Psychosexual health 5 years after hysterectomy: population-based comparison with endometrial ablation for dysfunctional uterine bleeding.
We report a population-based comparison of psychosexual health 5 years after contrasting amounts of surgical treatments for heavy periods [dysfunctional uterine bleeding (DUB)]. Women's fears about sexual function after hysterectomy might not be unfounded. The psychosexual problems may return and/or develop with time. The removal of ovaries at the time of hysterectomy is associated with greater deterioration of self-reported sexual function. Surgical menopause significantly impairs sexual wellbeing. We failed to observe uniform beneficial effects of hormone replacement therapy (HRT) on reported psychosexual health. To compare self-reported bothersome sexual function; loss of interest in sex, difficulty in becoming sexually excited and vaginal dryness 5 years after surgical management of DUB [transcervical endometrial resection/ablation (TCRE) or subtotal and total hysterectomy, with and without prophylactic bilateral oophorectomy (BO)]. Prospective cohort study up to 5 years post-surgery for DUB, TCRE or hysterectomy, with or without BO. Over 400 NHS and private hospitals in England, Northern Ireland and Wales. Of 11,325 women who responded to the 5-year questionnaire, over 9500 (84%) were valid cases, and over 8900 (94%) did complete the questions relating to psychosexual function. Most were between the ages of 39 and 45 years, married or cohabiting. Self-reported experience of bother, recorded as 'some', 'severe' and 'extreme', to questions on (1) libido loss, (2) difficulty with sexual arousal, and (3) vaginal dryness during the past 4 weeks, 5 years after surgery. Five years after surgery for DUB, the crude and adjusted prevalence of psychosexual problems was higher after hysterectomy than after TCRE. Amongst the women with concurrent BO, the age- and HRT-adjusted odds ratios for extreme psychosexual problems were increased by 80% (libido loss), 82% (difficult sex arousal) and 69% (vaginal dryness) compared with TCRE. Five years after hysterectomy more women reported having bothersome psychosexual function than did the women who had a less invasive operation. Hormone therapy, although related to surgical method, did not reduce this long-term detrimental effect. The odds were particularly high amongst women with concurrent BO. Women should be advised that they might be at higher risk of psychosexual problems following hysterectomy, compared with a less invasive procedure.


Pulmonary surfactant protein A mediates enhanced phagocytosis of Mycobacterium tuberculosis by a direct interaction with human macrophages.
During initial infection with Mycobacterium tuberculosis, bacteria that reach the distal airspaces of the lung are phagocytosed by alveolar macrophages in the presence of pulmonary surfactant. Here we have examined the role of surfactant-associated protein A (SP-A) in phagocytosis of the virulent Erdman strain of M. tuberculosis by human monocyte-derived macrophages (MDMs) and human alveolar macrophages (HAMs). Macrophage monolayers incubated with soluble SP-A from alveolar proteinosis patients (APP SP-A4) and recombinant rat SP-A (SP-Ahyp) demonstrated enhanced adherence of M. tuberculosis, 82 +/- 17% and 49 +/- 18%, respectively. Removal of SP-A from monolayers by washing before adding bacteria did not diminish the enhanced adherence. Fluorescence microscopy demonstrated that washed monolayers contained intracellular rather than surface-bound SP-A. These studies indicated a direct interaction between SP-A and the macrophage in mediating enhanced adherence of M. tuberculosis. Consistent with this interpretation, macrophage monolayers formed on human or rat SP-A (substrate SP-A) demonstrated enhanced adherence of M. tuberculosis to their apical surface (APP SP-A and native rat SP-A increased M. tuberculosis adherence by 102 +/- 16% and 102 +/- 25%, respectively). Electron microscopy demonstrated increased numbers of phagocytosed bacteria in APP SP-A-treated MDM cross-sections. SP-A proteins devoid of carbohydrate failed to enhance M. tuberculosis adherence to macrophages. In contrast, heat-denatured APP SP-A enhanced adherence of bacteria equivalent to that of intact glycoprotein. Thus, the carbohydrate moieties of SP-A appear to be critical in the SP-A-macrophage interaction. Finally, mannan and anti-mannose receptor Ab completely inhibited the enhanced phagocytosis of M. tuberculosis observed with APP SP-A, providing evidence for up-regulation of macrophage mannose receptor activity. These studies implicate SP-A as an important modulator of alveolar macrophage function that results in an enhanced potential for M. tuberculosis to gain access to its intracellular niche.


A unique form of endemic pemphigus in northern Colombia.
Endemic forms of pemphigus are a unique group of autoimmune diseases that represent opportunities to study interactions of the environment and genetics with the immune system. The restriction to relatively well-defined regions of South and Central America and perhaps Africa characterizes these diseases. The aims of this study were to confirm the endemic nature of a new type of autoimmune disease occurring in a mining town in northeastern Colombia in the El Bagre area, to characterize it, and to compare it with other forms of endemic pemphigus. A 10-year prospective, controlled epidemiologic, humanitarian, and immunologic fieldwork case-control survey was performed in El Bagre, Colombia. Our work revealed that this disease is endemic in rural areas surrounding El Bagre. The disease appeared in 4.7% of middle-aged and older men and postmenopausal women from these rural areas. This disease differs from previously described forms of endemic pemphigus. It shares some heterogeneous immunoreactivity with paraneoplastic pemphigus but is not associated with malignant tumors. The disease resembles Senear-Usher syndrome (pemphigus and lupus) but occurs endemically either with a localized stable clinical course or in a systemic form. This systemic form may affect organs other than skin and is characterized by episodic relapses and poor prognosis in comparison with the localized form. We have confirmed endemic pemphigus foliaceus in El Bagre as an autoimmune disease that shares features with Senear-Usher syndrome but occurs in an endemic fashion. Heterogeneous antigenic reactivity is observed as in paraneoplastic pemphigus but with no evidence of association with neoplasia. In addition, constant exogenous antigenic stimulation and a genetic predisposition may be required in the pathogenesis of this disease.


Conditional Approximate Bayesian Computation: A New Approach for Across-Site Dependency in High-Dimensional Mutation-Selection Models.
A key question in molecular evolutionary biology concerns the relative roles of mutation and selection in shaping genomic data. Moreover, features of mutation and selection are heterogeneous along the genome and over time. Mechanistic codon substitution models based on the mutation-selection framework are promising approaches to separating these effects. In practice, however, several complications arise, since accounting for such heterogeneities often implies handling models of high dimensionality (e.g., amino acid preferences), or leads to across-site dependence (e.g., CpG hypermutability), making the likelihood function intractable. Approximate Bayesian Computation (ABC) could address this latter issue. Here, we propose a new approach, named Conditional ABC (CABC), which combines the sampling efficiency of MCMC and the flexibility of ABC. To illustrate the potential of the CABC approach, we apply it to the study of mammalian CpG hypermutability based on a new mutation-level parameter implying dependence across adjacent sites, combined with site-specific purifying selection on amino-acids captured by a Dirichlet process. Our proof-of-concept of the CABC methodology opens new modeling perspectives. Our application of the method reveals a high level of heterogeneity of CpG hypermutability across loci and mild heterogeneity across taxonomic groups; and finally, we show that CpG hypermutability is an important evolutionary factor in rendering relative synonymous codon usage. All source code is available as a GitHub repository (https://github.com/Simonll/LikelihoodFreePhylogenetics.git).


Stress training improves performance during a stressful flight.
This study investigated whether stress training introduced during the acquisition of simulator-based flight skills enhances pilot performance during subsequent stressful flight operations in an actual aircraft. Despite knowledge that preconditions to aircraft accidents can be strongly influenced by pilot stress, little is known about the effectiveness of stress training and how it transfers to operational flight settings. For this study, 30 participants with no flying experience were assigned at random to a stress-trained treatment group or a control group. Stress training consisted of systematic pairing of skill acquisition in a flight simulator with stress coping mechanisms in the presence of a cold pressor. Control participants received identical flight skill acquisition training but without stress training. Participants then performed a stressful flying task in a Piper Archer aircraft. Stress-trained research participants flew the aircraft more smoothly, as recorded by aircraft telemetry data, and generally better, as recorded by flight instructor evaluations, than did control participants. Introducing stress coping mechanisms during flight training improved performance in a stressful flying task. The results of this study indicate that stress training during the acquisition of flight skills may serve to enhance pilot performance in stressful operational flight and, therefore, might mitigate the contribution of pilot stress to aircraft mishaps.


Deinococcus metallilatus sp. nov. and Deinococcus carri sp. nov., isolated from a car air-conditioning system.
Two bacterial strains, designated MA1002(T) and MA1003(T), were isolated from the air-conditioning system of a car. Cells of both strains were Gram-reaction-positive, non-motile, non-spore-forming coccoids, catalase- and oxidase-positive and UV-radiation resistant. The major fatty acids of strain MA1002(T) were iso-C17 : 0 and iso-C15 : 0 and those of strain MA1003(T) were iso-C16 : 0 and iso-C16 : 1 H. The polar lipid profile of MA1002(T) contained phosphatidylethanolamine, two unidentified phosphoglycolipids, an unidentified phospholipid, an unidentified aminophospholipid, an unidentified aminolipid and an unidentified lipid. MA1003(T) had three unidentified phosphoglycolipids, six unidentified phospholipids, two unidentified glycolipids and two unidentified polar lipids as the polar lipids. The G+C contents of the genomic DNA of MA1002(T) and MA1003(T) were 70.5 and 76.0 mol%, respectively. MK-8 was the predominant respiratory quinone for both strains. 16S rRNA gene sequence analysis showed that strain MA1002(T) was phylogenetically related to Deinococcus apachensis DSM 19763(T), D. geothermalis DSM 11300(T), D. aerius TR0125(T) and D. aetherius ST0316(T) (92.9, 92.6, 92.0 and 91.9% sequence similarity, respectively), and MA1003(T) showed the highest sequence similarity to Deinococcus hopiensis KR-140(T) (92.9%) and D. xinjiangensis X-82(T) (91.4%). The results of genotypic and phenotypic characterizations showed that both strains could be distinguished from phylogenetically related species, and that the strains represented novel species within the genus Deinococcus, for which we propose the names Deinococcus metallilatus sp. nov. (type strain MA1002(T) = KACC 17964(T) = NBRC 110141(T)) and Deinococcus carri sp. nov. (type strain is MA1003(T) = KACC 17965(T) = NBRC 110142(T)).


