Factors associated with access to care and healthcare utilisation in the homeless population of England

Introduction: People experiencing homelessness are known to have complex health needs which are often compounded by poor access to healthcare. This study investigates the individual-level factors associated with access to care and healthcare utilisation among homeless people in England. Methods: A cross-sectional sample of 2,505 homeless people from 19 areas of England was used to investigate associations with access to care and healthcare utilisation. Results: Rough sleepers were much less likely to be registered with a GP (OR 0.45, CI 0.30-0.66) than single homeless in accommodation (reference group) or the hidden homeless (OR 1.48 CI 0.88-2.50). Those who had recently been refused registration by a GP or dentist also had lower odds of being admitted to hospital (OR 0.67, CI 0.49-0.91) or using an ambulance (OR 0.73, CI 0.54-0.99). Conclusions: The most vulnerable homeless people appear to face the greatest barriers to utilising healthcare. Rough sleepers have particularly low rates of GP registration and this appears to have a knock-on effect on admission to hospital. Improving primary care access for the homeless population could ensure that some of the most vulnerable people in society are able to access vital services which they are currently missing out on

Scim: Intelligent Skimming Support for Scientific Papers

Researchers need to keep up with immense literatures, though it is time-consuming and difficult to do so. In this paper, we investigate the role that intelligent interfaces can play in helping researchers skim papers, that is, rapidly reviewing a paper to attain a cursory understanding of its contents. After conducting formative interviews and a design probe, we suggest that skimming aids should aim to thread the needle of highlighting content that is simultaneously diverse, evenly-distributed, and important. We introduce Scim, a novel intelligent skimming interface that reifies this aim, designed to support the skimming process by highlighting salient paper contents to direct a skimmer's focus. Key to the design is that the highlights are faceted by content type, evenly-distributed across a paper, with a density configurable by readers at both the global and local level. We evaluate Scim with an in-lab usability study and deployment study, revealing how skimming aids can support readers throughout the skimming experience and yielding design considerations and tensions for the design of future intelligent skimming tools

Structural Optimization of Dental Restorations using the Principle of Adaptive Growth

ABSTRACT Fracture of restored teeth is a problem in restorative dentistry since it has been estimated that 92 percent of fractured teeth have been previously restored. In a restored tooth, the stresses that occur at the tooth-restoration interface during loading could become large enough to fracture the tooth and/or restoration. The tooth preparation process for a dental restoration is therefore a classical optimization problem: tooth reduction must be minimized to preserve tooth tissue whilst stress levels must be kept low to avoid fracture of the restored tooth. The objective of the present study was to propose alternative optimized designs for a second upper premolar cavity preparation by means of structural shape optimization based on the finite element method and biological adaptive growth. Restored tooth models using the optimized cavity shapes exhibited significant reduction of stresses along the tooth-restoration interface. In the best case, the maximum stress value was reduced by more than 50 percent

A Geographically-Restricted but Prevalent Mycobacterium tuberculosis Strain Identified in the West Midlands Region of the UK between 1995 and 2008

Background: We describe the identification of, and risk factors for, the single most prevalent Mycobacterium tuberculosis strain in the West Midlands region of the UK.Methodology/Principal Findings: Prospective 15-locus MIRU-VNTR genotyping of all M. tuberculosis isolates in the West Midlands between 2004 and 2008 was undertaken. Two retrospective epidemiological investigations were also undertaken using univariable and multivariable logistic regression analysis. The first study of all TB patients in the West Midlands between 2004 and 2008 identified a single prevalent strain in each of the study years (total 155/3,056 (5%) isolates). This prevalent MIRU-VNTR profile (32333 2432515314 434443183) remained clustered after typing with an additional 9-loci MIRU-VNTR and spoligotyping. The majority of these patients (122/155, 79%) resided in three major cities located within a 40 km radius. From the apparent geographical restriction, we have named this the "Mercian" strain. A multivariate analysis of all TB patients in the West Midlands identified that infection with a Mercian strain was significantly associated with being UK-born (OR = 9.03, 95% CI = 4.56-17.87, p 65 years old (OR = 0.25, 95% CI = 0.09-0.67, p < 0.01). A second more detailed investigation analyzed a cohort of 82 patients resident in Wolverhampton between 2003 and 2006. A significant association with being born in the UK remained after a multivariate analysis (OR = 9.68, 95% CI = 2.00-46.78, p < 0.01) and excess alcohol intake and cannabis use (OR = 6.26, 95% CI = 1.45-27.02, p = .01) were observed as social risk factors for infection.Conclusions/Significance: The continued consistent presence of the Mercian strain suggests ongoing community transmission. Whilst significant associations have been found, there may be other common risk factors yet to be identified. Future investigations should focus on targeting the relevant risk groups and elucidating the biological factors that mediate continued transmission of this strain

Phase 1 safety, tolerability, pharmacokinetics and pharmacodynamic results of KCL‐286, a novel retinoic acid receptor‐β agonist for treatment of spinal cord injury, in male healthy participants

