Exploring polygenic contributors to subgroups of comorbid conditions in autism spectrum disorder

Individuals with autism spectrum disorder (ASD) have heterogeneous comorbid conditions. This study examined whether comorbid conditions in ASD are associated with polygenic risk scores (PRS) of ASD or PRS of comorbid conditions in non-ASD specific populations. Genome-wide single nucleotide polymorphism (SNP) data were obtained from 1386 patients with ASD from the Autism Genetic Resource Exchange (AGRE) study. After excluding individuals with missing clinical information concerning comorbid conditions, a total of 707 patients were included in the study. A total of 18 subgroups of comorbid conditions (‘topics’) were identified using a machine learning algorithm, topic modeling. PRS for ASD were computed using a genome-wide association meta-analysis of 18,381 cases and 27,969 controls. From these 18 topics, Topic 6 (over-represented by allergies) (p = 1.72 × 10−3) and Topic 17 (over-represented by sensory processing issues such as low pain tolerance) (p = 0.037) were associated with PRS of ASD. The associations between these two topics and the multi-locus contributors to their corresponding comorbid conditions based on non-ASD specific populations were further explored. The results suggest that these two topics were not associated with the PRS of allergies and chronic pain disorder, respectively. Note that characteristics of the present AGRE sample and those samples used in the original GWAS for ASD, allergies, and chronic pain disorder, may differ due to significant clinical heterogeneity that exists in the ASD population. Additionally, the AGRE sample may be underpowered and therefore insensitive to weak PRS associations due to a relatively small sample size. Findings imply that susceptibility genes of ASD may contribute more to the occurrence of allergies and sensory processing issues in individuals with ASD, compared with the susceptibility genes for their corresponding phenotypes in non-ASD individuals. Since these comorbid conditions (i.e., allergies and pain sensory issues) may not be attributable to the corresponding comorbidity-specific biological factors in non-ASD individuals, clinical management for these comorbid conditions may still depend on treatments for core symptoms of ASD

Effect of individual patient risk, centre, surgeon and anaesthetist on length of stay in hospital after cardiac surgery: Association of Cardiothoracic Anaesthesia and Critical Care (ACTACC) consecutive cases series study of 10 UK specialist centres.

OBJECTIVES: To determine the relative contributions of patient risk profile, local and individual clinical practice on length of hospital stay after cardiac surgery. DESIGN: Ten-year audit of prospectively collected consecutive cardiac surgical cases. Case-mix adjusted outcomes were analysed in models that included random effects for centre, surgeon and anaesthetist. SETTING: UK centres providing adult cardiac surgery. PARTICIPANTS: 10 of 36 UK specialist centres agreed to provide outcomes for all major cardiac operations over 10 years. After exclusions (duplicates, cases operated by more than one consultant, deaths and procedures for which the EuroSCORE risk score for cardiac surgery is not appropriate), there were 107 038 cardiac surgical procedures between April 2002 and March 2012, conducted by 127 consultant surgeons and 190 consultant anaesthetists. MAIN OUTCOME MEASURE: Length of stay (LOS) up to 3 months postoperatively. RESULTS: The principal component of variation in outcomes was patient risk (represented by the EuroSCORE and remaining patient heterogeneity), accounting for 95.43% of the variation for postoperative LOS. The impact of the surgeon and centre was moderate (intra-class correlation coefficients ICC=2.79% and 1.59%, respectively), whereas the impact of the anaesthetist was negligible (ICC=0.19%). Similarly, 96.05% of the variation for prolonged LOS (>11 days) was attributable to the patient, with surgeon and centre less but still influential components (ICC=2.12% and 1.66%, respectively, 0.17% only for anaesthetists). Adjustment for year of operation resulted in minor reductions in variation attributable to surgeons (ICC=2.52% for LOS and 2.23% for prolonged LOS). CONCLUSIONS: Patient risk profile is the primary determinant of variation in LOS, and as a result, current initiatives to reduce hospital stay by modifying consultant performance are unlikely to have a substantial impact. Therefore, substantially reducing hospital stay requires shifting away from a one-size-fits-all approach to cardiac surgery, and seeking alternative treatment options personalised to high-risk patients

Physics of Ultra-Peripheral Nuclear Collisions

Moving highly-charged ions carry strong electromagnetic fields that act as a field of photons. In collisions at large impact parameters, hadronic interactions are not possible, and the ions interact through photon-ion and photon-photon collisions known as {\it ultra-peripheral collisions} (UPC). Hadron colliders like the Relativistic Heavy Ion Collider (RHIC), the Tevatron and the Large Hadron Collider (LHC) produce photonuclear and two-photon interactions at luminosities and energies beyond that accessible elsewhere; the LHC will reach a $\gamma p$ energy ten times that of the Hadron-Electron Ring Accelerator (HERA). Reactions as diverse as the production of anti-hydrogen, photoproduction of the $\rho^0$, transmutation of lead into bismuth and excitation of collective nuclear resonances have already been studied. At the LHC, UPCs can study many types of `new physics.'Comment: 47 pages, to appear in Annual Review of Nuclear and Particle Scienc

