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Background: Collaborative relationships between academic oncology and industry (pharmaceutical, biotechnology, "omic," and medical device companies) are essential for therapeutic development in oncology; however, limited research on engagement in and perceptions of these relationships has been done. Methods: Survey questions were developed to evaluate relationships between academic oncology and industry. An electronic survey was delivered to 1000 randomly selected members of the American Society of Clinical Oncology, a professional organization for oncologists, eliciting respondents' views around oncology‐industry collaborations. The responses were analyzed according to prespecified plans. Results: There were 225 survey respondents. Most were from the United States (70.0%), worked at an academic institution (60.1%), worked in medical oncology (81.2%), and had an active relationship with industry (85.8%). One quarter (26.7%) of respondents reported difficulty establishing a relationship with industry collaborators, and most respondents (75%) did not report having had mentorship in developing these relationships. The majority (85.3%) of respondents considered these collaborations important to their careers. Respondents generally thought that scientific integrity was preserved (92%), and most respondents (95%) had little concern over the quality of the collaborative product. Many (60%) shared concerns over potential conflict of interest if an individual with a compensated relationship promoted an industry product for clinical care/research, yet most respondents (67%) stated these relationships did not shape their interactions with patients. Conclusions: This study provides novel data characterizing the nature of collaborative relationships between clinicians, researchers, and industry in oncology. Although respondents considered these collaborations an important part of clinical and academic oncology, formal education or mentorship around these relationships was rare. Conflicting findings around conflict of interest highlight the importance of more dedicated research in this area. Plain Language Summary: Business enterprises in health care play a central role in cancer research and care, driving the development of new medical testing, drugs, and devices. Effective working relationships among clinicians, researchers, and these industry partners can promote innovative research and enhance patient care. Study of these collaborations has been limited to date. Through distribution of a questionnaire to cancer clinicians and researchers, we found that most participants consider these relationships valuable, though they find establishing such relationships challenging partly because of gaps in educational programs in this area. Our findings also highlight the need for further policy around the potential bias these relationships can introduce. Oncology‐industry collaborations can be mutually beneficial relationships that contribute to both scientific and clinical innovation. Despite their value, a deficit of education and policy around these collaborations is recognized by cancer clinicians and researchers. [ABSTRACT FROM AUTHOR]

Background and Aims: The impacts of the COVID‐19 pandemic have not been equal, with a disproportionate impact among ethnic minority communities. Structural inequalities in social determinants of health such as housing and employment have contributed to COVID‐19's impact on deprived communities, including many ethnic minority communities. To compare (1) how the UK government's "social distancing" restrictions and guidance were perceived and implemented by ethnic minority populations compared to white populations, (2) the impact of restrictions and guidance upon these groups. Methods: An explanatory sequential mixed methods study incorporated a quantitative survey and qualitative semi‐structured interviews to explore individual perceptions and experiences of COVID‐19 and the national restrictions. Survey participants (n = 1587) were recruited from North West England; 60 (4%) participants were from ethnic minority communities. Forty‐nine interviews were conducted; 19 (39%) participants were from ethnic minority communities. Interviews were transcribed verbatim and analysed using a thematic approach. Data collection was between April and August 2020. Results: Significant differences in demographics and household overcrowding were observed between white vs ethnic minority survey respondents, who were also significantly less confident in their knowledge of COVID‐19, less likely to be high‐risk drinkers, and marginally more likely to have experienced job loss and/or reduced household income. There were no group differences in wellbeing, perceptions, or nonfinancial impacts. Two inter‐related themes included: (1) government guidance, incorporating people's knowledge and understanding of the guidance and their confusion/frustration over messaging; (2) the impacts of restrictions on keyworkers, home‐schooling, working from home and changes in lifestyle/wellbeing. Conclusions: Further research is needed on the long‐term impacts of COVID‐19 on ethnic minority communities. If policy responses to COVID‐19 are to benefit ethnic minority communities, there is a need for future studies to consider fundamental societal issues, such as the role of housing and economic disadvantage. Highlights: What is known about this topic? The COVID‐19 pandemic has impacted the entire world, however it has had disproportionate impacts on ethnic minority communities.'Social distancing' is a public health intervention that has been utilised in previous pandemics where measures are put in place to encourage individuals to undertake a number of changes to their social behaviours to increase physical distance from others and to reduce number of contacts with other people.Living conditions such as overcrowding are a risk factor for ill health, including from COVID‐19. What this paper add? Ethnic minority respondents were significantly more concerned about the educational impacts on their children.Living in overcrowded homes significantly affected the ethnic minority respondents with regard to increased risk within their home environment, less space for privacy for working from home and education/welfare needs of children.More practical and relevant government guidance is needed for ethnic minority communities and future policy should consider the economic and societal impacts for ethnic minority workers. [ABSTRACT FROM AUTHOR]

