Three-dimensional shape measurement of aspheric mirrors with fringe reflection photogrammetry.
Three-dimensional (3D) shape measurement of an aspheric mirror with fringe reflection photogrammetry involves three steps: correspondence matching, triangulation, and bundle adjustment. Correspondence matching is realized by absolute phase tracking and triangulation is computed by the intersection of reflection and incidence rays. The main contribution in this paper is constraint bundle adjustment for carefully dealing with lens distortion in the process of ray intersection, as compared to the well-known grating reflection photogrammetry. Additionally, a free frame is proposed to alleviate troublesome system geometrical calibration, and constraint bundle adjustment is operated in the free frame to refine the 3D shape. Simulation and experiment demonstrate that constraint bundle adjustment can improve absolute measurement accuracy of aspheric mirrors.


Importance of inhaler device use status in the control of asthma in adults: the asthma inhaler treatment study.
Proper education and training in correct inhalation technique has been reported to have a substantial role in the achievement of optimal therapeutic benefit and asthma control. The present study was designed to evaluate inhaler technique and the role of education in relation to asthma control among patients with persistent asthma in Turkey. A total of 572 patients with persistent asthma (mean ± SD age 42.7 ± 12.2 y, 76% females) were included in this non-interventional, observational, registry study conducted across Turkey. Data on the effective and correct use of inhaler devices were collected via the Ease of Use for the Inhaler Device Questionnaire to patients and physicians. Asthma control (overall 61.5% at baseline, and increased to 87.3% during follow-up) was better, with significant improvement in technique and decrease in basic errors to the range 0-1, regardless of the inhaler type. Overall, the most common basic error associated with inhalation maneuvers was failure to exhale before inhaling through the device (18.9%). There was concordance between the patients and physicians in the ratio of correct inhaler technique only for spray-type inhalers. Close follow-up with repeated checking of the patient's inhaler technique and correction of errors each time by a physician seem to be associated with a significant decrease in the percent of patients who make basic errors in inhalation maneuvers and device-independent errors, and with better control of persistent asthma.


Effect of glycocalyx on shear-dependent albumin uptake in endothelial cells.
The glycocalyx layer on the surface of an endothelial cell is an interface barrier for uptake of macromolecules, such as low-density lipoprotein and albumin, in the cell. The shear-dependent uptake of macromolecules thus might govern the function of the glycocalyx layer. We therefore studied the effect of glycocalyx on the shear-dependent uptake of macromolecules into endothelial cells. Bovine aorta endothelial cells were exposed to shear stress stimulus ranging from 0.5 to 3.0 Pa for 48 h. The albumin uptake into the cells was then measured using confocal laser scanning microscopy, and the microstructure of glycocalyx was observed using electron microscopy. Compared with the uptake into endothelial cells under static conditions (no shear stress stimulus), the albumin uptake at a shear stress of 1.0 Pa increased by 16% and at 3.0 Pa decreased by 27%. Compared with static conditions, the thickness of the glycocalyx layer increased by 70% and the glycocalyx charge increased by 80% at a shear stress of 3.0 Pa. The albumin uptake at a shear stress of 3.0 Pa for cells with a neutralized (no charge) glycocalyx layer was almost twice that of cells with charged layer. These findings indicate that glycocalyx influences the albumin uptake at higher shear stress and that glycocalyx properties (thickness and charge level) are involved with the shear-dependent albumin uptake process.


Hif-1alpha regulates differentiation of limb bud mesenchyme and joint development.
Recent evidence suggests that low oxygen tension (hypoxia) may control fetal development and differentiation. A crucial mediator of the adaptive response of cells to hypoxia is the transcription factor Hif-1alpha. In this study, we provide evidence that mesenchymal condensations that give origin to endochondral bones are hypoxic during fetal development, and we demonstrate that Hif-1alpha is expressed and transcriptionally active in limb bud mesenchyme and in mesenchymal condensations. To investigate the role of Hif-1alpha in mesenchymal condensations and in early chondrogenesis, we conditionally inactivated Hif-1alpha in limb bud mesenchyme using a Prx1 promoter-driven Cre transgenic mouse. Conditional knockout of Hif-1alpha in limb bud mesenchyme does not impair mesenchyme condensation, but alters the formation of the cartilaginous primordia. Late hypertrophic differentiation is also affected as a result of the delay in early chondrogenesis. In addition, mutant mice show a striking impairment of joint development. Our study demonstrates a crucial, and previously unrecognized, role of Hif-1alpha in early chondrogenesis and joint formation.


Attitude, social influence, and self-efficacy among Chinese participants of chronic disease self-management program: a latent growth curve modeling study.
This study aimed to examine temporal relationships among psychological parameters (readiness to change, changes in self-efficacy [SE], social norm [SN], attitude [AT]) and two self-management behaviors: cognitive symptom management (CSM) and tangible help-seeking (TH) by constructing latent growth change models. This was a longitudinal study of 60 Chinese participants with various chronic diseases who completed a 6-week chronic disease self-management program. Psychological and behavioral variables were assessed at the beginning of the 1st, 4th, and 6th week of the program. Latent growth change curve analysis revealed that, in the early stages of engagement in CSM, SE was a key determinant of behavior. During the 6-week period, changes in SE were influenced directly by both SN and AT. When engaging in TH, SE influenced the behavior with direct and indirect effect from AT and SN. Readiness for change, on the other hand, appeared to be more associated with psychological rather than behavioral changes. This study revealed different underlying change mechanisms for two types of self-management behaviors. The findings shed light on program modifications that could further strengthen the therapeutic effects of the program.


A case study of school support and the psychological, emotional and behavioural consequences of HIV and AIDS on adolescents.
Various studies have reported a huge increase in the numbers of orphaned adolescents in Sub-Saharan Africa and its effects on their psychological, emotional and behavioural development. Yet, their needs are seldom recognised or adequately addressed in policy and programmes.This article uses a qualitative study to report the experiences of 11 orphaned adolescents (5 boys and 6 girls aged between 15 and 18 years) affected by HIV and AIDS in a secondary school (in Atteridgeville, Pretoria, South Africa) and the school support provided by them. The primary data-generation strategies were informal interviews and the Beck Youth Inventories-II (BYI-II) (adopted to measure the participants' level of emotional, behavioural and psychological problems). All interview transcriptions with the participants were thematically analysed. BYI-II data were subjected to T scores (in percentages) to know the participant's psychological, behavioural and emotional problems in order to compare it with their perceptions on the degree of support provided by the school. Result shows that participants have a high prevalence of psychological, behavioural and emotional problems and that the school support provided to them (teachers' support, the general school environment and the degree of discrimination, labelling and bullying that exists in the school) was not sufficient. The participants, however, reported a high level of support from the principal. In conclusion, we have suggested the urgent need for teachers to acquire and possess basic knowledge and skills in caring and paying attention to learners affected by HIV and AIDS and for government agencies and NGOs working with HIV-and AIDS-affected children, to focus on proposals that address the psychological, behavioural and emotional problems in such affected adolescents.


Patient Expectations and Perceptions of Goal-setting Strategies for Disease Management in Rheumatoid Arthritis.
To identify how patients perceive the broad effect of active rheumatoid arthritis (RA) on their daily lives and indicate how RA disease management could benefit from the inclusion of individual goal-setting strategies. Two multinational surveys were completed by patients with RA. The "Good Days Fast" survey was conducted to explore the effect of disease on the daily lives and relationships of women with RA. The "Getting to Your Destination Faster" survey examined RA patients' treatment expectations and goal-setting practices. Respondents from all countries agreed that RA had a substantial negative effect on many aspects of their lives (work productivity, daily routines, participation in social and leisure activities) and emotional well-being (loss of self-confidence, feelings of detachment, isolation). Daily pain was a paramount issue, and being pain- and fatigue-free was considered the main indicator of a "good day." Setting personal, social, and treatment goals, as well as monitoring disease progress to achieve these, was considered very beneficial by patients with RA, but discussion of treatment goals seldom appeared to be a part of medical appointments. Many patients with RA feel unable to communicate their disease burden and treatment goals, which are critically important to them, to their healthcare provider (HCP). Insights gained from these 2 surveys should help to guide patients and HCP to better focus upon mutually defined goals for continued improvement of management and achievement of optimal care in RA.


Patient and parent preferences for immunoglobulin treatments: a conjoint analysis.
The purpose was to quantify patient and parent preferences for administration attributes of immunoglobulin (IG) treatments; and determine which administration attributes were most important to users of IG treatment and whether patients and parents have similar preferences for administration attributes. US adult patients and parents of children with a self-reported physician diagnosis of a primary immunodeficiency disorder completed a best-practice web-enabled choice-format conjoint survey that presented a series of 12 choice questions, each including a pair of hypothetical IG-treatment profiles. After reviewing current therapies, each profile was defined by mode of administration, frequency, location, number of needle sticks, and treatment duration. Before answering the choice questions, respondents were told to assume all treatments worked equally well. Choice questions were based on a D-efficient experimental design. Preference weights for attribute levels were estimated using random-parameters logit for each sample (adult patients and parents). Tests were performed to determine potential interactions among the administration attributes. All respondents provided online informed consent. In total, 252 patients and 66 parents completed the choice questions appropriately. Overall, both groups preferred a home setting, monthly frequency, fewer needle sticks, and shorter treatment durations of IG treatment relative to alternative choices (p<0.05). Mode of administration was the least important attribute to both samples; however, parents strongly preferred self-administration to an appointment with a healthcare professional (p<0.05), whereas patients slightly preferred self-administration but were indifferent to the two modes. Respondents evaluate hypothetical treatments and differences can arise between stated and actual choices. Considering the hypothetical treatments evaluated, IG treatments that provide the option of a home setting, monthly frequency, fewer needle sticks, and shorter treatment durations may address the needs of both patients and parents. Patients and parents have different preferences for administration attributes of IG treatments.


