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A novel method aimed at evaluating the active drag profile during front-crawl swimming is proposed. Fourteen full trials were conducted with each trial using a stationary load cell set-up and a commercial resistance trainer to record the tension force in a rope, caused by an athlete swimming. Seven different stroke cycles in each experiment were identified for resampling time dependent data into position dependent data. Active drag was then calculated by subtracting resistance trainer force data away from the stationary load cell force data. Mean active drag values across the stroke cycle were calculated for comparison with existing methods, with mean active drag values calculated between 76 and 140 N depending on the trial. Comparing results with established active drag methods, such as the Velocity Perturbation Method (VPM), shows agreement in the magnitude of the mean active drag forces. Repeatability was investigated using one athlete, repeating the load cell set-up experiment, indicating results collected could range by 88 N depending on stroke cycle position. Variation in results is likely due to inconsistencies in swimmer technique and power output, although further investigation is required. The method outlined is proposed as a representation of the active drag profile over a full stroke cycle. [ABSTRACT FROM AUTHOR]

Background: Despite an increase in the professionalism and participation of female cricket, the coaching of female pace bowling is still reliant on male-derived knowledge. Objectives: To investigate the association between key malederived kinematic and anthropometric parameters and ball release speed (BRS) in female pace bowlers. Methods: Eleven female pace bowlers participated in this study. BRS, and four anthropometric and five kinematic parameters were determined. Stepwise linear regression and Pearson Product Moment correlations were used to identify anthropometric and kinematic parameters linked to BRS. Results: The best predictor of BRS explaining 89% of the observed variance was the bowling shoulder angle at ball release. The best anthropometric predictor of BRS was height explaining 53% of the observed variance. Other parameters correlated with BRS included: run-up speed (r = 0.75, p = 0.013) and arm length (r = 0.61, p = 0.046). When height was controlled for, the front knee angle at front foot contact was also correlated to BRS (r = 0.68, p = 0.044). No relationship was found between trunk flexion and BRS. Conclusion: Faster BRS were characterised by faster run-up speeds, straighter front knees, and delayed arm circumduction similar to male pace bowlers. The lack of relationship between trunk flexion and BRS may highlight female pace bowlers adopting a bowling technique where BRS is contributed to by trunk rotation as well as trunk flexion. This knowledge is likely to be useful in the talent identification and coaching of female pace bowlers. [ABSTRACT FROM AUTHOR]

Increasing access to university for those currently under-represented is a UK government priority. Understanding the views of under-represented students can help direct widening participation activities. In recent years, a positive trend finds increasing numbers of Black students attending university, but it is not clear why White disadvantaged student numbers have not increased. Thus, we aimed to explore the student viewpoint on barriers and facilitators to university access in disadvantaged adolescents and how this might differ by ethnicity. We used an online semi-structured interview with questions about applying to university. Seventy adolescents (mean 16.9 yr.) were recruited who are currently under-represented at university level, based on various measures of disadvantage. Black, Asian, and ethnic minority students (BAME) reported similar barriers and facilitators to applying to university as White disadvantaged students. However, there were some differences, for example, BAME participants stated 'having no choice' was a reason to apply to university while White participants did not mention this. Also ~60% of BAME students said they would prefer to study close by compared to far away, while only 46% of White participants said this. Our results support previous findings that financial issues are a key barrier to university access and that outreach activities can act as facilitators to increase university access. However, we compare the unique viewpoints on the barriers and facilitators to university access in Black, Asian and White under-represented students. Based on these views we also make recommendations for future widening participation events targeted at different ethnicities. [ABSTRACT FROM AUTHOR]

The field of dark matter detection is a highly visible and highly competitive one. In this paper, we propose recommendations for presenting dark matter direct detection results particularly suited for weak-scale dark matter searches, although we believe the spirit of the recommendations can apply more broadly to searches for other dark matter candidates, such as very light dark matter or axions. To translate experimental data into a final published result, direct detection collaborations must make a series of choices in their analysis, ranging from how to model astrophysical parameters to how to make statistical inferences based on observed data. While many collaborations follow a standard set of recommendations in some areas, for example the expected flux of dark matter particles (to a large degree based on a paper from Lewin and Smith in 1995), in other areas, particularly in statistical inference, they have taken different approaches, often from result to result by the same collaboration. We set out a number of recommendations on how to apply the now commonly used Profile Likelihood Ratio method to direct detection data. In addition, updated recommendations for the Standard Halo Model astrophysical parameters and relevant neutrino fluxes are provided. The authors of this note include members of the DAMIC, DarkSide, DARWIN, DEAP, LZ, NEWS-G, PandaX, PICO, SBC, SENSEI, SuperCDMS, and XENON collaborations, and these collaborations provided input to the recommendations laid out here. Wide-spread adoption of these recommendations will make it easier to compare and combine future dark matter results. [ABSTRACT FROM AUTHOR]

The effects of three seeding rates (250, 350 and 450 seeds/m2), six applied N rates (40, 70, 100, 130, 160 and 190 kg N/ha) and the application of plant growth regulator on the grain quality of two spring oat cultivars (Husky and Keely) were evaluated at four spring-sown sites over a 3-year period (2016–2018). The same cultivars, seeding rates and five applied N rates (80, 110, 140, 170 and 200 kg N/ha) were evaluated at three winter-sown sites, in 2017–2019. Keely had a significantly higher kernel content (KC) in spring (0.7%) and winter-sown (0.6%) oats. Specific weight (SW) decreased as N rate increased in spring-sown crops (1 kg/hl) with no effect observed in winter-sown oats. Hullability (HB) increased (0.92%) in spring-sown crops as N rate increased with a reduction (0.9%) observed when winter-sown. Increases in grain protein percentage (GPP) were observed in spring (1.8%) and winter (1.2%) sowings in response to N rate. The application of plant growth regulator reduced SW (0.4 kg/hl), GPP (0.3%), KC (0.6%) with no effect on HB. Kernel size was highly responsive too applied N rate, with reductions in grains >2.5 mm and increases in grains of smaller size observed as N rate increased. HB had a marked relationship to kernel size with GP inconsistently linked to SW. The results of this study suggest that cultivar, N rate and PGR application are of importance to milling quality and that changes in grain size in response to agronomic practices contribute to changes in specific weight and hullability. [ABSTRACT FROM AUTHOR]

