Time for change: a new training programme for morpho-molecular pathologists?

The evolution of cellular pathology as a specialty has always been driven by technological developments and the clinical relevance of incorporating novel investigations into diagnostic practice. In recent years, the molecular characterisation of cancer has become of crucial relevance in patient treatment both for predictive testing and subclassification of certain tumours. Much of this has become possible due to the availability of next-generation sequencing technologies and the whole-genome sequencing of tumours is now being rolled out into clinical practice in England via the 100 000 Genome Project. The effective integration of cellular pathology reporting and genomic characterisation is crucial to ensure the morphological and genomic data are interpreted in the relevant context, though despite this, in many UK centres molecular testing is entirely detached from cellular pathology departments. The CM-Path initiative recognises there is a genomics knowledge and skills gap within cellular pathology that needs to be bridged through an upskilling of the current workforce and a redesign of pathology training. Bridging this gap will allow the development of an integrated 'morphomolecular pathology' specialty, which can maintain the relevance of cellular pathology at the centre of cancer patient management and allow the pathology community to continue to be a major influence in cancer discovery as well as playing a driving role in the delivery of precision medicine approaches. Here, several alternative models of pathology training, designed to address this challenge, are presented and appraised

Identifying the top ten unanswered questions in community nursing: A James Lind Alliance Priority Setting Partnership in Community Nursing

Community nurses deliver comprehensive nursing care to patients living outside of hospital settings and play a crucial role in meeting individual and public health needs. Research is essential in providing evidence-based care for patients; however, most community nurses are not research active, with few relevant studies and little funding for community nursing research. To address this, four National Institute for Health Research senior nurse researchers in England conducted a James Lind Alliance priority setting partnership in community nursing with the aim of raising the international profle of community nursing research through the identifcation of meaningful research priorities that matter to this community. Community nurses, patients, and carers were integral to the process, which aimed to identify the top ten unanswered questions to inform community nursing practice. The Priority Setting Partnership process utilised a coproduction, mixed-methods approach. It involved consultation meetings with stakeholder partners and nested quantitative surveys. The study ran from March 2020 until September 2021, and numerous unanswered evidence uncertainties were identifed. The top ten priority questions included nursing and patient focussed issues, which refect the complexity of care delivered to patients and the workforce pressures community nurses face. Findings refect the views of community nurses, patients, and carers and highlight areas that need attention to ensure research is embedded within community nursing settings. Identifcation of the top ten priorities has provided an international platform for community nursing research. This must be sustained through engagement, collaboration, funding, and innovation and has widespread implications for developing the community nursing workforce and optimising the safety and quality of patient care

Empowering nurses through inclusive leadership to promote research capacity building: A James Lind Alliance priority setting Partnership in Community Nursing

Aims. This paper focuses on the benefits of inclusive leadership when undertaking a priority setting partnership in community nursing, through providing a collaborative and committed nurse-led forum for initiating impactful changes, identifying evidence uncertainties and driving research capacity-building initiatives. Design. This is a Discussion paper. The project was undertaken between 2020 and 2021. Data sources. This paper is based on shared reflections as 70@70 Senior Nurse Research Leaders and is supported by literature and theory. It draws on issues relating to collective leadership, stakeholder engagement, diversity, inclusivity and COVID-19. Implications for nursing. The James Lind Alliance Priority Setting Partnership catalysed the development of a rigorous evidence-base in community nursing. The collaborative opportunities, networks and connections developed with patients, carers, nursing leaders, policy makers and healthcare colleagues raised the profile of community nursing research. This will benefit nursing research, practice, education and patients in receipt of community nursing care. Collective buy in from national leaders in policy, education, funding and commissioning has secured a commitment that the evidence uncertainties will be funded. Conclusion. Four key learnings emerged: collective leadership can ensure learning is embedded and sustained; developing an engaged stakeholder community to promote community nursing research is essential; a diverse membership ensures inclusivity and representation; and insights into the impact of COVID-19 aid progress. The process increased research engagement and created capacity and capability-building initiatives. This will help community nurses feel empowered to lead changes to practice. Sustained engagement and commitment are required to integrate research priorities into community nursing research, education and practice and to drive forward changes to commissioning and service delivery. Impact. The study promoted research capacity building through inclusive leadership. This can increase community nurses' research engagement and career development and patient care quality and safety; this can incentivize funders and policy makers to prioritize community nursing research

Availability of long-acting and permanent family-planning methods leads to increase in use in conflict-affected northern Uganda: evidence from cross-sectional baseline and endline cluster surveys

