Urban Thirst and Rural Water: The Saga of the Southern Nevada Groundwater Development Project.

In 1989, the Southern Nevada Water Authority (SNWA) launched the Southern Nevada Groundwater Development Project-a bold plan to construct a series of deep wells in east-central Nevada to pump groundwater and send it to the Las Vegas region through 300 miles of pipeline. Before starting work on the project, SNWA conducted an environmental impact study and secured water rights in the valleys. Applications for additional new water rights were filed with Nevada State Engineer on the basis of uncaptured evapotranspiration. The SNWA spent decades and millions of dollars studying the hydrogeology of the region and developing computer models to demonstrate that the project would not have an unduly negative impact on the ecology or water users in the region. The project was opposed by environmental groups, native American tribes, and existing water rights holders. One of the protestants was the Cleveland Ranch in Spring Valley. Using the SNWA's own groundwater model, the ranch argued that the project would result in substantial harm to the ranch's water rights which included springs, wells, and a stream, and that the project would result in perpetual groundwater mining, which is forbidden by Nevada state policy. The Nevada State Engineer approved the project, but the decision was eventually reversed by Seventh District Court, which sided with the ranch and ruled that the project would never be sustainable and is therefore not compatible with Nevada policy. The project was formally abandoned in 2020.

Association of elevated plasma inflammatory biomarker levels with age-related macular degeneration but not cataract in persons with AIDS.

OBJECTIVE: To evaluate the relationship between plasma biomarkers of systemic inflammation and incident age-related macular degeneration (AMD) in persons with the AIDS. DESIGN: Case-control study. METHODS: Participants with incident intermediate-stage AMD (N = 26) in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) and controls (N = 60) without AMD. Cryopreserved baseline plasma specimens were assayed for biomarkers of inflammation, including high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, interferon-γ inducible protein (IP)-10, soluble CD14 (sCD14), soluble CD163 (sCD163), and intestinal fatty acid-binding protein (I-FABP). RESULTS: After adjustment for age, sex, and race/ethnicity, baseline mean ±â€Šstandard deviation (SD) log10(mg/ml) plasma levels of CRP (0.52 ±â€Š0.60 vs. 0.20 ±â€Š0.43; P = 0.01) and mean ±â€ŠSD log10(pg/ml) plasma levels of sCD14 (6.31 ±â€Š0.11 vs. 6.23 ±â€Š0.14; P = 0.008) were significantly higher among cases (incident AMD) than among controls (no AMD). There was a suggestion that mean ±â€ŠSD baseline log10(pg/ml) plasma IL-6 levels (0.24 ±â€Š0.33 vs. 0.11 ±â€Š0.29; P = 0.10) might be higher among cases than controls. In a separate analysis of 548 participants in LSOCA, elevated baseline levels of plasma inflammatory biomarkers were associated with a greater risk of mortality but not with an increased risk of incident cataract. CONCLUSION: These data suggest that systemic inflammatory biomarkers are associated with incident AMD but not incident cataract in persons with AIDS, and that systemic inflammation may play a role in the pathogenesis of AMD.

Cost of post-deployment screening for mental illness in the UK military: findings from a cluster randomised controlled trial.

BACKGROUND: Little is known about the economic impact of military mental health screening. AIMS: To investigate (a) whether post-deployment screening of military personnel affects use and cost of services and (b) the impact of psychiatric morbidity on costs. METHODS: Participants were recruited from UK Royal Marine and Army platoons and randomised to an intervention group (which received tailored advice predicated upon mental health status) or a control group (which received general advice following assessment of mental health status). The intervention costs were calculated while service use and associated costs were assessed at 12-month follow-up. RESULTS: Data were available for 6323 participants. Mean screening cost was £34. Service costs were slightly higher in the control group compared to the intervention group (£1197 vs. £1147) which was not statistically significant (bootstrapped 95%CI, -£363 to £434. In both groups, screening and control, costs were significantly higher for those who screened positive for mental health problems. CONCLUSIONS: Costs were not affected by screening. In countries that have already implemented post-deployment screening, the political cost of disinvestment needs careful consideration. Those who develop psychiatric morbidity have substantially higher care costs than those who do not.