Effects of Home Exercises on Shoulder Pain and Pathology in Chronic Spinal Cord Injury: A Randomized Controlled Trial.
The aims of this study were to replicate findings that a home exercise program intervention improved shoulder pain and function and to assess changes in supraspinatus tendon pathology associated with the home exercise program in persons with chronic spinal cord injury. The study is a single-blind randomized controlled trial. Individuals with spinal cord injury of at least 1 yr and chronic shoulder pain of moderate or greater average intensity were enrolled. Participants were randomized to a 12-wk home exercise program consisting of strengthening and stretching exercises or to an education-only control group, with immediate postintervention and 4-wk postintervention (16 wks) follow-ups. The main outcome measures were self-report measures of shoulder pain and impairment, the Physical Examination of the Shoulder Scale, quantitative ultrasound metrics of the supraspinatus tendon, and the Ultrasound Shoulder Pathology Rating Scale. Thirty-two participants were randomized to home exercise program or education-only control condition. The mean ± SD age was 44.8 ± 12.5; 81.3% were male; 65.6% had motor complete paraplegia. Using a per-protocol, within-group analysis method, significant differences were observed between baseline and postintervention for the home exercise program group for the least pain intensity (P = 0.02), number of days with shoulder pain (P = 0.042), Physical Examination of the Shoulder Scale scores (dominant side, P = 0.036; nondominant side, P = 0.008), the Disabilities of the Arm, Shoulder, and Hand (P = 0.028), and the Patient Global Impression of Change (P = 0.015). The education-only control condition group demonstrated significant changes in average unpleasantness of shoulder pain after the intervention period (P = 0.049). Comparisons in changes from baseline between groups showed that the home exercise program group had greater improvements in nondominant-side Physical Examination of the Shoulder Scale scores and global impression of change, whereas the education-only control condition group had greater improvements in depressive symptoms.For quantitative ultrasound measures, no significant changes were found with within-group analyses for the home exercise program group, although the education-only control condition group demonstrated a decrease in tendon width in the nondominant-side supraspinatus tendon (P = 0.036). Comparison of changes between groups suggests that the education-only control condition group had a greater increase in dominant shoulder supraspinatus tendon ultrasound contrast at the end of the study. Changes in several measures of shoulder pain and function occurred after the home exercise program intervention, although the magnitude of changes was only significantly greater than those of the education-only control condition group for two measures. Significant changes in supraspinatus pathology were not detected with quantitative ultrasound metrics.


Reduced 11beta-hydroxysteroid dehydrogenase type 1 activity in obese boys.
The incidence of childhood obesity and type 2 diabetes has reached epidemic proportions. Glucocorticoid excess causes central obesity and diabetes mellitus as seen in Cushing's syndrome. The 11beta-hydroxysteroid dehydrogenase type 1 enzyme (11beta-HSD1) regenerates active cortisol from inactive cortisone. Altered 11beta-HSD1 may cause tissue-specific Cushing's syndrome with central obesity and impaired glucose homeostasis. Clinical and laboratory characteristics, and anthropometric measurements were determined in 15 male and 6 female obese pubertal children (aged 12-18 years, Tanner stages 2-5). In addition, analyses of 24-h excretion rates of glucocorticoids were also performed in 21 age-, sex-, and pubertal stage-matched non-obese children using gas chromatographic-mass spectrometric (GC-MS) analysis. 11beta-HSD1 activity (urinary tetrahydrocortisol (THF) + 5alpha-THF/tetrahydrocortisone (THE) ratio) was lower in obese when compared with non-obese boys. In addition, obese children had a higher total cortisol metabolite excretion than non-obese children. 11beta-HSD1 activity was significantly related to age in lean and obese children. Standard deviation score (SDS)-body mass index did not correlate with 11beta-HSD1 activity, or with total cortisol metabolite excretion within each group. In obese children, 11beta-HSD1 activity and total cortisol metabolite excretion showed no correlation to waist-to-hip ratio, fat mass (percentage of body mass), or the homeostasis model assessment of insulin resistance index. In conclusion, our findings strongly suggest that 11beta-HSD1 activity increases with age, and is reduced in obese boys. In addition, obese children have a higher total cortisol metabolites excretion suggesting a stimulated hypothalamus-pituitary-adrenal axis.


Selective detection of acetone and hydrogen sulfide for the diagnosis of diabetes and halitosis using SnO(2) nanofibers functionalized with reduced graphene oxide nanosheets.
Sensitive detection of acetone and hydrogen sulfide levels in exhaled human breath, serving as breath markers for some diseases such as diabetes and halitosis, may offer useful information for early diagnosis of these diseases. Exhaled breath analyzers using semiconductor metal oxide (SMO) gas sensors have attracted much attention because they offer low cost fabrication, miniaturization, and integration into portable devices for noninvasive medical diagnosis. However, SMO gas sensors often display cross sensitivity to interfering species. Therefore, selective real-time detection of specific disease markers is a major challenge that must be overcome to ensure reliable breath analysis. In this work, we report on highly sensitive and selective acetone and hydrogen sulfide detection achieved by sensitizing electrospun SnO2 nanofibers with reduced graphene oxide (RGO) nanosheets. SnO2 nanofibers mixed with a small amount (0.01 wt %) of RGO nanosheets exhibited sensitive response to hydrogen sulfide (Rair/Rgas = 34 at 5 ppm) at 200 °C, whereas sensitive acetone detection (Rair/Rgas = 10 at 5 ppm) was achieved by increasing the RGO loading to 5 wt % and raising the operation temperature to 350 °C. The detection limit of these sensors is predicted to be as low as 1 ppm for hydrogen sulfide and 100 ppb for acetone, respectively. These concentrations are much lower than in the exhaled breath of healthy people. This demonstrates that optimization of the RGO loading and the operation temperature of RGO-SnO2 nanocomposite gas sensors enables highly sensitive and selective detection of breath markers for the diagnosis of diabetes and halitosis.


Quit attempts and quit rates among menthol and nonmenthol smokers in the United States.
We compared quit attempts and quit rates among menthol and nonmenthol cigarette smokers in the United States. We used data from the 2003 and 2006-2007 waves of the large, nationally representative Tobacco Use Supplement to the Current Population Survey with control for state-level tobacco control spending, prices, and smoke-free air laws. We estimated mean prevalence, quit rates, and multivariate logistic regression equations by using self-respondent weights for menthol and nonmenthol smokers. In 2003 and 2007, 70% of smokers smoked nonmenthol cigarettes, 26% smoked menthol cigarettes, and 4% had no preference. Quit attempts were 4.3% higher in 2003 and 8.8% higher in 2007 among menthol than nonmenthol smokers. The likelihood of quitting was 3.5% lower for quitting in the past year and 6% lower for quitting in the past 5 years in menthol compared with nonmenthol smokers. Quit success in the past 5 years was further eroded among menthol-smoking Blacks and young adults. Menthol smokers are more likely to make quit attempts, but are less successful at staying quit. The creation of menthol preference through marketing may reduce quit success.


"Catching your tail and firefighting": The impact of staffing levels on restraint minimization efforts.
WHAT IS KNOWN ON THE SUBJECT?: Mental health nursing in the UK and other countries faces an acute workforce crisis. Safe staffing levels are called for, and in some jurisdictions have been legislated for. The evidence base linking staffing levels and patient outcomes is limited. Staffing levels are implicated in adverse experiences of service users and staff within mental health ward settings, and they might contribute to levels of violence and aggression and the application of restrictive practices, such as physical restraint but there is limited research evidence to support this. Programmes such as Safewards, No Force First, the Engagement Model and the Six Core Strategies can reduce the use of restrictive practices. WHAT DOES THIS PAPER ADD TO EXISTING KNOWLEDGE?: Staffing levels on acute mental health wards appeared crucial in the implementation of a restraint minimization project. Both staff and service users implicate insufficient staffing for deficiencies in the relational elements of care, such as lack of face-to-face contact between nurses and service users. Similarly, staffing levels are associated with perceived problems in the cause of violence and aggression and responses to it. Despite successes in minimizing restrictive practices in this project, difficulties implementing alternative forms of practice that would reduce use of physical restraint, such as de-escalation, were also attributed to staffing levels. There is an irony that a project concerned with safety itself provoked concern over safe staffing levels. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Efforts to reduce restrictive practices will be hampered without adequate staffing levels. Restrictive practices may justifyably be framed as an employment relations matter. Organisations and policy makers ought to address environmental, contextual and resourcing factors, rather than identify problems exclusively in terms of perceived aberrant behaviour of staff or service users. ABSTRACT: Introduction Safe staffing and coercive practices are of pressing concern for mental health services. These are inter-dependent, and the relationship is under-researched. Aim To explore views on staffing levels in a context of attempting to minimize physical restraint practices on mental health wards. Findings emerged from a wider data set with the broader aim of exploring experiences of a restraint reduction initiative. Methods Thematic analysis of semi-structured interviews with staff (n = 130) and service users (n = 32). Results Five themes were identified regarding how staffing levels impact experiences and complicate efforts to minimize physical restraint. We titled the themes-"insufficient staff to do the job"; "detriment to staff and service users"; "a paperwork exercise: the burden of non-clinical tasks"; "false economies"; and, "you can't do these interventions." Discussion Tendencies detracting from relational aspects of care are not independent of insufficiencies in staffing. The relational, communicative and organizational developments that would enable reductions in use of restraint are labour intensive and vulnerable to derailment by insufficient and poorly skilled staff. Implications for practice Restrictive practices are unlikely to be minimized unless wards are adequately staffed. Inadequate staffing is not independent of restrictive practices and reduces access to alternative interventions for reducing individuals' distress.


Green Space Attachment and Health: A Comparative Study in Two Urban Neighborhoods.
The positive relationships between urban green space and health have been well documented. Little is known, however, about the role of residents' emotional attachment to local green spaces in these relationships, and how attachment to green spaces and health may be promoted by the availability of accessible and usable green spaces. The present research aimed to examine the links between self-reported health, attachment to green space, and the availability of accessible and usable green spaces. Data were collected via paper-mailed surveys in two neighborhoods (n = 223) of a medium-sized Dutch city in the Netherlands. These neighborhoods differ in the perceived and objectively measured accessibility and usability of green spaces, but are matched in the physically available amount of urban green space, as well as in demographic and socio-economic status, and housing conditions. Four dimensions of green space attachment were identified through confirmatory factor analysis: place dependence, affective attachment, place identity and social bonding. The results show greater attachment to local green space and better self-reported mental health in the neighborhood with higher availability of accessible and usable green spaces. The two neighborhoods did not differ, however, in physical and general health. Structural Equation Modelling confirmed the neighborhood differences in green space attachment and mental health, and also revealed a positive path from green space attachment to mental health. These findings convey the message that we should make green places, instead of green spaces.


