Schizophrenia is a severe psychiatric disorder with high heritability. Consortia efforts and technological advancements have led to a substantial increase in knowledge of the genetic architecture of ...schizophrenia over the past decade. In this article, we provide an overview of the current understanding of the genetics of schizophrenia, outline remaining challenges, and summarise future directions of research. World-wide collaborations have resulted in genome-wide association studies (GWAS) in over 56 000 schizophrenia cases and 78 000 controls, which identified 176 distinct genetic loci. The latest GWAS from the Psychiatric Genetics Consortium, available as a pre-print, indicates that 270 distinct common genetic loci have now been associated with schizophrenia. Polygenic risk scores can currently explain around 7.7% of the variance in schizophrenia case-control status. Rare variant studies have implicated eight rare copy-number variants, and an increased burden of loss-of-function variants in SETD1A, as increasing the risk of schizophrenia. The latest exome sequencing study, available as a pre-print, implicates a burden of rare coding variants in a further nine genes. Gene-set analyses have demonstrated significant enrichment of both common and rare genetic variants associated with schizophrenia in synaptic pathways. To address current challenges, future genetic studies of schizophrenia need increased sample sizes from more diverse populations. Continued expansion of international collaboration will likely identify new genetic regions, improve fine-mapping to identify causal variants, and increase our understanding of the biology and mechanisms of schizophrenia.
Late recovery of awareness in vegetative state (VS) is considered as an exceptional outcome, and has been reported prevalently after traumatic brain injury (TBI). The present prospective study aimed ...to verify frequency of late recovery (later than 1 year postonset in TBI and 3 months postonset in patients without TBI) of responsiveness and consciousness in traumatic and nontraumatic long-lasting (more than 6 months after onset) VS.
Fifty inpatients with long-lasting VS (36% TBI, 36% hemorrhagic, and 28% anoxic) were enrolled and followed up for a mean of 25.7 months from onset (5 patients for more than 4 years). Level of responsiveness and functional disability were evaluated by means of validated scales (Coma Recovery Scale-Revised and Disability Rating Scale).
At the end of the study, 21 patients (42%) had died, 17 patients (34%) were in VS, and 2 patients with TBI (4%) had recovered responsiveness within 12 months postonset. The remaining 10 (20%) patients with TBI and patients without TBI showed late recovery of responsiveness; 6 of them (12%) further progressed to consciousness. Late recovery was significantly associated with younger age and was relatively more frequent in TBI. Functional abilities were severely impaired in all patients.
This clinical study demonstrates that late recovery of responsiveness and consciousness is not exceptional in patients with traumatic and nontraumatic VS, although with residual severe disability.
► MSWI fly ash soluble salts have been optimally removed by washing with reduced water consumption. ► Washed ash can be stabilized for safer disposal to landfills for both non-reactive hazardous ...wastes and non-hazardous wastes. ► Stabilized fly ash can be submitted to material recovery in the field of road basement.
Fly ash from municipal solid waste incinerators (MSWI) is classified as hazardous in the European Waste Catalogue. Proper stabilization processes should be required before any management option is put into practice. Due to the inorganic nature of MSWI fly ash, cementitious stabilization processes are worthy of consideration. However, the effectiveness of such processes can be severely compromised by the high content of soluble chlorides and sulphates. In this paper, a preliminary washing treatment has been optimized to remove as much as possible soluble salts by employing as little as possible water. Two different operating conditions (single-step and two-step) have been developed to this scope. Furthermore, it has been demonstrated that stabilized systems containing 20% of binder are suitable for safer disposal as well as for material recovery in the field of road basement (cement bound granular material layer). Three commercially available cements (pozzolanic, limestone and slag) have been employed as binders.
Casing and cement impairment in oil and gas wells can lead to methane migration into the atmosphere and/or into underground sources of drinking water. An analysis of 75,505 compliance reports for ...41,381 conventional and unconventional oil and gas wells in Pennsylvania drilled from January 1, 2000—December 31, 2012, was performed with the objective of determining complete and accurate statistics of casing and cement impairment. Statewide data show a sixfold higher incidence of cement and/or casing issues for shale gas wells relative to conventional wells. The Cox proportional hazards model was used to estimate risk of impairment based on existing data. The model identified both temporal and geographic differences in risk. For post-2009 drilled wells, risk of a cement/casing impairment is 1.57-fold 95% confidence interval (CI) (1.45, 1.67); P < 0.0001 higher in an unconventional gas well relative to a conventional well drilled within the same time period. Temporal differences between well types were also observed and may reflect more thorough inspections and greater emphasis on finding well leaks, more detailed note taking in the available inspection reports, or real changes in rates of structural integrity loss due to rushed development or other unknown factors. Unconventional gas wells in northeastern (NE) Pennsylvania are at a 2.7-fold higher risk relative to the conventional wells in the same area. The predicted cumulative risk for all wells (unconventional and conventional) in the NE region is 8.5-fold 95% CI (7.16, 10.18); P < 0.0001 greater than that of wells drilled in the rest of the state.
Admixed populations are routinely excluded from genomic studies due to concerns over population structure. Here, we present a statistical framework and software package, Tractor, to facilitate the ...inclusion of admixed individuals in association studies by leveraging local ancestry. We test Tractor with simulated and empirical two-way admixed African-European cohorts. Tractor generates accurate ancestry-specific effect-size estimates and P values, can boost genome-wide association study (GWAS) power and improves the resolution of association signals. Using a local ancestry-aware regression model, we replicate known hits for blood lipids, discover novel hits missed by standard GWAS and localize signals closer to putative causal variants.
