A discrete choice experiment to elicit preferences for a chronic disease screening programme in Queensland, Australia.

OBJECTIVE: Patient-centred care, increasingly highlighted in healthcare strategies, necessitates understanding public preferences for healthcare service attributes. We aimed to understand the preferences of the Australian population regarding the attributes of chronic disease screening programmes. STUDY DESIGN: The preferences were elicited using the discrete choice experiment (DCE) methodology. METHODS: A DCE was administered to a sample of the Australian general population. Respondents were asked to make choices, each offering two hypothetical screening scenarios defined by screening conduct, quality and accuracy of the test results, cost to the patient, wait time and source of information. Data were analysed using a panel mixed multinomial logit model. RESULTS: A strong preference for highly accurate screening tests and nurse-led screenings at local health clinics was evident. They expressed disutility for waiting time and out-of-pocket costs but were indifferent about the source of information. Their preference for a nurse-led programme was highlighted by the fact that they were willing to pay $81 and $88 to get a nurse-led programme when they were offered a general practitioner-led and a specialist-led programme, respectively. Furthermore, they were willing to pay $32 to reduce a week of waiting time and $205 for a 95% accurate test compared to a 75% accurate test. Preferences remained consistent irrespective of the respondent's place of residence. CONCLUSIONS: Our findings highlight the importance of diagnostic test accuracy and nurse-led service delivery in chronic disease screening programmes. These insights could guide the development of patient-centric services by enhancing test accuracy, reducing waiting times and promoting nurse-led care models.

Functional outcomes after Medial Patellofemoral Ligament Reconstruction show inverted J-shaped relation with Body Mass Index.

PURPOSE: Medial patellofemoral ligament reconstruction (MPFL-R) is a recognised surgical procedure for the treatment of recurrent patellofemoral instability with excellent outcomes reported. The aim of this study is to determine if body mass index can influence these outcomes. METHODS: This is a single-centre retrospective analysis of a longitudinal patellofemoral database. Patients with recurrent patellar instability, without patellar alta or severe trochlear dysplasia were treated using a MPFL-R between 2015 and 2019 at The Robert Jones & Agnes Hunt Orthopaedic Hospital. The clinical efficacy following surgery was assessed by Kujula, International Knee Documentation Committee Score (IKDC), and EuroQol-5 score (EQ-5D) at baseline and up to 26 months post-operatively; their safety assessed by complication rate and requirement for further surgery. The effect of Body Mass Index (BMI) on clinical outcome was analysed using linear, curvilinear, and segmented models following propensity score weighting. RESULTS: A total of 97 patients (97 Knees, mean age 25y) were analysed. Of these, 61 patients had a BMI < 30 kg/m2 (mean age 23y, mean BMI 24) of which 7 patients (12.3%) required additional surgery. A further 36 patients had a BMI > 30 kg/m2 (mean age 27y, mean BMI 36) of which 2 patients (5.6%) required additional surgery. The re-dislocation rate was 0% in each BMI group. Both groups had a significantly improved mean outcome following surgery, with improvements in mean IKDC above the minimum clinical important differences (MCID) of 20.5. BMI had an inverted J-shaped association with functional outcome, showing peak outcomes at BMI of 20.5 (95% CI 18.5 to 22.4; IKDC and Kujala) or BMI of 28 (EQ-5D index). No evidence for an association between BMI and complication risk was found. CONCLUSION: BMI influences the functional outcomes in MPFL-R with an inverted J-shaped relation, without evidence it affected the complication or re-dislocation rate. In the absence of patella alta and severe trochlear dysplasia, an isolated MPFL reconstruction is a safe and effective procedure to treat patellar instability, with the best functional outcome in patients with a BMI around 20 to 21. LEVEL OF EVIDENCE: Level III.

Current ecotoxicity testing needs among selected U.S. federal agencies.

