Co-located Heroin Assisted Treatment within primary care: A preliminary analysis of the implications for healthcare access, cost, and treatment delivery in the UK.

The UK is experiencing its highest rate of drug related deaths in 25 years. Poor and inconsistent access to healthcare negatively impacts health outcomes for people who use drugs. Innovation in models of care which promote access and availability of physical treatment is fundamental. Heroin Assisted Treatment (HAT) is a treatment modality targeted at the most marginalised people who use drugs, at high risk of mortality and morbidity. The first service-provider initiated HAT service in the UK ran between October 2019 and November 2022 in Middlesbrough, England. The service was co-located within a specialist primary care facility offering acute healthcare treatment alongside injectable diamorphine. Analysis of anonymised health records for healthcare costs (not including drug treatment) took place using descriptive statistics prior and during engagement with HAT, at both three (n=15) and six (n=12) months. Primary outcome measures were incidents of wound care, skin and soft tissue infections (SSTIs), overdose (OD) events, unplanned overnight stays in hospital, treatment engagement (general and within hospital care settings) and ambulance incidents. Secondary outcome measures were costs associated with these events. A shift in healthcare access for participants during HAT engagement was observed. HAT service attendance appeared to support health promoting preventative care, and reduce reactive reliance on emergency healthcare systems. At three and six months, engagement for preventative wound care and treatment for SSTIs increased at the practice. Unplanned emergency healthcare interactions for ODs, overnight hospital stays, serious SSTIs, and ambulance incidents reduced, and there was an increase in treatment engagement (i.e. a reduction in appointments which were not engaged with). There was a decrease in treatment engagement in hospital settings. Changes in healthcare utilisation during HAT translated to a reduction in healthcare costs of 58% within six months compared to the same timeframe from the period directly prior to commencing HAT. This exploratory study highlights the potential for innovative harm reduction interventions such as HAT, co-located with primary care services, to improve healthcare access and engagement for a high-risk population. Increased uptake of primary healthcare services translated to reductions in emergency healthcare use and associated costs. Although costs of HAT provision are substantial, the notable cost-savings in health care should be an important consideration in service implementation planning. [Abstract copyright: Copyright © 2024. Published by Elsevier B.V.

Evaluation of local measurement-driven adjustments of modelled cloud-free atmospheric photolysis rate coefficients

Photolysis rate constants (j-values) play a crucial role in atmospheric chemistry modelling, but capturing the variability in local conditions needed for their accurate simulation is computationally challenging. One approach is to adjust modelled clear-sky estimates using ratios of measured-to-modelled j-values of a reference photolysis, typically j(NO2) or j(O1D). However, application of such adjustments to other photolysis reactions introduces uncertainty. Using spectral radiometer data from the UK, this study examines how hourly measurement driven adjustment factors (MDAF) across a set of 12 photolysis reactions group together using cluster analysis, and evaluates the uncertainties in using j(NO2) and j(O1D)-derived MDAF values to adjust modelled j-values of other photolysis reactions. The NO2-MDAF reference is suitable for adjusting photolysis reactions that absorb at λ > 360 nm (HONO, methylglyoxal, ClNO2, ClONO2 → Cl), which are largely independent of solar zenith angle and total ozone column (<31% error). In particular, NO2-MDAF is a good reference for j(HONO) and j(ClNO2). The O1D-MDAF performed better at adjusting modelled j-values for species that predominantly photodissociate at λ < 350 nm, such as HNO3, H2O2, CH3CHO, HCHO → H, HCHO → H2 and ClONO2 → ClO (errors ≤ 30%). However, j(O1D) radiometers require more data processing to account for local conditions. The maximum error determined using NO2-MDAF was within a factor of two (91% for j(H2O2)), which may still be acceptable in some instances. It is important that MDAFs are used to improve accuracy and uncertainty in simulated j-values caused by variation in local conditions

The bacterial microbiota regulates normal hematopoiesis via metabolite-induced type 1 interferon signaling

Antibiotic therapy, especially when administered long term, is associated with adverse hematologic effects such as cytopenia. Signals from the intestinal microbiota are critical to maintain normal hematopoiesis, and antibiotics can cause bone marrow suppression through depletion of the microbiota. We reported previously that STAT1 signaling is necessary for microbiota-dependent hematopoiesis, but the precise mechanisms by which the gut microbiota signals to the host bone marrow to regulate hematopoiesis remain undefined. We sought to identify the cell type(s) through which STAT1 promotes microbiota-mediated hematopoiesis and to elucidate which upstream signaling pathways trigger STAT1 signaling. Using conditional knockout and chimeric mice, we found that the microbiota induced STAT1 signaling in non-myeloid hematopoietic cells to support hematopoiesis and that STAT1 signaling was specifically dependent on type I interferons (IFNs). Indeed, basal type I IFN signaling was reduced in hematopoietic progenitor cells with antibiotic treatment. In addition, we discovered that oral administration of a commensal-derived product, NOD1 ligand, rescues the hematopoietic defects induced by antibiotics in mice. Using metabolomics, we identified additional microbially produced candidates that can stimulate type I IFN signaling to potentially rescue the hematopoietic defects induced by antibiotics, including phosphatidylcholine and γ-glutamylalanine. Overall, our studies define a signaling pathway through which microbiota promotes normal hematopoiesis and identify microbial metabolites that may serve as therapeutic agents to ameliorate antibiotic-induced bone marrow suppression and cytopenia

Identification of a triplet pair intermediate in singlet exciton fission in solution.