Background: Patients with high‐grade glioma (HGG) face unique challenges toward the end of life (EoL), given their aggressive trajectory and neurologic deterioration. Aggressiveness of medical care at EoL has been identified as an important quality metric for oncology patients. At this time, limited data exist around the nature of EoL care of patients with HGG. Methods: Patients with HGG and palliative care (PC) referral seen between 2010 and 2015 were identified (N = 80). Of these, N = 52 met inclusion criteria. Random selections of patients with (1) HGG not referred to PC (n = 80), and (2) non‐CNS cancers with PC referral (n = 80) were identified for comparison. A composite score of aggressiveness of medical care at EoL was calculated for each patient from predetermined variables. A time of eligibility for PC was defined for each patient when predetermined criteria based on symptom burden, functional status, and prognosis were met. Results: Among the patients analyzed with HGG referred to PC, 59.6% (N = 31) were referred as inpatients, and 53.8% (N = 28) were referred within the last 12 weeks of life. Patients with HGG had similar aggressiveness of care at EoL regardless of PC referral, and HGG patients had less aggressive care at EoL than patients with non‐CNS cancers (p = 0.007). Care was more aggressive at EoL in HGG patients who received late versus early PC referrals (p = 0.012). Motor weakness at time of eligibility (OR = 2.55, p = 0.002) and more disease progressions (OR = 1.25, p = 0.043) were associated with less aggressive care at EoL. Conclusions: Early clinical‐ and disease‐related features predict the aggressiveness of medical care at EoL in patients with HGG. Formal PC consultation is used infrequently and suboptimally in patients with HGG. Our data suggest that the role of PC in improving EoL outcomes in HGG warrants further evaluation. [ABSTRACT FROM AUTHOR]

Background: Although autism spectrum disorder (ASD) is heritable, the mechanisms through which genes contribute to symptom emergence remain unclear. Investigating candidate intermediate phenotypes such as the pupillary light reflex (PLR) prospectively from early in development could bridge genotype and behavioural phenotype. Methods: Using eye tracking, we longitudinally measured the PLR at 9, 14 and 24 months in a sample of infants (N = 264) enriched for a family history of ASD; 27 infants received an ASD diagnosis at 3 years. We examined the 9‐ to 24‐month developmental trajectories of PLR constriction latency (onset; ms) and amplitude (%) and explored their relation to categorical 3‐year ASD outcome, polygenic liability for ASD and dimensional 3‐year social affect (SA) and repetitive/restrictive behaviour (RRB) traits. Polygenic scores for ASD (PGSASD) were calculated for 190 infants. Results: While infants showed a decrease in latency between 9 and 14 months, higher PGSASD was associated with a smaller decrease in latency in the first year (β = −.16, 95% CI = −0.31, −0.002); infants with later ASD showed a significantly steeper decrease in latency (a putative 'catch‐up') between 14 and 24 months relative to those with other outcomes (typical: β =.54, 95% CI = 0.08, 0.99; other: β =.53, 95% CI = 0.02, 1.04). Latency development did not associate with later dimensional variation in ASD‐related traits. In contrast, change in amplitude was not related to categorical ASD or genetics, but decreasing 9‐ to 14‐month amplitude was associated with higher SA (β =.08, 95% CI = 0.01, 0.14) and RRB (β =.05, 95% CI = 0.004, 0.11) traits. Conclusions: These findings corroborate PLR development as possible intermediate phenotypes being linked to both genetic liability and phenotypic outcomes. Future work should incorporate alternative measures (e.g. functionally informed structural and genetic measures) to test whether distinct neural mechanisms underpin PLR alterations. [ABSTRACT FROM AUTHOR]

