Resonant X-ray photoelectron spectroscopy: identification of atomic contributions to valence states.

Valence electronic structure is crucial for understanding and predicting reactivity. Valence non-resonant X-ray photoelectron spectroscopy (NRXPS) provides a direct method for probing the overall valence electronic structure. However, it is often difficult to separate the varying contributions to NRXPS; for example, contributions of solutes in solvents or functional groups in complex molecules. In this work we show that valence resonant X-ray photoelectron spectroscopy (RXPS) is a vital tool for obtaining atomic contributions to valence states. We combine RXPS with NRXPS and density functional theory calculations to demonstrate the validity of using RXPS to identify atomic contributions for a range of solutes (both neutral and ionic) and solvents (both molecular solvents and ionic liquids). Furthermore, the one-electron picture of RXPS holds for all of the closed shell molecules/ions studied, although the situation for an open-shell metal complex is more complicated. The factors needed to obtain a strong RXPS signal are investigated in order to predict the types of systems RXPS will work best for; a balance of element electronegativity and bonding type is found to be important. Additionally, the dependence of RXPS spectra on both varying solvation environment and varying local-covalent bonding is probed. We find that RXPS is a promising fingerprint method for identifying species in solution, due to the spectral shape having a strong dependence on local-covalency but a weak dependence on the solvation environment.

Anemia risk factors among people living with HIV across the United States in the current treatment era: a clinical cohort study.

BACKGROUND: Anemia is common among people living with HIV infection (PLWH) and is associated with adverse health outcomes. Information on risk factors for anemia incidence in the current antiretroviral therapy (ART) era is lacking. METHODS: Within a prospective clinical cohort of adult PLWH receiving care at eight sites across the United States between 1/2010-3/2018, Cox proportional hazards regression analyses were conducted among a) PLWH free of anemia at baseline and b) PLWH free of severe anemia at baseline to determine associations between time-updated patient characteristics and development of anemia (hemoglobin < 10 g/dL), or severe anemia (hemoglobin < 7.5 g/dL). Linear mixed effects models were used to examine relationships between patient characteristics and hemoglobin levels during follow-up. Hemoglobin levels were ascertained using laboratory data from routine clinical care. Potential risk factors included: age, sex, race/ethnicity, body mass index, smoking status, hazardous alcohol use, illicit drug use, hepatitis C virus (HCV) coinfection, estimated glomerular filtration rate (eGFR), CD4 cell count, viral load, ART use and time in care at CNICS site. RESULTS: This retrospective cohort study included 15,126 PLWH. During a median follow-up of 6.6 (interquartile range [IQR] 4.3-7.6) years, 1086 participants developed anemia and 465 participants developed severe anemia. Factors that were associated with incident anemia included: older age, female sex, black race, HCV coinfection, lower CD4 cell counts, VL ≥400 copies/ml and lower eGFR. CONCLUSION: Because anemia is a treatable condition associated with increased morbidity and mortality among PLWH, hemoglobin levels should be monitored routinely, especially among PLWH who have one or more risk factors for anemia.

Imputation of Assay Bioactivity Data Using Deep Learning.

We describe a novel deep learning neural network method and its application to impute assay pIC50 values. Unlike conventional machine learning approaches, this method is trained on sparse bioactivity data as input, typical of that found in public and commercial databases, enabling it to learn directly from correlations between activities measured in different assays. In two case studies on public domain data sets we show that the neural network method outperforms traditional quantitative structure-activity relationship (QSAR) models and other leading approaches. Furthermore, by focusing on only the most confident predictions the accuracy is increased to R2 > 0.9 using our method, as compared to R2 = 0.44 when reporting all predictions.

Inequalities in health? An update on the effect of social deprivation for patients with breast cancer in South East Wales.

