The Safety and Efficacy of Psychedelic-Assisted Therapies for Older Adults: Knowns and Unknowns.

Psychedelics and related compounds have shown efficacy for the treatment of a variety of conditions that are prevalent among older adults, including mood disorders, the psychological distress associated with a serious medical illness, post-traumatic stress disorder (PTSD), and prolonged grief disorder. Psychedelics also have properties that could help provide therapeutic benefits for patients with dementing disorders, as well as promoting personal growth among healthy older adults. This article focuses on psilocybin, a classic psychedelic, and MDMA, a substituted amphetamine with properties similar to classic psychedelics. Both act on the 5HT2A receptor. Psychedelics can be safely administered to healthy adults in controlled conditions. However, both psilocybin and MDMA can increase blood pressure and heart rate, which could be a concern if used in older adults with cardiovascular disease. Very few older adults or patients with serious comorbidities have been included in clinical trials of psychedelics to date, raising the question of how generalizable study results are for the patients that most geropsychiatrists will be treating. Research on the neurophysiologic and mechanistic effects of psychedelics in older adults could also provide insights into the aging brain that could have clinical applications in the future. Given the potential of psychedelic compounds to benefit older adults, more research is needed to establish safety and efficacy among older adults, particularly those with multi-morbidity.

Development and validation of a prognostic model for death 30 days after adult emergency laparotomy.

The probability of death after emergency laparotomy varies greatly between patients. Accurate pre-operative risk prediction is fundamental to planning care and improving outcomes. We aimed to develop a model limited to a few pre-operative factors that performed well irrespective of surgical indication: obstruction; sepsis; ischaemia; bleeding; and other. We derived a model with data from the National Emergency Laparotomy Audit for patients who had emergency laparotomy between December 2016 and November 2018. We tested the model on patients who underwent emergency laparotomy between December 2018 and November 2019. There were 4077/40,816 (10%) deaths 30 days after surgery in the derivation cohort. The final model had 13 pre-operative variables: surgical indication; age; blood pressure; heart rate; respiratory history; urgency; biochemical markers; anticipated malignancy; anticipated peritoneal soiling; and ASA physical status. The predicted mortality probability deciles ranged from 0.1% to 47%. There were 1888/11,187 deaths in the test cohort. The scaled Brier score, integrated calibration index and concordance for the model were 20%, 0.006 and 0.86, respectively. Model metrics were similar for the five surgical indications. In conclusion, we think that this prognostic model is suitable to support decision-making before emergency laparotomy as well as for risk adjustment for comparing organisations.

Mosquito Magnet® traps as a potential means of monitoring blackflies of medical and veterinary importance.

Mosquito Magnet® traps, deployed in widespread parts of England as part of nationwide mosquito surveillance projects, also caught blackflies. As many as 1242 blackflies were caught in a trapping session lasting 4 days. Principal among the species caught were Simulium equinum, Simulium lineatum and Simulium ornatum s.l. As S. ornatum s.l. is a vector that transmits Onchocerca linealis to cattle and S. equinum is responsible for dermatitis ('sweet itch') in cattle and horses, it is suggested that Mosquito Magnet® traps could be used to monitor and partially control these pests, as well as nuisance anthropophilic blackflies such as Simulium posticatum that can cause simuliidosis in southern England.

Phosphorus stocks and flows in an intensive livestock dominated food system.

Current use and management of phosphorus (P) in our food systems is considered unsustainable and considerable improvements in the efficiency of P use are required to mitigate the environmental impact of poor P stewardship. The inherent low P use efficiency of food production from animals means food systems dominated by livestock agriculture can pose unique challenges for improving P management. This paper presents the results of a substance flow analysis for P in the Northern Ireland (NI) food system for the year 2017 as a case study for examining P stewardship in a livestock dominated agricultural system. Imported livestock feed was by far the largest flow of P into the NI food system in 2017 (11,700 t ± 1300 t) and P from livestock excreta the largest internal flow of P (20,400 ± 1900t). The P contained in livestock slurries and manures alone that were returned to agricultural land exceeded total crop and grass P requirement by 20% and were the largest contributor to an annual excess soil P accumulation of 8.5 ± 1.4 kg ha-1. This current livestock driven P surplus also limits the opportunities for P circularity and reuse from other sectors within the food system, e.g. wastewater biosolids and products from food processing waste. Management of livestock P demand (livestock numbers, feed P content) or technological advancements that facilitate the processing and subsequent export of slurries and manures are therefore needed.

