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Purpose: We present long-term outcomes from a phase 3 randomized controlled trial that compared helical tomotherapy with 3-dimensional conformal radiation therapy (3D-CRT) in the treatment of high-risk prostate cancer., Methods and Materials: Newly diagnosed patients with high-risk prostate cancer were randomly allocated to receive radical radiation therapy (RT) using 3D-CRT or helical tomotherapy. In both arms, patients received an initial dose of 46 Gy in 23 fractions to the prostate and pelvic lymph nodes, followed by an additional boost to the prostate of 32 Gy in 16 fractions. RT was combined with 3 years of adjuvant androgen deprivation. The primary endpoint was late (>90 days since RT initiation) rectal toxicity., Results: Overall,123 patients were randomly assigned to either the 3D-CRT (n = 60) or tomotherapy (n = 63) arms. The median follow-up was 161 months. Overall, the proportion of patients with grade ≥ 2 late rectal toxicity was 8.3% (95% CI, 3.1-19.1; n = 5) in the 3D-CRT arm and 11.1% (95% CI, 5.0-22.2; n = 7) in the tomotherapy arm with no significant between-arm difference (P = .83). There was no significant difference (P = .17) in the proportion of patients with late grade ≥ 2 genitourinary toxicity:10.0% (95% CI, 4.1-21.2) in the 3D-CRT arm and 20.6% (95% CI, 11.9-33.0) in the tomotherapy arm. There was no significant difference in the hazard of biochemical progression or death between the 2 groups (hazard ratio for the tomotherapy arm: 0.72; 95% CI, 0.46-1.15; P = .17)., Conclusions: In this phase 3 trial, the overall incidence of grade ≥ 2 rectal toxicity was low and was not significantly different between the 2 arms. There was no significant evidence of improved biochemical progression-free survival in patients treated with tomotherapy. These findings should be interpreted considering the possibility of type II errors due to limited sample size and low event rates., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Purpose: The number of older people in prisons is increasing across the globe. Many have poor physical and mental health, higher prevalence of head injury, cognitive impairment and dementia than found in community populations. Meeting the complex needs of this vulnerable group has become an increasing concern for prison and prison healthcare services. The aim of this multi method qualitative study was to investigate how men with diagnosed or suspected dementia were identified, assessed, and cared for in Scottish prisons. It also explored the lived experience of individuals being assessed for or diagnosed with dementia within four prisons. The data from twenty nine interviews was thematically analysed and used to collaboratively propose principles for dementia care in prison and present the resultant co-designed care pathway., Results: At the time of data collection almost all the men known to have a dementia diagnosis or suspected dementia had complex health and social care needs, and some were living with advanced dementia. Prison healthcare staff reported taking a 'case by case' approach to their pre- and post-diagnostic care. Meeting these prisoner's needs was complicated by the absence of organisational leads for care of older adults or people with dementia and there was no pathway or model in place to guide staff. Prison healthcare teams often had difficulty accessing specialist community services to support diagnosis. There was a lack of dementia education and knowledge about how to provide pre and post diagnostic dementia care in this setting amongst staff. The findings arising from this research have informed the co-production of two important evidence informed innovations namely a Model of Care and a pre- and post-diagnostic Care Pathway., Conclusion: This research adds insights critical to understanding the adequacy of current approaches to meeting dementia related needs within the prison setting. To our knowledge this paper offers the first co-produced evidence informed pre- and post- diagnostic dementia care pathway and model of care for use in prisons. These could serve as tools for change that could enable prison healthcare staff to deliver the right care, at the right time, by the right people, and provide an opportunity to assess risk and plan care for the future., (© 2024. The Author(s).)

Background/objectives: The importance of family carer dementia education is highlighted in research, practice guidance, and policy. Less attention is paid to how facilitators learn and prepare for their role. This research aimed to explore and describe facilitator learning experiences within a bespoke Scottish Carers' Academy designed around a theory-guided approach called Care Empathia. A healthcare and university partnership ensured integration with services and the fusion of dementia higher education know-how with clinical practice expertise., Methods: Nineteen facilitator questionnaires were completed from two Carer Academy hubs; thirteen participated in online focus groups., Results: The questionnaire findings highlighted the learning gained from being a facilitator, observing expert facilitators in action, and listening to the testimonies of family carers. The framework analysis of the focus group data identified six themes, including safe learning approaches, the art of facilitation, emotional work, team learning, and leadership. These findings highlight the importance of facilitator preparation and the advantages of co-delivery models that combine clinical and practice education expertise., Conclusion: Facilitators need to understand how to walk the talk of theory-guided educational models, be open to reciprocity in learning, and be prepared for the emotional work of delivering trauma-informed practical dementia care education to family carers.

Introduction: Anti-osteoclast treatment with denosumab or zoledronate is known to effectively reduce the need for radiotherapy to bone and other skeletal-related events (SREs) in patients with metastatic castration-resistant prostate cancer (mCRPC). In this study, we analyze primary versus secondary initiation of bone-targeting agents (BTAs) relative to first palliative bone radiotherapy in patients dying of mCRPC., Methods: Provincial administrative databases from Ontario, Canada identified patients with prostate cancer (2007-2018, n = 98 646) who received continuous androgen deprivation therapy (n = 29 453), died of prostate cancer (2013-2018, n = 3864), and received life-prolonging therapy for mCRPC (n = 1850). Variables were collected looking back 3 years from death. Multivariable analysis explored the relationship between clinical variables and BTAs., Results: Of the 58% (1066/1850) patients with mCRPC who received BTA, only 289 (25.4%) started BTA prior to first palliative bone radiotherapy as primary prevention. Eight hundred and forty-eight (74.6%) patients either never received BTA before death (n = 447) or started BTA only after first bone radiotherapy (n = 401). More patients received denosumab (n = 825, 77%) than zoledronic acid (n = 241, 23%). 51.2% (582/1137) of palliative bone radiotherapy was initiated in the last 12 months of life. Factors associated with the use of BTA included elevated alkaline phosphatase (OR = 1.0, P = .023), de novo metastases (OR = 1.4, P = .005), medical oncologist involvement (OR = 2.0, P = .007), diagnosis 2012-2017 versus 2007-2011 (OR = 0.75, P = .034), and academic center (OR = 0.061, P = .007)., Conclusion: A majority of patients with mCRPC never receive BTAs prior to first SRE, despite universal access and availability of these agents in Ontario. These results highlight an opportunity to improve outcomes by emphasizing early introduction of BTA in patients with mCRPC being started on systemic therapy., (© The Author(s) 2024. Published by Oxford University Press.)

