Should jaundice preclude resection in patients with gallbladder cancer? Results from a nation-wide cohort study

Background: It is controversial whether patients with gallbladder cancer (GBC) presenting with jaundice benefit from resection. This study re-evaluates the impact of jaundice on resectability and survival. Methods: Data was collected on surgically explored GBC patients in all Dutch academic hospitals from 2000 to 2018. Survival and prognostic factors were assessed. Results: In total 202 patients underwent exploration and 148 were resected; 124 non-jaundiced patients (104 resected) and 75 jaundiced patients (44 resected). Jaundiced patients had significantly (P < 0.05) more pT3/T4 tumors, extended (≥3 segments) liver- and organ resections, major post-operative complications and margin-positive resection. 90-day mortality was higher in jaundiced patients (14% vs. 0%, P < 0.001). Median overall survival (OS) was 7.7 months in jaundiced patients (2-year survival 17%) vs. 26.1 months in non-jaundiced patients (2-year survival 39%, P < 0.001). In multivariate analysis, jaundice (HR1.89) was a poor prognostic factor for OS in surgically explored but not in resected patients. Six jaundiced patients did not develop a recurrence; none had liver- or common bile duct (CBD) invasion on imaging. Conclusion: Jaundice is associated with poor survival. However, jaundice is not an independent adverse prognostic factor in resected patients. Surgery should be considered in patients with limited disease and no CBD invasion on imaging

Construction and psychometric testing of the EMPATHIC questionnaire measuring parent satisfaction in the pediatric intensive care unit

Abstract PURPOSE: To construct and test the reliability and validity of the EMpowerment of PArents in THe Intensive Care (EMPATHIC) questionnaire measuring parent satisfaction in the pediatric intensive care unit (PICU). METHODS: Structured development and psychometric testing of a parent satisfaction-with-care instrument with the results of two cohorts of parents (n = 2,046) from eight PICUs in the Netherlands. RESULTS: In the first cohort, 667/1,055 (63%) parents participated followed by 551/991 (56%) parents in the second cohort. The empirical structure of the instrument was established by confirmatory factor analysis with the first sample of parents confirming 65 statements within five theoretically conceptualized domains: information, care and cure, organization, parental participation, and professional attitude. The standardized factor loadings were greater than 0.40 in 63 statements. Cronbach's α, a measure of reliability, per domain ranged from 0.73 to 0.93 in both cohorts with no significant difference documenting the reliability over time. Beside rigorous content and face validity, the congruent validity of the instrument showed adequate correlation with four gold standard questions measuring overall satisfaction. The non-differential validity was confirmed with no significant differences between the population characteristics and the domains, except that parents with a child for a surgical admission were more satisfied on information issues. CONCLUSIONS: The final EMPATHIC questionnaire incorporates 65 statements. The empirical structure of the satisfaction statements and domains was satisfactory. The reliability and validity proved to be adequate. The EMPATHIC questionnaire is a valid quality performance indicator to measure quality of care as perceived by parents

Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general population

Almost all genetic risk factors for autism spectrum disorders (ASDs) can be found in the general population, but the effects of that risk are unclear in people not ascertained for neuropsychiatric symptoms. Using several large ASD consortia and population based resources, we find genetic links between ASDs and typical variation in social behavior and adaptive functioning. This finding is evidenced through both inherited and de novo variation, indicating that multiple types of genetic risk for ASDs influence a continuum of behavioral and developmental traits, the severe tail of which can result in an ASD or other neuropsychiatric disorder diagnosis. A continuum model should inform the design and interpretation of studies of neuropsychiatric disease biology

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Reliance on habits at the expense of goal-directed control following dopamine precursor depletion

Rationale Dopamine is well known to play an important role in learning and motivation. Recent animal studies have implicated dopamine in the reinforcement of stimulus-response habits, as well as in flexible, goal-directed action. However, the role of dopamine in human action control is still not well understood. Objectives We present the first investigation of the effect of reducing dopamine function in healthy volunteers on the balance between habitual and goal-directed action control. Methods The dietary intervention of acute dietary phenylalanine and tyrosine depletion (APTD) was adopted to study the effects of reduced global dopamine function on action control. Participants were randomly assigned to either the APTD or placebo group (ns = 14) to allow for a between-subjects comparison of performance on a novel three-stage experimental paradigm. In the initial learning phase, participants learned to respond to different stimuli in order to gain rewarding outcomes. Subsequently, an outcome-devaluation test and a slips-of-action test were conducted to assess whether participants were able to flexibly adjust their behaviour to changes in the desirability of the outcomes. Results APTD did not prevent stimulus-response learning, nor did we find evidence for impaired response-outcome learning in the subsequent outcome-devaluation test. However, when goal-directed and habitual systems competed for control in the slips-of-action test, APTD tipped the balance towards habitual control. These findings were restricted to female volunteers. Conclusions We provide direct evidence that the balance between goal-directed and habitual control in humans is dopamine dependent. The results are discussed in light of gender differences in dopamine function and psychopathologies

Leukocytic Toll-Like Receptor 2 Deficiency Preserves Cardiac Function And Reduces Fibrosis In Sustained Pressure Overload

