Early Outcomes of Scapholunate Injuries With Concomitant Distal Radius Fractures.
Background: There is limited literature regarding the treatment of concomitant scapholunate ligament (SL) injuries in acute distal radius fractures (DRFs). We hypothesized that surgical treatment of SL injuries in adult patients with DRFs leads to improved functional outcomes. Methods: A retrospective review was made of 42 adult patients who underwent surgical treatment of a DRF with a SL injury between 2005 and 2013. In all, 39 of the 42 patients sustained an intra-articular DRF (AO B or C). SL injury was diagnosed by SL diastasis > 3 mm on posteroanterior (PA) radiographs, magnetic resonance imaging, or with wrist arthroscopy. Patients were divided into 3 groups: 23 had a SL repair and were treated within 21 days of injury (acute), 8 underwent SL repair greater than 21 days from injury (subacute/chronic), and 11 did not undergo repair (non-operative). Median overall time to clinical follow-up was 5.1 years. Mayo Wrist Scores (MWS) and Disabilities of the Arm, Shoulder and Hand (DASH) scores were used to evaluate functional outcome. Results: Clinical outcomes measured by the MWS at final follow-up (6 months-12 years) showed no significant differences between the 3 groups. Of patients treated acutely, 17.3% had good to excellent MWS. MWS at 1-year follow-up was 68.4, 70, and 64 in the acute, subacute/chronic, and non-operative groups, respectively. DASH scores were 16.7, 14.3, and 11.8 in the acute, subacute/chronic, and nonoperative groups, respectively, at a mean of 7.8 years. Conclusions: At mid-term follow-up, all 3 treatment groups had similar DASH scores to the general population. There were no statistical functional differences between any of the groups based upon MWS or DASH scores.


Estimating Energy Expenditure with ActiGraph GT9X Inertial Measurement Unit.
The purpose of this study was to explore whether gyroscope and magnetometer data from the ActiGraph GT9X improved accelerometer-based predictions of energy expenditure (EE). Thirty participants (mean ± SD: age, 23.0 ± 2.3 yr; body mass index, 25.2 ± 3.9 kg·m) volunteered to complete the study. Participants wore five GT9X monitors (right hip, both wrists, and both ankles) while performing 10 activities ranging from rest to running. A Cosmed K4b was worn during the trial, as a criterion measure of EE (30-s averages) expressed in METs. Triaxial accelerometer data (80 Hz) were converted to milli-G using Euclidean norm minus one (ENMO; 1-s epochs). Gyroscope data (100 Hz) were expressed as a vector magnitude (GVM) in degrees per second (1-s epochs) and magnetometer data (100 Hz) were expressed as direction changes per 5 s. Minutes 4-6 of each activity were used for analysis. Three two-regression algorithms were developed for each wear location: 1) ENMO, 2) ENMO and GVM, and 3) ENMO, GVM, and direction changes. Leave-one-participant-out cross-validation was used to evaluate the root mean square error (RMSE) and mean absolute percent error (MAPE) of each algorithm. Adding gyroscope to accelerometer-only algorithms resulted in RMSE reductions between 0.0 METs (right wrist) and 0.17 METs (right ankle), and MAPE reductions between 0.1% (right wrist) and 6.0% (hip). When direction changes were added, RMSE changed by ≤0.03 METs and MAPE by ≤0.21%. The combined use of gyroscope and accelerometer at the hip and ankles improved individual-level prediction of EE compared with accelerometer only. For the wrists, adding gyroscope produced negligible changes. The magnetometer did not meaningfully improve estimates for any algorithms.


Mutation Screening of 1,237 Cancer Genes across Six Model Cell Lines of Basal-Like Breast Cancer.
Basal-like breast cancer is an aggressive subtype generally characterized as poor prognosis and lacking the expression of the three most important clinical biomarkers, estrogen receptor, progesterone receptor, and HER2. Cell lines serve as useful model systems to study cancer biology in vitro and in vivo. We performed mutational profiling of six basal-like breast cancer cell lines (HCC38, HCC1143, HCC1187, HCC1395, HCC1954, and HCC1937) and their matched normal lymphocyte DNA using targeted capture and next-generation sequencing of 1,237 cancer-associated genes, including all exons, UTRs and upstream flanking regions. In total, 658 somatic variants were identified, of which 378 were non-silent (average 63 per cell line, range 37-146) and 315 were novel (not present in the Catalogue of Somatic Mutations in Cancer database; COSMIC). 125 novel mutations were confirmed by Sanger sequencing (59 exonic, 48 3'UTR and 10 5'UTR, 1 splicing), with a validation rate of 94% of high confidence variants. Of 36 mutations previously reported for these cell lines but not detected in our exome data, 36% could not be detected by Sanger sequencing. The base replacements C/G>A/T, C/G>G/C, C/G>T/A and A/T>G/C were significantly more frequent in the coding regions compared to the non-coding regions (OR 3.2, 95% CI 2.0-5.3, P<0.0001; OR 4.3, 95% CI 2.9-6.6, P<0.0001; OR 2.4, 95% CI 1.8-3.1, P<0.0001; OR 1.8, 95% CI 1.2-2.7, P = 0.024, respectively). The single nucleotide variants within the context of T[C]T/A[G]A and T[C]A/T[G]A were more frequent in the coding than in the non-coding regions (OR 3.7, 95% CI 2.2-6.1, P<0.0001; OR 3.8, 95% CI 2.0-7.2, P = 0.001, respectively). Copy number estimations were derived from the targeted regions and correlated well to Affymetrix SNP array copy number data (Pearson correlation 0.82 to 0.96 for all compared cell lines; P<0.0001). These mutation calls across 1,237 cancer-associated genes and identification of novel variants will aid in the design and interpretation of biological experiments using these six basal-like breast cancer cell lines.


Hepatitis B and HIV co-infection in pregnant women: indication for routine antenatal hepatitis B virus screening in a high HIV prevalence setting.
Sub-Saharan Africa is endemic for hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections. HBV/HIV co-infection in women of reproductive age is of clinical and public health importance because these women constitute a significant reservoir for horizontal and perinatal HBV transmission. Childhood HBV vaccination from 6 weeks of age protects most children against chronic HBV infection. However, infants born to HBV/HIV co-infected women are more likely to be infected perinatally, with an increased risk of chronic hepatitis, than infants born to HBV mono-infected women. The aim of our study was to establish the prevalence of HBV infection and HBV/HIV co-infection in pregnant women in KwaZulu-Natal, South Africa, to inform antenatal HBV screening and childhood immunisation policies in South Africa. Stored plasma specimens obtained from 570 pregnant women were tested for hepatitis B surface antigen (HBsAg) and HBV infectivity, as characterised by the presence of hepatitis B e antigen (HBeAg) and/or HBV DNA load. The antenatal HIV prevalence and HBsAg prevalence in this study were 41.6% and 5.3% (95% confidence interval (CI) 3.4 - 7.1), respectively. Overall, 3.1% (95% CI 1.7 - 4.6) of pregnant women were HBV/HIV co-infected, with HBeAg positivity and the HBV DNA load being significantly higher in co-infected women. We report a 5.3% HBV prevalence and a 3.1% HBV/HIV co-infection prevalence in pregnant women from this HIV-endemic region. Routine antenatal HBV screening will allow early identification of neonates who require HBV active-passive immunoprophylaxis at birth. This strategy, together with antenatal antiretrovirals, will reduce the risk of perinatal HBV transmission, especially in high-risk HBV/ HIV co-infected pregnant women.


Long DNA constructs to study helicases and nucleic acid translocases using optical tweezers.
Single molecule biophysics experiments for the study of DNA-protein interactions usually require production of a homogeneous population of long DNA molecules with controlled sequence content and/or internal tertiary structures. Traditionally, Lambda phage DNA has been used for this purpose, but it is difficult to customize. In this article, we provide a detailed and simple protocol for cloning large (~25kbp) plasmids with bespoke sequence content, which can be used to generate custom DNA constructs for a range of single-molecule experiments. In particular, we focus on a procedure for making long single-stranded DNA (ssDNA) molecules, ssDNA-dsDNA hybrids and long DNA constructs with flaps, which are especially relevant for studying the activity of DNA helicases and translocases. Additionally, we describe how the modification of the free ends of such substrates can facilitate their binding to functionalized surfaces allowing immobilization and imaging using dual optical tweezers and confocal microscopy. Finally, we provide examples of how these DNA constructs have been applied to study the activity of human DNA helicase B (HELB). The techniques described herein are simple, versatile, adaptable, and accessible to any laboratory with access to standard molecular biology methods.


Urinary schistosomiasis contracted from an irrigation pool in Ramah, the southern Jordan Valley, Jordan.
Autochthonous cases of urinary schistosomiasis are reported for the second time in Jordan. Eight Jordanian juveniles (seven males and one female) ranging in age from 10 to 15 years were diagnosed in 1995 as having the disease. Urine examination using the membrane filtration technique showed varying intensities of infection. The patients were treated with praziquantel and a follow-up showed the passage of dead eggs in the urine of five patients one month after treatment. All had egg-negative urine three months post-treatment. Epidemiologic investigation showed that the patients did not leave Jordan and that the seven males swam frequently in 1994 in an irrigation pool present in a farm at Ramah, in the southern Jordan Valley. The female patient had frequent contact with the pool water since she often went to the farm to obtain water for domestic animals. Bulinus truncatus snails were found in the pool and in pools on other farms in the area. Two hundred snails collected from the site did not shed cercariae after six months of observation. Several foreign workers in the area were found infected with Schistosoma haematobium, suggesting they were the source of infection.


Cryptococcus neoformans Ilv2p confers resistance to sulfometuron methyl and is required for survival at 37 degrees C and in vivo.
Acetolactate synthase catalyses the first common step in isoleucine and valine biosynthesis and is the target of several classes of inhibitors. The Cryptococcus neoformans ILV2 gene, encoding acetolactate synthase, was identified by complementation of a Saccharomyces cerevisiae ilv2 mutant. C. neoformans is highly resistant to the commercially available acetolactate synthase inhibitor, sulfometuron methyl (SM). Expression of C. neoformans ILV2 in S. cerevisiae conferred SM resistance, indicating that the SM resistance of C. neoformans is due, at least in part, to C. neoformans Ilv2p. The C. neoformans ILV2 gene was disrupted. The ilv2 mutants were auxotrophic for isoleucine and valine and the auxotrophy was satisfied by these amino acids only when proline, and not ammonium, was the nitrogen source, indicating nitrogen regulation of amino acid transport. ilv2 mutants rapidly lost viability at 37 degrees C and when starved for isoleucine and valine. Consistent with these phenotypes, an ilv2 mutant was avirulent and unable to survive in mice. Because C. neoformans Ilv2p is required for virulence and survival in vivo, inhibitors of branched-chain amino acid biosynthesis may make valuable antifungal agents.