An observational study of group waterpipe use in a natural environment.
To date research on tobacco smoking with a waterpipe (hookah, narghile, and shisha) has focused primarily on the individual user in a laboratory setting. Yet, waterpipe tobacco smoking is often a social practice that occurs in cafés, homes, and other natural settings. This observational study examined the behavior of waterpipe tobacco smokers and the social and contextual features of waterpipe use among groups in their natural environment. Trained observers visited urban waterpipe cafés on multiple occasions during an 8-month period. Observations of 241 individual users in naturally formed groups were made on smoking topography (puff frequency, duration, and interpuff interval [IPI]) and engagement in other activities (e.g., food and drink consumption, other tobacco use, and media viewing). Most users were male in group sizes of 3-4 persons, on average, and each table had 1 waterpipe, on average. The predominant social features during observational periods were conversation and nonalcoholic drinking. Greater puff number was associated with smaller group sizes and more waterpipes per group, while longer IPIs were associated with larger group sizes and fewer waterpipes per group. Additionally, greater puff frequency was observed during media viewing and in the absence of other tobacco use. Overall, the results suggest that waterpipe smoking behavior is affected by group size and by certain social activities. Discussion focuses on how these findings enhance our understanding of factors that may influence exposure to waterpipe tobacco smoke toxicants in naturalistic environments.


Intelligence and quality of dietary treatment in phenylketonuria.
The records of the Phenylketonuria Register were examined to determine the factors associated with early intellectual progress in children who had received a diet low in phenylalanine from soon after birth. A total of 1031 children were born between 1964 and 1980 and started treatment before they were 4 months of age, and 808 of them were followed up prospectively. In 263 children born between 1964 and 1971 (cohort 1), the mean intelligence quotient (IQ) at 4 years rose with year of birth from 24 points below revised IQ norms to 10 points below; in 545 born between 1972 and 1980 (cohort 2) there was no further rise in IQ and the mean remained eight points below the norms. IQ fell progressively by roughly four points for each four weeks' delay in starting treatment, for each 300 mumol/l rise in mean phenylalanine concentrations during treatment, and for each five months during the first two years during which phenylalanine concentrations were below 120 mumol/l. Forty six children in cohort 2 had the most favourable treatment characteristics. Their mean IQ, after standardising for social class, was 112.6, and similar to the mean for the same group estimated by multiple regression, and to revised population IQ norms for the period during which the children were tested. The data suggest that many children who are treated early continue to suffer a mild degree of neurological impairment because of the difficulties in fully controlling the metabolic abnormality.


Association of Stimulant Medication Use With Bone Mass in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder.
Murine studies reveal that sympathetic nervous system activation leads to decreased bone mass. Stimulant medications used to treat attention-deficit/hyperactivity disorder (ADHD) increase sympathetic tone and may affect bone remodeling. Because bone mass accrual is completed by young adulthood, assessing stimulant effects on bone density in growing children is of critical importance. To investigate associations between stimulant use and bone mass in children and adolescents. This cross-sectional analysis used data collected from January 1, 2005, to December 31, 2010, from the National Health and Nutrition Examination Survey (NHANES) database. NHANES is a series of cross-sectional, nationally representative health and nutrition surveys of the US population. All children, adolescents, and young adults aged 8 to 20 years with dual-energy x-ray absorptiometry (DXA), anthropometric, demographic, and prescription medication use data were eligible for participation. Of the 6489 respondents included in the multivariable linear regression analysis, 159 were stimulant users and 6330 were nonusers. Data were analyzed from October 8, 2015, to December 31, 2016. Stimulant use, determined by questionnaires administered via interview. The association between stimulant use and total femur, femoral neck, and lumbar spine bone mineral content (BMC) and bone mineral density (BMD) was assessed using DXA. Study participants included 6489 NHANES participants with a mean (SD) age of 13.6 (3.6) years. Stimulant use was associated with lower bone mass after adjustment for covariates. Mean lumbar spine BMC was significantly lower in stimulant users vs nonusers (12.76 g; 95% CI, 12.28-13.27 g vs 13.38 g; 95% CI, 13.26-13.51 g; P = .02), as was mean lumbar spine BMD (0.90 g/cm2; 95% CI, 0.87-0.94 g/cm2 vs 0.94 g/cm2; 95% CI, 0.94-0.94 g/cm2; P = .03) and mean femoral neck BMC (4.34 g; 95% CI, 4.13-4.57 g vs 4.59 g; 95% CI, 4.56-4.62 g; P = .03). Mean BMD of the femoral neck (0.88 g/cm2; 95% CI, 0.84-0.91 g/cm2 vs 0.91 g/cm2; 95% CI, 0.90-0.91 g/cm2; P = .08) and total femur (0.94 g/cm2; 95% CI, 0.90-0.99 g/cm2 vs 0.99 g/cm2; 95% CI, 0.98-0.99 g/cm2; P = .05) were also lower in stimulant users vs nonusers. Participants treated with stimulants for 3 months or longer had significantly lower lumbar spine BMD (0.89 g/cm2; 95% CI, 0.85-0.93 g/cm2 vs 0.94 g/cm2; 95% CI, 0.94-0.94 g/cm2; P = .02) and BMC (12.71 g; 95% CI, 12.14-13.32 g vs 13.38 g; 95% CI, 13.25-13.51 g; P = .03) and femoral neck BMD (0.87 g/cm2; 95% CI, 0.74-0.83 g/cm2 vs 0.91 g/cm2; 95% CI, 0.83-0.84 g/cm2; P = .048) than nonusers. Children and adolescents reporting stimulant use had lower DXA measurements of the lumbar spine and femur compared with nonusers. These findings support the need for future prospective studies to examine the effects of stimulant use on bone mass in children.


Centripetal spread of arterial collateral endothelial cell hyperplasia after renal artery stenosis in the rat.
The factors responsible for collateral arterial growth after major artery occlusion remain obscure, despite their importance for tissue survival. An increase in endothelial cell labelling with tritiated thymidine, as an index of collateral arterial growth, occurs early after renal artery occlusion. Our working premise was that an increase in endothelial cell labelling would occur simultaneously throughout the length of the collateral arteries if biophysical factors related to blood flow were the responsible mechanism, because blood flow must be increased simultaneously throughout the length of the small, preformed collateral arterial vessels. On the other hand, if the information spread from the ischemic zone, one would anticipate centripetal spread of the endothelial cell hyperplasia in a retrograde direction from the ischemic zone. With the periureteric collateral arterial supply as the model, we performed serial studies of tritiated thymidine labelling following renal artery stenosis in the rat. As anticipated, endothelial cell labelling rose sharply within 24 to 48 hours, first evident in the area immediately adjacent to the renal hilum. Thereafter, a progressive, time-related centripetal gradient in endothelial cell tritiated thymidine labelling occurred (p less than 0.01). These findings indicate that the factors responsible for endothelial cell hyperplasia are less related to blood flow in the lumen than to downstream, ischemic events. Although the mechanism responsible for the centripetal spread remains speculative, the communication system is likely to involve cell-to-cell contact in the vessel wall.


Bypass of a protein barrier by a replicative DNA helicase.
Replicative DNA helicases generally unwind DNA as a single hexamer that encircles and translocates along one strand of the duplex while excluding the complementary strand (known as steric exclusion). By contrast, large T antigen, the replicative DNA helicase of the simian virus 40 (SV40), is reported to function as a pair of stacked hexamers that pumps double-stranded DNA through its central channel while laterally extruding single-stranded DNA. Here we use single-molecule and ensemble assays to show that large T antigen assembled on the SV40 origin unwinds DNA efficiently as a single hexamer that translocates on single-stranded DNA in the 3'-to-5' direction. Unexpectedly, large T antigen unwinds DNA past a DNA-protein crosslink on the translocation strand, suggesting that the large T antigen ring can open to bypass bulky adducts. Together, our data underscore the profound conservation among replicative helicase mechanisms, and reveal a new level of plasticity in the interactions of replicative helicases with DNA damage.


A protein interaction framework for human mRNA degradation.
The degradation of mRNA is an important regulatory step in the control of gene expression. However, mammalian RNA decay pathways remain poorly characterized. To provide a framework for studying mammalian RNA decay, a two-hybrid protein interaction map was generated using 54 constructs from 38 human proteins predicted to function in mRNA decay. The results provide evidence for interactions between many different proteins required for mRNA decay. Of particular interest are interactions between the poly(A) ribonuclease and the exosome and between the Lsm complex, decapping factors, and 5'-->3' exonucleases. Moreover, multiple interactions connect 5'-->3' and 3'-->5' decay proteins to each other and to nonsense-mediated decay factors, providing the opportunity for coordination between decay pathways. The interaction network also predicts the internal organization of the exosome and Lsm complexes. Additional interactions connect mRNA decay factors to many novel proteins and to proteins required for other steps in gene expression. These results provide an experimental insight into the organization of proteins required for mRNA decay and their coupling to other cellular processes, and the physiological relevance of many of these interactions are supported by their evolutionary conservation. The interactions also provide a wealth of hypotheses to guide future research on mRNA degradation and demonstrate the power of exhaustive protein interaction mapping in aiding understanding of uncharacterized protein complexes and pathways.