Receptive field optimisation and supervision of a fuzzy spiking neural network.
This paper presents a supervised training algorithm that implements fuzzy reasoning on a spiking neural network. Neuron selectivity is facilitated using receptive fields that enable individual neurons to be responsive to certain spike train firing rates and behave in a similar manner as fuzzy membership functions. The connectivity of the hidden and output layers in the fuzzy spiking neural network (FSNN) is representative of a fuzzy rule base. Fuzzy C-Means clustering is utilised to produce clusters that represent the antecedent part of the fuzzy rule base that aid classification of the feature data. Suitable cluster widths are determined using two strategies; subjective thresholding and evolutionary thresholding respectively. The former technique typically results in compact solutions in terms of the number of neurons, and is shown to be particularly suited to small data sets. In the latter technique a pool of cluster candidates is generated using Fuzzy C-Means clustering and then a genetic algorithm is employed to select the most suitable clusters and to specify cluster widths. In both scenarios, the network is supervised but learning only occurs locally as in the biological case. The advantages and disadvantages of the network topology for the Fisher Iris and Wisconsin Breast Cancer benchmark classification tasks are demonstrated and directions of current and future work are discussed.


Functional analysis of a human tumor necrosis factor alpha (TNF-alpha) promoter polymorphism related to joint damage in rheumatoid arthritis.
Functional heterogeneity in the tumor necrosis factor alpha (TNF-alpha) gene may be responsible for the TNF-alpha response in infectious and autoimmune diseases. Recently, the TNF-238 promoter polymorphism was observed as being associated with a more destructive disease in rheumatoid arthritis (RA). To determine the relation between TNF-238 and disease progression, the extent of joint destruction in a cohort of 101 RA patients followed for 12 years was analyzed. Furthermore, we have attempted to link this polymorphism to TNF-alpha gene transcription in monocytes and lymphocytes in vitro. The extent of joint destruction determined on X-rays of hands and feet assessed after 0, 3, 6, and 12 years was compared with TNF-238 genotypes. Functional consequences of TNF-alpha gene polymorphisms using reporter gene constructs were analyzed in cells of the monocyte and lymphocyte lineage by means of transient transfection systems. The rate of joint damage in -238GA patients was lower than that in the -238GG patients, independent of HLA-DR4. Damage after 12 years was 76 +/- 30 for the -238GA versus 126 +/- 13 for the -238GG patients as determined by the van der Heijde's modification of Sharp's method. Furthermore, TNF-238A was found to be in linkage disequilibrium with an additional polymorphism at position -376. Functional assays revealed no significant differences in the level of inducible reporter gene expression between the TNF-238/-376 promoter constructs in the cell types tested. In a prospective study, we show that the TNF-238GG genotype contributes to progression of joint destruction in RA, independent of the presence of HLA-DR4. However, in vitro transfection assays indicate that TNF-238A by itself or in combination with TNF-376A is not likely to be of direct functional relevance for transcriptional activation. Therefore, these polymorphisms may serve as markers for additional polymorphisms in the TNF/LT locus or neighboring genes that may influence disease severity.


Nucleic acid extraction efficiency and bacterial recovery from maxillary sinus mucosal samples obtained by brushing or biopsy.
Chronic rhinosinusitis (CRS) is a common disease with a complex pathophysiology involving a microbial component. Culture-independent molecular analysis represents a promising new approach to clarify the microbiology of CRS, but standardized, optimized sampling methods still have not been defined. This study was designed to compare nucleic acid extraction rates and recovery of bacteria for two methods of sampling the maxillary sinus, mucosal biopsy, and brushing. Samples were obtained from 20 patients undergoing maxillary sinus surgery. Total extracted nucleic acid concentration and bacterial burden were compared between sample types. Total nucleic acid concentration varied across patients. No statistically significant difference in mean total DNA concentration from mucosal biopsy specimens or brushings was observed. However, compared with biopsy specimens, brush samples possessed a significant (p < 0.035) increase in bacterial copy number. Endoscopically directed mucosal brushings of the maxillary sinus provide equivalent concentrations of total DNA to mucosal biopsy specimens but possess greater concentrations of bacterial DNA, likely because of the greater surface area sampled by this method. Given the additional advantage of lower risk associated with obtaining brush samples, we suggest they represent the preferred sampling method for future genomic sinus studies.


The neighborhood context of racial and ethnic disparities in arrest.
This study assesses the role of social context in explaining racial and ethnic disparities in arrest, with afocus on how distinct neighborhood contexts in which different racial and ethnic groups reside explain variations in criminal outcomes. To do so, I utilize a multilevel, longitudinal research design, combining individual-level data with contextual data from the Project on Human Development in Chicago Neighborhoods (PHDCN). Findings reveal that black youths face multiple layers of disadvantage relative to other racial and ethnic groups, and these layers work to create differences in arrest. At the family level, results show that disadvantages in the form of unstable family structures explain much of the disparities in arrest across race and ethnicity. At the neighborhood level, black youths tend to reside in areas with both significantly higher levels of concentrated poverty than other youths as well as lower levels of collective efficacy than white youths. Variations in neighborhood tolerance of deviance across groups explain little of the arrest disparities, yet tolerance of deviance does influence the frequency with which a crime ultimately ends in an arrest. Even after accounting for relevant demographic, family, and neighborhood-level predictors, substantial residual arrest differences remain between black youths and youths of other racial and ethnic groups.


Impact of Australia's introduction of tobacco plain packs on adult smokers' pack-related perceptions and responses: results from a continuous tracking survey.
To investigate the impact of Australia's plain tobacco packaging policy on two stated purposes of the legislation--increasing the impact of health warnings and decreasing the promotional appeal of packaging--among adult smokers. Serial cross-sectional study with weekly telephone surveys (April 2006-May 2013). Interrupted time-series analyses using ARIMA modelling and linear regression models were used to investigate intervention effects. 15,745 adult smokers (aged 18 years and above) in New South Wales (NSW), Australia. Random selection of participants involved recruiting households using random digit dialling and selecting the nth oldest smoker for interview. The introduction of the legislation on 1 October 2012. Salience of tobacco pack health warnings, cognitive and emotional responses to warnings, avoidance of warnings, perceptions regarding one's cigarette pack. Adjusting for background trends, seasonality, antismoking advertising activity and cigarette costliness, results from ARIMA modelling showed that, 2-3 months after the introduction of the new packs, there was a significant increase in the absolute proportion of smokers having strong cognitive (9.8% increase, p=0.005), emotional (8.6% increase, p=0.01) and avoidant (9.8% increase, p=0.0005) responses to on-pack health warnings. Similarly, there was a significant increase in the proportion of smokers strongly disagreeing that the look of their cigarette pack is attractive (57.5% increase, p<0.0001), says something good about them (54.5% increase, p<0.0001), influences the brand they buy (40.6% increase, p<0.0001), makes their pack stand out (55.6% increase, p<0.0001), is fashionable (44.7% increase, p<0.0001) and matches their style (48.1% increase, p<0.0001). Changes in these outcomes were maintained 6 months postintervention. The introductory effects of the plain packaging legislation among adult smokers are consistent with the specific objectives of the legislation in regard to reducing promotional appeal and increasing effectiveness of health warnings.


Fecal glucocorticoid metabolite response of captive koalas (Phascolarctos cinereus) to visitor encounters.
Physiological responses of wildlife species to zoo visitors should be studied to better understand how wildlife perceive human encounters. We conducted an experimental test of the effect of changes in zoo visitor encounter experiences on the glucocorticoid (GC) response of koalas (Phascolarctos cinereus) in a Sydney zoo. Koalas were housed in a multiple-bay enclosure (two to three koalas per bay) for photography sessions with zoo visitors (no touching of koalas permitted by visitors). Following a one-week no-photography baseline period, photography sessions were rotated between three enclosure bays for four weeks (Intensive photography), then between five enclosure bays for an additional four weeks (Standard photography). A sixth enclosure bay was never included in the photography sessions (control bay); koalas in this bay showed no significant change in fecal cortisol metabolites (FCMs) during the course of the study. In the five experimental bays differences were seen between male and female koalas. Males had higher mean FCMs than females, and individual FCM traces showed that two male koalas that were related and of similar age responded strongly to the experimental manipulation. These two males showed a peak in FCMs at the beginning of the Intensive photography period, then a decline when photography sessions returned to the Standard protocol. No systematic pattern in response to photography sessions was observed in females. Our results demonstrate successful application of a non-invasive endocrinology tool for assessing the stress biology and welfare of captive zoo wildlife.


Seasonal Food Insecurity among Farm Workers in the Northern Cape, South Africa.
Very little is known about seasonal hunger in South Africa, or about the food security and nutritional status of farm workers. This article identifies a pathway to seasonal hunger-through intra-annual fluctuations in agricultural employment and income-that is underanalyzed in the literature. We report on findings from a year-long data collection process, comprising baseline and endline surveys and monthly monitoring of three food security indicators, with a sample of 195 female farm workers in the Northern Cape province in South Africa. The three monthly monitoring indicators-the Household Food Insecurity Access Scale (HFIAS), Dietary Diversity Score (DDS), and Coping Strategies Index (CSI)-which measure different aspects of food insecurity, are analyzed to determine whether and to what extent food security fluctuates seasonally in our sample. HFIAS results show unambiguous evidence of seasonal food insecurity, with the highest prevalence (88 percent experiencing severe food insecurity) and severity during the low employment winter period, and lowest prevalence (49 percent) and severity during the summer harvest, which corresponds with relatively higher employment and earnings. The DDS results show evidence of highest dietary diversity during summer and the CSI results reveal the need to employ coping strategies to deal with intensified food insecurity during winter.


