Temporary threshold shift after noise exposure in hypobaric hypoxia at high altitude: results of the ADEMED expedition 2011.

OBJECTIVES: To evaluate whether there is an increased risk for noise-induced hearing loss at high altitude rsp. in hypobaric hypoxia. METHODS: Thirteen volunteers got standard audiometry at 125, 250, 500, 750, 1000, 1500, 2000, 3000, 4000, 6000, and 8000 Hz before and after 10 min of white noise at 90 dB. The system was calibrated for the respective altitude. Measurements were performed at Kathmandu (1400 m) and at Gorak Shep (5300 m) (Solo Khumbu/Nepal) after 10 days of acclimatization while on trek. Temporary threshold shift (TTS) was analyzed by descriptive statistics and by factor analysis. RESULTS: TTS is significantly more pronounced at high altitudes. Acclimatization does not provide any protection of the inner ear, although it increases arterial oxygen saturation. CONCLUSION: The thresholds beyond which noise protection is recommended (> 80 dB) or necessary (> 85 dB) are not sufficient at high altitudes. We suggest providing protective devices above an altitude of 1500 m ("ear threshold altitude") when noise level is higher than 75 dB and using them definitively above 80 dB. This takes the individual reaction on hypobaric hypoxia at high altitude into account.

Genomic Epidemiology as a Public Health Tool to Combat Mosquito-Borne Virus Outbreaks.

Next-generation sequencing technologies, exponential increases in the availability of virus genomic data, and ongoing advances in phylogenomic methods have made genomic epidemiology an increasingly powerful tool for public health response to a range of mosquito-borne virus outbreaks. In this review, we offer a brief primer on the scope and methods of phylogenomic analyses that can answer key epidemiological questions during mosquito-borne virus public health emergencies. We then focus on case examples of outbreaks, including those caused by dengue, Zika, yellow fever, West Nile, and chikungunya viruses, to demonstrate the utility of genomic epidemiology to support the prevention and control of mosquito-borne virus threats. We extend these case studies with operational perspectives on how to best incorporate genomic epidemiology into structured surveillance and response programs for mosquito-borne virus control. Many tools for genomic epidemiology already exist, but so do technical and nontechnical challenges to advancing their use. Frameworks to support the rapid sharing of multidimensional data and increased cross-sector partnerships, networks, and collaborations can support advancement on all scales, from research and development to implementation by public health agencies.

The Microalbuminuria Education Medication and Optimisation (MEMO) study: 4 years follow-up of multifactorial intervention in high-risk individuals with type 2 diabetes.

AIMS: The Microalbuminuria Education Medication and Optimisation (MEMO) study, revealed improved cardiovascular risk and glycaemic control with 18 months of intensive multifactorial intervention in high-risk people with type 2 diabetes, without any increase in severe hypoglycaemia. Our aim was to assess longer-term outcomes at 4-year follow-up in these participants. METHODS: Some 189 individuals with type 2 diabetes and microalbuminuria were recruited from a multi-ethnic population in Leicestershire, UK. The intervention group (n = 95) received multifactorial intervention with self-management education, and the control group (n = 94) received usual care. The primary outcome was change in HbA1c , and secondary outcomes were blood pressure (BP), cholesterol, microalbuminuria, estimated GFR, cardiovascular risk scores and major adverse cardiovascular events. RESULTS: Some 130 participants (68.7%), mean (sd) age 60.8 (10.4) years, duration of diabetes 11.5 (9.7) years, completed 4 years of follow-up. Mean change [95% confidence intervals (CI)] in HbA1c over 4 years was greater with intensive intervention compared with control (-3 mmol/mol, 95% CI -4.95,-1.11; -0.4%, 95% CI -0.67,-0.15; P = 0.002). Significant improvements over the 4 years were also seen in systolic BP (-7.3 mmHg, 95% CI -11.1, -3.5; P < 0.001), diastolic BP (-2.9 mmHg, 95% CI -5.4, -0.3; P = 0.026), cholesterol (-0.3 mmol/l, 95% CI -0.52,-0.12; P = 0.002), and 10-year coronary heart disease (-5.3, 95% CI -8.2,-2.3; P < 0.001) and stroke risk (-4.4, 95% CI -7.5, -1.3; P < 0.001). CONCLUSION: Multifactorial intervention with structured diabetes self-management education compared with usual diabetes care has benefits for cardio-metabolic risk factor profile. There was no increase in severe hypoglycaemia and cardiovascular mortality despite intensive glycaemic control, although the study was not powered to assess these outcomes.

