Haematological and biochemical reference intervals for free-ranging brown bears (Ursus arctos) in Sweden

Background: Establishment of haematological and biochemical reference intervals is important to assess health of animals on individual and population level. Reference intervals for 13 haematological and 34 biochemical variables were established based on 88 apparently healthy free-ranging brown bears (39 males and 49 females) in Sweden. The animals were chemically immobilised by darting from a helicopter with a combination of medetomidine, tiletamine and zolazepam in April and May 2006-2012 in the county of Dalarna, Sweden. Venous blood samples were collected during anaesthesia for radio collaring and marking for ecological studies. For each of the variables, the reference interval was described based on the 95% confidence interval, and differences due to host characteristics sex and age were included if detected. To our knowledge, this is the first report of reference intervals for free-ranging brown bears in Sweden.Results: The following variables were not affected by host characteristics: red blood cell, white blood cell, monocyte and platelet count, alanine transaminase, amylase, bilirubin, free fatty acids, glucose, calcium, chloride, potassium, and cortisol. Age differences were seen for the majority of the haematological variables, whereas sex influenced only mean corpuscular haemoglobin concentration, aspartate aminotransferase, lipase, lactate dehydrogenase, beta-globulin, bile acids, triglycerides and sodium.Conclusions: The biochemical and haematological reference intervals provided and the differences due to host factors age and gender can be useful for evaluation of health status in free-ranging European brown bears

Efficient Learning and Feature Selection in High Dimensional Regression

We present a novel algorithm for efficient learning and feature selection in high-dimensional regression problems. We arrive at this model through a modification of the standard regression model, enabling us to derive a probabilistic version of the well-known statistical regression technique of backfitting. Using the expectation-maximization algorithm, along with variational approximation methods to overcome intractability, we extend our algorithm to include automatic relevance detection of the input features. This variational Bayesian least squares (VBLS) approach retains its simplicity as a linear model, but offers a novel statistically robust black-box approach to generalized linear regression with high-dimensional inputs. It can be easily extended to nonlinear regression and classification problems. In particular, we derive the framework of sparse Bayesian learning, the relevance vector machine, with VBLS at its core, offering significant computational and robustness advantages for this class of methods. The iterative nature of VBLS makes it most suitable for real-time incremental learning, which is crucial especially in the application domain of robotics, brain-machine interfaces, and neural prosthetics, where real-time learning of models for control is needed. We evaluate our algorithm on synthetic and neurophysiological data sets, as well as on standard regression and classification benchmark data sets, comparing it with other competitive statistical approaches and demonstrating its suitability as a drop-in replacement for other generalized linear regression techniques

Relationship between Chlorophyll a Concentration, Light Attenuation and Diving Depth of the Southern Elephant Seal Mirounga leonina

Recently, a number of Antarctic marine environmental studies have used oceanographic parameters collected from instrumented top predators for ecological and physical information. Phytoplankton concentration is generally quantified through active measurement of chlorophyll fluorescence. In this study, light absorption coefficient (K(0.75)) was used as an indicator of phytoplankton concentration. This measurement, easy to obtain and requiring low electric power, allows for assessing of the fine scale horizontal structuring of phytoplankton. As part of this study, Southern elephant seals (SES) were simultaneously equipped with a fluorometer and a light logger. Along the SES tracks, variations in K(0.75) were strongly correlated with chlorophyll, a concentration measured by the fluorometer within the euphotic layer. With regards to SES foraging behaviour, bottom depth of the seal’s dive was highly dependent on light intensity at 150 m, indicating that the vertical distribution of SES’s prey such as myctophids is tightly related to light level. Therefore, change in phytoplankton concentration may not only have a direct effect on SES’s prey abundance but may also determine their vertical accessibility with likely consequences on SES foraging efficiency

Seasonal variation in haematological and biochemical variables in free-ranging subadult brown bears (Ursus arctos) in Sweden