We report the measurement of the helicity asymmetry E for the pπ^{0} and nπ^{+} final states using, for the first time, an elliptically polarized photon beam in combination with a longitudinally polarized target at the Crystal Ball experiment at MAMI. The results agree very well with data that were taken with a circularly polarized photon beam, showing that it is possible to simultaneously measure polarization observables that require linearly (e.g., G) and circularly polarized photons (e.g., E) and a longitudinally polarized target. The new data cover a photon energy range 270-1400 MeV for the pπ^{0} final state (230-842 MeV for the nπ^{+} final state) and the full range of pion polar angles, θ, providing the most precise measurement of the observable E. A moment analysis gives a clear observation of the pη cusp in the pπ^{0} final state.

Deep sea cold seeps are sites where hydrogen sulfide, methane, and other hydrocarbon-rich fluids vent from the ocean floor. They are an important component of Earth's carbon cycle in which subsurface hydrocarbons form the energy source for highly diverse benthic micro- and macro-fauna in what is otherwise vast and spartan sea scape. Passive continental margin cold seeps are typically attributed to the migration of hydrocarbons generated from deeply buried source rocks. Many of these seeps occur over salt tectonic provinces, where the movement of salt generates complex fault systems that can enable fluid migration or create seals and traps associated with reservoir formation. The elevated advective heat transport of the salt also produces a chimney effect directly over these structures. Here, we provide geophysical and geochemical evidence that the salt chimney effect in conjunction with diapiric faulting drives a subsurface groundwater circulation system that brings dissolved inorganic carbon, nutrient-rich deep basinal fluids, and potentially overlying seawater onto the crests of deeply buried salt diapirs. The mobilized fluids fuel methanogenic archaea locally enhancing the deep biosphere. The resulting elevated biogenic methane production, alongside the upward heat-driven fluid transport, represents a previously unrecognized mechanism of cold seep formation and regulation., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: As a result of improvements in cancer therapies, patients with metastatic malignancies are living longer, and the role of palliative radiotherapy has become increasingly recognized. However, access to adequate palliative radiotherapy may continue to be a challenge, as is evident from the high proportion of patients dying of prostate cancer who never receive palliative radiotherapy. The main objective of this investigation is to identify and describe the factors associated with the receipt of palliative radiation treatment in a decedent cohort of prostate cancer patients in Ontario., Methodology:  Population-based administrative databases from Ontario, Canada, were used to identify prostate cancer decedents, 65 years or older who received androgen deprivation therapy between January 1, 2013, and December 31, 2018. Baseline and treatment characteristics were analyzed using univariate and multivariate logistic regression models for association with receipt of radiotherapy in a two-year observation period before death., Results: We identified 3,788 prostate cancer decedents between 2013 and 2018; among these, 49.9% received radiotherapy in the two years preceding death. There were statistically significant positive associations between receipt of radiotherapy and younger age at diagnosis (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.1-2.3); higher stage at diagnosis (OR 1.3, 95% CI 1.1-1.7); receipt of care at a regional cancer center (OR 1.8, 95% CI 1.3-2.4); and involvement of radiation oncologists (OR 155.1, 95% CI 83.3-288.7) or medical oncologists (OR 1.4, 95% CI 1.1-1.8). However, there were no associations between receipt of radiotherapy and income, distance to the nearest cancer center, involvement of urologists in cancer care, healthcare administrative region, home-care involvement, or number of hospitalizations in the observation period., Conclusions: We found the utilization of palliative radiotherapy for prostate cancer patients in Ontario varies depending on age, stage at diagnosis, number of comorbidities, registration at regional cancer centers, and involvement of oncologists. There were no differences detected based on income or distance from a cancer center. The findings of this study represent an important opportunity to facilitate better access to palliative radiotherapy and referrals to multidisciplinary regional cancer centers, to improve the quality of life of this patient population., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Jooya et al.)

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.16177. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate., (© 2023 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.)

Purpose: To investigate the feasibility of a 4D Monte Carlo based dose reconstruction method to study the dosimetric impact of respiratory motion using surface motion measurements for patients undergoing VMAT treatments for Non-Small Cell Lung Cancer., Methods: The 4Ddefdosxyznrc/EGSnrc algorithm was used to reconstruct VMAT doses delivered to the patients using machine log files and respiratory traces measured with the RADPOS 4D dosimetry system. The RADPOS sensor was adhered to the patient's abdomen prior to each treatment fraction and its position was used as a surrogate for tumour motion. Treatment log files were synchronized with the patient respiratory traces. Patient specific respiratory models were generated from deformable registration of the inhale and exhale 4DCT images and the respiratory traces. The reconstructed doses were compared to planned doses calculated with DOSXYZnrc/EGSnrc on the average-intensity and the exhale phase CT images., Results: Respiratory motion measurements and log files were acquired for 2 patients over 5 treatment fractions each. The motion was predominantly along the anterior/posterior direction (A/P). The average respiratory amplitudes were 8.7 ± 2.7 mm and 10.0 ± 1.2 mm for Patient 1 and 2, respectively. Both patients displayed inter- and intra-fractional variations in the baseline position. Small inter-fractional differences were observed in the reconstructed doses for each patient. Differences between the reconstructed and planned doses were attributed to differences in organ volumes., Conclusion: The 4D reconstruction method was successfully implemented for the two patients studied. Small differences between the planned and reconstructed doses were observed due to the small tumour motion of these patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

With increasing numbers of persons living with dementia and their higher rates of hospitalizations, it is necessary to ensure they receive appropriate and effective acute care; yet, acute care environments are often harmful for persons with dementia. There is a lack of dementia education for acute health care providers in Canada. Scotland presently delivers a dementia education program for health care providers, known as the Scottish National Dementia Champions Programme. The objective of this Policy and Practice Note is to present the collaborative work of Scottish experts and Canadian stakeholders to adapt the Dementia Champions Programme for use in Canada. This work to date includes: (a) an environmental scan of Canadian dementia education for acute health care providers; (b) key informant interviews; and, (c) findings from a two-day planning meeting. The results of this collaborative work can and are being used to inform the next steps to develop and pilot a Canadian dementia education program.

Many powerful molecular biology tools have their origins in natural systems, including restriction modification enzymes and the CRISPR effectors, Cas9, Cas12, and Cas13. Heightened interest in these systems has led to mining of genomic and metagenomic data to identify new orthologs of these proteins, new types of CRISPR systems, and uncharacterized natural systems with novel mechanisms. To accelerate metagenomic mining, we developed a high-throughput, low-cost droplet microfluidic-based method for enrichment of rare sequences in a mixed starting population. Using a computational pipeline, we then searched in the enriched data for the presence of CRISPR-Cas systems, identifying a previously unknown CRISPR-Cas system. Our approach enables researchers to efficiently mine metagenomic samples for sequences of interest, greatly accelerating the search for nature's treasures.