Diabetic nephropathy.
Annual screening for microalbuminuria will allow the identification of patients with nephropathy at a point very early in its course. Improving glycemic control, aggressive antihypertensive treatment, and the use of ACE inhibitors will slow the rate of progression of nephropathy. In addition, protein restriction and other treatment modalities such as phosphate lowering may have benefits in selected patients.


Interval Debulking Surgery for Advanced Ovarian Cancer in Elderly Patients (≥70 y): Does the Age Matter?
Elderly ovarian cancer (OC) patients are more likely to be managed suboptimally, with worse clinical outcomes as a result. Strategies to decrease morbidity are lacking.Methodology: Consecutive patients with advanced stage OC (IIIC-IV) who were managed in our center between January 2016 and July 2018 were retrospectively analyzed. All patients underwent neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) according to our institution protocol. We divided patients into two groups: Group 1 (age ≥ 70 years) and Group 2 (age < 70 years). The primary outcome of the study was assessment of peri-operative morbidity amongst two groups. A total of 153 patients were referred during the study period. 114 patients underwent IDS after NACT (74.5%), 46 in Group 1 and 68 in Group 2. Elderly patients were more likely to receive more than three cycles of NACT prior to IDS compared to younger patients (39% vs. 19%, p = 0.03). Elderly patients were more frequently subjected to Cardiopulmonary Exercise Testing (CPET) as pre-operative assessment (63% vs. 27%, p = 0.002). Optimal/complete resection was achieved in all patients in Group 1 (100%) and in 97% of patients in Group 2. With the exception of higher postoperative cardiac arrhythmias in Group 1 (11% vs. 1%, p = 0.04), no significant differences in 30-day morbidity were observed. No 90-day death in both groups was registered. Older age should not preclude clinicians from offering ultra-radical resection to patients with advanced OC after NACT. In our series, elderly patients received the same treatment with similar outcomes to the younger group. Clinicians should be encouraged to use CPET for patients' selection following NACT.


Participatory training in monitoring and evaluation for maternal and newborn health programmes.
In the context of slow progress towards Millennium Development Goals for child and maternal health, an innovative participatory training programme in the monitoring and evaluation (M&E) of Maternal and Newborn Health programmes was developed and delivered in six developing countries. The training, for health professionals and programme managers, aimed: (i) to strengthen participants' skills in M&E to enable more effective targeting of resources, and (ii) to build the capacity of partner institutions hosting the training to run similar courses. This review aims to assess the extent to which these goals were met and elicit views on ways to improve the training. An online survey of training participants and structured interviews with stakeholders were undertaken. Data from course reports were also incorporated. There was clearly a benefit to participants in terms of improved knowledge and skills. There is also some evidence that this translated into action through M&E implementation and tool development. Evidence of capacity-building at an institutional level was limited. Lessons for professional development training can be drawn from several aspects of the training programme that were found to facilitate learning, engagement and application. These include structuring courses around participant material, focussing on the development of practical action plans and involving multi-disciplinary teams. The need for strengthening follow-up and embedding it throughout the training was highlighted to overcome the challenges to applying learning in the 'real world'.


Human domination of the biosphere: Rapid discharge of the earth-space battery foretells the future of humankind.
Earth is a chemical battery where, over evolutionary time with a trickle-charge of photosynthesis using solar energy, billions of tons of living biomass were stored in forests and other ecosystems and in vast reserves of fossil fuels. In just the last few hundred years, humans extracted exploitable energy from these living and fossilized biomass fuels to build the modern industrial-technological-informational economy, to grow our population to more than 7 billion, and to transform the biogeochemical cycles and biodiversity of the earth. This rapid discharge of the earth's store of organic energy fuels the human domination of the biosphere, including conversion of natural habitats to agricultural fields and the resulting loss of native species, emission of carbon dioxide and the resulting climate and sea level change, and use of supplemental nuclear, hydro, wind, and solar energy sources. The laws of thermodynamics governing the trickle-charge and rapid discharge of the earth's battery are universal and absolute; the earth is only temporarily poised a quantifiable distance from the thermodynamic equilibrium of outer space. Although this distance from equilibrium is comprised of all energy types, most critical for humans is the store of living biomass. With the rapid depletion of this chemical energy, the earth is shifting back toward the inhospitable equilibrium of outer space with fundamental ramifications for the biosphere and humanity. Because there is no substitute or replacement energy for living biomass, the remaining distance from equilibrium that will be required to support human life is unknown.


Satellite cells and myonuclei in young and elderly women and men.
The overall aim of this study was to assess the effects of aging on the satellite cell population. Muscle biopsies were taken from the tibialis anterior muscle of healthy, moderately active young (age range, 20-32 years; n = 31) and elderly (age range, 70-83 years; n = 27) women and men with comparable physical activity pattern. Satellite cells and myonuclei were visualized using a monoclonal antibody against neural cell adhesion molecule and counterstained with Mayer's hematoxylin. An average of 211 (range, 192-241) muscle fibers were examined for each individual. Compared with the young women and men, the elderly subjects had a significantly lower (P < 0.011) number of satellite cells per muscle fiber but a significantly higher (P < 0.004) number of myonuclei per muscle fiber. The number of satellite cells relative to the total number of nuclei [satellite cells/(myonuclei + satellite cells)] was significantly lower in the elderly than in the young women and men. These results imply that a reduction in the satellite cell population occurs as a result of increasing age in healthy men and women.


Prognostic determinants of community-acquired bloodstream infection in type 2 diabetic patients in ED.
The objective of the study is to describe the epidemiology and outcome of community-acquired bloodstream infection (BSI) in type 2 diabetic patients in emergency department (ED). All patients admitted to the ED of the university hospital from June 2010 to June 2011 with a history of type 2 diabetes mellitus and microbiologically documented BSI were retrospectively enrolled. Demographic characteristics, Charlson comorbidity index, antibiotic therapy, clinical severity, microbiological etiology, and diabetes-related complications were recorded in a standardized form. The major outcome measure was 30-day survival. χ2 Or Student t test was used for univariate analysis, and Cox proportional hazards models were used for multivariate analysis. Among 250 enrolled emergency patients with BSI, the overall 30-day mortality rate was 15.5%. Twenty-seven patients (10.7%) developed diabetic ketoacidosis (DKA), and 22 patients (8.8%) developed hyperosmolar hyperglycemic state. On univariate analysis, DKA rather than hyperosmolar hyperglycemic state was associated with adverse outcome. Other risk factors include higher mean glycated hemoglobin level, presence of underlying malignancy, long-term use of steroids, lower respiratory tract infection, and higher Charlson scores. Multivariate analysis identified 3 independent risk factors for early mortality when severity, comorbidity, age, and sex were under control: DKA (hazard ratio, 3.89; 95% confidence interval, 1.6-8.9), inappropriate antibiotics (2.25, 1.05-4.82), and chronic use of steroid (3.89, 1.1-13.2). In type 2 diabetic patients with BSI, a substantial proportion of patients developed DKA. This condition was probably underrecognized by clinicians and constituted an independent risk factor for short-term mortality. Other identified risk factors are potentially correctable and may allow preventive efforts to individuals at greatest potential benefit.


The Effect of Age and Competition Level on Subtle Motor Performance in Adolescents Medically Cleared Postconcussion: Preliminary Findings.
The aim of this study was to examine the effect of age and level of competition on subtle motor performance in adolescents who have recently been medically cleared postconcussion and never-injured controls. Thirty adolescents who were recently medically cleared postconcussion (12-18 yrs) and 30 never-concussed, typically developing controls were examined using the Revised Physical and Neurological Examination of Subtle Signs (PANESS) and the Immediate Post-Concussion Assessment and Cognitive Testing. Older age was associated with better Immediate Post-Concussion Assessment and Cognitive Testing scores in both groups, whereas only the control group showed improved motor performance on the PANESS with increasing age. Adolescents across both groups participating at a higher level of competition (school or travel level) had better motor performance on the PANESS than those participating at a lower level of competition (recreational level or no sports participation). Adolescents medically cleared postconcussion had greater motor deficits on the PANESS than controls did. After medical clearance, adolescents with a history of recent concussion demonstrate alterations in the relationship between motor function and age. The PANESS merits further exploration as a measure that is sensitive to factors affecting motor performance, such as age and level of athletic competition, as well as to persistent subtle motor deficits in adolescents medically cleared postconcussion.


Impact of Il28b-related single nucleotide polymorphisms on liver transient elastography in chronic hepatitis C infection.
Recently, several genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) in proximity to IL28B predict spontaneous clearance of hepatitis C virus (HCV) infection as well as outcome following pegylated interferon and ribavirin therapy among genotype 1 infected patients. Additionally the presence of the otherwise favorable IL28B genetic variants in the context of HCV genotype 3 infection reportedly entail more pronounced liver fibrosis and steatosis. The present study aimed to evaluate the impact of IL28B SNP variability on liver stiffness as accessed by transient elastography. Seven hundred and seventy-one Swedish HCV infected patients sequentially undergoing liver stiffness measurement by means of Fibroscan® in the context of a real-life trial had samples available for IL28B genotyping (rs12979860) and HCV genotyping. CC(rs12979860) was more common among HCV genotype 2 or 3 infected treatment-naïve patients than among those infected with genotype 1 (P<0.0001). Additionally CC(rs12979860) among HCV genotype 3 infected patients was associated with higher liver stiffness values (P = 0.004), and higher AST to platelet ratio index (APRI; p = 0.02) as compared to carriers of the T allele. Among HCV genotype 1 infected patients, CC(rs12979860) was significantly associated with higher viral load (P = 0.001), with a similar non-significant trend noted among HCV genotype 3 infected patients. This study confirms previous reports that the CC(rs12979860) SNP is associated with more pronounced liver pathology in patients chronically infected with HCV genotype 3 as compared to genotype 1, suggesting that IL28B genetic variants differently regulates the course of HCV infection across HCV genotypes.


