Are analysts' loss functions asymmetric?

Recent research by Gu and Wu (2003) and Basu and Markov (2004) suggests that the well-known optimism bias in analysts? earnings forecasts is attributable to analysts minimizing symmetric, linear loss functions when the distribution of forecast errors is skewed. An alternative explanation for forecast bias is that analysts have asymmetric loss functions. We test this alternative explanation. Theory predicts that if loss functions are asymmetric then forecast error bias depends on forecast error variance, but not necessarily on forecast error skewness. Our results confirm that the ex ante forecast error variance is a significant determinant of forecast error and that, after controlling for variance, the sign of the coefficient on forecast error skewness is opposite to that found in prior research. Our results are consistent with financial analysts having asymmetric loss functions. Further analysis reveals that forecast bias varies systematically across style portfolios formed on book-to-price and market capitalization. These firm characteristics capture systematic variation in forecast error variance and skewness. Within style portfolios, forecast error variance continues to play a dominant role in explaining forecast error.

Are analysts? loss functions asymmetric?

Recent research by Gu and Wu (2003) and Basu and Markov (2004) suggests that the well-known optimism bias in analysts? earnings forecasts is attributable to analysts minimizing symmetric, linear loss functions when the distribution of forecast errors is skewed. An alternative explanation for forecast bias is that analysts have asymmetric loss functions. We test this alternative explanation. Theory predicts that if loss functions are asymmetric then forecast error bias depends on forecast error variance, but not necessarily on forecast error skewness. Our results confirm that the ex ante forecast error variance is a significant determinant of forecast error and that, after controlling for variance, the sign of the coefficient on forecast error skewness is opposite to that found in prior research. Our results are consistent with financial analysts having asymmetric loss functions. Further analysis reveals that forecast bias varies systematically across style portfolios formed on book-to-price and market capitalization. These firm characteristics capture systematic variation in forecast error variance and skewness. Within style portfolios, forecast error variance continues to play a dominant role in explaining forecast error.

Pancreatic Allograft Thrombosis: Suggestion for a CT grading system and management algorithm

Pancreatic allograft thrombosis (PAT) remains the leading cause of non-immunological graft failure. Herein we propose a new CT grading system of PAT to identify risk factors for allograft loss and outline a management algorithm by retrospective review of consecutive pancreatic transplants between 2009-2014. Triple-phase CT scans were graded independently by two radiologists as; Grade 0 – no thrombosis, Grade 1 – peripheral thrombosis, Grade 2 – intermediate non-occlusive thrombosis and Grade 3 – central occlusive thrombosis. Twenty-four of 103 (23.3%) recipients were diagnosed with PAT (including grade 1). Three grafts (2.9%) were lost due to portal vein thrombosis. On multivariate analysis, pancreas after SPK/PAK transplant, acute rejection and CT finding peri-pancreatic oedema and/or inflammatory change were significant risk factors of PAT. Retrospective review of CT images revealed more grade 1 and 2 thromboses than were initially reported. There was no significant difference in graft or patient survival, post-operative stay or morbidity of recipients with grade 1 or 2 thrombosis who were or were not anticoagulated. Our data suggest that therapeutic anticoagulation is not necessary for grade 1 and 2 arterial and grade 1 venous thrombosis. The proposed grading system can assist clinicians in decision making and provide standardised reporting for future studies

Phenotypically distinct neutrophils patrol uninfected human and mouse lymph nodes.

Neutrophils play a key role in innate immunity. As the dominant circulating phagocyte, they are rapidly recruited from the bloodstream to sites of infection or injury to internalize and destroy microbes. More recently, neutrophils have been identified in uninfected organs, challenging the classical view of their function. Here we show that neutrophils were present in lymph nodes (LNs) in homeostasis. Using flow cytometry and confocal imaging, we identified neutrophils within LNs in naive, unchallenged mice, including LNs draining the skin, lungs, and gastrointestinal tract. Neutrophils were enriched within specific anatomical regions, in the interfollicular zone, a site of T cell activation. Intravital two-photon microscopy demonstrated that LN neutrophils were motile, trafficked into LNs from both blood and tissues via high endothelial venules and afferent lymphatics, respectively, and formed interactions with dendritic cells in LNs. Murine and human LN neutrophils had a distinct phenotype compared with circulating neutrophils, with higher major histocompatibility complex II (MHCII) expression, suggesting a potential role in CD4 T cell activation. Upon ex vivo stimulation with IgG immune complex (IC), neutrophils up-regulated expression of MHCII and costimulatory molecules and increased T cell activation. In vivo, neutrophils were capable of delivering circulating IC to LNs, suggesting a broader functional remit. Overall, our data challenge the perception that neutrophil patrol is limited to the circulation in homeostasis, adding LNs to their routine surveillance territory.L.S.C.L. was funded by Wellcome Trust (104384/Z/14/Z). M.R.C. is supported by National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre, Chan-Zuckerburg Initiative Human Cell Atlas Technology Development Grant, Medical Research Council New Investigator Research Grant (MR/N024907/1), Arthritis Research UK Cure Challenge Research Grant (21777), and NIHR Research Professorship (RP-2017-08- ST2-002)

Which aspects of health care are most valued by people living with HIV in high-income countries? A systematic review.