Zika transmission patterns: a meta-review.

OBJECTIVE: To assesses what is known and identify knowledge gaps for Zika virus (ZIKV) transmission patterns. METHODS: Meta-review searching the databases BioSys; Cochrane Infectious Diseases Group Specialised Register and Cochrane Central Register of Controlled Trials; EMBASE; Google Scholar; LILACS; MEDLINE (PubMed); Web of Science; and WHOLIS with the term 'ZIKA'. Systematic reviews and reviews specifying the search methods and describing potential modes of transmission were eligible for analysis. RESULTS: Of 5,401 hits for 'Zika', 44 studies were assessed and 11 included after applying in- and exclusion criteria: six systematic reviews and five reviews with specified methods, covering all ways of possible transmission. Results can be grouped into transmission routes with good evidence and agreement between the studies (evidence on vector, mother-to-child and sexual transmission) and transmission routes with limited evidence. Transmission by breastfeeding, intrapartum, by animal bites or laboratory-based remains inconclusive, as these routes are suggested by single studies only. The risk of transfusion transmission is described and public health measures for safe transfusion should be taken as available. CONCLUSION: Our results imply the need for public health measures to limit transmission via vectors, mother-to-child, sexual transmission and blood transfusion. Also needed are long-term prospective cohort studies covering periods of active Zika virus transmission and measuring epidemiological parameters to establish evidence on other routes of transmission; seroprevalence studies; transmission dynamics modelling and modelling health impacts by different modes of transmission.

OBJECTIF: Evaluer ce que l'on sait et identifier les lacunes dans les connaissances sur les profils de transmission du virus Zika (ZIKV). MÉTHODES: Méta-analyse de recherche dans les bases de données BioSys, Cochrane Infectious Diseases Specialised Register et le Registre Central Cochrane des Essais Contrôlés, EMBASE, Google Scholar, LILACS MEDLINE (PubMed), Web de la Science et WHOLIS avec le terme «Zika¼. Les revues systématiques et les revues spécifiant les méthodes de recherche et décrivant les modes de transmission potentiels étaient éligibles pour l'analyse. RÉSULTATS: Sur 5.401 résultats correspondant à «Zika¼, 44 études ont été évaluées et 11 incluses après application des critères d'inclusion et d'exclusion: 6 revues systématiques et 5 revues avec des méthodes spécifiées, couvrant tous les modes de transmission possibles. Les résultats peuvent être regroupés en voies de transmission avec des preuves solides et une concordance entre les études (preuves sur la transmission vectorielle, transmission mère-enfant et sexuelle) et les voies de transmission avec des preuves limitées. La transmission par l'allaitement, par voie intra-partum, par des morsures d'animaux ou via le laboratoire reste non conclusive, car ces voies ne sont suggérées que par des études uniques. Le risque de transmission par transfusion est décrit et des mesures de santé publique visant à garantir une transfusion sans danger doivent être prises dès que possible. CONCLUSION: Nos résultats insinuent la nécessité de prendre des mesures de santé publique pour limiter la transmission par le biais des vecteurs, la transmission mère-enfant, la transmission sexuelle et la transfusion sanguine. Des études de cohorte prospectives à long terme portant sur des périodes de transmission active du virus Zika et des mesures de paramètres épidémiologiques sont également nécessaires pour établir des preuves d'autres voies de transmission; des études de séroprévalence; la modélisation de la dynamique de transmission et la modélisation des impacts sur la santé par différents modes de transmission.