Humanitarian assistance standards require specific attention to address the reproductive health (RH) needs of conflict-affected populations. Despite these internationally recognised standards, access to RH services is still often compromised in war. We assessed the effectiveness of our programme in northern Uganda to provide family planning (FP) services through mobile outreach and public health centre strengthening. Baseline (n=905) and endline (n=873) cross-sectional surveys using a multistage cluster sampling design were conducted in the catchment areas of four public health centres in 2007 and 2010. Current use of any modern FP method increased from 7.1% to 22.6% (adjusted odds ratio [OR] 3.34 [95% confidence interval (CI) 2.27–4.92]); current use of long-acting and permanent methods increased from 1.2% to 9.8% (adjusted OR 9.45 [95%CI 3.99–22.39]). The proportion of women with unmet need for FP decreased from 52.1% to 35.7%. This study demonstrates that when comprehensive FP services are provided among conflict-affected populations, women will choose to use them. The combination of mobile teams and health systems strengthening can make a full range of methods quickly available while supporting the health system to continue to provide those services in challenging and resource-constrained settings

Regional-scale drivers of groundwater faunal distributions

Freshwater aquifers are a major source of drinking water; they also possess unique assemblages of organisms. However, little is known about the distributional drivers of obligate groundwater organisms at the regional scale. We examine the distribution and composition of stygobiont assemblages in a complex geological setting and explore the relationship between groundwater fauna, hydrogeology and water chemistry. In the study area we grouped similar geologies into five hydrogeological formations (hydro-units) within which habitats for groundwater fauna were broadly similar. We found that the occurrence of stygobionts differed significantly between hydro-units. Stygobionts were significantly less likely to be recorded in mudstone/siltstone and sandstone aquifers compared with carbonate rocks or with igneous/metamorphic rocks. Variance partitioning indicated that the hydro-units explained a greater proportion of the variance (7.52%) in the groundwater community than water chemistry (5.02%). However, much of the variation remained unexplained. The macrofaunal stygobiont species in our study area formed three groups: (1) Niphargus glenniei was recorded in a range of hydro- units but only in the west of the study area. (2) Niphargus kochianus , Niphargus fontanus, Proasellus cavaticus and Crangonyx subterraneus were predominately recorded in carbonate aquifers in the east of the study area. (3) Niphargus aquilex and Microniphargus leruthi, were found throughout the study area and in a range of hydro-units. We hypothesise that physical barriers exist that prevent some stygobiont taxa from colonizing apparently suitable geologies; the low permeability deposits dividing the western and eastern parts of the study area may partly explain the observed distributions

Patients' use of a home-based virtual reality system to provide rehabilitation of the upper limb following stroke

Background: A low cost, virtual reality system that translates movements of the hand, fingers and thumb into game play was designed to provide a flexible and motivating approach to increasing adherence to home based rehabilitation. Objective: Effectiveness depends on adherence, so did patients use the intervention to the recommended level. If not, what reasons did they give? Design: Prospective cohort study plus qualitative analysis of interviews. Methods: 17 patients recovering from stroke recruited to the intervention arm of a feasibility trial had the equipment left in their homes for eight weeks and were advised to use it three times a day for periods of no more than 20 minutes. Frequency and duration of use were automatically recorded. At the end of the intervention, participants were interviewed to determine barriers to using it in the recommended way. Results: Duration of use and how many days they used the equipment are presented for the 13 participants who successfully started the intervention. These figures were highly variable and could fall far short of our recommendations. There was a weak (p=0.053) positive correlation between duration and baseline reported activities of daily living. Participants reported familiarity with technology and competing commitments as barriers to use although appreciated the flexibility of the intervention and found it motivating

Comparing web-based mindfulness with loving-kindness and compassion training for promoting well-being in pregnancy: Protocol for a three-arm pilot randomized controlled trial

© Amy Louise Finlay-Jones, Jacqueline Ann Davis, Amanda O\u27Donovan, Keerthi Kottampally, Rebecca Anne Ashley, Desiree Silva, Jeneva Lee Ohan, Susan L Prescott, Jenny Downs. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 14.10.2020. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Research Protocols, is properly cited. The complete bibliographic information, a link to the original publication on http://www.researchprotocols.org, as well as this copyright and license information must be included. Background: Promoting psychological well-being and preventing distress among pregnant women is an important public health goal. In addition to adversely impacting the mother’s health and well-being, psychological distress in pregnancy increases the risk of poor pregnancy outcomes, compromises infant socioemotional development and bonding, and heightens maternal and child vulnerability in the postpartum period. Mindfulness and compassion-based interventions show potential for prevention and early intervention for perinatal distress. As there is an established need for accessible, scalable, flexible, and low-cost interventions, there is increased interest in the delivery of these programs on the web. This project aims to pilot a three-arm randomized controlled trial (RCT) to determine the feasibility of a full-scale RCT comparing 2 web-based interventions (mindfulness vs loving-kindness and compassion) with a web-based active control condition (progressive muscle relaxation). Objective: The primary objective of this study is to assess the feasibility of an RCT protocol comparing the 3 conditions delivered on the web as a series of instructional materials and brief daily practices over a course of 8 weeks. The second objective is to explore the experiences of women in the different intervention conditions. The third objective is to estimate SD values for the outcome measures to inform the design of an adequately powered trial to determine the comparative efficacy of the different conditions. Methods: Pregnant women (n=75) participating in a longitudinal birth cohort study (the ORIGINS project) will be recruited to this study from 18 weeks of gestational age. We will assess the acceptability and feasibility of recruitment and retention strategies and the participants’ engagement and adherence to the interventions. We will also assess the experiences of women in each of the 3 intervention conditions by measuring weekly changes in their well-being and engagement with the program and by conducting a qualitative analysis of postprogram interviews. Results: This project was funded in September 2019 and received ethics approval on July 8, 2020. Enrollment to the study will commence in September 2020. Feasibility of a full-scale RCT will be assessed using ADePT (a process for decision making after pilot and feasibility trials) criteria. Conclusions: If the study is shown to be feasible, results will be used to inform future full-scale RCTs. Evidence for flexible, scalable, and low-cost interventions could inform population health strategies to promote well-being and reduce psychological distress among pregnant women