BACKGROUND: Breast cancer, historically a disease of more affluent women, has increased in incidence for women from areas of greater social deprivation, yet prognosis is worse for these women. This study identifies differences in presentation, treatment and prognostic factors between the socioeconomic groups. METHODS: Patient data obtained from the prospectively maintained Welsh national Cancer Network Information System Cymru, for an 11-year period, were categorised according to Welsh Index of Multiple Deprivation quintiles. Quintiles were compared for differences in variables relating to patient characteristics, detection of cancer, tumour biology and treatment. RESULTS: 1570 patients were included. Analysis showed that in the more socially deprived quintiles, there are proportionally fewer women being diagnosed through the NHS breast cancer screening programme and as a consequence greater numbers of women from poorer areas being diagnosed outwith the screening age parameters. Screen detection is strongly associated with better prognosis in terms of Nottingham Prognostic Index. Similarly, increasing levels of social deprivation are associated with higher incidence of oestrogen receptor negative and triple negative tumours, both features associated with a shorter disease free and overall survival. Other variables of tumour biology, rates and type of surgical and adjuvant treatment were similar across social deprivation quintiles. CONCLUSION: There is a trend of reduced early detection of breast cancer in South East Wales in those patients living in areas of higher social deprivation. Given that there is equity in access to treatment within NHS, which is free for patients at the point of care, further study is warranted to address this existing disparity. Population cancer surveillance will need to inform both public health and NHS service responses, to continue to achieve improvements. Health trends may yet alter depending on current and future shifts in governmental health policy.

Who's challenging who training for staff empathy towards adults with challenging behaviour: cluster randomised controlled trial.

BACKGROUND: One in five adults with intellectual disabilities (ID) known to services display challenging behaviours (CBs), and these individuals are at risk for restrictive practices and poor care. Staff attitudes may contribute to the development and/or maintenance of CBs. We investigated the effectiveness of co-produced Who's Challenging Who? training delivered by people with ID to staff. METHOD: This study involved a cluster randomised controlled trial (RCT) of Who's Challenging Who? training with follow-up at six and 20 weeks post-randomisation. PARTICIPANTS: two staff from each of 118 residential care settings for adults with ID at least one of whom displayed aggressive CB. PRIMARY OUTCOME: Self-reported Staff Empathy for people with Challenging Behaviour Questionnaire. ANALYSIS: intention to treat of all randomised settings. ISCRTN registration: ISRCTN53763600. RESULTS: 118 residential settings (including 236 staff) were randomised to either receive training (59 settings) or to receive training after a delay (59 settings). The primary analysis included data from 121 staff in 76 settings (51% of staff, 64% of settings). The adjusted mean difference on the transformed (cubed) Staff Empathy for people with Challenging Behaviour Questionnaire score at the primary end point was 1073.2 (95% CI: -938.1 to 3084.5, P = 0.296) in favour of the intervention group (effect size Cohen's d = .19). CONCLUSIONS: This is the first large-scale RCT of a co-produced training course delivered by people with ID. Findings indicated a small positive (but statistically non-significant) effect on increased staff empathy at 20 weeks, and small to moderate effects for staff reported secondary outcomes in favour of the intervention group.

Simulated Soil Organic Carbon Response to Tillage, Yield, and Climate Change in the Southeastern Coastal Plains.

Intensive tillage, low-residue crops, and a warm, humid climate have contributed to soil organic carbon (SOC) loss in the southeastern Coastal Plains region. Conservation (CnT) tillage and winter cover cropping are current management practices to rebuild SOC; however, there is sparse long-term field data showing how these management practices perform under variable climate conditions. The objectives of this study were to use CQESTR, a process-based C model, to simulate SOC in the top 15 cm of a loamy sand soil (fine-loamy, kaolinitic, thermic Typic Kandiudult) under conventional (CvT) or CnT tillage to elucidate the impact of projected climate change and crop yields on SOC relative to management and recommend the best agriculture management to increase SOC. Conservation tillage was predicted to increase SOC by 0.10 to 0.64 Mg C ha for six of eight crop rotations compared with CvT by 2033. The addition of a winter crop [rye ( L.) or winter wheat ( L.)] to a corn ( L.)-cotton ( L.) or corn-soybean [ (L.) Merr.] rotation increased SOC by 1.47 to 2.55 Mg C ha. A continued increase in crop yields following historical trends could increase SOC by 0.28 Mg C ha, whereas climate change is unlikely to have a significant impact on SOC except in the corn-cotton or corn-soybean rotations where SOC decreased up to 0.15 Mg C ha by 2033. The adoption of CnT and cover crop management with high-residue-producing corn will likely increase SOC accretion in loamy sand soils. Simulation results indicate that soil C saturation may be reached in high-residue rotations, and increasing SOC deeper in the soil profile will be required for long-term SOC accretion beyond 2030.