U.S. regulatory and research agencies use ecotoxicity test data to assess the hazards associated with substances that may be released into the environment, including but not limited to industrial chemicals, pharmaceuticals, pesticides, food additives, and color additives. These data are used to conduct hazard assessments and evaluate potential risks to aquatic life (e.g., invertebrates, fish), birds, wildlife species, or the environment. To identify opportunities for regulatory uses of non-animal replacements for ecotoxicity tests, the needs and uses for data from tests utilizing animals must first be clarified. Accordingly, the objective of this review was to identify the ecotoxicity test data relied upon by U.S. federal agencies. The standards, test guidelines, guidance documents, and/or endpoints that are used to address each of the agencies' regulatory and research needs regarding ecotoxicity testing are described in the context of their application to decision-making. Testing and information use, needs, and/or requirements relevant to the regulatory or programmatic mandates of the agencies taking part in the Interagency Coordinating Committee on the Validation of Alternative Methods Ecotoxicology Workgroup are captured. This information will be useful for coordinating efforts to develop and implement alternative test methods to reduce, refine, or replace animal use in chemical safety evaluations.

Evaluating a Rapid Field Assessment System for Anticoagulant Rodenticide Exposure of Raptors.

Anticoagulant rodenticides (ARs) are commonly used to control rodent pests. However, worldwide, their use is associated with secondary and tertiary poisoning of nontarget species, especially predatory and scavenging birds. No medical device can rapidly test for AR exposure of avian wildlife. Prothrombin time (PT) is a useful biomarker for AR exposure, and multiple commercially available point-of-care (POC) devices measure PT of humans, and domestic and companion mammals. We evaluated the potential of one commercially available POC device, the Coag-Sense® PT/INR Monitoring System, to rapidly detect AR exposure of living birds of prey. The Coag-Sense device delivered repeatable PT measurements on avian blood samples collected from four species of raptors trapped during migration (Intraclass Correlation Coefficient > 0.9; overall intra-sample variation CV: 5.7%). However, PT measurements reported by the Coag-Sense system from 81 ferruginous hawk (Buteo regalis) nestlings were not correlated to those measured by a one-stage laboratory avian PT assay (r = - 0.017, p = 0.88). Although precise, the lack of agreement in PT estimates from the Coag-Sense device and the laboratory assay indicates that this device is not suitable for detecting potential AR exposure of birds of prey. The lack of suitability may be related to the use of a mammalian reagent in the clotting reaction, suggesting that the device may perform better in testing mammalian wildlife.

Toxicokinetics of Imidacloprid-Coated Wheat Seeds in Japanese Quail ( Coturnix japonica) and an Evaluation of Hazard.

Birds are potentially exposed to neonicotinoid insecticides by ingestion of coated seeds during crop planting. Adult male Japanese quail were orally dosed with wheat seeds coated with an imidacloprid (IMI) formulation at either 0.9 or 2.7 mg/kg body weight (BW) (∼3 and 9% of IMI LD50 for Japanese quail, respectively) for 1 or 10 days. Quail were euthanized between 1 and 24 h postexposure to assess toxicokinetics. Analysis revealed rapid absorption (1 h) into blood and distribution to the brain, muscle, kidney, and liver. Clearance to below detection limits occurred at both dose levels and exposure durations in all tissues within 24 h. Metabolism was extensive, with 5-OH-IMI and IMI-olefin detected at greater concentrations than IMI in tissues and fecal samples. There was no lethality or overt signs of toxicity at either dose level. Furthermore, no evidence of enhanced expression of mRNA genes associated with hepatic xenobiotic metabolism, oxidative DNA damage, or alterations in concentrations of corticosterone and thyroid hormones was observed. Application of the toxicokinetic data was used to predict IMI residue levels in the liver with reasonable results for some field exposure and avian mortality events. It would appear that some affected species of birds are either consuming larger quantities of seeds or exhibit differences in ADME or sensitivity than predicted by read-across from these data.

Trends and determinants of weight gains among OECD countries: an ecological study.