A (five-)level playing field for mental health conditions?: exploratory analysis of EQ-5D-5L-derived utility values.

PURPOSE: Economic evaluations of mental health interventions often measure health benefit in terms of utility values derived from the EQ-5D. For the five-level version of the EQ-5D, there are two methods of estimating utility [crosswalk and stated preference (5L-SP)]. This paper explores potential impacts for researchers and decision-makers when comparing utility values derived from either method in the specific context of mental health. METHODS: Baseline EQ-5D-5L data from three large randomised controlled trials of interventions for mental health conditions were analysed. Utility values were generated using each method. Mean utility values were compared using a series of t tests on pooled data and subgroups. Scenario analyses explored potential impacts on cost-effectiveness decisions. RESULTS: EQ-5D data were available for 1399 participants. The mean utility value for each trial was approximately 0.08 higher when estimated using the 5L-SP approach compared to crosswalk (p < 0.0001). The difference was greatest among people reporting extreme anxiety/depression (mean utility 5L-SP 0.309, crosswalk 0.084; difference = 0.225; p < 0.0001). Identical improvements in health status were associated with higher costs to gain one QALY with the 5L-SP approach; this is more pronounced when improvements are across all domains compared to improvements on the anxiety/depression domain only. CONCLUSIONS: The two approaches produce significantly different utility values in people with mental health conditions. Resulting differences in cost per QALY estimates suggest that thresholds of cost-effectiveness may also need to be reviewed. Researchers and decision-makers should exercise caution when comparing or synthesising data from trials of mental health interventions using different utility estimation approaches.

Rare, low frequency and common coding variants in CHRNA5 and their contribution to nicotine dependence in European and African Americans.

The common nonsynonymous variant rs16969968 in the α5 nicotinic receptor subunit gene (CHRNA5) is the strongest genetic risk factor for nicotine dependence in European Americans and contributes to risk in African Americans. To comprehensively examine whether other CHRNA5 coding variation influences nicotine dependence risk, we performed targeted sequencing on 1582 nicotine-dependent cases (Fagerström Test for Nicotine Dependence score⩾4) and 1238 non-dependent controls, with independent replication of common and low frequency variants using 12 studies with exome chip data. Nicotine dependence was examined using logistic regression with individual common variants (minor allele frequency (MAF)⩾0.05), aggregate low frequency variants (0.05>MAF⩾0.005) and aggregate rare variants (MAF<0.005). Meta-analysis of primary results was performed with replication studies containing 12 174 heavy and 11 290 light smokers. Next-generation sequencing with 180 × coverage identified 24 nonsynonymous variants and 2 frameshift deletions in CHRNA5, including 9 novel variants in the 2820 subjects. Meta-analysis confirmed the risk effect of the only common variant (rs16969968, European ancestry: odds ratio (OR)=1.3, P=3.5 × 10(-11); African ancestry: OR=1.3, P=0.01) and demonstrated that three low frequency variants contributed an independent risk (aggregate term, European ancestry: OR=1.3, P=0.005; African ancestry: OR=1.4, P=0.0006). The remaining 22 rare coding variants were associated with increased risk of nicotine dependence in the European American primary sample (OR=12.9, P=0.01) and in the same risk direction in African Americans (OR=1.5, P=0.37). Our results indicate that common, low frequency and rare CHRNA5 coding variants are independently associated with nicotine dependence risk. These newly identified variants likely influence the risk for smoking-related diseases such as lung cancer.

Research awareness, attitudes and barriers among clinical staff in a regional cancer centre. Part 1: a quantitative analysis.

Research is of key importance in delivering high-quality patient care through evidence-based practice. Attitude towards research and barriers to research can have an impact on research activity. A survey was conducted to establish the levels of research awareness and attitudes among clinical staff groups in this regional cancer centre and identify any barriers to participation in research. The survey consisted of 26 questions and was distributed electronically and completed online. The response rate was 22.3% (n = 123). All participants felt that clinical research will help the regional cancer centre develop and progress treatments in the future. A positive attitude towards research was evident and consistent across professional groups. The main identified barriers to research included lacking the required knowledge, skills and training, lacking support from managers, and lack of opportunity or time to be involved in research, in particular for allied health professionals. However, there appears to be the foundation of a healthy research culture for nurses supported by management. The results of the survey support the implementation of an action plan based on the recommendations of this journal article.

