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Background: Self-injurious behaviours (SIB) are repetitive, non-accidental movements that result in physical damage inflicted upon oneself, without suicidal intent. SIB are prevalent among children with autism spectrum disorder and can lead to permanent disability or death. Neuromodulation at a locus of neural circuitry implicated in SIB, the nucleus accumbens (NAc), may directly influence these behaviours. Methods: We completed a phase I, open-label clinical trial of deep brain stimulation (DBS) of the NAc in children with severe, treatment-refractory SIB (ClinicalTrials.gov NCT03982888). Participants were monitored for 12 months following NAc-DBS to assess the primary outcomes of safety and feasibility. Secondary outcomes included serial assessments of SIB, ambulatory actigraphy, and changes in brain glucose metabolism induced by DBS. Results: Six children underwent NAc-DBS without any serious adverse events. NAc-DBS resulted in significant reductions in SIB and SIB-associated behaviours across multiple standardized scales, concurrent with clinically meaningful improvements in quality-of-life. Ambulatory actigraphy showed reductions in high-amplitude limb movements and positron emission tomography revealed treatment-induced reductions in metabolic activity within the thalamus, striatum, and temporoinsular cortex. Conclusions: This first-in-children phase 1 clinical trial demonstrates the safety and feasibility of NAc-DBS in children with severe, refractory SIB at high risk of physical injury and death and supports further investigations.
Coronavirus disease 2019 can be indistinguishable from lower respiratory tract infections (LRTIs) caused by other viral and bacterial agents. This likely contributed to antimicrobial use (AU) and antimicrobial resistance (AMR) during the pandemic. Our antimicrobial stewardship program targeted the selection and duration of therapy for LRTIs and led to a reduction in AU and AMR.
Broad-spectrum antimicrobials are commonly used without indication and contribute to antimicrobial resistance (AMR). We implemented a syndrome-based stewardship intervention in a community hospital that targeted common infectious syndromes and antipseudomonal beta-lactam (APBL) use. Our intervention successfully reduced AMR, C. difficile rates, use of APBLs, and cost.
The ability to quickly refresh gas-jet targets without cycling the vacuum chamber makes them a promising candidate for laser-accelerated ion experiments at high repetition rate. Here we present results from the first high repetition rate ion acceleration experiment on the VEGA-3 PW-class laser at CLPU. A near-critical density gas-jet target was produced by forcing a 1000 bar H$_2$ and He gas mix through bespoke supersonic shock nozzles. Proton energies up to 2 MeV were measured in the laser forward direction and 2.2 MeV transversally. He$^{2+}$ ions up to 5.8 MeV were also measured in the transverse direction. To help maintain a consistent gas density profile over many shots, nozzles were designed to produce a high-density shock at distances larger than 1 mm from the nozzle exit. We outline a procedure for optimizing the laser–gas interaction by translating the nozzle along the laser axis and using different nozzle materials. Several tens of laser interactions were performed with the same nozzle which demonstrates the potential usefulness of gas-jet targets as high repetition rate particle source.
Blood-based biomarkers offer a more feasible alternative to Alzheimer’s disease (AD) detection, management, and study of disease mechanisms than current in vivo measures. Given their novelty, these plasma biomarkers must be assessed against postmortem neuropathological outcomes for validation. Research has shown utility in plasma markers of the proposed AT(N) framework, however recent studies have stressed the importance of expanding this framework to include other pathways. There is promising data supporting the usefulness of plasma glial fibrillary acidic protein (GFAP) in AD, but GFAP-to-autopsy studies are limited. Here, we tested the association between plasma GFAP and AD-related neuropathological outcomes in participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC).
Participants and Methods:
This sample included 45 participants from the BU ADRC who had a plasma sample within 5 years of death and donated their brain for neuropathological examination. Most recent plasma samples were analyzed using the Simoa platform. Neuropathological examinations followed the National Alzheimer’s Coordinating Center procedures and diagnostic criteria. The NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Measures of GFAP were log-transformed. Binary logistic regression analyses tested the association between GFAP and autopsy-confirmed AD status, as well as with semi-quantitative ratings of regional atrophy (none/mild versus moderate/severe) using binary logistic regression. Ordinal logistic regression analyses tested the association between plasma GFAP and Braak stage and CERAD neuritic plaque score. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate autopsy-confirmed AD status. All analyses controlled for sex, age at death, years between last blood draw and death, and APOE e4 status.
