseudomonas aeruginosa acquisition in young children with cystic fibrosis.

Initial infection with the sentinel respiratory pathogen in children with cystic fibrosis (CF), Pseudomonas aeruginosa (Pa), is generally with environmental strains of this ubiquitous organism. The purpose of this study was to evaluate the associations between meteorological and geographical factors and risk of initial Pa acquisition in young children with CF. Using the U.S. Cystic Fibrosis Foundation Patient Registry from 2003 to 2009, 3463 patients met inclusion criteria, of which 48% (n = 1659) acquired Pa during follow-up. From multivariable Weibull regression, increased risk of Pa acquisition was associated with increasing temperature [hazard ratio (HR) per 1 °C: 1·13; 95% confidence interval (CI) 1·08-1·13], dew point (HR per 1 °C: 1·10, 95% CI 1·07-1·13), rainfall (HR per cm: 1·10, 95% CI 1·07-1·12), latitude (HR per 1 °C northing: 1·15, 95% CI 1·11-1·20), longitude (HR per 1 °C easting: 1·01, 95% CI 1·01-1·02) and elevation (HR per 100 m: 1·05, 95% CI 1·03-1·07). These results suggest that environmental factors may play a previously unrecognized role in the aetiology of initial Pa acquisition.

Relative extent of double and single Auger decay in molecules containing C, N and O atoms.

We show that the proportion of double Auger decay following creation of single 1s core holes in molecules containing C, N and O atoms is greater than usually assumed, amounting to about 10% of single Auger decay in many cases. It varies from molecule to molecule, where the size of the molecule has a positive correlation to the amount of double Auger decay. In neon, examined as a related benchmark, the proportion of double Auger decay is similar to that in methane, and is in the order of 5%.

Dissociation of multiply charged ICN by Coulomb explosion.

The fragmentations of iodine cyanide ions created with 2 to 8 positive charges by photoionization from inner shells with binding energies from 59 eV (I 4d) to ca. 900 eV (I 3p) have been examined by multi-electron and multi-ion coincidence spectroscopy with velocity map imaging ion capability. The charge distributions produced by hole formation in each shell are characterised and systematic effects of the number of charges and of initial charge localisation are found.

Reduced glutamate in white matter of male neonates exposed to alcohol in utero: a (1)H-magnetic resonance spectroscopy study.

In utero exposure to alcohol leads to a spectrum of fetal alcohol related disorders (FASD). However, few studies used have used proton magnetic resonance spectroscopy ((1)H-MRS) to understand how neurochemical disturbances relate to the pathophysiology of FASD. Further, no studies to date have assessed brain metabolites in infants exposed to alcohol in utero. We hypothesize that neonates exposed to alcohol in utero will show decreased glutamatergic activity, pre-emptive of their clinical diagnosis or behavioural phenotype. Single voxel (1)H-MRS data, sampled in parietal white and gray matter, were acquired from 36 neonates exposed to alcohol in utero, and 31 control unexposed healthy neonates, in their 2nd-4th week of life. Metabolites relative to creatine with phosophocreatine and metabolites absolute concentrations using a water reference are reported. Male infants exposed to alcohol in utero were found to have reduced concentration of glutamate with glutamine (Glx) in their parietal white matter (PWM), compared to healthy male infants (p = 0.02). Further, male infants exposed to alcohol in utero had reduced concentration and ratio for glutamate (Glu) in their PWM (p = 0.02), compared to healthy male infants and female infants exposed to alcohol in utero. Female infants showed higher relative Glx and Glu ratios for parietal gray matter (PGM, p < 0.01), compared to male infants. We speculate that the decreased Glx and Glu concentrations in PWM are a result of delayed oligodendrocyte maturation, which may be a result of dysfunctional thyroid hormone activity in males exposed to alcohol in utero. Further study is required to elucidate the relationship between Glx and Glu, thyroid hormone activity, and oligodendrocyte maturation in infants exposure to alcohol in utero.