Factorial experiments were carried out on spring- and winter-sown oat crops in Ireland in 2016–2019 to identify plant responses in yield formation and grain filling procedures. Two cultivars (Husky and Keely), three seed rates (250, 350 and 450 seeds/m2), six applied nitrogen (N) rates (40, 70, 100, 130, 160 and 190 kg N/ha) with a plant growth regulator (PGR) were examined in spring and winter sowings, using the same cultivars at five rates of applied N (80, 110, 140, 170 and 200 kg N/ha). The applied N rate and seed rate significantly (P < 0.05) modified the yield components determining grains/m2 in spring- and winter-sown crops with increases in panicle number of key importance. Increases were also observed in the proportion of primary grain by weight (0.9–1.6%) and number (0.7–1.4%) ratios in spring-sown crops in response to applied N rate, with winter-sown crops exhibiting a more consistent pattern of grain fill. Seed rate and PGR application had minor effects on yield components and panicle conformation. Grain fill procedures played an important role in the maximization of grain yield under seasonal conditions. Significant positive correlations were observed between the number of aborted grain sites and yield under drought conditions (0.22), with negative associations observed in near-optimal conditions (−0.22 to −0.41). Agronomic effects on grain site abortion were minimal in comparison with seasonal effects. In seasons characterized by cool, consistent conditions, grain yield was maximized by the utilization of all available grain sites. Where assimilate shortages were encountered during grain fill the abortion of grains sites was positively associated with grain yield. [ABSTRACT FROM AUTHOR]

Adsorption of flexible oligomers into narrow cylindrical pores has been studied by means of several versions of classical density functional theory (CDFT) and Monte Carlo simulation. The adsorption process is interesting to study due to the competition between the entropic depletion of oligomers from the pores and the wall-oligomer attraction. It is also challenging to describe using current CDFTs, which tend to overestimate the amount of the adsorbed fluid. From a comparison of several different CDFT approaches, we find that this is due to the assumption of ideal or freely jointed chain conformations. Moreover, it is demonstrated that it is impossible to obtain a reasonable description of the adsorption isotherms without taking into account accurate contact values in the distribution functions describing the structure of the reference monomer fluid. At low densities, more accurate result are obtained in comparison with Monte Carlo simulation data when accurate contact values are incorporated into the theory rather than the more commonly used hard-sphere contact value. However, even the CDFT with accurate contact values still overestimates the amount of the adsorbed fluid due to the ideal or freely jointed chain approximation, used for the description of chain conformations in most CDFT approaches. We find that significant improvement can achieved by employing self-consistent field theory, which samples self-avoiding chain conformations and decreases the number of possible chain conformations, and, consequently, the amount of the adsorbed fluid. [ABSTRACT FROM AUTHOR]

Purpose: To assess the impact of modifications in preoperative instructions on parental understanding of preoperative fasting guidelines. Methods: A prospective postoperative parental survey was conducted to assess parental understanding of preoperative fasting requirements in patients undergoing surgery before and after institution of instructions that included visual aids. Data regarding demographics, procedure type, and time to surgery from preoperative visit were also captured. Survey data were compared between pre- and post-intervention groups using Chi-squared tests for categorical variables and Wilcoxon rank sum test for continuous variables. Results: 173 parents in the pre-intervention group and 162 parents in the post-intervention group were included in the analysis. Parent identification of aspiration risk as the reason for fasting almost doubled after intervention (72.2% vs. 38.2%). There was some evidence of demographic differences between groups; however, in an adjusted model, there was strong evidence (p < 0.001) that parents in the post-intervention group were more likely to identify aspiration as the reason for preoperative fasting (OR 4.73; 95% CI 2.93–7.63). Conclusions: Addition of visual aids in preoperative instructions was associated with improvement in parents' understanding of the rationale behind preoperative fasting instructions. Further studies are needed to determine whether improved understanding is associated with improved adherence. [ABSTRACT FROM AUTHOR]

Fatty acids constitute one of the main components of the lipid lamellae in the top layer of the skin, known as the stratum corneum, which acts as a barrier to foreign substances entering the body and to water leaving the body. To better understand the mechanics of the skin, a molecular-level understanding of the structure of the lamellae needs to be investigated. As a first step toward this goal, the current work involves the development of a coarse-grained model for fatty acids in an amorphous and a crystalline state. In order to retain the structural details of the atomistic molecules, radial distribution functions have been used to provide target data against which the coarse-grained force field is optimized. The optimization was achieved using the method developed by Reith, Pütz, and Müller-Plathe with a damping factor introduced into the updating scheme to facilitate the convergence against the crystalline radial distribution functions. Using this approach, a transferable force field has been developed for both crystalline and amorphous systems that can be used to describe fatty acids of different chain lengths. We are unaware of any other coarse-grained model in the literature that has been developed to study solid phases. Additionally, the amorphous force field has been shown to accurately model mixtures of different free fatty acids based on the potentials derived from pure lipid systems. [ABSTRACT FROM AUTHOR]

Realistic molecular simulations agree with previously published surface force experiments that n-dodecane confined between mica surfaces displays shear-thinning starting at shear rate orders of magnitude less than in the bulk fluid. We probe the origin of this behavior by studying rotational and diffusional relaxations in the simulated fluid and find a freezing-out of the rotational degrees of freedom and a power-law diffusional relaxation, resulting in over seven orders of magnitude increase in the relaxation time. © 2003 American Institute of Physics. [ABSTRACT FROM AUTHOR]

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Cancer-related pain ( CRP) is common and many patients continue to experience pain in spite of advances in pain management modalities. The lack of knowledge, inadequate assessment of CRP and/or organisational factors, such as lack of time due to heavy workload, can be a barrier to effective pain management of healthcare professionals. The purpose was to examine the evidence with regard to the knowledge and attitudes towards practice of healthcare professionals in relation to CRP management. A search of the literature (1999-2015) was conducted searching databases and journals including CINAHL, MEDLINE, Psyc INFO, PubMed, Science Direct and Wiley-Blackwell. The initial search revealed a total of 99 articles and following removal of those that did not meet the inclusion criteria, 19 articles were included in the final review. Recognition of the widespread under treatment of CRP has prompted recent corrective efforts in terms of education from healthcare professionals, however, there is a continuing deficit in healthcare professionals' knowledge with regard to CRP management and indicated that healthcare professionals still have negative attitudes that hinder the delivery of quality care to patients suffering from CRP. Further research on how and where education on this topic should be delivered is required. [ABSTRACT FROM AUTHOR]