Singlet exciton fission is the spin-conserving transformation of one spin-singlet exciton into two spin-triplet excitons. This exciton multiplication mechanism offers an attractive route to solar cells that circumvent the single-junction Shockley-Queisser limit. Most theoretical descriptions of singlet fission invoke an intermediate state of a pair of spin-triplet excitons coupled into an overall spin-singlet configuration, but such a state has never been optically observed. In solution, we show that the dynamics of fission are diffusion limited and enable the isolation of an intermediate species. In concentrated solutions of bis(triisopropylsilylethynyl)[TIPS]--tetracene we find rapid (<100 ps) formation of excimers and a slower (∼ 10 ns) break up of the excimer to two triplet exciton-bearing free molecules. These excimers are spectroscopically distinct from singlet and triplet excitons, yet possess both singlet and triplet characteristics, enabling identification as a triplet pair state. We find that this triplet pair state is significantly stabilized relative to free triplet excitons, and that it plays a critical role in the efficient endothermic singlet fission process.H.L.S was supported by the Winton Programme for the Physics of Sustainability and A.J.M received funding from the Engineering and Physical Sciences Research Council.This is the accepted manuscript. The final version is available at http://www.pnas.org/content/112/25/7656.abstract

The Importance of Capturing Local Measurement-Driven Adjustment of Modelled <i>j</i>(NO₂)

Accurate photolysis rate constants are essential for simulation of local air quality but their values can vary substantially with changes in local meteorological and surface conditions. This study demonstrates the use of local radiometer measurements for capturing via hourly measurement-driven adjustment factors (MDAF) the temporal resolution needed to adjust clear-sky or cloud-free model estimates of j(NO2). Measurements simultaneously at two sites in the UK (Auchencorth Moss and Manchester) showed that TUV (v5.3) model estimates of j(NO2)↓ in cloud-free conditions (used as an example of modelled j-values) were, on average, approximately 45% larger than measured j(NO2)↓, which would lead to substantial model bias in the absence of local adjustment. At Auchencorth Moss, MDAF values based on 4π and 2π radiometer inlets generally agreed very well with each other (<6% average difference). However, under conditions of particularly high surface albedo (such as snow cover), increased upwelling local diffuse radiation yielded an MDAF derived using total radiation (sum of ↓ and ↑ components) ~40% larger than the MDAF derived using only ↓ radiation. The study has demonstrated: (1) the magnitude of potential impact of local conditions—principally cloud cover, but also changes in surface albedo—on assumed j-values; (2) that whilst annual mean MDAF values are similar at Auchencorth Moss and Manchester, there is no contemporaneous correlation between them at hourly resolution; hence MDAF values derived at one site cannot readily be applied at another site. These data illustrate the need to routinely deploy long-term radiometer measurements alongside compositional measurements to support atmospheric chemistry modelling

Evaluating the Student Training Equity Project: An Upstream Recruitment Approach to Diversifying Clinical Psychology Graduate Programs

The U.S. psychology workforce is considerably less diverse than the population that it serves. While several recruitment and admission practices are effective for diversifying psychology training programs, upstream recruitment of underrepresented candidates is particularly promising. Aiming to diversify the clinical psychology graduate program applicant pool, the Student Training Equity Project (STEP) was developed to promote and evaluate upstream recruitment of undergraduate students of color interested in psychology graduate studies. This study used a mixed-method design to evaluate immediate outcomes for three STEP programmatic strategies. Survey results suggest that STEP networking events were associated with undergraduate research and mentorship opportunities. Findings suggest that STEP funding supported students in producing research products (e.g., manuscripts) that might bolster graduate application materials. STEP website engagement data showed over 1,000 views per year, and highlighted ways to improve outreach. More controlled evaluation is needed to determine whether STEP contributed to diversification of the applicant pool

The Deubiquitinase OTULIN Is an Essential Negative Regulator of Inflammation and Autoimmunity.

Methionine-1 (M1)-linked ubiquitin chains regulate the activity of NF-κB, immune homeostasis, and responses to infection. The importance of negative regulators of M1-linked chains in vivo remains poorly understood. Here, we show that the M1-specific deubiquitinase OTULIN is essential for preventing TNF-associated systemic inflammation in humans and mice. A homozygous hypomorphic mutation in human OTULIN causes a potentially fatal autoinflammatory condition termed OTULIN-related autoinflammatory syndrome (ORAS). Four independent OTULIN mouse models reveal that OTULIN deficiency in immune cells results in cell-type-specific effects, ranging from over-production of inflammatory cytokines and autoimmunity due to accumulation of M1-linked polyubiquitin and spontaneous NF-κB activation in myeloid cells to downregulation of M1-polyubiquitin signaling by degradation of LUBAC in B and T cells. Remarkably, treatment with anti-TNF neutralizing antibodies ameliorates inflammation in ORAS patients and rescues mouse phenotypes. Hence, OTULIN is critical for restraining life-threatening spontaneous inflammation and maintaining immune homeostasis.This work was supported by the Medical Research Council (U105192732 and U105178805), the European Research Council (309756), the Lister Institute for Preventive Medicine, and the EMBO Young Investigator Program (to D.K.); a Marie-Sklodowska Curie Individual Fellowship from the European Commission (MC-IF-654019) and a Research Fellowship from Corpus Christi College Cambridge (to R.B.D.); and Wellcome Trust (to N.V.M., E.R.M., and A.N.J.M [100963/Z/13/Z]), WellChild (to N.V.M. and E.R.M.), and UCB (to H.L.T., D.M. and E.R.M.).This is the final version of the article. It first appeared from Cell Press via http://dx.doi.org/10.1016/j.cell.2016.07.01