Sleep arrangements and behavior of bed-sharing families in the home setting.
We aimed to provide a quantitative analysis of the sleep arrangements and behaviors of bed-sharing families to further understand the risks and benefits as well as the effects of infant age and room temperature on bed-sharing behaviors. Forty infants who regularly bed shared with > or = 1 parent > or = 5 hours per night were recruited. Overnight video of the family and physiological monitoring of the infant was conducted in infants' homes. Infant sleep position, potential for exposure to expired air, head covering and uncovering, breastfeeding, movements, family sleep arrangements, responses to the infant, and interactions were logged. All infants slept with their mother. Fathers were included in 18 studies and siblings in 4. Infants usually slept beside the mother, separated from the father/siblings (if present), facing the mother, with head at mothers' breast level, touching, or with mother cradling. Median overnight breastfeeding duration was 40.5 minutes. Mothers commonly faced their infant, but infants were rarely in a position that potentially exposed them to maternal expired air. Fathers were seldom in contact with the infant during sleep. Of the 102 head-covering episodes observed in 22 infants, 80% were because of changes in adult sleep position. Sixty-eight percent of head uncovering was facilitated by the mother; half of these events were prompted by the infant. A 1 degree C increase in room temperature decreased infant head covering by 0.2 hours. The mother-infant relationship is of prime importance during bed sharing, whether the father is present or not. The focus around breastfeeding often dictates the sleep position of the infant and mother, though room temperature may also influence this. In colder rooms infants tend to spend more time with their face covered by bedding. Frequent maternal interactions rely on the ability of the mother to arouse with little stimulation. Mothers, perhaps impaired by alcohol, smoking, or overtiredness, may not be able to respond appropriately.


Polysubstituted 3-trifluoromethylpyrazoles: regioselective (3 + 2)-cycloaddition of trifluoroacetonitrile imines with enol ethers and functional group transformations.
Non-catalysed addition of trifluoroacetonitrile imines to enol ethers provided fully regioselectively (3 + 2)-cycloadducts, which either spontaneously or via Brønsted acid-induced elimination of ROH molecules led to the formation of 3-trifluoromethylated pyrazoles. In the case of 2,3-dihydrofuran, the respective bicyclic intermediate was isolated and its structure was confirmed by X-ray analysis. Using the developed protocol the synthesis of a known antitumor compound SC-560 was performed in 45% yield. Subsequent functionalisations of selected 4-(ω-hydroxyalkyl)pyrazoles at C(5) through lithiation/addition, cross-coupling reactions or via intramolecular Pd-catalysed C-H arylations opened up an access to polysubstituted pyrazoles including unusual tricyclic systems comprising 7-membered rings (oxepane, thiepane and azepane) as the central unit.


Designing a stepped wedge trial: three main designs, carry-over effects and randomisation approaches.
There is limited guidance on the design of stepped wedge cluster randomised trials. Current methodological literature focuses mainly on trials with cross-sectional data collection at discrete times, yet many recent stepped wedge trials do not follow this design. In this article, we present a typology to characterise the full range of stepped wedge designs, and offer guidance on several other design aspects. We developed a framework to define and report the key characteristics of a stepped wedge trial, including cluster allocation and individual participation. We also considered the relative strengths and weaknesses of trials according to this framework. We classified recently published stepped wedge trials using this framework and identified illustrative case studies. We identified key design choices and developed guidance for each. We identified three main stepped wedge designs: those with a closed cohort, an open cohort, and a continuous recruitment short exposure design. In the first two designs, many individuals experience both control and intervention conditions. In the final design, individuals are recruited in continuous time as they become eligible and experience either the control or intervention condition, but not both, and then provide an outcome measurement at follow-up. While most stepped wedge trials use simple randomisation, stratification and restricted randomisation are often feasible and may be useful. Some recent studies collect outcome information from individuals exposed a long time before or after the rollout period, but this contributes little to the primary analysis. Incomplete designs should be considered when the intervention cannot be implemented quickly. Carry-over effects can arise in stepped wedge trials with closed and open cohorts. Stepped wedge trial designs should be reported more clearly. Researchers should consider the use of stratified and/or restricted randomisation. Trials should generally not commit resources to collect outcome data from individuals exposed a long time before or after the rollout period. Though substantial carry-over effects are uncommon in stepped wedge trials, researchers should consider their possibility before conducting a trial with closed or open cohorts.


Disruption of a putative working memory task and selective expression of brain c-fos following microwave-induced hyperthermia.
To discern the effects of hyperthermia on working memory, we recorded the ability of rats to discriminate between objects following microwave radiation exposure. Memory changes were evaluated by measuring relative exploration time of a familiar vs. a new stimulus object. A subject that extensively reexplores a stimulus with which it has previous experience is presumed to exhibit memory loss associated with that object. Between training and testing, rats were exposed to various doses of microwave radiation, were sham irradiated, or remained in their home cage. Brain (dural) and rectal temperatures were recorded. To discern brain regions activated or possibly damaged by microwave exposure, we also used immunocytochemistry techniques to identify sites of c-fos protein expression in the brains of several irradiated/sham-irradiated subjects. Rats exposed to > 5 W/kg exhibited hyperthermia when compared to nonirradiated controls. Normothermic control subjects (sham-irradiated rats and rats exposed to 0.1 W/kg) showed a distinct preference for the new object although other microwave-exposed rats (1, 5, 8.5, 9.3, 10 W/kg) did not. Microwave hyperthermia evoked prominent c-fos expression in periventricular strata, hypothalamic nuclei, amygdala, and several areas of the cortex. These data suggest that performance on a putative working memory task may be disrupted by a sufficiently intense microwave-induced hyperthermia. The pattern of expression of the early proto-oncogene c-fos may suggest candidate brain nuclei that mediate the behavioral changes we observed.


Environmental implications of United States coal exports: a comparative life cycle assessment of future power system scenarios.
Stricter emissions requirements on coal-fired power plants together with low natural gas prices have contributed to a recent decline in the use of coal for electricity generation in the United States. Faced with a shrinking domestic market, many coal companies are taking advantage of a growing coal export market. As a result, U.S. coal exports hit an all-time high in 2012, fueled largely by demand in Asia. This paper presents a comparative life cycle assessment of two scenarios: a baseline scenario in which coal continues to be burned domestically for power generation, and an export scenario in which coal is exported to Asia. For the coal export scenario we focus on the Morrow Pacific export project being planned in Oregon by Ambre Energy that would ship 8.8 million tons of Powder River Basin (PRB) coal annually to Asian markets via rail, river barge, and ocean vessel. Air emissions (SOx, NOx, PM10 and CO2e) results assuming that the exported coal is burned for electricity generation in South Korea are compared to those of a business as usual case in which Oregon and Washington's coal plants, Boardman and Centralia, are retrofitted to comply with EPA emissions standards and continue their coal consumption. Findings show that although the environmental impacts of shipping PRB coal to Asia are significant, the combination of superior energy efficiency among newer South Korean coal-fired power plants and lower emissions from U.S. replacement of coal with natural gas could lead to a greenhouse gas reduction of 21% in the case that imported PRB coal replaces other coal sources in this Asian country. If instead PRB coal were to replace natural gas or nuclear generation in South Korea, greenhouse gas emissions per unit of electricity generated would increase. Results are similar for other air emissions such as SOx, NOx and PM. This study provides a framework for comparing energy export scenarios and highlights the importance of complete life cycle assessment in determining net emissions effects resulting from energy export projects and related policy decisions.


Allergic rhinoconjunctivitis in the Australian population: burden of disease and attitudes to intranasal corticosteroid treatment.
Allergic rhinoconjunctivitis (AR/C) is a global health problem causing significant morbidity and has a major impact on quality of life (QOL) and health expenditure. Despite the widespread prevalence, the overall health impact of AR/C may be underappreciated. The results of a survey designed to capture the burden of allergic rhinitis within the Asia-Pacific region have been published recently. Of particular note when evaluating treatment in this region was the fact that despite the value of intranasal corticosteroid (INCS) use, only a small percentage of patients used them. Whether this same trend is present within the population of Australian sufferers is unknown. This study examines the burden of AR/C and explores use of, and attitudes, to INCS sprays in the Australian population. Three hundred three completed interviews from adults and children who had physician-diagnosed AR/C and who were symptomatic or had received treatment in the previous 12 months were analyzed for QOL measures and attitudes to INCS use. Most patients surveyed had received their diagnosis from a general practitioner (GP), and in most cases, a GP provided the majority of ongoing medical care. Only 8% of respondents had consulted a relevant specialist. Diagnostic tests had not been performed in 55% of respondents. The major symptoms causing most distress were nasal congestion and ocular symptoms. The burden of AR/C was considerable; 42% described significant work or school interference because of symptoms, one-third reporting moderate-to-extreme interference with sleep. Despite the significant impact on QOL reported by this sample, 17% had never used INCS and 27% had not used them in the previous 12 months. Respondents' knowledge about INCSs was poor. AR/C is a common disease associated with significant morbidity and impairment of QOL. Improvement in diagnosis, management, and patient education is needed.


Liability concerns and shared use of school recreational facilities in underserved communities.
In underserved communities, schools can provide the physical structure and facilities for informal and formal recreation as well as after-school, weekend, and summer programming. The importance of community access to schools is acknowledged by authoritative groups; however, fear of liability is believed to be a key barrier to community access. The purpose of this study was to investigate perceptions of liability risk and associated issues among school administrators in underserved communities. A national survey of school administrators in underserved communities (n=360, response rate of 21%) was conducted in 2009 and analyzed in 2010. Liability perceptions in the context of community access were assessed through descriptive statistics. The majority of respondents (82.2%) indicated concern for liability should someone be injured on school property after hours while participating in a recreational activity. Among those that did not allow community access, 91% were somewhat to very concerned about liability and 86% believed that stronger legislation was needed to better protect schools from liability for after-hours recreational use. Among those who claimed familiarity with a state law that offered them limited liability protection, nearly three fourths were nevertheless concerned about liability. Liability concerns are prevalent among this group of school administrators, particularly if they had been involved in prior litigation, and even if they indicated they were aware of laws that provide liability protection where use occurs after hours. Reducing these concerns will be important if schools are to become locations for recreational programs that promote physical activity outside of regular school hours.


