A prospective cohort study of digital cushion and corium thickness. Part 2: Does thinning of the digital cushion and corium lead to lameness and claw horn disruption lesions?

The aim of this study was to determine whether a decrease in thickness of the sole soft tissues (SST) beneath the flexor tuberosity of the distal phalanx (i.e., the digital cushion and corium) predisposed a claw to develop claw horn disruption lesions (CHDL) or a leg to lameness. Data were analyzed from a longitudinal study of 179 cows, which had been examined at 5 assessment points −8, +1, +9, +17, and +29 wk relative to their first, second, third, or fourth calving. At each assessment point, SST were measured using ultrasonography. Additional assessment point data included sole lesions and back fat thickness (BFT), and cows had been locomotion scored every 2 wk from calving. One hundred fifty-eight cows completed the study. Separate logistic regression survival analyses were constructed to assess the outcomes, either lameness on a leg or CHDL on a claw; combinations of lameness and lesions were tested as outcomes. Cow level variables tested included farm and lactation number. Variables were tested describing previous SST thickness, minimum previous SST thickness, BFT, and change in either variable between prior assessment points. Prior lesions/lameness strongly predicted repeat cases and the final models had the outcome first lesion or lameness on a claw or leg. In the reported lameness models, lameness was defined as a leg being recorded as lame twice within 3 consecutive scores, and in the reported lesion models, lesion was defined as the first presence of either a sole ulcer or a severe sole hemorrhage on a claw. Thin SST increased the likelihood of lesion occurrence; thin SST on the lateral claw predicted subsequent lameness on a leg. Thin BFT and thinning of BFT between previous assessment points increased the likelihood of future lesion occurrence. Thin SST and thinning of BFT had additional effects on the likelihood of lesion occurrence, suggesting that BFT and sole SST had independent effects on lesion occurrence. However, change in SST thickness between assessment points did not influence the likelihood of future lesions or lameness. This suggests that thin SST were not simply a result of depletion of body fat and challenges the theory that thinning of the digital cushion with body fat mobilization leads to CHDL. Other possible mechanisms by which SST become thin are discussed and could include changes in integrity of the suspensory apparatus with physiological events

Isolation of Primary Human Hepatocytes from Normal and Diseased Liver Tissue: A One Hundred Liver Experience

Successful and consistent isolation of primary human hepatocytes remains a challenge for both cell-based therapeutics/transplantation and laboratory research. Several centres around the world have extensive experience in the isolation of human hepatocytes from non-diseased livers obtained from donor liver surplus to surgical requirement or at hepatic resection for tumours. These livers are an important but limited source of cells for therapy or research. The capacity to isolate cells from diseased liver tissue removed at transplantation would substantially increase availability of cells for research. However no studies comparing the outcome of human hepatocytes isolation from diseased and non-diseased livers presently exist. Here we report our experience isolating human hepatocytes from organ donors, non-diseased resected liver and cirrhotic tissue. We report the cell yields and functional qualities of cells isolated from the different types of liver and demonstrate that a single rigorous protocol allows the routine harvest of good quality primary hepatocytes from the most commonly accessible human liver tissue samples

Pre-Whaling Genetic Diversity and Population Ecology in Eastern Pacific Gray Whales: Insights from Ancient DNA and Stable Isotopes

Commercial whaling decimated many whale populations, including the eastern Pacific gray whale, but little is known about how population dynamics or ecology differed prior to these removals. Of particular interest is the possibility of a large population decline prior to whaling, as such a decline could explain the ∼5-fold difference between genetic estimates of prior abundance and estimates based on historical records. We analyzed genetic (mitochondrial control region) and isotopic information from modern and prehistoric gray whales using serial coalescent simulations and Bayesian skyline analyses to test for a pre-whaling decline and to examine prehistoric genetic diversity, population dynamics and ecology. Simulations demonstrate that significant genetic differences observed between ancient and modern samples could be caused by a large, recent population bottleneck, roughly concurrent with commercial whaling. Stable isotopes show minimal differences between modern and ancient gray whale foraging ecology. Using rejection-based Approximate Bayesian Computation, we estimate the size of the population bottleneck at its minimum abundance and the pre-bottleneck abundance. Our results agree with previous genetic studies suggesting the historical size of the eastern gray whale population was roughly three to five times its current size

Changes in chromatin structure during processing of wax-embedded tissue sections

The use of immunofluorescence (IF) and fluorescence in situ hybridisation (FISH) underpins much of our understanding of how chromatin is organised in the nucleus. However, there has only recently been an appreciation that these types of study need to move away from cells grown in culture and towards an investigation of nuclear organisation in cells in situ in their normal tissue architecture. Such analyses, however, especially of archival clinical samples, often requires use of formalin-fixed paraffin wax-embedded tissue sections which need addition steps of processing prior to IF or FISH. Here we quantify the changes in nuclear and chromatin structure that may be caused by these additional processing steps. Treatments, especially the microwaving to reverse fixation, do significantly alter nuclear architecture and chromatin texture, and these must be considered when inferring the original organisation of the nucleus from data collected from wax-embedded tissue sections

Free will is not a testable hypothesis

Much recent work in neuroscience aims to shed light on whether we have free will. Can it? Can any science? To answer, we need to disentangle different notions of free will, and clarify what we mean by ‘empirical’ and ‘testable’. That done, my main conclusion is, duly interpreted: that free will is not a testable hypothesis. In particular, it is neither verifiable nor falsifiable by empirical evidence. The arguments for this are not a priori but rather are based on a posteriori consideration of the relevant neuroscientific investigations, as well as on standard philosophy of science work on the notion of testability