OBJECTIVES: Obesity has become a global issue with abundant evidence to indicate that the prevalence of obesity in many nations has increased over time. The literature also reports a strong association between obesity and economic development, but the trend that obesity growth rates may converge over time has not been examined. We propose a conceptual framework and conduct an ecological analysis on the relationship between economic development and weight gain. We also test the hypothesis that weight gain converges among countries over time and examine determinants of weight gains. STUDY DESIGN: This is a longitudinal study of 34 Organisation for Economic Cooperation and Development (OECD) countries in the years 1980-2008 using publicly available data. METHODS: We apply a dynamic economic growth model to test the hypothesis that the rate of weight gains across countries may converge over time. We also investigate the determinants of weight gains using a longitudinal regression tree analysis. RESULTS: We do not find evidence that the growth rates of body weight across countries converged for all countries. However, there were groups of countries in which the growth rates of body weight converge, with five groups for males and seven groups for females. The predicted growth rates of body weight peak when gross domestic product (GDP) per capita reaches US$47,000 for males and US$37,000 for females in OECD countries. National levels of consumption of sugar, fat and alcohol were the most important contributors to national weight gains. CONCLUSION: National weight gains follow an inverse U-shape curve with economic development. Excessive calorie intake is the main contributor to weight gains.

Noncontact Strain Monitoring of Osseointegrated Prostheses.

The objective of this study was to develop a noncontact, noninvasive, imaging system for monitoring the strain and deformation states of osseointegrated prostheses. The proposed sensing methodology comprised of two parts. First, a passive thin film was designed such that its electrical permittivity increases in tandem with applied tensile loading and decreases while unloading. It was found that patterning the thin films could enhance their dielectric property's sensitivity to strain. The film can be deposited onto prosthesis surfaces as an external coating prior to implant. Second, an electrical capacitance tomography (ECT) measurement technique and reconstruction algorithm were implemented to capture strain-induced changes in the dielectric property of nanocomposite-coated prosthesis phantoms when subjected to different loading scenarios. The preliminary results showed that ECT, when coupled with strain-sensitive nanocomposites, could quantify the strain-induced changes in the dielectric property of thin film-coated prosthesis phantoms. The results suggested that ECT coupled with embedded thin films could serve as a new noncontact strain sensing method for scenarios when tethered strain sensors cannot be used or instrumented, especially in the case of osseointegrated prostheses.

Biomarker responses of Peromyscus leucopus exposed to lead and cadmium in the Southeast Missouri Lead Mining District.

Biomarker responses and histopathological lesions have been documented in laboratory mammals exposed to elevated concentrations of lead and cadmium. The exposure of white-footed mice (Peromyscus leucopus) to these metals and the potential associated toxic effects were examined at three contaminated sites in the Southeast Missouri Lead Mining District and at a reference site in MO, USA. Mice from the contaminated sites showed evidence of oxidative stress and reduced activity of red blood cell δ-aminolevulinic acid dehydratase (ALAD). Histological examinations of the liver and kidney, cytologic examination of blood smears, and biomarkers of lipid peroxidation and DNA damage failed to show indications of toxic effects from lead. The biomagnification factor of cadmium (hepatic concentration/soil concentration) at a site with a strongly acid soil was 44 times the average of the biomagnification factors at two sites with slightly alkaline soils. The elevated concentrations of cadmium in the mice did not cause observable toxicity, but were associated with about a 50% decrease in expected tissue lead concentrations and greater ALAD activity compared to the activity at the reference site. Lead was associated with a decrease in concentrations of hepatic glutathione and thiols, whereas cadmium was associated with an increase. In addition, to support risk assessment efforts, we developed linear regression models relating both tissue lead dosages (based on a previously published a laboratory study) and tissue lead concentrations in Peromyscus to soil lead concentrations.

When an object appears unexpectedly: anticipatory movement and object circumvention in individuals with and without Developmental Coordination Disorder.