Behavior, reproduction, and immunity of crated pregnant gilts: effects of high dietary fiber and rearing environment.
The objective of this study was to examine effects of increased gut fill and diverse developing environments on pregnant gilts' behavior and physiology. Gilts were cross-fostered at 1 d of age and transferred to either an indoor or outdoor production unit. Littermate gilts remained in their different environments during development and were moved into individual gestation crates in an indoor gestation unit. Of the 42 gilts, 19 were fed a control diet of fortified sorghum-soybean meal and 23 were fed the same diet with 25% beet pulp (high fiber). Control sows ate 2.0 kg/d and high-fiber sows ate 2.67 kg/d in a large pellet (thus resulting in approximately equal energy intake and differing total dietary intakes). Pregnant gilts had behavior and immune measures sampled at 30, 60, and 90 d of gestation. The day x diet interaction was significant (P = 0.01) for duration of standing: sows fed high-fiber diets stood less on d 30, but on d 60 and 90 they and the control sows stood for a similar duration. Sham chewing duration and frequency showed significant (P < 0.05) effects of gestation stage x diet x environment. Gilts reared outdoors and fed high fiber increased sham chewing over gestation, whereas all other treatment groups decreased this behavior over time. Outdoor-reared gilts had greater (P < 0.05) frequency and duration of drinking behavior than indoor-reared gilts. White blood cell numbers were higher (P < 0.05) for gilts fed high-fiber diets than for gilts fed the control diet. Immune (humoral and cellular systems) and reproductive measures (farrowing rate and litter size) and plasma cortisol concentrations were generally not influenced (P > 0.10) by diets and rearing environments, suggesting that in spite of significant changes in behavior and feed intake gilts' immune systems were not suppressed or enhanced. Behavioral data alone suggested that indoor-reared gilts showed fewer behavioral adaptations to the crates than outdoor-reared gilts. However, immune measures did not indicate that any treatments resulted in physiological effects indicative of stress.


GRPR-selective PET imaging of prostate cancer using [(18)F]-lanthionine-bombesin analogs.
The gastrin-releasing peptide receptor (GRPR) is overexpressed in a variety of human malignancies, including prostate cancer. Bombesin (BBN) is a 14 amino acids peptide that selectively binds to GRPR. In this study, we developed two novel Al(18)F-labeled lanthionine-stabilized BBN analogs, designated Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN, for positron emission tomography (PET) imaging of GRPR expression using xenograft prostate cancer models. (Methyl)lanthionine-stabilized 4,7-lanthionine-BBN and 2,6-lanthionine-BBN analogs were conjugated with a NOTA chelator and radiolabeled with Al(18)F using the aluminum fluoride strategy. Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN was labeled with Al(18)F with good radiochemical yield and specific activity>30 GBq/μmol for both radiotracers. The logD values measured for Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN were -2.14 ± 0.14 and -2.34 ± 0.15, respectively. In athymic nude PC-3 xenografts, at 120 min post injection (p.i.), the uptake of Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN in prostate cancer (PC-3) mouse models was 0.82 ± 0.23% ID/g and 1.40 ± 0.81% ID/g, respectively. An excess of unlabeled ɛ-aminocaproic acid-BBN(7-14) (300-fold) was co-injected to assess GRPR binding specificity. Tumor uptake of Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN in PC-3 tumors was evaluated by microPET (μPET) imaging at 30, 60 and 120 min p.i. Blocking studies showed decreased uptake in PC-3 bearing mice. Stabilized 4,7-lanthionine-BBN and 2,6-lanthionine-BBN peptides were rapidly and successfully labeled with (18)F. Both tracers may have potential for GRPR-positive tumor imaging.


Humoral and cell-mediated immune responses to an early 2-dose measles vaccination regimen in the United States.
Shifts in peak measles incidence to children <12 months old and the associated high mortality support the study of an early 2-dose measles vaccine regimen. Fifty-five infants were vaccinated with measles vaccine at age 6 (n=32) or 9 (n=23) months, followed by measles-mumps-rubella (MMR)-II vaccine at age 12 months. A control group received MMR-II only at age 12 months. Measles-specific humoral and cell-mediated immunity were evaluated before, 12 weeks after measles immunization, and 24 weeks after MMR-II. Measles-specific T cell proliferation after both doses of vaccine was equivalent, regardless of age or the presence of passive antibodies. Seroconversion rates, geometric mean titers, and the percentage of infants with antibody titers >120 mIU after the first measles vaccine were lower in infants vaccinated at age 6 months, regardless of the presence of passive antibodies, but measles humoral responses increased after the administration of MMR-II vaccine in children initially vaccinated at age 6 or 9 months. Measles vaccination elicits T cell responses in infants as young as 6 months old, which may prime the humoral response to the second dose. Initiating measles vaccination as an early 2-dose regimen results in an immunologic response that is likely to have clinical benefits in developed and developing countries.


Transcranial Doppler ultrasound findings in middle cerebral artery occlusion.
We evaluated the efficacy of transcranial Doppler ultrasonography in 23 patients suffering from acute middle cerebral artery occlusion. The diagnosis of occlusion was most suggestive when all basal arteries except the affected middle cerebral artery were detectable. Enhanced blood flow velocity in the anterior cerebral artery due to leptomeningeal collateralization was used as a corroborating criterion. With frequent follow-up examinations, we monitored reperfusion of the M1 segment resulting from recanalization or embolus migration in 16 patients. Those patients undergoing recanalization within days after onset of the first symptoms revealed variable clinical courses and lesion patterns on computed tomography, indicating the crucial importance of early and efficient leptomeningeal collateral blood supply. Transcranial Doppler ultrasonography was able to exclude middle cerebral artery occlusion with accuracy, which provides important clinical information. However, distal branch occlusions could not be detected with sufficient exactness.


Berberis vulgaris root bark extract prevents hyperoxaluria induced urolithiasis in rats.
Berberis vulgaris is a widely used plant for the treatment of urolithiasis. To evaluate its antiurolithic potential, the crude aqueous-methanol extract of Berberis vulgaris root bark (Bv.Cr) was tested in an animal model of urolithiasis, developed in male Wistar rats by adding 0.75% ethylene glycol in drinking water. Bv.Cr (50 mg/kg) inhibited CaOx crystal deposition in renal tubules and protected against associated changes including polyuria, weight loss, impaired renal function and the development of oxidative stress in kidneys. Activity-guided fractionation revealed the concentration of antiurolithic constituent(s) mainly in the aqueous fraction. These data, indicating the presence of antiurolithic activity in Berberis vulgaris root bark, rationalize its medicinal use for the treatment of urolithiasis.


Optical scattering by biological aerosols: experimental and computational results on spore simulants.
We present both a computational and an experimental approach to the problem of biological aerosol characterization, joining the expertises reached in the field of theoretical optical scattering by complex, arbitrary shaped particles (multipole expansion of the electromagnetic fields and Transition Matrix), and a novel experimental technique based on two-dimensional angular optical scattering (TAOS). The good agreement between experimental and computational results, together with the possibility for a laboratory single-particle angle-resolved investigation, opens a new scenario in biological particle modelling, and might have major implications for a rapid discrimination of airborne particles.


Medical care expenditure in suicides from non-illness-related causes.
Several epidemiological studies on medical care utilization prior to suicide have considered the motivation of suicide, but focused on the influence of physical illnesses. Medical care expenditure in suicide completers with non-illness-related causes has not been investigated. Suicides motivated by non-illness-related factors were identified using the investigator's note from the National Police Agency, which was then linked to the Health Insurance Review and Assessment data. We investigated the medical care expenditures of cases one year prior to committing suicide and conducted a case-control study using conditional logistic regression analysis after adjusting for age, gender, area of residence, and socioeconomic status. Among the 4515 suicides motivated by non-illness-related causes, medical care expenditures increased in only the last 3 months prior to suicide in the adolescent group. In the younger group, the proportion of total medical expenditure for external injuries was higher than that in the older groups. Conditional logistic regression analysis showed significant associations with being a suicide completer and having a rural residence, low socioeconomic status, and high medical care expenditure. After stratification into the four age groups, a significant positive association with medical care expenditures and being a suicide completer was found in the adolescent and young adult groups, but no significant results were found in the elderly groups for both men and women. Younger adults who committed suicide motivated by non-illness-related causes had a higher proportion of external injuries and more medical care expenditures than their controls did. This reinforces the notion that suicide prevention strategies for young people with suicidal risk factors are needed.


[Assessment of the impact of the NGO Refazer on medical care for children at social risk].
Assess the impact of activities by the nongovernmental organization Refazer in support of medical care for children at social risk. A longitudinal study was conducted of 77 patients from Rio de Janeiro in treatment at the Fernandes Figueira Institute and supported by Refazer. The assessment period was two years, one before and the other during the intervention period while being supported by the NGO. The percentage of hospitalizations, average length of stay, severity of the illness, use of technology, number of outpatient consultations, and clinical conditions involved were compared. The indicators linked with the hospitalizations revealed changes during the intervention period. There was a reduction in the average time and percentage of hospitalization. The most common pathologies were congenital malformations, chromosomal anomalies, and diseases of the nervous system. These diseases and HIV/AIDS were more prevalent in children that remained hospitalized even after receiving support from the NGO. Analysis of the indicators showed that the outcomes are adequate to the NGO's mission and that the population helped benefits from participation in the social support network. Although it cannot be stated that the benefits found are due exclusively to the activities of the NGO, a simple and easy-to-use evaluation of adequacy was developed that NGOs themselves can use, representing progress toward the institutional use of evaluations by NGOs working in health.