Results:
Of the 45 brain donors, 29 (64.4%) had autopsy-confirmed AD. The mean (SD) age of the sample at the time of blood draw was 80.76 (8.58) and there were 2.80 (1.16) years between the last blood draw and death. The sample included 20 (44.4%) females, 41 (91.1%) were White, and 20 (44.4%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having autopsy-confirmed AD (OR=14.12, 95% CI [2.00, 99.88], p=0.008). ROC analysis showed plasma GFAP accurately discriminated those with and without autopsy-confirmed AD on its own (AUC=0.75) and strengthened as the above covariates were added to the model (AUC=0.81). Increases in GFAP levels corresponded to increases in Braak stage (OR=2.39, 95% CI [0.71-4.07], p=0.005), but not CERAD ratings (OR=1.24, 95% CI [0.004, 2.49], p=0.051). Higher GFAP levels were associated with greater temporal lobe atrophy (OR=10.27, 95% CI [1.53,69.15], p=0.017), but this was not observed with any other regions.
Conclusions:
The current results show that antemortem plasma GFAP is associated with non-specific AD neuropathological changes at autopsy. Plasma GFAP could be a useful and practical biomarker for assisting in the detection of AD-related changes, as well as for study of disease mechanisms.
Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.
Method
To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.
Results
The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.
Conclusion
These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.
We compared systematic and random survey techniques to estimate breeding population sizes of burrow-nesting petrel species on Marion Island. White-chinned (Procellaria aequinoctialis) and blue (Halobaena caerulea) petrel population sizes were estimated in systematic surveys (which attempt to count every colony) in 2009 and 2012, respectively. In 2015, we counted burrows of white-chinned, blue and great-winged (Pterodroma macroptera) petrels within 52 randomized strip transects (25 m wide, total 144 km). Burrow densities were extrapolated by Geographic Information System-derived habitat attributes (geology, vegetation, slope, elevation, aspect) to generate island-wide burrow estimates. Great-winged petrel burrows were found singly or in small groups at low densities (2 burrows ha−1); white-chinned petrel burrows were in loose clusters at moderate densities (3 burrows ha−1); and blue petrel burrows were in tight clusters at high densities (13 burrows ha−1). The random survey estimated 58% more white-chinned petrels but 42% fewer blue petrels than the systematic surveys. The results suggest that random transects are best suited for species that are widely distributed at low densities, but become increasingly poor for estimating population sizes of species with clustered distributions. Repeated fixed transects provide a robust way to monitor changes in colony density and area, but might fail to detect the formation/disappearance of new colonies.
The ability of the aorta to buffer blood flow and provide diastolic perfusion (Windkessel function) is a determinant of cardiovascular health. We have reported cardiac dysfunction indicating downstream vascular abnormalities in young adult baboons who were intrauterine growth restricted (IUGR) at birth as a result of moderate maternal nutrient reduction. Using 3 T MRI, we examined IUGR offspring (eight male, eight female; 5.7 years; human equivalent 25 years) and age-matched controls (eight male, eight female; 5.6 years) to quantify distal descending aortic cross-section (AC) and distensibility (AD). ANOVA showed decreased IUGR AC/body surface area (0.9±0.05 cm2/m2v. 1.2±0.06 cm2/m2, M±s.e.m., P<0.005) and AD (1.7±0.2 v. 4.0±0.5×10−3/mmHg, P<0.005) without sex difference or group-sex interaction, suggesting intrinsic vascular pathology and impaired development persisting in adulthood. Future studies should evaluate potential consequences of these changes on coronary perfusion, afterload and blood pressure.