Ethanol acutely stimulates islet blood flow, amplifies insulin secretion, and induces hypoglycemia via nitric oxide and vagally mediated mechanisms.
Hypoglycemia induced by alcohol ingestion is a well-known problem in diabetic patients. However, the mechanisms underlying this phenomenon have largely remained elusive. Because insulin secretion in vivo can be rapidly tuned by changes in pancreatic microcirculation, we evaluated the influence of acute alcohol administration on pancreatic islet blood flow (IBF), and dynamic changes in insulin secretion and glycemia in the rat. Ethanol (10%) or saline was iv injected as a bolus into Wistar rats, yielding serum ethanol concentrations of approximately 8 mmol/liter. Measurements of pancreatic blood flow (PBF) were performed by a microsphere technique in combination with a freeze-thawing technique after 10-min injection. Ethanol preferentially and significantly increased pancreatic IBF approximately 4-fold, whereas not influencing whole PBF. The alcohol also augmented late-phase insulin secretion and induced late hypoglycemia upon ip glucose tolerance tests. The nitric oxide synthase inhibitor N-w-nitro-L-arginine methyl ester and atropine prevented the increased pancreatic IBF, enhanced insulin secretion, and hypoglycemia evoked by ethanol. Thus, our findings demonstrate that ethanol acutely exerts substantial influences on pancreatic microcirculation by evoking a massive redistribution of PBF from the exocrine into the endocrine part via mechanisms mediated by nitric oxide and vagal stimuli, augmenting late-phase insulin secretion, and thereby evoking hypoglycemia. This effect may in part underlie the well-known hypoglycemic properties of alcohol in diabetic patients or in alcoholics with hepatic failure.


A Multicenter Phase I/II Study of the BCNU Implant (Gliadel® Wafer) for Japanese Patients with Malignant Gliomas.
Carmustine (BCNU) implants (Gliadel® Wafer, Eisai Inc., New Jersey, USA) for the treatment of malignant gliomas (MGs) were shown to enhance overall survival in comparison to placebo in controlled clinical trials in the United States and Europe. A prospective, multicenter phase I/II study involving Japanese patients with MGs was performed to evaluate the efficacy, safety, and pharmacokinetics of BCNU implants. The study enrolled 16 patients with newly diagnosed MGs and 8 patients with recurrent MGs. After the insertion of BCNU implants (8 sheets maximum, 61.6 mg BCNU) into the removal cavity, various chemotherapies (including temozolomide) and radiotherapies were applied. After placement, overall and progression-free survival rates and whole blood BCNU levels were evaluated. In patients with newly diagnosed MGs, the overall survival rates at 12 months and 24 months were 100.0% and 68.8%, and the progression-free survival rate at 12 months was 62.5%. In patients with recurrent MGs, the progression-free survival rate at 6 months was 37.5%. There were no grade 4 or higher adverse events noted due to BCNU implants, and grade 3 events were observed in 5 of 24 patients (20.8%). Whole blood BCNU levels reached a peak of 19.4 ng/mL approximately 3 hours after insertion, which was lower than 1/600 of the peak BCNU level recorded after intravenous injections. These levels decreased to less than the detection limit (2.00 ng/mL) after 24 hours. The results of this study involving Japanese patients are comparable to those of previous studies in the United States and Europe.


Role of oxidative stress in a rat model of radiation-induced erectile dysfunction.
Chronic oxidative stress is one of the major factors playing an important role in radiation-induced normal tissue injury. However, the role of oxidative stress in radiation-induced erectile dysfunction (ED) has not been fully investigated. Aims. To investigate role of oxidative stress after prostate-confined irradiation in a rat model of radiation-induced ED. Fifty-four young adult male rats (10-12 weeks of age) were divided into age-matched sham radiotherapy (RT) and RT groups. Irradiated animals received prostate-confined radiation in a single 20 Gy fraction. Intracavernous pressure (ICP) measurements with cavernous nerve electrical stimulation were conducted at 2, 4, and 9 weeks following RT. The protein expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits (Nox4 and gp91(phox)), markers of oxidative DNA damage (8-hydroxy-2'-deoxyguanosine [8-OHdG]), lipid peroxidation (4-hydroxynonenal [4HNE]), and inflammatory response including inducible nitric oxide synthase, macrophage activation (ED-1), and nitrotyrosine, and endogenous antioxidant defense by nuclear factor erythroid 2-related factor (Nrf2) were evaluated in irradiated prostate tissue and corpora cavernosa (CC). In addition, we investigated the relationships between results of ICP/mean arterial pressure (MAP) ratios and expression level of oxidative stress markers. In the RT group, hemodynamic functional studies demonstrated a significant time-dependent decrease in ICP. Increased expression of Nox4, gp91(phox), 8-OHdG, and 4HNE were observed in the prostate and CC after RT. Similarly, expressions of inflammatory markers were significantly increased. There was a trend for increased Nrf2 after 4 weeks. ICP/MAP ratio negatively correlated with higher expression level of oxidative markers. NADPH oxidase activation and chronic oxidative stress were observed in irradiated prostate tissue and CC, which correlated with lower ICP/MAP ratio. Persistent inflammatory responses were also found in both tissues after RT. These findings suggest that oxidative stress plays a crucial role in the development of radiation-induced ED.


Accurate reconstruction of the temporal order of mutations in neoplastic progression.
The canonical route from normal tissue to cancer occurs through sequential acquisition of somatic mutations. Many studies have constructed a linear genetic model for tumorigenesis using the genetic alterations associated with samples at different stages of neoplastic progression from cross-sectional data. The common interpretation of these models is that they reflect the temporal order within any given tumor. Linear genetic methods implicitly neglect genetic heterogeneity within a neoplasm; each neoplasm is assumed to consist of one dominant clone. We modeled neoplastic progression of colorectal cancer using an agent-based model of a colon crypt and found clonal heterogeneity within our simulated neoplasms, as observed in vivo. Just 7.3% of cells within neoplasms acquired mutations in the same order as the linear model. In 41% of the simulated neoplasms, no cells acquired mutations in the same order as the linear model. We obtained similarly poor results when comparing the temporal order with oncogenetic tree models inferred from cross-sectional data. However, when we reconstructed the cell lineage of mutations within a neoplasm using several biopsies, we found that 99.7% cells within neoplasms acquired their mutations in an order consistent with the cell lineage mutational order. Thus, we find that using cross-sectional data to infer mutational order is misleading, whereas phylogenetic methods based on sampling intratumor heterogeneity accurately reconstructs the evolutionary history of tumors. In addition, we find evidence that disruption of differentiation is likely the first lesion in progression for most cancers and should be one of the few regularities of neoplastic progression across cancers.


Impact of Bariatric Surgery on the Long-term Disease Course of Inflammatory Bowel Disease.
An association between inflammatory bowel disease (IBD) and obesity has been observed. Little is known about the effect of weight loss on IBD course. Our aim was to determine the impact of bariatric surgery on long-term clinical course of obese patients with IBD, either Crohn's disease (CD) or ulcerative colitis (UC). Patients with IBD who underwent bariatric surgery subsequent to IBD diagnosis were identified from 2 tertiary IBD centers. Complications after bariatric surgery were recorded. Patients were matched 1:1 for age, sex, IBD subtype, phenotype, and location to patients with IBD who did not undergo bariatric surgery. Controls started follow-up at a time point in their disease similar to the disease duration in the matched case at the time of bariatric surgery. Inflammatory bowel disease medication usage and disease-related complications (need for corticosteroids, hospitalizations, and surgeries) among cases and controls were compared. Forty-seven patients met inclusion criteria. Appropriate matches were found for 25 cases. Median follow-up among cases (after bariatric surgery) and controls was 7.69 and 7.89 years, respectively. Median decrease in body mass index after bariatric surgery was 12.2. Rescue corticosteroid usage and IBD-related surgeries were numerically less common in cases than controls (24% vs 52%; odds ratio [OR], 0.36; 95% confidence interval [CI], 0.08-1.23; 12% vs 28%; OR, 0.2; 95% CI, 0.004-1.79). Two cases and 1 control were able to discontinue biologics during follow-up. Inflammatory bowel disease patients with weight loss after bariatric surgery had fewer IBD-related complications compared with matched controls. This observation requires validation in a prospective study design.


Transferring Racial/Ethnic Marketing Strategies From Tobacco to Food Corporations: Philip Morris and Kraft General Foods.
Objectives. To investigate the transfer of marketing knowledge and infrastructure for targeting racial/ethnic minorities from the tobacco to the food and beverage industry in the United States.Methods. We analyzed internal industry documents between April 2018 and April 2019 from the University of California San Francisco Truth Tobacco Industry Documents Library, triangulated with other sources.Results. In the 1980s, Philip Morris Companies purchased General Foods and Kraft Foods and created Kraft General Foods. Through centralized marketing initiatives, Philip Morris Companies directly transferred expertise, personnel, and resources from its tobacco to its food subsidiaries, creating a racial/ethnic minority-targeted food and beverage marketing program modeled on its successful cigarette program. When Philip Morris Companies sold Kraft General Foods in 2007, Kraft General Foods had a "fully integrated" minority marketing program that combined target marketing with racial/ethnic events promotion, racial/ethnic media outreach, and corporate donations to racial/ethnic leadership groups, making it a food industry leader.Conclusions. The tobacco industry directly transferred racial/ethnic minority marketing knowledge and infrastructure to food and beverage companies. Given the substantial growth of food and beverage corporations, their targeting of vulnerable populations, and obesity-related disparities, public policy and community action is needed to address corporate target marketing.