Effects of the inverse alpha-agonist doxazosin in allergic rhinitis.

BACKGROUND: We examined the paradoxical hypothesis that the alpha-receptor inverse agonist doxazosin might produce beneficial effects in allergic rhinitis. OBJECTIVES: To evaluate single and chronic dosing effects of doxazosin on nasal airflow and symptoms in allergic rhinitis. METHODS: Fifteen patients randomized to receive 3-5 weeks of oral doxazosin 4 mg daily or placebo in crossover fashion. Measurements were taken at baseline and after first and last doses. RESULTS: There was a fall in peak nasal inspiratory flow (PNIF) between baseline vs. first dose of doxazosin: mean difference -19 L/min (95% CI -35 to -2) P = 0.03, with recovery between first and last doses: 21 L/min (95% CI 7-34) P = 0.006. Nasal visual analogue scale (VAS) and blockage scores were worse between baseline vs. first dose of doxazosin: mean difference VAS -10 mm (95% CI -18 to -2) P = 0.02, blockage -0.7 (95% CI -1.3 to -0.1) P = 0.02, with recovery between first and last doses: VAS 15 mm (95% CI 4-25) P = 0.009, blockage 1.1 (95% CI 0.5-1.6) P = 0.001. The oxymetazoline dose-response for PNIF was blunted after single vs chronic dosing with doxazosin: mean difference -17 L/min (95% CI -30 to -4) P = 0.01. Heart rate and diastolic blood pressure showed the same pattern. There was a significant difference between doxazosin and placebo for nasal blockage score and heart rate after single but not chronic dosing. CONCLUSIONS: There was a disconnect between single and chronic dosing effects of doxazosin for nasal symptoms, oxymetazoline response and cardiovascular outcomes, in turn suggesting alpha-1 receptor up-regulation.

Osteonecrosis of the jaw (ONJ): diagnosis and management in 2015.

Osteonecrosis of the jaw (ONJ) has been associated with the use of aminobisphosphonates and denosumab. The vast majority (>90%) of cases occur in the oncology patient population receiving high doses of intravenous bisphosphonates or subcutaneous denosumab. The incidence of ONJ in the osteoporosis patient population is very low and is estimated at 1-90 per 100,000 patient-years of exposure. In the oncology patient population the incidence appears to be related to dose and duration of exposure, and prevalence has been estimated to be as high as 18.6%. A number of risk factors in addition to antiresorptive therapy have been identified. These include the presence of periodontal disease, oral surgical procedures with extractions or implants, radiation therapy, chemotherapy, diabetes, glucocorticoid use, and smoking. Antiangiogenic agents appear to contribute to the risk of ONJ, however, data at this time are limited and further evidence is required prior to confirming a causal relationship. ONJ may be prevented with optimization of oral hygiene, the use of oral antimicrobial mouth rinses, as well as systemic antibiotic therapy. Individuals not responding to conservative management or in the advanced stages of ONJ may be considered for surgery, as data over the past several years have demonstrated surgical success in this patient population. Case reports have indicated that teriparatide may enhance healing. A number of experimental therapies are being evaluated and include the use of bone marrow stem cell intralesional transplantation, local application of platelet-derived growth factor, hyperbaric oxygen, tissue grafting, and low-level laser therapy. This paper summarizes the current research as well as the international consensus on the diagnosis and management of ONJ.

A randomised trial of the cool pad pillow topper versus standard care for sleep disturbance and hot flushes in women on endocrine therapy for breast cancer.

