TURN-IT: a novel turning intervention program to improve quality of turning in daily life in people with Parkinson's disease.

BACKGROUND: People with Parkinson's disease (PD) have a high fall rate and many falls are associated with turns. Despite this, there is minimal research on effects of rehabilitation on the quality of turns. Further, quantifying turns in the home may have broader implications since rehabilitation of turns would ideally improve turning in real world mobility. METHODS: Sixty people with PD and a history of falls will be randomized to receive either a novel TURNing InTervention (TURN-IT) or no intervention (control group). The TURN-IT group will be seen for 6 weeks (18 visits) for an individualized, progressive program that is based on the specific constraints of turning in PD. Wearable sensors will be used to measure 7 days of mobility, including turns, before and after intervention or control period. In addition, blinded assessments of gait, mobility and turns will occur before and after intervention for both groups and falls will be monitored for twelve months post intervention with bimonthly email questionnaires. DISCUSSION: This study has the potential to change how we rehabilitate and assess turning in people with PD and falls. There are several novel aspects to our study including a comprehensive turning-focused intervention that is tailored to the underlying constraints that impair turning in people with PD. Further, our outcome measure of turning quality during 7 days of daily life is novel and has implications for determining real-life changes after rehabilitation. The ultimate goal of this rehabilitation intervention is to improve how patients turn in daily life and to reduce falls. TRIALS REGISTRATION: This protocol is registered at clinicaltrials.gov; #NCT04897256; https://clinicaltrials.gov/ct2/show/NCT04897256?term=Horak&cond=Parkinson+Disease&draw=2&rank=4 .

Assessing the impact of the global subsea telecommunications network on sedimentary organic carbon stocks.

The sequestration of organic carbon in seafloor sediments plays a key role in regulating global climate; however, human activities can disturb previously-sequestered carbon stocks, potentially reducing the capacity of the ocean to store CO2. Recent studies revealed profound seafloor impacts and sedimentary carbon loss due to fishing and shipping, yet most other human activities in the ocean have been overlooked. Here, we present an assessment of organic carbon disturbance related to the globally-extensive subsea telecommunications cable network. Up to 2.82-11.26 Mt of organic carbon worldwide has been disturbed as a result of cable burial, in water depths of up to 2000 m. While orders of magnitude lower than that disturbed by bottom fishing, it is a non-trivial amount that is absent from global budgets. Future offshore developments that disturb the seafloor should consider the safeguarding of carbon stocks, across the full spectrum of Blue Economy industries.

An asymptotically consistent approximant method with application to soft- and hard-sphere fluids.

A modified Padé approximant is used to construct an equation of state, which has the same large-density asymptotic behavior as the model fluid being described, while still retaining the low-density behavior of the virial equation of state (virial series). Within this framework, all sequences of rational functions that are analytic in the physical domain converge to the correct behavior at the same rate, eliminating the ambiguity of choosing the correct form of Padé approximant. The method is applied to fluids composed of "soft" spherical particles with separation distance r interacting through an inverse-power pair potential, φ = ε(σ∕r)(n), where ε and σ are model parameters and n is the "hardness" of the spheres. For n < 9, the approximants provide a significant improvement over the 8-term virial series, when compared against molecular simulation data. For n ≥ 9, both the approximants and the 8-term virial series give an accurate description of the fluid behavior, when compared with simulation data. When taking the limit as n → ∞, an equation of state for hard spheres is obtained, which is closer to simulation data than the 10-term virial series for hard spheres, and is comparable in accuracy to other recently proposed equations of state. By applying a least square fit to the approximants, we obtain a general and accurate soft-sphere equation of state as a function of n, valid over the full range of density in the fluid phase.

General Practitioner satisfaction with a radiographer-led general radiography reporting service at a district general hospital in the UK.