Objective: Impaired neurocognitive function (NCF) is a well-established consequence of pediatric medulloblastoma (MB) and its treatments. However, the frequency and features of neurocognitive dysfunction in adult-onset MB patients are largely unknown.Methods: Adult patients (≥ 18 years) with MB who had received formal neurocognitive evaluation (N = 27) were identified. Demographic, medical, and treatment histories were extracted from the medical record. Lesion properties on MRI were analyzed and used to evaluate lesion-symptom mapping further. Demographically adjusted z-scores were calculated for each neurocognitive test and used to assess impairment frequency. Regression analyses were conducted to identify clinical and paraclinical factors associated with impaired NCF.Results: Mean age of the patient sample was 33 years (SD = 11) at the time of MB diagnosis. Prior therapy included surgical resection (89%), radiation (70%), and chemotherapy (26%). A significant proportion of patients were impaired on tests of verbal learning and memory (32%), executive function (29%), and naming (18%). Age, education, lesion size, time from surgery, and number of chemotherapy cycles had the greatest contribution to test performance in random-forest regression models.Conclusion: This study identifies frequent impairment of NCF in adult patients with MB, particularly in the domains of learning and memory and executive function. Neurocognitive impairment is influenced by patients' demographic, disease, and treatment history. Further study is warranted to characterize the clinical impact of adult MB more fully. [ABSTRACT FROM AUTHOR]

Background: Persistent post‐stroke headache is a clinical entity that has recently entered the International Classification of Headache Disorders, 3rd edition. In contrast to acute headache attributed to stroke, the epidemiology, clinical features, potential pathophysiology, and management of persistent post‐stroke headache have not been reviewed. Methods: We summarize the literature describing persistent headache attributed to stroke. Results: Persistent headache after ischemic or hemorrhagic stroke affects up to 23% of patients. These persistent headaches tend to have tension‐type features and are more frequent and severe than acute stroke‐related headaches. Risk factors include younger age, female sex, pre‐existing headache disorder, and comorbid post‐stroke fatigue or depression. Other factors including obstructive sleep apnea or musculoskeletal imbalances may contribute to headache persistence. Although more evidence is needed, it may be reasonable to treat persistent post‐stroke headache according to headache semiology. Conclusion: Recognition of persistent post‐stroke headache as a separate clinical entity from acute stroke‐attributed headache is the first step toward better defining its natural history and most effective treatment strategies. [ABSTRACT FROM AUTHOR]

ABSTRACT: Movement connects otherwise isolated populations, influencing demographic persistence and promoting gene flow. We evaluated the effect of movement on the genetic and demographic viability of the red wolf (Canis rufus) and tested the application of metapopulation theory to management of this endangered predator. The establishment of a captive subpopulation in the 1970s allowed persistence of the species and facilitated a reintroduction program that supported 2 wild subpopulations, one of which persists today. We assessed the effect of historical and potential future movement between the wild and captive subpopulations on the genetic and demographic viability of the metapopulation. We analyzed approximately 30 years of individual‐level data to quantify the effects of historical movement among subpopulations and constructed an individual‐based metapopulation model to predict the effects of future potential movement (i.e., releases of captive wolves) on the species’ persistence and genetic diversity. Counter to theory, increased movement has had positive demographic effects, with higher per capita movement rates leading to increased metapopulation growth and decreased subpopulation synchrony. These counter‐theoretical results are likely due to differences in reproduction and survival rates among subpopulations and the small size of the metapopulation. Furthermore, higher rates of movement did not increase retention of genetic diversity, likely because of the active pedigree‐based breeding management of the species already maximizing gene retention. Our model indicates that future releases of captive wolves are necessary, but not sufficient, for the survival of the species, and must be combined with changes to demographic rates in both the captive and northeastern North Carolina subpopulations. Our results highlight the need for models and field data that more adequately describe the viability of small metapopulations. © 2017 The Wildlife Society. [ABSTRACT FROM AUTHOR]

