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Background HIV pre-exposure prophylaxis (PrEP) is a medication that prevents the acquisition of HIV. It has been targeted towards men who have sex with men (MSM). Since its introduction there have been concerns raised around changes in sexual behaviour such as increased condomless anal intercourse (CAI), leading to an elevation in sexually transmitted infections (STIs). With antimicrobial resistant strains of STIs rising, there are concerns that PrEP may be contributing to this growth. This study aims to understand how MSM conceptualise the relationship between PrEP, STIs and antimicrobial resistance (AMR). Methods Twenty semi-structured interviews were conducted online using Zoom. Participants include a mix of PrEP related experiences (never used, currently use, previously used). Reflexive thematic analysis was undertaken by the lead author with 10% of transcripts double coded. Results MSM in Wales have positive views and a good knowledge of PrEP and awareness of bacterial STIs. PrEP is perceived by many to lead to a reduction in condom use and increase in STIs but reported condom use behaviours presented to be stable in terms of PrEP initiation. PrEP use is influenced by increased concern for HIV and minimal concern for bacterial STIs. Awareness of AMR STIs was lacking. Conclusions There is a belief that PrEP use will lead to an increase in STI rates through reduced condom use, despite reported behaviours often being stable in relation to PrEP initiation, PrEP stigma may be influencing this dichotomy. Concern and awareness for resistant STIs is low, with little association to PrEP.

Background. Invasive aspergillosis (IA) is an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. The purpose of this study was to evaluate factors associated with mortality in transplant patients with IA. Methods. Transplant patients from 23 US centers were enrolled from March 2001 to October 2005 as part of the Transplant Associated Infection Surveillance Network. IA cases were identified prospectively in this cohort through March 2006, and data were collected. Factors associated with 12-week all-cause mortality were determined by logistic regression analysis and Cox proportional hazards regression. Results. Six-hundred forty-two cases of proven or probable IA were evaluated, of which 317 (49.4%) died by the study endpoint. All-cause mortality was greater in HSCT patients (239 [57.5%] of 415) than in SOT patients (78 [34.4%] of 227; ). Independent poor P < .001 prognostic factors in HSCT patients were neutropenia, renal insufficiency, hepatic insufficiency, early-onset IA, proven IA, and methylprednisolone use. In contrast, white race was associated with decreased risk of death. Among SOT patients, hepatic insufficiency, malnutrition, and central nervous system disease were poor prognostic indicators, whereas prednisone use was associated with decreased risk of death. Among HSCT or SOT patients who received antifungal therapy, use of an amphotericin B preparation as part of initial therapy was associated with increased risk of death. Conclusions. There are multiple variables associated with survival in transplant patients with IA. Understanding these prognostic factors may assist in the development of treatment algorithms and clinical trials.

BackgroundWe conducted a pilot randomised controlled trial (the PHaCT study), including a process evaluation to assess the acceptability of a housing-led Critical Time Intervention (CTI) for prison leavers and the use of a trial design. This paper presents the process evaluation findings.ObjectiveTo explore the acceptability of both the intervention and the trial design to participants and those delivering the intervention, and to assess whether the intervention was delivered with fidelity.DesignA process evaluation following Medical Research Council guidelines. Data collection included semi-structured interviews with participants and CTI caseworkers and observations of intervention delivery. A thematic analysis of interviews and observations was conducted to understand the intervention’s implementation and contextual factors as well as the trial process acceptability.SettingParticipants for the pilot trial were recruited from three prisons in England and Wales where the intervention was being delivered.ParticipantsWhile 28 out of 34 trial participants consented to interviews, only one was completed. Seven caseworkers were interviewed.InterventionA housing-led CTI to support people leaving prison at risk of homelessness, involving phased, time-limited support from caseworkers, starting prerelease and continuing postrelease, to help secure stable housing and build independence, without directly providing housing.ResultsThe intervention’s acceptability was primarily reflected through the positive feedback and success stories shared by CTI caseworkers, as well as observational data indicating high acceptance among service users. The trial design’s acceptability was challenged by concerns about randomisation and equipoise, with staff viewing randomisation as unethical due to limited support for vulnerable populations. The fidelity to the CTI intervention housing-led approach was adhered to as best as possible; stable housing was prioritised for service users before addressing other needs. Despite these efforts, both sites encountered significant challenges due to limited housing availability and complex systems for securing social housing, particularly for single men leaving prison.ConclusionsThis wider study faced significant challenges which impacted the process evaluation. Despite these issues, the evaluation provides important insights into the challenges of conducting trials on interventions for people leaving prison. The challenges experienced should inform future study designs with similar populations and in similar settings.Trial registration numberISRCTN46969988.