World Health Organization Estimates of the Relative Contributions of Food to the Burden of Disease Due to Selected Foodborne Hazards: A Structured Expert Elicitation.
The Foodborne Disease Burden Epidemiology Reference Group (FERG) was established in 2007 by the World Health Organization (WHO) to estimate the global burden of foodborne diseases (FBDs). This estimation is complicated because most of the hazards causing FBD are not transmitted solely by food; most have several potential exposure routes consisting of transmission from animals, by humans, and via environmental routes including water. This paper describes an expert elicitation study conducted by the FERG Source Attribution Task Force to estimate the relative contribution of food to the global burden of diseases commonly transmitted through the consumption of food. We applied structured expert judgment using Cooke's Classical Model to obtain estimates for 14 subregions for the relative contributions of different transmission pathways for eleven diarrheal diseases, seven other infectious diseases and one chemical (lead). Experts were identified through international networks followed by social network sampling. Final selection of experts was based on their experience including international working experience. Enrolled experts were scored on their ability to judge uncertainty accurately and informatively using a series of subject-matter specific 'seed' questions whose answers are unknown to the experts at the time they are interviewed. Trained facilitators elicited the 5th, and 50th and 95th percentile responses to seed questions through telephone interviews. Cooke's Classical Model uses responses to the seed questions to weigh and aggregate expert responses. After this interview, the experts were asked to provide 5th, 50th, and 95th percentile estimates for the 'target' questions regarding disease transmission routes. A total of 72 experts were enrolled in the study. Ten panels were global, meaning that the experts should provide estimates for all 14 subregions, whereas the nine panels were subregional, with experts providing estimates for one or more subregions, depending on their experience in the region. The size of the 19 hazard-specific panels ranged from 6 to 15 persons with several experts serving on more than one panel. Pathogens with animal reservoirs (e.g. non-typhoidal Salmonella spp. and Toxoplasma gondii) were in general assessed by the experts to have a higher proportion of illnesses attributable to food than pathogens with mainly a human reservoir, where human-to-human transmission (e.g. Shigella spp. and Norovirus) or waterborne transmission (e.g. Salmonella Typhi and Vibrio cholerae) were judged to dominate. For many pathogens, the foodborne route was assessed relatively more important in developed subregions than in developing subregions. The main exposure routes for lead varied across subregions, with the foodborne route being assessed most important only in two subregions of the European region. For the first time, we present worldwide estimates of the proportion of specific diseases attributable to food and other major transmission routes. These findings are essential for global burden of FBD estimates. While gaps exist, we believe the estimates presented here are the best current source of guidance to support decision makers when allocating resources for control and intervention, and for future research initiatives.


Depletion of CD25+ regulatory cells uncovers immune responses to shared murine tumor rejection antigens.
Although it is known that the immune system can mount responses to a variety of tumors it is clear that most tumors exhibit weak or even undetectable immunogenicity. Recent findings suggest that the lack of tumor immunogenicity is partly due to a population of cells called CD4+ CD25+ regulatory T cells since depletion of these cells in mice can result in tumor rejection. These cells have also been shown to inhibit the development of organ-specific autoimmune diseases suggesting that they inhibit immune responses to tissue-specific self-antigens. Such immune responses may also mediate tumor rejection. Alternatively, immune responses in mice depleted of regulatory cells may target tumor antigens that are not tissue-specific, but which are shared by tumors of diverse origins. In experiments performed to discriminate between these possibilities we found, using the murine colorectal tumor CT26, that tumor immunity stimulated in the absence of regulatory cells is not restricted to tumors of colorectal origin, but is effective against tumors of different histological types such as B cell lymphomas and a renal cell carcinoma. By comparing this to CT26-induced immunity through the use of adjuvant we show that the generation of cross-reactive tumor immunity is a specific manifestation of CD25+ regulatory cell depletion. The generation of CD4+ T cells capable of mediating tumor rejection is another important feature of tumor immunity induced in the absence of CD25+ cells.


The relationship among guilt, dysphoria, anxiety and obsessions in a normal population--an attempted replication.
The results of a previous study indicated that guilt as rated on the Perceived Guilt Index (PGI), predicted unpleasant intrusive thoughts, but self-reported anxiety and depression did not. In the present investigation, subjects indicated whether or not they experienced both pleasant and unpleasant intrusive thoughts, their frequency and a rating of how pleasant or unpleasant these thoughts were. They also completed self report ratings of depression, anxiety, obsessional ritualizing, and the PGI. Results of a regression analysis indicate that the best standardised questionnaire predictor of unpleasant intrusive thoughts is depression as rated on the BDI, and anxiety as rated on the BAI. The best standardised questionnaire predictor of pleasant intrusive thoughts is low anxiety. The PGI does not independently predict pleasant or unpleasant intrusive thoughts.


The prevalence of enduring postnatal perineal morbidity and its relationship to type of birth and birth risk factors.
To investigate the prevalence of perineal morbidity at 12 months postnatal and its relationship to type of birth and birth risk factors. It is well documented that women endure short-term postnatal perineal morbidity following childbirth (e.g. incontinence, perineal pain and sexual morbidity). However, to date, very little research has been carried out on the long-term effects of perineal morbidity and its relationship to the type of birth the women experienced and other birth risk factors (e.g. ethnic origin, age, parity, length of labour, epidural anaesthesia). A retrospective, cross-sectional community survey of postnatal women within two maternity units in Birmingham. A total population sample of 2,100 women were surveyed using a self-administered postal questionnaire. The questionnaire included self-assessment of perineal pain, perineal healing, urinary incontinence, flatus incontinence, faecal incontinence, sexual morbidity and dyspareunia. Demographic details, type of birth and birth risk factors were taken from the hospital's computerized maternity information system. Four hundred and eighty-two women responded to the questionnaire (23.3%). Overall, a high level of enduring perineal morbidity was reported with 87% complaining of at least one index of morbidity. Instrumental births were associated with higher levels of certain types of perineal morbidity than women following a caesarean section or normal vaginal birth (stress and urge urinary incontinence, flatus incontinence, sexual morbidity and dyspareunia). In particular, women following a forceps birth reported higher levels of morbidity than normal or ventouse birth (continual, stress and urge urinary incontinence and flatus incontinence), even when comparing with the same degree of perineal trauma. Increasing age, increasing birth weight, length of labour and particularly Asian ethnic origin were also identified as risk factors for certain types of perineal morbidity. The study concludes that enduring perineal morbidity in women following childbirth is common, especially with women following a forceps birth and certain birth risk factors (i.e. age, ethnic origin, length of labour and birth weight). These findings highlight the need for further research and provide a number of challenges for health-care services and health-care professionals.


Manipulation of Guaiacyl and Syringyl Monomer Biosynthesis in an Arabidopsis Cinnamyl Alcohol Dehydrogenase Mutant Results in Atypical Lignin Biosynthesis and Modified Cell Wall Structure.
Modifying lignin composition and structure is a key strategy to increase plant cell wall digestibility for biofuel production. Disruption of the genes encoding both cinnamyl alcohol dehydrogenases (CADs), including CADC and CADD, in Arabidopsis thaliana results in the atypical incorporation of hydroxycinnamaldehydes into lignin. Another strategy to change lignin composition is downregulation or overexpression of ferulate 5-hydroxylase (F5H), which results in lignins enriched in guaiacyl or syringyl units, respectively. Here, we combined these approaches to generate plants enriched in coniferaldehyde-derived lignin units or lignins derived primarily from sinapaldehyde. The cadc cadd and ferulic acid hydroxylase1 (fah1) cadc cadd plants are similar in growth to wild-type plants even though their lignin compositions are drastically altered. In contrast, disruption of CAD in the F5H-overexpressing background results in dwarfism. The dwarfed phenotype observed in these plants does not appear to be related to collapsed xylem, a hallmark of many other lignin-deficient dwarf mutants. cadc cadd, fah1 cadc cadd, and cadd F5H-overexpressing plants have increased enzyme-catalyzed cell wall digestibility. Given that these CAD-deficient plants have similar total lignin contents and only differ in the amounts of hydroxycinnamaldehyde monomer incorporation, these results suggest that hydroxycinnamaldehyde content is a more important determinant of digestibility than lignin content.


Transient expression of a promoter-reporter construct in differentiated adult salivary glands and embryos of the mosquito Aedes aegypti.
Vector-borne pathogens develop in close association with specific tissues in their insect hosts. Efforts are being made to characterize insect genes that are expressed in tissues that have important roles in pathogen propagation. Successful transfection and expression of exogenous genes in terminally differentiated tissues of insects has previously proven difficult. Here we report a method that should allow the analysis of genes that are expressed in adult tissues and organs. Transient expression assays have been developed using the salivary glands of the mosquito, Aedes aegypti, which can now be used to analyze salivary gland-specific promoter sequences. A liposome-based transfection reagent was used to transfect cultured adult salivary glands with a DNA construct carrying the luciferase reporter gene under the control of the Drosophila melanogaster heat shock 70 promoter. Luciferase activity was detected in glands 18-20 hr post-transfection. This assay can now be used to determine the regulatory activity of other putative promoter sequences from salivary gland-specific genes. Alternatively, the assay may be used to study the effect of recombinant gene expression on parasite invasion and development. In addition, transient expression of gene constructs in embryos is shown to be a powerful tool for analyzing genes that are expressed at this stage of the mosquito life cycle.


Virtue Existential Career Model: A Dialectic and Integrative Approach Echoing Eastern Philosophy.
Our Virtue Existential Career (VEC) model aims at complementing western modernism and postmodernism career theories with eastern philosophy. With dialectical philosophy and virtue-practice derived from the Classic of Changes, the VEC theoretical foundation incorporates merits from Holland typology, Minnesota Theory of Work Adjustment, Social Cognitive Career Theory, Meaning Therapy, Narrative Approach Career Counseling, and Happenstance Learning Theory. While modernism considers a matched job as an ideal career vision and prefers rational strategies (controlling and realizing) to achieve job security; postmodernism prefers appreciating and adapting strategies toward openness and appreciates multiple possible selves and occupations, our model pursues a blending of security and openness via controlling-and-realizing and appreciating-and-adapting interwoven with each other in a dialectical and harmonious way. Our VEC counseling prototype aims at a secular goal of living on the earth with ways and harmony () and an ultimate end to spiral up to the wisdom of living up to the way of heaven () with mind and virtue (). A VEC counseling process of five major career strategies, metaphorical stories of qian and kun, and experiential activities are developed to deliver VEC concepts. The VEC model and prototype presented in this research is the product of an action research following Lewin's (1946) top-to-down model. Situated structure analyses were conducted to further investigate the adequacy of this version of VEC model and prototype. Data from two groups (one for stranded college graduates and the other for growing college students) revealed empirical supports. Yang type of career praxes tends to induce actualization, which resulting in realistic goals and concrete action plans; yin type of career praxes tends to increase self-efficacy, which resulting in positive attitude toward current situatedness and future development. Acceptance and dialectic thinking often result from yin-yang-blending career praxes. Growing developers benefit from a strategy sequence of yang-yin-synthesized; stranded developers from a strategy sequence of yin-yang-synthesized. Our contributions and limitations are discussed in the context of developing indigenous career theories and practices for a globalized and ever-changing world.


