Surface/Interfacial Engineering of Inorganic Low-Dimensional Electrode Materials for Electrocatalysis.
Exploitation of highly active and cost-effective electrode materials for the design of new types of renewable energy storage and conversion systems has been tremendously stimulated by the higher attention being paid to global energy security and invention of alternative clean sustainable energy technologies. Low-dimensional solid materials with special atomic and electronic structures are deemed desirable platforms for establishing clear relationships between surface/interface structure characteristics and electrocatalytic activity, representing enormous potential in the pursuit of high-performance electrocatalysts. Recent achievements revealed that surface and interfacial atomic engineering is capable of achieving novel physical and chemical properties as well as superior synergistic effects in inorganic low-dimensional nanomaterials for electrocatalysis. Compared to bulk counterparts, the electronic structure in the surface of inorganic low-dimensional nanomaterials is more sensitive to and can thus be regulated more easily by surface and interfacial modification strategies, resulting in greatly optimized electrocatalytic performance. In this Account, we focus on recent progress in surface and interfacial modification strategies to efficaciously engineer the electrocatalytic performance of inorganic low-dimensional electrode materials. We summarize several important regulation strategies of dimensional confinement, incorporation, surface reconstruction, interface modulation, and defect engineering, which immensely optimize the spin configuration, electrical conductivity, catalytic active site exposure, and reaction energy barrier of inorganic electrode material. At dimensionally confined atomic-scale thickness, more surface-facet atoms are exposed as active sites, which provide an ideal platform for applying surface incorporation and defect engineering, subsequently producing more catalytic active sites and better adsorption free energy for the improvement of catalytic activity. Moreover, regulation of the interfacial character of electrode materials, such as the surface strain, contact area, and bridged bonds, can optimize the electron transfer capacity and reaction kinetics process. On the other hand, once exposed to a strong alkaline solution under oxidizing potentials, the real active layer of electrode materials (such as transition-metal sulfides, nitrides, and phosphides) could be activated by a surface reconstruction strategy, realizing a unique core-shell structure with a highly conductive electron transfer channel inside and highly active catalytic sites outside for electrocatalysis. Based on these points of view, focusing on inorganic low-dimensional electrode materials, the proper choice of surface and interfacial modification strategies would effectively modulate their electrocatalytic activity, realizing unlimited potential applications in promising areas of electrocatalytic water splitting, rechargeable metal batteries, and fuel cells. Overall, we anticipate that surface and interfacial regulation approaches can provide a new understanding of the design of inorganic electrode materials, facilitating the rapid promotion of electrocatalytic performance in electrode materials for electrocatalysis.


Costs of a successful public-private partnership for TB control in an urban setting in Nepal.
In South Asia a large number of patients seek treatment for TB from private practitioners (PPs), and there is increasing international interest in involving PPs in TB control. To evaluate the feasibility, effectiveness and costs of public-private partnerships (PPPs) for TB control, a PPP was developed in Lalitpur municipality, Nepal, where it is estimated that 50% of patients with TB are managed in the private sector. From the clinical perspective the PPP was shown to be effective. The aim of this paper is to assess and report on the costs involved in the PPP scheme. The approach to costing took a comprehensive view, with inclusion of costs not only incurred by health facilities but also social costs borne by patients and their escorts. Semi-structured questionnaires and guided interviews were used to collect start-up and recurrent costs for the scheme. Overall costs for treating a TB patient under the PPP scheme averaged US$89.60. Start-up costs per patient represented 12% of the total budget. Half of recurrent costs were incurred by patients and their escorts, with institutional costs representing most of the rest. Female patients tended to spend more and patients referred from the private sector had the highest reported costs. Treating TB patients in the PPP scheme had a low additional cost, while doubling the case notification rate and maintaining a high success rate. Costs incurred by patients and their escorts were the largest contributors to the overall total. This suggests a focus for follow-up studies and for cost-minimisation strategies.


Epidemiology of RBC Transfusions in Patients With Severe Acute Kidney Injury: Analysis From the Randomized Evaluation of Normal Versus Augmented Level Study.
To assess the epidemiology and outcomes associated with RBC transfusion in patients with severe acute kidney injury requiring continuous renal replacement therapy. Post hoc analysis of data from a multicenter, randomized, controlled trial. Thirty-five ICUs in Australia and New Zealand. Cohort of 1,465 patients enrolled in the Randomized Evaluation of Normal versus Augmented Level replacement therapy study. Daily information on morning hemoglobin level and amount of RBC transfused were prospectively collected in the Randomized Evaluation of Normal versus Augmented Level study. We analyzed the epidemiology of such transfusions and their association with clinical outcomes. Overall, 977 patients(66.7%) received a total of 1,192 RBC units. By day 5, 785 of 977 transfused patients (80.4%) had received at least one RBC transfusion. Hemoglobin at randomization was lower in transfused than in nontransfused patients (94 vs 111 g/L; p < 0.001). Mean daily hemoglobin was 88 ± 7 and 99 ± 12 g/L in transfused and nontransfused patients. Among transfused patients, 228 (46.7%) had died by day 90 when compared with 426 (43.6%) of nontransfused patients (p = 0.27). Survivors received on average 316 ± 261 mL of RBC, whereas nonsurvivors received 302 ± 362 mL (p = 0.42). On multivariate Cox regression analysis, RBC transfusion was independently associated with lower 90-day mortality (hazard ratio, 0.55; 95% CI, 0.38-0.79). However, we found no independent association between RBC transfusions and mortality when the analyses were restricted to patients surviving at least 5 days (hazard ratio, 1.29; 95% CI, 0.90-1.85). We found no independent association between RBC transfusion and renal replacement therapy-free days, mechanical ventilator-free days, or length of stay in ICU or hospital. In patients with severe acute kidney injury treated with continuous renal replacement therapy, we found no association of RBC transfusion with 90-day mortality or other patient-centered outcomes. The optimal hemoglobin threshold for RBC transfusion in such patients needs to be determined in future randomized controlled trials.


[Prospective study of favorable factors in follow-up of drug addicted patients--apropos of 257 patients of the Cassini Center in Paris].
Assessing the effectiveness of treatment is one of the main concerns of any medical process. The different ways proposed for assuming the responsibility of drug addicts and their efficacy are greatly heterogeneous since drug-abusing takes on diverse forms. Thus, in order to closely target the request of drug addicts and adjust their follow-up, we undertook to study prospectively, for 3 months, a population of drug addicts taking medical advice for the first time at the Cassini center in Paris, with the assumption that some predictors may forecast outcomes. Data were obtained at the admission with a structured interview about socio-economic and demographic status, psychiatric disorders (assessed clinically according to DSM III-R and with HAD and MADRS scales), substance use and prior treatment history, environmental data (as well as familial substance use or support lending). Medical and paramedical referents have been interviewed after their first contact with the patient about his expectations and his motivation. Familial attendance at this first contact was noted as well as its implication in the programme. At the end of the study, we noted length of stay, regularity of follow up and clinical changes with a last interview of the staff. Half the time, patients' follow up doesn't last a month, drug abuse doesn't change in 6 out of 10 cases, and we only note 14% of durable abstinence. Polydrug abuse (over 80%) is not linked, here, with pejorative outcomes, in opposition to the usual literature. Heroin is the main substance used by our population (over 80%), other opiates, sedatives and alcohol are associated by more than 30% of these patients; cocaine is associated in a quarter of the cases. More than 10% of the patients are concerned by ecstasy and LSD. Cannabis use is common. Medical complaint (mainly viral diseases) at the beginning of the programme, concerns one of two patients. Only a few are initially known as being HIV positive, suggesting a great lack of information. Over forty percent of the patients are given a DSM III-R diagnosis at the end of the first medical advice, when a doubt subsists for a third of the other patients. Major depressive disorder for the first axis and borderline personality disorder for the second axis are the main disorders we founded. We also noted a large ratio (n = 13.5%) of schizophrenic disorders. Univariate analysis: length and regularity of the programmes are key factors of their efficacy. A long follow-up is also required to improve patients' socio-economical status. Initial psychiatric disorders are linked, in our study as well as in literature, with longer stays in therapeutic programms. By revenge, psychiatric disorders at the third month (over 10%) are linked with poorer outcomes. We noted with interest that, in our sample, neither imprisonment in the past (over 40%, but we noted several imprisonments in a case out of two), or intraveinous route at any moment of the patient's life time (40%), or else a programm caused by a court (a quarter of the patients) are of wrong prognosis. Relatives' implication in the programm is linked with favorable outcomes. Multivariate analysis draws 3 independent clusters about the length of stay. One concerns patient's motivation as assessed by medical staff. An other one concerns patient's relatives' implication in the care. A third one is about the begining of the treatment: an initial medical prescrition and a psychological help are linked with favorable outcomes. About the efficacy, multivariate analysis isolates 4 independant clusters. Prior drug abuse programmes (one out of three patients) are associated with poorer outcomes, when, by revenge, familial relationship initially seen by the patient as (very) satisfying, patient's motivation, and, again, an initial medical prescription are linked with better outcomes. The study of those of the patients whose programme lasted more then 3 months but without any appreciable benefit shows that a long follow-up is successful when it is regular, when it provides a socio-economical status improvement and when the patient is given access to insight. For these patients, the (old) age is associated with better outcomes. By revenge, such a 3 months follow-up is not able to reduce drug abuse when a psychiatric disorder exists at the third month. Patients whose treatment was referred by a court don't differ from the others: their length of stay and outcomes are the same. Our study confirms our initial hypothesis according to witch subgroups in our population of drug abusers should be isolated and that some predictors of outcomes should be described. Three points seem important to be discussed. First, a medical prescription appears to be important to initiate the relationship between the patient and his practicioner. We have never see any report about this particular point. (ABSTRACT TRUNCATED)


Dose-Dependent Application of Straw-Derived Fulvic Acid on Yield and Quality of Tomato Plants Grown in a Greenhouse.
Fulvic acids are organic compounds widely distributed in soils, and the application of fulvic acids is thought to increase crop yield and quality. However, the effects vary among various sources and doses of fulvic acids and environmental and growth conditions of crops. Here, we investigated the effects of bioresource-derived (corn straw) fulvic acids on plant production and quality of tomato plants and soil chemical properties in soil cultures while experiments on seed germination and hydroponics were conducted to explore the underlying mechanism. Base dressing with 2.7 g kg-1 increased the yield of tomato by 35.0% at most as increased fruit number. Fulvic acids increased the concentrations of minerals, such as Ca, Fe, and Zn and the concentrations of citric, malic, and some amino acids in berries of tomato but did not affect the concentrations of soluble sugars and aromatic substances in tomato fruits. Similarly, fulvic acids at 80-160 mg L-1 increased germination rate, growth vigor, and radicle elongation of tomato seeds while it increased plant biomass, concentrations of nutrients, and root length of tomato plants in hydroponics to the greatest extent in general. The increases in yield and quality can be attributed to the improvement in root growth and, thus, increased nutrient uptake. In addition, the base application of fulvic acids improved soil cation exchange capacity and soil organic matter to an extent. In conclusion, base dressing and the addition into solution of fulvic acids at moderate doses facilitate root growth and nutrient uptake and, thus, vegetable production and quality; therefore, fulvic acids can be an effective component for designing new biofertilizers for sustainable agricultural production.