The relationship between Type D personality, affective symptoms and hemoglobin levels in chronic heart failure.
Anemia is associated with poor prognosis in heart failure (HF) patients. Contributors to the risk of anemia in HF include hemodilution, renal dysfunction and inflammation. Hemoglobin levels may also be negatively affected by alterations in stress regulatory systems. Therefore, psychological distress characterized by such alterations may adversely affect hemoglobin in HF. The association between hemoglobin and Type D personality and affective symptomatology in the context of HF is poorly understood. To examine the relationship between Type D personality and affective symptomatology with hemoglobin levels at inclusion and 12-month follow-up, controlling for relevant clinical factors. Plasma levels of hemoglobin and creatinine were assessed in 264 HF patients at inclusion and at 12-month follow-up. Type D personality and affective symptomatology were assessed at inclusion. At inclusion, hemoglobin levels were similar for Type D and non-Type D HF patients (p = .23), and were moderately associated with affective symptomatology (r = -.14, p = .02). Multivariable regression showed that Type D personality (β = -.15; p = .02), was independently associated with future hemoglobin levels, while controlling for renal dysfunction, gender, NYHA class, time since diagnosis, BMI, the use of angiotensin-related medication, and levels of affective symptomatology. Change in renal function was associated with Type D personality (β = .20) and hemoglobin at 12 months (β = -.25). Sobel mediation analysis showed significant partial mediation of the Type D - hemoglobin association by renal function deterioration (p = .01). Anemia prevalence increased over time, especially in Type D patients. Female gender, poorer baseline renal function, deterioration of renal function and a longer HF history predicted the observed increase in anemia prevalence over time, while higher baseline hemoglobin was protective. Type D personality, but not affective symptomatology, was associated with reduced future hemoglobin levels, independent of clinical factors. The relation between Type D personality and future hemoglobin levels was mediated by renal function deterioration.


Evaluation of the forum theatre approach for public engagement around antibiotic use in Myanmar.
The risk of emergence and spread of antibiotic resistance is high in Southeast Asian countries and various strategies are being used to raise awareness about appropriate antibiotic use and antibiotic resistance within communities. Public engagement in science has not been widely practised in Myanmar. We describe the use of a forum theatre to engage with the community about antibiotic use. The engagement activities took place in a peri-urban township in Yangon, Myanmar. Five preliminary story gathering workshops with the community were carried out to develop scripts and songs for the forum theatre. After that, we organised forum theatre plays between September and October 2018. Following each play we provided four simple key messages based on WHO's world antibiotic awareness week advocacy materials; 1) Antibiotics are medicines used to treat bacterial infections 2) Antibiotics are not useful for coughs and colds 3) Never use leftover antibiotics or share antibiotics with others 4) Prevent infections by regularly washing hands, preparing food hygienically, avoiding close contact with sick people, and keeping vaccinations up to date. We evaluated the engagement activities by conducting focus group discussions (FGD) with audience members. Ten forum theatre plays were performed on two topics; "Fever and antibiotics" and "Mixed medicines", reaching 1175 community members. Four themes emerged from our thematic analysis: 1) Knowledge dissemination, 2) Enjoyment and fun, 3) Willingness to support and recommendations for future engagement activities and 4) Preference over traditional methods of health education. We found improvement of antibiotic related knowledge and enjoyment among audience who were also willing to support future engagement activities and preferred forum theatre approach over formal health talks. We conclude that forum theatre is an effective innovative approach to engage and disseminate knowledge on appropriate use of antibiotics with the community in a participatory way.


Measurement and simulation of filamentation in (Al,In)GaN laser diodes.
(Al,In)GaN-based laser diodes with ridge widths broader than a few micrometer tend to show filamentation effects in the lateral direction. By time-resolved scanning near-field optical microscopy, we find different kinds of filaments depending on ridge width and lateral position. We investigate these effects systematically and compare them to the results of corresponding simulations, which are based on a simple rate equation model including the lateral dimension. By this comparison we find a consistent and reasonable set of material parameters that can describe the laser diode. Furthermore, we discuss several reasons for filamentation dynamics like ridge asymmetry or spatial hole-burning, as well as critical temperatures that induce filamentation.


Urethral strictures in childhood.
Thirty-six children have been treated for a non-hypospadiac urethral stricture. Of 12 patients with meatal or submeatal stenosis, 10 had undergone circumcision for balanitis xerotica obliterans. The strictures were successfully treated by meatoplasty or meatal dilatation. Twenty-four children had a more proximal urethral stricture: 16 were caused by urethral catheterisation, 4 were post-traumatic, 2 were congenital and 2 were idiopathic. Sixteen children were treated by visual urethrotomy; this was successful in 12 after a maximum of 2 urethrotomies. Two children required 4 or more urethrotomies and 2 required urethroplasty for restricturing. Seven children were treated by a formal urethroplasty. There were no complications. Two patients died of unrelated medical conditions. Follow-up was for a mean of 2 years.


Essential oil composition of diploid and tetraploid clones of ginger (Zingiber officinale Roscoe) grown in Australia.
Ginger oil, obtained by steam distillation of the rhizome of Zingiber officinale Roscoe, is used in the beverage and fragrance industries. Ginger oil displays considerable compositional diversity, but is typically characterized by a high content of sesquiterpene hydrocarbons, including zingiberene, ar-curcumene, beta-bisabolene, and beta-sesquiphellandrene. Australian ginger oil has a reputation for possessing a particular "lemony" aroma, due to its high content of the isomers neral and geranial, often collectively referred to as citral. Fresh rhizomes of 17 clones of Australian ginger, including commercial cultivars and experimental tetraploid clones, were steam distilled 7 weeks post-harvest, and the resulting oils were analyzed by GC-MS. The essential oils of 16 of the 17 clones, including the tetraploid clones and their parent cultivar, were found to be of substantially similar composition. These oils were characterized by very high citral levels (51-71%) and relatively low levels of the sesquiterpene hydrocarbons typical of ginger oil. The citral levels of most of these oils exceeded those previously reported for ginger oils. The neral-to-geranial ratio was shown to be remarkably constant (0.61 +/- 0.01) across all 17 clones. One clone, the cultivar "Jamaican", yielded oil with a substantially different composition, lower citral content and higher levels of sesquiterpene hydrocarbons. Because this cultivar also contains significantly higher concentrations of pungent gingerols, it possesses unique aroma and flavor characteristics, which should be of commercial interest.


Polish Translation and Validation of the Tinnitus Handicap Inventory and the Tinnitus Functional Index.
Objective: The need for validated measures enabling clinicians to classify tinnitus patients according to the severity of tinnitus and screen the progress of therapies in our country led us to translate into Polish and to validate two tinnitus questionnaires, namely the Tinnitus Handicap Inventory (THI) and the Tinnitus Functional Index (TFI). Design: The original English versions of the questionnaires were translated into Polish and translated back to English by three independent translators. These versions were then finalized by the authors into a Polish THI (THI-Pl) and a Polish TFI (TFI-Pl). Participants from three laryngological centers in Poland anonymously answered the THI-Pl (N = 98) and the TFI-Pl (N = 108) in addition to the Polish versions of the Center for Epidemiologic Studies Depression Scale as a measure of self-perceived level of depression, and the Satisfaction With Life Scale to assess self-perceived quality of life. Both were used to determine discriminant validity. Two Visual Analog Scales were used to measure tinnitus annoyance and tinnitus loudness in order to determine convergent validity. Results: Similar to the original version of the THI, the THI-Pl showed a high internal consistency (Cronbach's α = 0.93). The exploratory factor analysis revealed that the questionnaire has a three-factorial structure that does not correspond to the original division for functional, catastrophic, and emotional subscales. Convergent and discriminant validities were confirmed. The TFI-Pl showed high internal consistency (Cronbach's α = 0.96) with the reliability ranging from 0.82 to 0.95 for its different subscales. Factor analysis confirmed an eight-factorial structure with factors assigning all items to appropriate subscales reported in the original version of the questionnaire. Discriminant and convergent validities were also confirmed for the TFI-Pl. Conclusion: We translated and validated the Polish versions of the THI and the TFI to make them suitable for clinical use in Poland.


Interaction of water temperature and challenge model on xenoma development rates for Loma salmonae (Microspora) in rainbow trout, Oncorhynchus mykiss (Walbaum).
This study evaluated the regulatory effects of water temperature on the development of branchial xenomas caused by Loma salmonae using a high-dose per os-challenge model compared with a low-dose cohabitation-challenge model. Approximately 275 juvenile rainbow trout (RBT), Oncorhynchus mykiss, were randomly distributed to six tanks with two tanks each maintained at 11, 15 and 19 degrees C. Fish in one tank from each temperature setting were exposed per os to macerated L. salmonae-infected gill material and fish in the other tank from each temperature setting were exposed to L. salmonae using the cohabitation-challenge model. Fish were monitored for the development of branchial xenomas beginning at day 21 post-exposure. Survival analyses were used to evaluate the effect of water temperature and challenge model on the number of days until the first visible branchial xenoma was detected. The survivor curves for the per os-challenge model revealed that there was at least one significant difference, whereas the cohabitation challenge did not reveal any significant differences amongst the temperature settings. The proportional hazards model revealed a significant interaction between the challenge model used and water temperature. This indicated that the effect of water temperature was different depending on challenge model. Additionally, from the mean xenoma intensities, on average, the per os-challenged fish showed higher xenoma intensity compared with the cohabitation-challenged fish. Overall, the impact of water temperature on disease pathogenesis was greater when the RBT were per os challenged compared with using the cohabitation model.