Combat exposure and co-occurring mental health problems in UK Armed Forces personnel.

BACKGROUND: Mental disorders and alcohol misuse are often comorbid, and this comorbidity is more common in those who develop mental disorders following exposure to traumatic events. AIMS: To investigate the relationship between combat exposure and operational role (support versus combat) with mental disorders and associated comorbidity in a UK military cohort. METHODS: 4896 participants from a UK military cohort reported their operational role and frequency of exposure to combat events during deployment. Outcome measures included self-reported post-traumatic stress disorder, common mental disorder and alcohol misuse. RESULTS: Personnel reporting higher levels of combat exposure were more likely to meet criteria for two or more co-occurring mental disorders (odds ratio [OR] 3.90, 95% confidence interval [CI] 2.73-5.58). While having a combat role increased the risk of developing co-occurring disorders compared to having a support role (OR 1.67, 95% CI 1.26-2.23), this effect diminished following adjustment for variables including combat exposure (OR 0.89, 95% CI 0.62-1.27). CONCLUSIONS: Combat exposure may play a greater role in the development of comorbid mental disorders than operational role, i.e. job title. Clinicians treating military personnel should be alert to the increased risk of comorbid mental disorders and alcohol misuse among those with a history of combat exposure.

The TLR7 agonist vesatolimod induced a modest delay in viral rebound in HIV controllers after cessation of antiretroviral therapy.

Toll-like receptor 7 (TLR7) agonists, in combination with other therapies, can induce sustained control of simian-human immunodeficiency virus (SHIV) or simian immunodeficiency virus (SIV) in nonhuman primates. Here, we report the results of a randomized, double-blind, placebo-controlled phase 1b clinical trial of an oral TLR7 agonist, vesatolimod, in HIV-1-infected controllers on antiretroviral therapy (ART). We randomized participants 2:1 to receive vesatolimod (n = 17) or placebo (n = 8) once every other week for a total of 10 doses while continuing on ART. ART was then interrupted, and the time to viral rebound was analyzed using the Kaplan-Meier method. Vesatolimod was associated with induction of immune cell activation, decreases in intact proviral DNA during ART, and a modest increase in time to rebound after ART was interrupted. The delayed viral rebound was predicted by the lower intact proviral DNA at the end of vesatolimod treatment (13 days after the final dose). Inferred pathway analysis suggested increased dendritic cell and natural killer cell cross-talk and an increase in cytotoxicity potential after vesatolimod dosing. Larger clinical studies will be necessary to assess the efficacy of vesatolimod-based combination therapies aimed at long-term control of HIV infection.

Impaired immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19.

Secondary bacterial infections, including ventilator-associated pneumonia (VAP), lead to worse clinical outcomes and increased mortality following viral respiratory infections including in patients with coronavirus disease 2019 (COVID-19). Using a combination of tracheal aspirate bulk and single-cell RNA sequencing (scRNA-seq) we assessed lower respiratory tract immune responses and microbiome dynamics in 28 COVID-19 patients, 15 of whom developed VAP, and eight critically ill uninfected controls. Two days before VAP onset we observed a transcriptional signature of bacterial infection. Two weeks prior to VAP onset, following intubation, we observed a striking impairment in immune signaling in COVID-19 patients who developed VAP. Longitudinal metatranscriptomic analysis revealed disruption of lung microbiome community composition in patients with VAP, providing a connection between dysregulated immune signaling and outgrowth of opportunistic pathogens. These findings suggest that COVID-19 patients who develop VAP have impaired antibacterial immune defense detectable weeks before secondary infection onset.

Impaired immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19.