Pituitary tumor-transforming gene 1-binding factor (PTTG1IP; PBF) is a multifunctional glycoprotein, which is overexpressed in a wide range of tumours, and significantly associated with poorer oncological outcomes, such as early tumour recurrence, distant metastasis, extramural vascular invasion and decreased disease-specific survival. PBF transforms NIH 3T3 fibroblasts and induces tumours in nude mice, while mice harbouring transgenic thyroidal PBF expression show hyperplasia and macrofollicular lesions. Our assumption that PBF becomes an oncogene purely through increased expression has been challenged by the recent report of mutations in PBF within the Catalogue of Somatic Mutations in Cancer (COSMIC) database. We therefore sought to determine whether the first 10 PBF missense substitutions in human cancer might be oncogenic. Anisomycin half-life studies revealed that most mutations were associated with reduced protein stability compared to wild-type (WT) PBF. Proliferation assays narrowed our interest to two mutational events which significantly altered cell turnover: C51R and R140W. C51R was mainly confined to the endoplasmic reticulum while R140W was apparent in the Golgi apparatus. Both C51R and R140W lost the capacity to induce cellular migration and significantly reduced cell invasion. Colony formation and soft agar assays demonstrated that, in contrast to WT PBF, both mutants were unable to elicit significant colony formation or anchorage-independent growth. However, C51R and R140W retained the ability to repress radioiodide uptake, a functional hallmark of PBF. Our data reveal new insight into PBF function and confirm that, rather than being oncogenic, mutations in PBF are likely to be passenger effects, with overexpression of PBF the more important aetiological event in human cancer. [ABSTRACT FROM AUTHOR]

Background: Approximately 12% of all ureteral stents placed are retained or "forgotten." Forgotten stents are associated with significant safety concerns as well as increased costs and legal issues. Retained ureteral stents (RUS) often occur due to lack of clinical follow-up, communication or language barriers, and economic concerns. Methods: We describe a multiplatform application that facilitates data collection to prevent RUS. The "Stent Tracker" application can be installed on mobile devices and computers. The encrypted and password-protected information is accessible from any device and provides information about each procedure, stent placement and removal dates, as well as product description. This multicenter retrospective study included 194 patients who underwent stent placement between July and October 2015. Nominal data was tallied and ordinal data was divided into quartiles of 25, 50, and 75%. Results: A total of 194 patients from three institutions underwent ureteral stent placement. Reasons for stent placement include 122 cases post ureteroscopy (63%), 8 cases post percutaneous nephrolithotomy (PCNL) (4%), 14 cases post extracorporeal shock wave lithotripsy (SWL) (7%), 18 cases of cancer-related ureteral obstruction (9%), 21 cases of hydronephrosis (11%), and 11 for other reasons (6%). Of these patients, only one patient was lost to follow-up (0. 5%). On average, ureteral stents were removed within 14 days of placement (IQR: 8-26 days). Conclusions: The "Stent Tracker" is a patient safety application that provides a secure and simplified interface, which can significantly reduce the incidence of RUS. Further developments could include automated notifications to patients and staff, color-coding, and integrated information with electronic patient charts. [ABSTRACT FROM AUTHOR]

Objective To assess diagnostic efficacy of a modified tibial compression test in predicting medial meniscal injury in dogs with cranial cruciate ligament failure. Methods Dogs admitted for surgical stabilisation of stifles with cranial cruciate ligament failure were examined by five preoperative physical tests to assess medial meniscal injury. Results of each physical test were compared with findings at arthrotomy and used to calculate sensitivities, specificities, positive and negative predictive values. Results None of the physical tests were accurate in reflecting meniscal integrity for dogs with cranial cruciate failure. Out of the five tests, the modified tibial compression test exhibited the highest concordance and sensitivity for the detection of medial meniscal tears. A palpable click during the modified tibial compression test had a sensitivity and specificity up to 63 and 77%, respectively, for the detection of medial meniscal lesions. Concordance values were up to 40% for the modified tibial compression test, followed by the range of motion test (up to 25%), while all other physical tests had concordance values below 10%. Clinical Significance Physical tests are highly available, affordable and can be easily performed, but their efficacy in diagnosing medical meniscal injury is low. Meniscal clicks associated with meniscal tears were more frequently elicited during the modified tibial compression test when compared with other traditional tests. [ABSTRACT FROM AUTHOR]

BackgroundWe have previously shown that the selective serotonergic reuptake inhibitor, citalopram, reduces the neural response to reward and aversion in healthy volunteers. We suggest that this inhibitory effect might underlie the emotional blunting reported by patients on these medications. Bupropion is a dopaminergic and noradrenergic reuptake inhibitor and has been suggested to have more therapeutic effects on reward-related deficits. However, how bupropion affects the neural responses to reward and aversion is unclear.MethodSeventeen healthy volunteers (9 female, 8 male) received 7 days bupropion (150 mg/day) and 7 days placebo treatment, in a double-blind crossover design. Our functional magnetic resonance imaging task consisted of three phases; an anticipatory phase (pleasant or unpleasant cue), an effort phase (button presses to achieve a pleasant taste or to avoid an unpleasant taste) and a consummatory phase (pleasant or unpleasant tastes). Volunteers also rated wanting, pleasantness and intensity of the tastes.ResultsRelative to placebo, bupropion increased activity during the anticipation phase in the ventral medial prefrontal cortex (vmPFC) and caudate. During the effort phase, bupropion increased activity in the vmPFC, striatum, dorsal anterior cingulate cortex and primary motor cortex. Bupropion also increased medial orbitofrontal cortex, amygdala and ventral striatum activity during the consummatory phase.ConclusionsOur results are the first to show that bupropion can increase neural responses during the anticipation, effort and consummation of rewarding and aversive stimuli. This supports the notion that bupropion might be beneficial for depressed patients with reward-related deficits and blunted affect. [ABSTRACT FROM PUBLISHER]

