Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline.
A minority of patients having cardiac procedures (15% to 20%) consume more than 80% of the blood products transfused at operation. Blood must be viewed as a scarce resource that carries risks and benefits. A careful review of available evidence can provide guidelines to allocate this valuable resource and improve patient outcomes. We reviewed all available published evidence related to blood conservation during cardiac operations, including randomized controlled trials, published observational information, and case reports. Conventional methods identified the level of evidence available for each of the blood conservation interventions. After considering the level of evidence, recommendations were made regarding each intervention using the American Heart Association/American College of Cardiology classification scheme. Review of published reports identified a high-risk profile associated with increased postoperative blood transfusion. Six variables stand out as important indicators of risk: (1) advanced age, (2) low preoperative red blood cell volume (preoperative anemia or small body size), (3) preoperative antiplatelet or antithrombotic drugs, (4) reoperative or complex procedures, (5) emergency operations, and (6) noncardiac patient comorbidities. Careful review revealed preoperative and perioperative interventions that are likely to reduce bleeding and postoperative blood transfusion. Preoperative interventions that are likely to reduce blood transfusion include identification of high-risk patients who should receive all available preoperative and perioperative blood conservation interventions and limitation of antithrombotic drugs. Perioperative blood conservation interventions include use of antifibrinolytic drugs, selective use of off-pump coronary artery bypass graft surgery, routine use of a cell-saving device, and implementation of appropriate transfusion indications. An important intervention is application of a multimodality blood conservation program that is institution based, accepted by all health care providers, and that involves well thought out transfusion algorithms to guide transfusion decisions. Based on available evidence, institution-specific protocols should screen for high-risk patients, as blood conservation interventions are likely to be most productive for this high-risk subset. Available evidence-based blood conservation techniques include (1) drugs that increase preoperative blood volume (eg, erythropoietin) or decrease postoperative bleeding (eg, antifibrinolytics), (2) devices that conserve blood (eg, intraoperative blood salvage and blood sparing interventions), (3) interventions that protect the patient's own blood from the stress of operation (eg, autologous predonation and normovolemic hemodilution), (4) consensus, institution-specific blood transfusion algorithms supplemented with point-of-care testing, and most importantly, (5) a multimodality approach to blood conservation combining all of the above.


Landscape functionality of plant communities in the Impala Platinum mining area, Rustenburg.
The tremendous growth of the platinum mining industry in South Africa has affected the natural environment adversely. The waste produced by platinum mineral processing is alkaline, biologically sterile and has a low water-holding capacity. These properties in the environment may constitute dysfunctional areas that will create 'leaky' and dysfunctional landscapes, limiting biological development. Landscape Function Analysis (LFA) is a monitoring procedure that assesses the degradation of landscapes, as brought about by human, animal and natural activities, through rapidly assessing certain soil surface indicators which indicate the biophysical functionality of the system. The "Trigger-Transfer-Reserve-Pulse" (TTRP) conceptual framework forms the foundation for assessing landscape function when using LFA. The two main aspects of this framework are the loss of resources from the system and the utilisation of resources by the system. After a survey of landscape heterogeneity to reflect the spatial organisation of the landscape, soil surface indicators are assessed within different patch types (identifiable units that retains resources that pass through the system) and interpatches (units between patches where vital resources are not retained, but lost) to assess the capacity of patches with various physical properties in regulating the effectiveness of resource control in the landscape. Indices describing landscape organisation are computed by a spreadsheet analysis, as well as soil surface quality indices. When assembled in different combinations, three indices emerge that reflect soil productive potential, namely: the (1) surface stability, (2) infiltration capacity, and (3) the nutrient cycling potential of the landscape. In this study we compared the landscape functionality of natural thornveld areas, rehabilitated opencast mines and rehabilitated slopes of tailings dams in the area leased for mining in the Rustenburg area. Our results show that the rehabilitated areas had a higher total SSA functionality due to higher infiltration and nutrient cycling indices than the natural thornveld landscapes. The length of interpatches and the width of patches greatly influenced the landscape function of the studied areas. The natural thornveld areas had a marginally higher total patch area than the rehabilitated areas. Vegetated patches (grass-, sparse grass-, grassy forb-, and grassy shrub-patches) generally scored the highest functionality indices, whilst bare soil interpatches contributed to the landscape functionality of the various plant communities the least.


Effect of feed moisture, extrusion temperature and screw speed on properties of soy white flakes based aquafeed: a response surface analysis.
Soy white flakes (SWF) is an intermediate product during soy bean processing. It is an untoasted inexpensive product and contains around 51% of crude protein. It can be a potential source of protein to replace fish meal for developing aquafeed. The extrusion process is versatile and is used for the development of aquafeed. Our objective was to study the effects of inclusion of SWF (up to 50%) and other extrusion processing parameters such as barrel temperature and screw speed on the properties of aquafeed extrudates using a single-screw extruder. Extrudate properties, including pellet durability index, bulk density, water absorption and solubility indices and mass flow rate, were significantly (P < 0.05) affected by the process variables. SWF was the most significant variable with quadratic effects on most of the properties. Increasing temperature and screw speed resulted in increase in durability and mass flow rate of extrudates. Response surface regression models were established to correlate the properties of extrudates to the process variables. SWF was used as an alternative protein source of fish meal. Our study shows that aquafeed with high durability, lower bulk density and lower water absorption and higher solubility indices can be obtained by adding SWF up to 40%.


Conservation of the genes for dissimilatory sulfite reductase from Desulfovibrio vulgaris and Archaeoglobus fulgidus allows their detection by PCR.
The structural genes for dissimilatory sulfite reductase (desulfoviridin) from Desulfovibrio vulgaris Hilden-borough were cloned as a 7.2-kbp SacII DNA fragment. Nucleotide sequencing indicated the presence of a third gene, encoding a protein of only 78 amino acids, immediately downstream from the genes for the alpha and beta subunits (dsvA and dsvB). We designated this protein DsvD and the gene encoding it the dsvD gene. The alpha- and beta-subunit sequences are highly homologous to those of the dissimilatory sulfite reductase from Archaeoglobus fulgidus, a thermophilic archaeal sulfate reducer, which grows optimally at 83 degrees C. A gene with significant homology to dsvD was also found immediately downstream from the dsrAB genes of A. fulgidus. The remarkable conservation of gene arrangement and sequence across domain (bacterial versus archaeal) and physical (mesophilic versus thermophilic) boundaries indicates an essential role for DsvD in dissimilatory sulfite reduction and allowed the construction of conserved deoxyoligonucleotide primers for detection of the dissimilatory sulfite reductase genes in the environment.


[Regional healthcare labels: differences in care needs and psychosocial functioning].
Severe mental illnesses (SMI) are associated with high mental healthcare and other healthcare costs. In 2012, mental healthcare labels were developed to create more transparency between insurance companies, municipalities, and mental healthcare. The labels are based on care intensity, and should provide a regional overview of the present groups of patients with SMI.
 AIM: Explore the functionality and validity of the used labels in relation to needs for care and psychosocial functioning.
 METHOD: The ROM data (needs for care, functioning) from 706 patients were tested per label by Chi-square tests and ANOVAs. For two high complex labels (alarming care avoiders and persons with safety risks), repeated measures ANOVAs and McNemar tests were used to analyse changes in functioning and needs over time.
 RESULTS: To a limited extent, the labels were distinctive in care needs and functioning. The most restrictions in functioning and (unfulfilled) needs were present in the labels 'alarming care avoiders' and 'avoiding danger'. These findings were stable over time.
 CONCLUSION: The labels are not sufficiently distinctive. To enhance regional care planning, it is desirable to combine existing information on healthcare labels with information on care needs and functioning. KEY WORDS functioning, mental healthcare labels, needs for care, routine outcome monitoring, severe mental illness.


Effect of Sex and Menstrual Cycle on Skin Sensory Nerve Contribution to Local Heating.
The purpose of this study was to determine sex differences in the contribution of sensory nerves to rapid cutaneous thermal hyperemia. Healthy young females (n = 15, tested during both the early follicular (EF) and the mid-luteal (ML) phase of the menstrual cycle) and males (n = 15) had a 4 cm2 area of skin on one forearm and one leg treated with a eutectic mixture of local anesthetic (EMLA). EMLA sites, along with corresponding control sites, were instrumented with laser Doppler flowmetry probes and local skin heaters. Baseline (33 °C), rapid and sustained vasodilation (42 °C), and maximal vasodilation (44 °C) skin blood flow data were obtained and expressed as a percentage of maximal cutaneous vascular conductance (%CVCmax). Contribution of sensory nerve involvement was determined by comparing the EMLA site to its matched control site utilizing the formula [(% CVCmax control - % CVCmax treatment) / % CVCmax control] × 100. The contribution of sensory nerves to rapid cutaneous thermal hyperemia in the forearm was 24 ± 18 %CVCmax in males, 41 ± 17 %CVCmax in ML females (p = 0.02 vs. males), and 35 ± 17 %CVCmax in EF females (p > 0.05 vs. males). In the leg, the contribution of sensory nerves was 16 ± 15 %CVCmax in males, 34 ± 17 %CVCmax for ML females (p = 0.02 vs. males), and 28 ± 21 %CVCmax in EF females (p > 0.05 vs. males). ML females exhibited a greater contribution of sensory nerves to rapid cutaneous thermal hyperemia in the forearm and leg, possibly attributed to elevated reproductive hormones during the ML phase.


High mortality amongst adolescents and adults with bacterial meningitis in sub-Saharan Africa: an analysis of 715 cases from Malawi.
Mortality from bacterial meningitis in African adults is significantly higher than those in better resourced settings and adjunctive therapeutic interventions such as dexamethasone and glycerol have been shown to be ineffective. We conducted a study analysing data from clinical trials of bacterial meningitis in Blantyre, Malawi to investigate the clinical parameters associated with this high mortality. We searched for all clinical trials undertaken in Blantyre investigating bacterial meningitis from 1990 to the current time and combined the data from all included trial datasets into one database. We used logistic regression to relate individual clinical parameters to mortality. Adults with community acquired bacterial meningitis were included if the CSF culture isolate was consistent with meningitis or if the CSF white cell count was >100 cells/mm(3) (>50% neutrophils) in HIV negative participants and >5 cells/mm(3) in HIV positive participants. Outcome was measured by mortality at discharge from hospital (after 10 days of antibiotic therapy) and community follow up (day 40). Seven hundred and fifteen episodes of bacterial meningitis were evaluated. The mortality rate was 45% at day 10 and 54% at day 40. The most common pathogens were S.pneumoniae (84% of positive CSF isolates) and N.meningitidis (4%). 607/694 (87%) participants tested were HIV antibody positive. Treatment delays within the hospital system were marked. The median presenting GCS was 12/15, 17% had GCS<8 and 44.9% had a seizure during the illness. Coma, seizures, tachycardia and anaemia were all significantly associated with mortality on multivariate analysis. HIV status and pneumococcal culture positivity in the CSF were not associated with mortality. Adults with community acquired bacterial meningitis in Malawi present with a severe clinical phenotype. Predictors of high mortality are different to those seen in Western settings. Optimising in-hospital care and minimising treatment delays presents an opportunity to improve outcomes considerably.