INTRODUCTION: To evaluate General Practitioner (GP) satisfaction with a radiographer-led general radiography reporting service in a single district general hospital in order to identify areas for improvement. METHODS: A mixed method online survey was created and distributed to all GP surgeries in the catchment area of the hospital with a 6 week response period. RESULTS: Although the majority of GPs are satisfied with the service they receive, there were areas for improvement. Key areas included methods of contacting radiology department with queries, report content/terminology and recommendations for follow-up. CONCLUSIONS: Although the majority of GPs are happy for radiographers to report imaging examinations some resistance was encountered, particularly with regards to chest reporting. Recommendations are made for improvements designed to address these issues. IMPLICATIONS FOR PRACTICE: This article is one of the first in the UK to assess GP satisfaction with general X-ray reporting services. As the majority of GP reporting in the UK is now completed by radiographers, the results will allow reporting teams to tailor their service, in order to improve outcomes for both commissioners and patients.

The impact of the Covid-19 pandemic on the mental health and work morale of radiographers within a conventional X-ray department.

INTRODUCTION: There is a plethora of literature that has described the negative impact of the COVID-19 pandemic on the mental health of healthcare staff worldwide. Our aim was to investigate the physical and mental demands of mobile x-ray imaging on radiographers during the first wave of the COVID-19 pandemic, within a local NHS Trust. METHODS: A total of 16 participants from 1 NHS Trust took part within this study. Both quantitative and qualitative data was obtained through an online survey. Statistical data was obtained via the Trust Radiology Information System (RIS). Data was gathered for the thirteen weeks from 23rd March to 21st June 2020 (the first wave); direct comparison was made to the same period in 2019. RESULTS: Three key themes emerged from the data. These include mental health challenges/work morale in Radiology, demand of mobile imaging and departmental and Trust-wide mental health support. Results indicate a high demand in mobile imaging which has made a significant difference in the working life of some radiographers. CONCLUSION: The COVID-19 pandemic has significantly affected the mental health of a proportion of radiographers at this Trust. Results indicate high workload and demand in mobile imaging has made a significant difference to the working life of radiographers, specifically the ones who were relatively newly qualified. IMPLICATIONS FOR PRACTICE: Two key interventions are proposed from this study. The first one is to provide and promote mental health support within radiology departments. The second is to encourage dual working on mobile x-ray examinations to help manage the emotional and physical burden.

Adrenal suppression in bronchiectasis and the impact of inhaled corticosteroids.

The present study identified three patients with bronchiectasis receiving inhaled corticosteroids (ICSs) who had symptomatic adrenal suppression secondary to ICS. The prevalence of adrenal suppression is unknown in bronchiectasis. The frequency of adrenal suppression and the impact of ICS use in bronchiectasis patients were examined. In total, 50 outpatients (33 receiving ICSs) underwent a short Synacthen test and completed a St George's Respiratory Questionnaire (SGRQ). Symptoms of adrenal suppression, steroid use and lung function were compared between subjects who were suppressed and those who were not. Adrenal suppression was evident in 23.5% of subjects who did not receive ICSs and 48.5% of those who did. Basal cortisol and the increments by which cortisol increased 30 min after Synacthen were lower in suppressed than in nonsuppressed subjects. The incremental cortisol rise was negatively correlated with SGRQ impacts and total score, suggesting a worse quality of life in those who had an impaired adrenal response. The greatest frequency of generalised symptoms was seen in the suppressed group. A significant proportion of subjects with bronchiectasis have evidence of adrenal suppression, and this is increased when inhaled corticosteroids are also used. Impairment of the cortisol response to stimulation is associated with poorer health status.

Participatory action research into implementing open access in musculoskeletal X-ray: Management and staff perspectives.

INTRODUCTION: Neighbouring Trusts have implemented open access (walk-in) services to shorten waiting times in x-ray. Despite this, staff perceptions of their effectiveness have not yet been studied. This study forms the initial baseline evaluation phase of wider participatory action research investigating the implementation of an open access service for general practitioner musculoskeletal x-ray referrals. Staff perceptions regarding effectiveness of the current service were gathered, including their opinions regarding the effectiveness of open access services. METHODS: Qualitative data were obtained via three semi-structured interviews with radiology management and two (cross-site) staff focus groups over a 2 month period. Template analysis was used to interpret the data with the aid of NVIVO 11 to facilitate analysis. RESULTS: Template analysis uncovered several drivers for changing the current service including waiting times, external pressures, patient choice and administrative delays. 'Flexibility' was the key theme to arise during discussion regarding the effectiveness of the current service. Potential for improved access was highlighted as a major benefit to the implementation of open access, however 'workload', 'staffing' and 'communication' were all identified as potential barriers to its implementation. CONCLUSION: Although several staff members were satisfied with current service several drivers for change were identified that need to be addressed in order to truly deliver a service that fulfils the patients' needs. Results will inform the wider participatory action research that will investigate the barriers to implementing an open access service and identify whether this is indeed a suitable method of addressing the drivers for change.

