2,311 research outputs found
The influence of prior training on GPs’ attitudes to sickness absence certification post-fit note.
AimTo investigate the attitudes to health and work of general practitioners (GPs) with training in occupational medicine (OM) compared with non-OM trained GPs, since the introduction of the fit note.BackgroundChanges to the UK sickness certification system since 2010 and the introduction of the fit note required GPs to change their focus to what patients can do, rather than what they cannot do in relation to work. In an effort to reduce the UK sickness absence burden, GPs completion of the fit note should help to keep people in work, or assist patients to return to work as quickly as possible after a period of absence.MethodsQuestionnaire data were collected via the 7th National General Practitioner Worklife Survey.FindingsResults indicate that responses from GPs who had undertaken training in OM, and GPs having received some form of work and health training in the 12-month period before the study were associated with significantly more positive attitudes to patients’ returning to work and to the fit note. This study reveals evidence of a difference between trained and non-trained GPs in their attitude to the fit note, and to work and health generally. Further work investigating the effect of specific training in OM on the management and recognition of ill-health by GPs is recommended.</jats:sec
Supplementary information on early-stage floating offshore wind platform designs
This document serves as supplementary information to the authors' review paper on early-stage floating offshore wind turbine (FOWT) platform designs. The review paper is the second part in a study on FOWT platform designs, following a review of FOWT platforms which currently have or have previously had a prototype, demonstration, or farm scale project at-sea. The present review covers 86 past and current early-stage platform designs, ranging from early conceptual designs to platforms which have undergone lab tests simulating extreme conditions. In this supplementary information document, more details are provided about all 86 platforms reviewed. For each device, the following is included (if available): (i) a description of the platform and its unique features, (ii) a rough timeline of development, (iii) design goals and constraints, (iv) evolution of the design, (v) lab testing information, and (vi) published dimensions. Two sections are included: one section contains the platforms that are no longer in development (i.e., there has been no new development since 2018), and the other section contains the platforms still in development today. Within each sub-section, platforms designed to hold a single turbine are presented first, then platforms designed to hold multiple turbines, and finally hybrid platforms
Actions of Octocoral and Tobacco Cembranoids on Nicotinic Receptors
Nicotinic acetylcholine receptors (AChRs) are pentameric proteins that form agonist-gated cation channels through the plasma membrane. AChR agonists and antagonists are potential candidates for the treatment of neurodegenerative diseases. Cembranoids are naturally occurring diterpenoids that contain a 14-carbon ring. These diterpenoids interact with AChRs in complex ways: as irreversible inhibitors at the agonist sites, as noncompetitive inhibitors, or as positive modulators, but no cembranoid was ever shown to have agonistic activity on AChRs. The cembranoid eupalmerin acetate displays positive modulation of agonist-induced currents in the muscle-type AChR and in the related gamma-aminobutyric acid (GABA) type A receptor. Moreover, cembranoids display important biological effects, many of them mediated by nicotinic receptors. Cembranoids from tobacco are neuroprotective through a nicotinic anti-apoptotic mechanism preventing excitotoxic neuronal death which in part could result from anti-inflammatory properties of cembranoids. Moreover, tobacco cembranoids also have anti-inflammatory properties which could enhance their neuroprotective properties. Cembranoids from tobacco affect nicotine-related behavior: they increase the transient initial ataxia caused by first nicotine injection into naive rats and inhibit the expression of locomotor sensitization to repeated injections of nicotine. In addition, cembranoids are known to act as antitumor compounds. In conclusion, cembranoids provide a promising source of lead drugs for many clinical areas, including neuroprotection, smoking-cessation, and anti-cancer therapies
Model-Based Prediction of the Patient-Specific Response to Adrenaline
A model for the cardiovascular and circulatory systems has previously been validated in simulated cardiac and circulatory disease states. It has also been shown to accurately capture the main hemodynamic trends in porcine models of pulmonary embolism and PEEP (positive end-expiratory pressure) titrations at different volemic levels. In this research, the existing model and parameter identification process are used to study the effect of different adrenaline doses in healthy and critically ill patient populations, and to develop a means of predicting the hemodynamic response to adrenaline. The hemodynamic effects on arterial blood pressures and stroke volume (cardiac index) are simulated in the model and adrenaline-specific parameters are identified. The dose dependent changes in these parameters are then related to adrenaline dose using data from studies published in the literature. These relationships are then used to predict the future, patient-specific response to a change in dose or over time periods from 1-12 hours. The results are compared to data from 3 published adrenaline dosing studies comprising a total of 37 data sets. Absolute percentage errors for the identified model are within 10% when re-simulated and compared to clinical data for all cases. All identified parameter trends match clinically expected changes. Absolute percentage errors for the predicted hemodynamic responses (N=15) are also within 10% when re-simulated and compared to clinical data. Clinically accurate prediction of the effect of inotropic circulatory support drugs, such as adrenaline, offers significant potential for this type of model-based application. Overall, this work represents a further clinical, proof of concept, of the underlying fundamental mathematical model, methods and approach, as well as providing a template for using the model in clinical titration of adrenaline in a decision support role in critical care. They are thus a further justification in support of upcoming human clinical trials to validate this model