Are you tuned in? The challenges of seizure identification in children with intellectual disability - A potential for video-based care-pathway.
This qualitative study explores the challenges parents/carers face in seizure identification in children with coexisting epilepsy and intellectual disability (ID). Semi-structured interviews with parents/carers provided ten hours of data, transcribed verbatim for data analysis. Themes and subthemes were identified and grouped to reflect the findings. The importance of knowing the child's usual behavior and recognizing changes to this was a consistent theme. All participants reported that being 'in tune' with their child helped in seizure recognition. Participants felt that the healthcare professionals (HCP) were poor at recognizing seizures in their children at times. They had mixed thoughts on the difficulty the presence of an ID contributes to seizure recognition. The severity of ID and the seizure type were the two main variables discussed. The study concludes that knowing the child well and understanding the usual behavior of the child is crucial to seizure recognition. A video-based care pathway with videos of both usual behavior and seizure activity available to the HCP to classify the events correctly may be potentially beneficial to improve patient care.


Effects of two different anesthetic protocols on cardiac flow measured by two dimensional phase contrast magnetic resonance imaging.
Companion animals are routinely anesthetized or heavily sedated for cardiac MRI studies, however effects of varying anesthetic protocols on cardiac function measurements are incompletely understood. The purpose of this prospective study was to compare effects of two anesthetic protocols (Protocol A: Midazolam, fentanyl; Protocol B: Dexmedetomidine) on quantitative and qualitative blood flow values measured through the aortic, pulmonic, mitral, and tricuspid valves using two-dimensional phase contrast magnetic resonance imaging (2D PC MRI) in healthy dogs. Mean flow per heartbeat values through the pulmonary artery (Qp) and aorta (Qs) were compared to right and left ventricular stroke volumes (RVSV, LVSV) measured using a reference standard of 2D Cine balanced steady-state free precession MRI. Pulmonary to systemic flow ratio (Qp/Qs) was also calculated. Differences in flow and Qp/Qs values generated using 2D PC MRI did not differ between the two anesthetic protocols (P = 1). Mean differences between Qp and RVSV were 3.82 ml/beat (95% limits of agreement: 3.62, -11.26) and 1.9 ml/beat (-7.86, 11.66) for anesthesia protocols A and B, respectively. Mean differences between Qs and LVSV were 1.65 ml/beat (-5.04, 8.34) and 0.03 ml/beat (-4.65, 4.72) for anesthesia protocols A and B, respectively. Mild tricuspid or mitral reflux was seen in 2/10 dogs using 2D PC MRI. No aortic or pulmonic insufficiency was observed. Findings from the current study indicated that these two anesthetic protocols yield similar functional measures of cardiac blood flow using 2D PC MRI in healthy dogs. Future studies in clinically affected patients are needed.


Genome-wide association study of insect bite hypersensitivity in Dutch Shetland pony mares.
Insect bite hypersensitivity (IBH) is the most common allergic disease present in horses worldwide. It has been shown that IBH is under genetic control, but the knowledge of associated genes is limited. We conducted a genome-wide association study to identify and quantify genomic regions contributing to IBH in the Dutch Shetland pony population. A total of 97 cases and 91 controls were selected and matched on withers height, coat colour and pedigree to minimise the population stratification. A blood sample was collected from participating Shetland pony mares, their IBH phenotype was scored and the owner filled in a questionnaire. A total of 40 021 single-nucleotide polymorphisms (SNPs) were fitted in a univariable logistic model fitting an additive effect. Analysis revealed no effects of population stratification. Significant associations with IBH were detected for 24 SNPs on 12 chromosomes [-log(10) (P-value) > 2.5]. Odds ratios of allele substitution effects of the unfavourable allele were between 1.94 and 5.95. The most significant SNP was found on chromosome 27, with an odds ratio of 2.31 and with an allele frequency of the unfavourable allele of 0.72 in cases and 0.53 in controls. Genome-wide association studies on additional horse populations are desired to validate the identified associations, to identify the genes involved in IBH and to develop genomic tools to decrease IBH prevalence.


Gastrointestinal tract size, total-tract digestibility, and rumen microflora in different dairy cow genotypes.
The superior milk production efficiency of Jersey (JE) and Jersey × Holstein-Friesian (JE × HF) cows compared with Holstein-Friesian (HF) has been widely published. The biological differences among dairy cow genotypes, which could contribute to the milk production efficiency differences, have not been as widely studied however. A series of component studies were conducted using cows sourced from a longer-term genotype comparison study (JE, JE × HF, and HF). The objectives were to (1) determine if differences exist among genotypes regarding gastrointestinal tract (GIT) weight, (2) assess and quantify whether the genotypes tested differ in their ability to digest perennial ryegrass, and (3) examine the relative abundance of specific rumen microbial populations potentially relating to feed digestibility. Over 3 yr, the GIT weight was obtained from 33 HF, 35 JE, and 27 JE × HF nonlactating cows postslaughter. During the dry period the cows were offered a perennial ryegrass silage diet at maintenance level. The unadjusted GIT weight was heavier for the HF than for JE and JE × HF. When expressed as a proportion of body weight (BW), JE and JE × HF had a heavier GIT weight than HF. In vivo digestibility was evaluated on 16 each of JE, JE × HF, and HF lactating dairy cows. Cows were individually stalled, allowing for the total collection of feces and were offered freshly cut grass twice daily. During this time, daily milk yield, BW, and dry matter intake (DMI) were greater for HF and JE × HF than for JE; milk fat and protein concentration ranked oppositely. Daily milk solids yield did not differ among the 3 genotypes. Intake capacity, expressed as DMI per BW, tended to be different among treatments, with JE having the greatest DMI per BW, HF the lowest, and JE × HF being intermediate. Production efficiency, expressed as milk solids per DMI, was higher for JE than HF and JE × HF. Digestive efficiency, expressed as digestibility of dry matter, organic matter, N, neutral detergent fiber, and acid detergent fiber, was higher for JE than HF. In grazing cows (n=15 per genotype) samples of rumen fluid, collected using a transesophageal sampling device, were analyzed to determine the relative abundance of rumen microbial populations of cellulolytic bacteria, protozoa, and fungi. These are critically important for fermentation of feed into short-chain fatty acids. A decrease was observed in the relative abundance of Ruminococcus flavefaciens in the JE rumen compared with HF and JE × HF. We can deduce from this study that the JE genotype has greater digestibility and a different rumen microbial population than HF. Jersey and JE × HF cows had a proportionally greater GIT weight than HF. These differences are likely to contribute to the production efficiency differences among genotypes previously reported.


Chloroplast and cytosolic glutamine synthetase are encoded by homologous nuclear genes which are differentially expressed in vivo.
We have shown that the individual members of the plant gene family for glutamine synthetase (GS) are differentially expressed in vivo, and each encode distinct GS polypeptides which are targeted to different subcellular compartments (chloroplast or cytosol). At the polypeptide level, chloroplast GS (GS2) and cytosolic GS (GS1 and GSn) are distinct and show an organ-specific distribution. We have characterized full length cDNA clones encoding chloroplast or cytosolic GS of pea. In vitro translation products encoded by three different GS cDNA clones, correspond to the mature GS2, GS1, and GSn polypeptides present in vivo. pGS185 encodes a precursor to the chloroplast GS2 polypeptide as shown by in vitro chloroplast uptake experiments. The pGS185 translation product is imported into the chloroplast stroma and processed to a polypeptide which corresponds in size and charge to that of mature chloroplast stromal GS2 (44 kDa). The 49 amino terminal amino acids encoded by pGS185 are designated as a chloroplast transit peptide by functionality in vitro, and amino acid homology to other transit peptides. The cytosolic forms of GS (GS1 and GSn) are encoded by highly homologous but distinct mRNAs. pGS299 encodes the cytosolic GS1 polypeptide (38 kDa), while pGS341 (Tingey, S. V., Walker, E. L., and Coruzzi, G. M. (1987) EMBO. J. 6, 1-9) encodes a cytosolic GSn polypeptide (37 kDa). The homologous nuclear genes for chloroplast and cytosolic GS show different patterns of expression in vivo. GS2 expression in leaves is modulated by light, at the level of steady state mRNA and protein, while the expression of cytosolic GS is unaffected by light. The light-induced expression of GS2 is due at least in part to a phytochrome mediated response. Nucleotide sequence analysis indicates that chloroplast and cytosolic GS have evolved from a common ancestor and suggest a molecular mechanism for chloroplast evolution.


The relation between post concussion symptoms and neurocognitive performance in concussed athletes.
The objective of this study was to examine differences in neurocognitive performance between symptomatic concussed athletes, a group of concussed athletes with no subjective symptoms, and a non-concussed control group of athletes. All concussed athletes were evaluated within one week of injury using the ImPACT computerized test battery. Results indicate that concussed athletes who denied subjective symptoms demonstrated poorer performance than control subjects on all four composite scores of the ImPACT test batters (Verbal Memory, Visual Memory, Reaction Time and Processing Speed However, the concussed but asymptomatic group demonstrated significantly better performance than did the concussed and symptomatic group. Thus, concussed athletes who did not report subjective symptoms were not fully recovered based on neurocognitive testing. This study underscores the importance of neurocognitive testing in the assessment of concussion sequelae and recovery.