High-throughput profiling of alpha interferon- and interleukin-28B-regulated microRNAs and identification of let-7s with anti-hepatitis C virus activity by targeting IGF2BP1.
Hepatitis C virus (HCV) infection is a major cause of severe liver disease. Interferon (IFN)/ribavirin treatment remains the standard therapeutic regimen for HCV infection in most countries. IFN-stimulated genes are believed to contribute to antiviral effects. However, emerging evidence suggests that microRNAs (miRNAs), a class of noncoding small RNAs, are involved in the control of viral infection. Here, we systematically profiled the hepatocyte expression of a set of 750 miRNAs in response to alpha interferon (IFN-α) and interleukin-28B (IL-28B) treatments. The anti-HCV activity of differentially expressed miRNAs was evaluated using cell culture-derived HCV in vitro. The results demonstrate that let-7b had a significant anti-HCV effect by inhibiting HCV replication and viral protein translation in human hepatoma cells. In particular, we show that the inhibition of let-7b attenuated the anti-HCV effects of IFN-α and IL-28B. Furthermore, we show that the host factor insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is a target of let-7b. IGF2BP1 was required for HCV replication, and its expression was downregulated by IFN-α and IL-28B. Deletion of the wild-type seed region of let-7b abolished its antiviral activity. Finally, we demonstrate that other let-7 family miRNAs were able to inhibit HCV and to suppress IGF2BP1 expression. In conclusion, we provide an example of a host miRNA regulated by type I and type III IFNs that inhibits HCV replication and infectivity by targeting host targets. These results highlight the important role of miRNAs in the host antiviral immune response and provide a novel candidate for anti-HCV therapy.


Effects of aronia berry (poly)phenols on vascular function and gut microbiota: a double-blind randomized controlled trial in adult men.
Aronia melanocarpa is a rich source of (poly)phenols. Previous research has demonstrated that these berries may provide cardiovascular health benefits in high-risk populations. However, very few studies have investigated the effects of daily consumption of dietary achievable amounts of the berries in healthy subjects. The aim of this study was to investigate the effects of aronia berries on vascular function and gut microbiota composition in a healthy population. A double-blind, placebo-controlled, parallel designed study was conducted in 66 healthy men randomly allocated to consume a (poly)phenol-rich extract (116 mg, 75 g berries), a whole fruit powder (12 mg, 10 g berries), or placebo (maltodextrin) for 12 wk. Flow-mediated dilation (FMD), arterial stiffness, blood pressure, heart rate, and serum biochemistry were assessed. Plasma (poly)phenol metabolites were analyzed by LC-MS. Gut microbiota composition was determined via 16S rRNA sequencing in stool samples. Consumption of aronia whole fruit and extract powder for 12 wk led to a significant increase in FMD over control of 0.9% ± 0.4% (95% CI: 0.13%, 1.72%) and 1.2% ± 0.4% (95% CI: 0.36%, 1.97%), respectively. Acute improvements in FMD were also observed 2 h after consumption of aronia extract on day 1 (1.1% ± 0.3%, P = 0.003) and 12 wk later (1.5% ± 0.4%, P = 0.0001). Circulating plasma phenolic metabolites increased upon consumption of the aronia treatments. Although no changes were found in gut microbiota diversity, consumption of aronia extract increased the growth of Anaerostipes (+10.6%, P = 0.01), whereas aronia whole fruit showed significant increases in Bacteroides (+193%, P = 0.01). Correlation analysis identified significant associations between changes in FMD, aronia-derived phenolic metabolites, and specific gut microbial genera. In healthy men, consumption of aronia berry (poly)phenols improved endothelial function and modulated gut microbiota composition, indicating that regular aronia consumption has the potential to maintain cardiovascular health in individuals at low risk of cardiovascular disease. This trial was registered at CLINICALTRIALs.gov as NCT03041961.


Channelized hotelling and human observer correlation for lesion detection in hepatic SPECT imaging.
Mathematic "model" observers that predict human performance are of interest in medical imaging as substitutes in psychophysical studies. We have examined the correlations between human observers and several forms of the channelized Hotelling observer (CHO) for a tumor detection task with simulated SPECT liver images that were used to study the effects of scatter and scatter correction on detection. A receiver operating characteristic (ROC) study was devised to investigate the relative value of a scatter-subtraction strategy in SPECT imaging. The study used simulated images of the biodistribution of 99mTc-labeled FO23C5 anticarcinoembryonic antigen antibodies within the liver. Projection data for 3 separate tumor locations and 5 strategies for handling scatter were obtained using Monte Carlo software applied to an anthropomorphic phantom. The strategies were (a) perfect scatter rejection, (b) no scatter correction, (c) no scatter correction under an assumption of an elevated amount of scatter, (d) an energy-spectrum-based scatter compensation of the normal-scatter case (b), and (e) similar scatter compensation for the elevated-scatter case (c). Image reconstruction approximated current clinical procedures at the University of Massachusetts Medical School. Human performance for each combination of location and strategy was based on averaging the areas under the ROC curve for 7 individuals. A set of 15 signal-to-noise ratios (SNRs) was derived from these averages for comparison with SNRs for CHO models featuring constant-Q and difference-of-gaussian (DOG) filters. The Spearman rank correlation coefficient was 0.92 (P = 0.000001) when comparing task performances for the average human and a constant-Q CHO using 4 square-profile channels. For the DOG version of the CHO, comparison with the average human found a coefficient of 0.84 (P = 0.00005). The significant positive correlations found between the rankings of the average human observer and the CHOs for our detection task indicate that a channelized model observer could eventually serve as a replacement for human observers. The specific CHO models we have used are best suited to screen for significant differences between strategies before a human psychophysical study.


Effect of blood glucose level on standardized uptake value (SUV) in 18F- FDG PET-scan: a systematic review and meta-analysis of 20,807 individual SUV measurements.
To evaluate the effect of pre-scan blood glucose levels (BGL) on standardized uptake value (SUV) in 18F-FDG-PET scan. A literature review was performed in the MEDLINE, Embase, and Cochrane library databases. Multivariate regression analysis was performed on individual datum to investigate the correlation of BGL with SUVmax and SUVmean adjusting for sex, age, body mass index (BMI), diabetes mellitus diagnosis, 18F-FDG injected dose, and time interval. The ANOVA test was done to evaluate differences in SUVmax or SUVmean among five different BGL groups (< 110, 110-125, 125-150, 150-200, and > 200 mg/dl). Individual data for a total of 20,807 SUVmax and SUVmean measurements from 29 studies with 8380 patients was included in the analysis. Increased BGL is significantly correlated with decreased SUVmax and SUVmean in brain (p < 0.001, p < 0.001,) and muscle (p < 0.001, p < 0.001) and increased SUVmax and SUVmean in liver (p = 0.001, p = 0004) and blood pool (p = 0.008, p < 0.001). No significant correlation was found between BGL and SUVmax or SUVmean in tumors. In the ANOVA test, all hyperglycemic groups had significantly lower SUVs compared with the euglycemic group in brain and muscle, and significantly higher SUVs in liver and blood pool. However, in tumors only the hyperglycemic group with BGL of > 200 mg/dl had significantly lower SUVmax. If BGL is lower than 200 mg/dl no interventions are needed for lowering BGL, unless the liver is the organ of interest. Future studies are needed to evaluate sensitivity and specificity of FDG-PET scan in diagnosis of malignant lesions in hyperglycemia.


Variable-Temperature Tip-Enhanced Raman Spectroscopy of Single-Molecule Fluctuations and Dynamics.
Structure, dynamics, and coupling involving single-molecules determine function in catalytic, electronic or biological systems. While vibrational spectroscopy provides insight into molecular structure, rapid fluctuations blur the molecular trajectory even in single-molecule spectroscopy, analogous to spatial averaging in measuring large ensembles. To gain insight into intramolecular coupling, substrate coupling, and dynamic processes, we use tip-enhanced Raman spectroscopy (TERS) at variable and cryogenic temperatures, to slow and control the motion of a single molecule. We resolve intrinsic line widths of individual normal modes, allowing detailed and quantitative investigation of the vibrational modes. From temperature dependent line narrowing and splitting, we quantify ultrafast vibrational dephasing, intramolecular coupling, and conformational heterogeneity. Through statistical correlation analysis of fluctuations of individual modes, we observe rotational motion and spectral fluctuations of the molecule. This work demonstrates single-molecule vibrational spectroscopy beyond chemical identification, opening the possibility for a complete picture of molecular motion ranging from femtoseconds to minutes.