The identification and quantification of methane emissions from natural gas production has become increasingly important owing to the increase in the natural gas component of the energy sector. An ...instrumented aircraft platform was used to identify large sources of methane and quantify emission rates in southwestern PA in June 2012. A large regional flux, 2.0–14 g CH ₄ s ⁻¹ km ⁻², was quantified for a ∼2,800-km ² area, which did not differ statistically from a bottom-up inventory, 2.3–4.6 g CH ₄ s ⁻¹ km ⁻². Large emissions averaging 34 g CH ₄/s per well were observed from seven well pads determined to be in the drilling phase, 2 to 3 orders of magnitude greater than US Environmental Protection Agency estimates for this operational phase. The emissions from these well pads, representing ∼1% of the total number of wells, account for 4–30% of the observed regional flux. More work is needed to determine all of the sources of methane emissions from natural gas production, to ascertain why these emissions occur and to evaluate their climate and atmospheric chemistry impacts.
This paper reports the results of an investigation on material recovery by stabilization/solidification of bottom ash coming from a municipal solid waste incineration plant. ...Stabilization/solidification was carried out to produce artificial aggregate in a rotary plate granulator by adding hydraulic binders based on cement, lime and coal fly ash. Different mixes were tested in which the bottom ash content ranged between 60% and 90%. To avoid undesirable swelling in hardened products, the ash was previously milled and then granulated at room temperature. The granules were tested to assess their suitability to be used as artificial aggregate through the measurement of the following properties: density, water absorption capacity, compressive strength and heavy metals release upon leaching. It was demonstrated that the granules can be classified as lightweight aggregate with mechanical strength strongly dependent on the type of binder. Concrete mixes were prepared with the granulated artificial aggregate and tested for in-service performance, proving to be suitable for the manufacture of standard concrete blocks in all the cases investigated.
Pneumonia and respiratory infections impact infants and children with Down syndrome; pneumonia is a leading cause of mortality in adults with Down syndrome. We aimed to review the literature to ...evaluate gaps and address key questions. A series of key questions were formulated a priori to inform the search strategy and review process; addressed prevalence, severity, etiology, risk factors, preventive methods, screening, and financial costs, potential benefits or harms of screening. Using the National Library of Medicine database, PubMed, detailed literature searches on pneumonia and respiratory infections in Down syndrome were performed. Previously identified review articles were also assessed. The quality of available evidence was then evaluated and knowledge gaps were identified. Forty‐two relevant original articles were identified which addressed at least one key question. Study details including research design, internal validity, external validity, and relevant results are presented. Pneumonia and respiratory infections are more prevalent and more severe in individuals with Down syndrome compared to healthy controls through literature review, yet there are gaps in the literature regarding the etiology of pneumonia, the infectious organism, risk factors for infection, and to guide options for prevention and screening. There is urgent need for additional research studies in Down syndrome, especially in the time of the current COVID‐19 pandemic.
Background and purpose
Quantification of intraepidermal nerve fibers (IENFs) in skin biopsies is now the tool of choice to diagnose small fiber neuropathies. An adequate normative dataset, necessary ...to assess normality cutoffs, is available for brightfield microscopy but not for immunofluorescence.
Methods
Intraepidermal nerve fiber density data in distal leg skin samples processed with immunofluorescence were collected from 528 healthy individuals from four experienced laboratories worldwide. In all laboratories skin samples were collected, processed and analyzed according to standard procedures. Quantile regression analysis was employed to tailor the fit of the 5° percentile as the normal cutoff value and to test and measure the effect of age, gender, body mass index, race, biopsy site (lateral distal lower leg or medial posterior mid‐calf) and participating laboratory as possible influential variables.
Results
Age, gender and biopsy site showed an independent linear correlation with IENF density. For each decade the 5° quantile IENF cutoff showed a 0.54 fibers/mm decrease, whilst females exhibited a 1.0 fiber/mm cutoff greater than males. Compared to the lateral distal lower leg, biopsies from the calf showed a 3.4 fibers/mm lower 5° percentile cutoff, documenting a variation linked by site.
Conclusions
An age‐ and gender‐adjusted normative dataset for IENF density at the lateral distal lower leg obtained with indirect immunofluorescence is presented for the first time by sharing data from four experienced laboratories worldwide. This dataset can be used as reference for laboratories processing skin biopsies with this technique.
Sensory disturbances are part of the clinical picture of Parkinson's disease. Abnormalities in sensory processing, through a basal ganglia involvement, are thought to be responsible for the sensory ...dysfunction since sensory nerve conduction velocity (NCV) is usually normal. However, NCV does not examine small fibres or terminal endings of large sensory fibres, whereas skin biopsy is more suitable for these purposes. To evaluate peripheral sensory nerves in Parkinson's disease, we studied cutaneous free and encapsulated sensory nerve endings in 18 patients and 30 healthy controls using 3-mm punch biopsies from glabrous and hairy skin. Ten patients had additional skin biopsies from the contralateral side. Further evaluation included NCV and Quantitative Sensory Testing. Parkinson's disease patients showed a significant increase in tactile and thermal thresholds (P < 0.01), a significant reduction in mechanical pain perception (P < 0.01) and significant loss of epidermal nerve fibres (ENFs) and Meissner corpuscles (MCs) (P < 0.01). In patients with bilateral biopsies, loss of pain perception and ENFs was higher on the more affected side (P < 0.01). We found evidence suggesting attempts at counteracting degenerative processes as increased branching, sprouting of nerves and enlargement of the vascular bed. Morphological and functional findings did not correlate with age or disease duration. Disease severity correlated with loss of MCs and reduction in cold perception and pain perception. We demonstrated a peripheral deafferentation in Parkinson's disease that could play a major role in the pathogenesis of the sensory dysfunction.
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