Frequency-dependent, cell type-divergent signaling in the hippocamposeptal projection.
Hippocampal oscillations are critical for information processing, and are strongly influenced by inputs from the medial septum. Hippocamposeptal neurons provide direct inhibitory feedback from the hippocampus onto septal cells, and are therefore likely to also play an important role in the circuit; these neurons fire at either low or high frequency, reflecting hippocampal network activity during theta oscillations or ripple events, respectively. Here, we optogenetically target the long-range GABAergic projection from the hippocampus to the medial septum in rats, and thereby simulate hippocampal input onto downstream septal cells in an acute slice preparation. In response to optogenetic activation of hippocamposeptal fibers at theta and ripple frequencies, we elicit postsynaptic GABAergic responses in a subset (24%) of septal cells, most predominantly in fast-spiking cells. In addition, in another subset of septal cells (19%) corresponding primarily to cholinergic cells, we observe a slow hyperpolarization of the resting membrane potential and a decrease in input resistance, particularly in response to prolonged high-frequency (ripple range) stimulation. This slow response is partially sensitive to GIRK channel and D2 dopamine receptor block. Our results suggest that two independent populations of septal cells distinctly encode hippocampal feedback, enabling the septum to monitor ongoing patterns of activity in the hippocampus.


Pleiotropic role of VEGF-A in regulating fetal pulmonary mesenchymal cell turnover.
Tight regulation of VEGF-A production and signaling is important for the maintenance of lung development and homeostasis. VEGF null mice have provided little insight into the role of VEGF during the later stages of lung morphogenesis. Therefore, we examined the in vitro effects of autocrine and paracrine VEGF-A production and the inhibition of VEGF-A signaling on a Flk-1-negative subset of fetal pulmonary mesenchymal cells (pMC). We hypothesized that VEGF-A receptor signaling regulates turnover of fetal lung mesenchyme in a cell cycle-dependent manner. VEGF receptor blockade with SU-5416 caused cell spreading and decreased proliferation and bcl-2 localization. Nuclear expression of the cell cycle inhibitory protein, p21, was increased with SU-5416 treatment, and p27 was absent. Autocrine VEGF production by pMC resulted in proliferation and p21/p27-dependent contact inhibition. In contrast, exogenous VEGF-A increased cell progression through the cell cycle. Selective activation of Flt by placental growth factor demonstrated the importance of this receptor/kinase in the VEGF-A responsiveness of pMC. The expression and localization of the survival factor bcl-2 was dependent on VEGF. These results provide evidence that VEGF-A plays a critical role in the regulation of fetal pulmonary mesenchymal proliferation, survival, and the subsequent development of normal lung architecture through bcl-2 and p21/p27-dependent cell cycle control.


Trial Forge Guidance 2: how to decide if a further Study Within A Trial (SWAT) is needed.
The evidence base available to trialists to support trial process decisions-e.g. how best to recruit and retain participants, how to collect data or how to share the results with participants-is thin. One way to fill gaps in evidence is to run Studies Within A Trial, or SWATs. These are self-contained research studies embedded within a host trial that aim to evaluate or explore alternative ways of delivering or organising a particular trial process.SWATs are increasingly being supported by funders and considered by trialists, especially in the UK and Ireland. At some point, increasing SWAT evidence will lead funders and trialists to ask: given the current body of evidence for a SWAT, do we need a further evaluation in another host trial? A framework for answering such a question is needed to avoid SWATs themselves contributing to research waste.This paper presents criteria on when enough evidence is available for SWATs that use randomised allocation to compare different interventions.


Anti-inflammatory effect of exclusive enteral nutrition in patients with juvenile idiopathic arthritis.
There is extensive evidence for an influence of gut microbiota on the immune system, which has consequences for inflammatory diseases. Exclusive enteral nutrition (EEN), which may change the gut microbiota, is an effective anti-inflammatory treatment for Crohn's disease in children. We wanted to explore the immediate anti-inflammatory effect of EEN in children with juvenile idiopathic arthritis (JIA). Thirteen patients with JIA (7-17 years of age), in a disease flare-up, were included in the study. Six children dropped out within 1.5-2.0 weeks of treatment, and seven patients continued, constituting the study cohort. EEN was given for three to eight weeks, with clinical and laboratory status assessed before and after treatment periods. In addition to conventional laboratory tests, 92 inflammatory proteins were analysed with a multiplex system (Proseek Multiplex Inflammation I, Olink Bioscience). EEN had a significant anti-inflammatory effect on active joints (p=0.031), JADAS27 (p=0.016) and morning stiffness (p=0.031). In the multiplex analysis of inflammatory proteins, MMP-1 (matrix metalloproteinase), involved in the degradation of collagens in chondrocytes, decreased significantly (p=0.047), as did MCP-4 (p=0.031) and 4E-BP1 (p=0.031). Exclusive enteral nutrition for three to eight weeks had anti-inflammatory effect in all children with JIA that continued with EEN for more than two weeks. The study is only exploratory but the result supports an immunologically important role for the intestinal canal in these patients.


The multistate life table method: an application to contraceptive switching behavior.
In many demographic behaviors (e.g., those relating to marriage, contraception, migration, and health), people change among multiple statuses through time, sometimes leaving and then returning to the same status. Data on such behaviors are often collected in surveys as censored event histories. The multistate life table (MSLT) can be used to properly describe, in a single analysis, these complex transitions among multiple states measured in such data, but MSLT is rarely applied in the demographic literature because practical guidance is lacking on how to compute MSLTs with such data. We provide methods for computing MSLT quantities using censored event-history data: namely, transition intensities and probabilities, "state occupancy" probabilities and standard errors, average time spent in specified states, and average number of visits to specified states. Applying these methods to contraceptive use, we find high levels of switching back and forth, particularly between barrier methods and non-use, resulting in high rates of unintended pregnancy.


Feasibility of Attachable Ring Stimulator for Intraoperative Neuromonitoring during Thyroid Surgery.
Stimulator-attached dissecting instruments are useful for intraoperative nerve monitoring during thyroidectomy. The aim of this study was to evaluate the feasibility of an attachable ring stimulator (ARS) by comparing the electromyography (EMG) amplitudes evoked by an ARS and a conventional stimulator. Medical records of fourteen patients who underwent thyroidectomy using intraoperative neuromonitoring between June and August 2019 were retrospectively reviewed. The amplitudes of V1, R1, R2, and V2 signals were checked using both the ARS and a conventional stimulator, at the same point. Both stimulators were tested on 20 recurrent laryngeal nerves (RLNs) and 20 vagus nerves (VNs). In all the nerves, the amplitudes of V1, R1, R2, and V2 were greater than 500 μV. The mean amplitudes of V1, R1, R2, and V2 checked with the ARS were 1175, 1432, 1598, and 1279 μV, respectively. The mean amplitudes of V1, R1, R2, and V2 checked with the conventional stimulator were 1140, 1425, 1557, and 1217 μV, respectively. Difference between amplitudes evoked by the two stimulators for V1, R1, R2, and V2 was 77, 110, 102, and 99 μV, respectively. There was no statistical difference in the amplitudes between the two groups for V1, R1, R2, and V2. The ARS transferred electric stimulation as effectively as the conventional stimulator. It is an effective tool for repeated stimulation and facilitates continuous feedback regarding the functional integrity of nerves during thyroid surgery.


Similarity of arterial and intravenous vasopressin on portal and systemic hemodynamics.
The effects of superior mesenteric arterial and intravenous infusions of vasopressin and low and high dose intravenous infusions of vasopressin on splanchnic and systemic hemodynamics were compared in 20 anesthetized dogs. The following parameters were evaluated: flow in the superior mesenteric artery and portal vein, portal and systemic blood pressure, and cardiac output. In the comparison of selective arterial and intravenous infusions, no statistically significant difference was found between the degree of changes in portal flow, portal and systemic blood pressure, and cardiac output. Only the superior mesenteric artery flow showed a greater decrease with the selective arterial injection. In a comparison of intravenous high dose (corresponding to that used clinically) and low dose (one-fifth) infusions of vasopressin, a relatively high splanchnic and low systemic effectiveness of the low dose was found. It resulted in only a 15 to 20% smaller effect on flow in the superior mesenteric artery and portal vein and portal pressure; however, about 40% lesser systemic effect on arterial blood pressure and cardiac output than the high dose. The results of this experimental work warrant exploration in clinical practice, preferably by a controlled study. If clinical success in controlling hemorrhage confirms these hemodynamic results, an intravenous. low dose infusion of vasopressin would appear to be the method of choice in the vasoconstrictive therapy of gastrointestinal bleeding from varices.


Evolution of the scintillation index and the optical vortex density in speckle fields after removal of the least-squares phase.
Knowledge of the behavior of stochastic optical fields can aid the understanding of the scintillation of light propagating through a turbulent medium. For this purpose, we perform a numerical investigation of the evolution of the scintillation index and the optical vortex density in a speckle field after removing its continuous phase. We find that both the scintillation index and the vortex density initially drop and then increase again to reach an equilibrium level. It is also found that the initial rate of decrease in both cases is 1 order of magnitude faster than the eventual rate of increase. Their detail shapes are however different. Therefore different empirical functions are used to fit the shapes of these curves.


Suprarenal aortic flow reduction versus angiotensin I infusion in fetal sheep.
In the unanaesthetized fetal sheep, long-term suprarenal aortic blood flow reduction will cause upper body arterial blood pressure to increase. To see if the response to this procedure was entirely due to the concomitant increase in plasma renin activity, we gave an angiotensin I infusion of several days to 7 fetal sheep and compared their responses to those of 4 fetal sheep undergoing partial occlusion of the aorta above the renal arteries. Both protocols caused upper body arterial blood pressure to increase to comparable levels. Angiotensin I infusion had no effect upon venous blood pressure while suprarenal aortic blood flow reduction caused a significant increase in venous blood pressure as early as 1 day after blood flow reduction. Haematocrits were unchanged in the fetuses with flow restriction but increased in the infused fetuses. We conclude that long-term angiotensin I infusion in the fetus does not mimic the entire complex of responses to suprarenal aortic blood flow reduction.