Classification of global measles cases in 2013-17 as due to policy or vaccination failure: a retrospective review of global surveillance data.
Despite improvements in reported coverage of measles-containing vaccine (MCV) and progress towards elimination of measles, 172 939 measles cases were reported worldwide in 2017. Questions have been raised about whether measles cases are due to failure of immunisation programmes or vaccine policy failure, which might require changes to vaccination schedules or number of doses. This retrospective review of global surveillance data analysed case-based data for cases of measles occurring during 2013-17 submitted to WHO by its member states. Cases were classified as programmatically preventable (ie, did not receive the age-appropriate number of doses for that country) or programmatically non-preventable (ie, appropriately vaccinated as per national programme) on the basis of age at onset, year of birth, vaccination status, and eligibility for MCV doses in the country reporting the case. We grouped reasons why cases were non-preventable into four categories as follows: (1) received at least two doses of MCV; (2) too young for first dose; (3) received one dose but was too young to receive the second; or (4) was only eligible for one dose according to the national schedule. We analysed numbers and proportions of preventable and non-preventable cases of measles by region and year, reasons for non-preventable cases by year, preventable cases by age group, and preventable and non-preventable cases, including reasons for non-preventable cases, by measles elimination status of countries. Between Jan 1, 2013, and Dec 31, 2017, 634 139 measles cases were reported; 7850 (1%) cases were excluded because they did not provide age at onset, so 626 289 were included in our analysis. 191 333 (31%) of these cases had unknown vaccination status. 275 754 (63%) of the 434 956 cases with available vaccination data were categorised as programmatically preventable, 213 461 (77%) of whom were aged 1 year to less than 15 years. 156 384 (36%) cases were categorised as non-preventable, of whom 38 677 (25%) were two-dose vaccine recipients, 74 438 (48%) were too young to receive their first MCV dose, 11 914 (8%) received their first dose and were too young to receive their second dose, and 31 355 (20%), mostly in the Africa region, were non-preventable because they were only eligible for one dose on the basis of the national immunisation programme. Most measles cases during 2013-17 were programmatically preventable, highlighting the need for improving the effectiveness of immunisation programmes that already exist. Individual countries should do similar analyses to establish the changes needed in their country to decrease numbers of measles cases. None.


Quantifying bias in measuring insecticide-treated bednet use: meta-analysis of self-reported vs objectively measured adherence.
Insecticide-treated bednets (ITNs) are recommended for use by 3.4 billion people at risk of malaria world-wide. Policy makers rely on measurements of ITN use to optimize malaria prevention efforts. Self-reports are the most common means of assessing ITN use, but self-reports may be biased in a way that reduces their reliability as a proxy for ITN adherence. This meta-analysis compared self-reported and two methods which are more objective measures of ITN use to explore whether self-reports overestimate actual ITN adherence. A comprehensive search of electronic databases and hand searching reference lists resulted in screening 2885 records and 202 articles were read in full. Sixteen articles with comparable data were chosen for the meta-analysis. Comparable data was defined as self-reported and objectively measured ITN use (observation of a mounted ITN or surprise visits confirming use) at the same unit of analysis, covering the same time period and same population. A random effects model was used to determine a weighted average risk difference between self-reported and objectively measured ITN use. Additional stratified analyses were conducted to explore study heterogeneity. Self-reported ITN use is 8 percentage points (95% confidence interval CI: 3 to 13) higher than objectively measured ITN use, representing a 13.6% overestimation relative to the proportion measured as adherent to ITN use by objective measures. Wide variations in the discrepancies between self-reports and objective measures were unable to be explained using stratified analyses of variables including location, year of publication, seasonality and others. Self-reports overestimate ITN adherence relative to objectively measured ITN use by 13.6% and do so in an unpredictable manner that raises questions about the reliability of using self-reported ITN use alone as a surveillance tool and a guide for making policy decisions.


Neuroprotective effect of Pycnogenol® following traumatic brain injury.
Traumatic brain injury (TBI) involves primary and secondary injury cascades that underlie delayed neuronal dysfunction and death. Oxidative stress is one of the most celebrated secondary injury mechanisms. A close relationship exists between levels of oxidative stress and the pathogenesis of TBI. However, other cascades, such as an increase in proinflammatory cytokines, also play important roles in the overall response to the trauma. Pharmacologic intervention, in order to be successful, requires a multifaceted approach. Naturally occurring flavonoids are unique in possessing not only tremendous free radical scavenging properties but also the ability to modulate cellular homeostasis leading to a reduction in inflammation and cell toxicity. This study evaluated the therapeutic role of Pycnogenol (PYC), a patented combinational bioflavonoid. Young adult Sprague-Dawley rats were subjected to a unilateral moderate cortical contusion and treated post injury with PYC or vehicle. At either 48 or 96 h post trauma, the animals were killed and the cortex and hippocampus analyzed for changes in enzymatic and non-enzymatic oxidative stress markers. In addition, possible changes in both pre- and post-synaptic proteins (synapsin-1, PSD-95, drebrin, synapse associated protein-97) were analyzed. Finally, a separate cohort of animals was used to evaluate two proinflammatory cytokines (IL-6, TNF-α). Following the trauma there was a significant increase in oxidative stress in both the injured cortex and the ipsilateral hippocampus. Animals treated with PYC significantly ameliorated levels of protein carbonyls, lipid peroxidation, and protein nitration. The PYC treatment also significantly reduced the loss of key pre- and post-synaptic proteins with some levels in the hippocampus of PYC treated animals not significantly different from sham operated controls. Although levels of the proinflammatory cytokines were significantly elevated in both injury groups, the cohort treated with PYC showed a significant reduction compared to vehicle treated controls. These results are the first to show a neuroprotective effect of PYC following TBI. They also suggest that the diverse effects of bioflavonoids may provide a unique avenue for possible therapeutic intervention following head trauma.


An overview of 9/11 experiences and respiratory and mental health conditions among World Trade Center Health Registry enrollees.
To date, health effects of exposure to the September 11, 2001 disaster in New York City have been studied in specific groups, but no studies have estimated its impact across the different exposed populations. This report provides an overview of the World Trade Center Health Registry (WTCHR) enrollees, their exposures, and their respiratory and mental health outcomes 2-3 years post-9/11. Results are extrapolated to the estimated universe of people eligible to enroll in the WTCHR to determine magnitude of impact. Building occupants, persons on the street or in transit in lower Manhattan on 9/11, local residents, rescue and recovery workers/volunteers, and area school children and staff were interviewed and enrolled in the WTCHR between September 2003 and November 2004. A total of 71,437 people enrolled in the WTCHR, for 17.4% coverage of the estimated eligible exposed population (nearly 410,000); 30% were recruited from lists, and 70% were self-identified. Many reported being in the dust cloud from the collapsing WTC Towers (51%), witnessing traumatic events (70%), or sustaining an injury (13%). After 9/11, 67% of adult enrollees reported new or worsening respiratory symptoms, 3% reported newly diagnosed asthma, 16% screened positive for probable posttraumatic stress disorder (PTSD), and 8% for serious psychological distress (SPD). Newly diagnosed asthma was most common among rescue and recovery workers who worked on the debris pile (4.1%). PTSD was higher among those who reported Hispanic ethnicity (30%), household income < $25,000 (31%), or being injured (35%). Using previously published estimates of the total number of exposed people per WTCHR eligibility criteria, we estimate between 3,800 and 12,600 adults experienced newly diagnosed asthma and 34,600-70,200 adults experienced PTSD following the attacks, suggesting extensive adverse health impacts beyond the immediate deaths and injuries from the acute event.


A Multi-Country Study of Harms to Children Because of Others' Drinking.
This study aims to ascertain and compare the prevalence and correlates of alcohol-related harms to children cross-nationally. National and regional sample surveys of randomly selected households included 7,848 carers (4,223 women) from eight countries (Australia, Chile, Ireland, Lao People's Democratic Republic [PDR], Nigeria, Sri Lanka, Thailand, and Vietnam). Country response rates ranged from 35% to 99%. Face-to-face or telephone surveys asking about harm from others' drinking to children ages 0-17 years were conducted, including four specific harms: that because of others' drinking in the past year children had been (a) physically hurt, (b) verbally abused, (c) exposed to domestic violence, or (d) left unsupervised. The prevalence of alcohol-related harms to children varied from a low of 4% in Lao PDR to 14% in Vietnam. Alcohol-related harms to children were reported by a substantial minority of families in most countries, with only Lao PDR and Nigeria reporting significantly lower levels of harm. Alcohol-related harms to children were dispersed sociodemographically and were concentrated in families with heavy drinkers. Family-level drinking patterns were consistently identified as correlates of harm to children because of others' drinking, whereas sociodemographic factors showed few obvious correlations.


Monooxygenase enzyme activity in alcoholics with varying degrees of liver damage.
Monooxygenase enzymes are involved in the biotransformation of drugs and of environmental carcinogens. The activity of 7-ethoxycoumarin 0-deethylase and associated NADPH-cytochrome c reductase was determined in 9000 g supernatant from bioptically obtained liver specimens from patients with various liver diseases in order to study in vitro drug metabolising capacity. Monooxygenase and reductase activity was significantly higher in the livers of 21 patients with alcoholic liver disease (fatty liver, alcoholic hepatitis, cirrhosis of the liver) than in 22 normal controls or in six patients with chronic active hepatitis. The raised activity of drug-metabolising enzymes obtained from alcoholics with liver damage differs from normal values found in five alcoholics without liver disease. Both groups were comparable in respect to the amount of alcohol consumed and duration of abuse. A strikingly low monooxygenase activity was observed in eight patients with cirrhosis of the liver and ascites, with, however, no apparent effect on reductase activity. The results show that alcoholic liver disease is associated with enhanced monooxygenase and reductase activity, but alcoholism, per se, is not. This rise of drug-metabolising enzyme activity could lead to selectively increased rates of biotransformation in patients with alcoholic liver damage.


Ropivacaine attenuates endotoxin plus hyperinflation-mediated acute lung injury via inhibition of early-onset Src-dependent signaling.
Acute lung injury (ALI) is associated with high mortality due to the lack of effective therapeutic strategies. Mechanical ventilation itself can cause ventilator-induced lung injury. Pulmonary vascular barrier function, regulated in part by Src kinase-dependent phosphorylation of caveolin-1 and intercellular adhesion molecule-1 (ICAM-1), plays a crucial role in the development of protein-/neutrophil-rich pulmonary edema, the hallmark of ALI. Amide-linked local anesthetics, such as ropivacaine, have anti-inflammatory properties in experimental ALI. We hypothesized ropivacaine may attenuate inflammation in a "double-hit" model of ALI triggered by bacterial endotoxin plus hyperinflation via inhibition of Src-dependent signaling. C57BL/6 (WT) and ICAM-1 (-/-) mice were exposed to either nebulized normal saline (NS) or lipopolysaccharide (LPS, 10 mg) for 1 hour. An intravenous bolus of 0.33 mg/kg ropivacaine or vehicle was followed by mechanical ventilation with normal (7 ml/kg, NTV) or high tidal volume (28 ml/kg, HTV) for 2 hours. Measures of ALI (excess lung water (ELW), extravascular plasma equivalents, permeability index, myeloperoxidase activity) were assessed and lungs were homogenized for Western blot analysis of phosphorylated and total Src, ICAM-1 and caveolin-1. Additional experiments evaluated effects of ropivacaine on LPS-induced phosphorylation/expression of Src, ICAM-1 and caveolin-1 in human lung microvascular endothelial cells (HLMVEC). WT mice treated with LPS alone showed a 49% increase in ELW compared to control animals (p = 0.001), which was attenuated by ropivacaine (p = 0.001). HTV ventilation alone increased measures of ALI even more than LPS, an effect which was not altered by ropivacaine. LPS plus hyperinflation ("double-hit") increased all ALI parameters (ELW, EVPE, permeability index, MPO activity) by 3-4 fold compared to control, which were again decreased by ropivacaine. Western blot analyses of lung homogenates as well as HLMVEC treated in culture with LPS alone showed a reduction in Src activation/expression, as well as ICAM-1 expression and caveolin-1 phosphorylation. In ICAM-1 (-/-) mice, neither addition of LPS to HTV ventilation alone nor ropivacaine had an effect on the development of ALI. Ropivacaine may be a promising therapeutic agent for treating the cause of pulmonary edema by blocking inflammatory Src signaling, ICAM-1 expression, leukocyte infiltration, and vascular hyperpermeability.