Engineering plant membranes using droplet interface bilayers.

Droplet interface bilayers (DIBs) have become widely recognised as a robust platform for constructing model membranes and are emerging as a key technology for the bottom-up assembly of synthetic cell-like and tissue-like structures. DIBs are formed when lipid-monolayer coated water droplets are brought together inside a well of oil, which is excluded from the interface as the DIB forms. The unique features of the system, compared to traditional approaches (e.g., supported lipid bilayers, black lipid membranes, and liposomes), is the ability to engineer multi-layered bilayer networks by connecting multiple droplets together in 3D, and the capability to impart bilayer asymmetry freely within these droplet architectures by supplying droplets with different lipids. Yet despite these achievements, one potential limitation of the technology is that DIBs formed from biologically relevant components have not been well studied. This could limit the reach of the platform to biological systems where bilayer composition and asymmetry are understood to play a key role. Herein, we address this issue by reporting the assembly of asymmetric DIBs designed to replicate the plasma membrane compositions of three different plant species; Arabidopsis thaliana, tobacco, and oats, by engineering vesicles with different amounts of plant phospholipids, sterols and cerebrosides for the first time. We show that vesicles made from our plant lipid formulations are stable and can be used to assemble asymmetric plant DIBs. We verify this using a bilayer permeation assay, from which we extract values for absolute effective bilayer permeation and bilayer stability. Our results confirm that stable DIBs can be assembled from our plant membrane mimics and could lead to new approaches for assembling model systems to study membrane translocation and to screen new agrochemicals in plants.

Deep wound infection after proximal femoral fracture: consequences and costs.

The purpose of this study was to assess the impact of deep wound infection after surgery for proximal femoral fracture (PFF) on the patient in terms of mortality and social consequences, and on the National Health Service in terms of financial burden. Sixty-one cases of PFF over a six-year period were complicated with deep surgical wound infection. These cases were compared with a matched control group of 122 patients without infection. Infected cases had greatly increased hospital stay (P<0.001), were 4.5 times less likely to survive to discharge (P=0.002), and if they survived, were three times less likely to return to their original residence (P=0.05). The total cost of treatment per infected case was 24,410 pound sterling compared with 7210 pound sterling for controls (P<0.001). Meticillin-resistant Staphylococcus aureus (MRSA) infection increased admission length and cost compared with non-MRSA infection (P=0.02). Deep wound infection after PFF is a devastating and costly complication for both the patient and the healthcare services. The cost consequences should be considered when allocating resources to trauma services to ensure adequate provision to minimize infection risks and to accommodate treatment costs in this vulnerable group.

Outcome of surgery for reconstruction of fractures of the acetabulum. The time dependent effect of delay.

This is a retrospective case review of 237 patients with displaced fractures of the acetabulum presenting over a ten-year period, with a minimum follow-up of two years, who were studied to test the hypothesis that the time to surgery was predictive of radiological and functional outcome and varied with the pattern of fracture. Patients were divided into two groups based on the fracture pattern: elementary or associated. The time to surgery was analysed as both a continuous and a categorical variable. The primary outcome measures were the quality of reduction and functional outcome. Logistic regression analysis was used to test our hypothesis, while controlling for potential confounding variables. For elementary fractures, an increase in the time to surgery of one day reduced the odds of an excellent/good functional result by 15% (p = 0.001) and of an anatomical reduction by 18% (p = 0.0001). For associated fractures, the odds of obtaining an excellent/good result were reduced by 19% (p = 0.0001) and an anatomical reduction by 18% (p = 0.0001) per day. When time was measured as a categorical variable, an anatomical reduction was more likely if surgery was performed within 15 days (elementary) and five days (associated). An excellent/good functional outcome was more likely when surgery was performed within 15 days (elementary) and ten days (associated). The time to surgery is a significant predictor of radiological and functional outcome for both elementary and associated displaced fractures of the acetabulum. The organisation of regional trauma services must be capable of satisfying these time-dependent requirements to achieve optimal patient outcomes.