Obstacles often appear unexpectedly in our pathway and these require us to make adjustments to avoid collision. Previous research has demonstrated that healthy adults will make anticipatory adjustments to gait where they have been told there is the possibility of an obstacle appearing. One population that may find this type of anticipatory movement difficult is individuals with Developmental Coordination Disorder (DCD). The current study considered how individuals with and without DCD adjust to the possibility of an obstacle appearing which would require circumvention. Fortyfour individuals with DCD and 44 age-matched controls (aged from 7 to 34 years of age) walked down an 11 m walkway under three conditions. Initially they were told this was a clear pathway and nothing in the environment would change (1, no possibility of an obstacle, no obstacle). They then performed a series of trials in which a gate may (2, possibility of an obstacle, obstacle) or may not (3, possibility of an obstacle, no obstacle) partially obstruct their pathway. We found that all participants increased medio-lateral trunk acceleration when there was the possibility of an obstacle but before the obstacle appeared, in addition the typical adults and older children also increased step width. When describing circumvention we found that the younger children showed an increase in trunk velocity and acceleration in all three directions compared to older children and adults. We also found that the individuals with DCD adjusted their path sooner and deviated more than their peers. The degree of adjustment to step width in anticipation of an obstacle was related to later medio-lateral velocity and timing of the deviation. Therefore, the lack of 'readying' the system where there is the possibility of an obstacle appearing seen in the individuals with DCD and the younger typical children may explain the increased medio-lateral velocity seen during circumvention.

When an object appears unexpectedly: foot placement during obstacle circumvention in children and adults with Developmental Coordination Disorder.

Adjustments to locomotion to avoid an obstacle require a change to the usual pattern of foot placement, i.e. changes to step length and/or step width. Previous studies have demonstrated a difficulty in individuals with Developmental Coordination Disorder (DCD) in controlling stability while both stepping over and while circumventing an obstacle. In a previous study, we have considered the way in which individuals with DCD prepare for the possibility of an obstacle appearing (Wilmut and Barnett in Exp Brain Res 235:1531-1340, 2017). Using a parallel data set from this same task on the same individuals, the aim of the current study was to investigate the exact nature of changes in foot placement during obstacle avoidance, as this was not clear from previous work. Children and adults aged from 7 to 34 years of age took part in the study. Forty-four met the criteria for a diagnosis of DCD and there were 44 typically developing (TD) age and gender-matched controls. Participants walked at a comfortable pace down an 11 m walkway; on 6 out of 36 trials a 'gate' closed across their pathway which required circumvention. These 6 'gate close' trials were analysed for this study. The number and magnitude of step length and step width adjustments were similar across the DCD and TD groups, however, the younger children (7-11 years) made a greater number of early adjustments compared to the older children and adults (12-34 years of age). In contrast the adults made a greater number of adjustments later in the movement compared to the children. In terms of foot placement adjustments a clear preference was seen across all participants to use adjustments which resulted in reducing step length, stepping away from the obstacle and a combination of these. Apart from subtle differences, the individuals with DCD make step placements to circumvent an obstacle in line with their peers. It is suggested that the choice of foot placement strategy in individuals with DCD, although in line with their peers, may not be optimal for their level of motor ability.

Polyclonal and monoclonal antibodies for induction therapy in kidney transplant recipients.