The inhibitory action of kohamaic acid A derivatives on mammalian DNA polymerase beta.
We previously isolated a novel natural product, designated kohamaic acid A (KA-A, compound 1), as an inhibitor of the first cleavage of fertilized sea urchin eggs, and found that this compound could selectively inhibit the activities of mammalian DNA polymerases (pols). In this paper, we investigated the structure and bioactivity of KA-A and its chemically synthesized 11 derivatives (i.e., compounds 2-12), including KA-A - fatty acid conjugates. The pol inhibitory activity of compound 11 [(1S*,4aS*,8aS*)-17-(1,4,4a,5,6,7,8,8a-octahydro-2,5,5,8a-tetramethyl-naphthalen-1-yl)heptadecanoic acid] was the strongest among the synthesized compounds, and the range of IC(50) values for mammalian pols was 3.22 to 8.76 microM; therefore, the length of the fatty acid side chain group of KA-A is important for pol inhibition. KA-A derivatives could prevent human cancer cell (promyelocytic leukemia cell line, HL-60) growth with the same tendency as the inhibition of mammalian pols. Since pol beta is the smallest molecule, we used it to analyze the biochemical relationship with KA-A derivatives. From computer modeling analysis (i.e., docking simulation analysis), these compounds bound selectively to four amino acid residues (Leu11, Lys35, His51 and Thr79) of the N-terminal 8-kDa domain of pol beta, and the binding energy between compound 11 and pol beta was largest in the synthesized compounds. The relationship between the three-dimensional molecular structures of KA-A-related compounds and these inhibitory activities is discussed.


REFUGE Challenge: A unified framework for evaluating automated methods for glaucoma assessment from fundus photographs.
Glaucoma is one of the leading causes of irreversible but preventable blindness in working age populations. Color fundus photography (CFP) is the most cost-effective imaging modality to screen for retinal disorders. However, its application to glaucoma has been limited to the computation of a few related biomarkers such as the vertical cup-to-disc ratio. Deep learning approaches, although widely applied for medical image analysis, have not been extensively used for glaucoma assessment due to the limited size of the available data sets. Furthermore, the lack of a standardize benchmark strategy makes difficult to compare existing methods in a uniform way. In order to overcome these issues we set up the Retinal Fundus Glaucoma Challenge, REFUGE (https://refuge.grand-challenge.org), held in conjunction with MICCAI 2018. The challenge consisted of two primary tasks, namely optic disc/cup segmentation and glaucoma classification. As part of REFUGE, we have publicly released a data set of 1200 fundus images with ground truth segmentations and clinical glaucoma labels, currently the largest existing one. We have also built an evaluation framework to ease and ensure fairness in the comparison of different models, encouraging the development of novel techniques in the field. 12 teams qualified and participated in the online challenge. This paper summarizes their methods and analyzes their corresponding results. In particular, we observed that two of the top-ranked teams outperformed two human experts in the glaucoma classification task. Furthermore, the segmentation results were in general consistent with the ground truth annotations, with complementary outcomes that can be further exploited by ensembling the results.


Effect of age and occupational exposure to airway irritants on lung function in non-smoking individuals with alpha 1-antitrypsin deficiency (PiZZ).
Severe alpha 1-antitrypsin (AAT) deficiency (PiZZ) is associated with an increased risk of lung emphysema, especially in smokers. The aim of this study was to identify risk factors other than smoking for declining lung function. Lung function was studied in 225 self-reported never-smoking PiZZ individuals included in the Swedish AAT deficiency register. Lung function was poorer in men than in women (mean (SD) forced expiratory volume in one second (FEV1) 80 (30) versus 88 (17)% predicted) despite the fact that the men were younger (mean (SD) age 45 (18) versus 51 (17) years), and poorer in those aged 50 or older than in those aged under 50 (mean (SD) FEV1 70 (30) versus 98 (16)% predicted). Self-reported occupational exposure to gas, fumes, or dust occurred more frequently in men than in women. In those aged 50 or older lung function was lower in individuals exposed to airway irritants than those who were not exposed (mean (SD) FEV1 63 (29) versus 76 (31)% predicted). Male sex, increasing age, and previous symptoms of wheezing were independent risk factors for lung function impairment, and male sex, wheeziness, and occupational exposure to airway irritants were independent risk factors in the subjects aged 50 years or more. In non-smoking PiZZ individuals lung function declines with increasing age, especially after 50. Men are at greater risk of lung function deterioration than women. Asthmatic symptoms and occupational exposure to airway irritants appear to constitute additional risk factors.


Children With Autism Show Reduced Information Seeking When Learning New Tasks.
Information-seeking behaviours occur when children look to adults in order to gain further information about a novel stimulus/situation. The current study investigated information seeking in children with developmental delays (DD) and those with autism spectrum disorders (ASD) during a simulated teaching situation. Twenty preschool-aged children with ASD and 15 children with DD were exposed to a series of videos where a teacher provided novel instructions and demonstrated novel actions. We found that children with DD, but not those with ASD, demonstrated information-seeking behaviours in response to instructions that exceeded their level of understanding. This suggests that children with DD may use information-seeking behaviours to compensate for their cognitive and language difficulties when novel actions are being taught, while the same is not true for children with ASD.


Neurocognition with maraviroc compared with tenofovir in HIV.
The objective was to determine whether maraviroc (MVC) has unique neurocognitive benefits in the context of initial antiretroviral therapy (ART). Randomized, double-blind, placebo-controlled, 48-week trial. Participants were enrolled in US AIDS Clinical Trials Group clinical trial sites. Total 262 ART-naive, chemokine coreceptor 5 tropic HIV, and HIV RNA greater than 1000 copies/ml participants were randomized, 230 participants completed the study. Participants received MVC 150 mg or tenofovir disoproxil fumarate (TDF) 300 mg on a background of ritonavir-boosted darunavir and emtricitabine. The neuropsychological battery of 15 tests done at baseline, week 24 and week 48 assessed seven domains, and were standardized into z-scores then converted into deficit scores and a global deficit score. The 48-week changes from baseline in the neuropsychological scores and the global deficit score were compared by Wilcoxon or Kruskal-Wallis test between arms, and among baseline impairment groups [classified as normal, mild (2 deficit scores ≥1) and moderate (2 deficit scores ≥2)]. It was hypothesized that the MVC arm would have improved neuropsychological performance over TDF. In this double-blind, randomized, placebo-controlled trial, there were no differences in neuropsychological performance between MVC and TDF. Those with moderate neuropsychological impairment at baseline experienced greater ART-mediated neuropsychological improvement than those with mild or no neuropsychological impairment. Improvement in neurocognitive functioning was greater with more baseline impairment but was comparable with MVC or TDF.


Fast and accurate hybrid stream PCRTM-SOLAR radiative transfer model for reflected solar spectrum simulation in the cloudy atmosphere.
A hybrid stream PCRTM-SOLAR model has been proposed for fast and accurate radiative transfer simulation. It calculates the reflected solar (RS) radiances with a fast coarse way and then, with the help of a pre-saved matrix, transforms the results to obtain the desired high accurate RS spectrum. The methodology has been demonstrated with the hybrid stream discrete ordinate (HSDO) radiative transfer (RT) model. The HSDO method calculates the monochromatic radiances using a 4-stream discrete ordinate method, where only a small number of monochromatic radiances are simulated with both 4-stream and a larger N-stream (N ≥ 16)discrete ordinate RT algorithm. The accuracy of the obtained channel radiance is comparable to the result from N-stream moderate resolution atmospheric transmission version 5 (MODTRAN5). The root-mean-square errors are usually less than 5x 10-4 mW/cm2/sr/cm-1. The computational speed is three to four-orders of magnitude faster than the medium speed correlated-k option MODTRAN5. This method is very efficient to simulate thousands of RS spectra under multi-layer clouds/aerosols and solar radiation conditions for climate change study and numerical weather prediction applications.


Socioeconomic and lifestyle factors associated with depressive tendencies in general Japanese men and women: NIPPON DATA2010.
The gender-specific characteristics of individuals at an increased risk of developing depression currently remain unclear despite a higher prevalence of depression in women than in men. This study clarified socioeconomic and lifestyle factors associated with an increased risk of subclinical depression in general Japanese men and women. Study participants were residents not receiving psychiatric treatments in 300 sites throughout Japan in 2010 (1152 men, 1529 women). Multivariable-adjusted odds ratios (OR) and 95% confidence intervals (95%CIs) for socioeconomic factors and lifestyle factors were calculated using a logistic regression analysis. Risk of depressive tendencies was significantly higher in men who were single and living alone (OR, 3.27; 95% CI, 1.56-6.88) than those married. The risk was significantly lower in women who were not working and aged ≥ 60 years (OR, 0.39; 95% CI, 0.22-0.68) and higher in men who were not working and aged < 60 years (OR, 3.57; 95%CI, 1.31-9.72) compared with those who were working. Current smoking was also associated with a significantly increased risk of depressive tendencies in women (OR, 2.96; 95% CI, 1.68-5.22) but not in men. Socioeconomic and lifestyle factors were associated with an increased risk of depressive tendencies in general Japanese. Related factors were different by sex.


Fingerprinting Biomedical Terminologies--Automatic Classification and Visualization of Biomedical Vocabularies through UMLS Semantic Group Profiles.
To explore automatic methods for the classification of biomedical vocabularies based on their content. We create semantic group profiles for each source vocabulary in the UMLS and compare the vectors using a Euclidian distance. We explore several techniques for visualizing individual semantic group profiles and the entire distance matrix, including donut pie charts, heatmaps, dendrograms and networks. We provide donut pie charts for individual source vocavularies, as well as a heatmap, dendrogram and network for a subset of 78 vocabularies from the UMLS. Our approach to fingerprinting biomedical terminologies is completely automated and can easily be applied to all source vocabularies in the UMLS, including upcoming versions of the UMLS. It supports the exploration, selection and comparison of the biomedical terminologies integrated into the UMLS. The visualizations are available at (http://mor.-nlm.nih.gov/pubs/supp/2015-medinfo-br/index.html).