A comparison of two approaches for the closed treatment of low-energy tibial fractures in children.
Many orthopaedic surgeons treat tibial shaft fractures in children with a period of non-weight-bearing after application of a long leg cast, presumably to prevent fracture angulation and shortening. We hypothesized that allowing children to immediately bear weight as tolerated in a cast with the knee in 10° of flexion would lessen disability, without increasing the risk of unacceptable shortening or angulation. We divided eighty-one children, between the ages of four and fourteen years, with a low-energy, closed tibial shaft fracture into two groups. One group (forty children) received a long leg cast with the knee flexed 60° and were asked not to bear weight. The second group (forty-one children) received a long leg cast with the knee flexed 10° and were encouraged to bear weight as tolerated. All patients were switched to short leg walking casts at four weeks. We compared time to healing, overall alignment, shortening, and physical disability as determined by the Activities Scale for Kids-Performance (ASK-P) questionnaire. The mean time to fracture union was 10.8 weeks in both groups (p = 0.47). At the time of healing, mean coronal alignment was within 1.3° in both groups, mean sagittal alignment was within 1°, and mean shortening was <0.5 mm, with no significant differences. The ASK-P scores showed that both groups had overall improvement in physical functioning over time. However, at six weeks, the children who were allowed to bear weight as tolerated had better overall scores (p = 0.03) and better standing skills (p = 0.01) than those who were initially instructed to be non-weight-bearing. Children with low-energy tibial shaft fractures can be successfully managed by immobilizing the knee in 10° of flexion and encouraging early weight-bearing, without affecting the time to union or increasing the risk of angulation and shortening at the fracture site.


Obesity, alcohol, and tobacco as risk factors for cancers of the esophagus and gastric cardia: adenocarcinoma versus squamous cell carcinoma.
Adenocarcinomas of the esophagus and gastric cardia were once rare. However, for unknown reasons, their incidence has been increasing rapidly over the past 15 years in the United States and parts of Western Europe. In contrast, the incidence of esophageal squamous cell carcinomas has remained relatively constant. To investigate possible reasons for these diverging incidence rates we analyzed data from two population-based case-control studies of cancers of the esophagus and gastric cardia that were conducted among male and female residents of western Washington between 1983 and 1990. Information on body mass index, cigarette use, alcohol intake, and other possible risk factors was collected via personal interviews with 404 cases or their next of kin (including 298 adenocarcinomas and 106 squamous cell carcinomas) and 724 controls identified by random digit dialing. Use of alcohol and cigarettes were significant risk factors for both histological types. The increase in risk for current smokers of 80 or more pack-years compared to nonsmokers was substantially higher for squamous cell cancer [odds ratio (OR) = 16.9; 95% confidence interval (CI) = 4.1-69.1] than for adenocarcinoma (OR = 3.4; 95% CI = 1.4-8.0), as was the increase for persons who typically drank 21 or more drinks/week compared to those who drank <7/week (OR = 9.5; 95% CI = 4.1-22.3 versus OR = 1.8; 95% CI = 1.1-3.1). For squamous cell carcinoma, body mass index was inversely associated with risk, whereas for adenocarcinoma, the highest risk was observed among persons who were in the highest decile of body mass index (OR = 1.9; 95% CI = 1.1-3.2).(ABSTRACT TRUNCATED AT 250 WORDS)


A novel mutation in the GCM2 gene causing severe congenital isolated hypoparathyroidism.
To investigate the GCM2 gene in three siblings with congenital hypoparathyroidism and perform functional analysis. We sequenced the GCM2 gene by PCR and analyzed the functional consequence of the mutation by transient transfection studies. Haplotype analysis was performed. We identified a nucleotide change, c.408C>A, in exon 3 that is predicted to truncate the Gcm2 protein (p.Tyr136Ter). All three affected siblings were homozygous and both parents were heterozygous for the mutation. Transfection studies revealed the mutant mRNA but not expression of the Gcm2 protein. Haplotype analysis revealed that the two mutant GCM2 alleles shared genotypes on chromosome 6p24.2. We describe the first GCM2 mutation in exon 3 in patients with severe congenital hypoparathyroidism. Informative genetic markers could not exclude identity by descent for the mutant alleles. Gcm2 protein was not detected after transfection, suggesting that complete lack of Gcm2 action accounts for severe hypoparathyroidism.


Informal Breast Milk Sharing in a Muslim Country: The Frequency, Practice, Risk Perception, and Risk Reduction Strategies Used by Mothers.
Introduction: Turkey is the first and only Islamic country which has initiated a process to establish a milk bank. However, the effort was abandoned because of religious concerns. Informal breast milk sharing has become a practical alternative to some. Research Aims: To document the religious concerned views and attitudes toward breast milk sharing and to determine risk reduction strategies of mothers in an Islamic country. Materials and Methods: Participants comprised volunteers from relevant forums or members of social media groups on the Internet. The participants (n = 435) were divided into three groups: those who did not share milk (n = 371), donors (n = 48), and receivers (n = 16). A prepared questionnaire was used for each group as a data collection tool. Results: 14.7% of the participants were experienced in informal milk sharing. Seventy-five percent of the recipients and 85.4% of the donors did not enter into a written agreement. Religious rules on milk sharing were reflected in three ways: asking about the infant's gender, limiting the number of sharing parties to 3, and knowing the identity of the donor or recipient. Of the participants, 77.3% believed that it was necessary to establish a milk bank in Turkey. However, 19.5% of the respondents reported that they would not feed their infant with donor milk because of reasons related to the issue of "milk kinship" in Islam. Conclusions: Informal milk sharing is a reality and risks similar to those stated in the literature are undertaken. Milk sharing is frequently performed independent of religious concerns and commercial purposes, Comprehensive measures to minimize disease transmission are not routinely implemented.


Sexually dimorphic gene expression and neurite sensitivity to estradiol in fetal arcuate Kiss1 cells.
Kiss1 neurons of the arcuate (ARC) nucleus form an interconnected network of cells that communicate via neurokinin B (encoded by Tac2) and its receptor (encoded by Tacr3) and play key roles in the control of the reproductive axis through sex hormone-regulated synthesis and release of kisspeptin peptides (Kp, encoded by Kiss1). The aim of this study was to determine whether the Kiss1 cell population of the ARC already displays sexually dimorphic features at embryonic age E16.5 in mice. At this time of development, Kiss1-GFP- and Kp-immunoreactive cell bodies were restricted to the ARC and not found in the pre-optic area (POA). The Kiss1-GFP cell population was identical in size between sexes but had significantly lower Kiss1, Tac2, and Tacr3 mRNA levels and lower Kp-ir fiber density in the POA in male compared to female fetuses. Receptors for androgen (Ar) and estrogen (Esr1, Esr2, Gpr30) and the Cyp19a1 gene (encoding the estradiol-producing enzyme aromatase) transcripts were also detected in fetal ARC Kiss1-GFP cells with significant sex differences for Ar (higher in males) and Esr1 (higher in females). Functional studies on primary cultures of sorted fetal Kiss1-GFP cells revealed a significant negative effect of estradiol treatment on neurite outgrowth on the fourth day of culture in the female group specifically. We conclude that the ARC Kiss1 cell population is already sexually differentiated at E16.5 and that its morphogenetic development may be particularly vulnerable to estradiol exposure at this early developmental time.


Mutations adjacent to the dimple of the canine parvovirus capsid structure affect sialic acid binding.
The erythrocyte receptor on rhesus macaque erythrocytes used by canine parvovirus (CPV) for binding in hemagglutination (HA) was examined. Erythrocyte membrane proteins were electrophoresed and blotted to nitrocellulose and probed with [125I]-labeled CPV capsids, showing seven virus-binding proteins. Treatment of erythrocytes or isolated membranes with Clostridium perfringens neuraminidase virtually abolished virus binding. Binding was also affected by treatment with potassium periodate and inhibited by wheat germ agglutinin, but was not significantly affected by concanavalin A, peanut agglutinin, or soluble N-acetyl-neuraminlactose. A non-HA mutant of CPV failed to bind to erythrocytes or to blotted erythrocyte membrane proteins. The mutation was a single Arg-Lys difference of VP2 amino acid residue 377. The pH dependence of binding of the closely related feline panleukopenia virus was shown to result from a decreased binding in buffers with pH values of 6.8 or greater. The VP2 residues responsible for that difference have been shown to be 323 and 375. The sequences affecting binding were all adjacent to the dimple in the capsid, implicating that region of the capsid as the sialic acid binding site. The role of sialic acid in virus-host cell interactions was not defined, but the plaque sizes of the non-HA mutant and wild type CPV were indistinguishable.


Conditional generative adversarial network for 3D rigid-body motion correction in MRI.
Subject motion in MRI remains an unsolved problem; motion during image acquisition may cause blurring and artifacts that severely degrade image quality. In this work, we approach motion correction as an image-to-image translation problem, which refers to the approach of training a deep neural network to predict an image in 1 domain from an image in another domain. Specifically, the purpose of this work was to develop and train a conditional generative adversarial network to predict artifact-free brain images from motion-corrupted data. An open source MRI data set comprising T2 *-weighted, FLASH magnitude, and phase brain images for 53 patients was used to generate complex image data for motion simulation. To simulate rigid motion, rotations and translations were applied to the image data based on randomly generated motion profiles. A conditional generative adversarial network, comprising a generator and discriminator networks, was trained using the motion-corrupted and corresponding ground truth (original) images as training pairs. The images predicted by the conditional generative adversarial network have improved image quality compared to the motion-corrupted images. The mean absolute error between the motion-corrupted and ground-truth images of the test set was 16.4% of the image mean value, whereas the mean absolute error between the conditional generative adversarial network-predicted and ground-truth images was 10.8% The network output also demonstrated improved peak SNR and structural similarity index for all test-set images. The images predicted by the conditional generative adversarial network have quantitatively and qualitatively improved image quality compared to the motion-corrupted images.