BACKGROUND: Prolonging kidney transplant survival is an important clinical priority. Induction immunosuppression with antibody therapy is recommended at transplantation and non-depleting interleukin-2 receptor monoclonal antibodies (IL2Ra) are considered first line. It is suggested that recipients at high risk of rejection should receive lymphocyte-depleting antibodies but the relative benefits and harms of the available agents are uncertain. OBJECTIVES: We aimed to: evaluate the relative and absolute effects of different antibody preparations (except IL2Ra) when used as induction therapy in kidney transplant recipients; determine how the benefits and adverse events vary for each antibody preparation; determine how the benefits and harms vary for different formulations of antibody preparation; and determine whether the benefits and harms vary in specific subgroups of recipients (e.g. children and sensitised recipients). SEARCH METHODS: Randomised controlled trials (RCTs) comparing monoclonal or polyclonal antibodies with placebo, no treatment, or other antibody therapy in adults and children who had received a kidney transplant. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing monoclonal or polyclonal antibodies with placebo, no treatment, or other antibody therapy in adults and children who had received a kidney transplant. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed risk of bias. Dichotomous outcomes are reported as relative risk (RR) and continuous outcomes as mean difference (MD) together with their 95% confidence intervals (CI). MAIN RESULTS: We included 99 studies (269 records; 8956 participants; 33 with contemporary agents). Methodology was incompletely reported in most studies leading to lower confidence in the treatment estimates.Antithymocyte globulin (ATG) prevented acute graft rejection (17 studies: RR 0.63, 95% CI 0.51 to 0.78). The benefits of ATG on graft rejection were similar when used with (12 studies: RR 0.61, 0.49 to 0.76) or without (5 studies: RR 0.65, 0.43 to 0.98) calcineurin inhibitor (CNI) treatment. ATG (with CNI therapy) had uncertain effects on death (3 to 6 months, 3 studies: RR 0.41, 0.13 to 1.22; 1 to 2 years, 5 studies: RR 0.75, 0.27 to 2.06; 5 years, 2 studies: RR 0.94, 0.11 to 7.81) and graft loss (3 to 6 months, 4 studies: RR 0.60, 0.34 to 1.05; 1 to 2 years, 3 studies: RR 0.65, 0.36 to 1.19). The effect of ATG on death-censored graft loss was uncertain at 1 to 2 years and 5 years. In non-CNI studies, ATG had uncertain effects on death but reduced death-censored graft loss (6 studies: RR 0.55, 0.38 to 0.78). When CNI and older non-CNI studies were combined, a benefit was seen with ATG at 1 to 2 years for both all-cause graft loss (7 studies: RR 0.71, 0.53 to 0.95) and death-censored graft loss (8 studies: RR 0.55, 0.39 to 0.77) but not sustained longer term. ATG increased cytomegalovirus (CMV) infection (6 studies: RR 1.55, 1.24 to 1.95), leucopenia (4 studies: RR 3.86, 2.79 to 5.34) and thrombocytopenia (4 studies: RR 2.41, 1.61 to 3.61) but had uncertain effects on delayed graft function, malignancy, post-transplant lymphoproliferative disorder (PTLD), and new onset diabetes after transplantation (NODAT).Alemtuzumab was compared to ATG in six studies (446 patients) with early steroid withdrawal (ESW) or steroid minimisation. Alemtuzumab plus steroid minimisation reduced acute rejection compared to ATG at one year (4 studies: RR 0.57, 0.35 to 0.93). In the two studies with ESW only in the alemtuzumab arm, the effect of alemtuzumab on acute rejection at 1 year was uncertain compared to ATG (RR 1.27, 0.50 to 3.19). Alemtuzumab had uncertain effects on death (1 year, 2 studies: RR 0.39, 0.06 to 2.42; 2 to 3 years, 3 studies: RR 0.67, 95% CI 0.15 to 2.95), graft loss (1 year, 2 studies: RR 0.39, 0.13 to 1.30; 2 to 3 years, 3 studies: RR 0.98, 95% CI 0.47 to 2.06), and death-censored graft loss (1 year, 2 studies: RR 0.38, 0.08 to 1.81; 2 to 3 years, 3 studies: RR 2.45, 95% CI 0.67 to 8.97) compared to ATG. Creatinine clearance was lower with alemtuzumab plus ESW at 6 months (2 studies: MD -13.35 mL/min, -23.91 to -2.80) and 2 years (2 studies: MD -12.86 mL/min, -23.73 to -2.00) compared to ATG plus triple maintenance. Across all 6 studies, the effect of alemtuzumab versus ATG was uncertain on all-cause infection, CMV infection, BK virus infection, malignancy, and PTLD. The effect of alemtuzumab with steroid minimisation on NODAT was uncertain, compared to ATG with steroid maintenance.Alemtuzumab plus ESW compared with triple maintenance without induction therapy had uncertain effects on death and all-cause graft loss at 1 year, acute rejection at 6 months and 1 year. CMV infection was increased (2 studies: RR 2.28, 1.18 to 4.40). Treatment effects were uncertain for NODAT, thrombocytopenia, and malignancy or PTLD.Rituximab had uncertain effects on death, graft loss, acute rejection and all other adverse outcomes compared to placebo. AUTHORS' CONCLUSIONS: ATG reduces acute rejection but has uncertain effects on death, graft survival, malignancy and NODAT, and increases CMV infection, thrombocytopenia and leucopenia. Given a 45% acute rejection risk without ATG induction, seven patients would need treatment to prevent one having rejection, while incurring an additional patient experiencing CMV disease for every 12 treated. Excluding non-CNI studies, the risk of rejection was 37% without induction with six patients needing treatment to prevent one having rejection.In the context of steroid minimisation, alemtuzumab prevents acute rejection at 1 year compared to ATG. Eleven patients would require treatment with alemtuzumab to prevent 1 having rejection, assuming a 21% rejection risk with ATG.Triple maintenance without induction therapy compared to alemtuzumab combined with ESW had similar rates of acute rejection but adverse effects including NODAT were poorly documented. Alemtuzumab plus steroid withdrawal would cause one additional patient experiencing CMV disease for every six patients treated compared to no induction and triple maintenance, in the absence of any clinical benefit. Overall, ATG and alemtuzumab decrease acute rejection at a cost of increased CMV disease while patient-centred outcomes (reduced death or lower toxicity) do not appear to be improved.