Explosive vaporization of single droplets by lasers: comparison of models with experiments.
A computer model of the explosive vaporization of single water droplets by pulsed CO(2)-laser radiation is compared with the relevant experiments. The model shows excellent quantitative agreement with the experiments, to our knowledge the first time such agreement has been observed. The importance of fluid mechanics during the pulse is demonstrated, and a second computer model illustrates how a spherically symmetric explosion can evolve even under conditions of nonuniform heating. The two models reconcile the differences between predictions made by Mie theory and observations of droplet heating.


CYP-13A12 of the nematode Caenorhabditis elegans is a PUFA-epoxygenase involved in behavioural response to reoxygenation.
A specific behavioural response of Caenorhabditis elegans, the rapid increase of locomotion in response to anoxia/reoxygenation called the O2-ON response, has been used to model key aspects of ischaemia/reperfusion injury. A genetic suppressor screen demonstrated a direct causal role of CYP (cytochrome P450)-13A12 in this response and suggested that CYP-eicosanoids, which in mammals influence the contractility of cardiomyocytes and vascular smooth muscle cells, might function in C. elegans as specific regulators of the body muscle cell activity. In the present study we show that co-expression of CYP-13A12 with the NADPH-CYP-reductase EMB-8 in insect cells resulted in the reconstitution of an active microsomal mono-oxygenase system that metabolized EPA (eicosapentaenoic acid) and also AA (arachidonic acid) to specific sets of regioisomeric epoxy and hydroxy derivatives. The main products included 17,18-EEQ (17,18-epoxyeicosatetraenoic acid) from EPA and 14,15-EET (14,15-epoxyeicosatrienoic acid) from AA. Locomotion assays showed that the defective O2-ON response of C20-PUFA (polyunsaturated fatty acid)-deficient, Δ-12 and Δ-6 fatty acid desaturase mutants (fat-2 and fat-3 respectively) can be restored by feeding the nematodes AA or EPA, but not ETYA (eicosatetraynoic acid), a non-metabolizable AA analogue. Short-term incubation with 17,18-EEQ was sufficient to rescue the impaired locomotion of the fat-3 strain. The endogenous level of free 17,18-EEQ declined during anoxia and was rapidly restored in response to reoxygenation. On the basis of these results, we suggest that CYP-dependent eicosanoids such as 17,18-EEQ function as signalling molecules in the regulation of the O2-ON response in C. elegans. Remarkably, the exogenously administered 17,18-EEQ increased the locomotion activity under normoxic conditions and was effective not only with C20-PUFA-deficient mutants, but to a lesser extent also with wild-type worms.


pVHL/HIF-regulated CD70 expression is associated with infiltration of CD27+ lymphocytes and increased serum levels of soluble CD27 in clear cell renal cell carcinoma.
CD70, a member of the TNF ligand superfamily, has been shown frequently overexpressed in clear cell renal cell carcinoma (ccRCC). The mechanisms of CD70's upregulation and its role in ccRCC are unknown. CD70 expression was immunohistochemically analyzed in 667 RCCs and RCC metastases. Von Hippel-Lindau gene (VHL) mutations, expression patterns of VHL protein (pVHL), hypoxia-inducible factor (HIF) α, and several HIF targets were studied in tissues and cell lines and correlated with CD70 overexpression. Gene promoter analysis was performed to confirm CD70 as HIF target gene. Consecutive tissue sections were immunostained to reveal the relation between CD70-expressing RCCs and tumor-infiltrating lymphocytes positive for the CD70 receptor (CD27). CD70-mediated release of soluble CD27 in RCC was assessed by coculture experiments and sera analysis of patients with RCC. Elevated CD70 expression was seen in 80% of primary tumors and metastases of ccRCC and correlated with dysregulation of the pVHL/HIF pathway. In vitro analyses demonstrated that CD70 upregulation is driven by HIF. Furthermore, CD27(+) lymphocytes preferentially infiltrate CD70-expressing ccRCCs. CD70-dependent release of soluble CD27 in cocultures may explain the high CD27 levels observed in sera of patients with CD70-expressing ccRCC. The combination of lymphocyte infiltration and CD70 expression in RCC was associated with worse patient outcome. Our findings demonstrate that in ccRCC, CD70 expression is regulated by HIF as a consequence of pVHL inactivation. Increased serum levels of CD27 suggest the existence of CD70-expressing ccRCC, thus representing a potential serum marker for patients suffering from this disease.


Deterioration, drift, distraction, and denial: How the politics of austerity challenges the resilience of prison health governance and delivery in England.
Extant scholarship has demonstrated that macroeconomic austerity disproportionately harms marginalised end-users. Its impact on the governance and delivery of health provisions on such individuals, however, has received less attention. Drawing on interviews with 27 policy elites involved with England's prison health policy, interviewees perceive that austerity policies have shaped and constrained the prison health system through the politics of deterioration, drift, distraction, and denial. The deterioration of the prison workforce size has been linked to diminished prisoner access to healthcare, attendant with an increased number of riots, assaults, acts of self-harm, and suicides. Concurrently, the microeconomic structure of organised crime is filling the void in prison governance, thus conducing to heightened abuse of psychoactive substances, as well as a surge in associated medical emergencies and violence. Successful prosecution of prior sexual offences, continued incarceration of those imprisoned for indeterminate sentences, and harsh sentencing practices have created policy drift, unremitting overcrowding, and reinforced excessive dependency on prison healthcare resources. The rapid turnover of justice ministers and intensified push for prison privatisation have enabled widespread distraction. Moreover, despite well-documented crises besetting English prisons, politicians seemingly remain in a state of denial. Preventive imprisonment, recurrent spending, and enhanced financial and political accountability measures are necessary to mitigate the effects of austerity and germane policies fomenting inimical impacts on England's prison health system.


Inactivation of cephalothin and cephaloridine by Staphylococcus aureus.
Benner, Ernest J. (University of Washington School of Medicine, Seattle), John V. Bennett, Jean L. Brodie, and William M. M. Kirby. Inactivation of cephalothin and cephaloridine by Staphylococcus aureus. J. Bacteriol. 90:1599-1604. 1965.-Marked differences were observed in the susceptibility of penicillinase-producing staphylococci to cephalothin and cephaloridine. All of 100 strains of penicillin G-resistant Staphylococcus aureus, with the use of a large inoculum, were found to be susceptible to 2 mug/ml of cephalothin, whereas only 50% were susceptible to this concentration of cephaloridine, and 15% required 15 mug/ml or more for inhibition. In contrast, penicillin G-sensitive strains were more susceptible to cephaloridine and did not show the marked inoculum effect observed with the cephaloridine-resistant strains. These differences were due to a much greater destruction of cephaloridine than of cephalothin by staphylococcal penicillinase. Cephaloridine-resistant staphyloccoci were stronger penicillinase producers than were susceptible strains, and the resistant strains were found to inactivate cephaloridine by hydrolysis of the beta-lactam ring. In population studies, cephaloridine-resistant cells differed from methicillin-resistant cells in that they decreased in numbers as the drug concentration was increased, and the survivors in higher drug concentrations were no more resistant than was the parent strain. Treatment with acriflavine eliminated resistance of the cells to both penicillin G and cephaloridine. It was concluded that cephaloridine resistance was due to hydrolysis by penicillinase, and that this was related to the pyridine ring substitution in the cephalosporanic acid nucleus.


Changes in relative light fluence measured during laser heating: implications for optical monitoring and modelling of interstitial laser photocoagulation.
Dynamic changes in internal light fluence were measured during interstitial laser heating of tissue phantoms and ex vivo bovine liver. In albumen phantoms, the results demonstrate an unexpected rise in optical power transmitted approximately I cm away from the source during laser exposure at low power (0.5-1 W), and a decrease at higher powers (1.5-2.5 W) due to coagulation and possibly charring. Similar trends were observed in liver tissue, with a rise in interstitial fluence observed during 0.5 W exposure and a drop in interstitial fluence seen at higher powers (1-1.5 W) due to tissue coagulation. At 1.5 W irradiation an additional, later decrease was also seen which was most likely due to tissue charring. Independent spectrophotometric studies in Naphthol Green dye indicate the rise in fluence observed in the heated albumen phantoms may have been primarily due to light exposure causing photobleaching of the absorbing chromophore. and not due to heat effects. Experiments in liver tissue demonstrated that the observed rise in fluence is dependent on the starting temperature of the tissue. Correlating changes in light fluence with key clinical endpoints/events such as the onset of tissue coagulation or charring may be useful for on-line monitoring and control of laser thermal therapy via interstitial fluence sensors.


Association of healthy aging with parental longevity.
Various measures incorporated in geriatric assessment have found their way into frailty indices (FIs), which have been used as indicators of survival/mortality and longevity. Our goal is to understand the genetic basis of healthy aging to enhance its evidence base and utility. We constructed a FI as a quantitative measure of healthy aging and examined its characteristics and potential for genetic analyses. Two groups were selected from two separate studies. One group (OLLP for offspring of long-lived parents) consisted of unrelated participants at least one of whose parents was age 90 or older, and the other group of unrelated participants (OSLP for offspring of short-lived parents), both of whose parents died before age 76. FI34 scores were computed from 34 common health variables and compared between the two groups. The FI34 was better correlated than chronological age with mortality. The mean FI34 value of the OSLP was 31 % higher than that of the OLLP (P = 0.0034). The FI34 increased exponentially, at an instantaneous rate that accelerated 2.0 % annually in the OLLP (P = 0.024) and 2.7 % in the OSLP (P < < 0.0001) consequently yielding a 63 % larger accumulation in the latter group (P = 0.0002). The results suggest that accumulation of health deficiencies over the life course is not the same in the two groups, likely due to inheritance related to parental longevity. Consistent with this, sib pairs were significantly correlated regarding FI34 scores, and heritability of the FI34 was estimated to be 0.39. Finally, hierarchical clustering suggests that the OLLP and OSLP differ in their aging patterns. Variation in the FI34 is, in part, due to genetic variation; thus, the FI34 can be a phenotypic measure suitable for genetic analyses of healthy aging.