Thr 163 Phosphorylation Causes Mcl-1 Stabilization when Degradation is Independent of the Adjacent GSK3-Targeted Phosphodegron, Promoting Drug Resistance in Cancer
The antiapoptotic Bcl-2 family member Mcl-1 is a PEST protein (containing sequences enriched in proline, glutamic acid, serine, and threonine) and is subject to rapid degradation via multiple pathways. Impaired degradation leading to the maintenance of Mcl-1 expression is an important determinant of drug resistance in cancer. Phosphorylation at Thr 163 in the PEST region, stimulated by 12-O-tetradecanoylphorbol acetic acid (TPA)-induced activation of extracellular signal-regulated kinase (ERK), is associated with Mcl-1 stabilization in BL41-3 Burkitt lymphoma cells. This contrasts with the observation that Thr 163 phosphorylation in normal fibroblasts primes glycogen synthase kinase (GSK3)-induced phosphorylation at Ser 159, producing a phosphodegron that targets Mcl-1 for degradation. In the present follow-up studies in BL41-3 cells, Mcl-1 degradation was found to be independent of the GSK3-mediated pathway, providing a parallel to emerging findings showing that Mcl-1 degradation through this pathway is lost in many different types of cancer. Findings in Mcl-1-transfected CHO cells corroborated those in BL41-3 cells in that the GSK3-targeted phosphodegron did not play a major role in Mcl-1 degradation, and a phosphomimetic T163E mutation resulted in marked Mcl-1 stabilization. TPA-treated BL41-3 cells, in addition to exhibiting Thr 163 phosphorylation and Mcl-1 stabilization, exhibited an ∼10-fold increase in resistance to multiple chemotherapeutic agents, including Ara-C, etoposide, vinblastine, or cisplatin. In these cancer cells in which Mcl-1 degradation is not dependent on the GSK3/phosphodegron-targeted pathway, ERK activation and Thr 163 phosphorylation are associated with pronounced Mcl-1 stabilization and drug resistance – effects that can be suppressed by inhibition of ERK activation
Improving trial recruitment through improved communication about patient and public involvement : an embedded cluster randomised recruitment trial
Background: Evidence is emerging that patient and public involvement in research (PPIR) may improve recruitment into randomised controlled trials, but the best methods to achieve improvement are unclear. Although many trials use PPIR to improve design and conduct, many do not communicate their use of PPIR clearly to potential participants. Directly communicating PPIR might encourage participation through increased patient confidence and trust in a trial. We aimed to develop and evaluate the impact on recruitment an intervention communicating PPIR in a trial to potential participants. Methods: This study was embedded in EQUIP, a cluster randomised controlled trial which allocated mental health teams in England to either a training intervention group to improve service user and carer involvement in care planning, or to a control group (no training). We conducted a cluster randomised trial of a recruitment intervention communicating PPIR, embedded within the EQUIP trial. The principles underlying the intervention were informed by a systematic review and a workshop that included mental health service users and trialists. Working with EQUIP PPIR partners (service users and carers) we developed the intervention using a leaflet to advertise the nature and function of the PPIR. Professional graphic design optimised readability and impact. Patients identified as potentially eligible for EQUIP were randomised to receive the leaflet or not, alongside the standard trial information. The primary outcome was the proportion of participants enrolled in EQUIP. The secondary outcome was the proportion expressing interest in taking part. Results: 34 clusters (mental health teams) were recruited, and 8182 potential participants were randomised. Preliminary analyses show that for the primary outcome, 4% of patients receiving the PPIR leaflet were enrolled vs. 5.3% in the control group. For the secondary outcome 7.3% of potential participants receiving the PPIR leaflet responded positively to the invitation to participate, vs. 7.9% in the control group. Future analyses will be by intention-to-treat and use logistic regression to estimate between-group odds ratios (ORs) and corresponding 95% confidence intervals. A planned secondary analysis will explore whether the impact of the intervention is moderated by age and gender. Conclusion: In preliminary analysis of this large trial, communicating PPIR demonstrated no benefits for improving the numbers of potential participants expressing interest in the trial, and reduced trial enrolment. Our findings contrast with the literature suggesting PPIR benefits recruitment. We will discuss the potential reasons for this finding, along with implications for future recruitment practice and research
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