Aims p53 immunostaining in Barrett's oesophagus ( BO) has been shown to be predictive of progression, but data regarding its generalizability to routine practice are lacking. This study compared the reliability of p53 and dysplasia interpretation and grading. Methods and results Seventy-two cases encompassing the full spectrum of BO were circulated to 10 pathologists from four institutions after a brief training session in p53 interpretation. Each pathologist classified cases on haematoxylin and eosin (H&E) alone using the Vienna classification and assessed the p53 staining using a qualitative system. Agreement was assessed using kappa statistics. For the four-tier Vienna system, the average unweighted kappa was 0.30. Weighted kappa values varied from 0.27 to 0.69 with an average of 0.47. When grouped into definite dysplasia versus no definite dysplasia the average kappa was 0.55, but the kappa for low-grade dysplasia ( LGD) versus high-grade dysplasia ( HGD) was only 0.31. For p53, using the three recognized patterns, the unweighted kappa was 0.6 (confidence interval 0.58-0.63). When cases were evaluated with both H&E and p53 the average kappa was 0.61 for definite dysplasia versus the rest. Conclusions p53 immunohistochemistry interpretation is more reliable than dysplasia diagnosis, even with limited training. As it is predictive of prognosis and improves diagnostic reproducibility, it is suitable for routine use by pathologists as an adjunct to dysplasia diagnosis. The distinction of LGD versus HGD was poor. This study supports simplifying dysplasia diagnosis into 'present', 'indefinite' or 'absent', and the use of p53 as an ancillary marker in difficult cases. This should help to prevent overdiagnosis of dysplasia and inappropriate treatment. [ABSTRACT FROM AUTHOR]

Norwood M G A, Bailey N, Nanji M, Gillies R S, Nicholson A, Ubhi S, Darnton J J, Steyn R S, Womack C, Hughes A, Hemingway D, Harrison R, Waters R & Jankowski J A (2010) Histopathology 57, 101–111 Cytoplasmic β-catenin accumulation is a good prognostic marker in upper and lower gastrointestinal adenocarcinomas Aims: β-Catenin is an important molecule in cancer biology. Membranous β-catenin enhances cellular differentiation and inhibits invasion by its action on E-cadherin. The aim was to ascertain whether the cellular expression of these molecules in colorectal and oesophageal cancer specimens is associated with survival in patients with gastrointestinal cancer. Methods and results: Tumour samples from 149 patients undergoing resection for colorectal adenocarcinoma and 147 patients undergoing resection for oesophageal adenocarcinoma were retrospectively analysed using immunohistochemical techniques to assess β-catenin expression. Increasing β-catenin expression in the cytoplasm was associated with improved survival for colorectal cancer cases on both univariate ( P = 0.003) and multivariate ( P = 0.01) analysis. In addition, increased expression in the most recent cohort of oesophageal adenocarcinoma patients was associated with improved TNM staging ( P = 0.007). Membrane expression was weakly associated with survival in colorectal cancer on univariate analysis ( P = 0.09), but not on multivariate analysis ( P = 0.21). Complete absence of β-catenin expression at all three sites was associated with reduced 5-year survival in colorectal cancer. Conclusions: This is one of the largest prognostic studies of β-catenin in gastrointestinal adenocarcinoma. It shows that low levels of cytoplasmic β-catenin expression are associated with reduced survival in patients with colorectal cancer as well as worse TNM staging in oesophageal adenocarcinoma (a recognized surrogate end-point for survival). We believe this is the first time that this has been reported. This finding should be tested prospectively in oncological trials to validate whether the presence of cytoplasmic β-catenin could be used as a prognostic marker for less aggressive disease. [ABSTRACT FROM AUTHOR]

The hippocampus is critical for spatial memory. Recently, subregional differences in the function of hippocampus have been described in a number of behavioral tasks. The present experiments assessed the effects of reversibly lesioning either the dorsal (dHip) or ventral hippocampus (vHip) on spontaneous tests of spatial recognition and temporal order memory. We report that although the dHip is necessary for spatial recognition memory (RM) (distinguishing a novel from a familiar spatial location), the vHip is involved in temporal order memory (the capacity to distinguish between two spatial locations visited at different points in time), but not RM. These findings and others are consistent with the hypothesis that temporal order memory is supported by an integrated circuit of limbic areas including the vHip and the medial prefrontal cortex. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]