Next-Generation Biomarkers for Iron Status.
Iron is needed for oxygen transport, muscle activity, mitochondrial function, DNA synthesis, and sensing of hypoxia. The hierarchical master determinant of dietary iron absorption and iron distribution within the body is the peptide hormone hepcidin. Hepcidin itself is regulated by a combination of signals derived from iron stores, inflammation, and erythropoietic expansion. Iron deficiency and iron deficiency anemia are common and important conditions that can be treated with iron preparations. However, other factors besides iron deficiency can cause anemia, especially inflammation, which responds poorly to iron treatment, and inherited disorders of red blood cells, which are associated with accumulation of excess pathogenic iron. Assessment of iron status is challenging, and indices such as serum ferritin, soluble transferrin receptor, and zinc protoporphyrin have specific weaknesses. Moreover, a diagnosis of iron deficiency or iron deficiency anemia is most useful if the diagnosis also leads to effective treatment. Low levels of hepcidin allow iron absorption and effective iron incorporation into red blood cells. The best 'biomarker' to guide treatment may therefore be the physiological 'determinant' of iron utilization. Iron is also important in transplantation medicine and influences clinical outcome of arterial pulmonary hypertension; here too, biomarkers including hepcidin may be useful to actively and beneficially manage iron status.


Structures and mechanism of transcription initiation by bacterial ECF factors.
Bacterial RNA polymerase (RNAP) forms distinct holoenzymes with extra-cytoplasmic function (ECF) σ factors to initiate specific gene expression programs. In this study, we report a cryo-EM structure at 4.0 Å of Escherichia coli transcription initiation complex comprising σE-the most-studied bacterial ECF σ factor (Ec σE-RPo), and a crystal structure at 3.1 Å of Mycobacterium tuberculosis transcription initiation complex with a chimeric σH/E (Mtb σH/E-RPo). The structure of Ec σE-RPo reveals key interactions essential for assembly of E. coli σE-RNAP holoenzyme and for promoter recognition and unwinding by E. coli σE. Moreover, both structures show that the non-conserved linkers (σ2/σ4 linker) of the two ECF σ factors are inserted into the active-center cleft and exit through the RNA-exit channel. We performed secondary-structure prediction of 27,670 ECF σ factors and find that their non-conserved linkers probably reach into and exit from RNAP active-center cleft in a similar manner. Further biochemical results suggest that such σ2/σ4 linker plays an important role in RPo formation, abortive production and promoter escape during ECF σ factors-mediated transcription initiation.


Patient satisfaction and clinical outcome following outpatient radiofrequency catheter ablation of supraventricular tachycardia.
Catheter ablation is an effective and safe treatment for various arrhythmic disorders. Patients are frequently admitted for an overnight stay after the ablation procedure to monitor for possible postprocedural complications or recurrence of the arrhythmia. The aim of this study was to assess patient satisfaction in patients with supraventricular tachycardia following catheter ablation on an outpatient basis. 243 consecutive patients (129 male, 53%; mean age 49 +/- 17 years) underwent electrophysiological study and radiofrequency catheter ablation either on an outpatient basis or a hospitalisation that included at least an overnight hospital stay (inpatient) at a university hospital. All patients were asked to complete a specially designed questionnaire that addressed patient satisfaction as well as the clinical outcome after ablation at six months. The ablation procedure was performed on an outpatient basis in 119 patients (49%). The long-term procedural success rate was 99%. The overall patient satisfaction with the ablation procedure and with the clinical outcome at six months was 90%. There were no significant differences between outpatient and inpatient groups with respect to ablation results and patient satisfaction. Patients in the outpatient group returned to work after 2.8 +/- 1.9 days as compared to 3.9 +/- 2.2 days in the in hospital group (p = 0.001). Overall patient satisfaction and self-reported clinical outcome are comparable for outpatient and inpatient catheter ablations. Patients undergoing outpatient procedures may return to work earlier. Therefore, outpatient ablation procedures may be considered for selected patients without significant comorbidities.


Heritability of the dimensions, compliance and distensibility of the human internal jugular vein wall.
The elasticity of the internal jugular vein (IJV) is a major determinant of cerebral venous drainage and right atrium venous return. However, the level of genetic determination of IJV dimensions, compliance and distensibility has not been studied yet. 170 adult Caucasian twins (43 monozygotic [MZ] and 42 dizygotic [DZ] pairs) were involved from the Italian twin registry. Anteroposterior and mediolateral diameters of the IJV were measured bilaterally by ultrasonography. Measurements were made both in the sitting and supine positions, with or without Valsalva maneuver. Univariate quantitative genetic modeling was performed. Genetic factors are responsible for 30-70% of the measured properties of IJV at higher venous pressure even after adjustment for age and gender. The highest level of inheritance was found in the supine position regarding compliance (62%) and venous diameter during Valsalva (69%). Environmental and measurement-related factors instead are more important in the sitting position, when the venous pressure is low and the venous lumen is almost collapsed. The range of capacity changes between the lowest and highest intraluminal venous pressure (full distension range) are mainly determined by genetic factors (58%). Our study has shown substantial heritability of IJV biomechanics at higher venous pressures even after adjustment for age and gender. These findings yield an important insight to what degree the geometric and elastic properties of the vascular wall are formed by genetic and by environmental factors in humans.


Autism genes are selectively targeted by environmental pollutants including pesticides, heavy metals, bisphenol A, phthalates and many others in food, cosmetics or household products.
The increasing incidence of autism suggests a major environmental influence. Epidemiology has implicated many candidates and genetics many susceptibility genes. Gene/environment interactions in autism were analysed using 206 autism susceptibility genes (ASG's) from the Autworks database to interrogate ∼1 million chemical/gene interactions in the comparative toxicogenomics database. Any bias towards ASG's was statistically determined for each chemical. Many suspect compounds identified in epidemiology, including tetrachlorodibenzodioxin, pesticides, particulate matter, benzo(a)pyrene, heavy metals, valproate, acetaminophen, SSRI's, cocaine, bisphenol A, phthalates, polyhalogenated biphenyls, flame retardants, diesel constituents, terbutaline and oxytocin, inter alia showed a significant degree of bias towards ASG's, as did relevant endogenous agents (retinoids, sex steroids, thyroxine, melatonin, folate, dopamine, serotonin). Numerous other suspected endocrine disruptors (over 100) selectively targeted ASG's including paraquat, atrazine and other pesticides not yet studied in autism and many compounds used in food, cosmetics or household products, including tretinoin, soy phytoestrogens, aspartame, titanium dioxide and sodium fluoride. Autism polymorphisms influence the sensitivity to some of these chemicals and these same genes play an important role in barrier function and control of respiratory cilia sweeping particulate matter from the airways. Pesticides, heavy metals and pollutants also disrupt barrier and/or ciliary function, which is regulated by sex steroids and by bitter/sweet taste receptors. Further epidemiological studies and neurodevelopmental and behavioural research is warranted to determine the relevance of large number of suspect candidates whose addition to the environment, household, food and cosmetics might be fuelling the autism epidemic in a gene-dependent manner.


Monoclonal antibodies which distinguish certain classes of neuronal and supporting cells in the nervous tissue of the nematode Caenorhabditis elegans.
Monoclonal antibodies were generated using mice immunized with total homogenates of Caenorhabditis elegans adults or early larvae. Two of them were shown to distinguish a certain class of neuronal or supporting cells in the nervous tissue of this animal. Their histological specificities were studied in detail by indirect immunofluorescence on a whole mount preparation of animal head (or tail); for one of the antibodies further analysis was done by immunoelectron microscopy with the aid of a colloidal gold probe. An application of this antibody to a mutant of C. elegans is also described.


Association of socioeconomic status with inflammation markers in black and white men and women in the Coronary Artery Risk Development in Young Adults (CARDIA) study.
Inflammatory processes are implicated in a number of diseases for which there are known socioeconomic status (SES) disparities, including heart disease and diabetes. Growing evidence also suggests SES gradients in levels of peripheral blood markers of inflammation. However, we know little about potential gender and racial/ethnic differences in associations between SES and inflammation, despite the fact that the burden of inflammation-related diseases varies by gender and race. The present study examines SES (education and income) gradients in levels of two inflammatory biomarkers, C-reactive protein (CRP) and interleukin-6 (IL-6), in a biethnic (White and Black) sample of men and women (n=3549, aged 37-55 years) in the USA from the CARDIA Study. Health status, behavioral and psychosocial variables that may underlie SES differences in inflammatory biomarker levels were also examined. Age-adjusted CRP and IL-6 levels were inversely associated with education level in each race/gender group except Black males. Income gradients were also observed in each race/gender group for IL-6 and in White females and males for CRP. In general, differences in CRP and IL-6 levels between low and high SES groups were reduced in magnitude and significance with the addition of health status, behavioral, and psychosocial variables, although the impact of the addition of model covariates varied across race/gender groups and different SES-inflammation models. Overall, findings indicate SES gradients in levels of inflammation burden in middle-aged White and Black males and females.


Changing therapeutic geographies of the Iraqi and Syrian wars.
The health consequences of the ongoing US-led war on terror and civil armed conflicts in the Arab world are much more than the collateral damage inflicted on civilians, infrastructure, environment, and health systems. Protracted war and armed conflicts have displaced populations and led to lasting transformations in health and health care. In this report, we analyse the effects of conflicts in Iraq and Syria to show how wars and conflicts have resulted in both the militarisation and regionalisation of health care, conditions that complicate the rebuilding of previously robust national health-care systems. Moreover, we show how historical and transnational frameworks can be used to show the long-term consequences of war and conflict on health and health care. We introduce the concept of therapeutic geographies--defined as the geographic reorganisation of health care within and across borders under conditions of war.