Recombination of the Phase-Variable spnIII Locus Is Independent of All Known Pneumococcal Site-Specific Recombinases.

Streptococcus pneumoniae is one of the world's leading bacterial pathogens, causing pneumonia, septicemia, and meningitis. In recent years, it has been shown that genetic rearrangements in a type I restriction-modification system (SpnIII) can impact colony morphology and gene expression. By generating a large panel of mutant strains, we have confirmed a previously reported result that the CreX (also known as IvrR and PsrA) recombinase found within the locus is not essential for hsdS inversions. In addition, mutants of homologous recombination pathways also undergo hsdS inversions. In this work, we have shown that these genetic rearrangements, which result in different patterns of genome methylation, occur across a wide variety of serotypes and sequence types, including two strains (a 19F and a 6B strain) naturally lacking CreX. Our gene expression analysis, by transcriptome sequencing (RNAseq), confirms that the level of creX expression is impacted by these genomic rearrangements. In addition, we have shown that the frequency of hsdS recombination is temperature dependent. Most importantly, we have demonstrated that the other known pneumococcal site-specific recombinases XerD, XerS, and SPD_0921 are not involved in spnIII recombination, suggesting that a currently unknown mechanism is responsible for the recombination of these phase-variable type I systems.IMPORTANCEStreptococcus pneumoniae is a leading cause of pneumonia, septicemia, and meningitis. The discovery that genetic rearrangements in a type I restriction-modification locus can impact gene regulation and colony morphology led to a new understanding of how this pathogen switches from harmless colonizer to invasive pathogen. These rearrangements, which alter the DNA specificity of the type I restriction-modification enzyme, occur across many different pneumococcal serotypes and sequence types and in the absence of all known pneumococcal site-specific recombinases. This finding suggests that this is a truly global mechanism of pneumococcal gene regulation and the need for further investigation of mechanisms of site-specific recombination.

What do Key Stakeholders Think About HIV Self-Testing in Canada? Results from a Cross-Sectional Survey.

Human immunodeficiency virus (HIV) self-testing presents an empowering alternative to facility-based testing for reaching undiagnosed HIV infected individuals, but is not currently available in Canada. We surveyed stakeholders (clinical providers, public health professionals, researchers) engaged in HIV testing initiatives nationwide to identify the concerns, opportunities and challenges to implementing HIV self-testing in Canada. An online cross-sectional survey was disseminated by the Canadian Institutes of Health Research Centre for REACH 2.0 National HIV & sexually transmitted and blood borne infections working group to stakeholders nationwide, with a target sample size of 200. Quantitative and qualitative data were analyzed using a mixed-methods, respondent-informed approach, to inform subsequent HIV self-testing in a country where self-testing is not yet accessible. A total of 183 responses were received. A majority (70.7%) (128/181) felt that self-testing was a necessary investment to reach the undiagnosed. 64.6% (117/181) felt that self-tests should be made available to their clients and 71.5% (128/179) of respondents agreed that self-test instructions required improvements. However, 50% (90/180) felt that self-testing will pose an economic challenge to current HIV testing models. Regardless, 21% urged for timely action and availability of HIV self-tests. Thematic analyses reflected the following concerns: (a) need for affordable self-tests, (b) need for expedited, customized, and accessible linkages to counselling, (c) concern for patients to cope with positive self-test results, (d) accuracy of self-tests to detect acute HIV and (e) liability in the context of non-disclosure. Stakeholders agreed to the provision of an option of HIV self-testing to reach the undiagnosed individuals. Concerns regarding costs and accuracy of self-tests, expedited linkages to counselling, and integration of self-test within prevailing HIV testing models, will need to be addressed before their widespread implementation.