Novel Histone Deacetylase Inhibitor Modulates Cardiac Peroxisome Proliferator-Activated Receptors and Inflammatory Cytokines in Heart Failure.
Heart failure (HF) affects cardiac metabolism and inflammation. Histone deacetylases (HDACs) play a critical role in cardiac pathophysiology. This study investigated whether HDAC inhibition can regulate HF by modifying cardiac inflammation and peroxisome proliferator-activated receptor (PPAR) isoforms. Echocardiography, electrocardiography, ELISA and Western blot were performed in rats with isoproterenol-induced HF, with and without orally administered MPT0E014 (a novel HDAC inhibitor, 50 mg/kg for 7 consecutive days). The left ventricles (LVs) of HF rats expressed significantly higher levels of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 than the healthy LVs did. HF rats treated with MPT0E014 exhibited improved cardiac fraction shortening with reducing chamber size. The MPT0E014-treated HF LVs exhibited a smaller increase in the expression of interleukin (IL)-6, p22, SMAD2/3, extracellular signal-regulated kinase 1/2, PPAR isoforms and circulatory tumor growth factor-β1 than the untreated HF LVs did. Moreover, MPT0E014-treated HF LVs expressed less fibroblast growth factor receptor than untreated HF LVs did. HDAC inhibition can improve cardiac function and attenuate the effects of HF on cardiac metabolism and inflammation, which might contribute to the beneficial effects of HDAC inhibition in HF.


Ron receptor-dependent gene regulation in a mouse model of endotoxin-induced acute liver failure.
Prior experimentation has shown that loss of the tyrosine kinase (TK) signaling domain of the Ron receptor leads to marked hepatocyte protection in a model of lipopolysaccharide-induced acute liver failure (ALF) in D-galactosamine (GalN)-sensitized mice. The aim of this study was to identify the role of Ron in the regulation of hepatic gene expression. Microarray analyses were performed on liver RNA isolated sequentially from wild-type (WT) and TK-/- mice during the progression of ALF. Gene array data were validated using Western and immunohistochemistry analyses as well as with ex vivo culture systems. At baseline, 101 genes were differentially expressed between WT and TK-/- livers, which regulate processes involved in hypoxia, proliferation, apoptosis and metabolism. One hour after ALF induction, WT livers exhibited increased cytokine expression compared to TK-/- livers, and after 4 hours, an induction of suppressor of cytokine signaling (SOCS) genes as well as JAK-STAT pathway activation were prominent in TK-/- livers compared to controls. Our studies suggest a novel hepato-protective mechanism in Ron TK-/- mice wherein increased and sustained SOCS production and JAK-STAT activation in the hepatocyte may inhibit the destructive proinflammatory milieu and promote survival factors which blunt hepatic death and the ensuing development of ALF.


Stable or able? Effect of virtual reality stimulation on static balance of post-stroke patients and healthy subjects.
Over the last decades, virtual reality (VR) emerged as a potential tool for developing new rehabilitation treatments in neurological patients. However, despite the increasing number of studies, a clear comprehension about the impact of immersive VR-treatment on balance and posture is still scarce. In the present study, we aimed to investigate the effects of VR cues on balance performances of subjects affected by stroke, age-matched healthy subjects, and young healthy subjects. Fifteen patients with sub-acute stroke, fifteen healthy elderly subjects and fifteen healthy young adults took part in this study. All groups were immersed in a CAVE system on a stabilometric platform. The experiment consisted in fourteen trials: (i) ten VR trials, which differed in term of speed and movement direction; (ii) two-stabilometric static sessions, with opened and closed eyes (one at the start and one at the end of the experimental session). Results showed that VR trials increased the sway path length (representative of the body sway amplitudes), in young subjects. Elderly and patients showed less changes in postural sway during virtual reality stimulation than young group. These findings may suggest that a physiological postural performance is not simply evaluable assessing stability, but also assessing the ability of adapting body oscillations to the external stimuli.


[Resurgence of the measles epidemic: situation in Minas Gerais, Brazil].
This study aims to describe the measles vaccination campaigns that have been carried out in the state of Minas Gerais, Brazil, since 1988; to highlight their importance in the control of the disease, and to pinpoint the age groups at risk during the recent epidemic, which began in 1996, spread all over the country, and declined in 1998. However, the analysis includes only data up to September 1997. The methodology used was based on the birth cohort analysis design. Data compared by cohorts included target population and vaccination coverage for each campaign, and measles incidence rates during the present epidemic. Results show that the more opportunities for exposure to vaccination campaigns, the lesser the risk for having measles in any birth cohort. In 1997, the relative risk for getting measles was 15.38 (IC 95%: 9.89 to 23.93) for the cohort under 2 years of age, which had not had the opportunity to be exposed to any vaccination campaigns, as compared to cohorts between 3 and 19 years of age with two or more opportunities of exposure to vaccination campaigns. On the basis of the experiences analyzed, catch-up measles vaccination campaigns as well as follow-up campaigns--particularly when routine vaccination did not achieve sufficient coverage--have had an outstanding role in controlling the measles epidemic in the state of Minas Gerais. We therefore suggest making the measles vaccine immediately available to all birth cohorts that did not have the opportunity for exposure to past vaccination campaigns and intensifying epidemiological surveillance. Moreover, it is necessary to find ways to improve routine vaccination coverage in order to achieve the 95% goal set by the National Plan to Eliminate Measles by the Year 2000.


The role of regulated protein degradation in auxin response.
Auxin-regulated gene expression is mediated by two families of transcription factors. The ARF proteins bind to a conserved DNA sequence called the AuxRE and activate transcription. The Aux/IAA proteins repress ARF function, presumably by forming dimers with ARF proteins. Recent genetic studies in Arabidopsis indicate that auxin regulates this system by promoting the ubiquitin-mediated degradation of the Aux/IAA proteins, thus permitting ARF function. Mutations in components of SCF(TIR1), a ubiquitin protein ligase (E3) result in stabilization of Aux/IAA proteins and decreased auxin response. Further, recent biochemical experiments indicate that the Aux/IAA proteins bind SCF(TIR1) in an auxin-dependent manner.


Complete genome sequence and bioinformatics analyses of Bacillus thuringiensis strain BM-BT15426.
This study aimed to investigate the genetic characteristics of Bacillus thuringiensis strain BM-BT15426. B. thuringiensis strain was identified by sequencing the PCR product (amplifying 16S rRNA gene) using ABI Prism 377 DNA Sequencer. The genome was sequenced using PacBio RS II sequencers and assembled de novo using HGAP. Also, further genome annotation was performed. The genome of B. thuringiensis strain BM-BT15426 has a length of 5,246,329 bp and contains 5409 predicted genes with an average G + C content of 35.40%. Three genes were involved in the "Infectious diseases: Amoebiasis" pathway. A total of 21 virulence factors and 9 antibiotic resistant genes were identified. The major pathogenic factors of B. thuringiensis strain BM-BT15426 were identified through complete genome sequencing and bioinformatics analyses which contributes to further study on pathogenic mechanism and phenotype of B. thuringiensis.


Nonprofessionals' perceptions of the causes of behavioral and substance addictions.
We assessed nonprofessionals' perceptions of etiological explanations of behavioral and substance addictions in a nationwide sample. A total of 612 adults (51% male) residing in the United States were recruited using Mechanical Turk. Participants rated the perceived likelihood of seven psychosocial and biological etiologies for one of five randomly assigned types of "addiction" (i.e., alcohol, marijuana, heroin, gambling, or pornography). Significantly fewer participants rated social pressure a likely cause of addiction to pornography (31%) than to marijuana (53%), alcohol (55%), and heroin (64%); significantly fewer rated traumatic childhood events a likely cause of addiction to gambling (33%) and marijuana (36%) than to pornography (56%), heroin (57%), and alcohol (64%); significantly fewer rated the way a person was raised a likely cause of addiction to marijuana (37%) than to heroin (55%) and alcohol (65%); and significantly more rated genetics a likely cause of an addiction to alcohol (65%) than to pornography (26%), marijuana (33%), gambling (41%), and heroin (45%). The proportions who rated stressful circumstances and character problem as likely causes were not significantly associated with type of addiction. In addition, participants rated an average of three or four separate etiologies as likely causes of each target addiction. Our results suggest that lay individuals recognize the multi-determined nature of addictive disorders and rate some causes as more or less likely depending on the specific addictive substance or behavior.


Glycolytic Functions Are Conserved in the Genome of the Wine Yeast Hanseniaspora uvarum, and Pyruvate Kinase Limits Its Capacity for Alcoholic Fermentation.
Hanseniaspora uvarum (anamorph Kloeckera apiculata) is a predominant yeast on wine grapes and other fruits and has a strong influence on wine quality, even when Saccharomyces cerevisiae starter cultures are employed. In this work, we sequenced and annotated approximately 93% of the H. uvarum genome. Southern and synteny analyses were employed to construct a map of the seven chromosomes present in a type strain. Comparative determinations of specific enzyme activities within the fermentative pathway in H. uvarum and S. cerevisiae indicated that the reduced capacity of the former yeast for ethanol production is caused primarily by an ∼10-fold-lower activity of the key glycolytic enzyme pyruvate kinase. The heterologous expression of the encoding gene, H. uvarumPYK1 (HuPYK1), and two genes encoding the phosphofructokinase subunits, HuPFK1 and HuPFK2, in the respective deletion mutants of S. cerevisiae confirmed their functional homology.IMPORTANCEHanseniaspora uvarum is a predominant yeast species on grapes and other fruits. It contributes significantly to the production of desired as well as unfavorable aroma compounds and thus determines the quality of the final product, especially wine. Despite this obvious importance, knowledge on its genetics is scarce. As a basis for targeted metabolic modifications, here we provide the results of a genomic sequencing approach, including the annotation of 3,010 protein-encoding genes, e.g., those encoding the entire sugar fermentation pathway, key components of stress response signaling pathways, and enzymes catalyzing the production of aroma compounds. Comparative analyses suggest that the low fermentative capacity of H. uvarum compared to that of Saccharomyces cerevisiae can be attributed to low pyruvate kinase activity. The data reported here are expected to aid in establishing H. uvarum as a non-Saccharomyces yeast in starter cultures for wine and cider fermentations.