Antagonism of the proinflammatory and pronociceptive actions of canonical and biased agonists of protease-activated receptor-2.

BACKGROUND AND PURPOSE: Diverse proteases cleave protease-activated receptor-2 (PAR2) on primary sensory neurons and epithelial cells to evoke pain and inflammation. Trypsin and tryptase activate PAR2 by a canonical mechanism that entails cleavage within the extracellular N-terminus revealing a tethered ligand that activates the cleaved receptor. Cathepsin-S and elastase are biased agonists that cleave PAR2 at different sites to activate distinct signalling pathways. Although PAR2 is a therapeutic target for inflammatory and painful diseases, the divergent mechanisms of proteolytic activation complicate the development of therapeutically useful antagonists. EXPERIMENTAL APPROACH: We investigated whether the PAR2 antagonist GB88 inhibits protease-evoked activation of nociceptors and protease-stimulated oedema and hyperalgesia in rodents. KEY RESULTS: Intraplantar injection of trypsin, cathespsin-S or elastase stimulated mechanical and thermal hyperalgesia and oedema in mice. Oral GB88 or par2 deletion inhibited the algesic and proinflammatory actions of all three proteases, but did not affect basal responses. GB88 also prevented pronociceptive and proinflammatory effects of the PAR2-selective agonists 2-furoyl-LIGRLO-NH2 and AC264613. GB88 did not affect capsaicin-evoked hyperalgesia or inflammation. Trypsin, cathepsin-S and elastase increased [Ca(2+) ]i in rat nociceptors, which expressed PAR2. GB88 inhibited this activation of nociceptors by all three proteases, but did not affect capsaicin-evoked activation of nociceptors or inhibit the catalytic activity of the three proteases. CONCLUSIONS AND IMPLICATIONS: GB88 inhibits the capacity of canonical and biased protease agonists of PAR2 to cause nociception and inflammation.

Bovine tuberculosis in New Zealand: epidemiology and models.

Bovine tuberculosis is New Zealand's most serious animal health problem because of its threat as a nontariff trade barrier to livestock export, and because a wildlife reservoir of 70 million brushtail possums seriously constrains its control. Mathematical models have contributed significantly to current control strategies and have highlighted some key questions of wider epidemiological significance.

Demonstration of elevated levels of active cathepsin S in dextran sulfate sodium colitis using a new activatable probe.

BACKGROUND: Proteases play a major role in inflammatory diseases of the gastrointestinal tract. Activatable probes are a major technological advance, enabling sensitive detection of active proteases in tissue samples. Our aim was to synthesize an activatable probe for cathepsin S and validate its use in a mouse model of colitis. METHODS: We designed and synthesized a new fluorescent activatable probe, NB200, for the detection of active cathepsin S. Colitis was induced in C57BL/6 mice by the administration of 3% dextran sulfate sodium (DSS). Homogenized mouse colons, with or without the addition of the specific cathepsin S inhibitor MV026031, were incubated with NB200 in a fluorescent plate reader. KEY RESULTS: NB200 selectively detected purified cathepsin S and not other common inflammatory proteases. Homogenates of colon from mice with DSS colitis induced a significant fluorescent increase when compared to control animals (control vs DSS: p < 0.05 at 200 min and p < 0.01 at 220-240 min), indicating cathepsin S activation. The cathepsin S inhibitor abolished this increase in fluorescence (DSS vs DSS + MV026031: p < 0.05 at 140 min, p < 0.01 at 180 min, p < 0.001 at 200-240 min), which confirms cathepsin S activation. Cathepsin S activity correlated with the disease activity index (Spearman r = 0.77, p = 0.017). CONCLUSIONS & INFERENCES: Our investigation has demonstrated the utility of activatable probes for detecting protease activity in intestinal inflammation. Panels of such probes may allow 'signature' protease profiles to be established for a range of inflammatory diseases and disorders.

A model for nematodiasis in New Zealand lambs.