Ethnic and socio-economic differences in the prevalence of wheeze, severe wheeze, asthma, eczema and medication usage at 4 years of age: Findings from the Born in Bradford birth cohort.
Asthma, wheeze and eczema are common in early childhood and cause considerable morbidity. Generally rates of these conditions are higher in high income compared to low income countries. Rates in developed nations are generally higher than in less developed countries. After migration to Western countries, differences in risks of developing these conditions may between migrant and non-migrant may diminish. A convenience sample of 1648 children of White British, Pakistani or Other ethnicity aged between 4 and 5 years were recruited from the main Born in Bradford cohort. Children's parents or guardians were asked to report on a range of potential risk factors and their associations with wheeze, asthma and eczema. Relationships between ethnicity and disease outcomes were examined using logistic regression after adjustment for other relevant risk factors and confounders. Ethnic differences in doctor diagnosed asthma were evident, with children of other ethnic Origin being less likely and children of Pakistani origin more likely to have a diagnosis than White British or other origin children, although after adjustment for other risk factors this difference only remained significant for the Other Ethnic group. Ethnic differences were not observed in other outcomes including wheeze in the past 12 months, severe wheeze and taking medications for breathing problems. In UK born children, traditional risk factors such as gender, family history, socio-economic status and child's medical history may be stronger risk factors than ethnicity or familial migration patterns.


Patient centredness in integrated care: results of a qualitative study based on a systems theoretical framework.
Health care providers seek to improve patient-centred care. Due to fragmentation of services, this can only be achieved by establishing integrated care partnerships. The challenge is both to control costs while enhancing the quality of care and to coordinate this process in a setting with many organisations involved. The problem is to establish control mechanisms, which ensure sufficiently consideration of patient centredness. Seventeen qualitative interviews have been conducted in hospitals of metropolitan areas in northern Germany. The documentary method, embedded into a systems theoretical framework, was used to describe and analyse the data and to provide an insight into the specific perception of organisational behaviour in integrated care. The findings suggest that integrated care partnerships rely on networks based on professional autonomy in the context of reliability. The relationships of network partners are heavily based on informality. This correlates with a systems theoretical conception of organisations, which are assumed autonomous in their decision-making. Networks based on formal contracts may restrict professional autonomy and competition. Contractual bindings that suppress the competitive environment have negative consequences for patient-centred care. Drawbacks remain due to missing self-regulation of the network. To conclude, less regimentation of integrated care partnerships is recommended.


Heterologous and in Vitro Reconstitution of Fuscanodin, a Lasso Peptide from Thermobifida fusca.
Lasso peptides are a class of ribosomally derived natural products typified by their threaded rotaxane structure. The conversion of a linear precursor peptide into a lasso peptide structure requires two enzymatic activities: cleavage of the precursor via a cysteine protease and cyclization via isopeptide bond formation. In vitro studies of lasso peptide enzymology have been hampered by difficulties in obtaining pure, soluble enzymes. We reasoned that thermophilic bacteria would be a good source for well-behaved lasso peptide biosynthetic enzymes. The genome of the thermophilic actinobacterium Thermobifida fusca encodes for a lasso peptide with an unprecedented Trp residue at its N-terminus, a peptide we have named fuscanodin. Here we reconstitute fuscanodin biosynthesis in vitro with purified components, establishing a minimal fuscanodin synthetase. These experiments have allowed us to probe the kinetics of lasso peptide biosynthesis for the first time, and we report initial rates of fuscanodin biosynthesis. The fuscanodin biosynthetic enzymes are insensitive to substrate concentration and operate in a near single-turnover regime in vitro. While lasso peptides are often touted for their stability to both chaotropic and thermal challenges, fuscanodin is found to undergo a conformational change consistent with lasso peptide unthreading in organic solvents at room temperature.


Antiproliferative and antiangiogenic effect of Amblyomma sculptum (Acari: Ixodidae) crude saliva in endothelial cells in vitro.
Neovascularization, a process that includes vasculogenesis and angiogenesis, may be a physiological or pathologic event, but in any cases the phenomenon is related to the formation of vascular net and sprouting of endothelial cells from preexisting blood vessel. The tumor environment, which counts on the tumor cell proliferation, is plenty of proangiogenic factors, such as angiogenin, TGF (α and β), FGF, VEGF, all of them playing a crucial role in angiogenesis, an important hallmark of cancer frequently related to a poor prognosis. Therefore, therapies focusing the inhibition of cancer neovasculogenesis have become an interesting strategy for the development of antitumor therapies. In this work, we investigate the effect of tick saliva on the human endothelial cells, in order to understand its inhibitory effects on angiogenesis. To this end, the HUVEC cells were used as model of angiogenesis in vitro and the anti-proliferative, anti-migratory, cytotoxicity was evaluated. Our data depicts that saliva impairs cell development by causing structural changes while precludes cell proliferation and migration, that are crucial events related to angiogenesis. Aiming the identification of the bioactive components related to antiangiogenic activity, saliva was analyzed through the Mass Spectrometry and among all molecules identified, disintegrins and cathepsin L seems to be primarily responsible for the antiangiogenic effects of saliva.


Interstellar medium. Pseudo-three-dimensional maps of the diffuse interstellar band at 862 nm.
The diffuse interstellar bands (DIBs) are absorption lines observed in visual and near-infrared spectra of stars. Understanding their origin in the interstellar medium is one of the oldest problems in astronomical spectroscopy, as DIBs have been known since 1922. In a completely new approach to understanding DIBs, we combined information from nearly 500,000 stellar spectra obtained by the massive spectroscopic survey RAVE (Radial Velocity Experiment) to produce the first pseudo-three-dimensional map of the strength of the DIB at 8620 angstroms covering the nearest 3 kiloparsecs from the Sun, and show that it follows our independently constructed spatial distribution of extinction by interstellar dust along the Galactic plane. Despite having a similar distribution in the Galactic plane, the DIB 8620 carrier has a significantly larger vertical scale height than the dust. Even if one DIB may not represent the general DIB population, our observations outline the future direction of DIB research.


Biocide and antimicrobial susceptibility of methicillin-resistant staphylococcal isolates from horses.
The aim of this study was to evaluate the biocide and antimicrobial susceptibility of methicillin-resistant staphylococcal isolates from horses. Fourteen methicillin-resistant staphylococci (MRS) were subjected to an extensive genotype characterization, including SCCmec, dru, spa, PFGE and MLST typing. Antimicrobial susceptibility testing was performed and resistance genes were detected by PCR. Minimum bactericidal concentrations (MBCs) of four biocides [chlorhexidine acetate (CHA), benzalkonium chloride (BAC), triclosan (TCL) and glutaraldehyde (GLA)] were determined following the recommendations of document NF EN 1040. The presence of qac and sh-fabI genes was investigated by PCR. Several antimicrobial resistance patterns and genes were detected. When MRS strains were exposed for a longer period of time, a lower concentration of the biocide was needed to achieve lethality. TCL had the lowest MBC values. All MBC values were lower than the recommended in-use concentrations for veterinary medicine. S. haemolyticus and S. cohnii subsp. cohnii carried plasmid-borne qacA and sh-fabI or qacB and a qacH-like genes, respectively. Biocides appear to be a reliable antiseptic option against MRS, since even in the presence of bacterial efflux mechanisms, the recommended concentration is much higher than the in vitro MBC.


Malignant arrhythmia in apical ballooning syndrome: risk factors and outcomes.
We sought to determine the frequency and outcomes with symptomatic arrhythmia in patients with apical ballooning syndrome (ABS). A retrospective review of the Mayo Clinic Angiography database was conducted to identify patients who met the Mayo criteria for ABS. Patients with documented arrhythmias formed the study group, and 31 randomly selected patients with ABS but without arrhythmia formed the control group. Out of 105 patients identified with ABS, 6 (5.7%) women aged 69 +/- 9 years experienced significant arrhythmia (ventricular fibrillation, asystole), 2 patients died, and 1 required permanent pacemaker implantation. When compared with controls, the study group showed no significant difference with respect to ECG characteristics (QT, QRS duration or axis) except for R-R interval variability (see comments below) (30.6+/-6 vs 14.5+/-17 p = 0.0004), QTc, and P-R interval. Patients without arrhythmia were more likely to be on beta-blocker therapy than the study population (33% vs 80.6% p = 0.02). Life-threatening arrhythmia is uncommon (5.7%) with ABS despite marked, structural abnormalities. When arrhythmias do occur, the outcome is poor. Prominent variability in R-R intervals appears to be predictive of significant arrhythmias in ABS. The role of beta-blocker therapy in preventing arrhythmia with ABS requires further investigation.


Effect of two carbohydrate-modified tube-feeding formulas on metabolic responses in patients with type 2 diabetes.
This study evaluated the glycemic, insulinemic, and glucagon-like peptide-1 (GLP-1) responses of subjects with type 2 diabetes mellitus to consumption of two diabetes-specific tube-feeding formulas (slowly digested carbohydrate formula [SDC] and diabetes-specific formula [DSF]) and one formula intended for individuals without diabetes (standard formula [STND]). Forty-eight subjects controlled with diet and/or oral antihyperglycemic medications received the SDC, DSF, and STND. Postprandial glucose, insulin, and GLP-1 were measured on three occasions after an overnight fast in a double-blinded, randomized, three-treatment, crossover design. The positive area under the curve for glucose and insulin with the STND was higher (P < 0.001) compared with the SDC and DSF. The adjusted GLP-1 concentration at 60 min was higher for the SDC compared with the DSF and STND (P < 0.05). Both lower-carbohydrate diabetes-specific formulas resulted in a lower postprandial blood glucose response compared with the STND. The formula also rich in slowly digested carbohydrate and monounsaturated and omega-3 fatty acids (SDC) produced significantly lower blood glucose and insulin responses and higher levels of GLP-1 in the presence of significantly lower insulin concentrations. These results support the view that the quantity and quality of carbohydrate and fat may play important roles in the management of patients with type 2 diabetes mellitus and could result in improved beta-cell function over the long term.