The outcome of patients in traumatic cardiac arrest presenting to deployed military medical treatment facilities: data from the UK Joint Theatre Trauma Registry.

BACKGROUND: The UK military was continuously engaged in armed conflict in Iraq and Afghanistan between 2003 and 2014, resulting in 629 UK fatalities. Traumatic cardiac arrest (TCA) is a precursor to traumatic death, but data on military outcomes are limited. In order to better inform military treatment protocols, the aim of this study was to define the epidemiology of TCA in the military population with a particular focus on survival rates and injury patterns. METHODS: A retrospective database analysis of the UK Joint Theatre Trauma Registry was undertaken. Patients who were transported to a UK deployed hospital between 2003 and 2014 and suffered TCA were included. Those patients injured by asphyxiation, electrocution, burns without other significant trauma and drowning were excluded. Data included mechanism of injury, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS) for each body region and survival to deployed (Role 3) field hospital discharge. RESULTS: 424 TCA patients were identified during the study period; median age was 23 years, with a median ISS of 45. The most common mechanism of injury was explosive (55.7%), followed by gunshot wound (38.9%), road traffic collision (3.5%), crush (1.7%) and fall (0.2%). 45 patients (10.6% (95% CI 8.0% to 13.9%)) survived to deployed (Role 3) hospital discharge. The most prevalent body region with a severe to maximum AIS injury was the head, followed by the lower limbs, thorax and abdomen. Haemorrhage secondary to abdominal and lower limb injury was associated with survival; traumatic brain injury was associated with death. CONCLUSIONS: This study has shown that short-term survival from TCA in a military population is 10.6%. With appropriate and aggressive early management, although unlikely, survival is still potentially possible in military patients who suffer traumatic cardiac arrest.

Pathogenicity, tissue distribution, shedding and environmental detection of two strains of IBDV following infection of chickens at 0 and 14 days of age.

Infectious bursal disease virus (IBDV) is endemic to most poultry-producing countries worldwide. Immunosuppressive classical and variant IBDV strains endemic to Australia are genetically distinct from other international strains. We report the results of infection experiments with Australian classical strain 06/95 and variant strain 02/95 in SPF chickens. We tested the effects of strain and age of infection on bursal atrophy, viral RNA (vRNA) load in bursa of Fabricius (bursa), spleen, thymus, caecal tonsils, faeces, litter and exhaust dust as determined by real-time reverse transcriptase polymerase chain reaction. The two IBDV strains did not differ in the degree of bursal atrophy induced, lymphoid organ distribution and faecal shedding but variant strain 02/95 induced a greater antibody response to the infection than classical strain 06/95 which was associated with a more rapid decline in IBDV vRNA genome copy number (VCN) in lymphoid organs and faeces. Infection at 14 days of age induced greater bursal atrophy and higher vRNA copy number in lymphoid tissues than infection on the day of hatching, indicating true age susceptibility independent of maternal antibody (Mab) status. The direction of the association between rankings for IBDV vRNA load in bursa and relative bursal weight changed from positive at 3 and 6 days post-infection to negative at 28 days post-infection. Intra-tracheal administration of dust collected from chickens infected with IBDV resulted in successful transmission of IBDV. IBDV vRNA was detected successfully at high levels in the environmental litter and dust samples.