Purpose: Both oncologic outcomes and patient-reported outcomes are pivotal in prostate cancer (PCa). However, it remains unknown if there is any association between these 2 outcomes. In this secondary analysis of a randomized controlled trial, we investigated the association of short-term changes in patient-reported outcome with long-term event-free survival (EFS) and metastasis-free survival (MFS) in localized PCa., Methods and Materials: Localized PCa patients with a Gleason score ≤7, clinical stage T1b to T3a, and prostate-specific antigen (PSA) <30 ng/mL were randomized to neoadjuvant and concurrent androgen deprivation therapy (ADT) for 6 months starting 4 months before prostate radiation therapy or concurrent and adjuvant ADT for 6 months starting simultaneously with radiation therapy. Patient-reported symptom burden was evaluated using the European Organisation for Research and Treatment of Cancer quality of life questionnaire (QLQ)-PR.25. Clinically meaningful deterioration (CMD) was defined as a ≥10-point worsening at any time within 10 months postrandomization regardless of subsequent improvement. Landmark analyses were performed to determine the association of CMD of urinary and bowel symptoms separately with EFS and MFS in patients who responded to the baseline questionnaire, were alive, and were event free at 10 months., Results: Overall, 393 patients had responded to the baseline QLQ. One patient died, and 1 patient had failure within 10 months. Therefore, 391 patients were eligible for the landmark analyses. After adjusting for age, Gleason score, PSA, performance status, and treatment group, CMD of urinary symptoms was associated with worse EFS (hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.21-2.65) and MFS (HR, 1.69; 95% CI, 1.11-2.57). Considering deaths as competing events, CMD of urinary symptoms was associated with a significant increase in the relative incidence of progression (subdistribution HR, 2.42; 95% CI, 1.12-5.20). However, no association was found between CMD of bowel symptoms and EFS or MFS., Conclusions: In this study, short-term CMD of urinary symptoms was associated with significantly inferior EFS and MFS and an increase in the relative incidence of progression. Further investigations are needed to explore the biological rationale of such association in the context of ADT and radiation therapy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: Although health-related quality of life (HR-QoL) outcomes are pivotal in oncology, the prognostic significance of patient-reported HR-QoL metrics is largely undefined in localised prostate cancer. We report the association of baseline HR-QoL metrics with overall survival and toxicity in localised prostate cancer., Materials and Methods: This was a secondary analysis of a phase III randomised controlled study conducted in a single-payer health system. Patients with Gleason score ≤7, clinical stage T1b-T3a and prostate-specific antigen <30 ng/ml were randomised to neoadjuvant and concurrent androgen deprivation therapy (ADT) for 6 months starting 4 months before prostate radiotherapy or concurrent and adjuvant ADT for 6 months starting simultaneously with prostate radiotherapy. HR-QoL scores were estimated using the European Organisation for Research and Treatment of Cancer QoL questionnaire. A multistate Markov model was used to determine the association of baseline HR-QoL metrics with overall survival and a multilevel multivariable Cox regression was used to determine the association with the incidence of delayed-onset grade ≥3 radiotherapy-related toxicities. To adjust for multiple analyses, P < 0.025 was considered as statistically significant., Results: Overall, 393 patients with baseline HR-QoL data were included in this analysis: 194 in the neoadjuvant arm and 199 in the adjuvant arm. Baseline financial difficulty (hazard ratio 1.020, 95% confidence interval 1.010-1.030, P = 0.02) and dyspnoea (hazard ratio 1.020, 95% confidence interval 1.003-1.030, P = 0.01) were associated with inferior overall survival. Baseline dyspnoea was associated with a higher incidence of grade ≥3 toxicity (hazard ratio 1.020, 95% confidence interval 1.010-1.030, P = 0.023)., Conclusion: In a cohort of localised prostate cancer patients treated with radiotherapy and short-term ADT, a 10-point higher baseline financial difficulty or dyspnoea was associated with a 20% increased risk of death. With each 10-point increase in baseline dyspnoea, we noted a 20% increase in the associated risk of grade ≥3 delayed-onset radiotherapy-related toxicity., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: The importance of dementia education in improving the care and support that people living with dementia is well established. Previous research has shown ceiling effects in pre and post educational intervention measures of dementia knowledge using Knowledge in Dementia Scale (KIDE) on post-registered health and social care staff in Scotland. The aim was to test the sensitivity of two dementia knowledge instruments, namely the (KIDE) and the Dementia Knowledge Assessment Scale (DKAS)., Design: A pre and post evaluation comparison of two dementia knowledge scales., Setting: The tenth cohort of Scotland's National Dementia Champions Education Programme, September 2019-March 2020., Participants: Post-registered Health and Social Care staff (n = 117)., Methods: Both the DKAS and KIDE scales were administered pre and post programme delivery. Wilcoxon signed-rank tests were performed to examine T1 - T2 differences in dementia knowledge for both validated measures., Results: Ceiling effects continued to be present for the KIDE scale at T1 and T2. The DKAS responses showed a different score distribution than that achieved by the KIDE. Ceiling effects noted for KIDE at T1 were not present for the DKAS. Further, at T2, only 6% of respondents scored the maximum on the DKAS., Conclusions: The DKAS appears to be a more useful instrument for measuring knowledge in post-registered health and social care staff; however, there was some evidence of ceiling effects post-intervention. There is a need for both scales to be tested in more educationally diverse populations, so educators and researchers can make informed decisions about the instrument's target range. Additionally, further research is needed to develop new sets of dementia knowledge items suitable for use in trained health and social care staff., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: To present an overview of the issues related to the well-being of people affected by cancer and dementia. To highlight the evidence from dementia care that can help improve the care experiences of people with dementia and cancer., Data Sources: Electronic databases such as PubMed and CINAHL were used to retrieve relevant literature published between 2010 and 2020., Conclusion: Having a dual diagnosis of dementia and cancer poses several challenges across the cancer care pathway. Communication, treatment decision-making, environment ,and time-related issues were all identified. The literature suggests the need for evidence-based guidelines taking into consideration the person and the environment to support this population., Implications for Nursing Practice: To address these challenges and offer an optimal care experience for this group and their families, solutions need to focus both on the workforce and the environment. Offering dementia education for professionals working in acute cancer care, as well as adapting local environments that facilitate people navigate the space can be a starting point to offer person-centered, rights-based dementia sensitive care., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Frequent testing of large population groups combined with contact tracing and isolation measures will be crucial for containing Coronavirus Disease 2019 outbreaks. Here we present LAMP-Seq, a modified, highly scalable reverse transcription loop-mediated isothermal amplification (RT-LAMP) method. Unpurified biosamples are barcoded and amplified in a single heat step, and pooled products are analyzed en masse by sequencing. Using commercial reagents, LAMP-Seq has a limit of detection of ~2.2 molecules per µl at 95% confidence and near-perfect specificity for severe acute respiratory syndrome coronavirus 2 given its sequence readout. Clinical validation of an open-source protocol with 676 swab samples, 98 of which were deemed positive by standard RT-qPCR, demonstrated 100% sensitivity in individuals with cycle threshold values of up to 33 and a specificity of 99.7%, at a very low material cost. With a time-to-result of fewer than 24 h, low cost and little new infrastructure requirement, LAMP-Seq can be readily deployed for frequent testing as part of an integrated public health surveillance program., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate., (© 2021 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.)

