Fate and transport of bensulfuron-methyl and imazosulfuron in paddy fields: Experiments and model simulation

Experiments were conducted to determine the fate of bensulfuron-methyl (BSM) and imazosulfuron (IMS) under paddy conditions. Initially, laboratory experiments were conducted and the photolysis half-lives of the two herbicides were found to be much shorter than their hydrolysis half-lives in aqueous solutions. In the aerobic water–soil system, dissipation followed first-order kinetics with water half-lives of 9.1 and 11.0 days and soil half-lives of 12.4 and 18.5 days (first phase) and 35.0 and 44.1 days (second phase) for bensulfuron-methyl and imazosulfuron, respectively. However, the anaerobic soil half-lives were only 12.7 and 9.8 days for BSM and IMS, respectively. The values of K d were determined to be 16.0 and 13.8 for BSM and IMS, respectively. Subsequent field measurements for the two herbicides revealed that dissipation of both herbicides in paddy water involved biphasic first-order kinetics, with the dissipation rates in the first phase being much faster than those in the second phase. The dissipation of bensulfuron-methyl and imazosulfuron in the paddy surface soil were also followed biphasic first-order kinetics. These results were then used as input parameters for the PCPF-1 model to simulate the fate and transport of BSM and IMS in the paddy environment (water and 1-cm surface soil layer). The measured and simulated values agreed well and the mass balance error during the simulation period was −1.2 and 2.8% of applied pesticide, respectively, for BSM and IMS.

Nitrogen-doped graphene films from chemical vapor deposition of pyridine: Influence of process parameters on the electrical and optical properties

Graphene films were produced by chemical vapor deposition (CVD) of pyridine on copper substrates. Pyridine-CVD is expected to lead to doped graphene by the insertion of nitrogen atoms in the growing sp2 carbon lattice, possibly improving the properties of graphene as a transparent conductive film. We here report on the influence that the CVD parameters (i.e., temperature and gas flow) have on the morphology, transmittance, and electrical conductivity of the graphene films grown with pyridine. A temperature range between 930 and 1070 °C was explored and the results were compared to those of pristine graphene grown by ethanol-CVD under the same process conditions. The films were characterized by atomic force microscopy, Raman and X-ray photoemission spectroscopy. The optical transmittance and electrical conductivity of the films were measured to evaluate their performance as transparent conductive electrodes. Graphene films grown by pyridine reached an electrical conductivity of 14.3 × 105 S/m. Such a high conductivity seems to be associated with the electronic doping induced by substitutional nitrogen atoms. In particular, at 930 °C the nitrogen/carbon ratio of pyridine-grown graphene reaches 3%, and its electrical conductivity is 40% higher than that of pristine graphene grown from ethanol-CVD.

Convergence of regenerative medicine and synthetic biology to develop standardized and validated models of human diseases with clinical relevance

In order to progress beyond currently available medical devices and implants, the concept of tissue engineering has moved into the centre of biomedical research worldwide. The aim of this approach is not to replace damaged tissue with an implant or device but rather to prompt the patient's own tissue to enact a regenerative response by using a tissue-engineered construct to assemble new functional and healthy tissue. More recently, it has been suggested that the combination of Synthetic Biology and translational tissue-engineering techniques could enhance the field of personalized medicine, not only from a regenerative medicine perspective, but also to provide frontier technologies for building and transforming the research landscape in the field of in vitro and in vivo disease models.

Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10−8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10−4, Bonferroni corrected), of which six reached P < 5 × 10−8, including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1–3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region4, 5, 6, 7, 8, 9, 10, 11. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods—recursive partitioning and regression...

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5–89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.