Solubility of alkali metal halides in the ionic liquid [C4C1im][OTf].

The solubilities of the metal halides LiF, LiCl, LiBr, LiI, NaF, NaCl, NaBr, NaI, KF, KCl, KBr, KI, RbCl, CsCl, CsI, were measured at temperatures ranging from 298.15 to 378.15 K in the ionic liquid 1-butyl-3-methylimidazolium trifluoromethanesulfonate ([C4C1im][OTf]). Li(+), Na(+) and K(+) salts with anions matching the ionic liquid have also been investigated to determine how well these cations dissolve in [C4C1im][OTf]. This study compares the influence of metal cation and halide anion on the solubility of salts within this ionic liquid. The highest solubility found was for iodide salts, and the lowest solubility for the three fluoride salts. There is no outstanding difference in the solubility of salts with matching anions in comparison to halide salts. The experimental data were correlated employing several phase equilibria models, including ideal mixtures, van't Hoff, the λh (Buchowski) equation, the modified Apelblat equation, and the non-random two-liquid model (NRTL). It was found that the van't Hoff model gave the best correlation results. On the basis of the experimental data the thermodynamic dissolution parameters (ΔH, ΔS, and ΔG) were determined for the studied systems together with computed gas phase metathesis parameters. Dissolution depends on the energy difference between enthalpies of fusion and dissolution of the solute salt. This demonstrates that overcoming the lattice energy of the solid matrix is the key to the solubility of inorganic salts in ionic liquids.

Force protection in contingency operations: an evaluation of temperature monitoring in Sierra Leone.

OBJECTIVES: The deployment of the UK-led Joint Inter-Agency Taskforce to Sierra Leone in September 2014 brought the era of contingency operations into focus. Daily health screening of such deployed personnel forms a key element of medical force protection. We have performed a service evaluation of an existing screening programme and detail the comparison of the two thermometers used in this role. METHODS: Data from the existing screening programme were used to inform a sample size required to enable statistically and clinically significant differences to be detected between the two interchangeably used thermometer systems in use. A prospective service evaluation on these devices was then carried out over a 10-day period and the data analysed by parametric tools. 10 personnel had their temperature recorded by both devices at the same time by a single operator every day. RESULTS: For the screened population, a mean temperature of 36.55°C and SD of 0.32°C was revealed. Powered to 80% with a two-tailed α of 0.05, the evaluation of the two thermometers revealed no significant difference between recordings taken with either device (p=0.115). The low SD meant that a pyrexial patient (>37.5°C) would require a recording over 3 SD from the population mean. DISCUSSION: Evaluations of medical force protection will carry increasing consequence as the UK deploy on short notice operations to regions of considerable endemic threat. Presence of pyrexia is a key early indicator of illness affecting deployed personnel, and two different thermometer types are provided for this function. We have shown for the first time with statistical and clinical significance that the two thermometers used in contingency force protection are interchangeable. The narrow variance is reassuring and confirms that the chosen trigger (>37.5°C) would warrant further investigation in the pyrexial patient.

Education and Ebola: initiating the cascade of emergency healthcare training.

In response to the 2014 Ebola virus outbreak in West Africa, the UK deployed a Joint Inter-Agency Task Force to Sierra Leone. As well as constructing Ebola treatment units, the force supported a rapidly upscaled mass programme of training for host nation healthcare workers in basic knowledge of Ebola and personal protective equipment. A bespoke training course was developed in collaboration with the WHO and other partners over a period of 2 weeks, taught to 119 trainers the following week, and then cascaded to over 4000 Ebola workers over the following month. This article describes curriculum design, content delivery and assessment of this unique Training The Trainers course delivered in austere circumstances. Key learning points are highlighted and supplementary material is provided to inform future deployed clinical education initiatives.

Bending the curve: force health protection during the insertion phase of the Ebola outbreak response.