The Role of Shed PrPc in the Neuropathogenesis of HIV Infection.
HIV-1 enters the CNS soon after peripheral infection and causes chronic neuroinflammation and neuronal damage that leads to cognitive impairment in 40-70% of HIV-infected people. The nonpathogenic cellular isoform of the human prion protein (PrPc) is an adhesion molecule constitutively expressed in the CNS. Previously, our laboratory showed that shed PrPc (sPrPc) is increased in the cerebrospinal fluid of HIV-infected people with cognitive deficits as compared with infected people with no impairment. In this article, we demonstrate that CCL2 and TNF-α, inflammatory mediators that are elevated in the CNS of HIV-infected people, increase shedding of PrPc from human astrocytes by increasing the active form of the metalloprotease ADAM10. We show that the consequence of this shedding can be the production of inflammatory mediators, because treatment of astrocytes with rPrPc increased secretion of CCL2, CXCL-12, and IL-8. Supernatants from rPrPc-treated astrocytes containing factors produced in response to this treatment, but not rPrPc by itself, cause increased chemotaxis of both uninfected and HIV-infected human monocytes, suggesting a role for sPrPc in monocyte recruitment into the brain. Furthermore, we examined whether PrPc participates in glutamate uptake and found that rPrPc decreased uptake of this metabolite in astrocytes, which could lead to neurotoxicity and neuronal loss. Collectively, our data characterize mediators involved in PrPc shedding and the effect of this sPrPc on monocyte chemotaxis and glutamate uptake from astrocytes. We propose that shedding of PrPc could be a potential target for therapeutics to limit the cognitive impairment characteristic of neuroAIDS.


Characterizing the EEG correlates of exploratory behavior.
This study aims to characterize the electroencephalography (EEG) correlates of exploratory behavior. Decision making in an uncertain environment raises a conflict between two opposing needs: gathering information about the environment and exploiting this knowledge in order to optimize the decision. Exploratory behavior has already been studied using functional magnetic resonance imaging (fMRI). Based on a usual paradigm in reinforcement learning, this study has shown bilateral activation in the frontal and parietal cortex. To our knowledge, no previous study has been done on it using EEG. The study of the exploratory behavior using EEG signals raises two difficulties. First, the labels of trial as exploitation or exploration cannot be directly derived from the subject action. In order to access this information, a model of how the subject makes his decision must be built. The exploration related information can be then derived from it. Second, because of the complexity of the task, its EEG correlates are not necessarily time locked with the action. So the EEG processing methods used should be designed in order to handle signals that shift in time across trials. Using the same experimental protocol as the fMRI study, results show that the bilateral frontal and parietal areas are also the most discriminant. This strongly suggests that the EEG signal also conveys information about the exploratory behavior.


Protocol for a mixed-methods exploratory investigation of care following intensive care discharge: the REFLECT study.
A substantial number of patients discharged from intensive care units (ICUs) subsequently die without leaving hospital. It is unclear how many of these deaths are preventable. Ward-based management following discharge from ICU is an area that patients and healthcare staff are concerned about. The primary aim of REFLECT (Recovery Following Intensive Care Treatment) is to develop an intervention plan to reduce in-hospital mortality rates in patients who have been discharged from ICU. REFLECT is a multicentre mixed-methods exploratory study examining ward care delivery to adult patients discharged from ICU. The study will be made up of four substudies. Medical notes of patients who were discharged from ICU and subsequently died will be examined using a retrospective case records review (RCRR) technique. Patients and their relatives will be interviewed about their post-ICU care, including relatives of patients who died in hospital following ICU discharge. Staff involved in the care of patients post-ICU discharge will be interviewed about the care of this patient group. The medical records of patients who survived their post-ICU stay will also be reviewed using the RCRR technique. The analyses of the substudies will be both descriptive and use a modified grounded theory approach to identify emerging themes. The evidence generated in these four substudies will form the basis of the intervention development, which will take place through stakeholder and clinical expert meetings. Ethical approval has been obtained through the Wales Research and Ethics Committee 4 (17/WA/0107). We aim to disseminate the findings through international conferences, international peer-reviewed journals and social media. ISRCTN14658054.


Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila.
Proteins with expanded polyglutamine repeats cause Huntington's disease and other neurodegenerative diseases. Transcriptional dysregulation and loss of function of transcriptional co-activator proteins have been implicated in the pathogenesis of these diseases. Huntington's disease is caused by expansion of a repeated sequence of the amino acid glutamine in the abnormal protein huntingtin (Htt). Here we show that the polyglutamine-containing domain of Htt, Htt exon 1 protein (Httex1p), directly binds the acetyltransferase domains of two distinct proteins: CREB-binding protein (CBP) and p300/CBP-associated factor (P/CAF). In cell-free assays, Httex1p also inhibits the acetyltransferase activity of at least three enzymes: p300, P/CAF and CBP. Expression of Httex1p in cultured cells reduces the level of the acetylated histones H3 and H4, and this reduction can be reversed by administering inhibitors of histone deacetylase (HDAC). In vivo, HDAC inhibitors arrest ongoing progressive neuronal degeneration induced by polyglutamine repeat expansion, and they reduce lethality in two Drosophila models of polyglutamine disease. These findings raise the possibility that therapy with HDAC inhibitors may slow or prevent the progressive neurodegeneration seen in Huntington's disease and other polyglutamine-repeat diseases, even after the onset of symptoms.


Reduction of inflammatory biomarker response by abatacept in treatment of rheumatoid arthritis.
Abatacept, a soluble selective costimulation modulator, selectively modulates T cell activation via the CD80/CD86:CD28 costimulation pathway. Data from a Phase II trial showed efficacy in patients with active rheumatoid arthritis (RA) and inadequate response to methotrexate when treated with abatacept (10 mg/kg or 2 mg/kg). To determine the mechanism of action of abatacept, we analyzed changes in the serum levels of inflammatory biomarkers in the patients enrolled in this trial. Following 12 months' treatment, serum levels of interleukin 6 (IL-6), soluble IL-2 receptor, C-reactive protein, soluble E-selectin, and soluble intercellular adhesion molecule-1 were significantly lower in patients receiving abatacept 10 mg/kg versus placebo. Smaller reductions in tumor necrosis factor-a and rheumatoid factor were also observed in the abatacept 10 mg/kg group compared with the placebo group. Although there was no evidence for efficacy of the 2 mg/kg dose, small reductions in inflammatory biomarkers at this dosage support the biologic effect of this therapy. These findings reveal the antiinflammatory and immunomodulatory effects of abatacept in patients with RA, and are consistent with the concept that modulating T cell activation improves clinical signs and symptoms and inhibits the progression of structural damage. These data suggest that selective modulation of the CD80/CD86:CD28 pathway with abatacept may affect several inflammatory cell types and cytokines that are involved in the proinflammatory cascade.


Genetic variation in circadian regulation of nocturnal stomatal conductance enhances carbon assimilation and growth.
Circadian resonance, whereby a plant's endogenous rhythms are tuned to match environmental cues, has been repeatedly shown to be adaptive, although the underlying mechanisms remain elusive. Concomitantly, the adaptive value of nocturnal transpiration in C3 plants remains unknown because it occurs without carbon assimilation. These seemingly unrelated processes are interconnected because circadian regulation drives temporal patterns in nocturnal stomatal conductance, with maximum values occurring immediately before dawn for many species. We grew individuals of six Eucalyptus camaldulensis genotypes in naturally lit glasshouses and measured sunset, predawn and midday leaf gas exchange and whole-plant biomass production. We tested whether sunrise anticipation by the circadian clock and subsequent increases in genotype predawn stomatal conductance led to rapid stomatal opening upon illumination, ultimately affecting genotype differences in carbon assimilation and growth. We observed faster stomatal responses to light inputs at sunrise in genotypes with higher predawn stomatal conductance. Moreover, early morning and midday stomatal conductance and carbon assimilation, leaf area and total plant biomass were all positively correlated with predawn stomatal conductance across genotypes. Our results lead to the novel hypothesis that genotypic variation in the circadian-regulated capacity to anticipate sunrise could be an important factor underlying intraspecific variation in tree growth.


Prospects for dedicated energy crop production and attitudes towards agricultural straw use: The case of livestock farmers.
Second generation biofuels utilising agricultural by-products (e.g. straw), or dedicated energy crops (DECs) produced on 'marginal' land, have been called for. A structured telephone survey of 263 livestock farmers, predominantly located in the west or 'marginal' upland areas of England captured data on attitudes towards straw use and DECs. Combined with farm physical and business data, the survey results show that 7.2% and 6.3% of farmers would respectively consider growing SRC and miscanthus, producing respective maximum potential English crop areas of 54,603 ha and 43,859 ha. If higher market prices for straw occurred, most livestock farmers would continue to buy straw. Reasons for not being willing to consider growing DECs include concerns over land quality, committing land for a long time period, lack of appropriate machinery, profitability, and time to financial return; a range of moral, land quality, production conflict and lack of crop knowledge factors were also cited. Results demonstrate limited potential for the production of DECs on livestock farms in England. Changes in policy support to address farmer concerns with respect to DECs will be required to incentivise farmers to increase energy crop production. Policy support for DEC production must be cognisant of farm-level economic, tenancy and personal objectives.


Complexity of the Genetics and Clinical Presentation of Spinocerebellar Ataxia 17.
Spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominant neurodegenerative disease caused by a CAG repeat expansion in the TATA-box binding protein gene (TBP). The disease has a varied age at onset and clinical presentation. It is distinct from other SCAs for its association with dementia, psychiatric symptoms, and some patients presenting with chorea. For this reason, it is also called Huntington's disease-like 4 (HDL-4). Here we examine the distribution of SCA17 allele repeat sizes in a United Kingdom-based cohort with ataxia and find that fully penetrant pathogenic alleles are very rare (5 in 1,316 chromosomes; 0.38%). Phenotype-genotype correlation was performed on 30 individuals and the repeat structure of their TBP genes was examined. We found a negative linear correlation between total CAG repeat length and age at disease onset and, unlike SCA1, there was no correlation between the longest contiguous CAG tract and age at disease onset. We were unable to identify any particular phenotypic trait that segregated with particular CAG/CAA repeat tract structures or repeat lengths. One individual within the cohort was homozygous for variable penetrance range SCA17 alleles. This patient had a similar age at onset to heterozygotes with the same repeat sizes, but also presented with a rapidly progressive dementia. A pair of monozygotic twins within the cohort presented 3 years apart with the sibling with the earlier onset having a more severe phenotype with dementia and chorea in addition to the ataxia observed in their twin. This appears to be a case of variable expressivity, possibly influenced by other environmental or epigenetic factors. Finally, there was an asymptomatic father with a severely affected child with an age at onset in their twenties. Despite this, they share the same expanded allele repeat sizes and sequences, which would suggest that there is marked difference in the penetrance of this 51-repeat allele. We therefore propose that the variable penetrance range extend from 48 repeats to incorporate this allele. This study shows that there is variability in the presentation and penetrance of the SCA17 phenotype and highlights the complexity of this disorder.