Development and internal validation of a novel risk adjustment model for adult patients undergoing emergency laparotomy surgery: the National Emergency Laparotomy Audit risk model.

BACKGROUND: Among patients undergoing emergency laparotomy, 30-day postoperative mortality is around 10-15%. The risk of death among these patients, however, varies greatly because of their clinical characteristics. We developed a risk prediction model for 30-day postoperative mortality to enable better comparison of outcomes between hospitals. METHODS: We analysed data from the National Emergency Laparotomy Audit (NELA) on patients having an emergency laparotomy between December 2013 and November 2015. A prediction model was developed using multivariable logistic regression, with potential risk factors identified from existing prediction models, national guidelines, and clinical experts. Continuous risk factors were transformed if necessary to reflect their non-linear relationship with 30-day mortality. The performance of the model was assessed in terms of its calibration and discrimination. Interval validation was conducted using bootstrap resampling. RESULTS: There were 4458 (11.5%) deaths within 30-days among the 38 830 patients undergoing emergency laparotomy. Variables associated with death included (among others): age, blood pressure, heart rate, physiological variables, malignancy, and ASA physical status classification. The predicted risk of death among patients ranged from 1% to 50%. The model demonstrated excellent calibration and discrimination, with a C-statistic of 0.863 (95% confidence interval, 0.858-0.867). The model retained its high discrimination during internal validation, with a bootstrap derived C-statistic of 0.861. CONCLUSIONS: The NELA risk prediction model for emergency laparotomies discriminates well between low- and high-risk patients and is suitable for producing risk-adjusted provider mortality statistics.

Short communication: Associations of feeding behavior and milk production in dairy cows.

Identification of the associations of cow feeding behavior with productivity is important for supporting recommendations of strategies that optimize milk yield and composition. The objective of this study was to identify associations between measures of feeding behavior and milk production using data collated from studies of the feeding behavior of lactating dairy cows. A database containing behavior and production data for 132 dairy cow-week observations (mean of 7 d of consecutive data per cow) was assembled from 5 studies. Cows averaged (mean ± standard deviation) 1.8 ± 0.9 lactations, 108.4 ± 42.7 d in milk, and 654.6 ± 71.4 kg of body weight during each observation week. Production data included dry matter intake (27.0 ± 3.1 kg/d), milk yield (43.0 ± 7.0 kg/d), milk fat content (3.60 ± 0.49%), and milk protein content (3.05 ± 0.25%). Behavioral data included feeding time (230.4 ± 35.5 min/d), feeding rate (0.13 ± 0.03 kg/min), meal frequency (9.0 ± 2.0 meals/d), meal size (3.2 ± 0.9 kg/meal), daily mealtime (279.6 ± 51.7 min/d), and rumination time (516.0 ± 90.7 min/d). Data were analyzed in multivariable mixed-effect regression models to identify which behavioral variables, when accounting for other cow-level factors (days in milk, parity, and body weight) and dietary characteristics (forage level, nutrient content, and particle distribution), were associated with measures of production. Dry matter intake was associated with feeding time (+0.02 kg/min) and tended to be associated with rumination time (+0.003 kg/min) and meal frequency (+0.2 kg/meal). Similarly, milk yield was associated with feeding time (+0.03 kg/min) and rumination time (+0.02 kg/min), and tended to be associated with meal frequency (+0.3 kg/meal). Milk fat yield was associated with meal frequency (+0.02 kg/meal). Overall, our results suggest that milk yield and component production may be improved in situations where cows are able to increase their time spent feeding, in more frequent meals, and time spent ruminating.

Adaptive coarse graining method for energy transfer and dissociation kinetics of polyatomic species.

