Search

Significance There is no nonhormonal contraceptive pill for men, although hundreds of genes have been identified to play roles during spermatogenesis and fertilization in the male reproductive tract. To address the absence of contraceptive drugs for men, we established a DNA-encoded chemistry technology (DEC-Tec) platform. Our drug discovery campaign on BRDT, a validated spermatogenic-specific contraceptive target, yielded rapid discovery of potent and specific inhibitors of the second bromodomain of BRDT that have unique binding characteristics to BRDT-BD2 relative to BRDT-BD1. Our study emphasizes the robustness and validation of the DEC-Tec platform where the obtained structure–affinity relationship data would allow us to identify specific protein binders immediately without performing exhaustive medicinal chemistry optimization of compounds with potential as male contraceptives., Bromodomain testis (BRDT), a member of the bromodomain and extraterminal (BET) subfamily that includes the cancer targets BRD2, BRD3, and BRD4, is a validated contraceptive target. All BET subfamily members have two tandem bromodomains (BD1 and BD2). Knockout mice lacking BRDT-BD1 or both bromodomains are infertile. Treatment of mice with JQ1, a BET BD1/BD2 nonselective inhibitor with the highest affinity for BRD4, disrupts spermatogenesis and reduces sperm number and motility. To assess the contribution of each BRDT bromodomain, we screened our collection of DNA-encoded chemical libraries for BRDT-BD1 and BRDT-BD2 binders. High-enrichment hits were identified and resynthesized off-DNA and examined for their ability to compete with JQ1 in BRDT and BRD4 bromodomain AlphaScreen assays. These studies identified CDD-1102 as a selective BRDT-BD2 inhibitor with low nanomolar potency and >1,000-fold selectivity over BRDT-BD1. Structure–activity relationship studies of CDD-1102 produced a series of additional BRDT-BD2/BRD4-BD2 selective inhibitors, including CDD-1302, a truncated analog of CDD-1102 with similar activity, and CDD-1349, an analog with sixfold selectivity for BRDT-BD2 versus BRD4-BD2. BROMOscan bromodomain profiling confirmed the great affinity and selectivity of CDD-1102 and CDD-1302 on all BET BD2 versus BD1 with the highest affinity for BRDT-BD2. Cocrystals of BRDT-BD2 with CDD-1102 and CDD-1302 were determined at 2.27 and 1.90 Å resolution, respectively, and revealed BRDT-BD2 specific contacts that explain the high affinity and selectivity of these compounds. These BD2-specific compounds and their binding to BRDT-BD2 are unique compared with recent reports and enable further evaluation of their nonhormonal contraceptive potential in vitro and in vivo.

Objectives State-transition models (STMs) applied in oncology have given limited considerations to modeling postprogression survival data. This study presents an application of an STM focusing on methods to evaluate the postprogression transition and its impact on survival predictions. Methods Data from the lenalidomide plus dexamethasone arm of the ASPIRE trial was used to estimate transition rates for an STM. The model accounted for the competing risk between the progression and preprogression death events and included an explicit structural link between the time to progression and subsequent death. The modeled transition rates were used to simulate individual disease trajectories in a discrete event simulation framework, based on which progression-free survival and overall survival over a 30-year time horizon were estimated. Survival predictions were compared with the observed trial data, matched external data, and estimates obtained from a more conventional partitioned survival analysis approach. Results The rates of progression and preprogression death were modeled using piecewise exponential functions. The rate of postprogression mortality was modeled using an exponential function accounting for the nonlinear effect of the time to progression. The STM provided survival estimates that closely fitted the trial data and gave more plausible long-term survival predictions than the best-fitting Weibull model applied in a partitioned survival analysis. Conclusions The fit of the STM suggested that the modeled transition rates accurately captured the underlying disease process over the modeled time horizon. The considerations of this study may apply to other settings and facilitate a wider use of STMs in oncology.