ObjectiveTo determine whether a full-scale randomised control trial (RCT) assessing the efficacy and cost-effectiveness of a housing led Critical Time Intervention (CTI) is feasible and acceptable.DesignPilot parallel two-arm individual level RCT, including process evaluation and embedded exploratory health economic evaluation.SettingFour prisons for men across England and Wales, UK.ParticipantsMen leaving prison at risk of homelessness and intervention delivery staff.InterventionCTI has four components: (1) pre-engagement phase: assessing the needs of the client and implementing a plan pre-discharge; (2) transition to community: forming relationships and goal setting; (3) try out: encouraging problem-solving and managing practical issues and (4) transfer of care: developing long-term goals and transferring responsibilities to community providers.Outcome measuresProgression criteria: recruitment, retention, acceptability of the processes (CTI and trial method) and fidelity of intervention delivery. We also assessed the completeness of primary, secondary and exploratory outcome measures and estimated intervention costs.ResultsThe recruitment progression criterion was met, with 92% (34/37) of approached individuals consenting to participate (target: 50%). However, the overall recruitment target of 80 was not achieved, and retention was low, only 18% (6/34) provided follow-up data, well below the 60% threshold. Retention was hindered by systemic challenges, including changes to prison release policies and reduced probation support. While the CTI model was acceptable to staff and service users, the trial design, particularly randomisation, was not. Intervention fidelity met the progression criteria. Baseline data collection for health economics and resource use was feasible, and intervention costs were estimated.ConclusionThis pilot trial identified significant challenges to conducting a full-scale RCT of CTI in this context, particularly around retention, trial acceptability and systemic instability. While CTI remains a promising model, a traditional RCT design may not be viable in this setting without substantial structural and ethical adaptations.Trial registration numberISRCTN46969988.

ABSTRACT Slipped capital femoral epiphysis (SCFE) is a common adolescent hip disorder that can lead to complex proximal femur deformities and devastating consequences such as avascular necrosis, femoroacetabular impingement syndrome and early-onset osteoarthritis. Existing surgical techniques are often insufficient to fully address the constellation of multiplanar deformities in patients with severe SCFE. Therefore, the McMaster Osteotomy, a novel intertrochanteric proximal femur osteotomy, was developed to improve anatomic correction and hip mechanics in patients with chronic SCFE. The McMaster Osteotomy was implemented in two patients (A: 16-year-old male, B: 17-year-old female) with proximal femur deformities due to chronic SCFE. Surgical planning was facilitated with a 3D-printed pelvic model generated from a CT scan of a patient with the SCFE deformity. Patient B also underwent concurrent arthroscopic osteochondroplasty and labral repair. Pre- and post-operative function and radiographic measurements were recorded. Post-operatively, patient A’s neck-shaft angle improved from 125° to 136°, Southwick angle from 52° to 33°, neck length from 66 mm to 80 mm and hip internal rotation from 5° to 25°. Patient B’s post-operative neck-shaft angle improved from 122° to 136°, Southwick angle from 25° to 15°, neck length from 76 mm to 84 mm, hip internal rotation from 5° to 20° and alpha angle from 87.6° to 44.3°. Both patients are pain-free and have obtained full union of their osteotomies. The McMaster Osteotomy is a versatile technique that can produce a more anatomic reconstruction of hip anatomy and restoration of abductor mechanics. As an extracapsular technique, the risk of femoral head avascular necrosis is minimized.

Autonomous cislunar spacecraft navigation is critical to mission success as communication to ground stations and access to global positioning system (GPS) signals could be lost. However, if the satellite has a camera of sufficient quality, geometric line-of-sight (unit vector) measurements can be made to known lunar landmarks (e.g., Tycho Crater) to provide observations that enable autonomous estimation of the position and velocity of the spacecraft. In this study, an improved batch gaussian initial orbit determination (IOD) differential corrector (DC) algorithm, based on the approximated values of the two-body f and g series, is applied to initialize a (non-conic based) circular restricted three body problem (CR3BP) extended Kalman Filter (EKF) navigator. This navigator collects geometric line-of-sight unit vector (angle only) measurements to a known location on the Moon to sequentially estimate the position and velocity of an observer spacecraft flying on an approximate southern L1 Halo orbit. In this study, it was found that the best approach is to initialize the CR3BP EKF (navigator) using the solution from the batch DC filter with at least 10 measurements taken against the perceived centroid of Tycho Crater. Thereafter, it is best to continue the navigator with subsequent measurements taken against the same center coordinates of the Tycho Crater, where these coordinates are now expressed in the CR3BP rotating frame. For successful conic-based batch filter initialization and long-term CR3BP EKF convergence, it was found that the cadence for all optical measurements should be taken at 10 minutes for a simulated measurement noise of 0.1° one sigma uncertainty about the line-of-sight measurement unit vector.