PURPOSE: Quality of life in women receiving adjuvant endocrine therapy for breast cancer (BC) may be impaired by hot flushes and night sweats. The cool pad pillow topper (CPPT) is a commercial product, promoted to improve quality of sleep disrupted by hot flushes. This study aimed to identify if the CPPT reduces severity of sleep disturbance by minimising effects of hot flushes. METHODS: This randomised phase II trial, recruited women with BC, on adjuvant endocrine therapy, experiencing hot flushes and insomnia. Participants were randomised (stratified by baseline sleep efficiency score (SES) and menopausal status) to the intervention arm (CPPT + standard care) or control arm (standard care). Participants completed Hospital Anxiety and Depression Scale and Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaires and fortnightly sleep/hot flush diaries (where responses were averaged over 2-week periods). The primary endpoint was change in average SES from -2 to 0 weeks to 2 to 4 weeks. RESULTS: Seventy-four pre- (68.9 %) and post-menopausal (31.1 %) women were recruited. Median age was 49.5 years. Endocrine therapies included tamoxifen (93.2 %). Median SES at weeks 2 to 4 improved in both arms but the increase on the intervention arm was almost twice that on the control arm (p = 0.024). There were significantly greater reductions in hot flushes and HADS depression in the intervention arm (p = 0.09 and p = 0.036, respectively). There were no significant differences in FACT-B or HADS anxiety. CONCLUSION: This study supports the use of the CPPT as an aid to reduce sleep disturbance and the frequency/severity of hot flushes.

An evaluation of regulatory and commercial barriers to stratified medicine development and adoption.

Today, a range of products based on genomics, proteomics and metabolomics have facilitated the development of 'stratified' medicines and companion diagnostics. This investigation profiles a series of targeted medicines and corresponding diagnostics, and their role(s) in supporting evidence-based medicine. Despite their potential benefits we found that scientific, financial and regulatory barriers impede the development and adoption of companion diagnostics. Therefore, in order to realise improvements to the risk/benefit profiles of health-care interventions-notably reducing clinical uncertainty-conferred by the use of companion diagnostics, industry representatives, health-care providers and regulators will need a coordinated response to overcome these barriers.

Psychotic experiences and PTSD: exploring associations in a population survey.

BACKGROUND: Extensive evidence has shown that experiencing a traumatic event and post-traumatic stress disorder (PTSD) are associated with experiences of psychosis. However, less is known about specific PTSD symptoms and their relationship with psychotic experiences. This study aimed to examine the relationship between symptoms of PTSD with paranoia and auditory hallucinations in a large-scale sample. METHOD: The Adult Psychiatric Morbidity Survey (APMS) was utilized to examine the prevalence of lifetime trauma, symptoms of PTSD, and experiences of paranoia and auditory hallucinations (n = 7403). RESULTS: There were significant bivariate associations between symptoms of PTSD and psychotic experiences. Multiple logistic regression analyses indicated that reliving and arousal symptoms were significant predictors for paranoia while reliving, but not arousal symptoms, also significantly predicted auditory hallucinations. A dose-response relationship was found, the greater the number of PTSD symptoms, the greater the odds were of experiencing both paranoia and hallucinations. CONCLUSIONS: These findings illustrate that symptoms of PTSD are associated with increased odds of experiencing auditory hallucinations and paranoia. Overlaps appear to be present between the symptoms of PTSD and psychotic experiences. Increasing awareness of this association may advance work in clinical practice.

Negative cognition, affect, metacognition and dimensions of paranoia in people at ultra-high risk of psychosis: a multi-level modelling analysis.