This article, part of a series in Nursing Older People exploring the nursing care of people living with advanced dementia, considers learning and leadership. It outlines learning opportunities about advanced dementia and what developments are needed. The need for strong leadership at all levels and settings is explored along with the challenges of educating those who care for the person with advanced dementia. It also outlines educational opportunities and programmes before illustrating how one nurse leads advanced dementia care in practice., Competing Interests: None declared, (© 2020 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.)

Background: To assess correlation of pretreatment specific growth rate (SGR) value of 0.43 × 10 -2 with overall and failure-free survival of patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT)., Methods: A retrospective chart review of 160 patients with pathologically confirmed stage I NSCLC treated with SBRT between June 2010 and December 2012 in a large, tertiary cancer institute was undertaken. Both diagnostic and archived planning CT were uploaded to the treatment planning system to determine tumor volume at diagnosis (GTV1) and planning time (GTV2). The time (t) between both CTs was recorded. SGR was calculated using GTV1, GTV2, and t. The median SGR (0.43 × 10 -2 ) from our previous data was used to group patients into low and high SGR cohorts. Log-rank test was used to compare overall (OS) and failure-free survivals (FFS) of SGR groups., Results: The median time interval between diagnostic and planning CT scans was 87 days. The median OS was 38 and 66 months for high and low SGR cohorts, respectively (P = 0.03). The median FFS was 27 and 55 months for high and low SGR cohorts, respectively (P = 0.005). High SGR (P < 0.05), male gender (P = <0.01), and GTV2 (P = <0.05) were associated with poorer FFS., Conclusions: High SGR was associated with poorer outcome in patients with early-stage NSCLC treated with SBRT. SGR can be used in conjunction with other well-known predictive factors to formulate a practical predictive model to identify subgroups of the patient at higher risk of recurrence after SBRT., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Despite growing understanding in recent years of the biological, psychological, social, environmental and spiritual aspects of dementia, people with advanced dementia continue to experience inequalities in accessing healthcare capable of improving their lives. The complexities of advanced dementia challenge professional competence and demand the highest level of skilled, compassionate care. This article, the last in a series on living with advanced dementia, considers the status and direction of palliative care as it applies to people with dementia and explores contemporary issues regarding advanced dementia and end of life, with a focus on guidance for practitioners and support for best practice. It identifies that open communication, clear information and a person-centred approach adopted as early as possible in the syndrome can make this period less distressing. Crucially, people at the end of life should be offered care in line with best practice in palliative and end of life approaches., Competing Interests: None declared, (© 2020 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.)

This is the second article in a six-part series in Nursing Older People exploring the nursing care of people living with advanced dementia. This article considers the complexity of providing personal care, including the need for expert nursing practice to assess and lead the fundamentals of care: washing, dressing, continence care, nutrition and hydration. The contemporary evidence base for effective assessment, care planning, partnership working and evaluation of personal care for people with advanced dementia is presented, supported by sources of further information., Competing Interests: None declared, (© 2020 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.)

Purpose: Dose-escalated radiotherapy (RT) with androgen-deprivation therapy (ADT) is a standard definitive treatment of localized prostate cancer (LPCa). The optimal sequencing of these therapies is unclear. Our phase III trial compared neoadjuvant versus concurrent initiation of ADT in combination with dose-escalated prostate RT (PRT)., Patients and Methods: Patients with newly diagnosed LPCa with Gleason score ≤ 7, clinical stage T1b to T3a, and prostate-specific antigen < 30 ng/mL were randomly allocated to neoadjuvant and concurrent ADT for 6 months starting 4 months before RT (neoadjuvant group) or concurrent and adjuvant ADT for 6 months starting simultaneously with RT (concurrent group). The primary end point was biochemical relapse-free survival (bRFS). Stratified log-rank test was used to compare bRFS and overall survival (OS). Incidence of grade ≥ 3 late RT-related toxicities was compared by log-rank test., Results: Overall, 432 patients were randomly assigned to the neoadjuvant (n = 215) or concurrent group (n = 217). At 10 years, bRFS rates for the two groups were 80.5% and 87.4%, respectively. Ten-year OS rates were 76.4% and 73.7%, respectively. There was no significant difference in bRFS ( P = .10) or OS ( P = .70) between the two groups. Relative to the neoadjuvant group, the hazard ratio for the concurrent group was 0.66 (95% CI, 0.41 to 1.07) for bRFS and 0.94 (95% CI, 0.68 to 1.30) for OS. No significant difference was observed in the 3-year incidence of late RT-related grade ≥ 3 GI (2.5% v 3.9%) or genitourinary toxicity (2.9% v 2.9%)., Conclusion: In our study, there was no statistically significant difference in bRFS between the two treatment groups. Similarly, no difference was seen in OS or late RT-related toxicities. On the basis of these results, both neoadjuvant and concurrent initiations of short-term ADT with dose-escalated PRT are reasonable standards of care for LPCa.

Purpose/Objective Published preclinical and phase I clinical trial data suggest that fractionated lesional radiotherapy with 60 Gy in 10 fractions can serve as an alternative approach to single fraction radiosurgical boost for brain oligometastases.  Methods and Materials A phase II clinical trial (NCT01543542) of a total of 60 Gy in 10 fractions of lesional (one to three) radiotherapy (given simultaneously with whole-brain helical tomotherapy with 30 Gy in 10 fractions) was conducted at five institutions. We hypothesized that fractionated radiotherapy would be considered unsuitable if the median overall survival (OS) was degraded by two months or if six-month intracranial control (ICC) and intracranial lesion (ILC) were inferior by 10% compared with the published RTOG 9508 results. Results A total of 87 patients were enrolled over a 4.5-year accrual period. Radiological lesion and extralesional central nervous system progression were documented in 15/87 (17%) and 11/87 (13%) patients, respectively. Median OS for all patients was 5.4 months. Six-month actuarial estimates of ICC and ILC were 78% and 89%, respectively. However, only the ILC estimate achieved statistical significance (p=0.02), demonstrating non-inferiority to the a priori historical controls (OS: p=0.09, ICC=0.31). Two patients developed suspected asymptomatic radionecrosis. Conclusions The phase II estimates of ILC were demonstrated to be non-inferior to the results of the RTOG 9508., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2019, Rodrigues et al.)