HTT-OMNI: A Web-based Platform for Huntingtin Interaction Exploration and Multi-omics Data Integration.
Huntington's disease (HD) is a progressive neurological disorder that is caused by polyglutamine expansion of the huntingtin (HTT) protein. With the hope to uncover key modifiers of disease, a focus of the field of HD research has been on characterizing HTT-interacting proteins (HIPs) and the effect of the HTT polyglutamine expansion on the cellular omics landscape. However, while hundreds of studies have uncovered over 3000 potential HIPs to date, a means to interrogate these complementary interaction and omics datasets does not exist. The lack of a unified platform for exploring this breadth of potential HIPs and associated omics data represents a substantial barrier toward understanding the impact of HTT polyQ expansion and identifying interactions proximal to HD pathogenesis. Here, we describe the development of a web-based platform called HTT-OMNI (HTT OMics and Network Integration). This application facilitates the visualization and exploration of ∼3400 potential HTT interactors (from the HINT database) and their associated polyQ-dependent omics measurements, such as transcriptome and proteome abundances. Additionally, HTT-OMNI allows for the integration of user-generated datasets with existing HIPs and omic measurements. We first demonstrate the utility of HTT-OMNI for filtering existing HTT PPIs based on a variety of experimental metadata parameters, highlighting its capacity to select for HIPs detected in specific model organisms and tissues. Next, we leverage our application to visualize the relationships between HTT PPIs, genetic disease modifiers, and their multiomic landscape. Finally, we generate and analyze a previously unreported dataset of HTT PPIs, aimed at defining tissue-specific HTT interactions and the polyQ-dependent modulation of their relative stabilities in the cortex and striatum of HD mouse models.


Interactions of plakoglobin and beta-catenin with desmosomal cadherins: basis of selective exclusion of alpha- and beta-catenin from desmosomes.
Plakoglobin and beta-catenin are homologous armadillo repeat proteins found in adherens junctions, where they interact with the cytoplasmic domain of classical cadherins and with alpha-catenin. Plakoglobin, but normally not beta-catenin, is also a structural constituent of desmosomes, where it binds to the cytoplasmic domains of the desmosomal cadherins, desmogleins and desmocollins. Here, we report structural, biophysical, and biochemical studies aimed at understanding the molecular basis of selective exclusion of beta-catenin and alpha-catenin from desmosomes. The crystal structure of the plakoglobin armadillo domain bound to phosphorylated E-cadherin shows virtually identical interactions to those observed between beta-catenin and E-cadherin. Trypsin sensitivity experiments indicate that the plakoglobin arm domain by itself is more flexible than that of beta-catenin. Binding of plakoglobin and beta-catenin to the intracellular regions of E-cadherin, desmoglein1, and desmocollin1 was measured by isothermal titration calorimetry. Plakoglobin and beta-catenin bind strongly and with similar thermodynamic parameters to E-cadherin. In contrast, beta-catenin binds to desmoglein-1 more weakly than does plakoglobin. beta-Catenin and plakoglobin bind with similar weak affinities to desmocollin-1. Full affinity binding of desmoglein-1 requires sequences C-terminal to the region homologous to the catenin-binding domain of classical cadherins. Although pulldown assays suggest that the presence of N- and C-terminal beta-catenin "tails" that flank the armadillo repeat region reduces the affinity for desmosomal cadherins, calorimetric measurements show no significant effects of the tails on binding to the cadherins. Using purified proteins, we show that desmosomal cadherins and alpha-catenin compete directly for binding to plakoglobin, consistent with the absence of alpha-catenin in desmosomes.


Enhancing the biotransformation of isoflavones in soymilk supplemented with lactose using probiotic bacteria during extended fermentation.
Soymilk (SM) lacks lactose; hence supplementation of SM with lactose is likely to enhance the growth of probiotic bacteria and biotransformation of isoflavone glycosides to isoflavone aglycones. In this study, 11 strains of probiotic bacteria including Lactobacillus rhamnosus, L. salivarius, L. plantarum, L. acidophilus, L. paracasei, HOWARU L. rhamnosus, L. delbrueckii subsp. bulgaricus, Bifidobacterium lactis type Bi-07, B. longum, HOWARU B. bifidum, and B lactis type Bi-04 were inoculated individually or as mixed cultures into SM and soymilk supplemented with lactose (SML). A total of 2% of lactose was added to 1 L of SM with the aim of improving the growth of probiotic organisms and promoting the biotransformation of isoflavone isomers to bioactive isoflavone aglycomes. Samples of SM were incubated at 37 degrees C and 10 mL aliquots of SM were taken at 0, 24, 48, and 72 h to monitor the growth of probiotic bacteria and changes in isoflavone contents using high-performance liquid chromatography (HPLC). Results indicated that SML fermented with probiotics had higher viable counts by >2.4 log CFU/mL than that in SM at the end of the 72 h fermentation period. Mixed cultures grew at different rates and in general Lactobacilius spp. had >1.02 log CFU/mL more cells than Bifidobacterium spp. at the end of the fermentation period. The total aglycone content in SM at 72 h of fermentation was 0.924 mg/100 mL, whereas that in SML was 1.623 mg/100 mL. Addition of lactose not only improved the growth of probiotic bacteria in SM but also enhanced the biotransformation of isoflavone glucosides to the more bioactive isoflavone aglycones. Mixed cultures did not improve the biotransformation of bioactive isoflavones when compared to single cultures.


F-18 Fluorodeoxyglucose Positron Emission Tomography/ Computed Tomography Findings of Isolated Gastric Tuberculosis mimicking Gastric Cancer and Lymphoma.
Tuberculosis (TB) infection is still a challenging health issue, especially in developing countries. Diagnosing extrapulmonary infections, especially isolated organ involvement, is difficult in most cases even with the radiological, endoscopic, and histopathological examinations done for accurate diagnosis. Here we describe a case of isolated gastric TB with specific F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) findings mimicking gastric cancer/ lymphoma. A 20-year-old male patient was admitted to our hospital with abdominal pain in the epigastric region, weight loss, and fever especially at nights for 2 months. Physical examination was normal. Hemoglobin was 9.6 gm/dL; the patient had iron deficiency anemia. Upper gastrointestinal (GI) endoscopy was suggestive of gastric ulcer mimicking malignancy. F-18 FDG PET/CT revealed multiple hypermetabolic malignant lymphadenopathies in the abdomen and diffuse gastric wall thickening as linitis plastica and multiple hypermetabolic peritoneal implants in the omentum. Exploratory laparotomy was done for tissue diagnosis and exploration of the peritoneum for TB infection, lymphoma, and Crohn's disease to make differential diagnosis. Histopathology revealed granulomatous lymphadenitis with granulomas including giant cells, suspecting TB. Patient was put on antituberculosis treatment (ATT). After treatment, the complaints resolved, and he gained weight. Fusion PET/CT exhibited a complete response to ATT with no residual disease. According to our knowledge, this is the first report about F-18 FDG PET/CT findings in the diagnosis of isolated gastric TB. F-18 FDG PET/CT may provide help in the diagnosis and follow-up of isolated gastric TB in challenging cases.How to cite this article: Akdogan RA, Rakici H, Güngör S, Bedir R, Akdogan E. F-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Findings of Isolated Gastric Tuberculosis mimicking Gastric Cancer and Lymphoma. Euroasian J Hepato-Gastroenterol 2018;8(1):93-96.


MC1R Functions, Expression, and Implications for Targeted Therapy.
The G protein-coupled MC1R is expressed in melanocytes and has a pivotal role in human skin pigmentation, with reduced function in human genetic variants exhibiting a red hair phenotype and increased melanoma predisposition. Beyond its role in pigmentation, MC1R is increasingly recognized as promoting UV-induced DNA damage repair. Consequently, there is mounting interest in targeting MC1R for therapeutic benefit. However, whether MC1R expression is restricted to melanocytes or is more widely expressed remains a matter of debate. In this paper, we review MC1R function and highlight that unbiased analysis suggests that its expression is restricted to melanocytes, granulocytes, and the brain.


Self-injected semiconductor distributed feedback lasers for frequency chirp stabilization.
It is well known that semiconductor distributed feedback lasers (DFB) are key devices for optical communications. However direct modulation applications are limited by the frequency chirp induced by current modulation. We demonstrate that a proper external control laser operation leads to chirp-to-power ratio (CPR) stabilization over a wide range of modulation frequencies as compared to the free-running case. Under experimentally selected optical feedback conditions, the CPR decreases significantly in the adiabatic regime from about 650 MHz/mW in the solitary case down to 65 MHz/mW. Experimental results are also confirmed by numerical investigations based on the transfer matrix method. Simulations point out the possible optimization of the CPR in the adiabatic regime by considering a judicious cavity design in conjunction with a proper external control. These results demonstrate important routes for improving the transmission performance in optical telecommunication systems.


[Preinvasive lesions in gynecology - vulva].
For preinvasive lesions of vulva, a common term VIN - vulval intraepithelial neoplasia is used. VIN is a histological dia-gnosis based on abnormal squamous epithelial proliferation. There are two types of VIN apart from their association with human papillomavirus (HPV). Undifferentiated (usual) vulval intraepithelial neoplasia is commonly associated with carcinogenic genotypes of HVP, whereas differentiated vulval intraepithelial neoplasia is not associated with high-risk genotypes of HPV. The article presents an overview of VIN occurence and epidemiology, its classification system and dia-gnostics. In conclusion, VIN therapeutical possibilities are presented. It can be treated with surgical therapy (local excision, partial vulvectomy, vulvectomy, laser vaporization) or medical therapy (imiquimod).


Organizational Failure in an NHS Hospital Trust: A Qualitative Study.
The objective was to explore the key factors associated with organizational failure in an NHS Hospital Trust. This case study adopted a qualitative design. Fifty-seven semistructured interviews and document analyses were conducted as well. Data were analyzed using a framework analysis method. A range of symptoms of organizational performance failure was identified. These relate to a financial deficit, lack of good external relationships, inability to meet core targets, a lack of clear management systems, and low staff morale. These markers had not been taken seriously by the previous senior management team. Symptoms of failure were the reflection of presence of secondary and primary causes of failure. Poor managerial leadership, poor financial control and performance management, lack of open culture, distraction by 2 large projects, and the lack of clinician engagement were perceived as internal causes of failure and the high level of policy changes within the NHS as the key external cause. The level of deprivation in the area was also thought to have had a negative impact on performance. The findings reinforce and expand on those of recent studies across the public sector. Tracking an organization's performance and early diagnosis of performance problems, focusing on performance management systems, and taking into account contextual factors are issues that should be considered.