Mortality of workers exposed to ethylene oxide: extended follow up of a British cohort.
To obtain further information about the risks of cancer associated with occupational exposure to ethylene oxide Follow up was extended by 13 years for a cohort of 2876 men and women with definite or potential exposure to ethylene oxide in the chemical industry or in hospital sterilising units. Subjects were traced through National Health Service and social security records, and their mortality was compared with that expected from rates in the national population by the person-years method. Analysis was based on 565 deaths, of which 339 had occurred during the additional period of follow up. Mortality was close to or below expectation for all causes (565 deaths v 607.6 expected), all cancers (188 v 184.2), and for all specific categories of malignancy including stomach cancer (10 v 11.6), breast cancer (11 v 13.2), non-Hodgkin's lymphoma (7 v 4.8), and leukaemia (5 v 4.6). All five deaths from leukaemia occurred in the subset of subjects with greatest potential for exposure to ethylene oxide, but even in this group the excess of deaths was small (2.6 expected). The balance of evidence from this and other epidemiological investigations indicates that any risk of human cancer from ethylene oxide is low, particularly at the levels of occupational exposure that have occurred in Britain over recent decades. This may reflect the capacity of human cells to repair DNA damage caused by the chemical, which is a potent genotoxin and animal carcinogen.


Exploration of the protein requirement during weight loss in obese older adults.
Currently there is no consensus on protein requirements for obese older adults during weight loss. Here we explore the potential use of a new method for assessment of protein requirements based on changes in appendicular muscle mass during weight loss. 60 obese older adults were subjected to 13 wk weight loss program, including hypocaloric diet and resistance training. Assessment of appendicular muscle mass was performed by DXA at baseline and after 13 wk challenge period, and the difference calculated as muscle mass change. Protein intake (g/kg body weight and g/kg fat free mass (FFM)) at 13wks was used as marker of protein intake during 13 wk period. 30 subjects received 10 times weekly 20 g protein supplement throughout the 13 week hypocaloric phase which is included in the calculation of total protein intake. Receiver operating characteristic (ROC) curve analysis was used to explore the optimal cutoff point for protein intake (g/kg) versus increase in appendicular muscle mass of more than 250 g over 13 wks (y/n). Subsequently, logistic regression analysis was performed for protein intake cutoff and muscle mass accretion, adjusted for sex, age, baseline BMI, and training compliance. ROC curve analysis provided a protein intake level per day of 1.2 g/kg bw and 1.9 g/kg FFM as cutoff point. Presence of muscle mass accretion during 13 wk challenge period was significantly higher with protein intake higher than 1.2 g/kg bw (OR 5.4, 95%CI 1.4-20.6, p = 0.013) or higher than 1.9 g/kg FFM (OR 8.1, 95%CI 2.1-31.9, p = 0.003). Subjects with a protein intake higher than 1.2 g/kg had significantly more often muscle mass accretion, compared to subjects with less protein intake (10/14 (72%) vs 15/46 (33%), p = 0.010). For 1.9 g/kg FFM this was 70% vs 28% (p = 0.002). This exploratory study provided a level of at least 1.2 g/kg body weight or 1.9 g/kg fat free mass as optimal daily protein intake for obese older adults under these challenged conditions of weight loss, based on muscle mass accretion during the challenge. Dutch Trial Register under number NTR2751.


MHC-resident variation affects risks after unrelated donor hematopoietic cell transplantation.
Blood malignancies can be cured with hematopoietic cell transplantation from human leukocyte antigen (HLA)-matched unrelated donors; however, acute graft-versus-host disease (GVHD) affects up to 80% of patients and contributes to increased mortality. To test the hypothesis that undetected patient-donor differences for non-HLA genetic variation within the major histocompatibility complex (MHC) could confer risks after HLA-matched transplantation, we conducted a discovery-validation study of 4205 transplants for 1120 MHC region single-nucleotide polymorphisms (SNPs). Two SNPs were identified as markers for disease-free survival and acute GVHD. Among patients with two or more HLA-matched unrelated donors identified on their search, SNP genotyping of patients and their potential donors demonstrated that most patients have a choice of SNP-matched donors. In conclusion, the success of HLA-matched unrelated donor hematopoietic cell transplantation depends on non-HLA MHC region genetic variation. Prospective SNP screening and matching provides an approach for lowering risks to patients.


Chlamydomonas fla mutants reveal a link between deflagellation and intraflagellar transport.
Cilia and flagella are often lost in anticipation of mitosis or in response to stress. There are two ways that a cell can lose its flagella: resorption or deflagellation. Deflagellation involves active severing of the axoneme at the base of the flagellum; this process is defective in Chlamydomonas fa mutants. In contrast, resorption has been thought to occur as a consequence of constitutive disassembly at the tip in the absence of continued assembly, which requires intraflagellar transport (IFT). Chlamydomonas fla mutants are unable to build and maintain flagella due to defects in IFT. fla10 cells, which are defective in kinesin-II, the anterograde IFT motor, resorb their flagella at the restrictive temperature (33 degrees C), as previously reported. We find that in standard media containing approximately 300 microM calcium, fla10 cells lose flagella by deflagellation at 33 degrees C. This temperature-induced deflagellation of a fla mutant is not predicted by the IFT-based model for flagellar length control. Other fla mutants behave similarly, losing their flagella by deflagellation instead of resorption, if adequate calcium is available. These data suggest a new model whereby flagellar resorption involves active disassembly at the base of the flagellum via a mechanism with components in common with the severing machinery of deflagellation. As predicted by this model, we discovered that deflagellation stimuli induce resorption if deflagellation is blocked either by mutation in a FA gene or by lack of calcium. Further support for this model comes from our discovery that fla10-fa double mutants resorb their flagella more slowly than fla10 mutants. Deflagellation of the fla10 mutant at the restrictive temperature is indicative of an active disassembly signal, which can manifest as either resorption or deflagellation. We propose that when IFT is halted by either an inactivating mutation or a cellular signal, active flagellar disassembly is initiated. This active disassembly is distinct from the constitutive disassembly which plays a role in flagellar length control.


Attachment and depression differentially influence nicotine dependence among male and female undergraduates: a preliminary study.
The authors surveyed a convenience sample of 208 undergraduate students who reported that they smoked cigarettes. The primary hypothesis they tested was whether gender predicted nicotine dependence. They further tested whether depression and attachment would mediate or moderate this relationship. Hierarchical regression analyses with social desirability and smoking stage of change entered as covariates indicated that women exhibited greater nicotine dependence than men did (p < .01). Lower attachment scores fully mediated this relationship, whereas elevated depression scores moderated the relationship. These findings suggest that depression and the inability to bond with peers may promote nicotine dependence among young female students.


Semi-elective intraosseous infusion after failed intravenous access in pediatric anesthesia.
Intraosseous (IO) infusion is a well-established intervention to obtain vascular access in pediatric emergency medicine but is rarely used in routine pediatric anesthesia. In this observational study, we report on a series of 14 children in whom semi-elective IO infusion was performed under inhalational anesthesia after peripheral intravenous (IV) access had failed. Patient and case characteristics, technical details, and estimated timings of IO infusion as well as associated complications were reviewed. Data are median and range. IO infusion was successfully established in fourteen children [age: 0.1-6.00 years (median 0.72 years); weight: 3.5-12.0 kg (median 7.0 kg)]. The majority suffered from chronic cardiac, metabolic, or dysmorphic abnormalities. Estimated time taken from inhalational induction of anesthesia until insertion of an intraosseous needle was 26.5 min (15-65 min). The proximal tibia was cannulated in all patients. The automated EZIO IO system was used in eight patients and the manual COOK system in six patients. Drugs administered included hypnotics, opioids, neuromuscular blocking agents and reversals, cardiovascular drugs, antibiotics, and IV fluids. The IO cannulas were removed either in the operating theatre (n = 5), in the recovery room (n = 5), or in the ward (n = 4), after 73 min (19-225 min) in situ. There were no significant complications except one accidental postoperative dislocation. IO access represents a quick and reliable alternative for pediatric patients with prolonged difficult or failed IV access after inhalational induction of anesthesia.


Pulmonary sarcoidosis is associated with high-level inducible co-stimulator (ICOS) expression on lung regulatory T cells--possible implications for the ICOS/ICOS-ligand axis in disease course and resolution.
Sarcoidosis is a granulomatous inflammatory disorder of unknown aetiology. The increased frequency of activated lung CD4(+) T cells with a T helper type 1 (Th1) cytokine profile in sarcoidosis patients is accompanied by a reduced proportion and/or impaired function of regulatory T cells (Tregs ). Here we evaluated the expression of the inducible co-stimulator (ICOS) on lung and blood CD4(+) T cell subsets in sarcoidosis patients with different prognosis, by flow cytometry. Samples from the deep airways were obtained by bronchoalveolar lavage (BAL). We show that Tregs from the inflamed lung of sarcoidosis patients were characterized by a unique ICOS(high) phenotype. High-level ICOS expression was restricted to Tregs from the inflamed lung and was absent in blood Tregs of sarcoidosis patients as well as in lung and blood Tregs of healthy volunteers. In addition, lung Tregs exhibited increased ICOS expression compared to sarcoid-specific lung effector T cells. Strikingly, ICOS expression on Tregs was in particularly high in the lungs of Löfgren's syndrome (LS) patients who present with acute disease which often resolves spontaneously. Moreover, blood monocytes from LS patients revealed increased ICOS-L levels compared to healthy donors. Sarcoidosis was associated with a shift towards a non-classical monocyte phenotype and the ICOS-L(high) phenotype was restricted to this particular monocyte subset. We propose a potential implication of the ICOS/ICOS-L immune-regulatory axis in disease activity and resolution and suggest to evaluate further the suitability of ICOS as biomarker for the prognosis of sarcoidosis.