Conceptualizing the dynamics of workplace stress: a systems-based study of nursing aides.
Workplace stress is a complex phenomenon that may often be dynamic and evolving over time. Traditional linear modeling does not allow representation of recursive feedback loops among the implicated factors. The objective of this study was to develop a multidimensional system dynamics model (SDM) of workplace stress among nursing aides and conduct simulations to illustrate how changes in psychosocial perceptions and workplace factors might influence workplace stress over time. Eight key informants with prior experience in a large study of US nursing home workers participated in model building. Participants brainstormed the range of components related to workplace stress. Components were grouped together based on common themes and translated into feedback loops. The SDM was parameterized through key informant insight on the shape and magnitude of the relationship between model components. Model construction was also supported utilizing survey data collected as part of the larger study. All data was entered into the software program, Vensim. Simulations were conducted to examine how adaptations to model components would influence workplace stress. The SDM included perceptions of organizational conditions (e.g., job demands and job control), workplace social support (i.e., managerial and coworker social support), workplace safety, and demands outside of work (i.e. work-family conflict). Each component was part of a reinforcing feedback loop. Simulations exhibited that scenarios with increasing job control and decreasing job demands led to a decline in workplace stress. Within the context of the system, the effects of workplace social support, workplace safety, and work-family conflict were relatively minor. SDM methodology offers a unique perspective for researchers and practitioners to view workplace stress as a dynamic process. The portrayal of multiple recursive feedback loops can guide the development of policies and programs within complex organizational contexts with attention both to interactions among causes and avoidance of adverse unintended consequences. While additional research is needed to further test the modeling approach, findings might underscore the need to direct workplace interventions towards changing organizational conditions for nursing aides.


Phylogenetic molecular function annotation.
It is now easier to discover thousands of protein sequences in a new microbial genome than it is to biochemically characterize the specific activity of a single protein of unknown function. The molecular functions of protein sequences have typically been predicted using homology-based computational methods, which rely on the principle that homologous proteins share a similar function. However, some protein families include groups of proteins with different molecular functions. A phylogenetic approach for predicting molecular function (sometimes called "phylogenomics") is an effective means to predict protein molecular function. These methods incorporate functional evidence from all members of a family that have functional characterizations using the evolutionary history of the protein family to make robust predictions for the uncharacterized proteins. However, they are often difficult to apply on a genome-wide scale because of the time-consuming step of reconstructing the phylogenies of each protein to be annotated. Our automated approach for function annotation using phylogeny, the SIFTER (Statistical Inference of Function Through Evolutionary Relationships) methodology, uses a statistical graphical model to compute the probabilities of molecular functions for unannotated proteins. Our benchmark tests showed that SIFTER provides accurate functional predictions on various protein families, outperforming other available methods.


On the Mechanisms Underlying Directional Selectivity.
Recent efforts in the understanding of motion detection and directional selectivity include electrophysiological studies using single photoreceptor stimulations and a combination of electrophysiology and neuropharmacology. Results of the former have been interpreted in favor of facilitator motion detection models while results of the latter have been interpreted in favor of inhibitory models. In this paper, this conflicting data interpretation problem is addressed by mathematically modeling some effects of neuropharmacological substances and by applying this formalism to a neural network model of directionally selective motion perception. The study offers a possible resolution to the paradox.


Clinical experience of MRI4D QUASAR motion phantom for latency measurements in 0.35T MR-LINAC.
In MRgRT, accuracy of treatment depends on the gating latency, when real-time targeting and gating is enabled. Gating latency is dependent on image acquisition, processing time, accuracy, efficacy of target tracking algorithms, and radiation beam delivery latency. In this report, clinical experience of the MRI4D QUASAR motion phantom for latency measurements on a 0.35-T magnetic resonance-linear accelerator (MR-LINAC) with two imaging speeds and four tracking algorithms was studied. Beam-control latency was measured on a 0.35-T MR-LINAC system with four target tracking algorithms and two real-time cine imaging sequences [four and eight frames per second (FPS)]. Using an MR-compatible motion phantom, the delays between phantom beam triggering signal and linac radiation beam control signal were evaluated for three motion periods with a rigid target. The gating point was set to be 8 mm above the full exhalation position. The beam-off latency was measured for a total of 24 combinations of tracking algorithm, imaging FPS, and motion periods. The corresponding gating target margins were determined using the target motion speed multiplied by the beam-off latency. The largest measured beam-off latency was 302 ± 20 ms with the Large Deforming Targets (LDT) algorithm and 4 s motion period imaged with 8-FPS cine MRI. The corresponding gating uncertainty based on target motion speed was 3.0 mm. The range of the average beam-off latency was 128-243 ms in 4-FPS imaging and 47-302 ms in 8-FPS imaging. The gating latency was measured using an MRI4D QUASAR motion phantom in a 0.35-T MR-LINAC. The latency measurements include time delay related to MR imaging method, target tracking algorithm and system delay. The gating uncertainty was estimated based on the beam-off latency measurements and the target motion.


Reducing contact resistance in graphene devices through contact area patterning.
Performance of graphene electronics is limited by contact resistance associated with the metal-graphene (M-G) interface, where unique transport challenges arise as carriers are injected from a 3D metal into a 2D-graphene sheet. In this work, enhanced carrier injection is experimentally achieved in graphene devices by forming cuts in the graphene within the contact regions. These cuts are oriented normal to the channel and facilitate bonding between the contact metal and carbon atoms at the graphene cut edges, reproducibly maximizing "edge-contacted" injection. Despite the reduction in M-G contact area caused by these cuts, we find that a 32% reduction in contact resistance results in Cu-contacted, two-terminal devices, while a 22% reduction is achieved for top-gated graphene transistors with Pd contacts as compared to conventionally fabricated devices. The crucial role of contact annealing to facilitate this improvement is also elucidated. This simple approach provides a reliable and reproducible means of lowering contact resistance in graphene devices to bolster performance. Importantly, this enhancement requires no additional processing steps.


Register of dietary assessment calibration-validation studies: a status report.
A register of dietary assessment calibration-validation studies was created to improve communication between investigators, avoid duplication of effort, and identify gaps in knowledge. Calibration-validation studies were defined as investigations in which the participants completed at least two different dietary measurements. A questionnaire soliciting descriptive information about such studies was widely distributed. Completed questionnaires were received from October 1993 through September 1994 and the data from them were entered into a computer database. Preliminary individual reports were mailed to all contributors in September 1994 for revision or updating. Responses received by the end of October 1994 were incorporated into the database. A status report was published in December 1994. The report includes descriptions of 84 studies, 15 summary tables, and 6 reference indexes. Of the 84 studies included, 44 (52%) were conducted in North America, 35 (42%) in Europe, 2 (2%) in South America, 2 (2%) in Asia, and 1 (1%) in Australia. Sixty-three of the 84 studies (75%) used food-frequency questionnaires, 52 (62%) used food records, 35 (42%) used one or more dietary recalls, 11 (13%) used biological measures, and 8 (10%) used diet histories. Plans for maintaining and updating the register are being developed.


A comparison of the nutritional quality of food products advertised in grocery store circulars of high- versus low-income New York City zip codes.
Grocery stores can be an important resource for health and nutrition with the variety and economic value of foods offered. Weekly circulars are a means of promoting foods at a sale price. To date, little is known about the extent that nutritious foods are advertised and prominently placed in circulars. This study's aim was to compare the nutritional quality of products advertised on the front page of online circulars from grocery stores in high- versus low-income neighborhoods in New York City (NYC). Circulars from grocery stores in the five highest and five lowest median household income NYC zip codes were analyzed. Nutrition information for food products was collected over a two-month period with a total of 805 products coded. The study found no significant difference between the nutritional quality of products advertised on the front page of online circulars from grocery stores in high- versus low-income neighborhoods in New York City (NYC). In both groups, almost two-thirds of the products advertised were processed, one-quarter were high in carbohydrates, and few to no products were low-sodium, high-fiber, or reduced-, low- or zero fat. Through innovative partnerships with health professionals, grocery stores are increasingly implementing in-store and online health promotion strategies. Weekly circulars can be used as a means to regularly advertise and prominently place more healthful and seasonal foods at an affordable price, particularly for populations at higher risk for nutrition-related chronic disease.


Chiral recognition of proteins having L-histidine residues on the surface with lanthanide ion complex incorporated-molecularly imprinted fluorescent nanoparticles.
In this study, lanthanide ion complex incorporated molecularly imprinted fluorescent nanoparticles were synthesized. A combination of three novel approaches was applied for the purpose. First, lanthanide ions [Terbium(III)] were complexed with N-methacryloyl-L-histidine (MAH), polymerizable derivative of L-histidine amino acid, in order to incorporate the complex directly into the polymeric backbone. At the second stage, L-histidine molecules imprinted nanoparticles were utilized instead of whole protein imprinting in order to avoid whole drawbacks such as fragility, complexity, denaturation tendency, and conformation dependency. At the third stage following the first two steps mentioned above, imprinted L-histidine was coordinated with cupric ions [Cu(II)] to conduct the study under mild conditions. Then, molecularly imprinted fluorescent nanoparticles synthesized were used for L-histidine adsorption from aqueous solution to optimize conditions for adsorption and fluorimetric detection. Finally, usability of nanoparticles was investigated for chiral biorecognition using stereoisomer, D-histidine, racemic mixture, D,L-histidine, proteins with surface L-histidine residue, lysozyme, cytochrome C, or without ribonuclease A. The results revealed that the proposed polymerization strategy could make significant contribution to the solution of chronic problems of fluorescent component introduction into polymers. Additionally, the fluorescent nanoparticles reported here could be used for selective separation and fluorescent monitoring purposes.


The importance of HCV on the burden of chronic liver disease in Italy: a multicenter prevalence study of 9,997 cases.
Knowledge of the current epidemiology of chronic liver disease in Italy is mostly obsolete and fragmentary for the lack of up-to-date consistent data. In 2001, a 6-month prevalence study was undertaken in 79 hospitals to assess the characteristics of chronic liver disease in Italy. Both prevalent and incident cases were enrolled. A total of 9,997 patients were recruited, of whom 939 (9.4%) had normal liver biochemistry, 6,210 (62.1%) had chronic hepatitis, 1,940 (19.4%) had liver cirrhosis, and 341 (3.4%) had hepatocellular carcinoma (HCC). In 567 patients (5.7%) the diagnosis was not established. Hepatitis C virus (HCV) was found in 69.9% of the patients and was the only etiological factor in 56.3% of all the patients. Hepatitis B surface antigen (HBsAg) was present in the serum of 13.4% of the cases (in 10% it was the only etiological factor). A history of alcohol abuse was found in 23% of the cases (9.4% without viral infection). The prevalence of HCV-related cases was significantly lower in incident than in prevalent cases (44.9% vs. 59.9%, P < 0.0001), while the proportion of patients with alcohol abuse was much higher in incident than in prevalent cases (18.1% vs. 6.6%, P < 0.0001). These findings indicate that nearly one quarter of patients with chronic liver diseases in Italy have a severe disease such as liver cirrhosis and HCC represents a not negligible burden for the national health system. Hepatitis B fell in importance as an etiological factor. Hepatitis C is the important pathogenic factor for chronic liver disease in Italy. However, a comparison between the prevalent and incident cases suggests that in future HCV infection will also play a progressively decreasing role, in part as a consequence of treatment.