Development of a practical spatial-spectral analysis protocol for breast histopathology using Fourier transform infrared spectroscopic imaging.
Breast cancer screening provides sensitive tumor identification, but low specificity implies that a vast majority of biopsies are not ultimately diagnosed as cancer. Automated techniques to evaluate biopsies can prevent errors, reduce pathologist workload and provide objective analysis. Fourier transform infrared (FT-IR) spectroscopic imaging provides both molecular signatures and spatial information that may be applicable for pathology. Here, we utilize both the spectral and spatial information to develop a combined classifier that provides rapid tissue assessment. First, we evaluated the potential of IR imaging to provide a diagnosis using spectral data alone. While highly accurate histologic [epithelium, stroma] recognition could be achieved, the same was not possible for disease [cancer, no-cancer] due to the diversity of spectral signals. Hence, we employed spatial data, developing and evaluating increasingly complex models, to detect cancers. Sub-mm tumors could be very confidently predicted as indicated by the quantitative measurement of accuracy via receiver operating characteristic (ROC) curve analyses. The developed protocol was validated with a small set and statistical performance used to develop a model that predicts study design for a large scale, definitive validation. The results of evaluation on different instruments, at higher noise levels, under a coarser spectral resolution and two sampling modes [transmission and transflection], indicate that the protocol is highly accurate under a variety of conditions. The study paves the way to validating IR imaging for rapid breast tumor detection, its statistical validation and potential directions for optimization of the speed and sampling for clinical deployment.


The niacin/butyrate receptor GPR109A suppresses mammary tumorigenesis by inhibiting cell survival.
GPR109A, a G-protein-coupled receptor, is activated by niacin and butyrate. Upon activation in colonocytes, GPR109A potentiates anti-inflammatory pathways, induces apoptosis, and protects against inflammation-induced colon cancer. In contrast, GPR109A activation in keratinocytes induces flushing by activation of Cox-2-dependent inflammatory signaling, and the receptor expression is upregulated in human epidermoid carcinoma. Thus, depending on the cellular context and tissue, GPR109A functions either as a tumor suppressor or a tumor promoter. However, the expression status and the functional implications of this receptor in the mammary epithelium are not known. Here, we show that GPR109A is expressed in normal mammary tissue and, irrespective of the hormone receptor status, its expression is silenced in human primary breast tumor tissues, breast cancer cell lines, and in tumor tissues of three different murine mammary tumor models. Functional expression of this receptor in human breast cancer cell lines decreases cyclic AMP production, induces apoptosis, and blocks colony formation and mammary tumor growth. Transcriptome analysis revealed that GPR109A activation inhibits genes, which are involved in cell survival and antiapoptotic signaling, in human breast cancer cells. In addition, deletion of Gpr109a in mice increased tumor incidence and triggered early onset of mammary tumorigenesis with increased lung metastasis in MMTV-Neu mouse model of spontaneous breast cancer. These findings suggest that GPR109A is a tumor suppressor in mammary gland and that pharmacologic induction of this gene in tumor tissues followed by its activation with agonists could be an effective therapeutic strategy to treat breast cancer.


Efficacy and Safety of Terbinafine Hydrochloride 1% Cream vs. Sertaconazole Nitrate 2% Cream in Tinea Corporis and Tinea Cruris: A Comparative Therapeutic Trial.
To the best of our knowledge, till date no study comparing the efficacy and safety of terbinafine hydrochloride 1% cream and sertaconazole nitrate 2% cream has been done in localized tinea corporis and tinea cruris. This clinical trial was carried out to study and compare the efficacy of topical terbinafine hydrochloride 1% cream and sertaconazole nitrate 2% cream in localized tinea corporis and tinea cruris and to know the adverse effects of these antifungal creams. In this prospective, single blind, randomized control trial with two arms, patient were randomized into two groups Group A (treatment with terbinafine cream) and Group B (treatment with sertaconazole cream). A total of 38 patients were enrolled for the study, 20 patients in group A and 18 patients in group B. But five patients of group A and three patients of group B were lost for follow-ups. Therefore sample size was of 30 patients with 15 patients in group A and group B each. Patients in group A and B were treated with twice daily topical 1% terbinafine hydrochloride and 2% sertaconazole nitrate cream respectively for a total duration of three weeks. Clinical improvement in signs and symptoms of each clinical parameter, namely itching, erythema, papules, pustules, vesicles, and scaling were graded weekly and clinical cure was assessed. KOH mount and culture was done weekly up to 3 weeks to access mycological cure. Fungal culture was done on Sabouraud's dextrose agar with chloramphenicol and cycloheximide. Statistical analysis was done using students paired and unpaired t-tests from the data obtained. Comparison between Group A and Group B for complete cure (clinical and mycological) showed that at the end of 3 weeks both terbinafine and sertaconazole groups had 100% complete cure. When the two groups were compared for complete cure, at the end of 1(st) and 2(nd) week, statistically non-significant results were observed (P = 0.461 and P = 0.679 respectively). However, at the end of 2(nd) week, complete cure rate for terbinafine was 80% as compared to 73.35% for sertaconazole with no statistical significance. In both Group A and Group B, clinically significant local side effects like erythema, swelling, stinging sensation, or increased itching were not noticed. A majority of our patients in both the group showed Trichophyton rubrum followed by Trichophyton mentagrophytes growth on culture. In Group A, 11 patients showed growth of T. rubrum, 2 patients showed growth of T. mentagrophytes, and 1 patient had only KOH test positive. In Group B, 10 patients revealed growth of T. rubrum, followed by growth of T. mentagrophytes in 3 and Microsporum canis in 2 patients. The therapeutic response is more or less same in infection with different species. The newer fungistatic drug sertaconazole nitrate 2% cream was as effective as terbinafine hydrochloride 1% cream which is one of the fungicidal drugs, though terbinafine hydrochloride 1% cream has higher rates of complete cure at the end of 2 weeks as compared to sertaconazole nitrate 2% cream. Both the drugs showed good tolerability with no adverse effects.


The potential for thermal damage posed by microbubble ultrasound contrast agents.
The development of coated microbubble ultrasound contrast agents for use in imaging applications and as carriers in drug and gene delivery applications has intensified the need for a clear understanding of their behaviour and potential bioeffects. Previous studies have focused on the risks posed by unencapsulated bubbles as representing the "worst case scenario". They have concluded that the risk of thermal damage should be minimal provided the threshold for inertial cavitation is not exceeded. However, these treatments have ignored the heating effects due to viscous dissipation in the coatings of contrast agent particles. Simulations indicate that the temperature rise due to this process may be sufficient to generate harmful bioeffects even under conventionally "safe" insonation conditions. The implications of these findings and strategies for addressing the risks posed by contrast agents are discussed.


Cardiac Computed Tomography: Assessment of Coronary Inflammation and Other Plaque Features.
Unstable coronary plaques that are prone to erosion and rupture are the major cause of acute coronary syndromes. Our expanding understanding of the biological mechanisms of coronary atherosclerosis and rapid technological advances in the field of medical imaging has established cardiac computed tomography as a first-line diagnostic test in the assessment of suspected coronary artery disease, and as a powerful method of detecting the vulnerable plaque and patient. Cardiac computed tomography can provide a noninvasive, yet comprehensive, qualitative and quantitative assessment of coronary plaque burden, detect distinct high-risk morphological plaque features, assess the hemodynamic significance of coronary lesions and quantify the coronary inflammatory burden by tracking the effects of arterial inflammation on the composition of the adjacent perivascular fat. Furthermore, advances in machine learning, computational fluid dynamic modeling, and the development of targeted contrast agents continue to expand the capabilities of cardiac computed tomography imaging. In our Review, we discuss the current role of cardiac computed tomography in the assessment of coronary atherosclerosis, highlighting its dual function as a clinical and research tool that provides a wealth of structural and functional information, with far-reaching diagnostic and prognostic implications.


The National Eye Survey of Trinidad and Tobago (NESTT): Rationale, Objectives and Methodology.
This paper describes the rationale, study design and procedures of the National Eye Survey of Trinidad and Tobago (NESTT). The main objective of this survey is to obtain prevalence estimates of vision impairment and blindness for planning and policy development. A population-based, cross-sectional survey was undertaken using random multistage cluster sampling, with probability-proportionate-to-size methods. Eligible participants aged 5 years and older were sampled from the non-institutional population in each of 120 cluster segments. Presenting distance and near visual acuity were screened in their communities. People aged 40 years and older, and selected younger people, were invited for comprehensive clinic assessment. The interview included information on potential risk factors for vision loss, associated costs and quality of life. The examination included measurement of anthropometrics, blood glucose, refraction, ocular biometry, corneal hysteresis, and detailed assessment of the anterior and posterior segments, with photography and optical coherence tomography imaging. Adult participants were invited to donate saliva samples for DNA extraction and storage. The fieldwork was conducted over 13 months in 2013-2014. A representative sample of 10,651 individuals in 3410 households within 120 cluster segments identified 9913 people who were eligible for recruitment. The study methodology was robust and adequate to provide the first population-based estimates of the prevalence and causes of visual impairment and blindness in Trinidad and Tobago. Information was also gathered on risk factors, costs and quality of life associated with vision loss, and on normal ocular parameters for the population aged 40 years and older.


Joint analysis of BICEP2/keck array and Planck Data.
We report the results of a joint analysis of data from BICEP2/Keck Array and Planck. BICEP2 and Keck Array have observed the same approximately 400 deg^{2} patch of sky centered on RA 0 h, Dec. -57.5°. The combined maps reach a depth of 57 nK deg in Stokes Q and U in a band centered at 150 GHz. Planck has observed the full sky in polarization at seven frequencies from 30 to 353 GHz, but much less deeply in any given region (1.2 μK deg in Q and U at 143 GHz). We detect 150×353 cross-correlation in B modes at high significance. We fit the single- and cross-frequency power spectra at frequencies ≥150 GHz to a lensed-ΛCDM model that includes dust and a possible contribution from inflationary gravitational waves (as parametrized by the tensor-to-scalar ratio r), using a prior on the frequency spectral behavior of polarized dust emission from previous Planck analysis of other regions of the sky. We find strong evidence for dust and no statistically significant evidence for tensor modes. We probe various model variations and extensions, including adding a synchrotron component in combination with lower frequency data, and find that these make little difference to the r constraint. Finally, we present an alternative analysis which is similar to a map-based cleaning of the dust contribution, and show that this gives similar constraints. The final result is expressed as a likelihood curve for r, and yields an upper limit r_{0.05}<0.12 at 95% confidence. Marginalizing over dust and r, lensing B modes are detected at 7.0σ significance.