Photons across medicine: relating optical and nuclear imaging.
The Optics in the Life Sciences conference sponsored by the Optical Society of America was held in Waikoloa Beach, HI on April 14 - 18, 2013. Papers were presented in the areas of Bio-Optics: Design & Application, Novel Techniques in Microscopy, Optical Molecular Probes, Imaging & Drug Delivery, and Optical Trapping Applications. A focal point of the meeting was a special symposium entitled "Photons Across Medicine", organized by Adam Wax, Duke University, highlighting activities of joint interest between the Optical Society of America (OSA) and the Society for Nuclear Medicine and Molecular Imaging (SNMMI). This paper is a synopsis of the presentations made at this joint symposium. Central to the special symposium presentations was the fact that the optical and nuclear imaging communities share common interests and challenges. These are highlighted in this article. Also discussed was the fact that the nuclear technologies in imaging have found their way into general clinical utility, a feat that has yet to be achieved by optical methods. Because of the common ground shared by the two technologies, coordination between the two societies should be planned.


A multicenter experience with novel implantable cardioverter defibrillator configurations in the pediatric and congenital heart disease population.
In pediatric and congenital heart disease patients, transvenous ICD implantation may be limited secondary to patient size, venous, or cardiac anatomy. Epicardial patches require a thoracotomy, and may lead to a restrictive pericardial process. Because of these issues, we have explored novel ICD configurations. Retrospective review at 10 centers implanting ICDs without a transvenous shocking coil or epicardial patches. Twenty-two patients underwent implant at a mean age of 8.9 years (range: 0.3-43.5), with a mean weight of 25.5 kg (range: 5.2-70). Diagnoses included complex CHD, intracardiac tumors, cardiomyopathy, idiopathic VT, LV noncompaction, and long QT syndrome. Three configurations were used: subcutaneous array, a transvenous design ICD lead placed on the epicardium, or a transvenous design ICD lead placed subcutaneously. Difficulties were found at implant in 8 patients: 4 had difficulty inducing VT/VF, and 4 had high DFTs. Over a mean follow-up of 2.2 years (range: 0.2-10.5), 7 patients had appropriate shocks. Inappropriate shocks occurred in 4 patients. System revisions were required in 7 patients: 2 generator changes (in 1 patient), 3 pace-sense lead replacement, 1 additional subcutaneous coil placement due to increased DFT, 1 upgrade to a transvenous system, and 1 revision to epicardial patch system. ICD implantation can be performed without epicardial patches or transvenous high-energy leads in this population, using individualized techniques. This will allow ICD use in patients who have intracardiac shunting or are deemed too small for transvenous ICD leads. The long-term outcome and possible complications are as yet unknown in this population, and they should be monitored closely with follow-up DFTs.


The efficacy of eribulin mesylate for patients with cutaneous angiosarcoma previously treated with taxane: a multicentre prospective observational study.
Taxanes are the current first-line treatment for advanced cutaneous angiosarcoma (CAS) for patients who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity. However, no effective second-line therapy for such patients has been established. We designed a single-arm prospective observational study of eribulin mesylate (ERB) administered at a dose of 1·4 mg m-2 on days 1 and 8 in a 21-day cycle. Patients with advanced CAS who were previously treated with a taxane and were scheduled to begin ERB treatment were enrolled. The primary endpoint was overall survival (OS) and the secondary endpoints were response rate (RR), progression-free survival (PFS) and toxicity assessment. We enrolled a total of 25 patients. The median OS and PFS were 8·6 months and 3·0 months, respectively. The best overall RR was 20% (five of 25). In total, 16 grade 3/4 severe adverse events (SAEs) occurred; however, all patients recovered. Patients who achieved partial response or stable disease as best response had longer OS than those with progressive disease (median OS not reached and 3·3 months, respectively; P < 0·001). Patients who did not experience SAEs showed longer OS than those who did (median OS 18·8 months and 7·5 months, respectively; P < 0·05). Patients with distant metastasis had shorter median OS than those with locoregional disease, but without statistically significant difference. ERB showed a promising RR and is a potential candidate for second-line treatment for patients with CAS, after treatment with taxanes. However, owing to the occurrence of SAEs in over half of the participants, caution should be exercised regarding ERB use in elderly patients. What is already known about this topic? Taxanes are the current first-line treatment for patients with advanced cutaneous angiosarcoma (CAS) who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity. No effective therapy for taxane-resistant CAS has been established thus far. Eribulin suppresses microtubule polymerization and elicits an antitumour effect similar to that of taxanes. What does this study add? In our single-arm prospective observational study to evaluate the efficacy of eribulin for treating patients with advanced CAS who previously received taxanes, the median overall survival and progression-free survival were 8·6 and 3·0 months, respectively. Response rates at weeks 7, 13 and 25 were 20%, 17% and 14%, respectively. Although 16 grade 3/4 severe adverse events occurred, all patients recovered. Eribulin showed a promising response rate and is a potential candidate for second-line treatment in CAS after taxane treatment. Linked Comment: Smrke and Benson. Br J Dermatol 2020; 183:797-798.


Colon cancer: a civilization disorder.
Colorectal cancer arises in individuals with acquired or inherited genetic predisposition who are exposed to a range of risk factors. Many of these risk factors are associated with affluent Western societies. More than 95% of colorectal cancers are sporadic, arising in individuals without a significant hereditary risk. Geographic variation in the incidence of colorectal cancer is considerable with a higher incidence observed in the West. Environmental factors contribute substantially to this variation. A number of these risk factors are associated with a Western lifestyle and could be considered a product of 'civilization'. Recently, smoking has been recognized as a risk factor. Energy consumption also influences colorectal cancer risk, with obesity increasing risk and exercise reducing risk. However, the strongest contribution to environmental risk for colorectal cancer is dietary. Consumption of fat, alcohol and red meat is associated with an increased risk. Fresh fruit and vegetables and dietary fibre may be protective. Much has been learnt recently about the molecular pathogenesis of colorectal cancer. Colorectal cancer always arises in the context of genomic instability. There is inactivation of the tumour suppressor genes adenomatous polyposis coli, p53, transforming growth factor-β, activation of oncogene pathways including K-ras, and activation of the cyclooxygenase-2, epidermal growth factor receptor and vascular endothelial growth factor pathways. The mechanisms by which some environmental factors modify the mutation risk in these pathways have been described.


The personality trait openness is related to cerebral 5-HTT levels.
Potentiation of serotonergic transmission increases cognitive flexibility, but can in other circumstances increase sensitivity to stressful environmental cues. The personality trait Openness to Experience reflects and is also associated with an increased risk for mood disorders. We hypothesized that the personality trait has an association with a biomarker of serotonergic transmission, the plasma membrane serotonin transporter (5-HTT). In 50 healthy volunteers, we tested for correlations between scores on the NEO-PI-R scale Openness to Experience and its subscales, and cerebral binding of the 5-HTT selective PET radioligand [11C]DASB. Subjects were genotyped for the 5-HTT long/short polymorphism, and for a single nucleotide polymorphism in the long allele, designated LA/LG. Midbrain [11C]DASB binding correlated negatively with scores for Openness to Experience and its two subscales, Openness to Actions and Openness to Values. The latter subscore was negatively correlated with [11C]DASB binding in all brain regions in which [11C]DASB binding was quantified. Genetic analysis showed that homozygote LA carriers had significantly higher [11C]DASB binding in the caudate nucleus, but no significant differences in openness scores. Thus, high scores in personality facets indicative of cognitive flexibility and openness to change are associated with lower [11C]DASB binding. Lower abundance of 5-HTT sites may result in potentiation of serotonergic signaling, which occurs during treatment with SSRIs. We speculate that the set-point of serotonergic signaling in an individual represents a trade-off between flexibility and vulnerability when exposed to environmental stress.


Vertical integration of high-Q silicon nitride microresonators into silicon-on-insulator platform.
We demonstrate a vertical integration of high-Q silicon nitride microresonators into the silicon-on-insulator platform for applications at the telecommunication wavelengths. Low-loss silicon nitride films with a thickness of 400 nm are successfully grown, enabling compact silicon nitride microresonators with ultra-high intrinsic Qs (~ 6 × 10(6) for 60 μm radius and ~ 2 × 10(7) for 240 μm radius). The coupling between the silicon nitride microresonator and the underneath silicon waveguide is based on evanescent coupling with silicon dioxide as buffer. Selective coupling to a desired radial mode of the silicon nitride microresonator is also achievable using a pulley coupling scheme. In this work, a 60-μm-radius silicon nitride microresonator has been successfully integrated into the silicon-on-insulator platform, showing a single-mode operation with an intrinsic Q of 2 × 10(6).


A dual task priming investigation of right hemisphere inhibition for people with left hemisphere lesions.
During normal semantic processing, the left hemisphere (LH) is suggested to restrict right hemisphere (RH) performance via interhemispheric suppression. However, a lesion in the LH or the use of concurrent tasks to overload the LH's attentional resource balance has been reported to result in RH disinhibition with subsequent improvements in RH performance. The current study examines variations in RH semantic processing in the context of unilateral LH lesions and the manipulation of the interhemispheric processing resource balance, in order to explore the relevance of RH disinhibition to hemispheric contributions to semantic processing following a unilateral LH lesion. RH disinhibition was examined for nine participants with a single LH lesion and 13 matched controls using the dual task paradigm. Hemispheric performance on a divided visual field lexical decision semantic priming task was compared over three verbal memory load conditions, of zero-, two- and six-words. Related stimuli consisted of categorically related, associatively related, and categorically and associatively related prime-target pairs. Response time and accuracy data were recorded and analyzed using linear mixed model analysis, and planned contrasts were performed to compare priming effects in both visual fields, for each of the memory load conditions. Control participants exhibited significant bilateral visual field priming for all related conditions (p < .05), and a LH advantage over all three memory load conditions. Participants with LH lesions exhibited an improvement in RH priming performance as memory load increased, with priming for the categorically related condition occurring only in the 2- and 6-word memory conditions. RH disinhibition was also reflected for the LH damage (LHD) group by the removal of the LH performance advantage following the introduction of the memory load conditions. The results from the control group are consistent with suggestions of an age related hemispheric asymmetry reduction and indicate that in healthy aging compensatory bilateral activation may reduce the impact of inhibition. In comparison, the results for the LHD group indicate that following a LH lesion RH semantic processing can be manipulated and enhanced by the introduction of a verbal memory task designed to engage LH resources and allow disinhibition of RH processing.