Switching of a TEA CO(2) laser with its own UV emitting parallel spark channels.
The efficient operation of a TEA CO(2) laser wherein the parallel spark channel preioniser of the laser itself functioned as a switch is reported. Simultaneous closure of the parallel gaps without an external switch has been achieved by ballasting them with mutually coupled inductances. The repetitive operation capability of such a laser is also discussed.


Syndrome of inappropriate anti-diuretic hormone in non-small cell lung carcinoma: a case report.
Paraneoplastic syndrome (PNS) related to lung cancer is very common. However, the syndrome of inappropriate anti-diuretic hormone secretion (SIADH) is rare in non-small cell lung cancer (NSCLC). We are reporting the case of a 58-year-old female presenting with dyspnea, cough, weight loss, digital clubbing, and one week of haemoptysis. CT showed a mediastinal mass completely encasing her superior vena cava, causing significant narrowing of the trachea and right mainstem bronchus. Bronchoscopy and biopsy identified a non-resectable NSCLC. Palliative radiation therapy was initiated. The day after her first radiation treatment, the patient developed asymptomatic hyponatremia, confirmed to be SIADH by laboratory evaluation. NSCLC-associated SIADH has been reported only thrice over the past two decades and never following radiation therapy with clinical improvement. The patient was discharged home on fluid restriction after her respiratory status improved to continue outpatient radiation and chemotherapy. SIADH in the setting of NSCLC is discussed.


Homotypic clusters of transcription factor binding sites are a key component of human promoters and enhancers.
Clustering of multiple transcription factor binding sites (TFBSs) for the same transcription factor (TF) is a common feature of cis-regulatory modules in invertebrate animals, but the occurrence of such homotypic clusters of TFBSs (HCTs) in the human genome has remained largely unknown. To explore whether HCTs are also common in human and other vertebrates, we used known binding motifs for vertebrate TFs and a hidden Markov model-based approach to detect HCTs in the human, mouse, chicken, and fugu genomes, and examined their association with cis-regulatory modules. We found that evolutionarily conserved HCTs occupy nearly 2% of the human genome, with experimental evidence for individual TFs supporting their binding to predicted HCTs. More than half of the promoters of human genes contain HCTs, with a distribution around the transcription start site in agreement with the experimental data from the ENCODE project. In addition, almost half of the 487 experimentally validated developmental enhancers contain them as well--a number more than 25-fold larger than expected by chance. We also found evidence of negative selection acting on TFBSs within HCTs, as the conservation of TFBSs is stronger than the conservation of sequences separating them. The important role of HCTs as components of developmental enhancers is additionally supported by a strong correlation between HCTs and the binding of the enhancer-associated coactivator protein Ep300 (also known as p300). Experimental validation of HCT-containing elements in both zebrafish and mouse suggest that HCTs could be used to predict both the presence of enhancers and their tissue specificity, and are thus a feature that can be effectively used in deciphering the gene regulatory code. In conclusion, our results indicate that HCTs are a pervasive feature of human cis-regulatory modules and suggest that they play an important role in gene regulation in the human and other vertebrate genomes.


Tactile spatial acuity and roughness discrimination: impairments due to aging and Parkinson's disease.
We used gratings of alternating ridges and grooves in a quantitative psychophysical investigation of tactile perception in patients with Parkinson's disease (PD) and age-matched normal controls. The groove width required for threshold discrimination of grating orientation was 25% higher in the control subjects compared to younger individuals studied previously (p = 0.004), indicating a small but significant decline in tactile spatial acuity with age. Relative to age-matched controls, patients with PD showed a twofold increase in the tactile spatial threshold (p = 3.07 x 10(-8), with somewhat greater impairment on the side more affected clinically (p = 0.03). Testing with the forearm prone, as compared to supine, produced a small improvement in the acuity of patients (p = 0.01) but not controls (p = 0.26). PD patients were also impaired in tactually discriminating grating roughness: their difference limens were over three times higher than those of controls (p = 5.74 x 10(-5)) for gratings differing in groove width, and over twice as high (p = 0.0003) for gratings differing in ridge width. We conclude that PD significantly impairs performance on these tactile tasks.


Public Beliefs About Somatic Symptom Disorders.
Objectives: Despite satisfactory effectiveness of treatment for somatic symptom disorders (SSD), treatment rates are low and treatment is usually initiated many years after first symptoms. In order to understand whether a lack of public mental health literacy might contribute to these poor treatment rates, we aimed to focus on two research questions: (1) What does the German public know and think about SSD? (2) Are knowledge and beliefs associated with socio-demographic factors and experiences with the disorder? Methods: Two vignettes with symptoms of a SSD were used in a national telephone survey in Germany (N = 1,004). Vignettes differed regarding main type of symptom (pain vs. fatigue) and existence of an earlier somatic disease (yes vs. no). Respondents were asked concerning knowledge and beliefs about causes, symptoms, and treatment using a standardized questionnaire. Results: 66% of the respondents agreed that a possible cause of the symptoms is a misinterpretation of body signals. About 1/3 recognized a mental health problem when confronted with the vignettes of cases with SSD. This rate was lower in case of a SSD with pain as the main symptom without a comorbid somatic disease (24.8%, 95%-CI: 21.1-28.6) compared to a case with fatigue as the main symptom and an earlier severe somatic disease (44.0%, 95%-CI: 39.6-48.3). Female respondents tended to have a more positive view on treatability and effectiveness of psychotherapy, while associations of knowledge and beliefs with education and age were inconsistent. Respondents who had contact with a person with SSD were more likely to think that psychotherapy is effective and that they know a lot about SSD compared to those who never had contact. Conclusions: While most of the German public seems to be well informed about causes of SSD as well as treatability and the effectiveness of psychotherapy, the majority has problems with interpreting symptoms and does not think they know a lot about symptoms like that. Increasing knowledge about SSD by education interventions may help to promote adequate help seeking.


Analysis of inflammatory cells in uveal melanoma after prior irradiation.
Primary uveal melanomas with a poor prognosis contain high numbers of infiltrating macrophages, especially of the M2 phenotype, as well as lymphocytes. We wondered whether local inflammatory responses were affected by irradiation and therefore determined the presence of inflammatory cells in uveal melanomas enucleated after prior irradiation. We analyzed 46 uveal melanoma-containing eyes that had to be enucleated due to nonresponsiveness, tumor recurrence, or complications. Immunofluorescent staining was performed to determine the presence of CD68(+) and CD68(+)CD163(+) macrophages, and of CD4(+), CD8(+), and Foxp3(+) regulatory T lymphocytes. Outcomes were compared with clinical and histologic parameters. Numbers of CD68(+) and CD68(+)CD163(+) macrophages in secondarily enucleated eyes varied widely, but did not differ from primarily enucleated eyes and were not related to the reason for enucleation. Similarly, the number of CD4(+), CD8(+), and Foxp3(+) T lymphocytes showed great variability. Tumors with epithelioid cells showed significantly more lymphocytes than spindle cell tumors. In the first 2 years after enucleation, previously irradiated tumors showed increased numbers of lymphocytes compared with primarily enucleated eyes. Numbers of infiltrating T lymphocytes and macrophages varied widely between tumors, but tumors with high numbers of macrophages also contained more lymphocytes. Irradiation had no effect on the number and type of macrophages, but led to an increased amount of T lymphocytes up to 24 months postirradiation. Because the presence of infiltrating cells was related to the tumor cell type, it is conceivable that the presence of an infiltrate is especially a consequence of the primary tumor characteristics before irradiation.


Pheromone chirality of asian palm weevils,Rhynchophorus ferrugineus (Oliv.) andR. vulneratus (Panz.) (Coleoptera: Curculionidae).
Production of 4-methyl-5-nonanol, and 4-methyl-5-nonanone by two sympatric Asian palm weevils,Rhynchophorus ferrugineus (Oliv.) andR. vulneratus (Panz.) suggested that enantiospecificity of either compound could impart species specificity of pheromone communication. Weevil-produced, racemic 4-methyl-5-nonanol and 4-methyl-5-nonanone and their stereoselectively synthesized optical isomers were subjected to gas chromatographic-electroantennographic detection (GC-EAD) and GC-mass spectrometry (MS) on a chiral Cyclodex-B column. Only theS,S stereoisomer of 4-methyl-5-nonanol was EAD active and was produced by bothR. ferrugineus andR. vulneratus. Production and EAD activity of (S)-4-methyl-5-nonanone exceeded that of its antipode in both weevils. In field experiments in Java. (4S, 5S)-4-methyl-5-nonanol and the stereoisomeric mixture were equally attractive. The 4R,5R stereoisomer was inactive. The corresponding ketone enantiomers neither enhanced nor reduced attraction to (4S,5S)-4-methyl-5-nonanol. Lack of apparent differences betweenR. ferrugineus andR. vulneratus pheromones suggests that synonomy of both weevils should be considered unless other pre- or postzygotic reproductive isolating mechanisms are disclosed in future studies.