Background: Sparse relative effectiveness evidence is a frequent problem in Health Technology Assessment (HTA). Where evidence directly pertaining to the decision problem is sparse, it may be feasible to expand the evidence-base to include studies that relate to the decision problem only indirectly: for instance, when there is no evidence on a comparator, evidence on other treatments of the same molecular class could be used; similarly, a decision on children may borrow-strength from evidence on adults. Usually, in HTA, such indirect evidence is either included by ignoring any differences (‘lumping‘) or not included at all (‘splitting‘). However, a range of more sophisticated methods exists, primarily in the biostatistics literature. The objective of this study is identify and classify the breadth of the available information-sharing methods. Methods: Forwards and backwards citation-mining techniques were used on a set of seminal papers on the topic of information-sharing. Papers were included if they specified (network) meta-analytic methods for combining information from distinct populations, interventions, outcomes or study-designs. Results: Overall, 89 papers were included. A plethora of evidence synthesis methods have been used for information-sharing. Most papers (n = 78) described methods that shared information on relative treatment effects. Amongst these, there was a strong emphasis on methods for information-sharing across multiple outcomes (n = 39) and treatments (n = 23), with fewer papers focusing on study-designs (n = 10) or populations (n = 6). We categorise and discuss the methods under four ’core’ relationships of information-sharing: functional, exchangeability-based, prior-based and multivariate relationships, and explain the assumptions made within each of these core approaches. Conclusions: This study highlights the range of information-sharing methods available. These methods often impose more moderate assumptions than lumping or splitting. Hence, the degree of information-sharing that they impose could potentially be considered more appropriate. Our identification of four ‘core‘ methods of information-sharing allows for an improved understanding of the assumptions underpinning the different methods. Further research is required to understand how the methods differ in terms of the strength of sharing they impose and the implications of this for health care decisions.

This chapter offers a collection of brief case studies to illustrate the application of coaching psychology within real-world settings. Topics covered include coaching and stress, mindful walk and talk, life and career planning, internal coaching within organisations, and equine-facilitated coaching. Each case study aims to set out the background context of the area and a summary example of coaching psychology within that setting.

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.

Objectives\ud \ud Partitioned survival models (PSMs) are routinely used to inform reimbursement decisions for oncology drugs. We discuss the appropriateness of PSMs compared to the most common alternative, state transition models (STMs).\ud \ud \ud \ud Methods\ud \ud In 2017, we published a National Institute for Health and Care Excellence (NICE) Technical Support Document (TSD 19) describing and critically reviewing PSMs. This article summarizes findings from TSD 19, reviews new evidence comparing PSMs and STMs, and reviews recent NICE appraisals to understand current practice.\ud \ud \ud \ud Results\ud \ud PSMs evaluate state membership differently from STMs and do not include a structural link between intermediate clinical endpoints (eg, disease progression) and survival. PSMs directly consider clinical trial endpoints and can be developed without access to individual patient data, but limit the scope for sensitivity analyses to explore clinical uncertainties in the extrapolation period. STMs facilitate these sensitivity analyses but require development of robust survival models for individual health-state transitions. Recent work has shown PSMs and STMs can produce substantively different survival extrapolations and that extrapolations from STMs are heavily influenced by specification of the underlying survival models. Recent NICE appraisals have not generally included both model types, reviewed individual clinical event data, or scrutinized life-years accrued in individual health states.\ud \ud \ud \ud Conclusions\ud \ud The credibility of survival predictions from PSMs and STMs, including life-years accrued in individual health states, should be assessed using trial data on individual clinical events, external data, and expert opinion. STMs should be used alongside PSMs to support assessment of clinical uncertainties in the extrapolation period, such as uncertainty in post-progression survival.