After >10 years of enduring operations in Iraq and Afghanistan, Defence Strategic Direction is returning to a contingency posture. As the first post-Afghanistan operation, in September 2014, a UK Joint Inter-Agency Task Force deployed to Sierra Leone in response to the Ebola virus disease (EVD) epidemic in West Africa. The aims were expanding treatment capacity, assisting with training and supporting host nation resilience. The insertion phase of this deployment created a unique set of challenges for force health protection. In addition to the considerable risk of tropical disease and trauma, deployed personnel faced the risks of working in an EVD epidemic. This report explores how deployed medical assets overcame the difficulties of mounting a short-notice contingent operation in a region of the world with inherent major climatic and health challenges.

Three-year experience with access to nationally funded growth hormone (GH) replacement for GH-deficient adults.

OBJECTIVE: Treatment of growth hormone (GH)-deficient adults with GH has been shown to improve a range of metabolic abnormalities and enhance quality of life. However, the results of access to nationally funded treatment have not been reported. DESIGN: Retrospective case series auditing nationally funded treatment of defined GH-deficient adults in New Zealand, with carefully designed entry and exit criteria overseen by a panel of endocrinologists. PATIENTS: Applications for 201 patients were assessed and 191 approved for funded treatment over the initial 3 years since inception. The majority had GH deficiency following treatment of pituitary adenomas or tumours adjacent to the pituitary. RESULTS: After an initial 9-month treatment period using serum IGF-I measurements to adjust GH dosing, all patients reported a significant improvement in quality of life (QoL) score on the QoL-AGHDA(®) instrument (baseline (95%CI) 19 (18-21), 9 months 6 (5-7.5)), and mean serum IGF-I SD scores rose from -3 to zero. Mean waist circumference decreased significantly by 2.8 ± 0.6 cm. The mean maintenance GH dose after 9 months of treatment was 0.39 mg/day. After 3 years, 17% of patients had stopped treatment, and all of the remaining patients maintained the improvements seen at 9 months of treatment. CONCLUSION: Carefully designed access to nationally funded GH replacement in GH-deficient adults was associated with a significant improvement in quality of life over a 3-year period with mean daily GH doses lower than in the majority of previously reported studies.

Soil physicochemical conditions, denitrification rates, and abundance in north Carolina coastal plain restored wetlands.

Over the last century, North Carolina has seen a severe reduction in the percentage of wetlands and a rise in negative environmental impacts related to this loss. To counter these effects, efforts have been enacted to mitigate wetland loss and create new wetland areas. The objective of this study was to assess the impact of hydrological restoration at several sites in the North Carolina coastal plain. Nine sites were selected for study. Hydrologically restored wetlands were compared with natural wetlands and prior converted (PC) croplands (i.e., historic wetlands under agricultural production). Each site was analyzed along a relative wetness gradient, and physicochemical properties, denitrification enzyme activity, and NO reductase gene () abundances using real-time PCR were measured. Physicochemically, restoration resulted in significantly increased levels of total C as compared with PC cropland sites. Restored wetland sites also saw pH, soil moisture, P, and NO+NO approximate levels similar to those of natural wetlands. Denitrification enzyme activity rates varied based on relative wetness within individual sites, generally increasing with increasing soil moisture. However, denitrification tended to be lower in restored wetland sites relative to natural wetlands. Gene abundances of saw statistically significant decreases in restored wetland soils. In conclusion, although analysis of restored wetlands reveals clear changes in several physicochemical characteristics and significant decreases in gene abundances, restoration efforts appear to have not significantly affected the denitrification component of the N cycle.

Challenging the dogma of traumatic cardiac arrest management: a military perspective.

Attempts to resuscitate patients in traumatic cardiac arrest (TCA) have, in the past, been viewed as futile. However, reported outcomes from TCA in the past five years, particularly from military series, are improving. The pathophysiology of TCA is different to medical causes of cardiac arrest, and therefore, treatment priorities may also need to be different. This article reviews recent literature describing the pathophysiology of TCA and describes how the military has challenged the assumption that outcome is universally poor in these patients.