Secondary bacterial infections, including ventilator-associated pneumonia (VAP), lead to worse clinical outcomes and increased mortality following viral respiratory infections including in patients with coronavirus disease 2019 (COVID-19). Using a combination of tracheal aspirate bulk and single-cell RNA sequencing we assessed lower respiratory tract immune responses and microbiome dynamics in 23 COVID-19 patients, 10 of whom developed VAP, and eight critically ill uninfected controls. At a median of three days (range: 2-4 days) before VAP onset we observed a transcriptional signature of bacterial infection. At a median of 15 days prior to VAP onset (range: 8-38 days), we observed a striking impairment in immune signaling in COVID-19 patients who developed VAP. Longitudinal metatranscriptomic analysis revealed disruption of lung microbiome community composition in patients with VAP, providing a connection between dysregulated immune signaling and outgrowth of opportunistic pathogens. These findings suggest that COVID-19 patients who develop VAP have impaired antibacterial immune defense detectable weeks before secondary infection onset.

Single-Cell Mapping of Progressive Fetal-to-Adult Transition in Human Naive T Cells.

Whereas the human fetal immune system is poised to generate immune tolerance and suppress inflammation in utero, an adult-like immune system emerges to orchestrate anti-pathogen immune responses in post-natal life. It has been posited that cells of the adult immune system arise as a discrete ontological "layer" of hematopoietic stem-progenitor cells (HSPCs) and their progeny; evidence supporting this model in humans has, however, been inconclusive. Here, we combine bulk and single-cell transcriptional profiling of lymphoid cells, myeloid cells, and HSPCs from fetal, perinatal, and adult developmental stages to demonstrate that the fetal-to-adult transition occurs progressively along a continuum of maturity-with a substantial degree of inter-individual variation at the time of birth-rather than via a transition between discrete waves. These findings have important implications for the design of strategies for prophylaxis against infection in the newborn and for the use of umbilical cord blood (UCB) in the setting of transplantation.

Shared Mechanisms Govern HIV Transcriptional Suppression in Circulating CD103+ and Gut CD4+ T Cells.

Latent HIV infection is the main barrier to cure, and most HIV-infected cells reside in the gut, where distinct but unknown mechanisms may promote viral latency. Transforming growth factor ß (TGF-ß), which induces the expression of CD103 on tissue-resident memory T cells, has been implicated in HIV latency. Using CD103 as a surrogate marker to identify cells that have undergone TGF-ß signaling, we compared the HIV RNA/DNA contents and cellular transcriptomes of CD103+ and CD103- CD4 T cells from the blood and rectum of HIV-negative (HIV-) and antiretroviral therapy (ART)-suppressed HIV-positive (HIV+) individuals. Like gut CD4+ T cells, circulating CD103+ cells harbored more HIV DNA than did CD103- cells but transcribed less HIV RNA per provirus. Circulating CD103+ cells also shared a gene expression profile that is closer to that of gut CD4 T cells than to that of circulating CD103- cells, with significantly lower expression levels of ribosomal proteins and transcriptional and translational pathways associated with HIV expression but higher expression levels of a subset of genes implicated in suppressing HIV transcription. These findings suggest that blood CD103+ CD4 T cells can serve as a model to study the molecular mechanisms of HIV latency in the gut and reveal new cellular factors that may contribute to HIV latency.IMPORTANCE The ability of HIV to establish a reversibly silent, "latent" infection is widely regarded as the main barrier to curing HIV. Most HIV-infected cells reside in tissues such as the gut, but it is unclear what mechanisms maintain HIV latency in the blood or gut. We found that circulating CD103+ CD4+ T cells are enriched for HIV-infected cells in a latent-like state. Using RNA sequencing (RNA-seq), we found that CD103+ T cells share a cellular transcriptome that more closely resembles that of CD4+ T cells from the gut, suggesting that they are homing to or from the gut. We also identified the cellular genes whose expression distinguishes gut CD4+ or circulating CD103+ T cells from circulating CD103- T cells, including some genes that have been implicated in HIV expression. These genes may contribute to latent HIV infection in the gut and may serve as new targets for therapies aimed at curing HIV.

Pre-service Military-related and Mental Disorder Factors Associated with Leaving the UK Armed Forces.