Reliably modelling the demographic and distributional responses of a species to environmental changes can be crucial for successful conservation and management planning. Process-based models have the potential to achieve this goal, but so far they remain underused for predictions of species’ distributions. Individual-based models offer the additional capability to model inter-individual variation and evolutionary dynamics and thus capture adaptive responses.We present RangeShiftR, an R package that provides flexible and fast simulations of spatial eco-evolutionary dynamics and species’ responses to environmental changes. It implements the individual-based simulation software RangeShifter for the widely used statistical programming platform R. The package features additional auxiliary functions to support model specification and analysis of results. We provide an outline of the package’s functionality, describe the underlying model structure with its main components and present a short example.RangeShiftR offers substantial model complexity, especially for the demographic and dispersal processes. It comes with comprehensive documentation and elaborate tutorials to provide a low entry level. Thanks to the implementation of the core code in C++, the computations are fast. The complete source code is published under a public licence, making adaptations and contributions feasible.The RangeShiftR package facilitates the application of individual-based and mechanistic modelling to eco-evolutionary questions by operating a flexible and powerful simulation model from R. It allows effortless interoperation with existing packages to create streamlined workflows that can include data preparation, integrated model specification, and results analysis. Moreover, the implementation in R strengthens the potential for coupling RangeShiftR with other models.

Background: For novel migraine therapies, economic evaluations will be required to understand the trade-offs between additional health benefit and additional cost. The purpose of this study was to conduct a systematic literature review (SLR) to identify previous economic evaluations in migraine from the United Kingdom or Irish perspective to critically appraise these evaluations and to propose, if necessary, a novel modelling approach that can be used for future economic evaluations of migraine therapies. Methods: An SLR was conducted to identify previous economic evaluations of preventive migraine treatments. Key opinion leaders were consulted to determine the criteria for a robust migraine economic evaluation. Economic evaluations identified in the SLR were appraised against these criteria, and a novel cost-effectiveness model structure was then proposed. Results: Eight records reporting on published economic evaluations were identified and critically appraised for general quality. Expert consultation provided 6 recommendations on the ideal model structure for migraine that is both clinically and economically meaningful. A decision-tree plus Markov structure was then developed as a cost-effectiveness model for migraine therapies where each health state is associated with a patient distribution across monthly migraine day (MMD) frequencies. Conclusions: Future migraine economic evaluations should allow for assessments across the full spectrum of migraine, a response-based stopping rule, and the estimation of benefits and resource costs based on MMD frequency. The approach proposed in this paper captures all of the desired elements for an economic evaluation of migraine therapy and is suitable to assess new migraine therapies.

The National Institute for Health and Care Excellence (NICE) is only one of several organisations internationally that uses economic evaluation as part of decision making regarding funding and pricing of new medical technologies. However, it can be argued that NICE has developed a more prominent international profile than most in their use of economics. After 20 years of operation, it is timely to assess the extent of NICE’s achievements, including the economic evaluation methods it has used and its willingness to adapt these as new evaluative approaches emerge and when NICE faces particular policy challenges. This paper considers some of the important policy and contextual developments in the UK over the last 20 years and how these may have shaped NICE’s approach to economic evaluation. It then assesses key areas of NICE methods, including perspective, defining benefits, modelling and uncertainty. The paper concludes that NICE has provided important support for the development of new methods, in particular through its role in identifying priorities for methods research funding and its sponsorship of the NICE Decision Support Unit. However, potentially important developments in methods in a number of important areas have yet to be formally included in NICE’s methods guidance and this should be addressed in the Institute’s 2019/2020 methods review.

This last decade has been marked by significant advances in the development of cell and gene (C&G) therapies, such as gene targeting or stem cell-based therapies. C&G therapies offer transformative benefits to patients but present a challenge to current health technology decision-making systems because they are typically reviewed when clinical efficacy data are very limited and when there is uncertainty about the long-term durability of outcomes. These challenges are not unique to C&G therapies, but they face more of these barriers, reflecting the need for adapting existing value assessment frameworks. Still, C&G therapies have the potential to be cost-effective even at very high price points. The impact on healthcare budgets will depend on the success rate of pipeline assets and on the extent to which C&G therapies will expand to wider pathologies beyond rare or ultra-rare diseases. Getting pricing and reimbursement models right is important for incentivising research and development investment while not jeopardising the sustainability of healthcare systems. Payers and manufacturers therefore need to acknowledge each other’s constraints—limitations in the evidence generation on the manufacturer side, budget considerations on the payer side—and embrace innovative thinking and approaches to ensure timely delivery of therapies to patients. Several experts in health technology assessment and clinical experts have worked together to produce this publication and identify methodological and policy options to improve the assessment of C&G therapies, and make it happen better, faster and sustainably in the coming years.