BACKGROUND: Paranoia is one of the commonest symptoms of psychosis but has rarely been studied in a population at risk of developing psychosis. Based on existing theoretical models, including the proposed distinction between 'poor me' and 'bad me' paranoia, we aimed to test specific predictions about associations between negative cognition, metacognitive beliefs and negative emotions and paranoid ideation and the belief that persecution is deserved (deservedness). METHOD: We used data from 117 participants from the Early Detection and Intervention Evaluation for people at risk of psychosis (EDIE-2) trial of cognitive­behaviour therapy, comparing them with samples of psychiatric in-patients and healthy students from a previous study. Multi-level modelling was utilized to examine predictors of both paranoia and deservedness, with post-hoc planned comparisons conducted to test whether person-level predictor variables were associated differentially with paranoia or with deservedness. RESULTS: Our sample of at-risk mental state participants was not as paranoid, but reported higher levels of 'bad-me' deservedness, compared with psychiatric in-patients. We found several predictors of paranoia and deservedness. Negative beliefs about self were related to deservedness but not paranoia, whereas negative beliefs about others were positively related to paranoia but negatively with deservedness. Both depression and negative metacognitive beliefs about paranoid thinking were specifically related to paranoia but not deservedness. CONCLUSIONS: This study provides evidence for the role of negative cognition, metacognition and negative affect in the development of paranoid beliefs, which has implications for psychological interventions and our understanding of psychosis.

Evaluation of a potassium removal filter on irradiated red cells stored in SAGM.

BACKGROUND AND OBJECTIVES: Irradiation of red cell concentrates RCCs) can lead to well-documented elevated extracellular potassium concentrations. Transfusion of these products has the potential, if given as a massive/rapid transfusion, to lead to transient hyperkalemia. A potassium absorption filter (PAF) has recently been developed and has been proven to effectively remove excess K(+) . However, data are lacking on the red cell quality parameters over storage after irradiation. METHODS: Thirty RCCs were pooled and split into 3 groups of 10. All RCCs were irradiated on day 14 and filtered on day 28 (group 1 control), day 15 (group 2) or day 17 (group 3). Pre-irradiation, pre- and post-filtration and day 28 samples were taken for each study. Standard red cell quality parameters were measured over storage at the above time points. RESULTS: Losses for haemoglobin, haematocrit and volume were minimal after filtration with all units containing >40 g Hgb unit(-1). Statistically, significant differences were observed for K(+) and Na(+) levels in groups filtered at either 24 or 72 h post-irradiation, and this was observed directly after filtration and remained by day 28. Filtration had no significant impact on any other parameters measured. CONCLUSIONS: PAF effectively removed supernatant potassium (93%) from all RCC units. Early removal of K(+) at either day 15 or 17 on RCCs subsequently stored to day 28 had no measurable effect on red cell quality, suggesting this may be a useful device to ensure further safety for at-risk immunocompromised patient groups requiring irradiated RCCs.

Workload during cardiopulmonary resuscitation.

OBJECTIVES: Lay resuscitation is crucial for the survival of the patients with out-of-hospital cardiac arrest. Therefore, lay CPR should be a basic skill for everyone. With the growing proportion of retired people in the Western societies, CPR performed by people with preexisting diseases and at risk of cardiac events is expected to grow. There is little knowledge about the workload during CPR and the minimum workload capacity of the rescuer. METHODS: Pulse frequency, oxygen uptake, and CO2 elimination were measured by telemetry, while CPR was performed using a manikin with digital equipment for the standardization of the procedure. The same parameters were measured during a standard exercise testing protocol (spiroergometry) on a bicycle to analyze the aerobic endurance range of the participants. Data from the resuscitation protocols were correlated with those from spiroergometry to establish a simple standard investigation procedure to check people at risk and to give minimum requirements to perform CPR in Watts/kg. The study consisted of two parts: 1 (n = 16) explored minimal workload cutoffs for the rescuer using the 1995 recommendations and 2 (n = 14) tested the latest 2010 guidelines to compare both recommendations. RESULTS: When tested according to the 1995 guidelines, heart frequency of rescuers increased from 83.0 bpm (±11.3) at rest to 109.9 bpm (±12.6; P = 0.0004). The newer 2010 guidelines increased the workload marginally more (n.s.). CONCLUSION: CPR can be performed by healthy people within the range of aerobic endurance. The minimal requirements for trainings are 1.6-1.8 W/kg body weight in standard cycling ergometry. People at risk should be trained very careful. Since there is no significant lower workload when following the 1995 recommendations, people at risk should be trained according to the latest recommendations. In the case of a real resuscitation, such trained individuals must additionally take into account any symptoms.