Trajectory of individual immunity and vaccination required for SARS-CoV-2 community immunity: a conceptual investigation.
SARS-CoV-2 is an international public health emergency; high transmissibility and morbidity and mortality can result in the virus overwhelming health systems. Combinations of social distancing, and test, trace, and isolate strategies can reduce the number of new infections per infected individual below 1, thus driving declines in case numbers, but may be both challenging and costly. These interventions must also be maintained until development and (now likely) mass deployment of a vaccine (or therapeutics), since otherwise, many susceptible individuals are still at risk of infection. We use a simple analytical model to explore how low levels of infection, combined with vaccination, determine the trajectory to community immunity. Understanding the repercussions of the biological characteristics of the viral life cycle in this scenario is of considerable importance. We provide a simple description of this process by modelling the scenario where the effective reproduction number [Formula: see text] is maintained at 1. Since the additional complexity imposed by the strength and duration of transmission-blocking immunity is not yet clear, we use our framework to probe the impact of these uncertainties. Through intuitive analytical relations, we explore how the necessary magnitude of vaccination rates and mitigation efforts depends crucially on the durations of natural and vaccinal immunity. We also show that our framework can encompass seasonality or preexisting immunity due to epidemic dynamics prior to strong mitigation measures. Taken together, our simple conceptual model illustrates the importance of individual and vaccinal immunity for community immunity, and that the quantification of individuals immunized against SARS-CoV-2 is paramount.


Combined copy number and mutation analysis identifies oncogenic pathways associated with transformation of follicular lymphoma.
Follicular lymphoma (FL) is typically an indolent disease, but 30-40% of FL cases transform into an aggressive lymphoma (tFL) with a poor prognosis. To identify the genetic changes that drive this transformation, we sequenced the exomes of 12 cases with paired FL and tFL biopsies and identified 45 recurrently mutated genes in the FL-tFL data set and 39 in the tFL cases. We selected 496 genes of potential importance in transformation and sequenced them in 23 additional tFL cases. Integration of the mutation data with copy-number abnormality (CNA) data provided complementary information. We found recurrent mutations of miR-142, which has not been previously been reported to be mutated in FL/tFL. The genes most frequently mutated in tFL included KMT2D (MLL2), CREBBP, EZH2, BCL2 and MEF2B. Many recurrently mutated genes are involved in epigenetic regulation, the Janus-activated kinase-signal transducer and activator of transcription (STAT) or the nuclear factor-κB pathways, immune surveillance and cell cycle regulation or are TFs involved in B-cell development. Of particular interest are mutations and CNAs affecting S1P-activated pathways through S1PR1 or S1PR2, which likely regulate lymphoma cell migration and survival outside of follicles. Our custom gene enrichment panel provides high depth of coverage for the study of clonal evolution or divergence.


Dependency denied: health inequalities in the neo-liberal era.
The ways in which inequality generates particular population health outcomes remains a major source of dispute within social epidemiology and medical sociology. Wilkinson and Pickett's The Spirit Level (2009), undoubtedly galvanised thinking across the disciplines, with its emphasis on how income inequality shapes the distribution of health and social problems. In this paper, we argue that their focus on income inequality, whilst important, understates the role of neoliberal discourses and practises in making sense of contemporary inequality and its health-related consequences. Many quantitative studies have demonstrated that more neoliberal countries have poorer health compared to less neoliberal countries, but there are few qualitative studies which explore how neoliberal discourses shape accounts and experiences and what protections and resources might be available to people. This article uses findings from a qualitative psycho-social study employing biographical-narrative interviews with women in Salford (England) to understand experiences of inequality as posited in The Spirit Level. We found evidence for the sorts of damages resulting from inequality as proposed in The Spirit Level. However, in addition to these, the most striking finding was the repeated articulation of a discourse which we have termed "no legitimate dependency". This was something both painful and damaging, where dependency of almost any sort was disavowed and responsibility was assumed by the self or "othered" in various ways. No legitimate dependency, we propose, is a partial (and problematic) internalisation of neoliberal discourses which becomes naturalised and unquestioned at the individual level. We speculate that these sorts of discourses in conjunction with a destruction of protective resources (both material and discursive), lead to an increase in strain and account in part for well-known damages consequent on life in an unequal society. We conclude that integrating understandings of neoliberalism into theorising about inequality enriches sociological perspectives in this area.


Enzymatic recycling of thermoplastic polyurethanes: Synergistic effect of an esterase and an amidase and recovery of building blocks.
Biological recycling of polyurethanes (PU) is a huge challenge to take up in order to reduce a large part of the environmental pollution from these materials. However, enzymatic depolymerization of PU still needs to be improved to propose valuable and green solutions. The present study aims to identify efficient PU degrading enzymes among a collection of 50 hydrolases. Screenings based on model molecules were performed leading to the selection of an efficient amidase (E4143) able to hydrolyze the urethane bond of a low molar mass molecule and an esterase (E3576) able to hydrolyze a waterborne polyester polyurethane dispersion. Degradation activities of the amidase, the esterase and a mix of these enzymes were then evaluated on four thermoplastic polyurethanes (TPU) specifically designed for this assay. The highest degradation was obtained on a polycaprolactone polyol-based polyurethane with weight loss of 33% after 51 days measured for the esterase. Deep cracks on the polymer surface observed by scanning electron microscopy and the presence of oligomers on the remaining TPU detected by size exclusion chromatography evidenced the polymer degradation. Mixing both enzymes led to an increased amount of urethane bonds hydrolysis of the polymer. 6-hydroxycaproic acid and 4,4'-methylene dianiline were recovered after depolymerization as hydrolysis products. Such building blocks could get a second life with the synthesis of new macromolecular architectures.


Habitat suitability analysis reveals high ecological flexibility in a "strict" forest primate.
Research of many mammal species tends to focus on single habitats, reducing knowledge of ecological flexibility. The Javan lutung (Trachypithecus auratus) is considered a strict forest primate, and little is known about populations living in savannah. In 2017-2018, we investigated the density and distribution of Javan lutung in Baluran National Park, Indonesia. We conducted ad libitum follows and line transect distance sampling with habitat suitability analysis of Javan lutung. Estimated density was 14.91 individuals km- 2 (95% CI 7.91-28.08), and estimated population size was 3727 individuals (95% CI 1979 - 7019). Long-tailed macaque (Macaca fascicularis) habitat suitability was the main driver of lutung habitat suitability as the probability of lutung occurrence increased greatly with macaque habitat suitability. Distance to roads, and distance to secondary forest had a negative relationship with lutung occurrence. Lutung habitat suitability decreased with increasing elevation, however, Mt Baluran and the primary forest on Mt Baluran was under-sampled due to treacherous conditions. Follows of six focus groups revealed considerable use of savannah, with terrestrial travel. The follows also revealed polyspecific associations with long-tailed macaques through shared sleeping sites and inter-specific vocalisations. Our study provides new knowledge on the general ecology of Javan lutung, such as use of savannah habitats, underlining our need to branch out in our study sites to understand the flexibility and adaptability of our study species. Another undocumented behaviour is the polyspecific association with long-tailed macaques. We encourage more research on this subject.


A global evaluation of metabolic theory as an explanation for terrestrial species richness gradients.
We compiled 46 broadscale data sets of species richness for a wide range of terrestrial plant, invertebrate, and ectothermic vertebrate groups in all parts of the world to test the ability of metabolic theory to account for observed diversity gradients. The theory makes two related predictions: (1) In-transformed richness is linearly associated with a linear, inverse transformation of annual temperature, and (2) the slope of the relationship is near -0.65. Of the 46 data sets, 14 had no significant relationship; of the remaining 32, nine were linear, meeting prediction 1. Model I (ordinary least squares, OLS) and model II (reduced major axis, RMA) regressions then tested the linear slopes against prediction 2. In the 23 data sets having nonlinear relationships between richness and temperature, split-line regression divided the data into linear components, and regressions were done on each component to test prediction 2 for subsets of the data. Of the 46 data sets analyzed in their entirety using OLS regression, one was consistent with metabolic theory (meeting both predictions), and one was possibly consistent. Using RMA regression, no data sets were consistent. Of 67 analyses of prediction 2 using OLS regression on all linear data sets and subsets, two were consistent with the prediction, and four were possibly consistent. Using RMA regression, one was consistent (albeit weakly), and four were possibly consistent. We also found that the relationship between richness and temperature is both taxonomically and geographically conditional, and there is no evidence for a universal response of diversity to temperature. Meta-analyses confirmed significant heterogeneity in slopes among data sets, and the combined slopes across studies were significantly lower than the range of slopes predicted by metabolic theory based on both OLS and RMA regressions. We conclude that metabolic theory, as currently formulated, is a poor predictor of observed diversity gradients in most terrestrial systems.


An Arabidopsis endo-1,4-beta-D-glucanase involved in cellulose synthesis undergoes regulated intracellular cycling.
The synthesis of cellulose microfibrils requires the presence of a membrane-bound endo-1,4-beta-D-glucanase, KORRIGAN1 (KOR1). Although the exact biochemical role of KOR1 in cellulose synthesis is unknown, we used the protein as a marker to explore the potential involvement of subcellular transport processes in cellulose synthesis. Using immunofluorescence and a green fluorescent protein (GFP)-KOR1 fusion that complemented the phenotype conferred by the kor1-1 mutant, we investigated the distribution of KOR1 in epidermal cells in the root meristem. KOR1 was localized in intracellular compartments corresponding to a heterogeneous population of organelles, which comprised the Golgi apparatus, FM4-64-labeled compartments referred to as early endosomes, and, in the case of GFP-KOR1, the tonoplast. Inhibition of cellulose synthesis by isoxaben promoted a net redistribution of GFP-KOR1 toward a homogeneous population of compartments, distinct from early endosomes, which were concentrated close to the plasma membrane facing the root surface. A redistribution of GFP-KOR1 away from early endosomes was also observed in the same cells at later stages of cell elongation. A subpopulation of GFP-KOR1-containing compartments followed trajectories along the plasma membrane, and this motility required intact microtubules. These observations demonstrate that the deposition of cellulose, like chitin synthesis in yeast, involves the regulated intracellular cycling of at least one enzyme required for its synthesis.