Background: The UK Armed Forces (UKAF) have a substantial manning deficit as more personnel leave than join. This article identified pre-service, military, and mental health factors giving rise to leaving the UKAF and estimated the contributions to leaving of those factors which are potentially amenable to modification. Methods: This study utilized data from a three-phase cohort study (2004-2006, 2007-2009 and 2014-2016), commencing while respondents were serving in the UKAF (n = 10,836; 6,046 (55.8%) had left service). Associations between leaving the services and socio-demographics, military career and experiences, and mental health were determined using Cox regression. Contribution to leaving was based on population attributable fractions (PAF) from Cox regression. Analyses were stratified by rank due to the different career structures of Commissioned Officers and enlisted personnel. Results: Leaving the UKAF was associated with joining when older, being a woman with a child/children, Army service, combat role, lower education level, and poor mental health. Factors contributing a significant proportion of leaving among enlisted personnel were joining over the age of 17, history of externalizing behavior, being female, common mental disorders, and alcohol misuse. Among Commissioned Officers only age at joining and sex contributed significant proportions to leaving. Conclusions: The key factors for leaving are education and higher age at recruitment. These are not amenable to intervention, for policy, equity, and legal reasons. Heavy drinking and common mental disorder symptoms may be more amenable to modification and hence reduce rates of leaving the UKAF. Women are more likely to leave due to childbearing.

Long-Term Correlates of Mild Traumatic Brain Injury on Postconcussion Symptoms After Deployment to Iraq and Afghanistan in the UK Military.

OBJECTIVES: We assessed whether mild traumatic brain injury (mTBI) reported by UK service personnel between 2007 and 2009 was associated with postconcussion symptoms (PCS) 7 to 8 years later. SETTING: United Kingdom. PARTICIPANTS: A total of 4601 service personnel all of whom had deployed to Iraq and/or Afghanistan. DESIGN: Longitudinal study. MAIN OUTCOME MEASURES: Nine PCS reported in a survey carried out between 2014 and 2016. The main independent variable was mTBI reported between 2007 and 2009. RESULTS: A total of 2318 (50.4%) out of 4601 participants completed the follow-up questionnaire. Mild traumatic brain injury was associated with 2 of 9 PCS. Mild traumatic brain injury at baseline was associated with dizziness at follow-up in the fully adjusted model, in comparison with either "other injury" or "no injury" group. Mild traumatic brain injury was associated with loss of concentration in comparison with "no injury" but in comparison with the "other injury" group, it was not in the fully adjusted model. The prevalence of 7 of the 9 PCS increased over time regardless of mTBI status. CONCLUSIONS: Mild traumatic brain injury reported in 2007-2009 was associated with dizziness and possibly with loss of concentration 7 years later but not with most PCS. The prevalence of most PCS increased over time independently of mTBI.

Circulating CD30+CD4+ T Cells Increase Before Human Immunodeficiency Virus Rebound After Analytical Antiretroviral Treatment Interruption.

BACKGROUND: Identification of nonviral markers of human immunodeficiency virus (HIV) infection that increase before viral rebound during analytical treatment interruption (ATI) may affect HIV persistence research. We previously showed that HIV ribonucleic acid (RNA) is enriched in CD30+CD4+ T cells in many individuals. Here, we studied CD30+CD4+ T-cell dynamics before ATI, during ATI (before detectable plasma RNA), and after HIV rebound. METHODS: Peripheral blood mononuclear cells from 23 participants collected longitudinally from 5 Adult AIDS Clinical Trials Group studies incorporating ATI were included in this study. Flow cytometric characterization of expression of CD30 and markers of T-cell activation and exhaustion were performed along with HIV-1 RNA and deoxyribonucleic acid quantification and measurement of soluble plasma CD30 and CD30 ligand. RESULTS: The percentage of CD4+ T cells expressing CD30 significantly increased from pre-ATI to postinterruption time points before detectible viremia (1.65 mean relative increase, P = .005). Seventy-seven percent of participants experienced an increase in CD30+ cells before viral rebound. In contrast, there were no significant differences between pre-ATI and postinterruption pre-rebound time points in percentages of lymphocytes expressing CD69, CD38/HLA-DR, or PD-1 until after HIV recrudescence. CONCLUSIONS: CD30 may be a surrogate marker of early replication or viral transcriptional activity before detection by routine peripheral blood sampling.