Storage of apheresis platelet concentrates after manual replacement of >95% of plasma with PAS 5.

BACKGROUND AND OBJECTIVES: Recently, a glucose- and bicarbonate-containing additive solution termed PAS 5 demonstrated acceptable 7-day platelet storage after >95% plasma replacement with PAS on the day of collection (Day 0). In this study, we examined platelet storage in >95% PAS 5 after manual washing of Day 1 apheresis platelets in plasma collected using either the Amicus or Trima plateletpheresis devices. MATERIAL AND METHODS: Triple platelet donations in plasma were obtained from Amicus (n = 10) and Trima (n = 10) plateletpheresis devices and stored overnight before being centrifuged and manually processed into three units with the following storage media: 100% plasma, >95% PAS 5 or 65% PAS 5/35% plasma. Platelet units were sampled on Days 1, 5 and 7 of storage using a range of tests recommended by the UK guidelines. RESULTS: The majority of in vitro assay results for platelets in PAS 5 were similar to results in paired 100% plasma platelets (controls). The pH of PAS 5 stored platelet units was above the UK recommended guidelines of 7·4 by Day 5. PAS 5 platelets were no more activated than controls as evidenced by comparable soluble P-selectin levels and CD62p and CD42b expression. PAS 5 platelets also exhibited adhesion and aggregation profiles higher than (Day 1) or comparable to (Days 5 and 7) controls as measured by Impact R. CONCLUSION: The 7-day in vitro storage parameters investigated were comparable between >95% PAS 5 and 100% plasma platelets derived from both Amicus and Trima plateletpheresis devices, with the exception that lactose dehydrogenase release rate and pH were significantly higher in PAS 5 units.

Plasma anti-Müllerian hormone in adult dairy cows and associations with fertility.

The objectives of this study were to identify factors associated with concentrations of anti-Müllerian hormone (AMH) in plasma of dairy cows and to investigate the relationships between plasma AMH and fertility responses during a 100-d breeding season. Lactating cows, 1,237 in 2 seasonally calving herds, had estrous cycles presynchronized and were enrolled in a timed artificial insemination (AI) protocol. All cows were inseminated on the first day of breeding season, considered study d 0. Blood was sampled on d -8 and analyzed for concentrations of AMH and progesterone. From d 19 to 35, detection of estrus was performed daily and cows detected in estrus were reinseminated. On d 36, bulls were placed with cows for 65 d of natural service breeding. Factors identified to be associated with concentrations of AMH in plasma were breed of the cow and lactation number. Concentrations of AMH were greater for Jerseys, followed by crossbreds, and then Holsteins. Cows on lactations 2 and 3 had greater concentrations of AMH than those on lactations 1 and ≥ 4. Although pregnancy per AI at the timed AI was not associated with concentrations of AMH, cows with low AMH had greater detection of estrus at timed AI, and the latter benefited pregnancy per AI, particularly in cows that had low progesterone at the beginning of the synchronization protocol. Pregnancy loss between gestation d 30 and 65 was greater in cows with low AMH compared with those with intermediate or high AMH. Return to estrus in cows that failed to become pregnant from the timed AI was not associated with AMH, but pregnancy rate in cows bred on estrus (reinsemination + natural service) was associated positively with AMH. In conclusion, breed and lactation number were identified to be associated with concentrations of AMH in plasma. Concentration of AMH was associated positively with maintenance of pregnancy at the first postpartum AI and with pregnancy rate in cows inseminated after detection of spontaneous estrus. Synchronization of ovulation might override positive associations between AMH and fertility.

Lead exposure by E-waste disposal and recycling in Agbogbloshie, Ghana.