A qualitative study of overweight and obese Australians' views of food addiction.

The concept of food addiction is increasingly used in the academic literature and popular media to explain some forms of overweight and obesity. However, there is limited evidence on how this term is understood by and impacts overweight and obese individuals. This qualitative study investigated the views of overweight and obese individuals on food addiction, and its likely impact upon stigma, treatment-seeking, and support for public policies to reduce overeating. Semi-structured interviews were conducted with 23 overweight and obese individuals (Mage = 38, MBMI = 33, 74% female) and analysed thematically. The concept of food addiction was consistent with many participants' personal experiences, and was accompanied by high perceptions of control and personal responsibility. Some participants believed "sugar" or "fat" addiction to be more accurate. Others were reluctant to be described as an "addict" owing to perceived negative connotations and the belief that it would increase self-stigma. Food addiction was seen as a motivator for seeking psychological services, but not pharmaceutical or surgical treatments. In light of food addiction being perceived as plausible and relevant, participants supported targeted public health policies (e.g., taxes, regulations for junk food container sizes) but did not believe these would affect their own purchasing or consumption behaviours. Education for interpreting food labels and reducing the costs of healthy foods were endorsed, leading to positive changes in food-related behaviours. This research suggests discretionary use of the food addiction label in a supportive and educational manner to minimise stigma while encouraging treatment-seeking.

Idelalisib and Rituximab Regimen.

The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net. The information presented in this review is based on published data and clinical expertise and includes information not included in the product labeling. Incorporation of such published data provides a more robust assessment of the drugs and assists pharmacists in evaluation of orders for off-label use of these agents.

Clinical outcomes with ABO antibody titer variability in a multicenter study of ABO-incompatible kidney transplantation in the United Kingdom.

BACKGROUND: ABO blood group-incompatible kidney transplantation (ABOiKTx) outcomes are good, but complications are more common than in conventional transplantation. Regimens that use extracorporeal antibody removal therapy (EART) and enhanced immunosuppression are guided by titration of ABO blood group antibodies (using hemagglutination [HA] dilution assays), and these assays vary significantly in performance between centers. This study aims to describe the differences in titer measurement and the effect on clinical practice and outcomes. STUDY DESIGN AND METHODS: This multicentre, prospective cohort study of 100 ABOiKTx recipients assessed treatment and outcome data, including HA assay results measured retrospectively in a single central laboratory. RESULTS: Patient and allograft survival at 1 year was 99% and 94%, respectively. There were significant differences in the number of pretransplantation EART sessions in centers undertaking plasma exchange (PEx), compared with immunoadsorption (IA) (median, 6 vs. 4 sessions; p = 0.007). The pre-EART HA titer in both groups was the same when centrally assayed. The local HA assay used to guide treatment yielded significantly higher titers in centers undertaking PEx compared with IA (median, 128 vs. 32; p < 0.005). Patients undergoing PEx rather than IA were significantly more likely to suffer postoperative hematoma (12.9% vs. 1.8%; p = 0.05) or any perioperative collection requiring drainage (19.4% vs. 3.6%; p = 0.02). CONCLUSION: The colinearity of HA assay sensitivity with the receipt of PEx and EART limits some conclusions regarding the likely direction of causation. However, the association of differences in clinical practice with recognized perioperative complications of ABOiKTx identifies targets for further investigation and quality improvement.

Gait patterns in children with Developmental Coordination Disorder.