The Learning Component of Dynamic Allocation Indices

For a multiarmed bandit problem with exponential discounting the optimal allocation rule is defined by a dynamic allocation index defined for each arm on its space. The index for an arm is equal to the expected immediate reward from the arm, with an upward adjustment reflecting any uncertainty about the prospects of obtaining rewards from the arm, and the possibilities of resolving those uncertainties by selecting that arm. Thus the learning component of the index is defined to be the difference between the index and the expected immediate reward. For two arms with the same expected immediate reward the learning component should be larger for the arm for which the reward rate is more uncertain. This is shown to be true for arms based on independent samples from a fixed distribution with an unknown parameter in the cases of Bernoulli and normal distributions, and similar results are obtained in other cases.

Small nerve fiber quantification in the diagnosis of diabetic sensorimotor polyneuropathy: Comparing corneal confocal microscopy with intraepidermal nerve fiber density

OBJECTIVE Quantitative assessment of small fiber damage is key to the early diagnosis and assessment of progression or regression of diabetic sensorimotor polyneuropathy (DSPN). Intraepidermal nerve fiber density (IENFD) is the current gold standard, but corneal confocal microscopy (CCM), an in vivo ophthalmic imaging modality, has the potential to be a noninvasive and objective image biomarker for identifying small fiber damage. The purpose of this study was to determine the diagnostic performance of CCM and IENFD by using the current guidelines as the reference standard. RESEARCH DESIGN AND METHODS Eighty-nine subjects (26 control subjects and 63 patients with type 1 diabetes), with and without DSPN, underwent a detailed assessment of neuropathy, including CCM and skin biopsy. RESULTS Manual and automated corneal nerve fiber density (CNFD) (P < 0.0001), branch density (CNBD) (P < 0.0001) and length (CNFL) (P < 0.0001), and IENFD (P < 0.001) were significantly reduced in patients with diabetes with DSPN compared with control subjects. The area under the receiver operating characteristic curve for identifying DSPN was 0.82 for manual CNFD, 0.80 for automated CNFD, and 0.66 for IENFD, which did not differ significantly (P = 0.14). CONCLUSIONS This study shows comparable diagnostic efficiency between CCM and IENFD, providing further support for the clinical utility of CCM as a surrogate end point for DSPN.

Decision trees for detection of activity intensity in youth with cerebral palsy

PURPOSE To develop and test decision tree (DT) models to classify physical activity (PA) intensity from accelerometer output and Gross Motor Function Classification System (GMFCS) classification level in ambulatory youth with cerebral palsy (CP); and 2) compare the classification accuracy of the new DT models to that achieved by previously published cut-points for youth with CP. METHODS Youth with CP (GMFCS Levels I - III) (N=51) completed seven activity trials with increasing PA intensity while wearing a portable metabolic system and ActiGraph GT3X accelerometers. DT models were used to identify vertical axis (VA) and vector magnitude (VM) count thresholds corresponding to sedentary (SED) (<1.5 METs), light PA (LPA) (>/=1.5 and <3 METs) and moderate-to-vigorous PA (MVPA) (>/=3 METs). Models were trained and cross-validated using the 'rpart' and 'caret' packages within R. RESULTS For the VA (VA_DT) and VM decision trees (VM_DT), a single threshold differentiated LPA from SED, while the threshold for differentiating MVPA from LPA decreased as the level of impairment increased. The average cross-validation accuracy for the VC_DT was 81.1%, 76.7%, and 82.9% for GMFCS levels I, II, and III, respectively. The corresponding cross-validation accuracy for the VM_DT was 80.5%, 75.6%, and 84.2%, respectively. Within each GMFCS level, the decision tree models achieved better PA intensity recognition than previously published cut-points. The accuracy differential was greatest among GMFCS level III participants, in whom the previously published cut-points misclassified 40% of the MVPA activity trials. CONCLUSION GMFCS-specific cut-points provide more accurate assessments of MVPA levels in youth with CP across the full spectrum of ambulatory ability.