Cardiac rehabilitation after myocardial infarction. Combined experience of randomized clinical trials.
Randomized clinical trials of cardiac rehabilitation following myocardial infarction have typically demonstrated a lower mortality in treated patients, but with a statistically significant reduction in only one trial. To overcome the problem of not being able to detect small but clinically important benefits in mortality in randomized clinical trials of exercise and risk factor rehabilitation after myocardial infarction with small numbers of patients, we carried out a meta-analysis on the combined results of ten randomized clinical trials that included 4347 patients (control, 2145 patients; rehabilitation, 2202 patients). The pooled odds ratios of 0.76 (95% confidence intervals, 0.63 to 0.92) for all-cause death and of 0.75 (95% confidence intervals, 0.62 to 0.93) for cardiovascular death were significantly lower in the rehabilitation group than in the control group, with no significant difference for nonfatal recurrent myocardial infarction. These results suggest that, for appropriately selected patients, comprehensive cardiac rehabilitation has a beneficial effect on mortality but not on nonfatal recurrent myocardial infarction.


Effects of the build-up and resetting of auditory stream segregation on temporal discrimination.
The tendency to hear a tone sequence as 2 or more streams (segregated) builds up, but a sudden change in properties can reset the percept to 1 stream (integrated). This effect has not hitherto been explored using an objective measure of streaming. Stimuli comprised a 2.0-s fixed-frequency inducer followed by a 0.6-s test sequence of alternating pure tones (3 low [L]-high [H] cycles). Listeners compared intervals for which the test sequence was either isochronous or the H tones were slightly delayed. Resetting of segregation should make identifying the anisochronous interval easier. The HL frequency separation was varied (0-12 semitones), and properties of the inducer and test sequence were set to the same or different values. Inducer properties manipulated were frequency, number of onsets (several short bursts vs. one continuous tone), tone:silence ratio (short vs. extended bursts), level, and lateralization. All differences between the inducer and the L tones reduced temporal discrimination thresholds toward those for the no-inducer case, including properties shown previously not to affect segregation greatly. Overall, it is concluded that abrupt changes in a sequence cause resetting and improve subsequent temporal discrimination.


Factors associated with severe disease from malaria, pneumonia and diarrhea among children in rural Tanzania - a hospital-based cross-sectional study.
Mild cases of malaria, pneumonia and diarrhea are readily treatable with complete recovery and with inexpensive and widely available first-line drugs. However, treatment is complicated and expensive, and mortality is higher when children present to the hospital with severe forms of these illnesses. We studied how care seeking behaviours and other factors contributed to severity of malaria, pneumonia and diarrhoea among children less than five years in rural Tanzania. We interviewed consecutive care-takers of children diagnosed with malaria, pneumonia and/or diarrhea at Korogwe and Muheza district hospitals, in north-eastern Tanzania, between July 2009 and January 2010, and compared characteristics of children presenting with severe and those with non-severe disease. A total of 293 children with severe and 190 with non-severe disease were studied. We found persistent associations between severity of disease and caretaker's lack of formal education (OR 6.6; 95% confidence interval (CI) 2.7-15.8) compared to those with post-primary education, middle compared to high socio-economic status (OR 1.9; 95% CI 1.2-3.2), having 4 or more children compared to having one child (OR 2.5; 95% CI 1.4-4.5), having utilized a nearer primary health care (PHC) facility for the same illness compared to having not (OR 5.2; 95% CI 3.0-9.1), and having purchased the first treatment other than paracetamol from local or drug shops compared to when the treatment was obtained from the public hospitals for the first time (OR 3.2; 95% CI 1.9-5.2). The old officially abandoned first line anti-malaria drug Sulfadoxin-pyrimethamine (SP) was found to still be in use for the treatment of malaria and was significantly associated with childrens' presentation to the hospital with severe malaria (OR 12.5; 95% CI 1.6-108.0). Our results indicate that caretakers with no formal education, with lower SES and with many children can be target groups for interventions in order to further reduce child mortality from treatable illnesses. Furthermore, the quality of the available drug shops and PHC facilities need to be closely monitored.


Risk factor control for coronary artery disease secondary prevention in large randomized trials.
This study evaluated data from 3 federally funded trials that focused on optimal medical therapy to determine if formalized attempts at risk factor control within clinical trials are effective in achieving guideline-driven treatment goals for diabetic patients with coronary artery disease (CAD). Despite clear evidence of benefit for CAD secondary prevention, the level of risk factor control in clinical practice has been disappointing. We obtained data from the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) diabetes subgroup, (n = 766 of 2,287), the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial (n = 2,368), and the FREEDOM (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes) trial (n = 1,900) to evaluate the proportion of patients achieving guideline-based, protocol-driven treatment targets for systolic blood pressure, low-density lipoprotein cholesterol, smoking cessation, and hemoglobin A1c. The primary outcome measure was the proportion of diabetic CAD patients meeting all 4 pre-specified targets at 1 year after enrollment. The pooled data include 5,034 diabetic patients. The percentages of patients achieving the 1-year low-density lipoprotein cholesterol targets compared with baseline increased from 55% to 77% in COURAGE, from 59% to 75% in BARI 2D, and from 34% to 42% in FREEDOM. Although similar improved trends were seen for systolic blood pressure, glycemic control, and smoking cessation, only 18% of the COURAGE diabetes subgroup, 23% of BARI 2D patients, and 8% of FREEDOM patients met all 4 pre-specified treatment targets at 1 year of follow-up. A significant proportion of diabetic CAD patients fail to achieve pre-specified targets for 4 major modifiable cardiovascular risk factors in clinical trials. We conclude that fundamentally new thinking is needed to explore approaches to achieve optimal secondary prevention treatment goals. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657) (Bypass Angioplasty Revascularization Investigation 2 Diabetes [BARI 2D]; NCT00006305) (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes [FREEDOM]; NCT00086450).


HSPC117 is regulated by epigenetic modification and is involved in the migration of JEG-3 cells.
The human hematopoietic stem/progenitor cell 117 (HSPC117) protein is an essential component of protein complexes and has been identified to be involved in many important functions. However, how this gene expression is regulated and whether the HSPC117 gene affects cell migration is still unknown. The aim of this study was to identify whether HSPC117 mRNA expression is regulated by epigenetic modification and whether HSPC117 expression level affects the expression of matrix metalloproteinase 2 (MMP 2), matrix metalloproteinase 14 (MMP 14), and tissue inhibitor of metalloproteinases 2 (TIMP 2), and further affects human placenta choriocarcinoma cell (JEG-3) migration speed. In our epigenetic modification experiment, JEG-3 cells were cultured in medium with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dC), the histone deacetylase (HDAC) inhibitor trichostatin A (TSA), or both inhibitors. Then, the HSPC117 mRNA and protein expressions were assessed using real-time quantitative PCR (qPCR) and Western blot assay. The results showed that, compared to the control, HSPC117 mRNA expression was increased by TSA or 5-aza-dC. The highest HSPC117 expression level was found after treatment with both 5-aza-dC and TSA. Further, in order to investigate the effect of HSPC117 on MMP 2, MMP 14, and TIMP 2 mRNA expressions, pEGFP-C1-HSPC117 plasmids were transfected into JEG-3 cells to improve the expression of HSPC117 in the JEG-3 cells. Then, the mRNA expression levels of MMP 2, MMP 14, TIMP 2, and the speed of cell migration were assessed using the scratch wound assay. The results showed that over-expression of HSPC117 mRNA reduced MMP 2 and MMP 14 mRNA expression, while TIMP 2 mRNA expression was up-regulated. The scratch wound assay showed that the migration speed of JEG-3 cells was slower than the non-transfected group and the C1-transfected group. All of these results indicate that HSPC117 mRNA expression is regulated by epigenetic modification; over-expression of HSPC117 decreases MMP 2 and MMP 14 transcription, reduces cell migration speed, and increases TIMP 2 transcription.


Urinary 2,5-hexanedione excretion in cryptogenic polyneuropathy compared to the general Swedish population.
2,5-hexanedione (2,5-HD) is the main neurotoxic metabolite of methyl-n-butyl ketone (MBK) and n-hexane, and known to cause polyneuropathy. The aim of our study was to compare the urinary levels of 2,5-HD between cases with cryptogenic polyneuropathy and the general Swedish population, and to elucidate the role of certain external factors. Morning urine samples were collected from 114 cases with cryptogenic polyneuropathy (77 men and 37 women) and 227 referents (110 men and 117 women) randomly selected from the population registry. None had any current occupational exposure to n-hexane or MBK. The urine samples were analysed by a gas chromatographic method based on acidic hydrolysis. Cases had statistically higher urinary levels of 2,5-HD (0.48 mg/L) than the general population (0.41 mg/L) and men higher excretion than women (0.48 mg/L and 0.38 mg/L, respectively). There was no difference in 2,5-HD levels between current smokers and non-smokers. Occupational exposure to xylene, alcohol consumption and ever exposed to general anaesthesia were associated with lower excretion in men while for occupational exposure to nitrous oxide in women higher excretion was seen. Higher excretion of 2,5 HD was inversely related to increasing age. Significantly higher levels of urinary 2,5-HD were seen in men and cryptogenic polyneuropathy cases seemingly unexposed to n-hexane. Hypothetically, this might be due to either differences in metabolic patterns or some concealed exposure. The difference in means between cases and the general population is small and can therefore not allow any firm conclusions of the causality, however.


Study of structural properties and defects of Ni-doped SnO2 nanorods as ethanol gas sensors.
An ethanol gas sensor with enhanced sensor response was fabricated using Ni-doped SnO2 nanorods, synthesized via a simple hydrothermal method. It was found that the response (R = R 0/R g) of a 5.0 mol% Ni-doped SnO2 (5.0Ni:SnO2) nanorod sensor was 1.4 × 104 for 1000 ppm C2H5OH gas, which is about 13 times higher than that of pure SnO2 nanorods, (1.1 × 103) at the operating temperature of 450 °C. Moreover, for 50 ppm C2H5OH gas, the 5.0Ni:SnO2 nanorod sensor still recorded a significant response reading, namely 2.0 × 103 with a response time of 30 s and recovery time of 10 min. To investigate the effect of Ni dopant (0.5-5.0 mol%) on SnO2 nanorods, structural characterizations were demonstrated using field emission scanning electron microscopy, high-resolution transmission electron microscopy, Fourier transform infrared spectroscopy, x-ray diffraction (XRD) analysis, x-ray photoelectron spectroscopy and an ultraviolet-visible spectrometer. XRD results confirmed that all the samples consisted of tetragonal-shaped rutile SnO2 nanorods. It was found that the average diameter and length of the nanorods formed in 5.0Ni:SnO2 were four times smaller (∼6 and ∼35 nm, respectively) than those of the nanorods formed in pure SnO2 (∼25 and 150 nm). Interestingly, both samples had the same aspect ratio, ∼6. It is proposed that the high response of the 5.0Ni:SnO2 nanorod sensor can be attributed to the particle size, which causes an increase in the thickness of the charge depletion layer, and the presence of oxygen vacancies within the matrix of SnO2 nanorods.