Does clinical improvement of symptomatic degenerative lumbar disease impact obesity?
OBJECTIVE Obesity and low-back pain associated with degenerative spondylosis or spondylolisthesis are common comorbid conditions. Many patients report that the pain and disability associated with degenerative lumbar disease are key factors in their inability to lose weight. The aim of this retrospective study was to determine if there is an association between improved functional status and weight loss following a successful transforaminal lumbar interbody fusion (TLIF) procedure. METHODS A retrospective cohort study of patients who underwent single-level TLIF was performed. Inclusion criteria were preoperative body mass index (BMI) greater than 30 kg/m2, achievement of minimum clinically important difference in the Oswestry Disability Index (ODI, defined as improvement of 15 points), and minimum 1-year postoperative followup BMI. Preoperative and postoperative BMI, ODI, and visual analog scale (VAS) scores were compared. A subgroup analysis of patients who achieved substantial clinical benefit (SCB, defined as a net improvement of 18.8 points on the ODI) was also performed. RESULTS A total of 56 patients met the inclusion criteria. The mean age of the study population was 55.6 ± 13.7 years. The mean preoperative BMI was 34.8 ± 4.6 kg/m2, the mean preoperative ODI was 66.2 ± 10.1, and the mean preoperative VAS score was 7.1 ± 1.7. The mean change in ODI was -33.1 ± 13.5 (p < 0.01) and the mean change in the VAS score was -4.1 ± 2.1 (p < 0.01). The mean change in BMI was +0.15 ± 2.1 kg/m2 (range -4.2 to +6.5 kg/m2; p = 0.6). SCB was achieved in 46 patients on the ODI. The mean preoperative BMI for patients with SCB was 34.8 ± 4.8 kg/m2, and the mean postoperative BMI was 34.7 ± 5.0 kg/m2. The mean change in BMI was -0.03 ± 1.9 kg/m2 (p = 0.9). CONCLUSIONS Despite successful surgical intervention via TLIF with achievement of improved function and pain, obese patients did not have significant change in weight postoperatively.


Utilization of Chiropractic Care at the World Games 2013.
The purpose of this study was to describe chiropractic care use at the World Games 2013. In this retrospective study, we reviewed treatment charts of athletes and non-athletes who sought chiropractic care at The World Games in Cali, Colombia, from July 25 to August 4, 2013. Doctors of chiropractic of the International Federation of Sports Chiropractic provided care. Chart notes included body region treated, treatment modality, and pretreatment and posttreatment pain ratings. Of the participants, 537 of 2964 accredited athletes and 403 of 4131 accredited non-athletes sought chiropractic treatment; these represent utilization rates of 18.1% for athletes and 9.8% for non-athletes. A total of 1463 treatments were recorded for athletes (n = 897) and non-athletes (n = 566). The athletes who were treated represented 28 of 33 sports and 68 of 93 countries that were present at the games. Among athletes, the thoracic spine was the most frequent area of treatment (57.2%), followed by the lumbar spine (48.7%) and the cervical spine (38.9%). Myotherapy was the most frequently used treatment method (80.9%), followed by chiropractic manipulation (78.5%), taping (38.0%), and mobilization (24.6%). Reports of acute injury were higher among athletes (45.4%) compared with non-athletes (23.8%). Reported pain was reduced after treatment (P < .001), and 86.9% patients reported immediate improvement after receiving chiropractic treatment. The majority of people seeking chiropractic care at an international sporting competition were athletes. For those seeking care, the injury rate was higher among athletes than among non-athletes. The majority of patients receiving chiropractic care reported improvement after receiving care.


Deep sclerectomy with supraciliary hema implant (Esnoper® V-2000): results and complications.
The aim was to report the results of deep sclerectomy (DS) with supraciliary hema implant and the influence of the surgical complications on intraocular pressure (IOP). Forty-eight eyes of 41 patients with open angle glaucoma (OAG), who underwent DS with supraciliary hema implant (Esnoper(®) V-2000), were included in this study. A significant IOP reduction was observed, changing from a preoperative mean of 24.6 ± 6.33 mmHg to 16.5 ± 4.4 mmHg (p < 0.001) at 12 months and 16.1 ± 3.4 mmHg (p < 0.001), at 24 months. Similarly, a significant reduction in the number of glaucoma drugs needed was observed, varying from 2.71 to 0.22 (p < 0.001) and 0.4 (p < 0.001), 1 and 2 years after surgery. Goniopuncture with the Nd:Yag Laser was performed in 30 eyes (62.5%) with a mean time between the surgery and the procedure of 150 days, producing a mean IOP reduction of 4.0 mmHg (p < 0.001). The main intraoperative complications were microperforation of the trabeculodescemetic membrane (TDM) in 1 eye (2.08%) The main early postoperative complications were seidel at 24 h in 11 eyes (22.91%), hyphema in 7 eyes (14.58%), choroidal detachment in 3 eyes (6.25%) with macular folds in 2 (4.16%) and need for additional mitomycin injections in 2 eyes (4.16%). All these complications were spontaneously resolved. No correlation between these complications and final IOP was found, but a significant correlation between the presence of hyphema and higher IOP 24 months postoperatively (p = 0.048) was observed. DS with supraciliary hema implant is a safe and effective technique for the management of OAG. The presence of hyphema during the first week after the surgery could be considered as a negative prognostic factor in DS with supraciliary implantation.


The Potential of Food Fortification to Add Micronutrients in Young Children and Women of Reproductive Age - Findings from a Cross-Sectional Survey in Abidjan, Côte d'Ivoire.
Poor micronutrient intakes are a major contributing factor to the high burden of micronutrient deficiencies in Côte d'Ivoire. Large-scale food fortification is considered a cost-effective approach to deliver micronutrients, and fortification of salt (iodine), wheat flour (iron and folic acid), and vegetable oil (vitamin A) is mandatory in Côte d'Ivoire. A cross-sectional survey on households with at least one child 6-23 months was conducted to update coverage figures with adequately fortified food vehicles in Abidjan, the capital of and largest urban community in Côte d'Ivoire, and to evaluate whether additional iron and vitamin A intake is sufficient to bear the potential to reduce micronutrient malnutrition. Information on demographics and food consumption was collected, along with samples of salt and oil. Wheat flour was sampled from bakeries and retailers residing in the selected clusters. In Abidjan, 86% and 97% of salt and vegetable oil samples, respectively, were adequately fortified, while only 32% of wheat flour samples were adequately fortified, but all samples contained some added iron. There were no major differences in additional vitamin A and iron intake between poor and non-poor households. For vitamin A in oil, the additional percentage of the recommended nutrient intake was 27% and 40% for children 6-23 months and women of reproductive age, respectively, while for iron from wheat flour, only 13% and 19% could be covered. Compared to previous estimates, coverage has remained stable for salt and wheat flour, but improved for vegetable oil. Fortification of vegetable oil clearly provides a meaningful additional amount of vitamin A. This is not currently the case for iron, due to the low fortification levels. Iron levels in wheat flour should be increased and monitored, and additional vehicles should be explored to add iron to the Ivorian diet.


Quasiparticle interference, quasiparticle interactions, and the origin of the charge density wave in 2H-NbSe2.
We show that a small number of intentionally introduced defects can be used as a spectroscopic tool to amplify quasiparticle interference in 2H-NbSe2 that we measure by scanning tunneling spectroscopic imaging. We show, from the momentum and energy dependence of the quasiparticle interference, that Fermi surface nesting is inconsequential to charge density wave formation in 2H-NbSe2. We demonstrate that, by combining quasiparticle interference data with additional knowledge of the quasiparticle band structure from angle resolved photoemission measurements, one can extract the wave vector and energy dependence of the important electronic scattering processes thereby obtaining direct information both about the fermiology and the interactions. In 2H-NbSe2, we use this combination to confirm that the important near-Fermi-surface electronic physics is dominated by the coupling of the quasiparticles to soft mode phonons at a wave vector different from the charge density wave ordering wave vector.


The Insulin Receptor Plays a Critical Role in T Cell Function and Adaptive Immunity.
T cell activation is an energy-demanding process fueled by increased glucose consumption and accompanied by upregulation of the insulin receptor (INSR). In this article, we report that silencing the INSR in inducible knockdown rats impairs selective T cell functions but not thymocyte development. Glucose transport and glycolysis in activated CD4+ T cells were compromised in the absence of the INSR, which was associated with alterations in intracellular signaling pathways. The observed metabolic defects coincided with reduced cytokine production, proliferation, and migration, as well as increased apoptosis of CD4+ T cells. The cytotoxicity of CD8+ T cells in response to alloantigens was also diminished under these conditions, whereas the frequency and suppressive capacity of regulatory T cells were unaffected. The observed impairments proved to be decisive in vivo because silencing of the INSR attenuated clinical symptoms in animal models of acute graft-versus-host disease and multiple sclerosis. Taken together, our results suggest that upregulation of the INSR on T cells following activation is required for efficient adaptive immunity.


Shifts in diversification rate with the origin of angiosperms.
The evolutionary success of flowering plants has been attributed to key innovations that originated at the base of that clade. Maximum likelihood methods were used to assess whether branching rate increases were correlated with the origin of these traits. Four hypotheses for the basal relationships of angiosperms were examined by methods that are robust to uncertainty about the timing of internal branch points. Recent hypotheses based on molecular evidence, or on a combination of molecular and morphological characters, imply that large increases in branching rate did not occur until after the putative key innovations of angiosperms had evolved.


Ecological mechanisms underlying the sustainability of the agricultural heritage rice-fish coculture system.
For centuries, traditional agricultural systems have contributed to food and livelihood security throughout the world. Recognizing the ecological legacy in the traditional agricultural systems may help us develop novel sustainable agriculture. We examine how rice-fish coculture (RF), which has been designated a "globally important agricultural heritage system," has been maintained for over 1,200 y in south China. A field survey demonstrated that although rice yield and rice-yield stability are similar in RF and rice monoculture (RM), RF requires 68% less pesticide and 24% less chemical fertilizer than RM. A field experiment confirmed this result. We documented that a mutually beneficial relationship between rice and fish develops in RF: Fish reduce rice pests and rice favors fish by moderating the water environment. This positive relationship between rice and fish reduces the need for pesticides in RF. Our results also indicate a complementary use of nitrogen (N) between rice and fish in RF, resulting in low N fertilizer application and low N release into the environment. These findings provide unique insights into how positive interactions and complementary use of resource between species generate emergent ecosystem properties and how modern agricultural systems might be improved by exploiting synergies between species.