A strategic model is described for the epidemiology of mixed nematode infections in New Zealand lambs. The model successfully reproduces known patterns of parasite epidemiology and production loss in lambs under currently implemented control strategies. The variation in model output during sensitivity analysis was within acceptable limits defined by field data. Model output was most sensitive to variation in parameters affecting survival and migration of the free-living stages and host resistance to infection, suggesting that these factors are most influential in regulating parasite populations. It is intended to use the model to focus research on key aspects of nematode epidemiology and control and, following the incorporation of appropriate genetic mechanisms, anthelmintic resistance.

A model for nematodiasis in New Zealand lambs: the effect of drenching regime and grazing management on the development of anthelmintic resistance.

A model for nematodiasis in lambs was expanded to incorporate both the contribution of ewes to nematode epidemiology and the genetic parameters required to simulate the development of anthelmintic resistance in the nematode population. The expanded model was used to assess the impact of various drench and grazing management strategies for ewes and lambs on the rate of development of anthelmintic resistance. Three grazing management options, under a range of drenching schedules, were compared: one in which lambs and ewes were rotationally grazed as separate flocks over the same area after weaning (common grazing); a second in which lambs were grazed, after weaning, on areas from which ewes were excluded (separate grazing); and a third in which lambs were moved to "safe" pasture at weaning and again in early autumn (integrated control). Drenching strategies examined under the first 2 grazing options included a 5 lamb-drench "preventive" programme with 0, 1, 2, 3 or 4 additional lamb drenches, and 0 or 1 ewe drench treatment at either tall-docking or mating. Under the third grazing option, lambs were given either 1 or 2 drench treatments at or following each move to safe pasture and ewes 0 or 1 drench treatment at either tail-docking (i.e., 3-4 weeks after lambing) or mating. Model output suggests that drenching ewes prior to any lamb drenching programme is likely to significantly increase selection for drench resistance by pre-selecting the larval challenge to the lambs and, under some grazing systems, by reducing the diluting effect of eggs of susceptible genotypes passed by undrenched ewes. The results highlight the potential importance of undrenched ewes as a refuge for susceptible worm genotypes and indicate that on its own, drenching frequency is likely to be a poor indicator of selection pressure for resistance and thus of limited value in selecting strategies for the management of anthelmintic resistance.

Androgen-mediated development in male rat offspring exposed to flutamide in utero: permanence and correlation of early postnatal changes in anogenital distance and nipple retention with malformations in androgen-dependent tissues.

Male offspring exposed in utero to antiandrogens often display alterations in androgen-dependent developmental markers (e.g., anogenital distance [AGD], nipple retention) together with clearly adverse responses such as genital malformations and reproductive tract lesions. The objectives of this study were to determine whether in utero exposure to flutamide results in permanent changes in male AGD and nipple retention, characterize the dose-response relationship between flutamide-mediated alterations in these landmarks and clearly adverse antiandrogenic effects, and establish the predictive value and relationship between AGD and nipple retention, and other adverse manifestations. Male offspring were exposed in utero to 0, 6.25, 12.5, 25, or 50 mg/kg/day (po) of flutamide from gestation days 12 to 21. Offspring were uniquely identified at birth, and various androgen-mediated end points (AGD, areola/nipple retention, cryptorchidism, reproductive tract weights, and malformation incidence) were examined throughout life. In utero flutamide exposure significantly decreased the AGD on postnatal day (PND) 1 and increased areola/nipple retention in male rats on PND 13. Flutamide-induced alterations in AGD and areolae/nipples in early postnatal life correlated with a reduction in AGD and retained nipples observed in the adult. Prenatal flutamide exposure resulted in dose-responsive increases in cryptorchidism. Hypospadias were observed in all flutamide-exposed offspring. In utero flutamide exposure induced partial or complete prostate agenesis and decreased the weights of the seminal vesicles, levator ani bulbocavernosus (LABC) muscle, testes, and epididymides in a dose-dependent manner. Epididymal malformations were observed mainly in the 50 mg/kg/day flutamide dose group. In general, flutamide-induced alterations in dihydrotestosterone (DHT)- and testosterone (T)-dependent development each had similar respective dose-response curves. DHT-mediated development was more sensitive to in utero flutamide exposure than T-dependent processes. However, the dose-response curves for flutamide-induced changes in cryptorchidism and seminal vesicle weight were intermediate between the dose-response curves for DHT- and T-mediated development, indicating that proper development of these tissues may require both androgens. The LABC also displayed a dose-dependent decrease in weight that was similar to dose-response observed with seminal vesicle weight and was the most sensitive T-dependent end point measured. Flutamide-induced decreases in AGD predicted subsequent malformations as evidenced by logistic regression and receiver operator characteristic analysis of malformations versus AGD. However, the AGD that would predict a 10% incidence of seminal vesicle malformations is equivalent to a female AGD. An almost fully feminized phenotype of 10-12 nipples was observed in animals that had malformations in T-dependent tissues, whereas 6 or more nipples were observed in animals with malformation in DHT-dependent tissues. These data suggest that flutamide-mediated changes in AGD and nipple retention are not sensitive predictors of altered T-mediated development.