In order to accurately estimate body composition at slaughter and to meet specific market targets, the influence of age at time of castration (surgical or immunological) on body composition and boar taint indicators must be determined for male pigs. In all, 48 males were randomly assigned to one of four management regimens: (1) entire male pigs (EM), (2) EM surgically castrated at ~40 kg BW and 10 weeks of age (late castrates; LC), (3) conventional, early surgical castrates (within 4 days of birth; EC) and (4) EM immunized with a gonadotropin-releasing hormone (GnRH) analog (primary dose at 30 kg BW and 8 weeks of age; booster dose at 70 kg and 14 weeks of age; IM). Pigs were fed corn and soybean meal-based diets that were not limiting in essential nutrients. Back fat was sampled on days −3, 8, 18 and 42, relative to administering the booster dose of GnRH analog at day 0, to determine androstenone concentrations (n=8 or 9/group). Fat androstenone concentrations in IM were lower than EM between days 8 and 42 after administering the booster dose (173 v. 863 ng/g, respectively; P<0.01), and were not different from surgically castrated males (EC and LC) after day 18. Slaughter occurred at ~115 kg BW, 42 days (6 weeks) after administering the booster dose for IM, and 10 and 20 weeks after surgical castration for LC and EC, respectively (n=8 or 9/group). At slaughter, live BW, liver weight as a percent of live BW, dissectible bone as a percent of cold carcass side, body protein and water contents and whole-body protein deposition decreased with time after surgical castration (linear; P<0.05), whereas dressing percentage, dissectible fat, probe fat depth and body fat content increased with time after surgical castration (linear; P<0.05). The IM had intermediate dressing percentage and dissected fat to EM and EC, whereas liver weight as a percent of live BW and body protein and lipid contents were not different from EM. Whole-body lipid deposition tended to be greater in IM than in EM between 14 and 20 weeks of age (373 v. 286 g/d; P=0.051). In conclusion, castration of male pigs after 6 weeks of age has a lasting effect on physical and chemical body composition. The relationship between time after castration and body composition may be developed to predict carcass composition and can be used to determine the ideal immunization schedule aimed at specific markets in the future.
Several authors claimed that expression of suicidal ideation is one of the most important predictors of completed suicide. However, the strength of the association between suicidal ideation and subsequent completed suicide has not been firmly established in different populations. Furthermore, the absolute suicide risk after expression of suicidal ideation is unknown. In this meta-analysis, we examined whether the expression of suicidal ideation predicted subsequent completed suicide in various populations, including both psychiatric and non-psychiatric populations.
Methods.
A meta-analysis of cohort and case–control studies that assessed suicidal ideation as determinant for completed suicide in adults. Two independent reviewers screened 5726 articles for eligibility and extracted data of the 81 included studies. Pooled risk ratios were estimated in a random effects model stratified for different populations. Meta-regression analysis was used to determine suicide risk during the first year of follow-up.
Results.
The risk for completed suicide was clearly higher in people who had expressed suicidal ideation compared with people who had not, with substantial variation between the different populations: risk ratio ranging from 2.35 (95% confidence interval (CI) 1.43–3.87) in affective disorder populations to 8.00 (95% CI 5.46–11.7) in non-psychiatric populations. In contrast, the suicide risk after expression of suicidal ideation in the first year of follow-up was higher in psychiatric patients (risk 1.40%, 95% CI 0.74–2.64) than in non-psychiatric participants (risk 0.23%, 95% CI 0.10–0.54). Past suicide attempt-adjusted risk ratios were not pooled due to large underreporting.
Conclusions.
Assessment of suicidal ideation is of priority in psychiatric patients. Expression of suicidal ideation in psychiatric patients should prompt secondary prevention strategies to reduce their substantial increased risk of suicide.