Therapeutic alliance in face-to-face and telephone-administered cognitive behavioral therapy.
Telephone-administered therapies have emerged as an alternative method of delivery for the treatment of depression, yet concerns persist that the use of the telephone may have a deleterious effect on therapeutic alliance. The purpose of this study was to compare therapeutic alliance in clients receiving cognitive behavioral therapy (CBT) for depression by telephone (T-CBT) or face-to-face (FtF-CBT). We randomized 325 participants to receive 18 sessions of T-CBT or FtF-CBT. The Working Alliance Inventory (WAI) was administered at Weeks 4 and 14. Depression was measured during treatment and over 1 year posttreatment follow-up using the Hamilton Rating Scale for Depression and Patient Health Questionnaire-9. There were no significant differences in client or therapist WAI between T-CBT or FtF-CBT (Cohen's f² ranged from 0 to .013, all ps > .05). All WAI scores predicted depression end of treatment outcomes (Cohen's f² ranged from .009 to .06, all ps < .02). The relationship between the WAI and depression outcomes did not vary by treatment group (Cohen's f² ranged from 0 to .004, ps > .07). The WAI did not significantly predict depression during posttreatment follow-up (all ps > .12). Results from this analysis do not support the hypothesis that the use of the telephone to provide CBT reduces therapeutic alliance relative to FtF-CBT.


Screening for bacillus isolates in the broiler gastrointestinal tract.
Spores from a number of different Bacillus species are currently being used as human and animal probiotics, although their mechanisms of action remain poorly understood. Here we describe the isolation of 237 presumptive gut-associated Bacillus spp. isolates that were obtained by heat and ethanol treatment of fecal material from organically reared broilers followed by aerobic plating. Thirty-one representative isolates were characterized according to their morphological, physiological, and biochemical properties as well as partial 16S rRNA gene sequences and screening for the presence of plasmid DNA. The Bacillus species identified included B. subtilis, B. pumilus, B. licheniformis, B. clausii, B. megaterium, B. firmus, and species of the B. cereus group, whereas a number of our isolates could not be classified. Intrinsic properties of potential importance for survival in the gut that could be advantageous for spore-forming probiotics were further investigated for seven isolates belonging to five different species. All isolates sporulated efficiently in the laboratory, and the resulting spores were tolerant to simulated gastrointestinal tract conditions. They also exhibited antimicrobial activity against a broad spectrum of bacteria, including food spoilage and pathogenic organisms such as Bacillus spp., Clostridium perfringens, Staphylococcus aureus, and Listeria monocytogenes. Importantly, the isolates were susceptible to most of the antibiotics tested, arguing that they would not act as donors for resistance determinants if introduced in the form of probiotic preparations. Together, our results suggest that some of the sporeformers isolated in this study have the potential to persist in or transiently associate with the complex gut ecosystem.


Nonmedical use of promethazine hydrochloride among heroin injectors in Vietnam: unrecognized risks and unintended consequences.
Surveillance studies have noted intravenous injection of promethazine hydrochloride (PHC) among populations that use heroin in south and southeast Asia. However, little is known about onset and initiation of PHC use and its relationship to habitual heroin use. As part of a longitudinal study of heroin initiation, a sample of 179 new heroin users, aged 15-27 years, were interviewed between October 2005 and December 2006 in Hanoi, Vietnam. Cox proportional hazard regression analysis was used to characterize age at promethazine initiation and its association with relevant covariates. 76% reported lifetime use of PHC. Mean age of PHC initiation was 21.3 years, on average 6 months following onset of heroin injection. In multivariate analysis, lifetime use of diazepam [HR = 1.69 (1.17, 2.44); p-value = .01] and injecting heroin for more than 1.58 years [HR = 1.46 (1.04, 2.06); p-value = .03] were associated with PHC initiation. Intravenous injection of PHC is a relatively common practice among young injection heroin users in Hanoi, Vietnam who use it on a situational basis to substitute for heroin (when heroin is not available or when heroin is too costly) or to augment the effects of an inadequate heroin dosing (delaying onset of heroin withdraw). Existing drug prevention strategies in Vietnam are focused primarily on heroin and most new heroin users initiate PHC use without prior knowledge of its high risk for serious vein damage. Future research is needed on the PHC use among heroin users, including long-term medical consequences of PHC exposure.


Synthesis of yellow and red fluorescent 1,3a,6a-triazapentalenes and the theoretical investigation of their optical properties.
To expand the originally developed fluorescent 1,3a,6a-triazapentalenes as fluorescent labelling reagents, the fluorescence wavelength of the 1,3a,6a-triazapentalenes was extended to the red color region. Based on the noteworthy correlation of the fluorescence wavelength with the inductive effect of the 2-substituent, electron-deficient 2-(2-cyano-4-methoxycarbonylphenyl)-1,3a,6a-triazapentalene and 2-(2,6-dicyano-4-methoxycarbonylphenyl)-1,3a,6a-triazapentalene were synthesized. The former exhibited yellow fluorescence and the latter exhibited red fluorescence, and both compounds exhibited large Stokes shifts, and the 1,3a,6a-triazapentalene system enabled the same fluorescent chromophore to cover the entire region of visible wavelengths. The potential applications of the 1,3a,6a-triazapentalenes as fluorescent probes in the fields of the life sciences were investigated, and the 1,3a,6a-triazapentalene system was clearly proven to be useful as a fluorescent reagent for live cell imaging. Quantum chemical calculations were performed to investigate the optical properties of the 1,3a,6a-triazapentalenes. These calculations revealed that the excitation involves a significant charge-transfer from the 1,3a,6a-triazapentalene skeleton to the 2-substituent. The calculated absorption and fluorescence wavelengths showed a good correlation with the experimental ones, and thus the system could enable the theoretical design of substituents with the desired optical properties.


Diabetogenic T-cell clones.
The role of T-cells in the pathogenesis of IDDM has been an area of much interest, and investigators have recently acquired new tools for studies on T-cells with the advent of T-cell clones that are reactive with islet antigens. Derived from NOD mice, diabetogenic T-cell lines and clones have for the most part been CD4+ and T-helper 1 (Th1)-like in their cytokine production. Some CD8+ cytotoxic clones have also been reported, although these have generally not transferred diabetes in the absence of CD4+ T-cells. The T-cell clones that have been described can also be separated on the basis of their antigen reactivity. While many of the T-cell lines and clones described react with islets, isolated islet cells, or islet membrane preparations, others have known antigen specificities, reacting with defined islet cell proteins such as insulin, GAD, and heat shock proteins. Particularly in the case of insulin-reactive clones, diabetogenicity has also been demonstrated. In light of the many possible T-cell reactivities that may arise from the islet lesion, the question of whether there is a dominant initiating antigen is a particularly intriguing one.


Successful management of refractory intracranial hypertension from acute hyperammonemic encephalopathy in a woman with ornithine transcarbamylase deficiency.
Ornithine transcarbamylase deficiency (OTCD) is the most common of the urea cycle disorders and results in an accumulation of ammonia and its metabolites. Excess ammonia in the brain is metabolized to glutamine, which increases intracellular osmolarity and contributes to cytotoxic edema. We report a case of a woman heterozygous for OTCD who developed acute hyperammonemic encephalopathy and increased intracranial pressure (ICP). Despite hemodialysis, protein restriction, and administration of pharmacologic nitrogen scavengers, she developed progressive cerebral edema and increased ICP that was refractory to maximal medical management. She underwent a bifrontal decompressive craniectomy resulting in resolution of her intracranial hypertension. Aggressive multimodality management of the patient coupled with bifrontal decompressive hemicraniectomy was a life-saving measure, offering the patient a reasonable outcome. At 6 month follow-up she had moderate disability on the Glasgow Outcome Score associated with cognitive difficulties.


Use of Bayesian statistics in drug development: Advantages and challenges.
MAINLY, TWO STATISTICAL METHODOLOGIES ARE APPLICABLE TO THE DESIGN AND ANALYSIS OF CLINICAL TRIALS: frequentist and Bayesian. Most traditional clinical trial designs are based on frequentist statistics. In frequentist statistics prior information is utilized formally only in the design of a clinical trial but not in the analysis of the data. On the other hand, Bayesian statistics provide a formal mathematical method for combining prior information with current information at the design stage, during the conduct of the trial, and at the analysis stage. It is easier to implement adaptive trial designs using Bayesian methods than frequentist methods. The Bayesian approach can also be applied for post-marketing surveillance purposes and in meta-analysis. The basic tenets of good trial design are same for both Bayesian and frequentist trials. It has been recommended that the type of analysis to be used (Bayesian or frequentist) should be chosen beforehand. Switching to an analysis method that produces a more favorable outcome after observing the data is not recommended.


In Sync: The Effect of Physiology Feedback on the Match between Heart Rate and Self-Reported Stress.
Over the past years self-tracking of physiological parameters has become increasingly common: more and more people are keeping track of aspects of their physiological state (e.g., heart rate, blood sugar, and blood pressure). To shed light on the possible effects of self-tracking of physiology, a study was conducted to test whether physiology feedback has acute effects on self-reported stress and the extent to which self-reported stress corresponds to physiological stress. In this study, participants executed several short tasks, while they were either shown visual feedback about their heart rate or not. Results show that self-reported stress is more in sync with heart rate for participants who received physiology feedback. Interactions between two personality factors (neuroticism and anxiety sensitivity) and feedback on the level of self-reported stress were found, indicating that while physiology feedback may be beneficial for individuals high in neuroticism, it may be detrimental for those high in anxiety sensitivity. Additional work is needed to establish how the results of this study may extend beyond immediate effects in a controlled lab setting, but our results do provide a first indication of how self-tracking of physiology may lead to better body awareness and how personality characteristics can help us predict which individuals are most likely to benefit from self-tracking of physiology.