Trypanosoma evansi infection in cattle, buffaloes and horses in Indonesia.
Cattle, buffaloes and horses in several areas of Indonesia were examined for evidence of infection with Trypanosoma evansi by the microhaematocrit centrifugation technique (MHCT) and an enzyme-linked immunosorbent assay (ELISA) for detection of antibodies to T. evansi. Evidence of infection was found in animals at each sampling site although differences were seen in prevalence rates between sites. Prevalence rates in buffalo were usually higher than in cattle in the same area while in horses they were much lower than in cattle or buffalo. An age-dependent prevalence rate was seen in buffalo and cattle with the highest rates seen in animals older than 2 years. These results concur with the view that T. evansi infection is widespread throughout most of the livestock-producing areas of Indonesia. The apparent lack of any obvious disease owing to T. evansi infection in the sampled animals suggests that a form of stability exists in most endemic areas which serves to ameliorate the effect of T. evansi infection and has an immunological basis linked to the parasite's limited antigenic diversity.


The current aetiology of malignant pleural effusion in the Western Cape Province, South Africa.
Malignant pleural effusion (MPE) represents a very common cause of pleural exudates, and is one of the most challenging pleural disorders to manage. This could be attributed to the paucity of high-quality experimental evidence, and inconsistent practice worldwide. South Africa (SA) currently has no data regarding the aetiology of MPE. To identify the most common malignancies causing MPE in a population served by a large tertiary hospital in SA, and specifically the relative contribution of mesothelioma. A secondary objective was to evaluate the efficacy of chemical pleurodesis in a subset of patients. We retrospectively included all known cases of MPE evaluated at our institution over a 3-year period with a tissue diagnosis of MPE. The most common causes of MPE in a total of 274 patients were lung cancer (n=174, 63.5%), breast cancer (n=32, 11.7%), unknown primary (n=22, 11.7%) and mesothelioma (n=27, 9.9%). Talc pleurodesis was performed in 81 of 194 patients (41.8%) referred to our division, and was radiologically successful in 22 of 25 (88.0%) followed up to 3 months. The main cause of MPE in our setting was lung cancer, followed by breast cancer, unknown primary and mesothelioma. Chemical pleurodesis was a viable palliative measure for MPE in this population.


Is a drain required after laparoscopic cholecystectomy?
Whether drains should be routinely used after laparoscopic cholecystectomy is still debated. We aimed to retrospectively evaluate the benefits of drain use after laparoscopic cholecystectomy for non-acute and non-inflamed gallbladders. Two hundred and fifty patients (mean age, 47±13.8 years; 200 females and 50 males) who underwent laparoscopic cholecystectomy for cholestasis were included in the study. The medical files of the patients were examined retrospectively to obtain data on patient demographics, cholecystitis attacks, complications during the operation, whether a drain was placed in the biliary tract during the operation, etc. The volume of the fluid collection detected in the subhepatic area by ultrasonography on the first postoperative day was recorded. Drains were placed in 51 patients (20.4%). The mean duration of drain placement was 3.1±1.9 (range 1-16) days. Fluid collection was detected in the gallbladder area in 67 patients (26.8%). The mean volume of collected fluid was 8.8±5.2 mL. There were no significant effects of age, gender, and previous cholecystitis attacks on the presence or volume of the fluid collection (P>0.05 for all). With regard to the relationship between fluid collection and drains, 52 of 199 (26.1%) patients without drains had postoperative fluid collection, compared to 15 of 51 (29.4%) patients with drains (P>0.05). In conclusion, there is no relationship between the presence of a drain after laparoscopic cholecystectomy and the presence of postoperative fluid collection. Thus, in patients without complications, it is not necessary to place a drain to prevent fluid collection.


Isolation and characterization of Dobrava hantavirus carried by the striped field mouse (Apodemus agrarius) in Estonia.
Dobrava hantavirus (DOB) was isolated from the striped field mouse (Apodemus agrarius) trapped on Saaremaa Island, Estonia, and its genetic and antigenic characteristics were subsequently analysed. Phylogenetic analysis showed that the Estonian DOB strain, together with several wild strains carried by Apodemus agrarius, forms a well-supported lineage within the DOB clade. The topography of the trees calculated for the S, M and L nucleotide sequences of the Estonian DOB suggests a similar evolutionary history for all three genes of this virus and, therefore, the absence of heterologous reassortment in its evolution. A cross-neutralization comparison of the Estonian virus with the prototype DOB, isolated from a yellow-necked mouse (A. flavicollis) in Slovenia, revealed 2- to 4-fold differences in the end-point titres of rabbit and human antisera. When studied with a panel of 25 monoclonal antibodies (MAbs), the Estonian and Slovenian DOB isolates showed similar antigenic patterns that could be distinguished by two MAbs. Genetic comparison showed sequence differences in all three genome segments of the two DOB isolates, including an additional N-glycosylation site in the deduced sequence of the G2 protein from the Estonian virus. Whether any of these mutations relates to the different rodent hosts rather than to the distant geographical origin of the two isolates remains to be resolved. Taken together, our observations suggest that A. agrarius, which is known to harbour Hantaan virus in Asia, carries another hantavirus, DOB, in north-east Europe.


Serotonin signaling in Schistosoma mansoni: a serotonin-activated G protein-coupled receptor controls parasite movement.
Serotonin is an important neuroactive substance in all the parasitic helminths. In Schistosoma mansoni, serotonin is strongly myoexcitatory; it potentiates contraction of the body wall muscles and stimulates motor activity. This is considered to be a critical mechanism of motor control in the parasite, but the mode of action of serotonin is poorly understood. Here we provide the first molecular evidence of a functional serotonin receptor (Sm5HTR) in S. mansoni. The schistosome receptor belongs to the G protein-coupled receptor (GPCR) superfamily and is distantly related to serotonergic type 7 (5HT7) receptors from other species. Functional expression studies in transfected HEK 293 cells showed that Sm5HTR is a specific serotonin receptor and it signals through an increase in intracellular cAMP, consistent with a 5HT7 signaling mechanism. Immunolocalization studies with a specific anti-Sm5HTR antibody revealed that the receptor is abundantly distributed in the worm's nervous system, including the cerebral ganglia and main nerve cords of the central nervous system and the peripheral innervation of the body wall muscles and tegument. RNA interference (RNAi) was performed both in schistosomulae and adult worms to test whether the receptor is required for parasite motility. The RNAi-suppressed adults and larvae were markedly hypoactive compared to the corresponding controls and they were also resistant to exogenous serotonin treatment. These results show that Sm5HTR is at least one of the receptors responsible for the motor effects of serotonin in S. mansoni. The fact that Sm5HTR is expressed in nerve tissue further suggests that serotonin stimulates movement via this receptor by modulating neuronal output to the musculature. Together, the evidence identifies Sm5HTR as an important neuronal protein and a key component of the motor control apparatus in S. mansoni.


Nisin-inducible secretion of a biologically active single-chain insulin analog by Lactococcus lactis NZ9000.
Oral delivery of insulin to diabetic patients is highly desirable because it would be non-invasive and more closely mimic normal physiology, but this route of administration typically results in low bioavailability due to low pH and enzymatic degradation along the gastrointestinal tract. To explore an alternative approach that may mitigate these obstacles and also facilitate local synthesis of new therapeutic protein molecules in the small intestine, we engineered the food-grade bacterium Lactococcus lactis (NZ9000) for nisin-inducible expression and secretion of a bioactive single-chain insulin (SCI) analog, SCI-57. We show that the addition of nisin during early-log phase has a modest inhibitory effect on cell growth but induction during mid-log phase has a negligible impact on proliferation, suggesting a tradeoff between cell growth rate and duration of induction. We find that a signal peptide such as usp45 is necessary for secretion of SCI-57 into the medium; furthermore, we demonstrate that this secreted SCI-57 is biologically active, as assessed by the ability of conditioned L. lactis medium to stimulate Akt signaling in differentiated 3T3-L1 adipocytes. Finally, we show that the biological activity of SCI-57 was enhanced by near-neutral or slightly alkaline pH during induction, which is comparable to the pH in the small intestine, and by removal of a C-terminal purification tag. This study demonstrates that food-grade bacteria can be engineered to secrete bioactive insulin analogs and opens up the possibility of oral insulin delivery using live microorganisms.


Domestic and foreign trends in the prevalence of heart failure and the necessity of next-generation artificial hearts: a survey by the Working Group on Establishment of Assessment Guidelines for Next-Generation Artificial Heart Systems.
A series of guidelines for development and assessment of next-generation medical devices has been drafted under an interagency collaborative project by the Ministry of Health, Labor and Welfare and the Ministry of Economy, Trade and Industry. The working group for assessment guidelines of next-generation artificial hearts reviewed the trend in the prevalence of heart failure and examined the potential usefulness of such devices in Japan and in other countries as a fundamental part of the process of establishing appropriate guidelines. At present, more than 23 million people suffer from heart failure in developed countries, including Japan. Although Japan currently has the lowest mortality from heart failure among those countries, the number of patients is gradually increasing as our lifestyle becomes more Westernized; the associated medical expenses are rapidly growing. The number of heart transplantations, however, is limited due to the overwhelming shortage of donor hearts, not only in Japan but worldwide. Meanwhile, clinical studies and surveys have revealed that the major causes of death in patients undergoing long-term use of ventricular assist devices (VADs) were infection, thrombosis, and mechanical failure, all of which are typical of VADs. It is therefore of urgent and universal necessity to develop next-generation artificial hearts that have excellent durability to provide at least 2 years of event-free operation with a superior quality of life and that can be used for destination therapy to save patients with irreversible heart failure. It is also very important to ensure that an environment that facilitates the development, testing, and approval evaluation processes of next-generation artificial hearts be established as soon as possible.


Microbial strategies to target, cross or disrupt epithelia.
Epithelia are highly organized structures adapted to protect the underlying tissues from external aggressions, including microbial infections. Consequently, pathogens have evolved various strategies to target directly or indirectly intercellular junctions and/or components that maintain the structure of epithelia. Interestingly, some extracellular pathogens secrete enzymes that modify the extracellular part of junction components. Others produce toxins that are endocytosed and act from the inside of the cell to disrupt epithelial junctions. Other pathogens may directly inject into cells factors that are targeted to and destabilize the junctions, or that interact with signaling cascades that affect junction stability. Finally invasive bacteria or viruses may, by entering into cells, destabilize the junctions by targeting junction components directly or by inducing a series of events that lead to chemokine secretion, polymorphonuclear recruitment and inflammation.