An exploration of knowledge and attitudes related to pre-pregnancy care in women with diabetes.
Pre-pregnancy care optimizes pregnancy outcome in women with pre-gestational diabetes, yet most women enter pregnancy unprepared. We sought to determine knowledge and attitudes of women with Type 1 and Type 2 diabetes of childbearing age towards pre-pregnancy care. Twenty-four women (18 with Type 1 diabetes and six with Type 2 diabetes) aged 17-40 years took part in one of four focus group sessions: young nulliparous women with Type 1 diabetes (Group A), older nulliparous women with Type 1 diabetes (Group B), parous women with Type 1 diabetes (Group C) and women with Type 2 diabetes of mixed parity (Group D). Content analysis of transcribed focus groups revealed that, while women were well informed about the need to plan pregnancy, awareness of the rationale for planning was only evident in parous women or those who had actively sought pre-pregnancy advice. Within each group, there was uncertainty about what pre-pregnancy advice entailed. Despite many women reporting positive healthcare experiences, frequently cited barriers to discussing issues around family planning included unsupportive staff, busy clinics and perceived social stereotypes held by health professionals. Knowledge and attitudes reported in this study highlight the need for women with diabetes, regardless of age, marital status or type of diabetes, to receive guidance about planning pregnancy in a motivating, positive and supportive manner. The important patient viewpoints expressed in this study may help health professionals determine how best to encourage women to avail of pre-pregnancy care.


Short communication: Effects of electrochemically activated drinking water on bovine milk production and composition, including chlorate, perchlorate, and fatty acid profile.
The objective of this study was to assess the effects of electrochemically activated drinking water (ECW) on milk chlorate, milk perchlorate, milk iodine, milk composition, milk fatty acid profile, and overall performance of dairy cows. Ten Red Danish cows in mid-lactation (203 ± 31 d in milk; average ± SD) were chosen from these 2 groups for intensive sampling. The treated group drank water with 4 ppm of ECW (29 mg/L of chlorate of Neuthox, Danish Clean Water A/S, Sønderborg, Denmark). The treatment lasted 60 consecutive days, with milk and water sampling on d 0, 30, and 60. Additionally, milk samples from both the control group and treated group were taken on d 90 to assess if any carry-over effect was present. Interactions between period and milk yield and somatic cell for the full group and period and milk fat content and milk urea nitrogen in the selected animals occurred. Milk yield was not significantly affected by treatments. Milk fat, milk fatty acid profile, chlorate, perchlorate, and iodine contents were not significantly different between treatments. Milk urea increased, whereas β-hydroxybutyrate and somatic cell count decreased significantly in the treated groups. Results showed that at a dosing of 4 ppm of ECW, both chlorate and perchlorate concentrations in milk (<0.002 mg/kg) were low, and no deleterious effects on milk production or milk chemical composition were observed. These data can be of use when assessing the effects of ECW on milk and milk powder chlorate and perchlorate levels and provide a context for assessing the potential for influencing human health under the conditions prevailing on a commercial dairy farm.


A five-gene hedgehog signature developed as a patient preselection tool for hedgehog inhibitor therapy in medulloblastoma.
Distinct molecular subgroups of medulloblastoma, including hedgehog (Hh) pathway-activated disease, have been reported. We identified and clinically validated a five-gene Hh signature assay that can be used to preselect patients with Hh pathway-activated medulloblastoma. Gene characteristics of the Hh medulloblastoma subgroup were identified through published bioinformatic analyses. Thirty-two genes shown to be differentially expressed in fresh-frozen and formalin-fixed paraffin-embedded tumor samples and reproducibly analyzed by RT-PCR were measured in matched samples. These data formed the basis for building a multi-gene logistic regression model derived through elastic net methods from which the five-gene Hh signature emerged after multiple iterations. On the basis of signature gene expression levels, the model computed a propensity score to determine Hh activation using a threshold set a priori. The association between Hh activation status and tumor response to the Hh pathway inhibitor sonidegib (LDE225) was analyzed. Five differentially expressed genes in medulloblastoma (GLI1, SPHK1, SHROOM2, PDLIM3, and OTX2) were found to associate with Hh pathway activation status. In an independent validation study, Hh activation status of 25 medulloblastoma samples showed 100% concordance between the five-gene signature and Affymetrix profiling. Further, in medulloblastoma samples from 50 patients treated with sonidegib, all 6 patients who responded were found to have Hh-activated tumors. Three patients with Hh-activated tumors had stable or progressive disease. No patients with Hh-nonactivated tumors responded. This five-gene Hh signature can robustly identify Hh-activated medulloblastoma and may be used to preselect patients who might benefit from sonidegib treatment.


Early structured surgical management plan for neonates with short bowel syndrome may improve outcomes.
In children with short bowel syndrome, maximal adaptation of the bowel after extensive resection is thought to occur during the first 2 years of life. The aim of the present study was to review children with short bowel syndrome from two intestinal rehabilitation centers, comparing those undergoing lengthening procedures <365 days of age (early) versus those whose lengthening procedure was carried out >365 days of age (late). Retrospective data collection was performed from January 2004 to December 2010 in Manchester, UK, and from December 2006 to December 2010 in Brussels, Belgium. Both medical centers follow a similar intestinal rehabilitation program (IRP). Data collected included population demographics, bowel length preoperatively and postoperatively, age at operation, parenteral nutrition (PN), central access, and complications. Complete data were available for eight children who underwent lengthening surgery at <365 days of age, and six who underwent the procedure at >365 days of age. Diagnoses were similar. Groups were matched for gestation and birthweight, with no statistical difference in preoperative and postoperative bowel lengths. The mean duration of PN postoperatively was 378 days in the early cohort and 589 days in the late cohort. This trended toward statistical significance (p = 0.071). Full enteral autonomy was achieved at 17 months (early) and 59 months (late) (p = 0.01). Patients in the early group required fewer central lines than those operated on later (p = 0.035). Enrolling children into an IRP involving early (<365 days of age) lengthening surgery allows a shorter postoperative time to allow weaning to full enteral nutrition, as well as fewer central lines. Both outcomes provide benefits for the child and family, allowing an earlier return to normal life.


Left ventricular hypertrophy with exercise and ACE gene insertion/deletion polymorphism: a randomized controlled trial with losartan.
Local cardiac renin-angiotensin systems may regulate left ventricular (LV) hypertrophic responses. The absence (deletion [D]) of a 287-bp marker in the ACE gene is associated with greater myocardial ACE levels and exercise-related LV growth than is its presence (insertion [I]), an effect potentially mediated through either increased activity of the cellular growth factor angiotensin II on the angiotensin type 1 (AT(1)) receptor or increased degradation of growth-inhibiting kinins. We sought to confirm ACE genotype-associated exertional LV growth and to clarify the role of the AT(1) receptor in this association. One hundred forty-one British Army recruits homozygous for the ACE gene (79 DD and 62 II) were randomized to receive losartan (25 mg/d, a subhypotensive dose inhibiting tissue AT(1) receptors) or placebo throughout a 10-week physical training program. LV mass, determined by cardiac magnetic resonance, increased with training (8.4 g, P:<0.0001 overall; 12.1 versus 4.8 g for DD versus II genotype in the placebo limb, P:=0.022). LV growth was similar in the losartan arm: 11.0 versus 3.7 g for DD versus II genotypes (P:=0.034). When indexed to lean body mass, LV growth in the II subjects was abolished, whereas it remained in the DD subjects (-0.022 versus 0.131 g/kg, respectively; P:=0.0009). ACE genotype dependence of exercise-induced LV hypertrophy is confirmed. Additionally, LV growth in DD (unlike II) subjects is in excess of the increase in lean body mass. These effects are not influenced by AT(1) receptor antagonism with the use of losartan (25 mg/d). The 2.4-fold greater LV growth in DD men may be due to the effects of angiotensin II on other receptors (eg, angiotensin type 4) or lower degradation of growth-inhibitory kinins.


Polyphenol intake and differentiated thyroid cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
Polyphenols are bioactive compounds with several anticarcinogenic activities; however, human data regarding associations with thyroid cancer (TC) is still negligible. Our aim was to evaluate the association between intakes of total, classes and subclasses of polyphenols and risk of differentiated TC and its main subtypes, papillary and follicular, in a European population. The European Prospective Investigation into Cancer and Nutrition cohort included 476,108 men and women from 10 European countries. During a mean follow-up of 14 years, there were 748 incident differentiated TC cases, including 601 papillary and 109 follicular tumors. Polyphenol intake was estimated at baseline using validated center/country-specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, no association between total polyphenol and the risks of overall differentiated TC (HRQ4 vs. Q1 = 0.99, 95% confidence interval [CI] 0.77-1.29), papillary (HRQ4 vs. Q1 = 1.06, 95% CI 0.80-1.41) or follicular TC (HRQ4 vs. Q1 = 1.10, 95% CI 0.55-2.22) were found. No associations were observed either for flavonoids, phenolic acids or the rest of classes and subclasses of polyphenols. After stratification by body mass index (BMI), an inverse association between the intake of polyphenols (p-trend = 0.019) and phenolic acids (p-trend = 0.007) and differentiated TC risk in subjects with BMI ≥ 25 was observed. In conclusion, our study showed no associations between dietary polyphenol intake and differentiated TC risk; although further studies are warranted to investigate the potential protective associations in overweight and obese individuals.