[Total cholesterol, HDL-cholesterol and blood pressure in relation to life style: results of the first population screening of the Swiss MONIKA Project].
To evaluate the association of individual health habits with levels of cardiovascular risk factors such as serum cholesterol and blood pressure, data from a representative population sample of 860 men and 788 women, aged 25 to 64 years and residing in Western Switzerland, were analyzed cross-sectionally. The data had been collected during 1984/85 as a part of the WHO MONICA project, an international research project on the epidemiology of cardiovascular diseases. In age-adjusted analysis, a score of prudent diet was a reasonably strong inverse correlate of total cholesterol in men (p less than 0.001) but less so in women (p = 0.11); the diet score was unrelated to HDL cholesterol. In both genders, alcohol consumption was associated with elevated levels of systolic and diastolic blood pressure (men: both p less than 0.001; women: p = 0.05 and 0.01 respectively) and of HDL cholesterol (men and women: p less than 0.001). Coffee consumption was unrelated to either blood lipids or blood pressure. In both men and women, leisure-time exercise was a predictor of a low-risk lipid profile, i.e. a low total cholesterol/HDL ratio (both p less than 0.001). Better educated persons, especially women, revealed consistently lower levels of cardiovascular risk factors. The independent character of these lifestyle-risk factor-associations was largely confirmed in a multivariate analysis, with cigarette smoking emerging as another significant predictor of a deteriorated lipid profile, while education was not an independent determinant of biological risk factors. Lifestyle variables, including body mass index, explained 9 to 19% of variance in cardiovascular risk factors, with relative weight being the strongest of the predictors related to behaviour. Entering age and sex into the regression models enhanced the predictive power of the equations to 16 to 26% explained risk factor variance. We conclude from this population-based, cross-sectional study that personal health habits such as diet, exercise, alcohol consumption and smoking, as well as body weight are significantly and independently related to blood lipid and blood pressure levels; the apparent size of effect of these behavioural traits on biological risk factors for cardiovascular diseases was only modest, but it may nevertheless be relevant to prevention.


Causal Evidence for Mnemonic Metacognition in Human Precuneus.
Metacognition is the capacity to introspectively monitor and control one's own cognitive processes. Previous anatomical and functional neuroimaging findings implicated the important role of the precuneus in metacognition processing, especially during mnemonic tasks. However, the issue of whether this medial parietal cortex is a domain-specific region that supports mnemonic metacognition remains controversial. Here, we focally disrupted this parietal area with repetitive transcranial magnetic stimulation in healthy human participants of both sexes, seeking to ascertain its functional necessity for metacognition in memory versus perceptual decisions. Perturbing precuneal activity selectively impaired metacognitive efficiency of temporal-order memory judgment, but not perceptual discrimination. Moreover, the correlation in individuals' metacognitive efficiency between domains disappeared when the precuneus was perturbed. Together, these findings provide evidence reinforcing the notion that the precuneal region plays an important role in mediating metacognition of episodic memory retrieval.SIGNIFICANCE STATEMENT Theories on the neural basis of metacognition have thus far been largely centered on the role of the prefrontal cortex. Here we refined the theoretical framework through characterizing a unique precuneal involvement in mnemonic metacognition with a noninvasive but inferentially powerful method: transcranial magnetic stimulation. By quantifying metacognitive efficiency across two distinct domains (memory vs perception) that are matched for stimulus characteristics, we reveal an instrumental role of the precuneus in mnemonic metacognition. This causal evidence corroborates ample clinical reports that parietal lobe lesions often produce inaccurate self-reports of confidence in memory recollection and establish the precuneus as a nexus for the introspective ability to evaluate the success of memory judgment in humans.


Prospective Disability in Different Combinations of Somatic and Mental Multimorbidity.
Multimorbidity (multiple co-occurring chronic conditions) may be an important contributor to disability and poor health-related quality of life. The functional consequences of specific combinations of somatic and mental health conditions are unclear. Nationally representative prospective cohort study using the National Health and Aging Trends Study data of Medicare beneficiaries. We included 4,017 participants aged 65 years or older interviewed in 2013 and 2014. The primary outcome was prospective activities of daily living (ADL)-instrumental ADL (IADL) index (range = 0-11) assessed in 2014. All other measures were assessed in 2013. Chronic conditions included heart disease, hypertension, stroke, diabetes, arthritis, lung disease, osteoporosis, cancer, depression, and cognitive impairment. Analyses were adjusted for age, sex, education, race/ethnicity, body mass index, and baseline ADL-IADL. Thirty-four percent of multimorbidity combinations included depression, cognitive impairment, or both. Relative to multimorbidity combinations of exclusively somatic conditions, combinations that included both depression and cognitive impairment were associated with 1.34 times greater ADL-IADL in adjusted models (95% confidence interval [CI]: 1.09, 1.64). Relative to combinations of both depression and cognitive impairment, combinations of cognitive impairment and somatic conditions were associated with 0.84 times lower ADL-IADL in adjusted models (95% CI: 0.74, 0.96); combinations of depression and somatic conditions were associated with 0.72 times lower ADL-IADL in adjusted models (95% CI: 0.62, 0.85). Depression and/or cognitive impairment was identified in one-third of older adults with multimorbidity, and these combinations were associated with substantially greater prospective disability than combinations comprised exclusively of somatic conditions. This argues for identifying and managing mental health conditions that co-occur with somatic conditions.


Fulminant liver failure model with hepatic encephalopathy in the mouse.
To develop a reliable murine model for fulminant liver failure (FLF). We treated three groups of male C57BL/6 mice:as controls, with azoxymethane (AOM), and with galactosamine (Gal) and tumor necrosis factor-alpha (TNFα). Effects of body temperature (BT) control on survival, in all three groups were investigated. Using BT control, survival, histopathological findings and biochemical/coagulation profiles were compared between the experimental groups. Effects of hydration on international normalized ratios of prothrombin time (PT-INR) were also checked. Dose-dependent survival curves were made for both experimental groups. Neurological behaviors were assessed using a coma scale. No unexpected BT effects were seen in the control group. The AOM group, but not the Gal+TNFα group, showed significant differences in survival curves between those with and without BT care. Histopathological assessment showed consistent FLF findings in both experimental groups with BT care. Between the experimental groups, there were significant differences in aspartate aminotransferase levels and PT-INR; and significant differences in PT-INRs between sufficiently- and insufficiently-hydrated groups. There were significant differences between FLF models, in the duration of each coma stage, with significant differences in stages 1 and 3 as percentages of the diseased state (stages 1-4). The two FLF models with BT care showed different survival curves in the dose-dependent survival study. Azoxymethane can provide a good FLF model, but requires a specialized environment and careful BT control. Other FLF models may also be useful, depending on research purpose. Thoughtful attention to caregiving and close observation are indispensable for successful FLF models.


Robust identification of investor beliefs.
This paper develops a method informed by data and models to recover information about investor beliefs. Our approach uses information embedded in forward-looking asset prices in conjunction with asset pricing models. We step back from presuming rational expectations and entertain potential belief distortions bounded by a statistical measure of discrepancy. Additionally, our method allows for the direct use of sparse survey evidence to make these bounds more informative. Within our framework, market-implied beliefs may differ from those implied by rational expectations due to behavioral/psychological biases of investors, ambiguity aversion, or omitted permanent components to valuation. Formally, we represent evidence about investor beliefs using a nonlinear expectation function deduced using model-implied moment conditions and bounds on statistical divergence. We illustrate our method with a prototypical example from macrofinance using asset market data to infer belief restrictions for macroeconomic growth rates.


TNRT profiles with the nucleus research platform 8 system.
This study investigates the effect of the Nucleus CI24RE implant's neural response telemetry (NRT) system, which has less internal noise compared to its predecessor, the CI24M/R implant, on the NRT threshold (TNRT) profile across the array. CI24M/R measurements were simulated by ignoring CI24RE measurements with response amplitudes below 50 uV. Comparisons of the estimated TNRTs from the CI24RE measurements and the CI24M/R simulations suggest that, apart from a constant level difference, the TNRT profiles from the newer implant generally would not have differed very much from those of its predecessor. This view was also reflected by principal component analysis (PCA) results which revealed a 'shift' component similar to that reported by Smoorenburg et al (2002). On the whole, there is no indication that current practices of using the TNRT profiles for assisting with speech processor programming need to be revised for the CI24RE implant.


Inhalational or total intravenous anaesthesia: is total intravenous anaesthesia useful and are there economic benefits?
The comparison of inhalational and intravenous anaesthesia has been the subject of many controlled trials and meta-analyses. These reported diverse endpoints typically including measures of the speed and quality of induction of anaesthesia, haemodynamic changes, operating conditions, various measures of awakening, postoperative nausea and vomiting and discharge from the recovery area and from hospital as well as recovery of psychomotor function. In a more patient-focused Health Service, measures with greater credibility are overall patient satisfaction, time to return to work and long-term morbidity and mortality. In practice, studies using easier to measure proxy endpoints dominate - even though the limitations of such research are well known. Recent study endpoints are more ambitious and include impact on survival from cancer and the possibility of differential neurotoxic impact on the developing brain and implications for neuro-behavioural performance. Economic analysis of anaesthesia is complex and most published studies are naive, focusing on drug acquisition costs and facility timings, real health economics are much more difficult. Preferred outcome measures would be whole institution costs or the ability to reliably add an extra case to an operating list, close an operating room and reduce the number of operating sessions offered or permanently decrease staffing. Alongside this, however, potential long-term patient outcomes should be considered.


Racial/Ethnic Diversity in Academic Public Health: 20-Year Update.
This study is a follow-up to an examination of the racial/ethnic composition of public health students (1996) and faculty (1997) at schools of public health that was conducted 20 years ago. We examined data on the race/ethnicity of students, graduates, and faculty among Association of Schools and Programs of Public Health (ASPPH)-member institutions during 2016-2017 and how these data have changed in the past 20 years. We obtained data on the race/ethnicity of students (in 1996 and 2016), graduates (in 1996 and 2016), and faculty (in 1997 and 2017) at ASPPH-member institutions from the ASPPH Data Center. We tabulated frequencies, percentages, and 20-year percentage-point changes by race/ethnicity. We examined data for all current ASPPH-member institutions and for comparable subcohorts of 1996 and 1997 member institutions that are current ASPPH members. In graduate student enrollment, the 20-year increase in each nonwhite racial/ethnic subgroup was ≤5 percentage points. Among tenured faculty, the 20-year increase was greatest among Asians (8 percentage points) but was <3 percentage points for black, Hispanic, and Native American faculty. The increasing racial/ethnic diversity among students, graduates, and faculty in schools and programs of public health contributes to parallel increases in racial/ethnic diversity in the public health workforce. Schools and programs of public health should recruit clusters of racial/ethnic minority students using holistic application review processes, provide enrolled students with racially/ethnically diverse role models and mentors, and dedicate staffing to ensure a student-centered approach. In addition, those who mentor racially/ethnically diverse students and junior faculty should be rewarded.