First derivative UV spectra of surface water as a monitor of chlorination in drinking water treatment.
Many countries require the presence of free chlorine at about 0.1 mg/l in their drinking water supplies. For various reasons, such as cast-iron pipes or long residence times in the distribution system, free chlorine may decrease below detection limits. In such cases it is important to know whether or not the water was chlorinated or if nonchlorinated water entered the system by accident. Changes in UV spectra of natural organic matter in lakewater were used to assess qualitatively the degree of chlorination in the treatment to produce drinking water. The changes were more obvious in the first derivative spectra. In lakewater, the derivative spectra have a maximum at about 280 nm. This maximum shifts to longer wavelengths by up to 10 nm, decreases, and eventually disappears with an increasing dose of chlorine. The water treatment system was monitored by this technique for over 1 year and changes in the UV spectra of water samples were compared with experimental samples treated with known amounts of chlorine. The changes of the UV spectra with the concentration of added chlorine are presented. On several occasions, water, which received very little or no chlorination, may have entered the drinking water system. The results show that first derivative spectra are potentially a tool to determine, in the absence of residual chlorine, whether or not surface water was chlorinated during the treatment to produce potable water.


Semiquantitative assessment of MR imaging in prediction of efficacy of gonadotropin-releasing hormone agonist for volume reduction of uterine leiomyoma: initial experience.
To prospectively determine if semiquantitative assessment of R2* images and T1-weighted magnetic resonance (MR) images of leiomyomas correlates with the efficacy of gonadotropin-releasing hormone (GnRH) agonist treatment for volume reduction. Internal review board approval and informed consent were obtained for this study. Twenty women (mean age, 36.3 years) with intramyometrial leiomyomas were enrolled in this study. Single-section double-echo dynamic MR imaging was performed before GnRH agonist administration. T2-weighted images were obtained before and after two or three GnRH agonist injections (1.88 mg leuprorelin acetate). The steepest signal intensity (SI) upslope on T1-weighted images and the area under the curve (AUC) on R2* images were determined by using a 16 x 16-voxel matrix that was placed in the center of a leiomyoma. Pearson correlation analysis was performed to compare the percentage of volume reduction with SI upslope and AUC. Unpaired t test was performed to evaluate the difference between leiomyomas with AUC and SI upslope values that were less than or greater than the mean. Percentage of volume reduction ranged from 6.2% to 51.1%. The mean AUC and mean SI upslope were 39.2 and 9.83% per second, respectively. There was a significant correlation between the AUC and the percentage of volume reduction (r = 0.81, P < .001), although no significant correlation was observed between the SI upslope and the percentage of volume reduction. A significant difference in percentage of volume reduction was observed in leiomyomas by using mean AUC as a cutoff value (P = .003). AUC on R2* images correlates with the efficacy of GnRH agonist before initiation of treatment for volume reduction of leiomyoma.


Insights from the Inclusive Environments and Metrics in Biology Education and Research Network: Our Experience Organizing Inclusive Biology Education Research Events.
In contrast to efforts focusing on improving inclusion in STEM classrooms from kindergarten through undergraduate (K-16), efforts to improve inclusion in scientific meetings and conferences, important hubs of STEM culture, are more recent. Markers of inclusion that are sometimes overlooked at these events can include the composition of panels, how workshops are run, the affordability of conferences, and various other mechanisms that maintain pre-existing hierarchies and norms that limit the participation of early-career researchers and individuals of minoritized cultural, linguistic, and economic backgrounds. The Inclusive Environments and Metrics in Biology Education and Research (iEMBER) network coordinates efforts of researchers from many fields interested in diversity and inclusion in biology education. Given the concerns regarding inclusion at professional meetings, iEMBER has developed and implemented several practices in planning and executing our meetings to make them more inclusive. In this report, we share our experiences developing inclusive meetings on biology education research and discuss the outcomes of such efforts. Specifically, we present our approach to planning and executing the iEMBER 2019 conference and the National Association of Biology Teachers iEMBER 2019 workshop. This report adds to the growing body of resources on inclusive meetings, provides readers with an account of how such an attempt at implementation might unfold, and complements existing theories and work relating to the importance and functioning of such meetings in terms of representation in STEM.


Influence of early quantitative food restriction on long bone growth at different environmental temperatures in broiler chickens.
1. This investigation was carried out to study the influence of early quantitative food restriction (40% of ad libitum intake from 7 to 14 d of age) and environmental rearing temperature (thermoneutral, cold and hot) on long bone (tibia, femur and humerus) development in broiler chickens. 2. Tibia, femur and humerus were obtained at the ages of 14, 21, 28, 35 and 42 d, and the variables studied were: length and width (mm, expressed as absolute values), bone breaking strength (kgf) and bone weight/bone length index (BW/BL, mg/mm). 3. All bone variables increased with bird age. Food restriction reduced bone length and width but did not affect bone weight. High environmental rearing temperature reduced bone length and width at 42 d of age. Bone strength was not affected by environmental temperature but the calculated BW/BL index was reduced by heat exposure. 4. The findings suggest that food restriction and high environmental rearing temperature reduce long bone growth; bone breaking strength was affected by bird age but not by food restriction nor rearing ambient temperature.


Integrated spectrometer design with application to multiphoton microscopy.
We present a prism-based spectrometer integrated into a multifocal, multiphoton microscope. The multifocal configuration facilitates interrogation of samples under different excitation conditions. Notably, the image plane of the microscope and the image plane of the spectrometer are coincident eliminating the need for an intermediate image plane containing an entrance slit. An EM-CCD detector provides sufficient gain for spectral interrogation of single-emitters. We employ this spectrometer to observe spectral shifts in the two-photon excitation fluorescence emission of single CdSe nanodots as a function of excitation polarization.


Meta-analysis of genome-wide association studies for personality.
Personality can be thought of as a set of characteristics that influence people's thoughts, feelings and behavior across a variety of settings. Variation in personality is predictive of many outcomes in life, including mental health. Here we report on a meta-analysis of genome-wide association (GWA) data for personality in 10 discovery samples (17,375 adults) and five in silico replication samples (3294 adults). All participants were of European ancestry. Personality scores for Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness were based on the NEO Five-Factor Inventory. Genotype data of ≈ 2.4M single-nucleotide polymorphisms (SNPs; directly typed and imputed using HapMap data) were available. In the discovery samples, classical association analyses were performed under an additive model followed by meta-analysis using the weighted inverse variance method. Results showed genome-wide significance for Openness to Experience near the RASA1 gene on 5q14.3 (rs1477268 and rs2032794, P=2.8 × 10(-8) and 3.1 × 10(-8)) and for Conscientiousness in the brain-expressed KATNAL2 gene on 18q21.1 (rs2576037, P=4.9 × 10(-8)). We further conducted a gene-based test that confirmed the association of KATNAL2 to Conscientiousness. In silico replication did not, however, show significant associations of the top SNPs with Openness and Conscientiousness, although the direction of effect of the KATNAL2 SNP on Conscientiousness was consistent in all replication samples. Larger scale GWA studies and alternative approaches are required for confirmation of KATNAL2 as a novel gene affecting Conscientiousness.


Medicare payments for common inpatient procedures: implications for episode-based payment bundling.
Aiming to align provider incentives toward improving quality and efficiency, the Center for Medicare and Medicaid Services is considering broader bundling of hospital and physician payments around episodes of inpatient surgery. Decisions about bundled payments would benefit from better information about how payments are currently distributed among providers of different perioperative services and how payments vary across hospitals. Using the national Medicare database, we identified patients undergoing one of four inpatient procedures in 2005 (coronary artery bypass [CABG], hip fracture repair, back surgery, and colectomy). For each procedure, price-standardized Medicare payments from the date of admission for the index procedure to 30 days postdischarge were assessed and categorized by payment type (hospital, physician, and postacute care) and subtype. Average total payments for inpatient surgery episodes varied from U.S.$26,515 for back surgery to U.S.$45,358 for CABG. Hospital payments accounted for the largest share of total payments (60-80 percent, depending on procedure), followed by physician payments (13-19 percent) and postacute care (7-27 percent). Overall episode payments for hospitals in the lowest and highest payment quartiles differed by U.S.$16,668 for CABG, U.S.$18,762 for back surgery, U.S.$10,615 for hip fracture repair, and U.S.$12,988 for colectomy. Payments to hospitals accounted for the largest share of variation in payments. Among specific types of payments, those associated with 30-day readmissions and postacute care varied most substantially across hospitals. Fully bundled payments for inpatient surgical episodes would need to be dispersed among many different types of providers. Hospital payments--both overall and for specific services--vary considerably and might be reduced by incentives for hospitals and physicians to improve quality and efficiency.


[Consumption of antibiotics of the general population of Segovia area during the period between 1999 to 2007].
The antibiotics are the medicaments most used after the analgesics, being prescribed more than 85 % in Primary Care. The aim of the study is to analyze the evolution of the prescription of antibiotics of systemic use in the general population of the Area of Segovia, during the years 1999-2007 and to know his trends evolution. Antibiotics prescribed to the general population on the part of the Family physicians were processed using the information system of drugstore "CONCYLIA" that supplies the information in the shape of defined daily dose (DDD), transformed later into the indicator DHD (DDD for 1.000 inhabitants per day) taking as a base the population information of sanitary card. The global prescription of antibiotics of systemic use was high, 18,06 DHD (IC:17,22-18,90), with a variable evolution along the study in the shape of basin of low concavity. The percentage of prescription of penicillins was 64.42 % of the total of prescriptions corresponding to the group J01. The prescription in the Area of Segovia has presented a contained consumption in relation to other studies, showing differences in the volume of prescription from each the subgroups. The centralization of the consumption emphasizes in the subgroup of penicillins that supposed almost two third parts of the prescribed DDD. A change in the habits of prescription is observed detailing a decrease of the amoxicillin use and an increase of amoxicillin-clavulanic acid.