Surgery in the rat during electrical analgesia induced by focal brain stimulation.
Chronic monopolar electrodes were implanted in the region of the midbrain central gray in eight rats. In three rats, continuous 60 cycle-per-second sine-wave stimulation resulted in an electrical analgesia defined by the elimination of responses to aversive stimulation while general motor responsiveness was retained. Exploratory laparotomy was carried out in these animals during continuous brain stimulation without the use of chemical anesthetics. Following surgery, brain stimulation was terminated, and responses to aversive stimuli returned. Electrodes effective in inducing electrical analgesia at the lowest currents were located at the dorsolateral perimeter of the midbrain central gray. It was concluded that focal brain stimulation in this region can induce analgesia in the absence of diffusely applied "whole brain" stimulation.


Exploiting the mosaic structure of trans-acyltransferase polyketide synthases for natural product discovery and pathway dissection.
Modular polyketide synthases (PKSs) are giant bacterial enzymes that synthesize many polyketides of therapeutic value. In contrast to PKSs that provide acyltransferase (AT) activities in cis, trans-AT PKSs lack integrated AT domains and exhibit unusual enzymatic features with poorly understood functions in polyketide assembly. This has retarded insight into the assembly of products such as mupirocin, leinamycin and bryostatin 1. We show that trans-AT PKSs evolved in a fundamentally different fashion from cis-AT systems, through horizontal recruitment and assembly of substrate-specific ketosynthase (KS) domains. The insights obtained from analysis of these KS mosaics will facilitate both the discovery of novel polyketides by genome mining, as we demonstrate for the thailandamides of Burkholderia thailandensis, and the extraction of chemical information from short trans-AT PCR products, as we show using metagenomic DNA of marine sponges. Our data also suggest new strategies for dissecting polyketide biosynthetic pathways and engineering polyketide assembly.


Measurements of magnetic field variations in the human brain using a 3D-FT multiple gradient echo technique.
A magnetic resonance 3DFT multiple gradient-echo technique was used for measurements of the proton spectrum for each voxel in the measured slice. Water, fat, magnetic field and T2 distributions in the head of a normal volunteer and a patient with intracerebral hematoma were computed. Magnetic field variations caused by the head were calculated after correction for the static magnetic field inhomogeneity. Large local magnetic field variations up to 3 ppm were found in the human brain near interfaces between air or bone and brain tissues and 0.5 ppm between hematoma and brain tissue. Information about magnetic field variations could be useful for shimming procedures in vivo and for correcting artifacts in imaging and spectroscopy.


Factors influencing the level of self-stigmatisation in people with mental illness.
The aim of this study was to assess sociodemographic factors and factors connected with treatment of mental illness and to decide whether they can influence the level of self-stigma. Sociodemographic characteristics (age, gender, family status, level of employment, level of education) and characteristics related to illness and treatment (diagnosis, length of treatment, adherence to treatment) were gathered in a group of patients in stable mental condition, without acute symptoms of mental illness. Self-stigma was measured using the Self-stigma of Mental Illness Scale - short form (SSMIS-SF). The sample included 197 patients: 99 patients in group 1 (G1) with psychosis and 98 in group 2 (G2) with anxious and affective disorders. The average age was 44.15 ± 12.91 years, the length of illness was 11.67 ± 9.21 years and 48% of patients were men. The total average SSMIS-SF score was 61.54 ± 23.34. We found no statistically significant difference in the total level of self-stigmatisation between these groups ( t(197) = 0.77; p = .441). The level of self-stigmatisation (total score of SSMIS-SF) in patients in G1 (psychosis) increased with the length of illness r(99) = .253; p = .011. Employment status seems to correlate with the level of self-stigmatisation ( F(3, 184) = 5.27; p = .002). Patients unemployed and on disability pension had higher levels of self-stigmatisation than patients working full-time. Patients who took medication regularly (full medical adherence) had lower scores of SSMIS-SF total scores in comparison with patients with lower compliance ( t(195) = 3.476; p = .001; Cohen's d = .25). According to our results, with regard to the factors that were followed, self-stigmatisation correlates with the presence of employment (social inclusion), duration of illness in patients with psychosis and treatment adherence. We did not find a statistically significant influence of age, gender, marital status or clinical diagnosis on the level of self-stigma.


Physiologically Based Pharmacokinetic (PBPK) Modeling of Pharmaceutical Nanoparticles.
With the great interests in the discovery and development of drug products containing nanoparticles, there is a great demand of quantitative tools for assessing quality, safety, and efficacy of these products. Physiologically based pharmacokinetic (PBPK) modeling and simulation approaches provide excellent tools for describing and predicting in vivo absorption, distribution, metabolism, and excretion (ADME) of nanoparticles administered through various routes. PBPK modeling of nanoparticles is an emerging field, and more than 20 PBPK models of nanoparticles used in pharmaceutical products have been published in the past decade. This review provides an overview of the ADME characteristics of nanoparticles and how these ADME processes are described in PBPK models. Recent advances in PBPK modeling of pharmaceutical nanoparticles are summarized. The major challenges in model development and validation and possible solutions are also discussed.


Who seeks physiotherapy or exercise treatment for hip and knee osteoarthritis? A cross-sectional analysis of the English Longitudinal Study of Ageing.
To determine the characteristics of individuals with hip and/or knee osteoarthritis who are recommended to seek physiotherapy or exercise treatment, and to explore which people are more or less likely to follow such recommendations. All data were obtained from Wave 4 of the English Longitudinal Study of Ageing (ELSA) cohort (2008-2009), a prospectively collected community-based dataset. Eligibility was justified by a patient-reported diagnosis of hip and/or knee osteoarthritis with a visual analog scale (VAS) pain score of 1 or above. Data were collected from a self-completed questionnaire and nurse assessment visit. Prevalence of being recommended to physiotherapy or exercise (or not) and then the actioning of this recommendation (or not) were calculated and presented as 95% confidence intervals (CI). Data on characteristics of those recommended (or not) were explored using univariate analyses and then a forward selection logistic regression model. In total, 1262 and 1877 individuals with hip and/or knee osteoarthritis pain were analyzed. This included 41% (95% CI: 0.38-0.44) who had been recommended to seek physiotherapy or exercise treatment. Subsequently, 83% of those recommended sought these treatments. Individuals who presented with isolated knee pain, those who reported "fair" self-reported general health and were younger had a greater chance of being recommended for physiotherapy or exercise treatment, respectively (P ≤ 0.02). Encouragement should be given to formal and informal care providers of older people to highlight this inequality. This may then improve current and future access to evidence-based treatments for this population.


Long noncoding RNA are aberrantly expressed in vivo in the cystic fibrosis bronchial epithelium.
Long non-coding RNAs (lncRNAs) have emerged recently as key regulatory molecules with diverse roles at almost every level of the regulation of gene expression. The roles of these RNAs in the pathogenesis of cystic fibrosis (CF); a lethal multisystem, autosomal recessive disorder have yet to be explored. Our aim was to examine the expression profile of lncRNA, in the airway epithelium of people with CF. We examined the expression of 30,586 lncRNAs by microarray (Human LncRNA Array v3.0, Arraystar, Inc.), in vivo in bronchial cells isolated from endobronchial brushings obtained from CF and non-CF individuals. In total, we identified 1,063 lncRNAs with differential expression between CF and non-CF individuals (fold change ≥3, p≤0.001). The microarray also contained probes for ∼26,109 protein coding transcripts, of which 720 were differentially expressed between CF and non-CF brush samples (fold change ≥3, p≤0.001). Confirmation of a selection of differentially expressed coding mRNA and lncRNA transcripts such as XIST and TLR8 was achieved using qRT-PCR. Gene ontology bioinformatics analysis highlighted that many processes over-represented in the CF bronchial epithelium are related to inflammation. These data show a significantly altered lncRNA and mRNA expression profile in CF bronchial cells in vivo. Dysregulation of some of these lncRNAs may play important roles in the chronic infection and inflammation that exists in the lungs of people with CF.


GRADE Evidence to Decision (EtD) frameworks for adoption, adaptation, and de novo development of trustworthy recommendations: GRADE-ADOLOPMENT.
Guideline developers can: (1) adopt existing recommendations from others; (2) adapt existing recommendations to their own context; or (3) create recommendations de novo. Monetary and nonmonetary resources, credibility, maximization of uptake, as well as logical arguments should guide the choice of the approach and processes. To describe a potentially efficient model for guideline production based on adoption, adaptation, and/or de novo development of recommendations utilizing the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision (EtD) frameworks. We applied the model in a new national guideline program producing 22 practice guidelines. We searched for relevant evidence that informs the direction and strength of a recommendation. We then produced GRADE EtDs for guideline panels to develop recommendations. We produced a total of 80 EtD frameworks in approximately 4 months and 146 EtDs in approximately 6 months in two waves. Use of the EtD frameworks allowed panel members understand judgments of others about the criteria that bear on guideline recommendations and then make their own judgments about those criteria in a systematic approach. The "GRADE-ADOLOPMENT" approach to guideline production combines adoption, adaptation, and, as needed, de novo development of recommendations. If developers of guidelines follow EtD criteria more widely and make their work publically available, this approach should prove even more useful.