Reliability and validity of objective measures of physical activity in youth with cerebral palsy who are ambulatory

BACKGROUND Physical therapy for youth with cerebral palsy (CP) who are ambulatory includes interventions to increase functional mobility and participation in physical activity (PA). Thus, reliable and valid measures are needed to document PA in youth with CP. OBJECTIVE The purpose of this study was to evaluate the inter-instrument reliability and concurrent validity of 3 accelerometer-based motion sensors with indirect calorimetry as the criterion for measuring PA intensity in youth with CP. METHODS Fifty-seven youth with CP (mean age=12.5 years, SD=3.3; 51% female; 49.1% with spastic hemiplegia) participated. Inclusion criteria were: aged 6 to 20 years, ambulatory, Gross Motor Function Classification System (GMFCS) levels I through III, able to follow directions, and able to complete the full PA protocol. Protocol activities included standardized activity trials with increasing PA intensity (resting, writing, household chores, active video games, and walking at 3 self-selected speeds), as measured by weight-relative oxygen uptake (in mL/kg/min). During each trial, participants wore bilateral accelerometers on the upper arms, waist/hip, and ankle and a portable indirect calorimeter. Intraclass coefficient correlations (ICCs) were calculated to evaluate inter-instrument reliability (left-to-right accelerometer placement). Spearman correlations were used to examine concurrent validity between accelerometer output (activity and step counts) and indirect calorimetry. Friedman analyses of variance with post hoc pair-wise analyses were conducted to examine the validity of accelerometers to discriminate PA intensity across activity trials. RESULTS All accelerometers exhibited excellent inter-instrument reliability (ICC=.94-.99) and good concurrent validity (rho=.70-.85). All accelerometers discriminated PA intensity across most activity trials. LIMITATIONS This PA protocol consisted of controlled activity trials. CONCLUSIONS Accelerometers provide valid and reliable measures of PA intensity among youth with CP.

Validity of the OMNI rating of perceived exertion scale for children and adolescents with cerebral palsy

Aim This study evaluated the validity of the OMNI Walk/Run Rating of Perceived Exertion (OMNI-RPE) scores with heart rate and oxygen consumption (VO2) for children and adolescents with cerebral palsy (CP). Method Children and adolescents with CP, aged 6 to 18 years and Gross Motor Function Classification System (GMFCS) levels I to III completed a physical activity protocol with seven trials ranging in intensity from sedentary to moderate-to-vigorous. VO2 and heart rate were recorded during the physical activity trials using a portable indirect calorimeter and heart rate monitor. Participants reported OMNI-RPE scores for each trial. Concurrent validity was assessed by calculating the average within-subject correlation between OMNI-RPE ratings and the two physiological indices. Results For the correlational analyses, 48 participants (22 males, 26 females; age 12y 6mo, SD 3y 4mo) had valid bivariate data for VO2 and OMNI-RPE, while 40 participants (21 males, 19 females; age 12y 5mo, SD 2y 9mo) had valid bivariate data for heart rate and OMNI-RPE. VO2 (r=0.80; 95% CI 0.66–0.88) and heart rate (r=0.83; 95% CI 0.70–0.91) were moderately to highly correlated to OMNI-RPE scores. No difference was found for the correlation of physiological data and OMNI-RPE scores across the three GMFCS levels. The OMNI-RPE scores increased significantly in a dose-response manner (F6,258=116.1, p<0.001) as exercise intensity increased from sedentary to moderate-to-vigorous. Interpretation OMNI-RPE is a clinically feasible option to monitor exercise intensity in ambulatory children and adolescents with CP.