Long-term effects of fetal exposure to low doses of the xenoestrogen bisphenol-A in the female mouse genital tract.
Developmental exposure to estrogenic chemicals induces morphological, functional, and behavioral anomalies associated with reproduction. Humans are routinely exposed to bisphenol-A (BPA), an estrogenic compound that leaches from dental materials and plastic food and beverage containers. The aim of the present study was to determine the effects of in utero exposure to low, environmentally relevant doses of BPA on the development of female reproductive tissues in CD-1 mice. In previous publications, we have shown that this treatment alters the morphology of the mammary gland and affects estrous cyclicity. Here we report that in utero exposure to 25 and 250 ng BPA/ kg of body weight per day via osmotic pumps implanted into pregnant dams at Gestational Day 9 induces alterations in the genital tract of female offspring that are revealed during adulthood. They include decreased wet weight of the vagina, decreased volume of the endometrial lamina propria, increased incorporation of bromodeoxyuridine into the DNA of endometrial gland epithelial cells, and increased expression of estrogen receptor-alpha (ERalpha) and progesterone receptor in the luminal epithelium of the endometrium and subepithelial stroma. Because ERalpha is known to be expressed in these estrogen-target organs at the time of BPA exposure, it is plausible that BPA may directly affect the expression of ER-controlled genes involved in the morphogenesis of these organs. In addition, BPA-induced alterations that specifically affect hypothalamic-pituitary-gonadal axis function may further contribute to the anomalies observed at 3 mo of age, long after the cessation of BPA exposure.


Ab Initio Kinetics of Hydrogen Abstraction from Methyl Acetate by Hydrogen, Methyl, Oxygen, Hydroxyl, and Hydroperoxy Radicals.
The kinetics of hydrogen abstraction by five radicals (H, O((3)P), OH, CH3, and HO2) from methyl acetate (MA) is investigated theoretically in order to gain further understanding of certain aspects of the combustion chemistry of biodiesels, such as the effect of the ester moiety. We employ ab initio quantum chemistry methods, coupled cluster singles and doubles with perturbative triples correction (CCSD(T)) and multireference averaged coupled pair functional theory (MRACPF2), to predict chemically accurate reaction energetics. Overall, MRACPF2 predicts slightly higher barrier heights than CCSD(T) for MA + H/CH3/O/OH, but slightly lower barrier heights for hydrogen abstraction by HO2. Based on the obtained reaction energies, we also report high-pressure-limit rate constants using transition state theory (TST) in conjunction with the separable-hindered-rotor approximation, the variable reaction coordinate TST, and the multi-structure all-structure approach. The fitted modified Arrhenius expressions are provided over a temperature range of 250 to 2000 K. The predictions are in good agreement with available experimental results. Abstractions from both of the methyl groups in MA are expected to contribute to consumption of the fuel as they exhibit similar rate coefficients. The reactions involving the OH radical are predicted to have the highest rates among the five abstracting radicals, while those initiated by HO2 are expected to be the lowest.


The Inflammasome Drives GSDMD-Independent Secondary Pyroptosis and IL-1 Release in the Absence of Caspase-1 Protease Activity.
Inflammasomes activate the protease caspase-1, which cleaves interleukin-1β and interleukin-18 to generate the mature cytokines and controls their secretion and a form of inflammatory cell death called pyroptosis. By generating mice expressing enzymatically inactive caspase-1C284A, we provide genetic evidence that caspase-1 protease activity is required for canonical IL-1 secretion, pyroptosis, and inflammasome-mediated immunity. In caspase-1-deficient cells, caspase-8 can be activated at the inflammasome. Using mice either lacking the pyroptosis effector gasdermin D (GSDMD) or expressing caspase-1C284A, we found that GSDMD-dependent pyroptosis prevented caspase-8 activation at the inflammasome. In the absence of GSDMD-dependent pyroptosis, the inflammasome engaged a delayed, alternative form of lytic cell death that was accompanied by the release of large amounts of mature IL-1 and contributed to host protection. Features of this cell death modality distinguished it from apoptosis, suggesting it may represent a distinct form of pro-inflammatory regulated necrosis.


The response of human marrow colony-forming units-granulocyte and macrophage to inhibition by prostaglandin E and acidic isoferritins is associated with expression of MHC class II antigens and requires the participation of a CD8+ T lymphokine.
The in vitro expression of MHC class II Ag by human bone marrow colony-forming unit-granulocyte and macrophage (CFU-GM) and their proliferative response to negative growth regulators in agar culture are transient and can be modulated in vitro by 24-h suspension culture in the presence of PGE. Analysis of the participation of accessory cells in this phenomenon indicates that the ability of PGE to modulate CFU-GM MHC class II expression, the proportion of CFU-GM in S-phase of the cell cycle and the responsiveness of CFU-GM to inhibition in vitro by two negative growth regulators, acidic isoferritin inhibitory activity and PGE itself, requires the participation of CD8+ T lymphocytes. This effect is mediated by a lymphokine of m.w. 27,000 that we have purified to apparent homogeneity. This lymphokine possesses neither colony stimulatory nor inhibitory activity, is produced by both peripheral blood and bone marrow CD8+ T lymphocytes, as well as the CEM T-ALL cell line, and requires the obligatory presence of PGE for activity.


Macrophage migration inhibitory factor: a mediator of matrix metalloproteinase-2 production in rheumatoid arthritis.
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by destruction of bone and cartilage, which is mediated, in part, by synovial fibroblasts. Matrix metalloproteinases (MMPs) are a large family of proteolytic enzymes responsible for matrix degradation. Macrophage migration inhibitory factor (MIF) is a cytokine that induces the production of a large number of proinflammatory molecules and has an important role in the pathogenesis of RA by promoting inflammation and angiogenesis. In the present study, we determined the role of MIF in RA synovial fibroblast MMP production and the underlying signaling mechanisms. We found that MIF induces RA synovial fibroblast MMP-2 expression in a time-dependent and concentration-dependent manner. To elucidate the role of MIF in MMP-2 production, we produced zymosan-induced arthritis (ZIA) in MIF gene-deficient and wild-type mice. We found that MMP-2 protein levels were significantly decreased in MIF gene-deficient compared with wild-type mice joint homogenates. The expression of MMP-2 in ZIA was evaluated by immunohistochemistry (IHC). IHC revealed that MMP-2 is highly expressed in wild-type compared with MIF gene-deficient mice ZIA joints. Interestingly, synovial lining cells, endothelial cells, and sublining nonlymphoid mononuclear cells expressed MMP-2 in the ZIA synovium. Consistent with these results, in methylated BSA (mBSA) antigen-induced arthritis (AIA), a model of RA, enhanced MMP-2 expression was also observed in wild-type compared with MIF gene-deficient mice joints. To elucidate the signaling mechanisms in MIF-induced MMP-2 upregulation, RA synovial fibroblasts were stimulated with MIF in the presence of signaling inhibitors. We found that MIF-induced RA synovial fibroblast MMP-2 upregulation required the protein kinase C (PKC), c-jun N-terminal kinase (JNK), and Src signaling pathways. We studied the expression of MMP-2 in the presence of PKC isoform-specific inhibitors and found that the PKCdelta inhibitor rottlerin inhibits MIF-induced RA synovial fibroblast MMP-2 production. Consistent with these results, MIF induced phosphorylation of JNK, PKCdelta, and c-jun. These results indicate a potential novel role for MIF in tissue destruction in RA.


Phytate intake and molar ratios of phytate to zinc, iron and calcium in the diets of people in China.
To assess the phytate intake and molar ratios of phytate to calcium, iron and zinc in the diets of people in China. 2002 China Nationwide Nutrition and Health Survey is a cross-sectional nationwide representative survey on nutrition and health. The information on dietary intakes was collected using consecutive 3 days 24 h recall by trained interviewers. The data of 68 962 residents aged 2-101 years old from 132 counties were analyzed. The median daily dietary intake of phytate, calcium, iron and zinc were 1186, 338.1, 21.2 and 10.6 mg, respectively. Urban residents consumed less phytate (781 vs 1342 mg/day), more calcium (374.5 vs 324.1 mg/day) and comparable amounts of iron (21.1 vs 21.2 mg/day) and zinc (10.6 vs 10.6 mg/day) than their rural counterparts. A wide variation in phytate intake among residents from six areas was found, ranging from 648 to 1433 mg/day. The median molar ratios of phytate to calcium, iron, zinc and phytate x calcium/zinc were 0.22, 4.88, 11.1 and 89.0, respectively, with a large variation between urban and rural areas. The phytate:zinc molar ratios ranged from 6.2 to 14.2, whereas the phytate x calcium/zinc molar ratios were from 63.7 to 107.2. The proportion of subjects with ratios above the critical values of phytate to iron, phytate to calcium, phytate to zinc and phytate x calcium/zinc were 95.4, 43.7, 23.1 and 8.7%, respectively. All the phytate/mineral ratios of rural residents were higher than that of their urban counterparts. The dietary phytate intake of people in China was higher than those in Western developed countries and lower than those in developing countries. Phytate may impair the bioavailability of iron, calcium and zinc in the diets of people in China.


[The GDS-8; a short, client- and user-friendly shortened version of the Geriatric Depression Scale for nursing homes].
The objective of this study was to construct a patient- and user-friendly shortened version of the Geriatric Depression Scale (GDS) that is especially suitable for nursing home patients. The study was carried out on two different data bases including 23 Dutch nursing homes. Data on the GDS (n=410), the Mini Mental State Examination (n=410) and a diagnostic interview (SCAN; n=333), were collected by trained clinicians. Firstly, the items of the GDS-15 were judged on their clinical applicability by three clinical experts. Subsequently, seven items that were identified as unsuitable were removed using the GDS-data of the Assess-project (n=77), and internal consistency was calculated. Secondly, with respect to criterion validity (sensitivity, specificity, area under ROC and positive and negative predictive values), the newly constructed 8-item version of the GDS was validated in the AGED data set (n=333), using DSM-IV diagnosis for depression as measured by the SCAN as 'gold standard'. In the AGED dataset, the GDS-8 was internally consistent (alpha=.80) and high sensitivity rates of 96.3% for major depression and 83.0% for minor depression were found, with a specificity rate of 71.7% at a cut-off point of 2/3. The GDS-8 has good psychometric properties. Given that the GDS-8 is less burdening for the patient, more comfortable to use and less time consuming, it may be a more feasible screening test for the frail nursing home population.