Purpose: The number of prisoners over 55 years is increasing and many are at risk of developing dementia. This has generated new responsibilities for prisons to provide health and social care for older persons. The purpose of this paper is to synthesize the existing research literature regarding the phenomenon of the health and social care needs of older persons living with dementia in correctional settings., Design/methodology/approach: Using an integrative review method based on Whittemore and Knafl, the inclusion criteria for the review are: articles written in English; a focus on some form of dementia and/or older persons with discussion of dementia; to be set in a correctional context (correctional facility, prison and jail); be derived from a published peer-reviewed journal or unpublished dissertation/thesis; and be a qualitative, quantitative or mixed methods study. Based on those criteria, a search strategy was developed and executed by a health sciences librarian in the following databases: Medline, CINAHL, Embase, PsychINFO, Proquest Nursing and Allied Health and Web of Science; searches were completed up to April 2019. After data were extracted from included studies, synthesis of findings involved an iterative process where thematic analysis was facilitated by Braun and Clarke's approach., Findings: Eight studies met the inclusion criteria. Key findings of the eight studies include recognition of dementia as a concern for correctional populations, dementia-related screening and programming for older persons and recommendations for improved screening and care practices. Most significant is the paucity of research available on this topic. Implications for research are discussed., Originality/value: This paper identified and synthesizes the limited existing international research on the health and social care needs of older persons with dementia living in correctional settings. Although existing research is scant, this review highlights the need for increased awareness of dementia as a concern among older persons living in correctional settings. As well, the review findings emphasize that enhanced screening and interventions, particularly tailored approaches, are imperative to support those living with dementia in correctional settings., (© Emerald Publishing Limited.)

Background: Little evidence has been generated for how best to manage patients with non-small-cell lung cancer (nsclc) presenting with rarer clinical scenarios, including oligometastases, oligoprogression, and pseudoprogression. In each of those scenarios, oncologists have to consider how best to balance efficacy with quality of life, while maximizing the duration of each line of therapy and ensuring that patients are still eligible for later options, including clinical trial enrolment., Methods: An expert panel was convened to define the clinical questions. Using case-based presentations, consensus practice recommendations for each clinical scenario were generated through focused, evidence-based discussions., Results: Treatment strategies and best-practice or consensus recommendations are presented, with areas of consensus and areas of uncertainty identified., Conclusions: In each situation, treatment has to be tailored to suit the individual patient, but with the intent of extending and maximizing the use of each line of treatment, while keeping treatment options in reserve for later lines of therapy. Patient participation in clinical trials examining these issues should be encouraged., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare the following interests: SAL has received honoraria from Pfizer, AstraZeneca, Boehringer Ingelheim, and Novartis; SB has served on advisory boards for AstraZeneca, Boehringer Ingelheim, Bristol–Myers Squibb, Eli Lilly, Novartis, Pfizer, and Roche, and has received research funding from AstraZeneca and Merck; NB has served on advisory boards for Amgen, AstraZeneca, Merck, Bayer, Boehringer Ingelheim, Bristol–Myers Squibb, Celgene, Eli Lilly, Novartis, Pfizer, Sanofi, and Roche; SB has received honoraria from AstraZeneca, Boehringer Ingelheim, Bristol–Myers Squibb, Eisai, and Merck; PKC has served as an advisor for AstraZeneca, Boehringer Ingelheim, Hoffmann–La Roche, Pfizer, Novartis, Takeda, Eli Lilly, and Bristol–Myers Squibb, and has received research funding from Boehringer Ingelheim and Hoffmann–La Roche; PC has received grants for investigator-initiated research projects from AbbVie, Pfizer, and Sanofi–Aventis; DH has served on advisory boards for AstraZeneca, Boehringer Ingelheim, Bristol–Myers Squibb, and Merck, and has received honoraria from Pfizer; VH has participated on advisory boards for AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol–Myers Squibb, Merck, Pfizer, and Roche; RJ has served as an advisor or consultant for AstraZeneca/MedImmune, Bristol–Myers Squibb, Merck, Pfizer/emd Serono, and Roche, has received honoraria from AstraZeneca, Bristol–Myers Squibb, Merck, Pfizer/emd Serono, and Roche, and has received research funding from AstraZeneca, Bristol–Myers Squibb, and Merck; JL has received honoraria for talks from AstraZeneca, Boehringer Ingelheim, Pfizer, and Roche, and her institution has received grant funding for research trials from AstraZeneca, Boehringer Ingelheim, Eli Lilly, and Roche; in the last 2 years, NL has received honoraria for independent unrelated continuing medical education from AstraZeneca, Bristol–Myers Squibb, and Merck; DR has received honoraria and support from Accuray, BrainLab, Elekta, Pfizer/emd Serono, Siemens Healthineers, and Varian Medical Systems; JR has received speaker and advisory board fees and institutional research support for clinical trials funded by Astra-Zeneca, Bristol–Myers Squibb, Merck, Pfizer, and Roche; DJS has received honoraria (2015–2018) from Roche Canada, Boehringer Ingelheim Canada, Novartis Canada, Merck Canada, AstraZeneca Canada, Bristol–Myers Squibb Canada, Exactis Innovation, and Pfizer Canada, and has received institutional research support from Boehringer Ingelheim, AstraZeneca, Novartis, Bristol– Myers Squibb, and Celgene; MST has received honoraria from AstraZeneca, Bristol–Myers Squibb, Merck, and Roche/Ventana, and a research grant from Merck. The remaining authors have no conflicts to disclose.

This article presents an integrative literature review of the experience of dementia care associated with the extended palliative phase of dementia. The aim was to highlight how dementia is defined in the literature and describe what is known about the symptomatology and management of advanced dementia regarding the needs and preferences of the person with dementia and their family carer/s. There was no consistent definition of advanced dementia. The extended palliative phase was generally synonymous with end-of-life care. Advanced care planning is purported to enable professionals to work together with people with dementia and their families. A lack of understanding of palliative care among frontline practitioners was related to a dearth of educational opportunities in advanced dementia care. There are few robust concepts and theories that embrace living the best life possible during the later stages of dementia. These findings informed our subsequent work around the concept, 'Dementia Palliare'.

