Explore the vast range of titles available.

This article examines how a branch of medicine based within the criminal justice system responded to a society which by the 1970s and 1980s was increasingly critical of the prison system and medical authority. The Prison Medical Service, responsible for the health care of prisoners in England and Wales, was criticised by prison campaigners and doctors alike for being unethical, isolated, secretive, and beholden to the interests of the Home Office rather than those of their patients. While prison doctors responded defensively to criticisms in the 1970s and 1980s, comparing their own standards of practice favourably with those found in the NHS, and arguing that doctors from outside would struggle to cope in the prison environment, by 1985 their attitudes had changed. Giving evidence to a House of Commons committee, prison doctors displayed a much greater willingness to discuss how the prison system made their work more difficult, and expressed a pronounced desire to engage openly with the rest of the profession to address these problems. The change of attitude partly reflects a desire by the Home Secretary William Whitelaw to make the Prison Service more open, and an acceptance of a need for greater accountability in medicine generally. Most important, however, was a greater interest in prison health care and appreciation of the difficulties of prison practice among the wider medical profession, encouraging prison doctors to speak out. This provides a case study of how a professional group could engage openly with criticisms of their work under favourable circumstances.

This thesis examines the practice of forensic medicine in Scotland in the period 1914 to 1939. This was a time of significant dynamism for the discipline, in which it enjoyed a high public profile and played an important role in the investigation of crime. The project focuses in particular on medico-legal practice at an elite level, based in specialist departments in the universities of Edinburgh and Glasgow. As well as producing a significant amount of research and textbook material, and thus constituting authorities within the discipline, representatives of these institutions gave expert evidence in a number of high-profile trials. Thus, an examination of their work can show how medico-legal knowledge was constructed, presented and challenged. To this end, four main areas of forensic medical practice are analysed, including the post-mortem examination, the laboratory analysis of trace evidence, the investigation of shootings and the use of photography. The development of the techniques contained within these categories is charted, as is the range of situations to which they were applied and the various ways in which their use was challenged in court by hostile legal counsel. Sources including textbooks and journal articles, medical case reports, photograph albums and trial transcripts are used. A fifth section explores an area of the public face of the discipline, specifically the popular output of two of its most famous practitioners, Sydney Smith and John Glaister Jr. Both produced memoirs and newspaper serials after retirement. These are used to explore the ways they reflected on their careers and spun their legacies, portraying themselves as impartial servants of science and justice. The thesis argues that the place of forensic medicine in wider institutional, investigative and geographical networks was central to its existence. The discipline collaborated extensively, both with representatives of other areas of the medical profession and with external authorities, professions and trades. Means of communication, such as written reports and samples taken at autopsy, allowed experts in the universities to lend their expertise to the non-specialists in peripheries by providing expert opinions based on materials sent to them. The scrutiny of post-mortem reports produced by peripheral generalists allowed medico-legists' expertise to be spread over a wide geographical area. The thesis also reflects on the ways in which medico-legists guarded against error. Techniques derived from other areas of medicine and science were not adopted for use in court until their reliability could be demonstrated satisfactorily, and controls and standards were built in to procedures.

1. Ecosystem restoration is an important tool for mitigating biodiversity loss and recovering critical ecosystem services to humanity, but restoration rarely takes into account the evolutionary attributes of the community being restored. Phylogenetic diversity (PD) represents a potentially valuable measure of restoration success because it can correlate with functional trait diversity that drives ecosystem function. However, PD patterns in restored communities are rarely assessed. 2. We surveyed plant communities in restored tallgrass prairies 2-19 years old and calculated two PD measures, SESMNTD and SESMPD, of the communities and seed mixture applied to sites. We also identified high-threat exotic species present in each site to determine whether PD of the seed mixture applied was related to resistance against invasion. 3. We show that PD in North American tallgrass prairie restorations, as measured by both SESMNTD and SESMPD, is maintained over time even as richness declines. Neither the resulting community PD nor invasion by high-threat exotic species was affected by PD of the seed mixture used in site restoration. Thus, simply maximizing PD of seed mixtures without considering the particular component species is unlikely to help achieve restoration goals. 4. Synthesis and applications. These results suggest that species losses over time are not biased towards species with or without close relatives in the community. If phylogenetic diversity (PD) reflects functional trait diversity in communities, then local declines in species richness may not necessarily mean the loss of ecosystem function in restoration projects. However, PD of restored communities may be limited by low establishment rates for most species. Conservation practitioners should consider PD with careful planning to maintain overall community diversity and potentially maximize ecosystem function and services in restorations. This perspective will require a deeper understanding of the relationships between phylogenetic relatedness and traits associated with competition and fitness.