Lessons learned from the design and implementation of myocardial infarction adjudication tailored for HIV clinical cohorts.

We developed, implemented, and evaluated a myocardial infarction (MI) adjudication protocol for cohort research of human immunodeficiency virus. Potential events were identified through the centralized Centers for AIDS Research Network of Integrated Clinical Systems data repository using MI diagnoses and/or cardiac enzyme laboratory results (1995-2012). Sites assembled de-identified packets, including physician notes and results from electrocardiograms, procedures, and laboratory tests. Information pertaining to the specific antiretroviral medications used was redacted for blinded review. Two experts reviewed each packet, and a third review was conducted if discrepancies occurred. Reviewers categorized probable/definite MIs as primary or secondary and identified secondary causes of MIs. The positive predictive value and sensitivity for each identification/ascertainment method were calculated. Of the 1,119 potential events that were adjudicated, 294 (26%) were definite/probable MIs. Almost as many secondary (48%) as primary (52%) MIs occurred, often as the result of sepsis or cocaine use. Of the patients with adjudicated definite/probable MIs, 78% had elevated troponin concentrations (positive predictive value = 57%, 95% confidence interval: 52, 62); however, only 44% had clinical diagnoses of MI (positive predictive value = 45%, 95% confidence interval: 39, 51). We found that central adjudication is crucial and that clinical diagnoses alone are insufficient for ascertainment of MI. Over half of the events ultimately determined to be MIs were not identified by clinical diagnoses. Adjudication protocols used in traditional cardiovascular disease cohorts facilitate cross-cohort comparisons but do not address issues such as identifying secondary MIs that may be common in persons with human immunodeficiency virus.

Application of synthetic photostable retinoids induces novel limb and facial phenotypes during chick embryogenesis in vivo.

We have recently developed a range of synthetic retinoid analogues which include the compounds EC23 and EC19. They are stable on exposure to light and are predicted to be resistant to the normal metabolic processes involved in the inactivation of retinoids in vivo. Based on the position of the terminal carboxylic acid groups in the compounds we suggest that EC23 is a structural analogue of all-trans retinoic acid (ATRA), and EC19 is an analogue of 13-cis retinoic acid. Their effects on the differentiation of pluripotent stem cells has been previously described in vitro and are consistent with this hypothesis. We present herein the first description of the effects of these molecules in vivo. Retinoids were applied to the anterior limb buds of chicken embryos in ovo via ion-exchange beads. We found that retinoid EC23 produces effects on the wing digits similar to ATRA, but does so at two orders of magnitude lower concentration. When larger quantities of EC23 are applied, a novel phenotype is obtained involving production of multiple digit 1s on the anterior limb. This corresponds to differential effects of ATRA and EC23 on sonic hedgehog (shh) expression in the developing limb bud. With EC23 application we also find digit 1 phenotypes similar to thumb duplications described in the clinical literature. EC23 and ATRA are shown to have effects on the entire proximal-distal axis of the limb, including hitherto undescribed effects on the scapula. This includes suppression of expression of the scapula marker Pax1. EC23 also produces effects similar to those of ATRA on the developing face, producing reductions of the upper beak at concentrations two orders of magnitude lower than ATRA. In contrast, EC19, which is structurally very similar to EC23, has novel, less severe effects on the face and rarely alters limb development. EC19 and ATRA are effective at similar concentrations. These results further demonstrate the ability of retinoids to influence embryonic development. Moreover, EC23 represents a useful new tool to investigate developmental processes and probe the mechanisms underlying congenital abnormalities in vertebrates including man.

Who's challenging who? Changing attitudes towards those whose behaviour challenges.