OBJECTIVE: To evaluate the cost-effectiveness of high-throughput, non-invasive prenatal testing (HT-NIPT) for fetal RhD genotype to guide antenatal prophylaxis with anti-D immunoglobulin compared to routine antenatal anti-D immunoglobulin prophylaxis (RAADP). DESIGN: Cost-effectiveness decision-analytic modelling. SETTING: Primary care. PARTICIPANTS: A simulated population of 100,000 RhD negative women not known to be sensitised to the RhD antigen. METHODS: A decision tree model was used to characterise the antenatal care pathway in England and the long-term consequences of sensitisation events. The diagnostic accuracy of HT-NIPT was derived from a systematic review and bivariate meta-analysis; estimates of other inputs were derived from relevant literature sources and databases. Women in whom the HT-NIPT was positive or inconclusive continued to receive RAADP, while women with a negative result received none. Five alternative strategies in which the use of HT-NIPT may affect the existing post-partum care pathway were considered. MAIN OUTCOME MEASURES: Costs expressed in 2015GBP and impact on health outcomes expressed in terms of quality adjusted life years (QALYs) over a lifetime. RESULTS: The results suggested that HT-NIPT appears cost saving but also less effective than current practice, irrespective of the post-partum strategy evaluated. A post-partum strategy in which inconclusive test results are distinguished from positive results performed best. HT-NIPT is only cost-effective when the overall test cost is £26.60 or less. CONCLUSIONS: HT-NIPT would reduce unnecessary treatment with routine anti-D immunoglobulin and is cost saving when compared to current practice. The extent of any savings and cost-effectiveness is sensitive to the overall test cost. This article is protected by copyright. All rights reserved.

Standard methods for indirect comparisons and network meta-analysis are based on aggregate data, with the key assumption that there is no difference between the trials in the distribution of effect-modifying variables. Methods which relax this assumption are becoming increasingly common for submissions to reimbursement agencies, such as the National Institute for Health and Care Excellence (NICE). These methods use individual patient data from a subset of trials to form population-adjusted indirect comparisons between treatments, in a specific target population. Recently proposed population adjustment methods include the Matching-Adjusted Indirect Comparison (MAIC) and the Simulated Treatment Comparison (STC). Despite increasing popularity, MAIC and STC remain largely untested. Furthermore, there is a lack of clarity about exactly how and when they should be applied in practice, and even whether the results are relevant to the decision problem. There is therefore a real and present risk that the assumptions being made in one submission to a reimbursement agency are fundamentally different to—or even incompatible with—the assumptions being made in another for the same indication. We describe the assumptions required for population-adjusted indirect comparisons, and demonstrate how these may be used to generate comparisons in any given target population. We distinguish between anchored and unanchored comparisons according to whether a common comparator arm is used or not. Unanchored comparisons make much stronger assumptions, which are widely regarded as infeasible. We provide recommendations on how and when population adjustment methods should be used, and the supporting analyses that are required to provide statistically valid, clinically meaningful, transparent and consistent results for the purposes of health technology appraisal. Simulation studies are needed to examine the properties of population adjustment methods and their robustness to breakdown of assumptions.

Decisions about the adoption of medical interventions are informed by evidence on their costs and effects. For a range of reasons, evidence relating to medical devices may be limited. The decision to adopt a device early in its life cycle when the evidence base is least mature may impact on the prospects of acquiring further evidence to reduce uncertainties. Equally, rejecting a device will result in no uptake in practice and hence no chance to learn about performance. Decision options such as 'only in research' or 'approval with research' can overcome these issues by allowing patients early access to promising new technologies while limiting the risks associated with making incorrect decisions until more evidence or learning is established. In this paper, we set out the issues relating to uncertainty and the value of research specific to devices: learning curve effects, incremental device innovation, investment and irrecoverable costs, and dynamic pricing. We show the circumstances under which an only in research or approval with research scheme may be an appropriate policy choice. We also consider how the value of additional research might be shared between the manufacturer and health sector to help inform who might reasonably be expected to conduct the research needed. © 2017 The Authors. Health Economics published by John Wiley & Sons, Ltd.