Mental Health, Help-Seeking Behaviour and Social Support in the UK Armed Forces by Gender.

Background: Little is known about gender differences in mental health, related help-seeking behavior and social support in UK military personnel. Methods: 1714 UK military serving personnel and ex-service veterans were randomly selected if, in a cohort study, they endorsed experiencing a subjective stress, emotional, alcohol or mental health problem in the previous three years. Following exclusions, the final sample size was 1448 (participation rate 84.5%; women n = 219). Structured telephone interviews assessed anxiety, depression, PTSD symptoms, alcohol use, help-seeking and social support occurring both currently and in the past three years. Outcomes were assessed using weighted unadjusted and adjusted logistic regression analyses. Results: Mental health problems assessed at interview were broadly similar for men and women; for both genders, levels of social support were high. One-fifth of respondents screened positive for probable mental disorder or alcohol misuse; although rates of mental disorder symptoms did not differ by gender, women were significantly less likely than men to report alcohol misuse. Women were significantly more likely to have sought help from formal medical sources but significantly less likely to access informal support such as friends, family or unit welfare sources; reasons for seeking formal medical support were similar for men and women except for problem recognition and acting on advice from others, which were both significantly more common among women. Conclusion: For military personnel with a history of mental ill-health, women should make greater use of informal support networks while for men, engagement with formal medical help sources should be encouraged.

Suicidal Ideation, Suicidal Attempts, and Self-Harm in the UK Armed Forces.

INTRODUCTION: In the UK military, suicide is infrequent and studies of self-harm behavior in this population are rare. OBJECTIVES: To compare lifetime self-harm rates estimated on three occasions between 2004 and 2016 and to explore the associates of lifetime self-harm. METHOD: Three phases of a UK AF cohort study (n = 10,272, 9,990, and 8,581, respectively) provided data. Telephone interviews assessed associates of self-harm among cohort members who reported subjective mental health problems in the past 3 years (n = 1,448). Validated measures of mental health and related stigmatization, social support, and help-seeking were obtained. RESULTS: Lifetime self-harm increased significantly (p < .001) from 1.8% among serving personnel and 3.8% among veterans in 2004/06 to 1.9% and 4.5% in 2007/09 and to 4.2% and 6.6% in 2014/16 in the two groups, respectively. Veterans were consistently significantly more likely to report lifetime self-harm than serving personnel. Significant determinants of lifetime self-harm included current mental disorder symptoms, stigmatization, poor social support, suicidal ideation, and seeking help from formal medical sources. CONCLUSION: Self-harm has increased over time in the UK serving and veteran community. Suicide prevention should focus on ameliorating mental disorder by encouraging engagement with health care, reducing negative views of mental illness, and fostering social support.

A Qualitative Evaluation of the Acceptability of a Tailored Smartphone Alcohol Intervention for a Military Population: Information About Drinking for Ex-Serving Personnel (InDEx) App.

BACKGROUND: Alcohol consumption in the UK Armed Forces is higher than in the general population, and this pattern continues after leaving the service. Smartphone apps may be useful to increase ex-serving personnel's awareness of their alcohol consumption, support self-monitoring, and prompt a change in behavior. OBJECTIVE: The study aimed to explore the acceptability of Information about Drinking in Ex-serving personnel (InDEx), a tailored smartphone app, combined with personalized short message service (SMS) text messaging designed to target ex-serving personnel who meet the criteria for hazardous alcohol use. METHODS: The InDEx intervention included 4 key modules: (1) assessment and normative feedback, (2) self-monitoring and feedback, (3) goal setting and review, and (4) personalized SMS text messaging. A semistructured telephone interview study was conducted with ex-serving personnel after using the app for a 28-day period. Interviews were used to explore the acceptability of app modules and its functionality and the perceived changes in participant's drinking. Interview transcripts were analyzed using inductive thematic analysis. RESULTS: Overall, 94% (29/31) participants who used InDEx agreed to take part in a telephone interview. Overall, 4 themes were identified: Credibility, Meeting their needs, Simplicity, and Helpful for ex-serving personnel. The importance of credibility, functionality, and meeting the individual needs of ex-serving personnel was emphasized. Acceptability and engagement with specific modules of the app and text messages were influenced by the following: (1) if they felt it provided credible information, (2) whether the content was appropriately personalized to them, (3) the ease of use, and (4) beliefs about their own drinking behaviors. Participants recommended that the app would be most suitable for personnel about to leave the Armed Forces. CONCLUSIONS: InDEx was an acceptable smartphone app for ex-serving personnel for monitoring alcohol consumption and in providing meaningful feedback to the individual. Pages that met the participant's interests and provided real time personalized, credible feedback on their drinking and text messages tailored to participant's interactions with the app were particularly favored.