Effect of Santhi Kriya on certain psychophysiological parameters: a preliminary study.
Santhi Kriya is a mixture of combined yogic practices of breathing and relaxation. Preliminary attempts were made to determine the effect of Santhi Kriya on certain psychophysiological parameters. Eight healthy male volunteers of the age group 25.9 +/- 3 (SD) years were subjected to Santhi Kriya practice daily for 50 minutes for 30 days. The volunteer's body weight, blood pressure, oral temperature, pulse rate, respiration, ECG and EEG were recorded before and after the practice on the 1st day and subsequently on 10th, 20th and 30th day of their practice. They were also given a perceptual acuity test to know their cognitive level on the 1st day and also at the end of the study i.e., on the 30th day. Results indicate a gradual and significant decrease in the body weight from 1st to 30th day (P less than 0.001) and an increase in alpha activity of the brain (P less than 0.001) during the course of 30 days of Santhi Kriya practice. Increase of alpha activity both in occipital and pre-frontal areas of both the hemispheres of the brain denotes an increase of calmness. This study also revealed that Santhi Kriya practice increases oral temperature by 3 degrees F and decreases respiratory rate significantly (P less than 0.05) on all practice days. Other parameters were not found to be altered significantly. It is concluded that the Santhi Kriya practice for 30 days reduces body weight and increases calmness.


Perioperative Dynamics of TLR2, TLR4, and TREM-1 Expression in Monocyte Subpopulations in the Setting of On-Pump Coronary Artery Bypass Surgery.
Hypercytokinemia plays a key role in the pathogenesis of systemic inflammatory response syndrome (SIRS). Monocytes are the main source of cytokines in the early inflammatory phase. Simultaneous stimulation of toll-like receptors (TLRs) and triggering receptor expressed on myeloid cells (TREM-1) activating receptor on monocytes results in the amplification of the inflammatory signal and multiple increase in proinflammatory cytokine production. The dynamics of those receptors expression on monocyte surface of patients with uncomplicated SIRS course followed coronary artery bypass surgery (CABG) was studied. The increase in TLR2 and TREM-1 expression on the first day after CABG induces proinflammatory and amplification potentials of monocytes in that period. The decrease in TLR2 surface expression on the seventh day compared to the preoperative values can be regarded as a mechanism limiting inflammatory response. The highest level of TLR2, TLR4, and TREM-1 surface expression was observed in CD14(hi)CD16(+) monocyte subpopulation, confirming its proinflammatory profile.


Identification of Soybean mosaic virus Strains by RT-PCR/RFLP Analysis of Cylindrical Inclusion Coding Region.
A reverse-transcriptase polymerase chain reaction/restriction fragment length polymorphism (RT-PCR/RFLP) was employed successfully for detection and identification of Soybean mosaic virus (SMV) strains. A primer pair amplifying a 1,385-bp fragment of the cylindrical inclusion (CI) coding region was used for RT-PCR and the RFLP profiles of the RT-PCR products were compared after restriction digestion with RsaI, EcoRI, or AccI restriction endonucleases. These enzymes were chosen based on the nucleotide sequences of SMV strains G2, G5, G5H, G7, and G7H in the CI coding region. These five strains, as well as seedborne SMV isolates from local soybean cultivars, could be differentiated by RT-PCR/RFLP analysis. The results correlated well with strain identification by symptom phenotypes produced on differential cultivars inoculated with strains and isolates. The sensitivity of RT-PCR enabled detection of SMV from plants with necrotic symptoms in which the number of virus particles was too low to be detected by enzyme-linked immunosorbent assay.


Outcome of Japanese Encephalitis Virus (JEV) Infection in Pediatric and Adult Patients at Mahosot Hospital, Vientiane, Lao PDR.
Although Japanese encephalitis virus (JEV) infection is an important cause of acute febrile illness in Lao PDR (Laos), patient outcome has not been evaluated. We prospectively followed up 123 JEV-infected patients (70 children < 15 years and 53 adults ≥ 15 years) admitted at Mahosot Hospital, Vientiane, from 2003 to 2013. Japanese encephalitis virus infection was diagnosed by the detection of anti-JEV IgM in cerebrospinal fluid and/or IgM seroconversion. Neurological sequelae were assessed using the Liverpool Outcome Score (LOS), total (maximum score = 75), and final (maximum score = 5). The median (interquartile range [IQR]) age of the patients was 12.0 (7.5-18.8) years, and 57% were male. The median (IQR) duration of patients' follow-up was 4.5 (3.2-7.3) years. Of all patients, 10/123 (8.1%) died during hospitalization, and 13/123 (10.6%) died at home after discharge, giving a mortality of 18.7% (23/123) (33 [26.8%] patients were lost to follow-up). The frequency of neurological sequelae at the last follow-up was 61.2% (48.4% in adults and 69.4% in children, P = 0.135). The proportion of patients with severe and moderate functional impairment at the last follow-up was significantly higher in children (25%) than in adults (6.5%), P = 0.042. Half of the patients who were still alive at the last follow-up (67) and for whom LOS data were available (22) had improvements in their total and final LOS between discharge and the last follow-up. The total and final LOS at discharge were not significantly different between children and adults, but total LOS at the last follow-up was significantly higher in adults than in children (median [IQR]: 74.5 [73-75] versus 73.0 [73-75], P = 0.019).


Flagellar adhesion in Chlamydomonas induces synthesis of two high molecular weight cell surface proteins.
Because our previous studies (Snell, W.J., and W.S. Moore, 1980, J. Cell Biol. 84:203- 210) on the mating reaction of chlamydomonas reinhardtii showed that there was an adhesion-induced turnover of proteins whose synthesis is induced during aggregation. Analysis by SDS PAGE and autoradiography showed that proteins of 220,000 M(r) and 165, 000 M(r) (designated A(1) and A(2) respectively) consistently showed a high rate of synthesis only in flagella or flagellar membrane-enriched fractions prepared from aggregating gametes. Since the two proteins were soluble in the non-ionic detergent NP-40 and were removed from intact cells by a brief pronase treatment, it is likely that A(1) and A(2) are membrane proteins expose on the cell surface. A(1) and A(2) were each synthesized by gametes of both mating types (mt(-) and mt(+)) and synthesis of these two proteins could be detected in the normal mating reaction (wild type mt(-) and mt(+)), in mixtures of mt(-) and impotent mt(+) gametes (which could aggregate but not fuse), and in mixtures of gametes of a single mating type with isolated flagella of the opposite mating type. Cells aggregating in tunicamycin, an inhibitor of protein glycosylation, lost their adhesiveness during aggregation and did not synthesize the 220,000 M(r) protein but instead produced a protein (possibly an underglycosylated form of A(1)) of slightly lower mol wt. The 220,000 and 165,000 M(R) proteins appeared to be flagellar proteins and not cell wall proteins because A(1) and A(2) did not co-migrate with previously identified cell wall proteins, and synthesis of the two proteins could not be detected in flagella-less (bald-2) mutant cells. Analysis of the adhesive activity of sucrose gradient fraction of detergent (octyl glucoside)-solubilized flagellar membranes revealed that fractions containing A(1) and A(2) did not have detectable adhesive activity. The possibility remains that A(1) and A(2) are adhesion molecules whose activity could not be measured in the assay we used. Alternatively, the 220,000 and 165,000 M(r) proteins may be inactivated adhesion molecules or else they may be flagellar surface proteins involved only indirectly in the adhesion process.


Dietary intake of cholesterol is positively associated and use of cholesterol-lowering medication is negatively associated with prevalent age-related hearing loss.
We aimed to assess associations between dietary intake of fats (saturated and monounsaturated fats and cholesterol) and certain food groups (butter, margarine, and nuts) with the prevalence, incidence, and progression of age-related hearing loss. We also aimed to investigate the link between serum lipids and cholesterol-lowering medication (statins) and hearing loss. The Blue Mountains Hearing Study is a population-based survey of age-related hearing loss. Hearing loss was measured in 2956 participants (aged ≥50 y) and was defined as the pure-tone average (PTA) of frequencies 0.5, 1.0, 2.0, and 4.0 kHz > 25 dB hearing level (PTA(0.5-4 kHz)). Dietary data were collected using a semiquantitative FFQ. After multivariable adjustment, the likelihood of prevalent hearing loss increased from the lowest (reference) to the highest quartile of dietary cholesterol intake (P-trend = 0.04). Among persons self-reporting statin use (n = 274), a 48% reduced odds of prevalent hearing loss was observed after multivariable adjustment [OR = 0.52 (95% CI = 0.29-0.93)]. Participants in the second and 3rd quartiles of dietary monounsaturated fat intake compared with those in the first quartile (reference) had a significantly reduced risk of hearing loss progression 5 y later [multivariable-adjusted OR = 0.39 (95% CI = 0.21-0.71)] and [OR = 0.51 (95% CI = 0.29-0.91)], respectively. Our results suggest that a diet high in cholesterol could have adverse influences on hearing, whereas treatment with statins and consumption of monounsaturated fats may have a beneficial influence.


Engaging the Family in the Care of Young Adults With Substance Use Disorders.
Efforts to engage young adults with substance use disorders in treatment often focus on the individual and do not consider the role that the family can play in the recovery process. In summarizing the proceedings of a longitudinal meeting on substance use among young adults, this special article outlines three key principles concerning the engagement of broader family units in substance use treatment: (1) care should involve family members (biological, extended, or chosen); (2) these family members should receive counseling on evidence-based approaches that can enhance their loved one's engagement in care; and (3) family members should receive counseling on evidence-based strategies that can improve their own health. For each principle, we provide an explanation of our guidance to practitioners, supportive evidence, and additional practice considerations.