Altered localization, abnormal modification and loss of function of Sigma receptor-1 in amyotrophic lateral sclerosis.

Intracellular accumulations of mutant, misfolded proteins are major pathological hallmarks of amyotrophic lateral sclerosis (ALS) and related disorders. Recently, mutations in Sigma receptor 1 (SigR1) have been found to cause a form of ALS and frontotemporal lobar degeneration (FTLD). Our goal was to pinpoint alterations and modifications of SigR1 in ALS and to determine how these changes contribute to the pathogenesis of ALS. In the present study, we found that levels of the SigR1 protein were reduced in lumbar ALS patient spinal cord. SigR1 was abnormally accumulated in enlarged C-terminals and endoplasmic reticulum (ER) structures of alpha motor neurons. These accumulations co-localized with the 20s proteasome subunit. SigR1 accumulations were also observed in SOD1 transgenic mice, cultured ALS-8 patient's fibroblasts with the P56S-VAPB mutation and in neuronal cell culture models. Along with the accumulation of SigR1 and several other proteins involved in protein quality control, severe disturbances in the unfolded protein response and impairment of protein degradation pathways were detected in the above-mentioned cell culture systems. Furthermore, shRNA knockdown of SigR1 lead to deranged calcium signaling and caused abnormalities in ER and Golgi structures in cultured NSC-34 cells. Finally, pharmacological activation of SigR1 induced the clearance of mutant protein aggregates in these cells. Our results support the notion that SigR1 is abnormally modified and contributes to the pathogenesis of ALS.

Feeding patients with preoperative symptoms of gastric outlet obstruction after pancreatoduodenectomy: Early oral or routine nasojejunal tube feeding?

BACKGROUND: Early oral feeding is currently considered the optimal routine feeding strategy after pancreatoduodenectomy (PD). Some have suggested that patients with preoperative symptoms of gastric outlet obstruction (GOO) who undergo PD have such a high risk of developing delayed gastric emptying that these patients should rather receive routine postoperative tube feeding. The aim of this study was to determine whether clinical outcomes after PD in these patients differ between postoperative early oral feeding and routine tube feeding. METHODS: We analyzed a consecutive multicenter cohort of patients with preoperative symptoms of GOO undergoing PD (2010-2013). Patients were categorized into two groups based on the applied postoperative feeding strategy (dependent on their center's routine strategy): early oral feeding or routine nasojejunal tube feeding. RESULTS: Of 497 patients undergoing PD, 83 (17%) suffered from preoperative symptoms of GOO. 49 patients received early oral feeding and 29 patients received routine tube feeding. Time to resumption of adequate oral intake (primary outcome; 14 vs. 12 days, p = 0.61) did not differ between these two feeding strategies. Furthermore, overall complications and length of stay were similar in both groups. Of the patients receiving early oral feeding, 24 (49%) ultimately required postoperative tube feeding. In patients with an uncomplicated postoperative course, early oral feeding was associated with shorter time to adequate oral intake (8 vs. 12 days, p = 0.008) and shorter hospital stay (9 vs. 13 days, p < 0.001). CONCLUSION: Also in patients with preoperative symptoms of GOO, early oral feeding can be considered the routine feeding strategy after PD.

Cardiovascular flexibility in middle-aged overweight South Asians vs. white Caucasians: response to short-term caloric restriction.