Association of Systemic Inflammation With Retinal Vascular Caliber in Patients With AIDS.

Purpose: To evaluate relationships among retinal vascular caliber and biomarkers of systemic inflammation in patients with AIDS. Methods: A total of 454 participants with AIDS had retinal vascular caliber (central retinal artery equivalent and central retinal vein equivalent) determined from enrollment retinal photographs by reading center graders masked to clinical and biomarker information. Cryopreserved plasma specimens were assayed for inflammatory biomarkers, including C-reactive protein (CRP), IL-6, interferon-γ inducible protein (IP)-10, kynurenine/tryptophan (KT) ratio, and intestinal fatty acid binding protein (I-FABP). Results: In the simple linear regression of retinal vascular caliber on plasma biomarkers, elevated CRP, IL-6, and IP-10 were associated with retinal venular dilation, and elevated KT ratio with retinal arteriolar narrowing. In the multiple linear regression, including baseline characteristics and plasma biomarkers, AMD was associated with dilation of retinal arterioles (mean difference: 9.1 µm; 95% confidence interval [CI] 5.2, 12.9; P < 0.001) and venules (mean difference, 10.9 µm; 95% CI, 5.3, 16.6; P < 0.001), as was black race (P < 0.001). Hyperlipidemia was associated with retinal venular narrowing (mean difference, -7.5 µm; 95% CI, -13.7, -1.2; P = 0.02); cardiovascular disease with arteriolar narrowing (mean difference, -5.2 µm; 95% CI, -10.3, -0.1; P = 0.05); age with arteriolar narrowing (slope, -0.26 µm/year; 95% CI, -0.46, -0.06; P = 0.009); and IL-6 with venular dilation (slope, 5.3 µm/standard deviation log10[plasma IL-6 concentration]; 95% CI, 2.7, 8.0; P < 0.001). Conclusions: These data suggest that retinal vascular caliber is associated with age, race, AMD, hyperlipidemia, cardiovascular disease, and selected biomarkers of systemic inflammation.

Do serving and ex-serving personnel of the UK armed forces seek help for perceived stress, emotional or mental health problems?

Background: UK armed forces personnel are at risk of occupational psychological injury; they are often reluctant to seek help for such problems. Objective: We aimed to examine and describe sources of support, prevalence and associates of help-seeking among UK serving and ex-serving personnel. Method: A total of 1450 participants who self-reported a stress, emotional or mental health problem in the past 3 years were sampled from a health and wellbeing study and subsequently completed a telephone interview comprising measures of mental disorder symptoms, alcohol misuse and help-seeking behaviour. Results: Seven per cent of participants had not sought any help, 55% had accessed medical sources of support (general practitioner or mental health specialist), 46% had received formal non-medical (welfare) support and 86% had used informal support. Gender, age, perceived health, functional impairment, social support, deployment, alcohol and comorbidity impacted upon the choice of help source. Conclusions: This study found that the majority of those with perceived mental health problems sought some form of help, with over half using formal medical sources of support.