International audienceBackground: Free-ranging brown bears exhibit highly contrasting physiological states throughout the year.They hibernate 6 months of the year, experiencing a decrease in body temperature, heart rate, respiratoryrate and metabolism. An increase in food consumption and the resulting weight gain (mostly through fatstorage) prior to hibernation are also part of the brown bear’s annual cycle. Due to these physiological changes,haematological and biochemical variables vary dramatically throughout the year. Seasonal changes in 12haematological and 34 biochemical variables were evaluated in blood samples collected from 40 free-ranging subadultbrown bears (22 females, 18 males) immobilised in Sweden in winter (February-March), spring (April-May), andsummer (June).Results: Higher levels of haemoglobin, haematocrit and red blood cell count, and a lower white blood cellcount and mean cell volume was found during hibernation than in spring and summer. Lower values of theenzymes; aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (AP), γ-glutamyltranspeptidase (GGT), glutamate dehydrogenase (GD) and amylase, and increased values of β-hydroxybutyrate(β-HBA) and blood lipids; triglycerides, cholesterol and free fatty acids, were present during hibernationcompared to spring and summer.Conclusions: This study documents significant shifts in haematological and biochemical variables in samplescollected from brown bears anaesthetised in winter (February-March) compared to in spring and summer(April-June), reflecting the lowered metabolic, renal and hepatic activity during hibernation. Lower values ofenzymes and higher values of blood lipids during hibernation, likely reflect a lipid-based metabolism

Seasonal variation in haematological and biochemical variables in free-ranging subadult brown bears (Ursus arctos) in Sweden

Background: Free-ranging brown bears exhibit highly contrasting physiological states throughout the year. They hibernate 6 months of the year, experiencing a decrease in body temperature, heart rate, respiratory rate and metabolism. An increase in food consumption and the resulting weight gain (mostly through fat storage) prior to hibernation are also part of the brown bear’s annual cycle. Due to these physiological changes, haematological and biochemical variables vary dramatically throughout the year. Seasonal changes in 12 haematological and 34 biochemical variables were evaluated in blood samples collected from 40 free-ranging subadult brown bears (22 females, 18 males) immobilised in Sweden in winter (February-March), spring (April-May), and summer (June). Results: Higher levels of haemoglobin, haematocrit and red blood cell count, and a lower white blood cell count and mean cell volume was found during hibernation than in spring and summer. Lower values of the enzymes; aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (AP), γ-glutamyl transpeptidase (GGT), glutamate dehydrogenase (GD) and amylase, and increased values of β-hydroxybutyrate (β-HBA) and blood lipids; triglycerides, cholesterol and free fatty acids, were present during hibernation compared to spring and summer. Conclusions: This study documents significant shifts in haematological and biochemical variables in samples collected from brown bears anaesthetised in winter (February-March) compared to in spring and summer (April-June), reflecting the lowered metabolic, renal and hepatic activity during hibernation. Lower values of enzymes and higher values of blood lipids during hibernation, likely reflect a lipid-based metabolism

Haematological and biochemical reference intervals for free-ranging brown bears (Ursus arctos) in Sweden

Background: Establishment of haematological and biochemical reference intervals is important to assess health of animals on individual and population level. Reference intervals for 13 haematological and 34 biochemical variables were established based on 88 apparently healthy free-ranging brown bears (39 males and 49 females) in Sweden. The animals were chemically immobilised by darting from a helicopter with a combination of medetomidine, tiletamine and zolazepam in April and May 2006 – 2012 in the county of Dalarna, Sweden. Venous blood samples were collected during anaesthesia for radio collaring and marking for ecological studies. For each of the variables, the reference interval was described based on the 95% confidence interval, and differences due to host characteristics sex and age were included if detected. To our knowledge, this is the first report of reference intervals for free-ranging brown bears in Sweden. Results: The following variables were not affected by host characteristics: red blood cell, white blood cell, monocyte and platelet count, alanine transaminase, amylase, bilirubin, free fatty acids, glucose, calcium, chloride, potassium, and cortisol. Age differences were seen for the majority of the haematological variables, whereas sex influenced only mean corpuscular haemoglobin concentration, aspartate aminotransferase, lipase, lactate dehydrogenase, β -globulin, bile acids, triglycerides and sodium. Conclusions: The biochemical and haematological reference intervals provided and the differences due to host factors age and gender can be useful for evaluation of health status in free-ranging European brown bear

Modulation of myeloid and T cells in vivo by Bruton's tyrosine kinase inhibitor ibrutinib in patients with metastatic pancreatic ductal adenocarcinoma.