Increasing numbers of people with dementia are living longer with a higher likelihood of requiring hospital care for physical conditions including falls, infections and stroke (Boaden, 2016). However, the literature is replete with descriptions of poor care and hospital care experiences that have fallen well below the expectations of people with dementia, their families and friends. Although poor care is unacceptable, it is unsurprising given that dementia education for health and social care professionals is often inadequate and inconsistent. This results in most healthcare staff being ill-equipped and lacking the confidence to work with people living with dementia. The first of Scotland's National Dementia Strategies committed to "improve the response to dementia in general hospital settings including alternatives to admission and better planning for discharge" (Scottish Government, 2010). The educational response was the commissioning of the Dementia Champions programme. Since 2011, the programme has developed over 800 health and social care professionals working in general hospital and related settings to be change agents in dementia care. This article will outline the theoretical underpinning of the programme and present pooled results from four cohorts (2014-2017) (n = 524). A repeated measure design (pre and post programme) was used to measure attitudes towards people with dementia; self-efficacy and knowledge of dementia. The findings suggest that the education had a statistically significant positive effect on all intended outcomes, indicating the potential for practice change. We discuss these findings in relation to the literature, and respond to the calls for high quality evaluation to measure the effectiveness of dementia education, the challenges and potential directions for measuring educational effectiveness and capturing transfer of learning., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

The prison population is aging at an alarming rate and many older persons have the potential to develop dementia while in prison. This case report aims to explore the needs of older people living with dementia in prison and discusses the interventions that exist to address these needs. As the condition progresses, persons with dementia become increasingly reliant on the support of others for their health and well-being because of the increasing complexity of physical healthcare and psychosocial needs. Very few interventions are cited in the research literature regarding the use, acceptability, and/or effectiveness of programming for people living with dementia in prison. To support the unique and complex needs of these persons, research is needed to guide the development of evidence-informed dementia programs and services as well as consideration of interdisciplinary collaboration with community organizations.

The order Herpesvirales includes viruses that infect aquatic and terrestrial vertebrates and several aquatic invertebrates (i.e. mollusks), and share the commonality of possessing a double-stranded DNA core surrounded by an icosahedral capsid. Herpesviruses of the family Alloherpesviridae that infect fish and amphibians, including channel catfish virus and koi herpesvirus, negatively impact aquaculture. Here, we describe a novel herpesvirus infection of wild European perch from lakes in Finland. Infected fish exhibited white nodules on the skin and fins, typically in the spring when prevalence reached nearly 40% in one of the sampled lakes. Transmission electron microscopic examination of affected tissues revealed abundant nuclear and cytoplasmic virus particles displaying herpesvirus morphology. Degenerate PCR targeting a conserved region of the DNA polymerase gene of large DNA viruses amplified a 520 bp product in 5 of 5 affected perch skin samples tested. Phylogenetic analysis of concatenated partial DNA polymerase and terminase (exon 2) gene sequences produced a well-supported tree grouping the European perch herpesvirus with alloherpesviruses infecting acipenserid, esocid, ictalurid, and salmonid fishes. The phenetic analysis of the European perch herpesvirus partial DNA polymerase and terminase nucleotide gene sequences ranged from 34.6 to 63.9% and 39.6 to 59.6% to other alloherpesviruses, respectively. These data support the European perch herpesvirus as a new alloherpesvirus, and we propose the formal species designation of Percid herpesvirus 2 (PeHV2) to be considered for approval by the International Committee on Taxonomy of Viruses.

Hydrogels comprised of alginate and gelatin have demonstrated potential as biomaterials in three dimensional (3D) bioprinting applications. However, as with all hydrogel-based biomaterials used in extrusion-based bioprinting, many parameters influence their performance and there is limited data characterising the behaviour of alginate-gelatin (Alg-Gel) hydrogels. Here we investigated nine Alg-Gel blends by varying the individual constituent concentrations. We tested samples for printability and print accuracy, compressive behaviour and change over time, and viability of encapsulated mesenchymal stem cells in bioprinted constructs. Printability tests showed a decrease in strand width with increasing concentrations of Alg-Gel. However due to the increased viscosity associated with the higher Alg-Gel concentrations, the minimum width was found to be 0.32mm before blends became too viscous to print. Similarly, printing accuracy was increased in higher concentrations, exceeding 90% in some blends. Mechanical properties were assessed through uniaxial compression testing and it was found that increasing concentrations of both Alg and Gel resulted in higher compressive modulus. We also deemed 15min crosslinking in calcium chloride to be sufficient. From our data, we propose a blend of 7%Alg-8%Gel that yields high printability, mechanical strength and stiffness, and cell viability. However, we found the compressive behaviour of Alg-Gel to reduce rapidly over time and especially when incubated at 37°C. Here we have reported relevant data on Alg-Gel hydrogels for bioprinting. We tested for biomaterial properties and show that these hydrogels have many desirable characteristics that are highly tunable. Though further work is needed before practical use in vivo can be achieved., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: There is a paucity of robust research concerning the care experiences of peoplewith advanced dementia within Europe. It is essential to understand these experiences if weare to address care inequalities and create impactful dementia policies to improve servicesthat support individuals and enable family caring., Objectives: To identify the strengths and weaknesses in daily life perceived by people with dementia and family caring across Europe by exemplifying experiences and the range of typical care settings for advanced dementia care in seven partner countries., Methods: Twenty two in-depth qualitative case studies were completed in seven European countries across a range of care settings considered typical within that country. Narrative accounts of care illuminated a unique set of experiences and highlighted what was working well (strengths or positive aspects) and not so well (weaknesses or negative aspects) for people with advanced dementia and family caring. A constant comparative method of analysis through thematic synthesis was used to identify the common themes., Results: Eight key themes were identified; Early diagnosis, good coordination between service providers, future planning, support and education for carers, enabling the person with dementia to live thebest life possible and education on advanced dementia for professional and family caregiverswere all significant and recurring issues considered important for care experiences to bepositive., Conclusion: People with advanced dementia may have limited opportunities for self-realization and become increasingly reliant on the support of others to maximize their health and well-being. Careful attention must be given to their psychosocial well-being, living environment and family caring to enable them to live the best life possible. Building on what the case studies tell us about what works well, we discuss the potential for integrating the findings into interprofesional learning solutions for the professional workforce across Europe to champion practice-based change.