While evidence-based psychotherapy (EBP) for posttraumatic stress disorder (PTSD) is a first-line treatment, its real-world effectiveness is unknown. We compared cognitive processing therapy (CPT) and prolonged exposure (PE) each to an individual psychotherapy comparator group, and CPT to PE in a large national healthcare system. We utilized effectiveness and comparative effectiveness emulated trials using retrospective cohort data from electronic medical records. Participants were veterans with PTSD initiating mental healthcare ( = 265 566). The primary outcome was PTSD symptoms measured by the PTSD Checklist (PCL) at baseline and 24-week follow-up. Emulated trials were comprised of 'person-trials,' representing 112 discrete 24-week periods of care (10/07-6/17) for each patient. Treatment group comparisons were made with generalized linear models, utilizing propensity score matching and inverse probability weights to account for confounding, selection, and non-adherence bias. There were 636 CPT person-trials matched to 636 non-EBP person-trials. Completing ⩾8 CPT sessions was associated with a 6.4-point greater improvement on the PCL (95% CI 3.1-10.0). There were 272 PE person-trials matched to 272 non-EBP person-trials. Completing ⩾8 PE sessions was associated with a 9.7-point greater improvement on the PCL (95% CI 5.4-13.8). There were 232 PE person-trials matched to 232 CPT person-trials. Those completing ⩾8 PE sessions had slightly greater, but not statistically significant, improvement on the PCL (8.3-points; 95% CI 5.9-10.6) than those completing ⩾8 CPT sessions (7.0-points; 95% CI 5.5-8.5). PTSD symptom improvement was similar and modest for both EBPs. Although EBPs are helpful, research to further improve PTSD care is critical.

Black Veterans have higher a incidence of localized and metastatic prostate cancer compared to White Veterans yet are underrepresented in reports of frequencies of somatic and germline alterations. This retrospective analysis of somatic and putative germline alterations was conducted in a large cohort of Veterans with prostate cancer (N = 835 Black, 1613 White) who underwent next generation sequencing through the VA Precision Oncology Program, which facilitates molecular testing for Veterans with metastatic cancer. No differences were observed in gene alterations for FDA approved targetable therapies (13.5% in Black Veterans vs. 15.5% in White Veterans, P = .21), nor in any potentially actionable alterations (25.5% vs. 28.7%, P =.1). Black Veterans had higher rates of BRAF (5.5% vs. 2.6%, P < .001) alterations, White Veterans TMPRSS2 fusions (27.2% vs. 11.7%, P < .0001). Putative germline alteration rates were higher in White Veterans (12.0% vs. 6.1%, P < .0001). Racial disparities in outcome are unlikely attributable to acquired somatic alterations in actionable pathways. Black veterans have higher incidence of prostate cancer than White veterans but are underrepresented in reports of frequencies of somatic and germline alterations. This retrospective analysis of somatic and putative germline alterations was conducted in a large cohort of veterans with prostate cancer who underwent next-generation sequencing through the VA Precision Oncology Program. No differences were observed in actionable alterations, suggesting disparities in prostate cancer outcomes are not attributable to acquired somatic alterations in actionable pathways.