Previous research has shown that adults with Developmental Coordination Disorder (DCD) show increased variability of foot placement measures and movement of the centre of mass (CoM) while walking. The current study considered the gait patterns of young and older children with DCD. Fourteen young children with DCD (7-12 years), 15 older children with DCD (12-17 years) and 29 age- and gender-matched typically developing children took part. Children were asked to walk up and down a flat 10-m-long pathway for 1 min, while the movement of their feet and trunk was recorded using motion analysis. The gait pattern of children with DCD was characterised by wider steps, elevated variability in the time spent in double support and stride time and greater medio-lateral velocity and acceleration compared to their peers. An elevated variability in medio-lateral acceleration was also seen in the young but not the older children with DCD. In addition, the young children showed a greater variability in velocity and acceleration in all three directions compared to the older children. The data suggest that the high incidence of trips and falls seen in children with DCD may be due to differences in the control of the CoM.

Electrical and ultraviolet characterization of 4H-SiC Schottky photodiodes.

Fabrication and electrical and optical characterization of 4H-SiC Schottky UV photodetectors with nickel silicide interdigitated contacts is reported. Dark capacitance and current measurements as a function of applied voltage over the temperature range 20 °C - 120 °C are presented. The results show consistent performance among devices. Their leakage current density, at the highest investigated temperature (120 °C), is in the range of nA/cm(2) at high internal electric field. Properties such as barrier height and ideality factor are also computed as a function of temperature. The responsivities of the diodes as functions of applied voltage were measured using a UV spectrophotometer in the wavelength range 200 nm - 380 nm and compared with theoretically calculated values. The devices had a mean peak responsivity of 0.093 A/W at 270 nm and -15 V reverse bias.

Novel therapeutics for type 2 diabetes: insulin resistance.

Insulin resistance (IR) plays an important role in the pathogenesis of type 2 diabetes (T2D) and cardiovascular disease. Hence improving IR is a major target of treatment in patients with T2D. Obesity and lack of exercise are major causes of IR. However, recent evidence implicates sleep disorders and disorders of the circadian rhythm in the pathogenesis of IR. Weight loss and lifestyle changes are the cornerstone and most effective treatments of IR, but adherence and patient's acceptability are poor. Bariatric surgery results in significant and sustainable long-term weight loss associated with beneficial impact on IR and glucose metabolism, making this an attractive treatment option for patients with T2D. Currently available pharmacological options targeting IR (such as metformin and thiazolidinediones) do not maintain glycaemic measures within targets long term and can be associated with significant side effects. Over the last two decades, many pharmacological agents targeting different aspects of the insulin signalling pathway were developed to improve IR, but only a minority reached clinical trials. Such treatments need to be specific and reversible as many of the components of the insulin signalling pathway are involved in other cellular functions such as apoptosis. Recent evidence highlighted the role of circadian rhythm and sleep-related disorders in the pathogenesis of IR. In this article, we review the latest developments in the pharmacological and non-pharmacological interventions targeting IR including bariatric surgery. We will also review the role of circadian rhythm and sleep-related disorders in the development and treatment of IR.

Investigating endocrine and physiological parameters of captive American kestrels exposed by diet to selected organophosphate flame retardants.

Organophosphate triesters are high production volume additive flame retardants (OPFRs) and plasticizers. Shown to accumulate in abiotic and biotic environmental compartments, little is known about the risks they pose. Captive adult male American kestrels (Falco sparverius) were fed the same dose (22 ng OPFR/g kestrel/d) daily (21 d) of tris(2-butoxyethyl) phosphate (TBOEP), tris(2-chloroethyl) phosphate (TCEP), tris(2-chloroisopropyl) phosphate (TCIPP), or tris(1,2-dichloro-2-propyl) phosphate (TDCIPP). Concentrations were undetected in tissues (renal, hepatic), suggesting rapid metabolism. There were no changes in glutathione status, indicators of hepatic oxidative status, or the cholinergic system (i.e., cerebrum, plasma cholinesterases; cerebrum muscarinic, nicotinic receptors). Modest changes occurred in hepatocyte integrity and function (clinical chemistry). Significant effects on plasma free triiodothyronine (FT3) concentrations occurred with exposure to TBOEP, TCEP, TCIPP, and TDCIPP; TBOEP and TCEP had additional overall effects on free thyroxine (FT4), whereas TDCIPP also influenced total thyroxine (TT4). Relative increases (32%-96%) in circulating FT3, TT3, FT4, and/or TT4 were variable with each OPFR at 7 d exposure, but limited thereafter, which was likely maintained through decreased thyroid gland activity and increased hepatic deiodinase activity. The observed physiological and endocrine effects occurred at environmentally relevant concentrations and suggest parent OPFRs or metabolites may have been present despite rapid degradation.