Background and Objective: Complex Regional Pain Syndrome (CRPS) is a chronic pain condition, often triggered by trauma to a limb and characterized by sensory, motor, autonomic and trophic changes within the affected limb. Due to the multi-faceted nature of the condition there are a wide range of potential health outcome measures for use within CRPS related clinical trials. This aim of this systematic literature review was to identify which patient or health professional questionnaire format outcome measures have been used in CRPS specific clinical trials, and which of these have been developed specifically for use in CRPS populations. Information gained from this review will inform an international consortium project to define a Core Outcome measurement set for CRPS Clinical trials.Databases and Data Treatment: The electronic databases EMBASE, Medline, PsycInfo, CINAHL and LILACS were systematically searched from January 2000 until April 2014.Results: One hundred and four full text papers were obtained with 68 questionnaire outcome measures identified. Five of these outcome measures were validated for CRPS. Of those outcome measures used since 2000, those addressing physical functioning were most prevalent.Conclusions: Currently, CRPS clinical trials use a wide range of outcome measures making the potential to synthesize evidence problematic. There is no internationally agreed core measurement set. This diversity of outcome measures demonstrates a clear need for the development of a core measurement set to be used in CRPS clinical trials. [ABSTRACT FROM AUTHOR]

The importance of presentation and evaluation of economic data with regard to the cost effectiveness of a health care intervention are discussed. [ABSTRACT FROM AUTHOR]

Study Question: Does triiodothyronine (T3) regulate the secretion of angiogenic growth factors and cytokines by human decidual cells isolated from early pregnancy?Summary Answer: T3 modulates the secretion of specific angiogenic growth factors and cytokines, with different regulatory patterns observed amongst various isolated subpopulations of human decidual cells and with a distinct change between the first and second trimesters of pregnancy.What Is Known Already: Maternal thyroid dysfunction during early pregnancy is associated with complications of malplacentation including miscarriage and pre-eclampsia. T3 regulates the proliferation and apoptosis of fetal-derived trophoblasts, as well as promotes the invasive capability of extravillous trophoblasts (EVT). We hypothesize that T3 may also have a direct impact on human maternal-derived decidual cells, which are known to exert paracrine regulation upon trophoblast behaviour and vascular development at the uteroplacental interface.Study Design, Size, Duration: This laboratory-based study used human decidua from first (8-11 weeks; n = 18) and second (12-16 weeks; n = 12) trimester surgical terminations of apparently uncomplicated pregnancies.Participants/materials, Setting, Methods: Primary cultures of total decidual cells, and immunomagnetic bead-isolated populations of stromal-enriched (CD10+) and stromal-depleted (CD10-) cells, uterine natural killer cells (uNK cells; CD56+) and macrophages (CD14+) were assessed for thyroid hormone receptors and transporters by immunocytochemistry. Each cell population was treated with T3 (0, 1, 10, 100 nM) and assessments were made of cell viability (MTT assay) and angiogenic growth factor and cytokine secretion (immunomediated assay). The effect of decidual cell-conditioned media on EVT invasion through Matrigel(®) was evaluated.Main Results and the Role Of Chance: Immunocytochemistry showed the expression of thyroid hormone transporters (MCT8, MCT10) and receptors (TRα1, TRβ1) required for thyroid hormone-responsiveness in uNK cells and macrophages from the first trimester. The viability of total decidual cells and the different cell isolates were unaffected by T3 so changes in cell numbers could not account for any observed effects. In the first trimester, T3 decreased VEGF-A secretion by total decidual cells (P < 0.05) and increased angiopoietin-2 secretion by stromal-depleted cells (P < 0.05) but in the second trimester total decidual cells showed only increased angiogenin secretion (P < 0.05). In the first trimester, T3 reduced IL-10 secretion by total decidual cells (P < 0.05), and reduced granulocyte macrophage colony stimulating factor (P < 0.01), IL-8 (P < 0.05), IL-10 (P < 0.01), IL-1β (P < 0.05) and monocyte chemotactic protein -1 (P < 0.001) secretion by macrophages, but increased tumour necrosis factor-α secretion by stromal-depleted cells (P < 0.05) and increased IL-6 by uNK cells (P < 0.05). In contrast, in the second trimester T3 increased IL-10 secretion by total decidual cells (P < 0.01) but did not affect cytokine secretion by uNK cells and macrophages. Conditioned media from first trimester T3-treated total decidual cells and macrophages did not alter EVT invasion compared with untreated controls. Thus, treatment of decidual cells with T3 resulted in changes in both angiogenic growth factor and cytokine secretion in a cell type-specific and gestational age-dependent manner, with first trimester decidual macrophages being the most responsive to T3 treatment, but these changes in decidual cell secretome did not affect EVT invasion in vitro.Limitations, Reasons For Caution: Our results are based on in vitro findings and we cannot be certain if a similar response occurs in human pregnancy in vivo.Wider Implications Of the Findings: Optimal maternal thyroid hormone concentrations could play a critical role in maintaining a balanced inflammatory response in early pregnancy to prevent fetal immune rejection and promote normal placental development through the regulation of the secretion of critical cytokines and angiogenic growth factors by human decidual cells. Our data suggest that there is an ontogenically determined regulatory 'switch' in T3 responsiveness between the first and second trimesters, and support the notion that the timely and early correction of maternal thyroid dysfunction is critical in influencing pregnancy outcomes.Study Funding/competing Interest(s): This study is funded by Wellbeing of Women (RG/1082/09 to S.Y.C., M.D.K., J.A.F., L.S.L., G.E.L.) and Action Medical Research - Henry Smith Charity (SP4335 to M.D.K., S.Y.C., L.S.L., J.A.F.). The authors have no conflicts of interest to disclose. [ABSTRACT FROM AUTHOR]

The ability to match individual patients to tailored treatments has the potential to greatly improve outcomes for individuals suffering from major depression. In particular, while the vast majority of antidepressant treatments affect either serotonin or noradrenaline or a combination of these two neurotransmitters, it is not known whether there are particular patients or symptom profiles which respond preferentially to the potentiation of serotonin over noradrenaline or vice versa. Experimental medicine models suggest that the primary mode of action of these treatments may be to remediate negative biases in emotional processing. Such models may provide a useful framework for interrogating the specific actions of antidepressants. Here, we therefore review evidence from studies examining the effects of drugs which potentiate serotonin, noradrenaline or a combination of both neurotransmitters on emotional processing. These results suggest that antidepressants targeting serotonin and noradrenaline may have some specific actions on emotion and reward processing which could be used to improve tailoring of treatment or to understand the effects of dual-reuptake inhibition. Specifically, serotonin may be particularly important in alleviating distress symptoms, while noradrenaline may be especially relevant to anhedonia. The data reviewed here also suggest that noradrenergic-based treatments may have earlier effects on emotional memory that those which affect serotonin. [ABSTRACT FROM AUTHOR]