BACKGROUND AND AIMS: South Asians have a higher risk of developing cardiovascular disease than white Caucasians. The underlying cause is unknown, but might be related to higher cardiac susceptibility to metabolic disorders. Short-term caloric restriction (CR) can be used as a metabolic stress test to study cardiac flexibility. We assessed whether metabolic and functional cardiovascular flexibility to CR differs between South Asians and white Caucasians. METHODS AND RESULTS: Cardiovascular function and myocardial triglycerides were assessed using a 1.5T-MRI/S-scanner in 12 middle-aged overweight male South Asians and 12 matched white Caucasians before and after an 8-day very low calorie diet (VLCD). At baseline South Asians were more insulin resistant than Caucasians. Cardiac dimensions were smaller, despite correction for body surface area, and pulse wave velocity (PWV) in the distal aorta was higher in South Asians. Systolic and diastolic function, myocardial triglycerides and pericardial fat did not differ significantly between groups. After the VLCD body weight reduced on average by 4.0 ± 0.2 kg. Myocardial triglycerides increased in both ethnicities by 69 ± 18%, and diastolic function decreased although this was not significant in South Asians. However, pericardial fat and PWV in the proximal and total aorta were reduced in Caucasians only. CONCLUSION: Myocardial triglyceride stores in middle-aged overweight and insulin resistant South Asians are as flexible and amenable to therapeutic intervention by CR as age-, sex- and BMI-matched but less insulin resistant white Caucasians. However, paracardial fat volume and PWV showed a differential effect in response to an 8-day VLCD in favor of Caucasians. CLINICAL TRIAL REGISTRATION: NTR 2473 (URL: http://www.trialregister.nl/trialreg/admin/rctsearch.asp?Term=2473).

Psychosocial predictors of fetoplacental blood flow during pregnancy.

BACKGROUND: Although a number of studies have found significant associations between maternal psychological distress, anxiety and changes in fetoplacental blood flow, findings remain inconsistent. A recent pilot study by our group highlighted some of these inconsistencies. In the current study, we expanded this pilot analysis to include psychological distress, anxiety and a range of antenatal variables, with the aim of identifying predictors of fetoplacental blood flow. METHODS: Healthy pregnant women (n=148) underwent Doppler flow studies on uterine, umbilical and fetal arteries; as well as assessments of distress, anxiety and other antenatal variables (e.g. perceived social support, resilience, nicotine and alcohol use) in each trimester. RESULTS: Stepwise regression analyses found that state anxiety was associated with lower mid-cerebral artery pulsatility index at trimester 3. LIMITATIONS: Subjects were recruited from selected midwife obstetric units in the same health district, so the generalizability of our results may be limited. While most subjects received Doppler assessment at trimesters 2 and 3, only approximately half of our sample was assessed at trimester 1. CONCLUSION: The finding that anxiety is associated with increased blood flow to the fetal brain during trimester 3 of pregnancy, coincide with previous work. The findings emphasize a growing appreciation of the potential importance of psychological well-being during pregnancy for infant development. However, as associations were small and variable, further research using multivariate models to determine the precise mechanisms underlying these associations would be warranted.

Patients' perspective on self-management in the recovery from depression.

BACKGROUND: Self-management appears to be a promising approach in the case of depression, which helps to stimulate patients' autonomy. However, a good and systematic description of the concept self-management from the patients' perspective, to our knowledge, has not yet been performed. OBJECTIVE: To determine: (i) what strategies patients think they can use themselves to recover from depression, (ii) which main themes of self-management strategies can be detected, and (iii) which of these strategies patients perceive as being most helpful. METHODS: We used concept mapping to explore the experiences of patients who recently recovered from a depressive episode. Patients generated self-management strategies in focus group discussions. The strategies were clustered on a two-dimensional concept map by a hierarchical cluster analysis. RESULTS: Patients generated 50 strategies that formed eight clusters: (i) proactive attitude towards depression and treatment, (ii) daily life strategies and rules, (iii) explanation of disease to others, (iv) remaining socially engaged, (v) engaging in activities, (vi) structured attention to oneself, (vii) contact with fellow sufferers, and (viii) other. Behavioural and cognitive strategies and a proactive attitude towards treatment were considered as the most helpful. DISCUSSION AND CONCLUSION: From the patients' perspective, there is a wide range of self-management strategies that they can use - and perceive as helpful- to contribute to their own recovery. Professionals could encourage patients to take an active role in achieving recovery. Further research could open new roads to improve patients' active contributions to current treatments for depression.