Behavioral modifications by a large-northern herbivore to mitigate warming conditions

Background: Temperatures in arctic-boreal regions are increasing rapidly and pose significant challenges to moose (Alces alces), a heat-sensitive large-bodied mammal. Moose act as ecosystem engineers, by regulating forest carbon and structure, below ground nitrogen cycling processes, and predator-prey dynamics. Previous studies showed that during hotter periods, moose displayed stronger selection for wetland habitats, taller and denser forest canopies, and minimized exposure to solar radiation. However, previous studies regarding moose behavioral thermoregulation occurred in Europe or southern moose range in North America. Understanding whether ambient temperature elicits a behavioral response in high-northern latitude moose populations in North America may be increasingly important as these arctic-boreal systems have been warming at a rate two to three times the global mean. Methods: We assessed how Alaska moose habitat selection changed as a function of ambient temperature using a step-selection function approach to identify habitat features important for behavioral thermoregulation in summer (June–August). We used Global Positioning System telemetry locations from four populations of Alaska moose (n = 169) from 2008 to 2016. We assessed model fit using the quasi-likelihood under independence criterion and conduction a leave-one-out cross validation. Results: Both male and female moose in all populations increasingly, and nonlinearly, selected for denser canopy cover as ambient temperature increased during summer, where initial increases in the conditional probability of selection were initially sharper then leveled out as canopy density increased above ~ 50%. However, the magnitude of selection response varied by population and sex. In two of the three populations containing both sexes, females demonstrated a stronger selection response for denser canopy at higher temperatures than males. We also observed a stronger selection response in the most southerly and northerly populations compared to populations in the west and central Alaska. Conclusions: The impacts of climate change in arctic-boreal regions increase landscape heterogeneity through processes such as increased wildfire intensity and annual area burned, which may significantly alter the thermal environment available to an animal. Understanding habitat selection related to behavioral thermoregulation is a first step toward identifying areas capable of providing thermal relief for moose and other species impacted by climate change in arctic-boreal regions.publishedVersio

Therapeutic targeting of integrin αvβ6 in breast cancer

BACKGROUND: Integrin ?v?6 promotes migration, invasion, and survival of cancer cells; however, the relevance and role of ?v?6 has yet to be elucidated in breast cancer.METHODS: Protein expression of integrin subunit beta6 (?6) was measured in breast cancers by immunohistochemistry (n &gt; 2000) and ITGB6 mRNA expression measured in the Molecular Taxonomy of Breast Cancer International Consortium dataset. Overall survival was assessed using Kaplan Meier curves, and bioinformatics statistical analyses were performed (Cox proportional hazards model, Wald test, and Chi-square test of association). Using antibody (264RAD) blockade and siRNA knockdown of ?6 in breast cell lines, the role of ?v?6 in Human Epidermal Growth Factor Receptor 2 (HER2) biology (expression, proliferation, invasion, growth in vivo) was assessed by flow cytometry, MTT, Transwell invasion, proximity ligation assay, and xenografts (n ? 3), respectively. A student's t-test was used for two variables; three-plus variables used one-way analysis of variance with Bonferroni's Multiple Comparison Test. Xenograft growth was analyzed using linear mixed model analysis, followed by Wald testing and survival, analyzed using the Log-Rank test. All statistical tests were two sided.RESULTS: High expression of either the mRNA or protein for the integrin subunit ?6 was associated with very poor survival (HR = 1.60, 95% CI = 1.19 to 2.15, P = .002) and increased metastases to distant sites. Co-expression of ?6 and HER2 was associated with worse prognosis (HR = 1.97, 95% CI = 1.16 to 3.35, P = .01). Monotherapy with 264RAD or trastuzumab slowed growth of MCF-7/HER2-18 and BT-474 xenografts similarly (P &lt; .001), but combining 264RAD with trastuzumab effectively stopped tumor growth, even in trastuzumab-resistant MCF-7/HER2-18 xenografts.CONCLUSIONS: Targeting ?v?6 with 264RAD alone or in combination with trastuzumab may provide a novel therapy for treating high-risk and trastuzumab-resistant breast cancer patients.<br/