Background Unusual symptoms such as digit misidentification and neglect-like phenomena have been reported in complex regional pain syndrome ( CRPS), which we hypothesized could be explained by parietal lobe dysfunction. Methods Twenty-two patients with chronic CRPS attending an in-patient rehabilitation programme underwent standard neurological examination followed by clinical assessment of parietal lobe function and detailed sensory testing. Results Fifteen (68%) patients had evidence of parietal lobe dysfunction. Six (27%) subjects failed six or more test categories and demonstrated new clinical signs consistent with their parietal testing impairments, which were impacting significantly on activities of daily living. A higher incidence was noted in subjects with >1 limb involvement, CRPS affecting the dominant side and in left-handed subjects. Eighteen patients (82%) had mechanical allodynia covering 3-57.5% of the body surface area. Allochiria (unilateral tactile stimulation perceived only in the analogous location on the opposite limb), sensory extinction (concurrent bilateral tactile stimulation perceived only in one limb), referred sensations (unilateral tactile stimulation perceived concurrently in another discrete body area) and dysynchiria (unilateral non-noxious tactile stimulation perceived bilaterally as noxious) were present in some patients. Greater extent of body surface allodynia was correlated with worse parietal function (Spearman's rho = −0.674, p = 0.001). Conclusion In patients with chronic CRPS, detailed clinical examination may reveal parietal dysfunction, with severity relating to the extent of allodynia. [ABSTRACT FROM AUTHOR]

Complex regional pain syndrome (CRPS) is difficult to diagnose and is characterised by burning pain in one or more limbs. Treatment is palliative not curative and focuses on improving function. This requires patients to make long-term changes to their behaviour. As with all such regimens, adherence is often poor. This study explored the lived experience of 10 patients who had returned home after completing a two-week in-patient treatment programme. The interviews focused on how they coped with the transition from hospital to home, and on the things that they considered had facilitated or hindered this transition. Battling for Control was an overarching theme that connected the four superordinate themes: ‘Gaining Momentum’ that facilitated the implementation of treatment advice, ‘Distance from the pool of expertise’ that detailed the barriers to adherence experienced; ‘It helped me realise it was not all in my head’ that detailed a facilitative process, and the ‘nag list’ that was a technique patients’ used to garner support. This article offers insights into the transition experience. A key outcome is the recognition of the need to better prepare patients for their transition back home. [ABSTRACT FROM PUBLISHER]

Background There is good evidence from studies conducted in a single-centre research setting for the efficacy of graded motor imagery ( GMI) treatment, a complex physiotherapy intervention, to reduce pain in long-standing complex regional pain syndrome ( CRPS). However, whether GMI is effective in clinical practice is not established. Aim To establish whether GMI is effective in clinical practice. Methods We undertook a prospective audit of GMI treatment at two UK centres with a special interest in the management of patients with CRPS. All patients received GMI, in conjunction with a range of other 'best practice' physical and psychological interventions. Results The patients' average pain intensities did not improve with treatment [centre 1: n = 20, pre-post numeric rating scale ( NRS) difference 0.6 [confidence interval ( CI) −0.3 to 1.5]; centre 2: n = 12, pre-post NRS difference 0.2 ( CI: −0.9 to 1.2)]. Patients at centre 1 reported significant functional improvement. Improved performance on left/right judgement replicated in both centres seen in the clinical trials. Conclusions The failure of our real-world implementation of GMI suggests that better understanding of both the GMI methodology and its interaction with other treatment methods is required to ensure that GMI research results can be translated into clinical practice. Our results highlight challenges with the translation of complex interventions for chronic pain conditions into clinical practice. [ABSTRACT FROM AUTHOR]

Cortical reorganisation of sensory, motor and autonomic systems can lead to dysfunctional central integrative control. This may contribute to signs and symptoms of Complex Regional Pain Syndrome (CRPS), including pain. It has been hypothesised that central neuroplastic changes may cause afferent sensory feedback conflicts and produce pain. We investigated autonomic responses produced by ambiguous visual stimuli (AVS) in CRPS, and their relationship to pain. Thirty CRPS patients with upper limb involvement and 30 age and sex matched healthy controls had sympathetic autonomic function assessed using laser Doppler flowmetry of the finger pulp at baseline and while viewing a control figure or AVS. Compared to controls, there were diminished vasoconstrictor responses and a significant difference in the ratio of response between affected and unaffected limbs (symmetry ratio) to a deep breath and viewing AVS. While viewing visual stimuli, 33.5% of patients had asymmetric vasomotor responses and all healthy controls had a homologous symmetric pattern of response. Nineteen (61%) CRPS patients had enhanced pain within seconds of viewing the AVS. All the asymmetric vasomotor responses were in this group, and were not predictable from baseline autonomic function. Ten patients had accompanying dystonic reactions in their affected limb: 50% were in the asymmetric sub-group. In conclusion, there is a group of CRPS patients that demonstrate abnormal pain networks interacting with central somatomotor and autonomic integrational pathways. [ABSTRACT FROM AUTHOR]

Background: Multi-parameter genomic tests identify patients with early-stage breast cancer who are likely to derive little benefit from adjuvant chemotherapy. These tests can potentially spare patients the morbidity from unnecessary chemotherapy and reduce costs. However, the costs of the test must be balanced against the health benefits and cost savings produced. This economic evaluation compared genomic test-directed chemotherapy using the Oncotype DX 21-gene assay with chemotherapy for all eligible patients with lymph node-positive, estrogen receptor-positive early-stage breast cancer.Methods: We performed a cost-utility analysis using a state transition model to calculate expected costs and benefits over the lifetime of a cohort of women with estrogen receptor-positive lymph node-positive breast cancer from a UK perspective. Recurrence rates for Oncotype DX-selected risk groups were derived from parametric survival models fitted to data from the Southwest Oncology Group 8814 trial. The primary outcome was the incremental cost-effectiveness ratio, expressed as the cost (in 2011 GBP) per quality-adjusted life-year (QALY). Confidence in the incremental cost-effectiveness ratio was expressed as a probability of cost-effectiveness and was calculated using Monte Carlo simulation. Model parameters were varied deterministically and probabilistically in sensitivity analysis. Value of information analysis was used to rank priorities for further research.Results: The incremental cost-effectiveness ratio for Oncotype DX-directed chemotherapy using a recurrence score cutoff of 18 was £5529 (US $8852) per QALY. The probability that test-directed chemotherapy is cost-effective was 0.61 at a willingness-to-pay threshold of £30 000 per QALY. Results were sensitive to the recurrence rate, long-term anthracycline-related cardiac toxicity, quality of life, test cost, and the time horizon. The highest priority for further research identified by value of information analysis is the recurrence rate in test-selected subgroups.Conclusions: There is substantial uncertainty regarding the cost-effectiveness of Oncotype DX-directed chemotherapy. It is particularly important that future research studies to inform cost-effectiveness-based decisions collect long-term outcome data. [ABSTRACT FROM AUTHOR]