We appreciate the thoughtful commentary on our piece, “Partnering with patients to bridge the gap in consent for acute care research” (Dickert et al. 2020). We are encouraged by the support for the...

Purpose The purpose of this paper is to identify essential psychological-informed executive coaching approaches that enhance the organisational learning and development process and outcomes through integrating existing research evidence. Since coaching has been widely used in leadership development related areas and previous studies confirmed that this generates positive effects on individual-level learning in the organisational setting. The identified frameworks and influential factors outlined in this paper can serve as explicit guidelines for the organisation and management team when setting selection and evaluation benchmarks for employing executive coaches. Design/methodology/approach An integrated review approach was applied to narratively synthesise 234 (k=234) identified peer-review articles between 1995 and 2018. This review followed a rigorous protocol that the authors consulted ten (n=10) experts in the field. Both qualitative and quantitative psychological-focused research evidence was included in this study. Findings First, certain psychological approaches, such as cognitive behavioural, solution-focused, GROW and strength-based approaches, were highlighted in current research evidence. Second, the essential factors and skills, for instance, building trust, transparency and rapport, and facilitating learning were identified. Third, the main organisational learning and development outcome evaluation methods were outlined in this review, such as the self-efficacy scale, organisational commitment, workplace psychological well-being, 360-degree feedback and the Multifactor Leadership Questionnaire. Research limitations/implications It is always challenging to integrate research evidence on coaching because of the diversity of theoretical disciplines upon which coaching interventions draw. Therefore, it is difficult to generate a meta-analytic review which can generate statistical results. This review also reveals room for improvement in the quality of existing coaching evidence in accordance with the criteria for evidence-based management or practice (Briner et al., 2009), such as research methodology and evaluation design. Moreover, there is a lack of evidence on this reflective process which helps professional coaches to ensure the quality of their practice and organisational support. Practical implications This review offers a new perspective on the role psychology plays in the organisational learning and development practices. The identified coaching approaches, influential interpersonal skills and outcome evaluation methods can serve as practical guidelines when applying external coaching to facilitate a better organisational learning and development process and outcome. Originality/value This is the first literature review to focus on contemporary psychological-informed coaching evidence (between 1995 and 2018) in the workplace setting. Despite the rapid growth in demand for professional coaching practitioners (International Coach Federation, 2016), there is a lack of research-informed evidence to overcome the challenges faced by organisations when employing external coaches, such as what selection criteria or evaluation benchmarks to use. This review takes a practical perspective to identify essential body of knowledge and behavioural indicators required for an executive coach to facilitate an effective learning and development outcome.

Understanding the dynamics of socio-ecological systems is crucial to the development of environmentally sustainable practices. Models of social or ecological sub-systems have greatly enhanced such understanding, but at the risk of obscuring important feedbacks and emergent effects. Integrated modelling approaches have the potential to address this shortcoming by explicitly representing linked socio-ecological dynamics. We developed a socio-ecological system model by coupling an existing agent-based model of land-use dynamics and an individual-based model of demography and dispersal. A hypothetical case-study was established to simulate the interaction of crops and their pollinators in a changing agricultural landscape, initialised from a spatially random distribution of natural assets. The bi-directional coupled model predicted larger changes in crop yield and pollinator populations than a unidirectional uncoupled version. The spatial properties of the system also differed, the coupled version revealing the emergence of spatial land-use clusters that neither supported nor required pollinators. These findings suggest that important dynamics may be missed by uncoupled modelling approaches, but that these can be captured through the combination of currently-available, compatible model frameworks. Such model integrations are required to further fundamental understanding of socio-ecological dynamics and thus improve management of socio-ecological systems.