Antecedentes: El personal de las Fuerzas Armadas del Reino Unido está en riesgo de sufrir alteraciones psicológicas ocupacionales; a menudo son reacios a buscar ayuda para tales problemas. Objetivo: El objetivo fue examinar y describir las fuentes de apoyo, la prevalencia y los asociados de búsqueda de ayuda entre el personal de servicio y ex personal de servicio del Reino Unido. Método: En un estudio de salud y bienestar se tomaron muestras de 1.450 participantes que informaron sobre un problema de estrés, de salud mental o emocional en los últimos tres años y posteriormente completaron una entrevista telefónica que incluía medidas de síntomas de trastornos mentales, abuso de alcohol y conductas de búsqueda de ayuda. Resultados: El 7% de los participantes no había buscado ninguna ayuda. El 55% accedió a fuentes médicas de apoyo (médico general o especialista en salud mental), el 46% recibió apoyo formal no médico (servicio social) y el 86% utilizó apoyo informal. El sexo, la edad, la salud percibida, el deterioro funcional, el apoyo social, el despliegue, el alcohol y la comorbilidad se ven afectados por la elección de la fuente de ayuda. Conclusiones: Este estudio encontró que la mayoría de las personas con problemas de salud mental percibidos buscaron algún tipo de ayuda, y más de la mitad usaron fuentes médicas formales de apoyo.

Association of Age-related Macular Degeneration With Mortality in Patients With Acquired Immunodeficiency Syndrome; Role of Systemic Inflammation.

PURPOSE: To evaluate the relationships among age-related macular degeneration (AMD), mortality, and biomarkers of systemic inflammation in patients with acquired immunodeficiency syndrome (AIDS). DESIGN: Case-control study. METHODS: In participants with intermediate-stage AMD at enrollment in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) and 2:1 controls matched for age and sex, cryopreserved baseline plasma specimens were assayed for biomarkers of inflammation, including high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, interferon-γ inducible protein (IP)-10, soluble CD14 (sCD14), soluble CD163 (sCD163), kynurenine/tryptophan (KT) ratio, and intestinal fatty acid binding protein (I-FABP). Main outcome measure was mortality. RESULTS: The study included 189 patients with AMD and 385 controls. In the unadjusted analysis, AMD was associated with mortality (hazard ratio [HR] 1.48; 95% confidence interval [CI] 1.02, 2.15; P = .04). In an adjusted analysis, CRP (HR 1.36; 95% CI 1.08, 1.71; P = .009), IL-6 (HR 1.45; 95% CI 1.11, 1.90; P = .006), and IP-10 (HR 1.41; 95% CI 1.08, 1.84; P = .01) were associated with mortality. In a Cox regression analysis adjusted for human immunodeficiency virus load, blood CD4+ T cell level, CRP, IL-6, and IP-10, the association of AMD with mortality was attenuated (HR 1.08; 95% CI 0.73, 1.59; P = .70), primarily by the addition of the inflammatory biomarkers. CONCLUSIONS: These data suggest that the increased mortality observed in patients with AIDS with AMD is, at least in part, a result of systemic inflammation.

Resilience-based intervention for UK military recruits: a randomised controlled trial.

OBJECTIVES: We evaluated a military resilience intervention which aimed to help UK military recruits to manage their personal health and well-being more effectively. METHODS: Trainers within six pre-existing training teams were randomly allocated by team to deliver a resilience-based intervention (SPEAR) or usual training (control) during recruit training. 23 trainers delivered SPEAR; 18 delivered the control training. 707 recruits participated (n=358 SPEAR and n=349 controls). Outcome measures were obtained before and after recruit training and 3 months later. Measures of post-traumatic stress disorder (PTSD), common mental disorder (CMD) symptoms, alcohol use, homesickness and mental health stigmatisation were obtained at baseline. Repeat baseline scales plus measures of help-seeking, cohesion, leadership and training impact were obtained at the two follow-up points. RESULTS: Response rates were 91.7% (baseline), 98.1% (post) and 73.6% (follow-up). Following adjustment for potential confounders, levels of PTSD, CMD symptoms, alcohol misuse, help-seeking and homesickness were not significantly different between groups at any measurement point. Stigmatisation was significantly lower among SPEAR recipients at baseline but was not significantly different at the two follow-up points. Following adjustment for mental health confounders, there were no significant between-group differences in perceptions of leadership and cohesion and in ratings of six training outcomes at the two follow-up points. CONCLUSIONS: We found no evidence that resilience-based training had any specific benefit to the health and well-being of UK military recruits.