BackgroundIn preclinical studies of pancreatic ductal adenocarcinoma (PDAC), ibrutinib improved the antitumor efficacy of the standard of care chemotherapy. This led to a phase 1b clinical trial to determine the safety, tolerability, and immunologic effects of ibrutinib treatment in patients with advanced PDAC.MethodsPreviously untreated patients with PDAC were enrolled in a phase 1b clinical trial (ClinicalTrials.gov) to determine the safety, toxicity, and maximal tolerated dose of ibrutinib when administered with the standard regimen of gemcitabine and nab-paclitaxel. To study the immune response to ibrutinib alone, the trial included an immune response arm where patients were administered with ibrutinib daily for a week followed by ibrutinib combined with gemcitabine and nab-paclitaxel. Endoscopic ultrasonography-guided primary PDAC tumor biopsies and blood were collected before and after ibrutinib monotherapy. Changes in abundance and functional state of immune cells in the blood was evaluated by mass cytometry by time of flight and statistical scaffold analysis, while that in the local tumor microenvironment (TME) were assessed by multiplex immunohistochemistry. Changes in B-cell receptor and T-cell receptor repertoire were assessed by sequencing and analysis of clonality.ResultsIn the blood, ibrutinib monotherapy significantly increased the frequencies of activated inducible T cell costimulator+(ICOS+) CD4+ T cells and monocytes. Within the TME, ibrutinib monotherapy led to a trend in decreased B-cell abundance but increased interleukin-10+ B-cell frequency. Monotherapy also led to a trend in increased mature CD208+dendritic cell density, increased late effector (programmed cell death protein 1 (PD-1-) eomesodermin (EOMES+)) CD8+ T-cell frequency, with a concomitantly decreased dysfunctional (PD-1+ EOMES+) CD8+ T-cell frequency. When ibrutinib was combined with chemotherapy, most of these immune changes were not observed. Patients with partial clinical responses had more diverse T and B cell receptor repertoires prior to therapy initiation.ConclusionIbrutinib monotherapy skewed the immune landscape both in the circulation and TME towards activated T cells, monocytes and DCs. These effects were not observed when combining ibrutinib with standard of care chemotherapy. Future studies may focus on other therapeutic combinations that augment the immunomodulatory effects of ibrutinib in solid tumors.Trial registration numberNCT02562898

Modulation of myeloid and T cells in vivo by Bruton\u27s tyrosine kinase inhibitor ibrutinib in patients with metastatic pancreatic ductal adenocarcinoma.

BACKGROUND: In preclinical studies of pancreatic ductal adenocarcinoma (PDAC), ibrutinib improved the antitumor efficacy of the standard of care chemotherapy. This led to a phase 1b clinical trial to determine the safety, tolerability, and immunologic effects of ibrutinib treatment in patients with advanced PDAC. METHODS: Previously untreated patients with PDAC were enrolled in a phase 1b clinical trial (ClinicalTrials.gov) to determine the safety, toxicity, and maximal tolerated dose of ibrutinib when administered with the standard regimen of gemcitabine and nab-paclitaxel. To study the immune response to ibrutinib alone, the trial included an immune response arm where patients were administered with ibrutinib daily for a week followed by ibrutinib combined with gemcitabine and nab-paclitaxel. Endoscopic ultrasonography-guided primary PDAC tumor biopsies and blood were collected before and after ibrutinib monotherapy. Changes in abundance and functional state of immune cells in the blood was evaluated by mass cytometry by time of flight and statistical scaffold analysis, while that in the local tumor microenvironment (TME) were assessed by multiplex immunohistochemistry. Changes in B-cell receptor and T-cell receptor repertoire were assessed by sequencing and analysis of clonality. RESULTS: In the blood, ibrutinib monotherapy significantly increased the frequencies of activated inducible T cell costimulator CONCLUSION: Ibrutinib monotherapy skewed the immune landscape both in the circulation and TME towards activated T cells, monocytes and DCs. These effects were not observed when combining ibrutinib with standard of care chemotherapy. Future studies may focus on other therapeutic combinations that augment the immunomodulatory effects of ibrutinib in solid tumors. TRIAL REGISTRATION NUMBER: NCT02562898