A comparative study of the effects of vitamin C, sirolimus, and paclitaxel on the growth of endothelial and smooth muscle cells for cardiovascular medical device applications.
Antiproliferative drugs such as sirolimus (SIR) and paclitaxel (PAT) are currently released from stents and vascular grafts to inhibit the growth of smooth muscle cells (SMCs), thereby preventing neointimal hyperplasia. However, these drugs delay or impair the growth of endothelial cells (ECs) on implant surfaces causing late thrombosis. Hence, there is a need to use alternative drugs in these implants to encourage the growth of ECs and to inhibit the growth of SMCs. Vitamin C (L-ascorbic acid [L-AA]) is one such drug which has been shown to encourage EC growth and inhibit SMC growth when orally administered or added directly to the cell cultures. In this research, four sets of in vitro cell culture experiments were carried out to compare the effects of L-AA, SIR, and PAT on the growth of ECs and SMCs under similar conditions, and to compare the effects of different doses of L-AA to determine the optimal dose for promoting maximum EC growth and inhibiting SMC growth. The ECs and SMCs treated with different drugs were characterized for their viability and proliferation, and morphology using the quantitative resazurin assay (as well as qualitative fluorescence microscopy characterization) and phase contrast microscopy, respectively, for up to 7 days. Also, the phenotype of ECs was characterized using immunofluorescence microscopy. Both SIR and PAT significantly inhibited the EC growth while L-AA significantly encouraged EC growth even more than that of the controls with no drugs. Also, L-AA significantly inhibited SMC growth although the inhibitory effect was inferior to that of SIR and PAT. The L-AA dosage study demonstrated that 100 μg and 300 μg of L-AA showed maximum EC growth after 7 days when compared to other dosages (1 μg, 500 μg, and 1000 μg) of L-AA and controls investigated in this study. Also, the 100 μg and 300 μg L-AA doses significantly inhibited the SMC growth. Thus, this study demonstrates that L-AA is a promising drug for potential use in stents and vascular grafts, to promote their endothelialization and inhibit neointimal hyperplasia.


Analysis of pesticide gas cartridges.
Charcoal and sodium nitrate, the active ingredients in pesticide gas cartridges, are quantified via carbon analysis and ion chromatography, respectively. Linearity was excellent (R(2) > 0.995) over a range consisting of 50-150% of the target concentration for both ingredients. The coefficient of variation for the replicate analyses of gas cartridges over multiple days was <4% for both analytes. Using the results from the analysis of two batches of gas cartridges, theoretical populations were modeled and used to determine practical sampling strategies to support a quality control program for a gas cartridge manufacturing operation. This modeling indicates that the analysis of three cartridges from each of five different lots would produce mean values for both active ingredients that are within 5% of the true mean >99% of the time.


The Social Interaction Phobia Scale: Continued support for the psychometric validity of the SIPS using clinical and non-clinical samples.
The present study sought to extend findings supporting the psychometric validity of a promising measure of social anxiety (SA) symptoms, the Social Interaction Phobia Scale (SIPS; Carleton et al., 2009). Analyses were conducted using three samples: social anxiety disorder (SAD) patients, generalized anxiety disorder (GAD) patients, and healthy controls. SIPS scores of SAD patients demonstrated internal consistency and construct validity, and the previously demonstrated three-factor structure of the SIPS was replicated. Further, the SIPS total score uniquely predicted SA symptoms, and SIPS scores were significantly higher for SAD patients than GAD patients or controls. Two cut-off scores that discriminated SAD patients from GAD patients and from healthy controls were identified. The current study is the first to replicate the SIPS three-factor model in a large, treatment-seeking sample of SAD patients and establish a cut-off score discriminating SAD from GAD patients. Findings support the SIPS as a valid, SAD-specific assessment instrument.


Metabolites related to gut bacterial metabolism, peroxisome proliferator-activated receptor-alpha activation, and insulin sensitivity are associated with physical function in functionally-limited older adults.
Identification of mechanisms underlying physical function will be important for addressing the growing challenge that health care will face with physical disablement in the expanding aging population. Therefore, the goals of the current study were to use metabolic profiling to provide insight into biologic mechanisms that may underlie physical function by examining the association between baseline and the 6-month change in serum mass spectrometry-obtained amino acids, fatty acids, and acylcarnitines with baseline and the 6-month change in muscle strength (leg press one repetition maximum divided by total lean mass, LP/Lean), lower extremity function [short physical performance battery (SPPB)], and mobility (400 m gait speed, 400-m), in response to 6 months of a combined resistance exercise and nutritional supplementation (whey protein or placebo) intervention in functionally-limited older adults (SPPB ≤ 10; 70-85 years, N = 73). Metabolites related to gut bacterial metabolism (cinnamoylglycine, phenol sulfate, p-cresol sulfate, 3-indoxyl sulfate, serotonin, N-methylproline, hydrocinnamate, dimethylglycine, trans-urocanate, valerate) that are altered in response to peroxisome proliferator-activated receptor-alpha (PPAR-α) activation (α-hydroxyisocaproate, α-hydroxyisovalerate, 2-hydroxy-3-methylvalerate, indolelactate, serotonin, 2-hydroxypalmitate, glutarylcarnitine, isobutyrylcarnitine, cinnamoylglycine) and that are related to insulin sensitivity (monounsaturated fatty acids: 5-dodecenoate, myristoleate, palmitoleate; γ-glutamylamino acids: γ-glutamylglutamine, γ-glutamylalanine, γ-glutamylmethionine, γ-glutamyltyrosine; branched-chain amino acids: leucine, isoleucine, valine) were associated with function at baseline, with the 6-month change in function or were identified in backward elimination regression predictive models. Collectively, these data suggest that gut microbial metabolism, PPAR-α activation, and insulin sensitivity may be involved in mechanisms that underlie physical function in functionally-limited older adults.


A computer simulation of vaccine prioritization, allocation, and rationing during the 2009 H1N1 influenza pandemic.
In the fall 2009, the University of Pittsburgh Models of Infectious Disease Agent Study (MIDAS) team employed an agent-based computer simulation model (ABM) of the greater Washington, DC, metropolitan region to assist the Office of the Assistant Secretary of Public Preparedness and Response, Department of Health and Human Services, to address several key questions regarding vaccine allocation during the 2009 H1N1 influenza pandemic, including comparing a vaccinating children (i.e., highest transmitters)-first policy versus the Advisory Committee on Immunization Practices (ACIP)-recommended vaccinating at-risk individuals-first policy. Our study supported adherence to the ACIP (instead of a children-first policy) prioritization recommendations for the H1N1 influenza vaccine when vaccine is in limited supply and that within the ACIP groups, children should receive highest priority.


Analyzing Immunoglobulin Repertoires.
Somatic assembly of T cell receptor and B cell receptor (BCR) genes produces a vast diversity of lymphocyte antigen recognition capacity. The advent of efficient high-throughput sequencing of lymphocyte antigen receptor genes has recently generated unprecedented opportunities for exploration of adaptive immune responses. With these opportunities have come significant challenges in understanding the analysis techniques that most accurately reflect underlying biological phenomena. In this regard, sample preparation and sequence analysis techniques, which have largely been borrowed and adapted from other fields, continue to evolve. Here, we review current methods and challenges of library preparation, sequencing and statistical analysis of lymphocyte receptor repertoire studies. We discuss the general steps in the process of immune repertoire generation including sample preparation, platforms available for sequencing, processing of sequencing data, measurable features of the immune repertoire, and the statistical tools that can be used for analysis and interpretation of the data. Because BCR analysis harbors additional complexities, such as immunoglobulin (Ig) (i.e., antibody) gene somatic hypermutation and class switch recombination, the emphasis of this review is on Ig/BCR sequence analysis.


Differences in working memory involvement in analytical and creative tasks: an ERP study.
If, as suggested, creative (insight) problem solving is less systematic and employs less planning than analytical problem solving, the former requires substantially less working memory (WM) than the latter. Subjects simultaneously solved problems and counted auditory stimuli (concurrent WM task), in response to which ERPs were recorded. Counting disrupted analytical, but not creative performance. Peak and time-window average P300 were more frontal during analytical problem solving as compared to insight or counting tones only (control). A PCA extracted two factors in the P3 range, one frontal and one broad left-lateralized, which distinguished analytical from creative problem solving. The findings indicate distinct processing pathways for the two types of tasks with more WM involvement in analytical tasks.


Current insights and controversies in the pathogenesis and diagnosis of disc-associated cervical spondylomyelopathy in dogs.
Disc-associated cervical spondylomyelopathy (DA-CSM) is the most common cause of cervical spondylomyelopathy in dogs. In this condition, progressive caudal cervical spinal cord compression is typically caused by protrusion of one or more intervertebral discs. This disc-associated compression is sometimes seen in combination with mild vertebral abnormalities and dorsal compression resulting from ligamentum flavum hypertrophy. The intervertebral disc space between the sixth (C6) and seventh (C7) cervical vertebrae is most commonly affected. Although several large breed dogs can be affected, the adult to older dobermann is overrepresented. Clinical signs vary from cervical hyperaesthesia to tetraplegia. Dogs can present with a chronic progressive or an acute onset of clinical signs. Many aspects of this multifactorial neurological syndrome are not completely understood and are the subject of controversy and debate. Although several factors have been proposed, the underlying pathology and aetiology remain unknown. Recently, new insights have been gained in the pathogenesis, diagnosis and treatment of this challenging neurological syndrome. This review outlines current controversies and new developments concerning the pathogenesis and diagnosis of DA-CSM.


Conserved Gammaherpesvirus Protein Kinase Selectively Promotes Irrelevant B Cell Responses.
Gammaherpesviruses are ubiquitous pathogens that are associated with B cell lymphomas. In the early stages of chronic infection, these viruses infect naive B cells and subsequently usurp the B cell differentiation process through the germinal center response to ensure latent infection of long-lived memory B cells. A unique feature of early gammaherpesvirus chronic infection is a robust differentiation of irrelevant, virus-nonspecific B cells with reactivities against self-antigens and antigens of other species. In contrast, protective, virus-specific humoral responses do not reach peak levels until a much later time. While several host factors are known to either promote or selectively restrict gammaherpesvirus-driven germinal center response, viral mechanisms that contribute to the irrelevant B cell response have not been defined. In this report we show that the expression and the enzymatic activity of the gammaherpesvirus-encoded conserved protein kinase selectively facilitates the irrelevant, but not virus-specific, B cell responses. Further, we show that lack of interleukin-1 (IL-1) receptor attenuates gammaherpesvirus-driven B cell differentiation and viral reactivation. Because germinal center B cells are thought to be the target of malignant transformation during gammaherpesvirus-driven lymphomagenesis, identification of host and viral factors that promote germinal center responses during gammaherpesvirus infection may offer an insight into the mechanism of gammaherpesvirus pathogenesis.IMPORTANCE Gammaherpesviruses are ubiquitous cancer-associated pathogens that usurp the B cell differentiation process to establish life-long latent infection in memory B cells. A unique feature of early gammaherpesvirus infection is the robust increase in differentiation of B cells that are not specific for viral antigens and instead encode antibodies that react with self-antigens and antigens of other species. Viral mechanisms that are involved in driving such irrelevant B cell differentiation are not known. Here, we show that gammaherpesvirus-encoded conserved protein kinase and host IL-1 signaling promote irrelevant B cell responses and gammaherpesvirus-driven germinal center responses, with the latter thought to be the target of viral transformation.