The Near-Sun Streamer Belt Solar Wind: Turbulence and Solar Wind Acceleration

The fourth orbit of Parker Solar Probe (PSP) reached heliocentric distances down to 27.9 Rs, allowing solar wind turbulence and acceleration mechanisms to be studied in situ closer to the Sun than previously possible. The turbulence properties were found to be significantly different in the inbound and outbound portions of PSP's fourth solar encounter, likely due to the proximity to the heliospheric current sheet (HCS) in the outbound period. Near the HCS, in the streamer belt wind, the turbulence was found to have lower amplitudes, higher magnetic compressibility, a steeper magnetic field spectrum (with spectral index close to -5/3 rather than -3/2), a lower Alfv\'enicity, and a "1/f" break at much lower frequencies. These are also features of slow wind at 1 au, suggesting the near-Sun streamer belt wind to be the prototypical slow solar wind. The transition in properties occurs at a predicted angular distance of ~4{\deg} from the HCS, suggesting ~8{\deg} as the full-width of the streamer belt wind at these distances. While the majority of the Alfv\'enic turbulence energy fluxes measured by PSP are consistent with those required for reflection-driven turbulence models of solar wind acceleration, the fluxes in the streamer belt are significantly lower than the model predictions, suggesting that additional mechanisms are necessary to explain the acceleration of the streamer belt solar wind

The Imperfect Fluid behind Kinetic Gravity Braiding

We present a standard hydrodynamical description for non-canonical scalar field theories with kinetic gravity braiding. In particular, this picture applies to the simplest galileons and k-essence. The fluid variables not only have a clear physical meaning but also drastically simplify the analysis of the system. The fluid carries charges corresponding to shifts in field space. This shift-charge current contains a spatial part responsible for diffusion of the charges. Moreover, in the incompressible limit, the equation of motion becomes the standard diffusion equation. The fluid is indeed imperfect because the energy flows neither along the field gradient nor along the shift current. The fluid has zero vorticity and is not dissipative: there is no entropy production, the energy-momentum is exactly conserved, the temperature vanishes and there is no shear viscosity. Still, in an expansion around a perfect fluid one can identify terms which correct the pressure in the manner of bulk viscosity. We close by formulating the non-trivial conditions for the thermodynamic equilibrium of this imperfect fluid.Comment: 23 pages plus appendices. New version includes extended discussion on diffusion and dynamics in alternative frames, as well as additional references. v3 reflects version accepted for publication in JHEP: minor comments added regarding suitability to numerical approache

The Precursors and Products of Justice Climates: Group Leader Antecedents and Employee Attitudinal Consequences

Drawing on the organizational justice, organizational climate, leadership and personality, and social comparison theory literatures, we develop hypotheses about the effects of leader personality on the development of three types of justice climates (e.g., procedural, interpersonal, and informational), and the moderating effects of these climates on individual level justice- attitude relationships. Largely consistent with the theoretically-derived hypotheses, the results showed that leader (a) agreeableness was positively related to procedural, interpersonal and informational justice climates, (b) conscientiousness was positively related to a procedural justice climate, and (c) neuroticism was negatively related to all three types of justice climates. Further, consistent with social comparison theory, multilevel data analyses revealed that the relationship between individual justice perceptions and job attitudes (e.g., job satisfaction, commitment) was moderated by justice climate such that the relationships were stronger when justice climate was high

翻訳 動物倫理の西洋文化(3)アンドレーアス・C・ビマー 動物に居場所はない : 人間の公共の場から動物を追放する動きをめぐるエッセイ(1991) (特集 新津嗣郎教授、ジョン・ブランデル教授退職記念号)