Changes in depressive symptoms and social functioning in the sequenced treatment alternatives to relieve depression study.
Major depressive disorder (MDD) profoundly affects social functioning, including the ability to enjoy social activities with peers, friends, and family members. We sought to compare changes in social functioning and depressive symptoms in the first level of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Adult outpatients (N = 2876) with diagnoses of MDD were treated using flexible doses of citalopram for up to 14 weeks. We compared the change over the course of treatment in the social activities item of the Work and Social Adjustment Scale to the change in individual items of the Quick Inventory of Depressive Symptoms-Self-Rated (QIDS-SR). Improvement in social functioning was modestly positively correlated with improvement in sad mood, concentration/decision making, involvement, and energy/fatigability. Only 16% to 22% of the variance in the change in social functioning was accounted for by these symptoms, and only 32% was accounted for by the total QIDS-SR score. In this large real-world sample of outpatients treated using citalopram, changes in depressive symptoms do not entirely explain improvements in social functioning.


Involvement of the SppA1 peptidase in acclimation to saturating light intensities in Synechocystis sp. strain PCC 6803.
The sll1703 gene, encoding an Arabidopsis homologue of the thylakoid membrane-associated SppA peptidase, was inactivated by interposon mutagenesis in Synechocystis sp. strain PCC 6803. Upon acclimation from a light intensity of 50 to 150 microE m(-2) s(-1), the mutant preserved most of its phycobilisome content, whereas the wild-type strain developed a bleaching phenotype due to the loss of about 40% of its phycobiliproteins. Using in vivo and in vitro experiments, we demonstrate that the DeltasppA1 strain does not undergo the cleavage of the L(R)(33) and L(CM)(99) linker proteins that develops in the wild type exposed to increasing light intensities. We conclude that a major contribution to light acclimation under a moderate light regime in cyanobacteria originates from an SppA1-mediated cleavage of phycobilisome linker proteins. Together with changes in gene expression of the major phycobiliproteins, it contributes an additional mechanism aimed at reducing the content in phycobilisome antennae upon acclimation to a higher light intensity.


Substance use disorders among first- and second- generation immigrant adults in the United States: evidence of an immigrant paradox?
A growing number of studies have examined the "immigrant paradox" with respect to the use of licit and illicit substances in the United States. However, there remains a need for a comprehensive examination of the multigenerational and global links between immigration and substance use disorders among adults in the United States. The present study, using data from the National Epidemiologic Survey on Alcohol and Related Conditions, aimed to address these gaps by comparing the prevalence of substance use disorders of first-generation (n = 3,338) and second-generation (n = 2,515) immigrants with native-born American adults (n = 15,733) in the United States. We also examined the prevalence of substance use disorders among first-generation emigrants from Asia, Africa, Europe, and Latin America in contrast to second-generation and native-born Americans. The prevalence of substance use disorders was highest among native-born Americans, slightly lower among second-generation immigrants, and markedly lower among first-generation immigrants. Adjusted risk ratios were largest among individuals who immigrated during adolescence (ages 12-17 years) and adulthood (age 18 years or older). Results were consistent among emigrants from major world regions. Consistent with a broad body of literature examining the links between the immigrant paradox and health outcomes, results suggest that nativity and age at arrival are significant factors related to substance use disorders among first- and second-generation immigrants in the United States.


The time course of encoding and maintenance of task-relevant versus irrelevant object features in working memory.
Access to WM can be restricted on the basis of goal-relevant properties such as spatial location. However, the extent of voluntary control over which features of an attended multi-feature object are encoded and maintained in WM is debated. Some evidence suggests that attending to an object leads to obligatory storage of all of its features, whereas other evidence suggests that access to WM can be restricted to only goal-relevant features. Another possibility is that all features are initially encoded, but irrelevant features are removed from WM over time. To address these various possibilities, we used pattern classification of EEG signals to track the temporal evolution of representations reflecting the encoding and storage of task-relevant and irrelevant features in WM. In different blocks, participants remembered the orientation, color or both orientation and color of a colored, oriented grating. The color and orientation of the grating was randomly drawn from two distinct feature bins on each trial. To examine trial-specific activity reflecting storage of the object's features, a support vector machine (SVM) classifier was trained to classify what bin the stimulus features came from. Importantly, for orientation, the classifier produced reliably above-chance classification across the delay when orientation was task-relevant but not when it was task-irrelevant. Interestingly, orientation could be accurately classified on trials for which both orientation and color were remembered. Moreover, a separate measure corresponding to the probability of a feature belonging to the correct bin was significantly higher when orientation was task-relevant compared to task-irrelevant during encoding. Above-chance classification for color was only present during the initial 500 msec across all conditions. Our results suggest that although information about all of an object's features is present in the initial stimulus-evoked neural response, information about the task-irrelevant features is attenuated during stimulus encoding and is largely absent throughout the delay.


Impact of characteristics of L1 literacy experience on picture processing: ERP data from trilingual non-native Chinese and English readers.
Previous studies involving ex-illiterate and young readers of alphabetic scripts have shown that processing of non-verbal visual stimuli may be affected by literacy, which is attributable to intensive perceptual training during reading acquisition. This study examined whether the characteristics of one's native writing system, with respect to visual complexity and overall shape of orthographic unit, would influence the processing of pictured objects using event-related potential (ERP) with linear mixed-effects modeling. Kanji and Hangul constitute an interesting contrast as they differ in visual complexity but are similar in orthographic shape. Neural responses to pictures were analyzed in N170 and N400 reflecting ease of recognition and access to semantic representation, respectively. Trilingual speakers with Japanese or Korean as L1, who learned to read Chinese and English as non-native languages, as well as native Chinese and native English readers participated in a repetition detection task in which mixed blocks of pictures and words (Chinese or English) were presented. The overall results showed bilaterally distributed N170 and N400, and group differences in the N400 were confined to the anterior region. More importantly, Japanese readers exhibited more negative N170 and less negative N400 than Korean participants regardless of language context. The present findings have provided insights into the possible impact of reading acquisition on non-linguistic visual processing, and suggest that one's early experience of a visually complex orthography has positive transfer to processing of line drawings in terms of more efficient visual recognition and semantic access.


Narrowband UVB phototherapy in pityriasis rosea.
Pityriasis rosea (PR) is an acute self-limiting disease. Despite vigorous efforts by generations of researchers since nearly 150 years, present treatment modalities for PR are not very gratifying. Ultraviolet radiation has been recommended in PR, although only a few studies validate this proposal. This study was conducted to explore the therapeutic effect of NBUVB on the symptoms, course, and severity of PR. This study involved a hundred patients who were randomly divided into two groups, using computer-generated randomization chart. Group A underwent treatment with fixed dose NBUVB of 250 mJ/cm(2) three times (nonconsecutive) a week for 4 weeks. Group B formed the placebo group who did not receive any treatment. The two groups were compared with each other for the intensity of pruritis, course and duration of disease, and PR severity score (PRSS). The t values of improvement in PRSS score in Group A (t = 12.796) were higher as compared with that in Group B (t = 10.066). Similarly, the t value of the pruritus scale in Group A (t = 7.758) was higher than Group B (t = 5.754) indicating the symptomatic improvement in itching. Fixed-dose NBUVB phototherapy resulted in marked improvement in the severity and symptoms of the disease as quantitatively assessed by PRSS.


Determining Key Local Vibrations in the Relaxation of Molecular Spin Qubits and Single-Molecule Magnets.
To design molecular spin qubits and nanomagnets operating at high temperatures, there is an urgent need to understand the relationship between vibrations and spin relaxation processes. Herein we develop a simple first-principles methodology to determine the modulation that vibrations exert on spin energy levels. This methodology is applied to [Cu(mnt)2]2- (mnt2- = 1,2-dicyanoethylene-1,2-dithiolate), a highly coherent complex. By theoretically identifying the most relevant vibrational modes, we are able to offer general strategies to chemically design more resilient magnetic molecules, where the energy of the spin states is not coupled to vibrations.


Coarse-Grained MD Simulations and Protein-Protein Interactions: The Cohesin-Dockerin System.
Coarse-grained molecular dynamics (CG-MD) may be applied as part of a multiscale modeling approach to protein-protein interactions. The cohesin-dockerin interaction provides a valuable test system for evaluation of the use of CG-MD, as structural (X-ray) data indicate a dual binding mode for the cohesin-dockerin pair. CG-MD simulations (of 5 μs duration) of the association of cohesin and dockerin identify two distinct binding modes, which resemble those observed in X-ray structures. For each binding mode, ca. 80% of interfacial residues are predicted correctly. Furthermore, each of the binding modes identified by CG-MD is conformationally stable when converted to an atomistic model and used as the basis of a conventional atomistic MD simulation of duration 20 ns.


Factors affecting treatment and recurrence of Clostridium difficile infections.
The antimicrobial agents vancomycin and metronidazole have been used to treat Clostridium difficile infections (CDIs). However, it remains unclear why patients are at risk of treatment failure and recurrence. Therefore, this study retrospectively examined 98 patients with CDIs who were diagnosed based on the detection of toxin-positive C. difficile to determine the risk factors affecting drug treatment responses and the recurrence of CDI. No significant difference was observed in the cure rate or dosage between the vancomycin and metronidazole groups. The 90-d mortality rate and total number of drugs associated with CDIs, including antiinfective agents used within 2 months before the detection of toxin-positive C. difficile, were significantly lower in the treatment success group than in the failure group. The total number of antiinfective agents and gastric acid-suppressive agents used during CDI therapy was also significantly lower in the success group than in the failure group. The period from the completion of CDI therapy to restarting the administration of anticancer agents and steroids was significantly longer in patients without than in patients with recurrence. These results indicate that the total number of drugs associated with CDIs should be minimized to reduce the risk of CDIs, that not only antibiotics but also gastric acid-suppressive agents should be discontinued during CDI therapy to increase therapeutic efficacy, and that the use of anticancer agents and steroids should be delayed as long as possible after patients are cured by CDI therapy to prevent recurrence.