West Nile virus drug discovery.
The outbreak of West Nile virus (WNV) in 1999 in the USA, and its continued spread throughout the Americas, parts of Europe, the Middle East and Africa, underscored the need for WNV antiviral development. Here, we review the current status of WNV drug discovery. A number of approaches have been used to search for inhibitors of WNV, including viral infection-based screening, enzyme-based screening, structure-based virtual screening, structure-based rationale design, and antibody-based therapy. These efforts have yielded inhibitors of viral or cellular factors that are critical for viral replication. For small molecule inhibitors, no promising preclinical candidate has been developed; most of the inhibitors could not even be advanced to the stage of hit-to-lead optimization due to their poor drug-like properties. However, several inhibitors developed for related members of the family Flaviviridae, such as dengue virus and hepatitis C virus, exhibited cross-inhibition of WNV, suggesting the possibility to re-purpose these antivirals for WNV treatment. Most promisingly, therapeutic antibodies have shown excellent efficacy in mouse model; one of such antibodies has been advanced into clinical trial. The knowledge accumulated during the past fifteen years has provided better rationale for the ongoing WNV and other flavivirus antiviral development.


Is navigation in virtual reality with FMRI really navigation?
Identifying the neural mechanisms underlying spatial orientation and navigation has long posed a challenge for researchers. Multiple approaches incorporating a variety of techniques and animal models have been used to address this issue. More recently, virtual navigation has become a popular tool for understanding navigational processes. Although combining this technique with functional imaging can provide important information on many aspects of spatial navigation, it is important to recognize some of the limitations these techniques have for gaining a complete understanding of the neural mechanisms of navigation. Foremost among these is that, when participants perform a virtual navigation task in a scanner, they are lying motionless in a supine position while viewing a video monitor. Here, we provide evidence that spatial orientation and navigation rely to a large extent on locomotion and its accompanying activation of motor, vestibular, and proprioceptive systems. Researchers should therefore consider the impact on the absence of these motion-based systems when interpreting virtual navigation/functional imaging experiments to achieve a more accurate understanding of the mechanisms underlying navigation.


Eraser-based eco-friendly fabrication of a skin-like large-area matrix of flexible carbon nanotube strain and pressure sensors.
This paper reports a new type of electronic, recoverable skin-like pressure and strain sensor, produced on a flexible, biodegradable pencil-eraser substrate and fabricated using a solvent-free, low-cost and energy efficient process. Multi-walled carbon nanotube (MWCNT) film, the strain sensing element, was patterned on pencil eraser with a rolling pin and a pre-compaction mechanical press. This induces high interfacial bonding between the MWCNTs and the eraser substrate, which enables the sensor to achieve recoverability under ambient conditions. The eraser serves as a substrate for strain sensing, as well as acting as a dielectric for capacitive pressure sensing, thereby eliminating the dielectric deposition step, which is crucial in capacitive-based pressure sensors. The strain sensing transduction mechanism is attributed to the tunneling effect, caused by the elastic behavior of the MWCNTs and the strong mechanical interlock between MWCNTs and the eraser substrate, which restricts slippage of MWCNTs on the eraser thereby minimizing hysteresis. The gauge factor of the strain sensor was calculated to be 2.4, which is comparable to and even better than most of the strain and pressure sensors fabricated with more complex designs and architectures. The sensitivity of the capacitive pressure sensor was found to be 0.135 MPa-1.To demonstrate the applicability of the sensor as artificial electronic skin, the sensor was assembled on various parts of the human body and corresponding movements and touch sensation were monitored. The entire fabrication process is scalable and can be integrated into large areas to map spatial pressure distributions. This low-cost, easily scalable MWCNT pin-rolled eraser-based pressure and strain sensor has huge potential in applications such as artificial e-skin in flexible electronics and medical diagnostics, in particular in surgery as it provides high spatial resolution without a complex nanostructure architecture.


Becoming a health promoting school: evaluating the process of effective implementation in Scotland.
Increasingly, researchers are exploring alternative ways of assessing the impact of 'Health Promoting School' (HPS) initiatives, in recognition of the model's emphasis on achieving change that is both enduring and far-reaching. However, it is still assumed that initiatives will lead to immediate change at the individual level. This paper challenges that view and argues that potential markers of success associated with process need to be identified earlier as a means of supporting schools and teachers. Notwithstanding differences in the way the HPS is conceptualized and implemented, four themes are highlighted that have relevance beyond any one school or country. These were drawn from a process evaluation of a European Network of HPSs Project in Scotland. They highlight the ways in which schools were able to successfully adopt HPS principles and the conditions that need to be in place for the HPS concept to flourish. Such indicators need to be given greater recognition as HPS outcomes if schools are to progress beyond the early stages of project implementation.


Time Series Analysis of Monthly Suicide Rates in West of Iran, 2006-2013.
Iran's western provinces have higher suicide rate compared to the other provinces of the country. Although suicide rates fluctuate over time, suitable statistical models can describe their underlying stochastic dynamics. This study was conducted to explore the fluctuations of the monthly suicide rates in the most populated western province of Iran using exponential smoothing state space model to compute the forecasts. For this reason, the monthly frequencies of completed suicides were converted to rates per 100,000 and a state-space approach was identified and fitted to the monthly suicide rates. Diagnostic checks were performed to determine the adequacy of the fitted model. A significant seasonal variation was detected in completed suicide with a peak in August. Diagnostic checks and the time series graph of the observed monthly suicide rates against predicted values from the fitted model showed that in the study period (from March 2006 to September 2013), the observed and predicted values were in agreement. Thus, the model was used to obtain the short-term forecasts of the monthly suicide rates. In this study, we had no significant trend but seasonal variations in the suicide rates that were identified. However, additional data from other parts of the country with longer duration are needed to visualize the reliable trend of suicide and identify seasonality of suicide across the country.


Contrast-enhanced MR angiography of the peripheral vasculature with a continuously moving table and modified elliptical centric acquisition.
This study was approved by the institutional review board and was HIPAA compliant. All subjects provided written informed consent, and subject confidentiality was protected. The purpose of this study was to prospectively evaluate the feasibility of integrating a modified elliptical centric (EC) acquisition with a continuously moving table technique to acquire high-spatial-resolution contrast material-enhanced magnetic resonance (MR) angiograms of the peripheral vasculature. Incorporation of two-dimensional homodyne reconstruction modified the EC view order, allowing improved spatial resolution per unit time while retaining the advantage of venous suppression intrinsic to the EC technique. Spatial resolution was dynamically improved when the table reached the distal-most station. The modified view order provided improved spatial resolution in phantom examinations compared with that in standard examinations. Peripheral MR angiograms were generated in a group of 13 volunteers (eight women; five men; age range, 51-72 years; mean age, 58.5 years +/- 7.9 [standard deviation]) at 1.5 T. Four arterial regions were evaluated on a five-point scale (scores ranged from 0 to 4; a score of 4 was considered excellent); venous suppression was also evaluated. The mean arterial scores exceeded 3.0 for all regions. There was no venous signal or only superficial venous signal in 10 of the 13 cases.


The vermicelli and capellini handling tests: simple quantitative measures of dexterous forepaw function in rats and mice.
Previous characterizations of rodent eating behavior have revealed that they use coordinated forepaw movements to manipulate food pieces. We have extended upon this work to develop a simple quantitative measure of forepaw dexterity that is sensitive to lateralized impairments and age-dependent changes. Rodents learn skillful forepaw and digit movements to manage thin pasta pieces, which they eagerly consume. We have previously described methods for quantifying vermicelli handling in rats and showed that the measures are very sensitive to forelimb impairments resulting from unilateral ischemic lesions, middle cerebral artery occlusions and unilateral striatal dopamine depletion [Allred, R.P., Adkins, D.L., Woodlee, M.T., Husbands, L.C., Maldonado M.A., Kane, J.R., Schallert, T. & Jones, T.A. The Vermicelli Handling Test: a simple quantitative measure of dexterous forepaw function in rats. J. Neurosci. Methods 170, 229-244 (2008)]. Here we present a more detailed protocol for this test in rats and compare it with a newly developed version for mice, the Capellini Handling Test. Rats and mice are videotaped while handling short lengths of uncooked vermicelli or capellini pasta, respectively, with a camera positioned to optimize the view of paw movements. Slow motion video playback allows for the identification of forepaw adjustments, defined as any distinct removal and replacement of the paw, or of any number of digits, on the pasta piece after eating commences. Forepaw adjustments per piece are averaged over trials per each testing session. Repeated testing permits sensitive quantitative analysis of changes in forepaw dexterity over time. Protocols for pre-testing habituation and handling practice, as well as procedures for characterizing atypical handling patterns, are described. Because rats and mice perform the pasta handling tests slightly differently, species-specific differences in administration and scoring of these tests are highlighted. All animal use was in accordance with protocols approved by the University of Texas at Austin Animal Care and Use Committee.


Coffee Intake, Recurrence, and Mortality in Stage III Colon Cancer: Results From CALGB 89803 (Alliance).
Observational studies have demonstrated increased colon cancer recurrence in states of relative hyperinsulinemia, including sedentary lifestyle, obesity, and increased dietary glycemic load. Greater coffee consumption has been associated with decreased risk of type 2 diabetes and increased insulin sensitivity. The effect of coffee on colon cancer recurrence and survival is unknown. During and 6 months after adjuvant chemotherapy, 953 patients with stage III colon cancer prospectively reported dietary intake of caffeinated coffee, decaffeinated coffee, and nonherbal tea, as well as 128 other items. We examined the influence of coffee, nonherbal tea, and caffeine on cancer recurrence and mortality using Cox proportional hazards regression. Patients consuming 4 cups/d or more of total coffee experienced an adjusted hazard ratio (HR) for colon cancer recurrence or mortality of 0.58 (95% CI, 0.34 to 0.99), compared with never drinkers (Ptrend = .002). Patients consuming 4 cups/d or more of caffeinated coffee experienced significantly reduced cancer recurrence or mortality risk compared with abstainers (HR, 0.48; 95% CI, 0.25 to 0.91; Ptrend = .002), and increasing caffeine intake also conferred a significant reduction in cancer recurrence or mortality (HR, 0.66 across extreme quintiles; 95% CI, 0.47 to 0.93; Ptrend = .006). Nonherbal tea and decaffeinated coffee were not associated with patient outcome. The association of total coffee intake with improved outcomes seemed consistent across other predictors of cancer recurrence and mortality. Higher coffee intake may be associated with significantly reduced cancer recurrence and death in patients with stage III colon cancer.


Reflection and transmission coefficients for diffuse photon density waves.
Diffuse photon density waves are proposed for use in characterizing diffuse media, similar to the use of electromagnetic waves to characterize reflection from materials. To this end basic expressions for the reflection and transmission coefficients at interfaces are put forward. Effects such as the existence of modes analogous with Brewster modes are shown. Also, we illustrate through numerical simulations how the diffusion optical parameters are estimated both with and without noise in the data.