The effects of distal interlocking screws on torsional stability in three-part intertrochanteric hip fractures.
Many surgeons currently use long cephomedullary nails for the treatment of intertrochanteric fractures. The optimal indications for deploying distal interlocks are still debatable. This study examined the torsional biomechanical properties of 3-part intertrochanteric femur fractures in a cadaveric bone model using two different distal fixation strategies, an unlocked long cephalomedullary nail versus a dynamically locked nail. Our hypothesis is that a long cephalomedullary nail does not require distal locking fixation when used for treatment of a 3-part intertrochanteric fracture. Five matched pairs of cadaveric femora were randomly assigned to one of two distal fixation treatment groups; a single distal interlock screw placed in the dynamic orientation or no distal fixation. A 3-part intertrochanteric fracture was produced. Specimens were potted and mounted in a double gimbal fixture facilitating unconstrained motion in the sagittal and coronal planes. Specimens were cyclically loaded dynamically in both internal and external rotation. Range of motion, internal and external rotation stiffness, torsion stiffness, torsion yield and ultimate torsion magnitude were calculated. The samples instrumented with a distal locking screw reported statistically greater external rotational stiffness than the unlocked samples in nondestructive testing. The results of the destructive data demonstrated no statistical difference between the locked and unlocked group with regard to yield torque (p = 0.282), peak torque (p = 0.340), stiffness (p = 0.220), displacement at yield torque (p = 0.0605), and displacement at peak torque (p = 0.280). Distal locking of a long cephalomedullary nail increases the stiffness of the nail-femur construct in a 3-part biomechanical fracture model. However, our testing illustrates that an unlocked construct will tolerate at least equal stress before catastrophic failure in a torsional loading model.


Increasing prevalence of smoke-free homes and decreasing rates of sudden infant death syndrome in the United States: an ecological association study.
This study utilises an ecological design to analyse the relation between concurrent temporal trends in sudden infant death syndrome (SIDS) rates and prevalence of smoke-free households with infants in the USA, controlling for an important risk factor, infant supine sleep position. Annual state-specific SIDS cases were computed using period linked birth/infant death files; the prevalence of 100% smoke-free homes with infants using Tobacco Use Supplement to the Current Population Survey data, and percentage of infants in supine sleep position from National Infant Sleep Position data, for years 1995-2006. Incidence rate ratios relating trends in SIDS cases and risk factors were determined using time-series negative binomial regression. Population-level health effects were assessed with secondhand smoke (SHS) exposure population attributable fractions and excess attributable SIDS deaths. For every 1% absolute increase in the prevalence of smoke-free homes with infants, SIDS rates decreased 0.4% from 1995 to 2006, controlling for supine sleep position. Nationally, it is possible that 20% of the 1326 total SIDS cases were attributable to childhood SHS exposure at home in 2006 with potentially 534 fewer infant deaths attributable to SHS exposure in 2006 than in 1995, owing to an increasing prevalence of 100% smoke-free homes with infants. Cumulatively, 4402 (lower 95% CI) to 6406 (upper 95% CI) excess SIDS cases may have been attributable to SHS exposure in the home over the 12-year study period. The uptake of voluntary restrictions on smoking inside the home may present a public health benefit for infants in their first year of life. In light of inherent ecological study design limitations, these results warrant further individual level research linking postnatal SHS exposure and SIDS.


GeneImp: Fast Imputation to Large Reference Panels Using Genotype Likelihoods from Ultralow Coverage Sequencing.
We address the task of genotype imputation to a dense reference panel given genotype likelihoods computed from ultralow coverage sequencing as inputs. In this setting, the data have a high-level of missingness or uncertainty, and are thus more amenable to a probabilistic representation. Most existing imputation algorithms are not well suited for this situation, as they rely on prephasing for computational efficiency, and, without definite genotype calls, the prephasing task becomes computationally expensive. We describe GeneImp, a program for genotype imputation that does not require prephasing and is computationally tractable for whole-genome imputation. GeneImp does not explicitly model recombination, instead it capitalizes on the existence of large reference panels-comprising thousands of reference haplotypes-and assumes that the reference haplotypes can adequately represent the target haplotypes over short regions unaltered. We validate GeneImp based on data from ultralow coverage sequencing (0.5×), and compare its performance to the most recent version of BEAGLE that can perform this task. We show that GeneImp achieves imputation quality very close to that of BEAGLE, using one to two orders of magnitude less time, without an increase in memory complexity. Therefore, GeneImp is the first practical choice for whole-genome imputation to a dense reference panel when prephasing cannot be applied, for instance, in datasets produced via ultralow coverage sequencing. A related future application for GeneImp is whole-genome imputation based on the off-target reads from deep whole-exome sequencing.


Probabilistic approach to predicting substrate specificity of methyltransferases.
We present a general probabilistic framework for predicting the substrate specificity of enzymes. We designed this approach to be easily applicable to different organisms and enzymes. Therefore, our predictive models do not rely on species-specific properties and use mostly sequence-derived data. Maximum Likelihood optimization is used to fine-tune model parameters and the Akaike Information Criterion is employed to overcome the issue of correlated variables. As a proof-of-principle, we apply our approach to predicting general substrate specificity of yeast methyltransferases (MTases). As input, we use several physico-chemical and biological properties of MTases: structural fold, isoelectric point, expression pattern and cellular localization. Our method accurately predicts whether a yeast MTase methylates a protein, RNA or another molecule. Among our experimentally tested predictions, 89% were confirmed, including the surprising prediction that YOR021C is the first known MTase with a SPOUT fold that methylates a substrate other than RNA (protein). Our approach not only allows for highly accurate prediction of functional specificity of MTases, but also provides insight into general rules governing MTase substrate specificity.


Molecular markers of carcinogenesis for risk stratification of individuals with colorectal polyps: a case-control study.
Risk stratification using number, size, and histology of colorectal adenomas is currently suboptimal for identifying patients at increased risk for future colorectal cancer. We hypothesized that molecular markers of carcinogenesis in adenomas, measured via immunohistochemistry, may help identify high-risk patients. To test this hypothesis, we conducted a retrospective, 1:1 matched case-control study (n = 216; 46% female) in which cases were patients with colorectal cancer and synchronous adenoma and controls were patients with adenoma but no colorectal cancer at baseline or within 5 years of follow-up. In phase I of analyses, we compared expression of molecular markers of carcinogenesis in case and control adenomas, blind to case status. In phase II of analyses, patients were randomly divided into independent training and validation groups to develop a model for predicting case status. We found that seven markers [p53, p21, Cox-2, β-catenin (BCAT), DNA-dependent protein kinase (DNApkcs), survivin, and O6-methylguanine-DNA methyltransferase (MGMT)] were significantly associated with case status on unadjusted analyses, as well as analyses adjusted for age and advanced adenoma status (P < 0.01 for at least one marker component). When applied to the validation set, a predictive model using these seven markers showed substantial accuracy for identifying cases [area under the receiver operation characteristic curve (AUC), 0.83; 95% confidence interval (CI), 0.74-0.92]. A parsimonious model using three markers performed similarly to the seven-marker model (AUC, 0.84). In summary, we found that molecular markers of carcinogenesis distinguished adenomas from patients with and without colorectal cancer. Furthermore, we speculate that prospective studies using molecular markers to identify individuals with polyps at risk for future neoplasia are warranted.


Human communication dynamics in digital footsteps: a study of the agreement between self-reported ties and email networks.
Digital communication data has created opportunities to advance the knowledge of human dynamics in many areas, including national security, behavioral health, and consumerism. While digital data uniquely captures the totality of a person's communication, past research consistently shows that a subset of contacts makes up a person's "social network" of unique resource providers. To address this gap, we analyzed the correspondence between self-reported social network data and email communication data with the objective of identifying the dynamics in e-communication that correlate with a person's perception of a significant network tie. First, we examined the predictive utility of three popular methods to derive social network data from email data based on volume and reciprocity of bilateral email exchanges. Second, we observed differences in the response dynamics along self-reported ties, allowing us to introduce and test a new method that incorporates time-resolved exchange data. Using a range of robustness checks for measurement and misreporting errors in self-report and email data, we find that the methods have similar predictive utility. Although e-communication has lowered communication costs with large numbers of persons, and potentially extended our number of, and reach to contacts, our case results suggest that underlying behavioral patterns indicative of friendship or professional contacts continue to operate in a classical fashion in email interactions.


Vaginal dysbiosis associated-bacteria Megasphaera elsdenii and Prevotella timonensis induce immune activation via dendritic cells.
Dysbiosis of the vaginal microbiome as a result of overgrowth of anaerobic bacteria leads to bacterial vaginosis (BV) which is associated with increased inflammation in the genital mucosa. Moreover, BV increases susceptibility to sexual transmitted infections (STIs) and is associated with adverse pregnancy outcomes. It remains unclear how specific vaginal aerobic and anaerobic bacteria affect health and disease. We selected different vaginal bacteria ranging from true commensals to species associated with dysbiosis and investigated their effects on activation of dendritic cells (DCs). Commensal Lactobacilli crispatus did not induce DC maturation nor led to production of pro-inflammatory cytokines. In contrast, BV-associated bacteria Megasphaera elsdenii and Prevotella timonensis induced DC maturation and increased levels of pro-inflammatory cytokines. Notably, DCs stimulated with Prevotella timonensis suppressed Th2 responses and induced Th1 skewing, typically associated with preterm birth. In contrast, Lactobacillus crispatus and Megasphaera elsdenii did not affect Th cell polarization. These results strongly indicate that the interaction of vaginal bacteria with mucosal DCs determines mucosal inflammation and we have identified the anaerobic bacterium Prevotella timonensis as a strong inducer of inflammatory responses. Specifically targeting these inflammation-inducing bacteria might be a therapeutic strategy to prevent BV and associated risks in STI susceptibility and preterm birth.