BACKGROUND: Although staff attitudes towards individuals with intellectual disability (ID) whose behaviour challenges may be an important part of a positive support culture, very little research has focused on the development of training specifically designed to change staff attitudes. Positive contact is hypothesised to be an effective way to change attitudes towards stigmatised groups. METHODS: We designed and developed a half day training package about the experiences of individuals whose behaviour challenges - Who's Challenging Who (WCW). The WCW package was delivered according to a manual by a trainer with ID and a professional without disability. Seventy-six staff from a variety of organisations participated in one of 10 WCW training sessions and provided data on their attitudes and empathy towards individuals whose behaviour challenges prior to the WCW training and immediately at the end of training. Staff also completed a post-training evaluation questionnaire. RESULTS: A training package was successfully developed collaboratively with individuals whose behaviour challenges, and received very positive evaluations from staff participants. Short-term positive change was shown for empowerment and similarity attitudes, and staff empathy and self-efficacy. These outcomes were associated with small to moderate effect sizes. CONCLUSIONS: Meaningful short-term positive staff attitude changes were found and the WCW training model was shown to be feasible. More robust research designs are needed for future evaluation. In addition, the function of an attitude change intervention such as WCW within organisations' training strategies requires further development.

Effect of statin therapy in reducing the risk of serious non-AIDS-defining events and nonaccidental death.

BACKGROUND: Excessive inflammation persists despite antiretroviral treatment. Statins decrease cardiovascular (CV) disease risk by reducing low-density lipoprotein cholesterol and inflammation. We performed an exploratory analysis to evaluate whether statin therapy decreased risk of non-AIDS-defining events and nonaccidental death. METHODS: A total of 3601 subjects not on a statin from the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials cohort were included. Outcome was time to first clinical event (CV event, renal or hepatic disease, incident diabetes, thrombotic/embolic event, nontraumatic fracture, non-AIDS-defining malignancy, serious bacterial infection, or nonaccidental death); event categories were also analyzed separately. Inverse probability of treatment and censoring weighted Cox proportional hazard models were used to assess the causal statin effect. Differential statin effects by baseline covariates were evaluated. RESULTS: Over 15 135 person-years (PY) of follow-up, 484 subjects initiated statins; 616 experienced an event (crude event rate, 4.4/100 PY on a statin and 4.1/100 PY not on a statin); the unadjusted hazard ratio (HR) was 1.17 (95% confidence interval [CI], .91-1.50). In a final weighted model, the adjusted HR (AHR) was 0.81 (95% CI, .53- 1.24). Results for other clinical events were similar, except for malignancies (AHR, 0.43 [95% CI, .19-.94]) and bacterial infections (AHR, 1.30 [95% CI, .64-2.65]). No differential statin effects by baseline covariates were detected. CONCLUSIONS: Although statin therapy was not associated with a reduction in time to all non-AIDS-defining event or nonaccidental death, it was associated with a statistically significant 57% reduction in non-AIDS-defining malignancies. Confirmatory studies are needed to evaluate statin-associated reduction in risk of cancer and non-AIDS-associated morbidities.

Effects of exercise and environmental complexity on deficits in trace and contextual fear conditioning produced by neonatal alcohol exposure in rats.

In rodents, voluntary exercise and environmental complexity increases hippocampal neurogenesis and reverses spatial learning and long-term potentiation deficits in animals prenatally exposed to alcohol. The present experiment extended these findings to neonatal alcohol exposure and to delay, trace, and contextual fear conditioning. Rats were administered either 5.25 g/kg/day alcohol via gastric intubation or received sham-intubations (SI) between Postnatal Day (PD) 4 and 9 followed by either free access to a running wheel on PD 30-41 and housing in a complex environment on PD 42-72 (wheel-running plus environmental complexity; WREC) or conventional social housing (SHSH) from PD 30 to 72. Adult rats (PD 80 ± 5) received 5 trials/day of a 10-s flashing-light conditioned stimulus (CS) paired with .8 mA footshock either immediately (delay conditioning) or after a 10-s trace interval (trace conditioning) for 2 days. Neonatal alcohol exposure impaired context and trace conditioning, but not short-delay conditioning. The WREC intervention did not reverse these deficits, despite increasing context-related freezing in ethanol-exposed and SI animals.