Evaluation of a workplace alcohol and other drug policy

BACKGROUND The current impetus for developing alcohol and/or other drugs (AODs) workplace policies in Australia is to reduce workplace AOD impairment, improve safety, and prevent AOD-related injury in the workplace. For these policies to be effective, they need to be informed by scientific evidence. Evidence to inform the development and implementation of effective workplace AOD policies is currently lacking. There does not currently appear to be conclusive evidence for the effectiveness of workplace AOD policies in reducing impairment and preventing AOD-related injury. There is also no apparent evidence regarding which factors facilitate or impede the success of an AOD policy, or whether, for example, unsuccessful policy outcomes were due to poor policy or merely poor implementation of the policy. It was the aim of this research to undertake a process, impact, and outcome evaluation of a workplace AOD policy, and to contribute to the body of knowledge on the development and implementation of effective workplace AOD policies. METHODS The research setting was a state-based power-generating industry in Australia between May 2008 and May 2010. Participants for the process evaluation study were individuals who were integral to either the development or the implementation of the workplace AOD policy, or both of these processes (key informants), and comprised the majority of individuals who were involved in the process of developing and/or implementing the workplace AOD policy. The sample represented the two main groups of interest—management and union delegates/employee representatives—from all three of the participating organisations. For the impact and outcome evaluation studies, the population included all employees from the three participating organisations, and participants were all employees who consented to participate in the study and who completed both the pre-and post-policy implementation questionnaires. Qualitative methods in the form of interviews with key stakeholders were used to evaluate the process of developing and implementing the workplace AOD policy. In order to evaluate the impact of the policy with regard to the risk factors for workplace AOD impairment, and the outcome of the policy in terms of reducing workplace AOD impairment, quantitative methods in the form of a non-randomised single group pre- and post-test design were used. Changes from Time 1 (pre) to Time 2 (post) in the risk factors for workplace AOD impairment, and changes in the behaviour of interest—(self-reported) workplace AOD impairment—were measured. An integration of the findings from the process, impact, and outcome evaluation studies was undertaken using a combination of qualitative and quantitative methods. RESULTS For the process evaluation study Study respondents indicated that their policy was developed in the context of comparable industries across Australia developing workplace AOD policies, and that this was mainly out of concern for the deleterious health and safety impacts of workplace AOD impairment. Results from the process evaluation study also indicated that in developing and implementing the workplace AOD policy, there were mainly ‗winners', in terms of health and safety in the workplace. While there were some components of the development and implementation of the policy that were better done than others, and the process was expensive and took a long time, there were, overall, few unanticipated consequences to implementing the policy and it was reported to be thorough and of a high standard. Findings also indicated that overall the policy was developed and implemented according to best-practice in that: consultation during the policy development phase (with all the main stakeholders) was extensive; the policy was comprehensive; there was universal application of the policy to all employees; changes in the workplace (with regard to the policy) were gradual; and, the policy was publicised appropriately. Furthermore, study participants' responses indicated that the role of an independent external expert, who was trusted by all stakeholders, was integral to the success of the policy. For the impact and outcome evaluation studies Notwithstanding the limitations of pre- and post-test study designs with regard to attributing cause to the intervention, the findings from the impact evaluation study indicated that following policy implementation, statistically significant positive changes with regard to workplace AOD impairment were recorded for the following variables (risk factors for workplace AOD impairment): Knowledge; Attitudes; Perceived Behavioural Control; Perceptions of the Certainty of being punished for coming to work impaired by AODs; Perceptions of the Swiftness of punishment for coming to work impaired by AODs; and Direct and Indirect Experience with Punishment Avoidance for workplace AOD impairment. There were, however, no statistically significant positive changes following policy implementation for Behavioural Intentions, Subjective Norms, and Perceptions of the Severity of punishment for workplace AOD impairment. With regard to the outcome evaluation, there was a statistically significant reduction in self-reported workplace AOD impairment following the implementation of the policy. As with the impact evaluation, these findings need to be interpreted in light of the limitations of the study design in being able to attribute cause to the intervention alone. The findings from the outcome evaluation study also showed that while a positive change in self-reported workplace AOD impairment following implementation of the policy did not appear to be related to gender, age group, or employment type, it did appear to be related to levels of employee general alcohol use, cannabis use, site type, and employment role. Integration of the process, impact, and outcome evaluation studies There appeared to be qualitative support for the relationship between the process of developing and implementing the policy, and the impact of the policy in changing the risk factors for workplace AOD impairment. That is, overall the workplace AOD policy was developed and implemented well and, following its implementation, there were positive changes in the majority of measured risk factors for workplace AOD impairment. Quantitative findings lend further support for a relationship between the process and impact of the policy, in that there was a statistically significant association between employee perceived fidelity of the policy (related to the process of the policy) and positive changes in some risk factors for workplace AOD impairment (representing the impact of the policy). Findings also indicated support for the relationship between the impact of the policy in changing the risk factors for workplace AOD impairment and the outcome of the policy in reducing workplace AOD impairment: positive changes in the risk factors for workplace AOD impairment (impact) were related to positive changes in self reported workplace AOD impairment (representing the main goal and outcome of the policy). CONCLUSIONS The findings from the research indicate support for the conclusion that the policy was appropriately implemented and that it achieved its objectives and main goal. The Doctoral research findings also addressed a number of gaps in the literature on workplace AOD impairment, namely: the likely effectiveness of AOD policies for reducing AOD impairment in the workplace, which factors in the development and implementation of a workplace AOD policy are likely to facilitate or impede the effectiveness of the policy to reduce workplace AOD impairment, and which employee groups are less likely to respond well to policies of this type. The findings from this research not only represent an example of translational, applied research—through the evaluation of the study industry's policy—but also add to the body of knowledge on workplace AOD policies and provide policy-makers with evidence which may be useful in the development and implementation of effective workplace AOD policies. Importantly, the findings espouse the importance of scientific evidence in the development, implementation, and evaluation of workplace AOD policies.