Measuring the population burden of fatal and nonfatal injury.
The value of measuring the population burden of fatal and nonfatal injury is well established. Population health metrics are important for assessing health status and health-related quality of life after injury and for integrating mortality, disability, and quality-of-life consequences. A frequently used population health metric is the disability-adjusted life-year. This metric was launched in 1996 in the original Global Burden of Disease and Injury study and has been widely adopted by countries and health development agencies alike to identify the relative magnitude of different health problems. Apart from its obvious advantages and wide adherence, a number of challenges are encountered when the disability-adjusted life-year is applied to injuries. Validation of disability-adjusted life-year estimates for injury has been largely absent. This paper provides an overview of methods and existing knowledge regarding the population burden of injury measurement. The review of studies that measured burden of injury shows that estimates of the population burden remain uncertain because of a weak epidemiologic foundation; limited information on incidence, outcomes, and duration of disability; and a range of methodological problems, including definition and selection of incident and fatal cases, choices in selection of assessment instruments and timings of use for nonfatal injury outcomes, and the underlying concepts of valuation of disability. Recommendations are given for methodological refinements to improve the validity and comparability of future burden of injury studies.


FoxO3a involved in neutrophil and T cell survival is overexpressed in rheumatoid blood and synovial tissue.
FoxO3a is a transcriptional factor implicated in cell cycle regulation and apoptosis. Since rheumatoid arthritis (RA) is associated with apoptosis defects, the expression level, regulation and phosphorylation status of FoxO3a was investigated in blood and synovium from patients with RA. In microarray experiments, an overexpression of FoxO3a mRNA was observed in blood from patients with RA compared with healthy controls. FoxO3a mRNA expression was quantified in polymorphonuclear cells (PMNs) and peripheral blood mononuclear cells from patients with RA by qRT-PCR. Total FoxO3a and phosphorylated FoxO3a (pFoxO3a) protein expression was analysed in blood leucocytes from patients with RA versus controls and in synovium from patients with RA versus patients with osteoarthritis (OA) by immunostaining. FoxO3a mRNA and protein expression levels were increased in blood from patients with RA compared with controls. FoxO3a overexpression was primarily observed in PMNs. In synovium from patients with RA, both total and inactive phosphorylated FoxO3a proteins were detected. FoxO3a was detected primarily in the sublining T lymphocytes of synovium from patients with RA compared with the lining layer tissue from patients with RA and OA, underlying a role for FoxO3a proteins in inflammation in RA. The overexpression of FoxO3a in blood from patients with RA, particularly in PMNs, suggests a potential role for this gene in the pathogenesis of RA through increased survival of blood PMNs. In synovium from patients with RA, FoxO3a mainly detected in inflammatory aggregates may also regulate the chronic survival of T lymphocytes.


Are Spouses' Sleep Problems a Mechanism Through Which Health is Compromised? Evidence Regarding Insomnia and Heart Disease.
Symptoms of insomnia have been widely identified as risk factors for health, including heart disease. Despite the expansive and growing literature on health concordance among coupled individuals, few studies have examined insomnia as a shared risk factor for heart disease among middle-aged and older couples. This study examined the association between insomnia and incident heart disease among couples. A dyadic modeling approach was employed to investigate the relationships between one's own insomnia and partners' insomnia for the risk of incident heart disease for each partner. Data from the 2010, 2012, and 2014 Health and Retirement Study were utilized in a prospective research design (N = 3,221 couples). Actor-partner interdependence models were employed to estimate actor and partner effects of insomnia symptoms for incident heart disease over the 4 year observation period. Insomnia symptoms measured at baseline were related to an increased risk for heart disease for husbands, whereas for wives the association was attenuated after other health measures were controlled. Wives' insomnia was related to an increased risk of incident heart disease for husbands but husbands' insomnia was not related to wives' risk of heart disease. This study showed how subjective insomnia symptoms among middle-aged and older adults in intimate partnerships are associated with their heart disease risk. Further research is needed to verify the results with objective measures of sleep problems and heart disease.


[Pulmonary hypertension due to chronic lung disease: Recommendations of the Cologne Consensus Conference 2016].
The 2015 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH) but also some aspects of pulmonary hypertension (PH) associated with chronic lung disease. The European Guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists, phosphodiesterase-5 inhibitors, sGC stimulators) have not been sufficiently investigated in other forms of PH. Therefore, the European Guidelines do not recommend the use of these drugs in patients with chronic lung disease and PH. This recommendation, however, is not always in agreement with medical ethics as physicians feel sometimes inclined to treat other form of PH which may affect quality of life and survival of these patients in a similar manner. To this end, it is crucial to consider the severity of both PH and the underlying lung disease. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany, to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. Several working groups were initiated, one of which was dedicated to the diagnosis and treatment of PH in patients with chronic lung disease. The recommendations of this working group are summarized in the present paper.


Suicidal ideation and mental health disorders in young school children across Europe.
The aim of this study is to measure the prevalence of suicidal ideation and thoughts of death in elementary school children in a European survey and to determine the associated socio-demographic and clinical factors. Data refer to children aged 6-12 (N=7062) from Italy, Turkey, Romania, Bulgaria, Lithuania, Germany, and the Netherlands randomly selected in primary schools. Suicidal thoughts and death ideation were measured using a computerized pictorial diagnostic tool from the Dominic Interactive (DI) completed by the children. The Strengths and Difficulties Questionnaire (SDQ) was administrated to teachers and parents along with a socio-demographic questionnaire. Suicidal ideation was present in 16.96% of the sample (from 9.9 in Italy to 26.84 in Germany), death thoughts by 21.93% (from 7.71% in Italy to 32.78 in Germany). SI and DT were more frequent in single-parent families and large families. Externalizing disorders were strongly correlated with SI and DT after controlling for other factors and this was true for internalizing disorders only when reported by the children. Recognizing suicidal ideation in young children may be recommended as part of preventive strategies such as screening in the context of the presence of any mental health problems whether externalizing or internalizing.


Family planning use and fertility desires among women living with HIV in Kenya.
Enabling women living with HIV to effectively plan whether and when to become pregnant is an essential right; effective prevention of unintended pregnancies is also critical to reduce maternal morbidity and mortality as well as vertical transmission of HIV. The objective of this study is to examine the use of family planning (FP) services by HIV-positive and HIV-negative women in Kenya and their ability to achieve their fertility desires. Data are derived from a random sample of women seeking family planning services in public health facilities in Kenya who had declared their HIV status (1887 at baseline and 1224 at endline) and who participated in a longitudinal study (the INTEGRA Initiative) that measured the benefits/costs of integrating HIV and sexual/reproductive health services in public health facilities. The dependent variables were FP use in the last 12 months and fertility desires (whether a woman wants more children or not). The key independent variable was HIV status (positive and negative). Descriptive statistics and multivariate logistic regression analysis were used to describe the women's characteristics and to examine the relationship between FP use, fertility desires and HIV status. At baseline, 13 % of the women sampled were HIV-positive. A slightly higher proportion of HIV-positive women were significantly associated with the use of FP in the last 12 months and dual use of FP compared to HIV-negative women. Regardless of HIV status, short-acting contraceptives were the most commonly used FP methods. A higher proportion of HIV-positive women were more likely to be associated with unintended (both mistimed and unwanted) pregnancies and a desire not to have more children. After adjusting for confounding factors, the multivariate results showed that HIV-positive women were significantly more likely to be associated with dual use of FP (OR = 3.2; p < 0.05). Type of health facility, marital status and household wealth status were factors associated with FP use. Factors associated with fertility desires were age, education level and household wealth status. The findings highlight important gaps related to utilization of FP among WLHIV. Despite having a greater likelihood of reported use of FP, HIV-positive women were more likely to have had an unintended pregnancy compared to HIV-negative women. This calls for need to strengthen family planning services for WLHIV to ensure they have better access to a wide range of FP methods. There is need to encourage the use of long-acting reversible contraceptive (LARC) to reduce the risk of unintended pregnancy and prevention of vertical transmission of HIV. However, such policies should be based on respect for women's right to informed reproductive choice in the context of HIV/AIDS. NCT01694862.


Patient education - evaluation of a complex intervention.
Diabetes education or self-management programmes are complex interventions. Their evaluation is difficult because of problems in identifying and separately assessing the effect of the various components of the intervention. A phased approach defining sequential stages of a continuum of increasing evidence has been proposed as a framework for the design and evaluation of such complex interventions. As an example we present the available evidence for diabetes treatment and teaching programmes implemented in Germany. Evidence is compiled for structured group treatment and teaching programmes for Type I diabetes, non-insulin dependent Type II diabetes, and hypertension according to the following sequential stages of increasing evidence: (i) preclinical or theoretical phase; (ii) modelling the components of the intervention; (iii) exploratory trials; (iv) randomized controlled trials; (v) phase of implementation including replication and transfer to different settings. Evidence for most of these phases has been generated for the three programmes, although individual studies do not fulfill all important quality criteria by today's standards. The time span for gathering the evidence from the theoretical phase to surveillance after implementation was about 20 years. It can only be speculated which parts of the programmes are the most active ones. The presentation of a continuum of increasing evidence for diabetes education or self-management programmes could provide useful information for the appraisal of such complex interventions. Since this evidence cannot be readily extracted from databases we suggest that other research groups present their data in a similar way.


Insights and approaches using deep learning to classify wildlife.
The implementation of intelligent software to identify and classify objects and individuals in visual fields is a technology of growing importance to operatives in many fields, including wildlife conservation and management. To non-experts, the methods can be abstruse and the results mystifying. Here, in the context of applying cutting edge methods to classify wildlife species from camera-trap data, we shed light on the methods themselves and types of features these methods extract to make efficient identifications and reliable classifications. The current state of the art is to employ convolutional neural networks (CNN) encoded within deep-learning algorithms. We outline these methods and present results obtained in training a CNN to classify 20 African wildlife species with an overall accuracy of 87.5% from a dataset containing 111,467 images. We demonstrate the application of a gradient-weighted class-activation-mapping (Grad-CAM) procedure to extract the most salient pixels in the final convolution layer. We show that these pixels highlight features in particular images that in some cases are similar to those used to train humans to identify these species. Further, we used mutual information methods to identify the neurons in the final convolution layer that consistently respond most strongly across a set of images of one particular species. We then interpret the features in the image where the strongest responses occur, and present dataset biases that were revealed by these extracted features. We also used hierarchical clustering of feature vectors (i.e., the state of the final fully-connected layer in the CNN) associated with each image to produce a visual similarity dendrogram of identified species. Finally, we evaluated the relative unfamiliarity of images that were not part of the training set when these images were one of the 20 species "known" to our CNN in contrast to images of the species that were "unknown" to our CNN.