Cross-sectional studies report an inverse association between BMI and serum carotenoid concentration. The present study examined the prospective association between BMI and the serum concentration of five carotenoids in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Serum carotenoids (α-carotene, β-carotene, β-cryptoxanthin, zeaxanthin/lutein, lycopene), BMI, dietary intake, physical activity and dietary supplement use were measured at years 0 and 7 in 3071 black and white male and female participants, who were either persistent smokers or non-smokers. Among non-smokers, year 0 BMI predicted year 7 serum carotenoid levels: obese subjects (BMI ≥30kg/m2) had an average concentration of the sum of four carotenoids (α-carotene +β-carotene + zeaxanthin/lutein +β-cryptoxanthin)that was 22% lower than the concentration among subjects with a BMI of less than 22kg/m2. In contrast, the sum of carotenoids among smokers was only 6% lower. Relationships between BMI and serum lycopene were weak. The change from year 0 to year 7 in serum carotenoids, except for lycopene, was inversely associated with the change in BMI among non-smokers but not among smokers. Parallel findings were observed for BMI and serum γ-glutamyl transferase level. In summary, the observation that BMI predicted the evolution of serum carotenoids during a 7-year follow-up among young non-smoking adults is consistent with the hypothesis that carotenoids are decreased in protecting against oxidative stress generated by adipose tissue, while smokers maintain a minimal level of serum carotenoids independent of adiposity. The results for lycopene were, however, discordant from those of the other carotenoids.

Although hyperinsulinemia, a surrogate of insulin resistance, may play a role in the pathogenesis of hypertension (HTN), the longitudinal association between fasting insulin level and HTN development is still controversial. We examined the relation between fasting insulin and incidence of HTN in a large prospective cohort. A prospective cohort of 3,413 Americans, aged 18-30 years, without HTN in 1985 (baseline) were enrolled. Six follow-ups were conducted in 1987, 1990, 1992, 1995, 2000, and 2005. Fasting insulin and glucose levels were assessed by a radioimmunoassay and hexokinase method, respectively. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% CIs of incident HTN (defined as the initiation of antihypertensive medication, systolic blood pressure ≥140 mmHg, or diastolic blood pressure ≥90 mmHg). During the 20-year follow-up, 796 incident cases were identified. After adjustment for potential confounders, participants in the highest quartile of insulin levels had a significantly higher incidence of HTN (HR 1.85 [95% CI 1.42-2.40]; P(trend) < 0.001) compared with those in the lowest quartile. The positive association persisted in each sex/ethnicity/weight status subgroup. A similar dose-response relation was observed when insulin-to-glucose ratio or homeostatic model assessment of insulin resistance was used as exposure. Fasting serum insulin levels or hyperinsulinemia in young adulthood was positively associated with incidence of HTN later in life for both men and women, African Americans and Caucasians, and those with normal weight and overweight. Our findings suggested that fasting insulin ascertainment may help clinicians identify those at high risk of HTN.

Lead exposure is known to cause apoptotic neurodegeneration and neurobehavioral abnormalities in developing and adult brain by impairing cognition and memory. Coriandrum sativum is an herb belonging to Umbelliferae and is reported to have a protective effect against lead toxicity. In the present investigation, an attempt has been made to evaluate the protective activity of the hydroalcoholic extract of C. sativum seed against lead-induced oxidative stress. Male Wistar strain rats (100–120 g) were divided into four groups: control group: 1,000 mg/L of sodium acetate; exposed group: 1,000 mg/L lead acetate for 4 weeks; C. sativum treated 1 (CST1) group: 250 mg/kg body weight/day for seven consecutive days after 4 weeks of lead exposure; C. sativum treated 2 (CST2) group: 500 mg/kg body weight/day for seven consecutive days after 4 weeks of lead exposure. After the exposure and treatment periods, rats were sacrificed by cervical dislocation, and the whole brain was immediately isolated and separated into four regions: cerebellum, hippocampus, frontal cortex, and brain stem along with the control group. After sacrifice, blood was immediately collected into heparinized vials and stored at 4 °C. In all the tissues, reactive oxygen species (ROS), lipid peroxidation products (LPP), and total protein carbonyl content (TPCC) were estimated following standard protocols. An indicator enzyme for lead toxicity namely delta-amino levulinic acid dehydratase (δ-ALAD) activity was determined in the blood. A significant (p < 0.05) increase in ROS, LPP, and TPCC levels was observed in exposed rat brain regions, while δ-ALAD showed a decrease indicating lead-induced oxidative stress. Treatment with the hydroalcoholic seed extract of C. sativum resulted in a tissue-specific amelioration of oxidative stress produced by lead.