AimAs the COVID-19 pandemic evolves, human milk banks world-wide continue to provide donor human milk to vulnerable infants who lack access to mother's own milk. Under these circumstances, ensuring the safety of donor human milk is paramount, as the risk of vertical transmission of SARS-CoV-2 is not fully understood. Here, we investigate the inactivation of SARS-CoV-2 in human milk by pasteurisation and the stability of SARS-CoV-2 in human milk under cold storage.MethodsSARS-CoV-2 was experimentally inoculated into human milk samples from healthy donors or into a control medium. Triplicates of each sample were layered onto uninfected cells after Holder pasteurisation (63°C for 30 min), heating to 56°C for 30 min, or after 48 h of storage at 4°C or -30°C. Infectious titres of virus were determined at 72 h post-infection by endpoint titration.ResultsFollowing heating to 63°C or 56°C for 30 min, replication competent (i.e. live) SARS-CoV-2 was undetected in both human milk and the control medium. Cold storage of SARS-CoV-2 in human milk (either at 4°C or -30°C) did not significantly impact infectious viral load over a 48 h period.ConclusionSARS-CoV-2 is effectively inactivated by Holder pasteurisation, suggesting that existing milk bank processes will effectively mitigate the risk of transmission of SARS-COV-2 to vulnerable infants through pasteurised donor human milk. The demonstrated stability of SARS-CoV-2 in refrigerated or frozen human milk may assist in the development of guidelines around safe expressing and storing of milk from COVID-19 infected mothers

We are all one together : peer educators\u27 views about falls prevention education for community-dwelling older adults - a qualitative study

Background: Falls are common in older people. Despite strong evidence for effective falls prevention strategies, there appears to be limited translation of these strategies from research to clinical practice. Use of peers in delivering falls prevention education messages has been proposed to improve uptake of falls prevention strategies and facilitate translation to practice. Volunteer peer educators often deliver educational presentations on falls prevention to community-dwelling older adults. However, research evaluating the effectiveness of peer-led education approaches in falls prevention has been limited and no known study has evaluated such a program from the perspective of peer educators involved in delivering the message. The purpose of this study was to explore peer educators’ perspective about their role in delivering peer-led falls prevention education for community-dwelling older adults. Methods: A two-stage qualitative inductive constant comparative design was used.In stage one (core component) focus group interviews involving a total of eleven participants were conducted. During stage two (supplementary component) semi-structured interviews with two participants were conducted. Data were analysed thematically by two researchers independently. Key themes were identified and findings were displayed in a conceptual framework. Results: Peer educators were motivated to deliver educational presentations and importantly, to reach an optimal peer connection with their audience. Key themes identified included both personal and organisational factors that impact on educators’ capacity to facilitate their peers’ engagement with the message. Personal factors that facilitated message delivery and engagement included peer-to-peer connection and perceived credibility, while barriers included a reluctance to accept the message that they were at risk of falling by some members in the audience. Organisational factors, including ongoing training for peer educators and formative feedback following presentations, were perceived as essential because they affect successful message delivery. Conclusions: Peer educators have the potential to effectively deliver falls prevention education to older adults and influence acceptance of the message as they possess the peer-to-peer connection that facilitates optimal engagement. There is a need to consider incorporating learnings from this research into a formal large scale evaluation of the effectiveness of the peer education approach in reducing falls in older adults

Tetraspanin (TSP-17) Protects Dopaminergic Neurons against 6-OHDA-Induced Neurodegeneration in <i>C. elegans</i>

Parkinson's disease (PD), the second most prevalent neurodegenerative disease after Alzheimer's disease, is linked to the gradual loss of dopaminergic neurons in the substantia nigra. Disease loci causing hereditary forms of PD are known, but most cases are attributable to a combination of genetic and environmental risk factors. Increased incidence of PD is associated with rural living and pesticide exposure, and dopaminergic neurodegeneration can be triggered by neurotoxins such as 6-hydroxydopamine (6-OHDA). In C. elegans, this drug is taken up by the presynaptic dopamine reuptake transporter (DAT-1) and causes selective death of the eight dopaminergic neurons of the adult hermaphrodite. Using a forward genetic approach to find genes that protect against 6-OHDA-mediated neurodegeneration, we identified tsp-17, which encodes a member of the tetraspanin family of membrane proteins. We show that TSP-17 is expressed in dopaminergic neurons and provide genetic, pharmacological and biochemical evidence that it inhibits DAT-1, thus leading to increased 6-OHDA uptake in tsp-17 loss-of-function mutants. TSP-17 also protects against toxicity conferred by excessive intracellular dopamine. We provide genetic and biochemical evidence that TSP-17 acts partly via the DOP-2 dopamine receptor to negatively regulate DAT-1. tsp-17 mutants also have subtle behavioral phenotypes, some of which are conferred by aberrant dopamine signaling. Incubating mutant worms in liquid medium leads to swimming-induced paralysis. In the L1 larval stage, this phenotype is linked to lethality and cannot be rescued by a dop-3 null mutant. In contrast, mild paralysis occurring in the L4 larval stage is suppressed by dop-3, suggesting defects in dopaminergic signaling. In summary, we show that TSP-17 protects against neurodegeneration and has a role in modulating behaviors linked to dopamine signaling