Background: The World Health Organization has identified developing the knowledge and skills of healthcare professionals who are involved in dementia care as a priority. Most healthcare professionals lack the necessary knowledge, skills and understanding to provide high quality dementia care. While dementia education amongst most UK university health and social care programmes is inconsistent, we know little about the provision of dementia education in European universities., Objectives: To examine the provision of accredited higher education on dementia in European countries, to illustrate that it is highly variable despite universities being the major provider of education for healthcare professionals internationally., Design: An exploratory research design was used., Settings: The providers of higher education undergraduate and postgraduate programmes in the Czech Republic, Portugal, Scotland, Slovenia, Spain, Sweden., Participants: Higher Education Institutions who provide undergraduate and postgraduate education in the fields of nursing, medicine, psychology, social work, physiotherapy, occupational therapy, and gerontology in six European countries., Methods: The data was collected using a structured questionnaire. Researchers in each country conducted an internet-based search using the websites of Higher Education Institutions to identify existing accredited dementia education., Results: These searches revealed a lack of dementia education in undergraduate health and social care study programmes. Three of the six countries offered postgraduate study programmes on dementia. There was a significant variation amongst the countries in relation to the provision of dementia education at undergraduate, postgraduate and doctoral levels., Conclusions: Dementia is a global challenge and educating and upskilling the workforce is a policy imperative. To deliver the best dementia care, investment in interprofessional evidence-based education is required if we are to respond effectively and compassionately to the needs of people living with dementia and their families. Higher Education Institutions have an important role to play in equipping health and social care professionals with the knowledge, skills and understanding to respond to this imperative., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The prediction of local recurrence (LR) of stage I non-small cell lung cancer (NSCLC) after definitive stereotactic body radiotherapy (SBRT) remains elusive. The purpose of this study was to assess whether quantitative imaging features on pre-treatment computed tomography (CT) can predict LR beyond 18 ( 18 F) fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/CT maximum standard uptake value (SUV max )., Methods: This retrospective study evaluated 36 patients with 37 stage I NSCLC who had local tumor control (LC; n=19) and (LR; n=18). Textural features were extracted on pre-treatment CT. Mann-Whitney U tests were used to compare LC and LR groups. Receiver-operating characteristic (ROC) curves were constructed and the area under the curve (AUC) calculated with LR as outcome., Results: Gray-level correlation and sum variance were greater in the LR group, compared with the LC group (P=0.02 and P=0.04, respectively). Gray-level difference variance was lower in the LR group (P=0.004). The logistic regression model generated using gray-level correlation and difference variance features resulted in AUC (SE) 0.77 (0.08) (P=0.0007). The addition of 18F-FDG PET/CT SUV max did not improve the AUC (P=0.75)., Conclusions: CT textural features were found to be predictors of LR of early stage NSCLC on baseline CT prior to SBRT., Competing Interests: Conflicts of Interest: CA Souza has received consultant fees from Pfizer and honoraria from Pfizer, Boehringer-Ingelheim and Hoffmann-LaRoche unrelated to the topic of this publication; the other authors have no conflicts of interest to declare.

Purpose: Frontline healthcare professionals are well positioned to improve the systems in which they work. Educational curricula, however, have not always equipped healthcare professionals with the skills or knowledge to implement and evaluate improvements. It is important to have a robust and standardized framework in order to evaluate the impact of such education in terms of improvement, both within and across European countries. The results of such evaluations will enhance the further development and delivery of healthcare improvement science (HIS) education. We aimed to describe the development and piloting of a framework for prospectively evaluating the impact of HIS education and learning., Methods: The evaluation framework was designed collaboratively and piloted in 7 European countries following a qualitative methodology. The present study used mixed methods to gather data from students and educators. The framework took the Kirkpatrick model of evaluation as a theoretical reference., Results: The framework was found to be feasible and acceptable for use across differing European higher education contexts according to the pilot study and the participants' consensus. It can be used effectively to evaluate and develop HIS education across European higher education institutions., Conclusion: We offer a new evaluation framework to capture the impact of HIS education. The implementation of this tool has the potential to facilitate the continuous development of HIS education.

Purpose: In this single institution retrospective study of patients with stage I medically inoperable non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR) we attempt to model overall survival (OS) using initial prognostic variables with specific attention on the Charlson co-morbidity index (CCI)., Methods: Between 2008 and 2013, 335 patients with medically inoperable stage I NSCLC were treated with SABR or hypofractionated radiotherapy (50-60 Gy in at least 5 Gy or 4 Gy fractions respectively) at our institution. Medical comorbidities and Charlson scores were determined by individual chart review. Patients were stratified into 3 groups based on the CCI score (0-1, 2-3, 4-9) and again based on the age-adjusted Charlson Comorbidity score (aCCI). Cumulative survival for each stratum was determined using the Kaplan-Meier method. Non-significant and confounding variables were identified and discounted from survival modeling. 3 sex stratified Cox regression models were tested: (1) aCCI with age and comorbidity combined; (2) age and CCI; (3) age alone, comorbidity removed., Results: The median survival was 4.4 years and the median follow up 4.7 years. The median CCI and aCCI scores were 2 and 5 respectively. Patients with aCCI 7-12 had an increased hazard of death on univariate analysis HR 2.45 (1.15-5.22 95%CI, p  = 0.02) and -excluding age as a competing variable- on multivariate analysis HR 2.25 (1.04-4.84 95%CI, p  = 0.04). Patients with CCI 4-9 had an increased hazard of death on univariate analysis HR 1.57(1.30-2.90) but not on multivariate analysis. On formalized testing - with either continuous or categorical variables- all three survival models yielded similar coefficients of effect., Conclusion: We identify male gender, weight loss greater than 10% and age as independent prognostic factors for patients treated with medically inoperable NSCLC treated with SABR or hypofractionated radiotherapy. Based on our survival models, age alone can be used interchangeably with aCCI or CCI plus age with the same prognostic value. Age is more reliably recorded, less prone to error and therefore a more useful metric than Charlson score in this group of patients.

The reactions γp→ηp and γp→η^{'}p are measured from their thresholds up to the center-of-mass energy W=1.96  GeV with the tagged-photon facilities at the Mainz Microtron, MAMI. Differential cross sections are obtained with unprecedented statistical accuracy, providing fine energy binning and full production-angle coverage. A strong cusp is observed in the total cross section for η photoproduction at the energies in the vicinity of the η^{'} threshold, W=1896  MeV (E&#95;{γ}=1447  MeV). Within the framework of a revised ηMAID isobar model, the cusp, in connection with a steep rise of the η^{'} total cross section from its threshold, can only be explained by a strong coupling of the poorly known N(1895)1/2^{-} state to both ηp and η^{'}p. Including the new high-accuracy results in the ηMAID fit to available η and η^{'} photoproduction data allows the determination of the N(1895)1/2^{-} properties.

Introduction: There is a limited body of research in the field of healthcare improvement science (HIS). Quality improvement and 'change making' should become an intrinsic part of everyone's job, every day in all parts of the healthcare system. The lack of theoretical grounding may partly explain the minimal transfer of health research into health policy., Methods: This article seeks to present the development of the definition for healthcare improvement science. A consensus method approach was adopted with a two-stage Delphi process, expert panel and consensus group techniques. A total of 18 participants were involved in the expert panel and consensus group, and 153 answers were analysed as a part of the Delphi survey. Participants were researchers, educators and healthcare professionals from Scotland, Slovenia, Spain, Italy, England, Poland, and Romania., Results: A high level of consensus was achieved for the broad definition in the 2nd Delphi iteration (86%). The final definition was agreed on by the consensus group: 'Healthcare improvement science is the generation of knowledge to cultivate change and deliver person-centred care that is safe, effective, efficient, equitable and timely. It improves patient outcomes, health system performance and population health.', Conclusions: The process of developing a consensus definition revealed different understandings of healthcare improvement science between the participants. Having a shared consensus definition of healthcare improvement science is an important step forward, bringing about a common understanding in order to advance the professional education and practice of healthcare improvement science., Competing Interests: Conflicts of interest:The authors report no conflicts of interest.