In economic evaluations in oncology, adjusted survival should be generated if imbalances in prognostic/predictive factors across treatment arms are present. To date, no formal guidance has been developed regarding how such adjustments should be made. We compared various covariate-adjusted survival modeling approaches, as applied to the ENDEAVOR trial in multiple myeloma that assessed carfilzomib plus dexamethasone (Cd) versus bortezomib plus dexamethasone (Vd). Overall survival (OS) data and baseline characteristics were used for a subgroup (bortezomib-naive/one prior therapy). Four adjusted survival modeling approaches were compared: propensity score weighting followed by fitting a Weibull model to the two arms of the balanced data (weighted data approach); fitting a multiple Weibull regression model including prognostic/predictive covariates to the two arms to predict survival using the mean value of each covariate and using the average of patient-specific survival predictions; and applying an adjusted hazard ratio (HR) derived from a Cox proportional hazard model to the baseline risk estimated for Vd. The mean OS estimated by the weighted data approach was 6.85 years (95% confidence interval [CI] 4.62–10.70) for Cd, 4.68 years (95% CI 3.46–6.74) for Vd, and 2.17 years (95% CI 0.18–5.06) for the difference. Although other approaches estimated similar differences, using the mean value of covariates appeared to yield skewed survival estimates (mean OS was 7.65 years for Cd and 5.40 years for Vd), using the average of individual predictions had limited external validity (implausible long-term OS predictions with > 10% of the Vd population alive after 30 years), and using the adjusted HR approach overestimated uncertainty (difference in mean OS was 2.03, 95% CI − 0.17 to 6.19). Adjusted survival modeling based on weighted or matched data approaches provides a flexible and robust method to correct for covariate imbalances in economic evaluations. The conclusions of our study may be generalizable to other settings. ClinicalTrials.gov identifier NCT01568866 (ENDEAVOR trial).

Background: Escaping from emotional pain is a recognized driver in suicidal patients' desire to die. Formal scales of emotional pain are rarely used during routine contact between patients and their care team. No study has explored facilitators and inhibitors of emotional pain communication between staff and suicidal patients during regular care. Aims: To identify factors impeding or facilitating emotional pain communication between patients at risk of suicide and mental health professionals. Method: Nine patients with a history of a medically serious suicide attempt and 26 mental health (NHS) staff participated in individualized and focus group interviews, respectively. Results: A typological model was created, describing how patients either speak out or inhibit communication, and professionals may hear the communication or fail to do so. Four permutations are possible: unspoken/unheard, spoken/unheard, spoken/heard, and unspoken/heard. We found 14 subthemes of impediments and facilitators, which include misaligned, alienated and, co-bearing. Limitations: No male patients participated. Conclusion: Numerous factors influence whether emotional pain communication is responded to, missed, or ignored. Patients may try more than one way to communicate. Some patients fear that being able to speak out results in their emotional pain being taken less seriously. Knowledge of this model should improve the care of suicidal patients.

The interacting impacts of habitat fragmentation and climate change present a substantial threat for biodiversity, constituting a ‘deadly anthropogenic cocktail’. A range of conservation actions has been proposed to allow biodiversity to respond to those environmental changes. However, determining the relative effectiveness of these actions has been hampered by incomplete evidence. Empirical studies have provided important insights to inform conservation, but the challenge of considering multiple actions at large spatial and temporal scales is considerable. We adopt an individual-based modelling approach to qualitatively assess the effectiveness of alternative conservation actions in facilitating range expansion and patch occupancy for eight virtual species. We test actions to: (i) improve the quality of existing habitat patches, (ii) increase the permeability of the surrounding matrix, (iii) restore degraded habitat, (iv) create new habitat patches to form stepping-stones or (v) create new habitat to enlarge existing habitat patches. These actions are systematically applied to six real landscapes of the UK, which differ in their degree of habitat fragmentation and availability. Creating new habitat close to existing patches typically provides the strongest benefits for both range expansion and patch occupancy across species and landscapes. However, some landscapes may be so degraded that even under unrealistically high levels of management action, species' performances cannot be rescued. We identify that it is possible to develop a triage of conservation actions at the landscape, species and investment level, thereby providing timely evidence to inform action on the ground to lessen the hangover from the deadly anthropogenic cocktail.