M cCABE C. & CRONIN P. (2010) European Journal of Cancer Care 20, 563-569 Issues for researchers to consider when using health-related quality of life outcomes in cancer research Maintaining quality of life for patients with cancer is a key factor when developing services related to diagnosis, treatment, recovery and/or terminal care. This paper questions whether health-related quality of life (HRQoL) is an appropriate measure of quality of life given that it does not assess factors reported by patients as being most influential, e.g. contact with family and social/cultural interaction. Ambiguity related to the definition and understanding of anxiety, depression and distress as outcomes commonly used by clinicians and researchers when measuring HRQoL in cancer research is also addressed by this paper. The findings of many cancer studies are interpreted and presented on very broad and poorly defined concepts thus preventing the development of a coherent and true understanding of how these outcomes influence quality of life for cancer patients. The authors of this paper conclude that the documentation and clear explanation of the concepts underpinning the choice of instrument and study design is essential but also the inclusion of outcomes related to social support and interaction would provide a more accurate account of quality of life issues in cancer research. [ABSTRACT FROM AUTHOR]

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All healthcare systems routinely make resource allocation decisions that trade off potential health gains to different patient populations. However, when such trade-offs relate to the introduction of new, promising health technologies, perceived 'winners' and 'losers' are more apparent. In recent years, public scrutiny over such decisions has intensified, raising the need to better understand how they are currently made and how they might be improved. The objective of this paper is to critically review and compare current processes for making health technology funding decisions at the regional, state/provincial and national level in 20 countries. A comprehensive search for published, peer-reviewed and grey literature describing actual national, state/provincial and regional/institutional technology decision-making processes was conducted. Information was extracted by two independent reviewers and tabulated to facilitate qualitative comparative analyses. To identify strengths and weaknesses of processes identified, websites of corresponding organizations were searched for commissioned reviews/evaluations, which were subsequently analysed using standard qualitative methods. A total of 21 national, four provincial/state and six regional/institutional-level processes were found. Although information on each one varied, they could be grouped into four sequential categories: (i) identification of the decision problem; (ii) information inputs; (iii) elements of the decision-making process; and (iv) public accountability and decision implementation. While information requirements of all processes appeared substantial and decision-making factors comprehensive, the way in which they were utilized was often unclear, as were approaches used to incorporate social values or equity arguments into decisions. A comprehensive inventory of approaches to implementing the four main components of all technology funding decision-making processes was compiled, from which areas for future work or research aimed at improving the acceptability of decisions were identified. They include the explication of decision criteria and social values underpinning processes. [ABSTRACT FROM AUTHOR]

Background: Trastuzumab has significantly improved survival outcomes for women with Human Epidermal growth factor Receptor 2 (HER2)-positive early breast cancer. Trastuzumab was established as a cost-effective adjuvant treatment in 2006. We present an updated cost-effectiveness analysis from the UK perspective, which explores assumptions about the duration of benefit from treatment, pattern of metastatic recurrence and long-term cardiac toxicity.Objective: The objective of this study was to calculate, from the UK NHS perspective, expected costs (year 2008 values) and benefits over the lifetime of an average cohort of women with HER2-positive early breast cancer treated with or without 1 year of adjuvant trastuzumab sequentially after chemotherapy.Methods: A cost-utility analysis was performed using a discrete-state time-dependent semi-Markov model. Probabilistic sensitivity analysis was used to characterize uncertainty around expected outcomes. Value-of-information (VOI) analysis was used to identify areas of priority for further research.Results: The cost-effectiveness estimates were highly sensitive to the estimated duration of treatment benefit. Trastuzumab remained a cost-effective treatment strategy at a willingness-to-pay threshold of £30,000 per QALY provided the duration of benefit was more than 3.6 years from treatment initiation, assuming the hazard ratio for disease-free survival was 0.63. An increasing proportion of brain metastases with trastuzumab produced a small change towards worse cost effectiveness. Long-term cardiac toxicity needed to rise to high levels to affect overall life expectancy and cost effectiveness. VOI analysis placed highest value on research into the duration of treatment benefit. The relationships between progression-free survival and overall survival and the costs of cancer recurrence were also important.Conclusion: The cost effectiveness of adjuvant trastuzumab remains uncertain and dependent on assumptions regarding its clinical effect. Uncertainty around cost effectiveness could be reduced by further research into the duration of treatment effect, particularly in subgroups where this may be shorter. Long-term follow-up is warranted and methods to accurately measure duration of treatment effect and late toxicities should be developed for future adjuvant drug studies. [ABSTRACT FROM AUTHOR]

Though largely controlled in developed countries, measles remains a major global public health issue. Regional and local transmission patterns are rooted in human mixing behaviour across spatial scales. Identifying spatial interactions that contribute to recurring epidemics helps define and predict outbreak patterns. Using spatially explicit reported cases from measles outbreaks in Niger, we explored how regional variations in movement and contact patterns relate to patterns of measles incidence. Because we expected to see lower rates of re-introductions in small, compared to large, populations, we measured the population-size corrected proportion of weeks with zero cases across districts to understand relative rates of measles re-introductions. We found that critical elements of spatial disease dynamics in Niger are agricultural seasonality, transnational contact clusters, and roads networks that facilitate host movement and connectivity. These results highlight the need to understand local patterns of seasonality, demographic characteristics, and spatial heterogeneities to inform vaccination policy. [ABSTRACT FROM AUTHOR]