A novel reduced-order method is presented for modeling reacting flows characterized by strong non-equilibrium of the internal energy level distribution of chemical species in the gas. The approach seeks for a reduced-order representation of the distribution function by grouping individual energy states into macroscopic bins, and then reconstructing state population using the maximum entropy principle. This work introduces an adaptive grouping methodology to identify and lump together groups of states that are likely to equilibrate faster with respect to each other. To this aim, two algorithms have been considered: the modified island algorithm and the spectral clustering method. Both methods require a measure of dissimilarity between internal energy states. This is achieved by defining "metrics" based on the strength of the elementary rate coefficients included in the state-specific kinetic mechanism. Penalty terms are used to avoid grouping together states characterized by distinctively different energies. The two methods are used to investigate excitation and dissociation of N2 (Σg+1) molecules due to interaction with N(Su4) atoms in an ideal chemical reactor. The results are compared with a direct numerical simulation of the state-specific kinetics obtained by solving the master equations for the complete set of energy levels. It is found that adaptive grouping techniques outperform the more conventional uniform energy grouping algorithm by providing a more accurate description of the distribution function, mole fraction and energy profiles during non-equilibrium relaxation.

Stakeholders' views of the introduction of assistive technology in the classroom: How family-centred is Australian practice for students with cerebral palsy?

BACKGROUND: With family-centred care widely recognized as a cornerstone for effective assistive technology service provision, the current study was undertaken to investigate to what extent such approaches were used by schools when assistive technology assessments and implementation occurred in the classroom. METHOD: In this cross-sectional study, we compare survey results from parents (n = 76), school staff (n = 33) and allied health professionals (n = 65) with experience in the use of high-tech assistive technology. Demographic characteristics and the stakeholders' perceived helpfulness and frequency attending assessment and set-up sessions were captured. To evaluate how family-centred the assistive technology services were perceived to be, the parents filled out the Measure of Processes of Care for Caregivers, and the professionals completed the Measure of Processes of Care for Service Providers. Descriptive statistics and one-way analysis of variance were used to conduct the data analysis. RESULTS: Findings show that parents are more involved during the assessment stage than during the implementation and that classroom teachers are often not involved in the initial stage. Speech pathologists in particular are seen to be to a great extent helpful when implementing assistive technology in the classroom. This study found that family-centred service is not yet fully achieved in schools despite being endorsed in early intervention and disability services for over 20 years. No statistically significant differences were found with respect to school staff and allied health professionals' roles, their years of experience working with students with cerebral palsy and the scales in the Measure of Processes of Care for Service Providers. CONCLUSION: To enhance the way technology is matched to the student and successfully implemented, classroom teachers need to be fully involved in the whole assistive technology process. The findings also point to the significance of parents' involvement, with the support of allied health professionals, in the process of selecting and implementing assistive technology in the classroom.

Analgesia, nil or placebo to babies, in trials that test new analgesic treatments for procedural pain.

UNLABELLED: This review assessed how often neonates in control groups experienced unnecessary pain during clinical trials involving procedural pain. We retrieved 45 studies in the 30 months up to June 2015 and found that in 29 (64%) the control babies received either placebos or no treatment. Placebos were used in 15/25 (60%) studies involving heel pricks and in 6/8 (75%) involving venepuncture. CONCLUSION: Despite international guidelines, neonates included in control groups during painful procedures do not receive analgesia in the majority of cases. Several historical reasons can explain this, but in the light of present knowledge, this should not continue. Ethical committees are thereof invited since now to not permit clinical trials that do not explicitly rule out pain during treatments and journals are invited to not publish them.

A Fourier-Transform Infrared Study of Biochar Aging in Soils.

We used diffuse reflectance Fourier-transform infrared (DR-FTIR) spectroscopy, X-ray diffraction (XRD), and chemical and isotopic analyses to characterize the light fraction of four contrasting soils (control and biocharamended soils) to determine changes in biochar properties after aging. Two Eucalyptus saligna Sm. wood biochars, produced at 450°C (B450) and 550°C (B550), were incubated separately in each of the four soils for up to 12 mo at 20, 40, and 60°C. Total C and isotopic (δ13C) methods were used to quantify the amounts of biochar C and native C mineralized during incubation. The DR-FTIR spectra of the light fraction showed distinct absorption bands representing native soil organic C, biochar C, and mineral constituents present in the soils; the mineral bands were consistent with XRD data of the clay fraction of the four soils. Analysis of the DR-FTIR spectra in the ν(C-H) bands showed that the ratio of the aromatic ν(C-H) bands systematically increased relative to the aliphatic ν(C-H) bands with increasing mineralization of biochar C in the B550 amended soils, and this relationship was unique for each soil type. In contrast, this relationship was not observed for the B450 amended soils that contained a relatively smaller proportion of aromatic C.