An involement of Toll-like receptor 2 (TLR2) has been established in cardiac dysfunction after acute myocardial infarction; however, its role in chronic pressure overload is unclear. We sought to evaluate the role of TLR2 in cardiac hypertrophy, fibrosis and dysfunction in sustained pressure overload. We induced pressure overload via transverse aortic constriction (TAC) in TLR2-/- and wild type (WT) mice, and followed temporal changes over 8 weeks. Despite similar increases in heart weight, left ventricular (LV) ejection fraction (EF) and diastolic function (mitral E/A ratio) were preserved in TLR2-/- mice but impaired in WT mice following TAC. TAC produced less LV fibrosis in TLR2-/- mice associated with lower mRNA levels of collagen genes (Col1a1 and Col3a1) and lower protein level of TGFbeta1, compared to WT mice. Following TAC, the influx of macrophages and CD3 T cells into LV was similar between TLR2-/- and WT mice, whereas levels of cyto/chemokines were lower in the heart and plasma in TLR2-/- mice. TLR2-/- bone marrow-derived cells protected against LVEF decline and fibrosis following TAC. Our findings show that leukocytic TLR2 deficiency protects against LV dysfunction and fibrosis probably via a reduction in inflammatory signaling in sustained pressure overload

Psychosocial functioning in adolescents growing up with chronic disease: The Dutch HBSC study

Many adolescents worldwide (indirectly) grow up with a chronic disease, which may impact their functioning and wellbeing. The objective of this study is to assess whether adolescents with a (family member with a) chronic disease differ from their healthy counterparts in terms of psychosocial functioning. Data from the Dutch 2013 HBSC-survey were used, including 7168 adolescents (Meanage = 13.7, SD = 1.57, 50.5% female). Participants indicated whether they or one of their family members had a long-term (> 3 months) disease or disability (mental/physical) and were categorized into four groups based on disease presence (none, other, self, both). Psychosocial functioning was assessed in terms of life satisfaction, self-rated health, psychosomatic health, mental health problems, support, substance use, physical exercise, screen time, and school liking. Chronically diseased adolescents (n = 162) reported lower life satisfaction, self-rated and psychosomatic health, more mental health problems, lower peer support, more substance use, and less physical exercise compared to healthy peers. Chronically diseased adolescents who also had a family member with a chronic disease (n = 74) showed comparable outcomes on these life domains, although they did not differ from their healthy peers regarding peer support, substance use, and physical activity. Healthy adolescents with a chronically diseased family member (n = 737) reported significantly lower life satisfaction, self-rated and psychosomatic health, more mental health problems, and less family support compared to healthy peers who grew up in healthy families; however, they reported more positive outcomes than adolescents who had a chronic disease themselves. Conclusion: Having a (family member with a) chronic disease is associated with impaired psychosocial functioning on various life domains. Our findings aid in understanding the psychosocial associates of chronic disease and imply that caregivers should be observant of psychosocial problems among vulnerable adolescents to provide appropriate guidance.What is Known:• Adolescents who grow up with a (family member with a) chronic disease encounter numerous challenges that may be related to poorer developmental outcomes on the long term.What is New:• This study adds a comprehensive overview of the psychosocial functioning of adolescents with a (family member with a) chronic disease, as compared to healthy counterparts that grow up in a healthy family

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function

Registered Replication Report on Fischer, Castel, Dodd, and Pratt (2003)

The attentional spatial-numerical association of response codes (Att-SNARC) effect (Fischer, Castel, Dodd, & Pratt, 2003)—the finding that participants are quicker to detect left-side targets when the targets are preceded by small numbers and quicker to detect right-side targets when they are preceded by large numbers—has been used as evidence for embodied number representations and to support strong claims about the link between number and space (e.g., a mental number line). We attempted to replicate Experiment 2 of Fischer et al. by collecting data from 1,105 participants at 17 labs. Across all 1,105 participants and four interstimulus-interval conditions, the proportion of times the effect we observed was positive (i.e., directionally consistent with the original effect) was .50. Further, the effects we observed both within and across labs were minuscule and incompatible with those observed by Fischer et al. Given this, we conclude that we failed to replicate the effect reported by Fischer et al. In addition, our analysis of several participant-level moderators (finger-counting habits, reading and writing direction, handedness, and mathematics fluency and mathematics anxiety) revealed no substantial moderating effects. Our results indicate that the Att-SNARC effect cannot be used as evidence to support strong claims about the link between number and space

A massive hot Jupiter orbiting a metal-rich early-M star discovered in the TESS full frame images

Observations and statistical studies have shown that giant planets are rare around M dwarfs compared with Sun-like stars. The formation mechanism of these extreme systems remains under debate for decades. With the help of the TESS mission and ground based follow-up observations, we report the discovery of TOI-4201b, the most massive and densest hot Jupiter around an M dwarf known so far with a radius of $1.22\pm 0.04\ R_J$ and a mass of $2.48\pm0.09\ M_J$, about 5 times heavier than most other giant planets around M dwarfs. It also has the highest planet-to-star mass ratio ($q\sim 4\times 10^{-3}$) among such systems. The host star is an early-M dwarf with a mass of $0.61\pm0.02\ M_{\odot}$and a radius of$0.63\pm0.02\ R_{\odot}$. It has significant super-solar iron abundance ([Fe/H]=$0.52\pm 0.08$ dex). However, interior structure modeling suggests that its planet TOI-4201b is metal-poor, which challenges the classical core-accretion correlation of stellar-planet metallicity, unless the planet is inflated by additional energy sources. Building on the detection of this planet, we compare the stellar metallicity distribution of four planetary groups: hot/warm Jupiters around G/M dwarfs. We find that hot/warm Jupiters show a similar metallicity dependence around G-type stars. For M dwarf host stars, the occurrence of hot Jupiters shows a much stronger correlation with iron abundance, while warm Jupiters display a weaker preference, indicating possible different formation histories.Comment: 21 pages, 11 figures, 4 tables, submitted to A