Transcription coactivator TRAP220 is required for PPAR gamma 2-stimulated adipogenesis.
The TRAP (thyroid hormone receptor-associated proteins) transcription coactivator complex (also known as Mediator) was first isolated as a group of proteins that facilitate the function of the thyroid hormone receptor. This complex interacts physically with several nuclear receptors through the TRAP220 subunit, and with diverse activators through other subunits. TRAP220 has been reported to show ligand-enhanced interaction with peroxisome proliferator-activated receptor gamma(2) (PPAR gamma(2)), a nuclear receptor essential for adipogenesis. Here we show that Trap220(-/-) fibroblasts are refractory to PPAR gamma(2)-stimulated adipogenesis, but not to MyoD-stimulated myogenesis, and do not express adipogenesis markers or PPAR gamma(2) target genes. These defects can be restored by expression of exogenous TRAP220. Further indicative of a direct role for TRAP220 in PPAR gamma(2) function via the TRAP complex, TRAP functions directly as a transcriptional coactivator for PPAR gamma(2) in a purified in vitro system and interacts with PPAR gamma(2) in a ligand- and TRAP220-dependent manner. These data indicate that TRAP220 acts, via the TRAP complex, as a PPAR gamma(2)-selective coactivator and, accordingly, that it is specific for one fibroblast differentiation pathway (adipogenesis) relative to another (myogenesis).


Uterine cervix conization based on Pap smear results: the "see and treat" approach.
The "see and treat" approach, proceeding without a biopsy directly to uterine cervix conization in women diagnosed with high grade squamous intraepithelial lesion (HGSIL) on Pap smear, shortens the treatment duration, lessens patient anxiety, and reduces health care costs. To evaluate the level of diagnostic accuracy and the over-treatment rate in the "see and treat" versus conventional management of women diagnosed with HGSIL. We retrospectively reviewed all women with HGSIL who had undergone the "see and treat" approach during 2001-2011 at Soroka University Medical Center. Similar cohorts, who were managed conventionally with a cervical biopsy prior to the conization, served as a comparison group. The study population consisted of 403 women: 72 (18%) had undergone the "see and treat" approach and 331 (82%) conventional management. The false positive rate was 11% for the "see and treat" group, compared to 6% for the conventional management group (P = 0.162). Similarly, no statistically significant difference was observed when comparing the positive predictive value (PPV) of high grade dysplasia diagnosed on Pap smear (PPV 88.9%) versus cervical biopsy (PPV 93.8%) (P = 0.204). Moreover, both the false positive rate and PPV remained similar in subgroups of patients, according to age, menopausal status, number of births, and colposcopy findings. The accuracy level of HGSIL diagnosis on Pap smear is similar to that of high grade dysplasia on a cervical biopsy. We therefore recommend referring patients with HGSIL directly to conization. Skipping the biopsy step was not associated with significant over-treatment or other adverse effects.


Privacy-Preserving Distributed Analytics in Fog-Enabled IoT Systems.
The Internet of Things (IoT) has evolved significantly with advances in gathering data that can be extracted to provide knowledge and facilitate decision-making processes. Currently, IoT data analytics encountered challenges such as growing data volumes collected by IoT devices and fast response requirements for time-sensitive applications in which traditional Cloud-based solution is unable to meet due to bandwidth and high latency limitations. In this paper, we develop a distributed analytics framework for fog-enabled IoT systems aiming to avoid raw data movement and reduce latency. The distributed framework leverages the computational capacities of all the participants such as edge devices and fog nodes and allows them to obtain the global optimal solution locally. To further enhance the privacy of data holders in the system, a privacy-preserving protocol is proposed using cryptographic schemes. Security analysis was conducted and it verified that exact private information about any edge device's raw data would not be inferred by an honest-but-curious neighbor in the proposed secure protocol. In addition, the accuracy of solution is unaffected in the secure protocol comparing to the proposed distributed algorithm without encryption. We further conducted experiments on three case studies: seismic imaging, diabetes progression prediction, and Enron email classification. On seismic imaging problem, the proposed algorithm can be up to one order of magnitude faster than the benchmarks in reaching the optimal solution. The evaluation results validate the effectiveness of the proposed methodology and demonstrate its potential to be a promising solution for data analytics in fog-enabled IoT systems.


Challenges for tree officers to enhance the provision of regulating ecosystem services from urban forests.
Urbanisation and a changing climate are leading to more frequent and severe flood, heat and air pollution episodes in Britain's cities. Interest in nature-based solutions to these urban problems is growing, with urban forests potentially able to provide a range of regulating ecosystem services such as stormwater attenuation, heat amelioration and air purification. The extent to which these benefits are realized is largely dependent on urban forest management objectives, the availability of funding, and the understanding of ecosystem service concepts within local governments, the primary delivery agents of urban forests. This study aims to establish the extent to which British local authorities actively manage their urban forests for regulating ecosystem services, and identify which resources local authorities most need in order to enhance provision of ecosystem services by Britain's urban forests. Interviews were carried out with staff responsible for tree management decisions in fifteen major local authorities from across Britain, selected on the basis of their urban nature and high population density. Local authorities have a reactive approach to urban forest management, driven by human health and safety concerns and complaints about tree disservices. There is relatively little focus on ensuring provision of regulating ecosystem services, despite awareness by tree officers of the key role that urban forests can play in alleviating chronic air pollution, flood risk and urban heat anomalies. However, this is expected to become a greater focus in future provided that existing constraints - lack of understanding of ecosystem services amongst key stakeholders, limited political support, funding constraints - can be overcome. Our findings suggest that the adoption of a proactive urban forest strategy, underpinned by quantified and valued urban forest-based ecosystem services provision data, and innovative private sector funding mechanisms, can facilitate a change to a proactive, ecosystem services approach to urban forest management.


Endoluminal graft repair for abdominal aortic aneurysms in high-risk patients and octogenarians: is it better than open repair?
To analyze the short-term and midterm results of open and endoluminal repair of abdominal aortic aneurysms (AAA) in a large single-center series and specifically in octogenarians. Between January 1997 and October 2000, 470 consecutive patients underwent elective repair of AAA. Conventional open repair (COR) was performed in 210 patients and endoluminal graft (ELG) repair in 260 patients. Ninety of the patients were 80 years of age or older; of these, 38 underwent COR and 52 ELG repair. Patient characteristics and risk factors were similar for both the entire series and the subgroup of patients 80 years or older. The overall complication rate was reduced by 70% or more in the ELG versus the COR groups. The postoperative death rate was similar for the COR and ELG groups in the entire series and lower (but not significantly) in the ELG 80 years or older subgroup versus the COR group. The 36-month rates of freedom from endoleaks, surgical conversion, and secondary intervention were 81%, 98.2%, and 88%, respectively. The short-term and midterm results of AAA repair by COR or ELG are similar. The death rate associated with this new technique is low and comparable, whereas the complication rate associated with COR in all patients and those 80 years or older in particular is greater and more serious than ELG repair. Long-term results will establish the role of ELG repair of AAA, especially in elderly and high-risk patients.


[Set of indicators for the assessment of the degree to which drug therapy guide is followed in primary care].
The constant gauging of drug prescription quality is part of the health-care process quality improvement programs as regards Primary Care, but generally speaking, there are no tried and true indicators which can be used in this assessment process. Measuring the degree to which certain set drugs are adhered to as a district-wide guide regarding which a consensus of opinion has been reached can be used as an overall indicator of prescribing-related quality. The objective of this study is that of setting out a method for selecting quality indicators of generalizing type, the same serving as an example with regard to selecting an indicator for gauging the degree to which the district guide is followed. Descriptive cross-sectional study entailing the general practitioners in the Health Care District of Avilés (n = 78) as the individual district analyzed, and the prescriptions written thereby which were invoiced in 1997 as the data source. Seven (7) indicators were prepared for gauging the degree to which the District Drug Therapy Guide was followed. A selection was made by studying the following aspects: reliability, ready availability, accuracy, sensitivity, specificity and coherence. The scores fell within the 10-23 range (out of a possible 28), the highest score being that of the percentage of prescriptions for active ingredients out of the guide in comparison to the total number of prescriptions written by each physician. The indicators used in assessing drug-prescribing quality must first be analyzed in detail before being implemented. An innovative method is suggested for testing indicators for monitoring the prescribing of drugs as a whole. The most useful of all of the indicators studied for gauging the degree to which the Primary Care drug therapy guide was being followed is the percentage of prescriptions written for active ingredients out of the total number of prescriptions written. The degree to which the District Drug Therapy Guide is followed is related positively to quality prescribing.


PPARγ coactivator-1α contributes to exercise-induced regulation of intramuscular lipid droplet programming in mice and humans.
Intramuscular accumulation of triacylglycerol, in the form of lipid droplets (LD), has gained widespread attention as a hallmark of metabolic disease and insulin resistance. Paradoxically, LDs also amass in muscles of highly trained endurance athletes who are exquisitely insulin sensitive. Understanding the molecular mechanisms that mediate the expansion and appropriate metabolic control of LDs in the context of habitual physical activity could lead to new therapeutic opportunities. Herein, we show that acute exercise elicits robust upregulation of a broad program of genes involved in regulating LD assembly, morphology, localization, and mobilization. Prominent among these was perilipin-5, a scaffolding protein that affects the spatial and metabolic interactions between LD and their surrounding mitochondrial reticulum. Studies in transgenic mice and primary human skeletal myocytes established a key role for the exercise-responsive transcriptional coactivator PGC-1α in coordinating intramuscular LD programming with mitochondrial remodeling. Moreover, translational studies comparing physically active versus inactive humans identified a remarkably strong association between expression of intramuscular LD genes and enhanced insulin action in exercise-trained subjects. These results reveal an intimate molecular connection between intramuscular LD biology and mitochondrial metabolism that could prove relevant to the etiology and treatment of insulin resistance and other disorders of lipid imbalance.