Disinfection of human skin allografts in tissue banking: a systematic review report.

The use of skin allografts to temporarily replace lost or damaged skin is practiced worldwide. Naturally occurring contamination can be present on skin or can be introduced at recovery or during processing. This contamination can pose a threat to allograft recipients. Bacterial culture and disinfection of allografts are mandated, but the specific practices and methodologies are not dictated by standards. A systematic review of literature from three databases found 12 research articles that evaluated bioburden reduction processes of skin grafts. The use of broad spectrum antibiotics and antifungal agents was the most frequently identified disinfection method reported demonstrating reductions in contamination rates. It was determined that the greatest reduction in the skin allograft contamination rates utilized 0.1 % peracetic acid or 25 kGy of gamma irradiation at lower temperatures.

Intrarenal B Cell Cytokines Promote Transplant Fibrosis and Tubular Atrophy.

Renal transplantation is the optimum treatment for end-stage renal failure. B cells have been identified in chronic allograft damage (CAD) and associated with the development of tertiary lymphoid tissue within the human renal allograft. We performed renal transplantation in mice to model CAD and identified B cells forming tertiary lymphoid tissue with germinal centers. Intra-allograft B220(+) B cells comprised of IgM(high) CD23(-) B cells, IgM(lo) CD23(+) B cells, and IgM(lo) CD23(-) B cells with elevated expression of CD86. Depletion of B cells with anti-CD20 was associated with an improvement in CAD but only when administered after transplantation and not before. Isolated intra-allograft B cells were cultured and shown to synthesize multiple cytokines, the most abundant of these were GRO-α (CXCL1), RANTES (CCL5), IL-6 and MCP-1 (CCL2). Tubular loss was observed with T cell accumulation within the allograft and development of interstitial fibrosis, whilst type III collagen deposition was observed in areas of F4/80(+) macrophages and PDGFR-ß(+) and transgelin(+) fibroblasts, all of which were reduced by B cell depletion. We have shown that intra-allograft B cells are key mediators of CAD. B cells possibly contribute to CAD by intra-allograft secretion of cytokines and chemokines.

Influence of less than full-time or full-time on totality of training and subsequent consultant appointment in anaesthesia.

Changes in medical training have increased the popularity of less than full-time training. However, there are no data on the impact on training time or consultant workforce. We reviewed a three-year cohort of trainees via the Royal College of Anaesthetist's training and recruitment databases. Eighty-eight (96%) less than full-time trainees and 677 (95%) full-time trainees were appointed to a substantive consultant post (p = 0.82). Three (3%) less than full-time trainees and 12 (2%) full-time trainees gained part-time consultant posts (p < 0.001). Average length of training (years, months, days) was 8 y, 5 m, 6 d (median (IQR [range]) 5 y, 0 m, 14 d (4 y, 11 m, 29 d - 9 y, 8 m, 3 d [4 y, 2 m, 18 d - 12 y, 0 m, 0 d]) for full-time and 10 y, 8 m, 23 d (median (IQR [range]) 7 y, 3 m, 28 d (6 y, 7 m, 24 d - 11 y, 1 m, 23 d [4 y, 11 m, 29 d - 11 y, 9 m, 10 d]) for less than full-time trainees. The average length of training for both groups is significantly longer than the seven years used in workforce planning.

Excess body mass is associated with T cell differentiation indicative of immune ageing in children.