Background: Treatment of long-standing complex regional pain syndrome (CRPS) is empirical and often of limited efficacy. Preliminary data suggest that the immune system is involved in sustaining this condition and that treatment with low-dose intravenous immunoglobulin (IVIG) may substantially reduce pain in some patients.Objective: To evaluate the efficacy of IVIG in patients with longstanding CRPS under randomized, controlled conditions.Design: A randomized, double-blind, placebo-controlled crossover trial. (National Research Registry number: N0263177713; International Standard Randomised Controlled Trial Number Registry: 63918259)Setting: University College London Hospitals Pain Management Centre.Patients: Persons who had pain intensity greater than 4 on an 11-point (0 to 10) numerical rating scale and had CRPS for 6 to 30 months that was refractory to standard treatment.Intervention: IVIG, 0.5 g/kg, and normal saline in separate treatments, divided by a washout period of at least 28 days.Measurements: The primary outcome was pain intensity 6 to 19 days after the initial treatment and the crossover treatment.Results: 13 eligible participants were randomly assigned between November 2005 and May 2008; 12 completed the trial. The average pain intensity was 1.55 units lower after IVIG treatment than after saline (95% CI, 1.29 to 1.82; P < 0.001). In 3 patients, pain intensity after IVIG was less than after saline by 50% or more. No serious adverse reactions were reported.Limitation: The trial was small, and recruitment bias and chance variation could have influenced results and their interpretation.Conclusion: IVIG, 0.5 g/kg, can reduce pain in refractory CRPS. Studies are required to determine the best immunoglobulin dose, the duration of effect, and when repeated treatments are needed.Primary Funding Source: Association of Anaesthetists of Great Britain and Ireland, University College London Hospitals Charity, and CSL-Behring. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine accurately the magnitude and changes of intra-cycle velocity fluctuation ( Vfluc), maximum ( Vmax) and minimum velocity ( Vmin) of the center of mass during a maximum 200 m frontcrawl swim, and to examine whether they are associated with performance. Performance was indicated by the mean velocity ( Vmean) of the stroke cycle (SC) in the swimming direction. The relative Vfluc, Vmax and Vmin were also calculated as a percentage of Vmean, while Vfluc was calculated for all three directions. Eleven male swimmers of national/international level participated in this study and their performance was recorded with four below- and two above-water-synchronized cameras. Four SCs were analyzed for the 200 m swim (one for each 50 m). Anthropometric data were calculated by the elliptical zone method. Vmean generally decreased throughout the test. Vmax and Vmin were positively correlated to performance and were significantly higher in SC1 than in the other SCs. However, the relative Vmax and Vmin values were remarkably consistent during the 200 m and not associated with performance. Despite the noteworthy magnitude of Vfluc in all directions, they were in general not correlated with performance and there were no significant changes during the test. [ABSTRACT FROM AUTHOR]

The Open Window project was established with the aim of creating a “virtual window” for each patient who is confined to protective isolation due to treatment for illness. This virtual window as developed provides a range of media or experiences. This paper describes the approach taken to the system design and discusses initial experiences with implementing such a system in a critical care setting. The system design was predicated on two guiding principles. Firstly it should be intuitive to use and the technology used to create the virtual window hidden from patient view. Secondly the system must be able to be installed at the point of care in a way that delivers the experience under the patient’s control, without compromising the function or safety of the clinical environment. Patient acceptance of the system is being measured as part of an on-going trial and at this interim phase of data analysis 100% (n=55) of participants in the intervention group have reported that the technology was easy to use. We conclude that the system as designed and installed is an effective, robust and reliable system upon which to base a multimedia interventions in a critical care room. [ABSTRACT FROM AUTHOR]

In healthcare, a tension sometimes arises between the injunction to do as much good as possible with scarce resources and the injunction to rescue identifiable individuals in immediate peril, regardless of cost (the "Rule of Rescue"). This tension can generate serious ethical and political difficulties for public policy makers faced with making explicit decisions about the public funding of controversial health technologies, such as costly new cancer drugs. In this paper we explore the appropriate role of the Rule of Rescue in public resource allocation decisions by health technology funding advisory bodies such as the National Institute for Health and Clinical Excellence. We consider practical approaches to operationalising the Rule of Rescue from Australia and the UK before examining the relevance of individual moral imperatives to public policy making. We conclude that that whilst public policy makers in a humane society should facilitate exceptional departures from a cost effectiveness norm in clinical decisions about identified individuals, it is not so obvious that they should, as a matter of national public policy, exempt any one group of unidentified individuals within society from the rules of opportunity cost at the expense of all others. [ABSTRACT FROM AUTHOR]

Selection experiments with Drosophila have revealed a possible evolutionary trade-off between cold resistance and starvation resistance that may be controlled by lipid metabolism. To test this trade-off in naturally occurring Drosophila simulans populations, flies were simultaneously collected from two temperate locales experiencing contrasting seasons. Flies from a tropical locale served as a control. Cold coma recovery, starvation resistance and lipid proportion were assayed on adult males and females from each locale. Compared with the summer-collected flies from Canberra, the winter-collected flies from San Diego recovered from cold coma more quickly, were less starvation resistant and had lower lipid levels. These results support an evolutionary trade-off between cold resistance and starvation resistance. Combined, these data also suggest that differences in lipid metabolism may be an underlying mechanism for this trade-off. [ABSTRACT FROM AUTHOR]

Consideration of quality-of-life issues by all members of the healthcare team is essential in caring for people with cancer. In cancer research, quality of life is generally classified as health-related quality of life or individual quality of life. This paper discusses the instruments used to measure quality-of-life outcomes, and the relevance of such findings for healthcare staff in planning and providing effective and patient-centred care. Visual analogue scales (VASs) and questionnaires are commonly used to measure quality of life; however, both types of instruments are criticized because the content may not be relevant to individual patients, and do not distinguish differences between statistical and clinical significances in the findings. Using a combination of questionnaires and VASs may overcome some of these criticisms. In order to interpret the difference between statistical and clinical significance of findings and the associated implications for patient care, a mixed-methods approach to data collection is recommended in quality-of-life studies. This provides meaning and understanding to the quantitative data and individual perspectives on patients' experiences of having cancer. Information from such studies may also be more effective in helping healthcare staff identify relevant issues when planning cancer care services at individual, local and national level. [ABSTRACT FROM AUTHOR]