Toxicity reference values for chlorophacinone and their application for assessing anticoagulant rodenticide risk to raptors.

Despite widespread use and benefit, there are growing concerns regarding hazards of second-generation anticoagulant rodenticides to non-target wildlife which may result in expanded use of first-generation compounds, including chlorophacinone (CPN). The toxicity of CPN over a 7-day exposure period was investigated in American kestrels (Falco sparverius) fed either rat tissue mechanically-amended with CPN, tissue from rats fed Rozol(®) bait (biologically-incorporated CPN), or control diets (tissue from untreated rats or commercial bird of prey diet) ad libitum. Nominal CPN concentrations in the formulated diets were 0.15, 0.75 and 1.5 µg/g food wet weight, and measured concentrations averaged 94 % of target values. Kestrel food consumption was similar among groups and body weight varied by less than 6 %. Overt signs of intoxication, liver CPN residues, and changes in prothrombin time (PT), Russell's viper venom time (RVVT) and hematocrit, were generally dose-dependent. Histological evidence of hemorrhage was present at all CPN dose levels, and most frequently observed in pectoral muscle and heart. There were no apparent differences in toxicity between mechanically-amended and biologically-incorporated CPN diet formulations. Dietary-based toxicity reference values at which clotting times were prolonged in 50 % of the kestrels were 79.2 µg CPN consumed/kg body weight-day for PT and 39.1 µg/kg body weight-day for RVVT. Based upon daily food consumption of kestrels and previously reported CPN concentrations found in small mammals following field baiting trials, these toxicity reference values might be exceeded by free-ranging raptors consuming such exposed prey. Tissue-based toxicity reference values for coagulopathy in 50 % of exposed birds were 0.107 µg CPN/g liver wet weight for PT and 0.076 µg/g liver for RVVT, and are below the range of residue levels reported in raptor mortality incidents attributed to CPN exposure. Sublethal responses associated with exposure to environmentally realistic concentrations of CPN could compromise survival of free-ranging raptors, and should be considered in weighing the costs and benefits of anticoagulant rodenticide use in pest control and eradication programs.

Reattachment of the proximal hamstring origin: outcome in patients with partial and complete tears.

PURPOSE: To assess the subjective and functional outcome in complete and partial injuries, both acute and chronic. METHODS: One hundred and thirty-two consecutive proximal hamstring reattachments were performed by a single surgeon between 1999 and 2009. The mean age at the time of operation was 42.5 years (SD 12.2), the mean duration of follow-up was 53.8 months (SD 19.5), and all patients with a minimum 2-year follow-up were included in the study. Patients were reviewed independently. Functional outcome was evaluated using quantitative assessments of pre-operative and postoperative hamstring strength and endurance, while subjective outcome was undertaken at the latest follow-up using a three-tier questionnaire. RESULTS: The most common cause of injury was waterskiing (29 patients). There were 96 complete injuries and 36 partial injuries. Overall, 112 of 132 patients rated their result as good/excellent, 91 had returned to their pre-injury level of sporting activity, and 114 said that they would undergo surgery again. Mean postoperative hamstring strength was 83 %, and mean hamstring endurance was 108 % compared to the contralateral limb. Patients with complete injuries and those operated and those operated on acutely (<6 weeks) were more likely to have a good/excellent result. There was no significant correlation between time to repair, type of injury (partial vs. complete) and functional outcome. CONCLUSION: Good to excellent results can be expected in the majority of patients, following surgical reattachment. Surgery is well tolerated with the vast majority of patients, reporting that they would undergo surgery again. LEVEL OF EVIDENCE: IV.