This paper examines the provision of integrated advanced dementia care within seven European countries and critically reviews the potential contribution of the Prudent Healthcare perspective as a starting point for reform. Progressive efforts to innovate, promote quality and integrate care are tempered with the reality of resource constraints. Some policy makers in Europe and North America have turned their attention to the principles of Prudent Healthcare as a potential mechanism to maximise benefits for patients within available resources. As dementia progresses, living well requires increasing levels of support and care, people living with advanced dementia have complex health and social care needs, are highly dependent on others but are not yet at the terminal end stage of the condition. People with advanced dementia can benefit from a dementia specific palliative approach to care ( Palliare ), that helps them to live the best life possible for the months and often years they live with advanced dementia. It is also highly desirable to align policy innovations with integrated palliative care practice models and the education of the dementia workforce to accelerate informed improvements in advanced dementia care. There may be some coherence, at least superficially between Prudent Healthcare and integrated palliative care models such as Palliare . It is argued that for successful implementation, both require practitioners to be equipped with knowledge and skills and be empowered to deliver high quality care often within impoverished care environments. Adoption of the prudent perspective will however require development of a repertoire of approaches to hear the voice or proxy voice of people living with advanced dementia and to commit to the development and implementation of new evidence for advanced dementia practice. Evidence informing this policy debate draws upon contemporary literature and policy and the findings from research activities undertaken by the Palliare project supported through the Erasmus+ K2 Strategic Partnerships funding programme.

We examined functional outcomes and quality of life of whole brain radiotherapy (WBRT) with integrated fractionated stereotactic radiotherapy boost (FSRT) for brain metastases treatment. Eighty seven people with 1-3 brain metastases (54/87 lung primary, 42/87 single brain metastases) were enrolled on this Phase II trial of WBRT (30 Gy/10) + simultaneous FSRT, (60 Gy/10). Median overall follow-up and survival was 5.4 months, 6 month actuarial intra-lesional control was 78 %; only 1 patient exhibited grade 4 toxicity (worsened seizures); most treatment related toxicity was grade 1 or 2; 2/87 patients demonstrated asymptomatic radiation necrosis on follow-up imaging. Mean (Min-Max) baseline KPS, Mini Mental Status Exam (MMSE) and FACT-BR quality of life were 83 (70-100), 28 (21-30) and 143 (98-153). Lower baseline MMSE (but not KPS or FACT-Br) was associated with worse survival after adjusting for age, number of metastases, primary and extra-cranial disease status. Crude rates of deterioration (>10 points decrease from baseline for KPS and FACT-Br, MMSE fall to <27) ranged from 26 to 38 % for KPS, 32-59 % for FACT-Br and 0-16 % for MMSE depending on the time-point assessed with higher rates generally noted at earlier time points (≤6 months post-treatment). Using a linear mixed models analysis, significant declines from baseline were noted for KPS and FACT-Br (largest effects at 6 weeks to 3 months) with no significant change in MMSE. The effects on function and quality of life of this integrated treatment of WBRT + simultaneous FSRT were similar to other published series combining WBRT + radiosurgery.

Background: Numerous international policy drivers espouse the need to improve healthcare. The application of Improvement Science has the potential to restore the balance of healthcare and transform it to a more person-centred and quality improvement focussed system. However there is currently no accredited Improvement Science education offered routinely to healthcare students. This means that there are a huge number of healthcare professionals who do not have the conceptual or experiential skills to apply Improvement Science in everyday practise., Methods: This article describes how seven European Higher Education Institutions (HEIs) worked together to develop four evidence informed accredited inter-professional Improvement Science modules for under and postgraduate healthcare students. It outlines the way in which a Policy Delphi, a narrative literature review, a review of the competency and capability requirements for healthcare professionals to practise Improvement Science, and a mapping of current Improvement Science education informed the content of the modules., Results: A contemporary consensus definition of Healthcare Improvement Science was developed. The four Improvement Science modules that have been designed are outlined. A framework to evaluate the impact modules have in practise has been developed and piloted., Conclusion: The authors argue that there is a clear need to advance healthcare Improvement Science education through incorporating evidence based accredited modules into healthcare professional education. They suggest that if Improvement Science education, that incorporates work based learning, becomes a staple part of the curricula in inter-professional education then it has real promise to improve the delivery, quality and design of healthcare., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Individuals with Williams syndrome (WS) often experience significant anxiety. A promising approach to anxiety intervention has emerged from cognitive studies of attention bias to threat. To investigate the utility of this intervention in WS, this study examined attention bias to happy and angry faces in individuals with WS (N = 46). Results showed a significant difference in attention bias patterns as a function of IQ and anxiety. Individuals with higher IQ or higher anxiety showed a significant bias toward angry, but not happy faces, whereas individuals with lower IQ or lower anxiety showed the opposite pattern. These results suggest that attention bias interventions to modify a threat bias may be most effectively targeted to anxious individuals with WS with relatively high IQ.

Introduction: Concurrent thoracic radiation and platinum-based chemotherapy is the standard of care for treatment of unresectable stage IIIA-IIIB non-small-cell lung cancer (NSCLC), but the optimal drug regimen has not been established., Patients and Methods: In the present single-arm phase II trial, patients with previously untreated, unresectable stage IIIA-IIIB NSCLC (all histologic types) were treated with pemetrexed-cisplatin (500 mg/m(2) intravenously on days 1 and 22, 20 mg/m(2) intravenously on days 1-5 and days 22-26) concurrent with radiotherapy (61-66 Gy in 31-35 fractions), followed by 2 cycles of consolidation pemetrexed-cisplatin (75 mg(2)) therapy. The primary endpoint was the 1-year overall survival (OS) rate. The study treatment was considered active if the 1-year OS rate was ≥ 70%., Results: A total of 39 patients, including 6 from the previous phase I trial who had been treated at the recommended phase II dose, were eligible for analysis. The most common drug-related grade 3 to 4 adverse events during the concurrent phase were hematologic and 5.1% of patients experienced grade 3 esophagitis. The response rate was 45.9% (17 of 37 patients), with no complete responses. The 1-, 2-, and 3-year OS survival rates were 79.5%, 56.4%, and 46.2%, respectively. The median OS, time to progressive disease, and progression-free survival was 30.3, 13.7, and 11.8 months, respectively., Conclusion: Full-dose cisplatin and pemetrexed can be administered concurrently with conventional doses of thoracic radiation. The median and 1-year OS rates were favorable compared with published clinical trials in this setting. The regimen was tolerable, and the toxicity profile was consistent with the known toxicity profiles of pemetrexed, cisplatin, and radiation., (Copyright © 2016 Elsevier Inc. All rights reserved.)