Consideration of quality-of-life issues by all members of the healthcare team is essential in caring for people with cancer. In cancer research, quality of life is generally classified as health-related quality of life or individual quality of life. This paper discusses the instruments used to measure quality-of-life outcomes, and the relevance of such findings for healthcare staff in planning and providing effective and patient-centred care. Visual analogue scales (VASs) and questionnaires are commonly used to measure quality of life; however, both types of instruments are criticized because the content may not be relevant to individual patients, and do not distinguish differences between statistical and clinical significances in the findings. Using a combination of questionnaires and VASs may overcome some of these criticisms. In order to interpret the difference between statistical and clinical significance of findings and the associated implications for patient care, a mixed-methods approach to data collection is recommended in quality-of-life studies. This provides meaning and understanding to the quantitative data and individual perspectives on patients' experiences of having cancer. Information from such studies may also be more effective in helping healthcare staff identify relevant issues when planning cancer care services at individual, local and national level. [ABSTRACT FROM AUTHOR]

The key mitotic regulator securin is expressed at low levels in fetal brain compared with adult, and modulates the proliferation of human embryonic neuronal N-Tera2 (NT2) cells. We now examine the function and expression of securin's interacting partner separase, along with Rad21, the functional component of cohesin, which is cleaved by separase following interaction with securin. In contrast to securin, the cleaved forms of separase and Rad21 were highly expressed in human fetal cerebral cortex compared with adult. In a murine model of absent securin expression – the PTTG knock-out mouse – separase and Rad21 were over-expressed in multiple brain regions. In addition, cDNA array analysis of other key mitotic regulators additionally identified cyclin C and sestrin 2 to be induced in the brains of securin-null mice compared with wild type. Further, Rad21 mRNA expression was highly correlated with that of securin, separase, cyclin C and sestrin 2 in fetal brains. In embryonic neuronal NT2 cells, siRNA repression of separase failed to significantly alter cell turnover, whereas repression of securin expression resulted in increased levels of the activated forms of Rad21 and separase, and promoted cell proliferation. Our data suggest that the co-ordinated expression of separase, securin and Rad21 is fundamental for the developing brain. J. Cell. Physiol. 213: 45–53, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Objectives. Conflict between sensory–motor central nervous processing generates somaesthetic disturbances, including pain, in healthy volunteers (HVs). Such conflict has been proposed as a potential cause of pain that occurs in the absence of injury or when the pain response is disproportionate to the injury. Fibromyalgia (FMS) exemplifies the former state. We hypothesized that the artificial generation of such conflict would exacerbate somaesthetic perceptions including pain in FMS greater than in HVs. [ABSTRACT FROM PUBLISHER]

The ability of the thyroid to accumulate iodide provides the basis for radioiodine ablation of differentiated thyroid cancers and their metastases. Most thyroid tumours exhibit reduced iodide uptake, although the mechanisms accounting for this remain poorly understood. Pituitary tumour transforming gene (PTTG) is a proto-oncogene implicated in the pathogenesis of thyroid tumours. We now show that PTTG and its binding factor PBF repress expression of sodium iodide symporter (NIS) messenger RNA (mRNA), and inhibit iodide uptake. This process is mediated at least in part through fibroblast growth factor-2. In detailed studies of the NIS promoter in rat FRTL-5 cells, PTTG and PBF demonstrated specific inhibition of promoter activity via the human upstream enhancer element (hNUE). Within this ∼1 kb element, a complex PAX8-upstream stimulating factor 1 (USF1) response element proved critical both to basal promoter activity and to PTTG and PBF repression of NIS. In particular, repression by PTTG was contingent upon the USF1, but not the PAX8, site. Finally, in human primary thyroid cells, PTTG and PBF similarly repressed the NIS promoter via hNUE. Taken together, our data suggest that the reported overexpression of PTTG and PBF in differentiated thyroid cancer has profound implications for activity of the NIS gene, and hence significantly impacts upon the efficacy of radioiodine treatment.Oncogene (2007) 26, 4344–4356; doi:10.1038/sj.onc.1210221; published online 5 February 2007 [ABSTRACT FROM AUTHOR]

Polyhedral oligomeric silsesquioxane (POSS) molecules are unique nanometre-size inorganic/organic hybrid structures based on a (SiO1.5)8 core. Depending on the functionalization of the POSS cages, the resulting systems can be solid or liquid, or, upon crosslinking, turned into a network. While much is known experimentally about the chemical synthesis of POSS systems, very little theoretical understanding exists at the molecular level or beyond. Of particular interest is the study of the effect of tether groups on the thermodynamic properties and phase behaviour of POSS fluids, which is addressed in this work through both molecular simulation and the statistical associating fluid theory for potentials of variable attractive range (SAFT-VR). In this application of SAFT-VR to POSS molecules the hetero-SAFT-VR approach is used. The POSS cage is represented as a single sphere and the tether groups by one or more smaller spheres, depending on chain length. Since very limited experimental data is available for the thermodynamic properties of POSS systems, molecular dynamics simulations are used to obtain pseudo-experimental data with which to validate the theoretical approach. Good agreement is obtained between the simulation data and the theoretical results and predictions are made for systems yet to be studied by simulation or experiment. [ABSTRACT FROM AUTHOR]

Conventional cytopathology is an excellent tool for distinguishing benign from malignant thyroid nodules with high sensitivity and specificity. However, significant numbers of cases are indeterminate, resulting in many ultimately unnecessary diagnostic thyroidectomies. Numerous molecular markers have been studied in an attempt to improve the diagnostic accuracy of thyroid fine-needle aspiration cytology. Several markers, such as galectin-3 and thyroid peroxidase, have been extensively assessed and shown not only to differentiate malignant tumors from benign thyroid lesions with high sensitivity and specificity, but also to identify tumors associated with poor outcome. More recently, four other genes (PTTG, PBF, BRAF and MUC1) have been identified that show real promise as potential molecular markers in thyroid cancer, offering discrimination between tumor subtypes and providing valuable prognostic information. However, larger, well-controlled studies are needed before their introduction into routine clinical practice. The search for molecular markers represents one of the most exciting areas in translational thyroid cancer research. We are optimistic that molecular markers will be used in the near future as adjuncts to conventional histological techniques to improve diagnostic accuracy of fine-needle aspiration cytology for thyroid lesions, particularly those that are cytologically indeterminate. [ABSTRACT FROM AUTHOR]

Catherine McCabe and Fiona Timmins undertook a study of nurses' assertiveness skills, which suggests that nurse managers play a vital role in both inhibiting and encouraging nurses to be assertive. [ABSTRACT FROM AUTHOR]