BACKGROUND: Increasing numbers of people with HIV are living into older age and experiencing comorbidities. The development of new models of care to meet the needs of this population is now a priority. It is important that the views and preferences of patients inform the development of services in order to maintain high levels of patient satisfaction and engagement. The aim of this systematic review was to determine which aspects of healthcare are particularly valued by people living with HIV. METHODS: We searched electronic databases and reference lists of relevant articles. The search strategy was developed to identify articles reporting on HIV positive patients' perceptions, evaluations or experiences of healthcare services and factors associated with satisfaction with care. Peer-reviewed papers and conference abstracts were included if the study reported on aspects of health care that were valued by people living with HIV, data were collected during the era of combination therapy (from 1996 onwards), and the paper was published in English. A thematic approach to data synthesis was used. RESULTS: Twenty-three studies met the inclusion criteria. Studies used both qualitative and quantitative methods. Six studies specifically reported on relative importance to patients of different aspects of care. The valued aspects of care identified were grouped into seven themes. These highlighted the importance to patients of: a good health care professional-patient relationship, HIV specialist knowledge, continuity of care, ease of access to services, access to high quality information and support, effective co-ordination between HIV specialists and other healthcare professionals, and involvement in decisions about treatment and care. We were unable to determine the relative importance to patients of different aspects of care because of methodological differences between the studies. CONCLUSIONS: This review identified several attributes of healthcare that are valued by people living with HIV, many of which would be relevant to any future reconfiguration of services to meet the needs of an ageing population. Further research is required to determine the relative importance to patients of different aspects of care

Local Expansion of Donation After Circulatory Death Kidney Transplant Activity Improves Waitlisted Outcomes and Addresses Inequities of Access to Transplantation

In the United Kingdom, donation after circulatory death (DCD) kidney transplant activity has increased rapidly, but marked regional variation persists. We report how increased DCD kidney transplant activity influenced waitlisted outcomes for a single center. Between 2002–2003 and 2011–2012, 430 (54%) DCD and 361 (46%) donation after brain death (DBD) kidney-only transplants were performed at the Cambridge Transplant Centre, with a higher proportion of DCD donors fulfilling expanded criteria status (41% DCD vs. 32% DBD; p = 0.01). Compared with U.K. outcomes, for which the proportion of DCD:DBD kidney transplants performed is lower (25%; p 65 years; waiting time 730 vs. 1357 days nationally; p < 0.001), who received predominantly DCD kidneys from older donors (mean donor age 64 years), whereas younger recipients received equal proportions of living donor, DBD and DCD kidney transplants. Death-censored kidney graft survival was nevertheless comparable for younger and older recipients, although transplantation conferred a survival benefit from listing for only younger recipients. Local expansion in DCD kidney transplant activity improves survival outcomes for younger patients and addresses inequity of access to transplantation for older recipients

Copper as a target for prostate cancer therapeutics: copper-ionophore pharmacology and altering systemic copper distribution

Copper-ionophores that elevate intracellular bioavailable copper display significant therapeutic utility against prostate cancer cells in vitro and in TRAMP (Transgenic Adenocarcinoma of Mouse Prostate) mice. However, the pharmacological basis for their anticancer activity remains unclear, despite impending clinical trails. Herein we show that intracellular copper levels in prostate cancer, evaluated in vitro and across disease progression in TRAMP mice, were not correlative with copper-ionophore activity and mirrored the normal levels observed in patient prostatectomy tissues (Gleason Score 7 & 9). TRAMP adenocarcinoma cells harbored markedly elevated oxidative stress and diminished glutathione (GSH)-mediated antioxidant capacity, which together conferred selective sensitivity to prooxidant ionophoric copper. Copper-ionophore treatments [CuII(gtsm), disulfiram & clioquinol] generated toxic levels of reactive oxygen species (ROS) in TRAMP adenocarcinoma cells, but not in normal mouse prostate epithelial cells (PrECs). Our results provide a basis for the pharmacological activity of copper-ionophores and suggest they are amendable for treatment of patients with prostate cancer. Additionally, recent in vitro and mouse xenograft studies have suggested an increased copper requirement by prostate cancer cells. We demonstrated that prostate adenocarcinoma development in TRAMP mice requires a functional supply of copper and is significantly impeded by altered systemic copper distribution. The presence of a mutant copper-transporting Atp7b protein (tx mutation: A4066G/Met1356Val) in TRAMP mice changed copper-integration into serum and caused a remarkable reduction in prostate cancer burden (64% reduction) and disease severity (grade), abrogating adenocarcinoma development. Implications for current clinical trials are discussed