Aim We still lack a comprehensive understanding of the relative importance of demographic, dispersal and landscape characteristics on species’ rates of range expansion (RRE) and on how these factors interact. Here, we provide an analysis of these effects for passive dispersers, by investigating how habitat characteristics, such as habitat quality, availability and fragmentation, interplay with species’ dispersal characteristics in determining species’ RRE. In addition, we assessed the predictability of RRE in cases where we have the knowledge of a species’ demography, dispersal and habitat availability. Methods Using the newly available individual-based modelling platform, RangeShifter we simulated the range expansion of species with different dispersal abilities, by varying mean dispersal distance and number of emigrants, on various landscapes. Landscapes varied in habitat quality (in terms of carrying capacity and species’ growth rates) and in habitat availability (in terms of the proportion of suitable habitat and its degree of fragmentation). Results Our results show that 55% of the total variation in RRE was explained by our six main effects, being considerably faster in landscapes with more suitable habitat, but only slightly affected by the degree of habitat fragmentation. Also, synergies between the amount of suitable habitat and species dispersal characteristics had significant positive effects on range expansion. Notably, however, 33% of variation in RRE was not explained by any of the tested factors or interactions between them and can be considered inherent and irreducible uncertainty. Main conclusions Simulation-based approaches provide important insights into the drivers of RRE that are relevant for conservation planning. For instance, our results indicate when it is likely to be better to allocate resources to improve existing habitat rather than creating new habitat, and vice versa. Additionally, our results emphasize that there will often be substantial uncertainty in the RRE, which needs to be taken into account for ecological management.

Background: The value of evidence about the performance of a technology and the value of access to a technology are central to policy decisions regarding coverage with, without, or only in research and managed entry (or risk-sharing) agreements. Objectives: We aim to outline the key principles of what assessments are needed to inform "only in research" (OIR) or "approval with research" (AWR) recommendations, in addition to approval or rejection. Methods: We developed a comprehensive algorithm to inform the sequence of assessments and judgments that lead to different types of guidance: OIR, AWR, Approve, or Reject. This algorithm identifies the order in which assessments might be made, how similar guidance might be arrived at through different combinations of considerations, and when guidance might change. Results: The key principles are whether the technology is expected to be cost-effective; whether the technology has significant irrecoverable costs; whether additional research is needed; whether research is possible with approval and whether there are opportunity costs that once committed by approval cannot be recovered; and whether there are effective price reductions. Determining expected cost-effectiveness is only a first step. In addition to AWR for technologies expected to be cost-effective and OIR for those not expected to be cost-effective, there are other important circumstances when OIR should be considered. Conclusions: These principles demonstrate that cost-effectiveness is a necessary but not sufficient condition for approval. Even when research is possible with approval, OIR may be appropriate when a technology is expected to be cost-effective due to significant irrecoverable costs. The Medical Research Council and the National Institute for Health Research Health Technology Assessment (NIHR HTA) program (project no. 06/90/99).

Introduction:National survey data from the US suggests that over the last decade there has been a growing crisis in confidence in business and political leadership, which is possibly one reason for the increased scientific research into the emerging field of Authentic Leadership – AL. Much evidence is starting to accumulate into both a conceptualisation of AL and its potential organisational benefits. However, what seems slow to follow is a scientific approach to Authentic Leadership Development – ALD. This study reports on the efficacy of one particular form of ALD, namely authentic leadership group-coaching.Design:Five 3-month long group-coaching interventions were run over a period of two years and a repeated measures design was employed to evaluate whether these AL coaching groups had an impact on the scores of two scientifically validated AL measures; the Authentic Leadership Questionnaire (ALQ) and the Authentic Leadership Inventory (ALI).Results:Analysis of the ALQ and ALI results found significant differences in the scores of both of these instruments. ALQ: t(24)=2.83, pConclusion:It was therefore concluded that the relatively short-term Authentic Leadership coaching group is an effective form of Authentic Leadership Development.

