Primary palliative care team perspectives on coordinating and managing people with advanced cancer in the community : a qualitative study

Background Primary health care teams are key to the delivery of care for patients with advanced cancer during the last year of life. The Gold Standards Framework is proposed as a mechanism for coordinating and guiding identification, assessment, and support. There are still considerable variations in practice despite its introduction. The aim of this qualitative study is to improve understanding of variations in practice through exploring the perspectives and experiences of members of primary health care teams involved in the care of patients with advanced cancer. Methods Qualitative, semi-structured interviews, focus groups, and non-participatory observations involving 67 members of primary health care teams providing palliative care. Data were analysed using a grounded theory approach. Results We identified distinct differences in the drivers and barriers of community advanced cancer care coordination, which relate to identification and management, and access to effective pain management, and go some way to understanding variations in practice. These include proactive identification processes, time and resource pressures, unclear roles and responsibilities, poor multidisciplinary working, and inflexible models for referral and prescribing. These provide valuable insight into how professionals work together and independently within an infrastructure that can both support and hinder the provision of effective community palliative care. Conclusions Whilst the GSF is a guide for good practice, alone it is not a mechanism for change. Rather it provides a framework for describing quality of practice that was already occurring. Consequently, there will continue to be variations in practice

Evaluating the effectiveness of agricultural adaptation to climate change in preindustrial society

The effectiveness of agricultural adaptation determines the vulnerability of this sector to climate change, particularly during the preindustrial era. However, this effectiveness has rarely been quantitatively evaluated, specifically at a large spatial and long-term scale. The present study covers this case of preindustrial society in AD 1500–1800. Given the absence of technological innovations in this time frame, agricultural production was chiefly augmented by cultivating more land (land input) and increasing labor input per land unit (labor input). Accordingly, these two methods are quantitatively examined. Statistical results show that within the study scale, land input is a more effective approach of mitigating climatic impact than labor input. Nonetheless, these observations collectively improve Boserup's theory from the perspective of a large spatial and long-term scale.postprin

Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist

"Background Pegvisomant is a new growth hormone receptor antagonist that improves symptoms and normalises insulin-like growth factor-1 (IGF-1) in a high proportion of patients with acromegaly treated for up to 12 weeks. We assessed the effects of pegvisomant in 160 patients with acromegaly treated for an average of 425 days. Methods Treatment efficacy was assessed by measuring changes in tumour volume by magnetic resonance imaging, and serum growth hormone and IGF-1 concentrations in 152 patients who received pegvisomant by daily subcutaneous injection for up to 18 months. The safety analysis included 160 patients some of whom received weekly injections and are excluded from the efficacy analysis. Findings Mean serum IGF-1 concentrations fell by at least 50%: 467 μg/L (SE 24), 526 μg/L (29), and 523 μg/L (40) in patients treated for 6, 12 and 18 months, respectively (p less than 0·001), whereas growth hormone increased by 12·5 μg/L (2·1), 12·5 μg/L (3·0), and 14·2 μg/L (5·7) (p less than 0·001). Of the patients treated for 12 months or more, 87 of 90 (97%) achieved a normal serum IGF-1 concentration. In patients withdrawn from pegvisomant (n=45), serum growth hormone concentrations were 8·0 μg/L (2·5) at baseline, rose to 15·2 μg/L (2·4) on drug, and fell back within 30 days of withdrawal to 8·3 μg/L (2·7). Antibodies to growth hormone were detected in 27 (16·9%) of patients, but no tachyphylaxis was seen. Serum insulin and glucose concentrations were significantly decreased (p less than 0·05). Two patients experienced progressive growth of their pituitary tumours, and two other patients had increased alanine and asparate aminotransferase concentrations requiring withdrawal from treatment. Mean pituitary tumour volume in 131 patients followed for a mean of 11·46 months (0·70) decreased by 0·033 cm3(0·057; p=0·353). Interpretation Pegvisomant is an effective medical treatment for acromegaly.

Imaging of bronchial pathology in antibody deficiency: Data from the European Chest CT Group

Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease

Priorities for synthesis research in ecology and environmental science

ACKNOWLEDGMENTS We thank the National Science Foundation grant #1940692 for financial support for this workshop, and the National Center for Ecological Analysis and Synthesis (NCEAS) and its staff for logistical support.Peer reviewedPublisher PD

Priorities for synthesis research in ecology and environmental science

ACKNOWLEDGMENTS We thank the National Science Foundation grant #1940692 for financial support for this workshop, and the National Center for Ecological Analysis and Synthesis (NCEAS) and its staff for logistical support.Peer reviewedPublisher PD

Tumor necrosis factor superfamily member APRIL contributes to fibrotic scar formation after spinal cord injury

BACKGROUND: Fibrotic scar formation contributes to the axon growth-inhibitory environment that forms following spinal cord injury (SCI). We recently demonstrated that depletion of hematogenous macrophages led to a reduction in fibrotic scar formation and increased axon growth after SCI. These changes were associated with decreased TNFSF13 (a proliferation inducing ligand (APRIL)) expression, but the role of APRIL in fibrotic scar formation after SCI has not been directly investigated. Thus, the goal of this study was to determine the role of APRIL in fibrotic scar formation after SCI. METHODS: APRIL knockout and wild-type mice received contusive SCI and were assessed for inflammatory cytokine/chemokine expression, leukocyte infiltration, fibrotic scar formation, axon growth, and cell proliferation. RESULTS: Expression of APRIL and its receptor BCMA is increased following SCI, and genetic deletion of APRIL led to reduced fibrotic scar formation and increased axon growth. However, the fibrotic scar reduction in APRIL KO mice was not a result of changes in fibroblast or astrocyte proliferation. Rather, APRIL knockout mice displayed reduced TNFα and CCL2 expression and less macrophage and B cell infiltration at the injury site. CONCLUSIONS: Our data indicate that APRIL contributes to fibrotic scar formation after SCI by mediating the inflammatory response

Symbiodinium Transcriptomes: Genome Insights into the Dinoflagellate Symbionts of Reef-Building Corals

Dinoflagellates are unicellular algae that are ubiquitously abundant in aquatic environments. Species of the genus Symbiodinium form symbiotic relationships with reef-building corals and other marine invertebrates. Despite their ecologic importance, little is known about the genetics of dinoflagellates in general and Symbiodinium in particular. Here, we used 454 sequencing to generate transcriptome data from two Symbiodinium species from different clades (clade A and clade B). With more than 56,000 assembled sequences per species, these data represent the largest transcriptomic resource for dinoflagellates to date. Our results corroborate previous observations that dinoflagellates possess the complete nucleosome machinery. We found a complete set of core histones as well as several H3 variants and H2A.Z in one species. Furthermore, transcriptome analysis points toward a low number of transcription factors in Symbiodinium spp. that also differ in the distribution of DNA-binding domains relative to other eukaryotes. In particular the cold shock domain was predominant among transcription factors. Additionally, we found a high number of antioxidative genes in comparison to non-symbiotic but evolutionary related organisms. These findings might be of relevance in the context of the role that Symbiodinium spp. play as coral symbionts

Sex differences in dementia risk and risk factors: Individual‐participant data analysis using 21 cohorts across six continents from the COSMIC consortium

Introduction: Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno‐regional groups. Methods: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta‐analysis. Sex‐specific hazard ratios (HRs), and women‐to‐men ratio of hazard ratios (RHRs) for associations between RFs and all‐cause dementia were derived from mixed‐effect Cox models. Results: Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low‐ and lower‐middle‐income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs. Discussion: Dementia risk was higher in women than men, with possible variations by country‐level income settings, but most RFs appear to work similarly in women and men