Prostate cancer (PCa) disproportionately affects African American men, but research evaluating the extent of racial and ethnic disparities across the PCa continuum in equal-access settings remains limited at the national level. The US Department of Veterans Affairs (VA) Veterans Hospital Administration health care system offers a setting of relatively equal access to care in which to assess racial and ethnic disparities in self-identified African American (or Black) veterans and White veterans. To determine the extent of racial and ethnic disparities in the incidence of PCa, clinical stage, and outcomes between African American patients and White patients who received a diagnosis or were treated at a VA hospital. This retrospective cohort study included 7 889 984 veterans undergoing routine care in VA hospitals nationwide from 2005 through 2019 (incidence cohort). The age-adjusted incidence of localized and de novo metastatic PCa was estimated. Treatment response was evaluated, and PCa-specific outcomes were compared between African American veterans and White veterans. Residual disparity in PCa outcome, defined as the leftover racial and ethnic disparity in the outcomes despite equal response to treatment, was estimated. Self-identified African American (or Black) and White race and ethnicity. Time to distant metastasis following PCa diagnosis was the primary outcome. Descriptive analyses were used to compare baseline demographics and clinic characteristics. Multivariable logistic regression was used to evaluate race and ethnicity association with pretreatment clinical variables. Multivariable Cox regression was used to estimate the risk of metastasis. Data from 7 889 984 veterans from the incidence cohort were used to estimate incidence, whereas data from 92 269 veterans with localized PCa were used to assess treatment response. Among 92 269 veterans, African American men (n = 28 802 [31%]) were younger (median [IQR], 63 [58-68] vs 65 [62-71] years) and had higher prostate-specific antigen levels (>20 ng/mL) at the time of diagnosis compared with White men (n = 63 467; [69%]). Consistent with US population-level data, African American veterans displayed a nearly 2-fold greater incidence of localized and de novo metastatic PCa compared with White men across VA centers nationwide. Among veterans screened for PCa, African American men had a 29% increased risk of PCa detection on a diagnostic prostate biopsy compared with White (hazard ratio, 1.29; 95% CI, 1.27-1.31; P < .001). African American men who received definitive primary treatment of PCa experienced a lower risk of metastasis (hazard ratio, 0.89; 95% CI, 0.83-0.95; P < .001). However, African American men who received nondefinitive treatment classified as “other” were more likely to develop metastasis (adjusted hazard ratio, 1.29; 95% CI, 1.17-1.42; P < .001). Using the actual rate of metastasis from veterans who received definitive primary treatment, a persistent residual metastatic burden for African American men was observed across all National Comprehensive Cancer Network risk groups (low risk, 4 vs 2 per 100 000; intermediate risk, 13 vs 6 per 100 000; high risk, 19 vs 9 per 100 000). This cohort analysis found significant disparities in the incidence of localized and metastatic PCa between African American veterans and White veterans. This increased incidence is a major factor associated with the residual disparity in PCa metastasis observed in African American veterans compared with White veterans despite their nearly equal response to treatment.

Bone formation during fracture repair inevitably initiates within or around extravascular deposits of a fibrin-rich matrix. In addition to a central role in hemostasis, fibrin is thought to enhance bone repair by supporting inflammatory and mesenchymal progenitor egress into the zone of injury. However, given that a failure of efficient fibrin clearance can impede normal wound repair, the precise contribution of fibrin to bone fracture repair, whether supportive or detrimental, is unknown. Here, we employed mice with genetically and pharmacologically imposed deficits in the fibrin precursor fibrinogen and fibrin-degrading plasminogen to explore the hypothesis that fibrin is vital to the initiation of fracture repair, but impaired fibrin clearance results in derangements in bone fracture repair. In contrast to our hypothesis, fibrin was entirely dispensable for long-bone fracture repair, as healing fractures in fibrinogen-deficient mice were indistinguishable from those in control animals. However, failure to clear fibrin from the fracture site in plasminogen-deficient mice severely impaired fracture vascularization, precluded bone union, and resulted in robust heterotopic ossification. Pharmacological fibrinogen depletion in plasminogen-deficient animals restored a normal pattern of fracture repair and substantially limited heterotopic ossification. Fibrin is therefore not essential for fracture repair, but inefficient fibrinolysis decreases endochondral angiogenesis and ossification, thereby inhibiting fracture repair.

Venous thromboembolism is a significant cause of mortality 1 , yet its genetic determinants are incompletely defined. We performed a discovery genome-wide association study in the Million Veteran Program and UK Biobank, with testing of approximately 13 million DNA sequence variants for association with venous thromboembolism (26,066 cases and 624,053 controls) and meta-analyzed both studies, followed by independent replication with up to 17,672 venous thromboembolism cases and 167,295 controls. We identified 22 previously unknown loci, bringing the total number of venous thromboembolism-associated loci to 33, and subsequently fine-mapped these associations. We developed a genome-wide polygenic risk score for venous thromboembolism that identifies 5% of the population at an equivalent incident venous thromboembolism risk to carriers of the established factor V Leiden p.R506Q and prothrombin G20210A mutations. Our data provide mechanistic insights into the genetic epidemiology of venous thromboembolism and suggest a greater overlap among venous and arterial cardiovascular disease than previously thought. Genome-wide analysis of venous thromboembolism identifies 22 new risk loci and facilitates construction of a polygenic risk score. Comparison to arterial vascular disease highlights shared pathophysiology and potential therapeutic strategies.