BACKGROUND: Agbogbloshie in Ghana is the world's biggest dumpsite for the informal recycling of electronic waste (e-waste). E-waste is dismantled by rudimentary methods without personal or environmental protection. Workers and occupants are exposed to lead. There are no data so far about the extent and the consequences. We therefore analyzed blood lead levels (BLL) and creatinine levels (CL). METHODS: Full blood samples and basic data (i.e. age, job, length of stay) were collected from dumpsite volunteers. BLL were measured by atomic absorption spectrometry; CL were assessed using the standard clinical laboratory procedures of Aachen Technical University. European BLL reference values were used as Ghana lacks its own. Statistical analysis was by non-parametric tests (Mann-Whitney U test), with p < 0.05. RESULTS: Participants of both sexes (n = 327; 12-68 years; median age 23 years) were assessed. Most workers were aged <30 years. The collective's BLL was in pathological range for 77.7%; 14% had a BLL >10.0 µg/dl with symptoms consistent with high lead exposure including severe (6.5%) and intermediate (39%) renal disorder. BLL above 15.0 µg/dl were found in 5.9% of all workers which is the German threshold for those working with lead. Elevated CL in a pathological range were found in 254 participants. This is problematic as 75% of the lead entering the body is excreted via urine. CONCLUSION: Most of our volunteers had pathological BLL and CL. Preventive strategies are necessary to reduce health risks, particularly for vulnerable populations (i.e. children, pregnant women).

The Strauss and Carpenter Prognostic Scale in subjects clinically at high risk of psychosis.

OBJECTIVE: To investigate the predictive value of the Strauss and Carpenter Prognostic Scale (SCPS) for transition to a first psychotic episode in subjects clinically at high risk (CHR) of psychosis. METHOD: Two hundred and forty-four CHR subjects participating in the European Prediction of Psychosis Study were assessed with the SCPS, an instrument that has been shown to predict outcome in patients with schizophrenia reliably. RESULTS: At 18-month follow-up, 37 participants had made the transition to psychosis. The SCPS total score was predictive of a first psychotic episode (P < 0.0001). SCPS items that remained as independent predictors in the Cox proportional hazard model were as follows: most usual quality of useful work in the past year (P = 0.006), quality of social relations (P = 0.006), presence of thought disorder, delusions or hallucinations in the past year (P = 0.001) and reported severity of subjective distress in past month (P = 0.003). CONCLUSION: The SCPS could make a valuable contribution to a more accurate prediction of psychosis in CHR subjects as a second-step tool. SCPS items assessing quality of useful work and social relations, positive symptoms and subjective distress have predictive value for transition. Further research should focus on investigating whether targeted early interventions directed at the predictive domains may improve outcomes.

Effect of intrathecal magnesium in the presence or absence of local anaesthetic with and without lipophilic opioids: a systematic review and meta-analysis.

Spinal anaesthesia is the primary anaesthetic technique for many types of surgery. Adjuncts to the local anaesthetics (LA) used in spinal anaesthesia can exhibit undesirable side-effects, limiting their use, but magnesium may have advantages in this respect. We sought randomized control trials (RCTs) in patients undergoing all types of surgery and in women in labour to compare the effect of intrathecal magnesium sulphate ± LA ± lipophilic opioid (experimental group) with the use of either intrathecal lipophilic opioids ± LA or LA only (control group). The primary outcome was the duration of spinal anaesthesia. Secondary outcomes were: onset and time to maximal sensory blockade, onset of motor block, and duration of sensory and motor blockade. We found 15 RCTs comprising 980 patients. The duration of spinal anaesthesia was significantly increased in the experimental group [standardized mean difference (SMD) -1.05 (-1.70, -0.41) (P = 0.001)], compared with the control group. This increased duration of spinal anaesthesia was seen in non-obstetric studies, SMD -1.38 (-2.11, -0.66) (P = 0.0002), but not in obstetric studies, SMD -0.55 (-1.87, 0.77) (P = 0.41). There was no delay in the onset of sensory or motor blockade. The incidence of hypotension and pruritus was similar in both groups. Heterogeneity was high in all outcome measures. The duration of spinal anaesthesia may be increased by the addition of magnesium to lipophilic opioids ± LA.