Aims: KCL‐286 is an orally available agonist taht activates the retinoic acid receptor (RAR) β2, a transcription factor which stimulates axonal outgrowth. The investigational medicinal product is being developed for treatment of spinal cord injury (SCI). This adaptive dose escalation study evaluated the tolerability, safety and pharmacokinetics and pharmacodynamic activity of KCL‐286 in male healthy volunteers to establish dosing to be used in the SCI patient population. Methods: The design was a double blind, randomized, placebo‐controlled dose escalation study in 2 parts: a single ascending dose adaptive design with a food interaction arm, and a multiple ascending dose design. RARβ2 mRNA expression was evaluated in white blood cells. Results: At the highest single and multiple ascending doses (100 mg), no trends or clinically important differences were noted in the incidence or intensity of adverse events (AEs), serious AEs or other safety assessments with none leading to withdrawal from the study. The AEs were dry skin, rash, skin exfoliation, raised liver enzymes and eye disorders. There was an increase in mean maximum observed concentration and area under the plasma concentration–time curve up to 24 h showing a trend to subproportionality with dose. RARβ2 was upregulated by the investigational medicinal product in white blood cells. Conclusion: KCL‐286 was well tolerated by healthy human participants following doses that exceeded potentially clinically relevant plasma exposures based on preclinical in vivo models. Target engagement shows the drug candidate activates its receptor. These findings support further development of KCL‐286 as a novel oral treatment for SCI

ClimateGPT: Towards AI Synthesizing Interdisciplinary Research on Climate Change

This paper introduces ClimateGPT, a model family of domain-specific large language models that synthesize interdisciplinary research on climate change. We trained two 7B models from scratch on a science-oriented dataset of 300B tokens. For the first model, the 4.2B domain-specific tokens were included during pre-training and the second was adapted to the climate domain after pre-training. Additionally, ClimateGPT-7B, 13B and 70B are continuously pre-trained from Llama~2 on a domain-specific dataset of 4.2B tokens. Each model is instruction fine-tuned on a high-quality and human-generated domain-specific dataset that has been created in close cooperation with climate scientists. To reduce the number of hallucinations, we optimize the model for retrieval augmentation and propose a hierarchical retrieval strategy. To increase the accessibility of our model to non-English speakers, we propose to make use of cascaded machine translation and show that this approach can perform comparably to natively multilingual models while being easier to scale to a large number of languages. Further, to address the intrinsic interdisciplinary aspect of climate change we consider different research perspectives. Therefore, the model can produce in-depth answers focusing on different perspectives in addition to an overall answer. We propose a suite of automatic climate-specific benchmarks to evaluate LLMs. On these benchmarks, ClimateGPT-7B performs on par with the ten times larger Llama-2-70B Chat model while not degrading results on general domain benchmarks. Our human evaluation confirms the trends we saw in our benchmarks. All models were trained and evaluated using renewable energy and are released publicly

Explaining the DAMA Signal with WIMPless Dark Matter

WIMPless dark matter provides a framework in which dark matter particles with a wide range of masses naturally have the correct thermal relic density. We show that WIMPless dark matter with mass around 2-10 GeV can explain the annual modulation observed by the DAMA experiment without violating the constraints of other dark matter searches. This explanation implies distinctive and promising signals for other direct detection experiments, GLAST, and the LHC.Comment: 8 pages; v2: discussion of channeling, CoGeNT, and references added; v3: published version; v4: annihilation signal correcte

FEM Simulation of Non-Progressive Growth from Asymmetric Loading and Vicious Cycle Theory: Scoliosis Study Proof of Concept

Scoliosis affects about 1-3% of the adolescent population, with 80% of cases being idiopathic. There is currently a lack of understanding regarding the biomechanics of scoliosis, current treatment methods can be further improved with a greater understanding of scoliosis growth patterns. The objective of this study is to develop a finite element model that can respond to loads in a similar fashion as current spine biomechanics models and apply it to scoliosis growth. Using CT images of a non-scoliotic individual, a finite element model of the L3-L4 vertebra was created. By applying asymmetric loading in accordance to the ‘vicious cycle’ theory and through the use of a growth modulation equation it is possible to determine the amount of growth each region of the vertebra will undergo; therefore predict scoliosis growth over a period of time. This study seeks to demonstrate how improved anatomy can expand researchers current knowledge of scoliosis

Combined treatment of rapamycin and dietary restriction has a larger effect on the transcriptome and metabolome of liver

Rapamycin (Rapa) and dietary restriction (DR) have consistently been shown to increase lifespan. To investigate whether Rapa and DR affect similar pathways in mice, we compared the effects of feeding mice ad libitum (AL), Rapa, DR, or a combination of Rapa and DR (Rapa + DR) on the transcriptome and metabolome of the liver. The principal component analysis shows that Rapa and DR are distinct groups. Over 2500 genes are significantly changed with either Rapa or DR when compared with mice fed AL; more than 80% are unique to DR or Rapa. A similar observation was made when genes were grouped into pathways; two-thirds of the pathways were uniquely changed by DR or Rapa. The metabolome shows an even greater difference between Rapa and DR; no metabolites in Rapa-treated mice were changed significantly from AL mice, whereas 173 metabolites were changed in the DR mice. Interestingly, the number of genes significantly changed by Rapa + DR when compared with AL is twice as large as the number of genes significantly altered by either DR or Rapa alone. In summary, the global effects of DR or Rapa on the liver are quite different and a combination of Rapa and DR results in alterations in a large number of genes and metabolites that are not significantly changed by either manipulation alone, suggesting that a combination of DR and Rapa would be more effective in extending longevity than either treatment alone.Keywords: metabolome, rapamycin, transcriptome, dietary restrictio