Obesity has been associated with accelerated biological ageing and immunosenescence. As the prevalence of childhood obesity is increasing, we wanted to determine if associations between obesity and immunosenescence would manifest in children. We studied 123 Mexican American adolescents aged 10-14 (mean 12·3 ± 0·7) years, with body weights ranging from 30·1 to 115·2 kg (mean 52·5 ± 14·5 kg). Blood samples were obtained to determine proportions of naive, central memory (CM), effector memory (EM), senescent and early, intermediate and highly differentiated subsets of CD4(+) and CD8(+) T cells. Overweight and obese children had significantly lowered proportions of early CD8(+) T cells (B = -11·55 and -5·51%, respectively) compared to healthy weight. Overweight children also had more EM (B = +7·53%), late (B = +8·90%) and senescent (B = +4·86%) CD8(+) T cells than healthy weight children, while obese children had more intermediate CD8(+) (B = +4·59%), EM CD8(+) (B = +5·49%), late CD4(+) (B = +2·01%) and senescent CD4(+) (B = +0·98%) T cells compared to healthy weight children. These findings withstood adjustment for potentially confounding variables, including age, gender and latent cytomegalovirus and Epstein-Barr virus infections. We conclude that excess body mass, even in adolescence, may accelerate immunosenescence and predispose children to increased risks of incurring immune-related health problems in adulthood.

Value of CT-PET after neoadjuvant chemoradiation in the prediction of histological tumour regression, nodal status and survival in oesophageal adenocarcinoma.

BACKGROUND: The role of CT-PET after neoadjuvant chemoradiation (nCRT) for prediction of pathological response and oncological outcome in oesophageal and junctional adenocarcinoma (OAC) is unclear. The relationship between complete metabolic response (cMR), pathological complete response (pCR) and nodal status has not been clarified. METHODS: Patients with locally advanced OAC selected to receive nCRT and surgery with curative intent, on the basis of staging that included CT-PET positivity, were included. Repeat scanning (PET2) with an identical protocol was performed 2-4 weeks after completion of nCRT (cisplatin and 5-fluorouracil plus 44 Gy radiation). Changes in [(18) F]fluorodeoxyglucose uptake, considered as either a maximum standardized uptake value (SUVmax) or a relative reduction (%ΔSUVmax), and PET-predicted nodal status following nCRT were compared with histopathological response, histological node positivity and survival. RESULTS: One hundred consecutive patients with PET-positive OAC were studied. Following nCRT, PET2 identified M1 disease in 2·0 per cent of patients. There were no significant associations between PET2 SUVmax or %ΔSUVmax with respect to primary tumour stage (ypT) (P = 0.216 and P = 0·975 respectively), tumour regression grade (P = 0·109 and P = 0·232), pCR (P = 0·633 and P = 0·870) or complete resection (R0) (P = 0·440 and P = 0·235). The sensitivity of PET2 for ypN was 10 per cent. %ΔSUVmax was not associated with disease-free or overall survival (P = 0·162 and P = 0·154 respectively). Of 46 patients with a cMR on PET2, 37 (80 per cent) had histological evidence of residual tumour in the resected specimen, and cMR was not associated with overall survival benefit (P = 0·478). CONCLUSION: CT-PET following nCRT for OAC has poor prognostic and discriminatory value for clinical application.

Highly durable fuel cell electrodes based on ionomers dispersed in glycerol.

A major, unprecedented improvement in the durability of polymer electrolyte membrane fuel cells is obtained by tuning the properties of the interface between the catalyst and the ionomer by choosing the appropriate dispersing medium. While a fuel cell cathode prepared from aqueous dispersion showed 90 mV loss at 0.8 A cm(-2) after 30,000 potential cycles (0.6-1.0 V), a fuel cell cathode prepared from glycerol dispersion exhibited only 20 mV loss after 70,000 cycles. This minimum performance loss occurs even though there was an over 80% reduction of electrochemical surface area of the Pt catalyst. These findings indicate that a proper understanding and control of the catalyst-water-ionomer (three-phase) interfaces is even more important for maintaining fuel cell durability in typical electrodes than catalyst agglomeration, and this opens up a novel path for tailoring the functional properties of electrified interfaces.