The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat.

Phthalate esters (PE) such as DEHP are high production volume plasticizers used in vinyl floors, food wraps, cosmetics, medical products, and toys. In spite of their widespread and long-term use, most PE have not been adequately tested for transgenerational reproductive toxicity. This is cause for concern, because several recent investigations have shown that DEHP, BBP, DBP, and DINP disrupt reproductive tract development of the male rat in an antiandrogenic manner. The present study explored whether the antiandrogenic action of DEHP occurs by (1) inhibiting testosterone (T) production, or by (2) inhibiting androgen action by binding to the androgen receptor (AR). Maternal DEHP treatment at 750 mg/kg/day from gestational day (GD) 14 to postnatal day (PND) 3 caused a reduction in T production, and reduced testicular and whole-body T levels in fetal and neonatal male rats from GD 17 to PND 2. As a consequence, anogenital distance (AGD) on PND 2 was reduced by 36% in exposed male, but not female, offspring. By GD 20, DEHP treatment also reduced testis weight. Histopathological evaluations revealed that testes in the DEHP treatment group displayed enhanced 3ss-HSD staining and increased numbers of multifocal areas of Leydig cell hyperplasia as well as multinucleated gonocytes as compared to controls at GD 20 and PND 3. In contrast to the effects of DEHP on T levels in vivo, neither DEHP nor its metabolite MEHP displayed affinity for the human androgen receptor at concentrations up to 10 microM in vitro. These data indicate that DEHP disrupts male rat sexual differentiation by reducing T to female levels in the fetal male rat during a critical stage of reproductive tract differentiation.

A comparison of 3-parameter, single-species population models, in relation to the management of brushtail possums in New Zealand.

A range of published 3-parameter, single-species models are compared using possums in New Zealand as an example. Most models yield similar population growth curves and similar estimates of maximum sustainable yield (MSY). A new model of competition for refuges, and interactive models of competition for food, both yield growth curves peaked to the right. In the second case, the relationship between the shape of the curve and the parameters of the interactive model is described. Three management consequences of asymmetric (rightward-peaked) growth as opposed to logistic growth are discussed. First, where the animal is a pest a greater control effort is required to reduce density. Second, for sustained yield harvesting the best policy is an adaptive one which initially requires no knowledge of the shape of the growth curve. Third, sustainable yields may be 50% higher than those predicted by the simple logistic model.

Modelling immunocontraception in disseminating systems.

Vectored immunocontraception is a novel technology and simple models are described to help predict whether, and how, it might work. That is, given that an effective immunocontraceptive agent can be produced, and given that it can be inserted into a microparasitic or macroparasitic infective vector, would the vector persist and reach a high prevalence in the host and, if so, would it sterilize a sufficient proportion of the host breeding population to significantly reduce its density? Both conditions are necessary for success. The first question is an epidemiological one, relating solely to disseminating systems and differing according to whether the vector itself is newly introduced or pre-existing. If it is newly introduced, the assumption is that it is present in some other geographical areas occupied by the same target species, or is found in closely-related species. If the vector already exists in the population, the issue is one of competition between the engineered and wild-type vectors. The second question is an ecological one, common to both non-disseminating and disseminating systems. Whatever level of sterilization the immunocontraception provides must translate into a significant reduction in population density, having regard to the nature and extent of compensatory, density-dependence mechanisms in the population. These two questions, together with other more minor issues, are addressed in turn with particular reference to models for immunocontraception of brushtail possums (Trichosurus vulpecula) in New Zealand.