This paper describes the process of adapting a face to face cognitive behavioural coaching (CBC) model, PRACTICE (Palmer, 2011), into a virtual self-coaching programme and presents the results from a pilot study concerning the usability of the programme. There are a lack of studies regarding effects of assisted and non-assisted cognitive behavioural virtual coaching programmes in the workplace. With the increasing public health focus on wellbeing and prevention of mental illness, coaching psychology (rather than psychotherapy) could play an important role. Virtual coaching programmes accessible on company intranets may take a preventive role and provide cost-effective ways to reach larger work populations. They may lower the threshold for seeking further assistance with issues at work that potentially, if not detected and handled, could lead to decreased wellbeing. The intervention group consisted of nine participants and the results suggested that the software/programme design/method were user-friendly. The results further indicated that post-test scores were higher than pre-test scores concerning wellbeing and goal attainment after the six-week self-coaching programme. The pilot study was however limited by a small sample size and the results should therefore be interpreted merely as indications. The primary conclusions drawn from this study were that the results suggested that the programme’s self-coaching and goal attainment process were designed in a methodical and user friendly way.

Introduction:It is suggested that authentic leaders can be distinguished by four self-related characteristics: ‘the salience of the leadership role in their self-concept, the level of self-concept clarity, the extent to which their goals are self-concordant, and the degree to which their behaviour is consistent with their self-concept’ (Shamir & Eilam, 2005, p.399). The aim of this research was to establish if and how authentic leadership group-coaching impacts a leader’s self-concept and self-concept clarity.Design:25 senior leaders participated in one of five authentic leadership coaching groups run over a two-year period. Each group met one day a month over three months to discuss how their past/present/future domains influence their leadership practice. The Self-Concept Clarity Scale (Campbell, Trapnell, Heine, Katz, Lavalle & Lehman, 1996) was administered at the beginning of day one and at the end of day three to see if there was any difference between pre-coaching and post-coaching scores.Results:Paired sample t-tests were conducted on the questionnaire data and results showed both statistical significance (pConclusion:This paper considers the relevance of the self-concept in the context of authentic leadership development and the results suggest that authentic leadership group-coaching works at a sufficiently deep level to increase participant’s self-concept-clarity. It examines how group-coaching can help individual’s achieve a greater clarity of their self-concept and proposes a combination of social psychology theories to explain why this group format may be so effective.

Sophie Cooper, Jacoline Bouvy and colleagues discuss the challenges that histology independent cancer drugs will pose for NICE and the NHS

Stress, resilience, health and wellbeing coaching have been described as speciality or niche areas of coaching with the shared aim of helping coachees achieve their health-related goals (Palmer, Tubbs, & Whybrow, 2003; Palmer, 2004). Coaching psychology has a significant contribution to make to this field of work. Underpinning the traditional health educational approach with psychological theories and models has been found to increase the likelihood that the individual will achieve and maintain the desired change (Palmer et al., 2003; Wolever et al., 2013).

Compassion Focused Coaching (CFC) is an integrated approach to coaching that draws upon numerous branches of science including evolutionary psychology, neuroscience, attachment theory, developmental psychology and social psychology. It aims to help individuals, groups and organisations become more aware of and skillful in engaging with difficulties, distress and suffering and in finding ways to alleviate difficulties and promote growth.

The coaching relationship is a fundamental and to some the foundational factor of coaching. Whilst various conceptual coaching approaches construe the nature and role of the coaching relationship differently, the importance of an effective working relationship between coachee and coach is a coaching prerequisite. The growing evidence for coaching as an effective interpersonal change process has been accompanied by a noticeable shift in emphasis from the earlier question of “Does coaching work?” to that of “How does coaching work?” Partly reflecting this shift, the coaching relationship has garnered greater interest and research attention in the past decade.