Achieving a national sample of nursing homes: Balancing probability techniques and practicalities

Sampling design is critical to the quality of quantitative research, yet it does not always receive appropriate attention in nursing research. The current article details how balancing probability techniques with practical considerations produced a representative sample of Australian nursing homes (NHs). Budgetary, logistical, and statistical constraints were managed by excluding some NHs (e.g., those too difficult to access) from the sampling frame; a stratified, random sampling methodology yielded a final sample of 53 NHs from a population of 2,774. In testing the adequacy of representation of the study population, chi-square tests for goodness of fit generated nonsignificant results for distribution by distance from major city and type of organization. A significant result for state/territory was expected and was easily corrected for by the application of weights. The current article provides recommendations for conducting high-quality, probability-based samples and stresses the importance of testing the representativeness of achieved samples.

Growth factor-loaded microparticles for tissue engineering: The discrepancies of in vitro characterization assays

Efficient and effective growth factor (GF) delivery is an ongoing challenge for tissue regeneration therapies. The accurate quantification of complex molecules such as GFs, encapsulated in polymeric delivery devices, is equally critical and just as complex as achieving efficient delivery of active GFs. In this study, GFs relevant to bone tissue formation, vascular endothelial growth factor (VEGF) and bone morphogenetic protein 7 (BMP-7), were encapsulated, using the technique of electrospraying, into poly(lactic-co-glycolic acid) microparticles that contained poly(ethylene glycol) and trehalose to assist GF bioactivity. Typical quantification procedures, such as extraction and release assays using saline buffer, generated a significant degree of GF interactions, which impaired accurate assessment by enzyme-linked immunosorbent assay (ELISA). When both dry BMP-7 and VEGF were processed with chloroform, as is the case during the electrospraying process, reduced concentrations of the GFs were detected by ELISA; however, the biological effect on myoblast cells (C2C12) or endothelial cells (HUVECs) was unaffected. When electrosprayed particles containing BMP-7 were cultured with preosteoblasts (MC3T3-E1), significant cell differentiation into osteoblasts was observed up to 3 weeks in culture, as assessed by measuring alkaline phosphatase. In conclusion, this study showed how electrosprayed microparticles ensured efficient delivery of fully active GFs relevant to bone tissue engineering. Critically, it also highlights major discrepancies in quantifying GFs in polymeric microparticle systems when comparing ELISA with cell-based assays.