In most countries, male pigs are physically castrated soon after birth to reduce the risk of boar taint and to avoid behaviours such as fighting and mounting. However, entire male pigs are more feed efficient and deposit less fat than barrows. In addition, many animal welfare organizations are lobbying for a cessation of castration, with a likelihood that this could lead to inferior pork unless an alternative method is used to control boar taint. An alternative to physical castration is immunization against gonadotrophin releasing factor (GnRF) which allows producers to capitalize on the superior feed efficiency and carcass characteristics of boars without the risk of boar taint. From a physiological perspective, immunized pigs are entire males until shortly after the second dose, typically given 4 to 6 weeks before slaughter. Following full immunization, there is a temporary suppression of testicular function and a hormonal status that resembles that of a barrow. Nutrient requirements will be different in these two phases, before and after full immunization. Given that there have been few published studies comparing the lysine requirements of entire males and barrows in contemporary genotypes, it is useful to use gilt requirements as a benchmark. A series of meta-analyses comparing anti-GnRF immunized boars and physical castrates and use of nutritional models suggest that the lysine requirement of entire males before the second immunization is 5% higher than for gilts, from 25 to 50 kg BW, and by 8% from 50 to 95 kg. Given that the penalty in growth performance for having inadequate dietary lysine is greater in males than in gilts or barrows, it is important to ensure that lysine requirements are met to obtain the maximum benefits of entire male production during this phase. After the second immunization, the lysine requirement of immunized males decreases and may become more like that of barrows. In addition, a consistent effect of full immunization is a marked increase in voluntary feed intake from about 10 days after the second dose. Putting these together, the estimated lysine requirement, expressed in terms of diet composition, falls to 94% of the gilt level. Although general principles can be described now, further research is needed to fully define the lysine requirements of immunized boars. It is important that the temporal pattern of tissue deposition rates and feed intake be explored to be incorporated into models to predict nutrient requirements over the period of rapidly changing metabolism.
In November 2009, we initiated a multistate investigation of Salmonella Montevideo infections with pulsed-field gel electrophoresis pattern JIXX01.0011. We identified 272 cases in 44 states with illness onset dates ranging from 1 July 2009 to 14 April 2010. To help generate hypotheses, warehouse store membership card information was collected to identify products consumed by cases. These records identified 19 ill persons who purchased company A salami products before onset of illness. A case-control study was conducted. Ready-to-eat salami consumption was significantly associated with illness (matched odds ratio 8·5, 95% confidence interval 2·1–75·9). The outbreak strain was isolated from company A salami products from an environmental sample from one manufacturing plant, and sealed containers of black and red pepper at the facility. This outbreak illustrates the importance of using membership card information to assist in identifying suspect vehicles, the potential for spices to contaminate ready-to-eat products, and preventing raw ingredient contamination of these products.
Understanding thermal transfer mechanisms in BOF converter is akey for higher energy efficiency, involving higher production capacityand lower CO2 emissions through low hot metal ratio capability.The developed model achieves a coupled description of the majorphenomena: refining reactions, mass transfers between phases, scrapmelting, post-combustion, slag formation. The calculated exhaustfumes enthalpy is fitting well the measured thermal balance trials withindustrial converter when implementing a detailed description of thepost-combustion. This model, compatible with real-time use, is also avaluable tool for further improvement in dynamic control of the process.
Energy efficiency in BOF process is related to hot metal and scrapratio and thus to production capacity potential and specific CO2emissions. A thermal balance in the fume system, using a selectedmetrology, can be calculated dynamically and provides a valuabletool for investigating the process parameters that are relevant foroptimizing and controlling energy efficiency. The method and firstresults are presented.
Substituting used tyres for anthracite in the EAF in France and inBelgium is reported. First trials have been carried out in Lorraine in1997 in the frame of a partnership between Usinor (now ArcelorMittal), Michelin and Ademe. The substitution process has beeneventually implemented by LME in cooperation with Aliapur over theyears 2002-2003. Industeel Belgium got started on substitution in2004. To day, both steel plants have achieved stable operation, witha regular load of 8 to 12 kg used tyres per ton of steel, thus allowingsignificant and sustainable savings on anthracite.
The SuperMACHO project has discovered light echoes from 3 ancient SNe in the LMC. These SNRs are three of the six youngest in the LMC, and are classified as likely SN Ia based on X-ray data.
Standard EAF operate with a large amount or air ingress (on theorder of 30 000 Nm3 for 150 t of steel). This air is at ambient temperaturethus, the nitrogen content and the non-reactive oxygen areonly heated through the furnace and exit with the fumes at high temperature(1000°C). This brings about significant thermal losses.Reference and airtight trials were carried out with the 6-t EAF ofArcelor Research for assessing the gains related to airtight furnaceoperation.