Free will is not a testable hypothesis

Much recent work in neuroscience aims to shed light on whether we have free will. Can it? Can any science? To answer, we need to disentangle different notions of free will, and clarify what we mean by ‘empirical’ and ‘testable’. That done, my main conclusion is, duly interpreted: that free will is not a testable hypothesis. In particular, it is neither verifiable nor falsifiable by empirical evidence. The arguments for this are not a priori but rather are based on a posteriori consideration of the relevant neuroscientific investigations, as well as on standard philosophy of science work on the notion of testability

Yki/YAP, Sd/TEAD and Hth/MEIS Control Tissue Specification in the Drosophila Eye Disc Epithelium

During animal development, accurate control of tissue specification and growth are critical to generate organisms of reproducible shape and size. The eye-antennal disc epithelium of Drosophila is a powerful model system to identify the signaling pathway and transcription factors that mediate and coordinate these processes. We show here that the Yorkie (Yki) pathway plays a major role in tissue specification within the developing fly eye disc epithelium at a time when organ primordia and regional identity domains are specified. RNAi-mediated inactivation of Yki, or its partner Scalloped (Sd), or increased activity of the upstream negative regulators of Yki cause a dramatic reorganization of the eye disc fate map leading to specification of the entire disc epithelium into retina. On the contrary, constitutive expression of Yki suppresses eye formation in a Sd-dependent fashion. We also show that knockdown of the transcription factor Homothorax (Hth), known to partner Yki in some developmental contexts, also induces an ectopic retina domain, that Yki and Scalloped regulate Hth expression, and that the gain-of-function activity of Yki is partially dependent on Hth. Our results support a critical role for Yki- and its partners Sd and Hth - in shaping the fate map of the eye epithelium independently of its universal role as a regulator of proliferation and survival

Diabetes susceptibility in ethnic minority groups from Turkey, Vietnam, Sri Lanka and Pakistan compared with Norwegians - the association with adiposity is strongest for ethnic minority women

<p>Abstract</p> <p>Background</p> <p>The difference in diabetes susceptibility by ethnic background is poorly understood. The aim of this study was to assess the association between adiposity and diabetes in four ethnic minority groups compared with Norwegians, and take into account confounding by socioeconomic position.</p> <p>Methods</p> <p>Data from questionnaires, physical examinations and serum samples were analysed for 30-to 60-year-olds from population-based cross-sectional surveys of Norwegians and four immigrant groups, comprising 4110 subjects born in Norway (n = 1871), Turkey (n = 387), Vietnam (n = 553), Sri Lanka (n = 879) and Pakistan (n = 420). Known and screening-detected diabetes cases were identified. The adiposity measures BMI, waist circumference and waist-hip ratio (WHR) were categorized into levels of adiposity. Gender-specific logistic regression models were applied to estimate the risk of diabetes for the ethnic minority groups adjusted for adiposity and income-generating work, years of education and body height used as a proxy for childhood socioeconomic position.</p> <p>Results</p> <p>The age standardized diabetes prevalence differed significantly between the ethnic groups (women/men): Pakistan: 26.4% (95% CI 20.1-32.7)/20.0% (14.9-25.2); Sri Lanka: 22.5% (18.1-26.9)/20.7% (17.3-24.2), Turkey: 11.9% (7.2-16.7)/12.0% (7.6-16.4), Vietnam: 8.1% (5.1-11.2)/10.4% (6.6-14.1) and Norway: 2.7% (1.8-3.7)/6.4% (4.6-8.1). The prevalence increased more in the minority groups than in Norwegians with increasing levels of BMI, WHR and waist circumference, and most for women. Highly significant ethnic differences in the age-standardized prevalence of diabetes were found for both genders in all categories of all adiposity measures (<it>p </it>< 0.001). The Odds Ratio (OR) for diabetes adjusted for age, WHR, body height, education and income-generating work with Norwegians as reference was 2.9 (1.30-6.36) for Turkish, 2.7 (1.29-5.76) for Vietnamese, 8.0 (4.19-15.14) for Sri Lankan and 8.3 (4.37-15.58) for Pakistani women. Men from Sri Lanka and Pakistan had identical ORs (3.0 (1.80-5.12)).</p> <p>Conclusions</p> <p>A high prevalence of diabetes was found in 30-to 60-year-olds from ethnic minority groups in Oslo, with those from Sri Lanka and Pakistan at highest risk. For all levels of adiposity, a higher susceptibility for diabetes was observed for ethnic minority groups compared with Norwegians. The association persisted after adjustment for socioeconomic position for all minority women and for men from Sri Lanka and Pakistan.</p

The assessment, serial evaluation, and subsequent sequelae of acute kidney injury (ASSESS-AKI) study: design and methods

<p>Abstract</p> <p>Background</p> <p>The incidence of acute kidney injury (AKI) has been increasing over time and is associated with a high risk of short-term death. Previous studies on hospital-acquired AKI have important methodological limitations, especially their retrospective study designs and limited ability to control for potential confounding factors.</p> <p>Methods</p> <p>The Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) Study was established to examine how a hospitalized episode of AKI independently affects the risk of chronic kidney disease development and progression, cardiovascular events, death, and other important patient-centered outcomes. This prospective study will enroll a cohort of 1100 adult participants with a broad range of AKI and matched hospitalized participants without AKI at three Clinical Research Centers, as well as 100 children undergoing cardiac surgery at three Clinical Research Centers. Participants will be followed for up to four years, and will undergo serial evaluation during the index hospitalization, at three months post-hospitalization, and at annual clinic visits, with telephone interviews occurring during the intervening six-month intervals. Biospecimens will be collected at each visit, along with information on lifestyle behaviors, quality of life and functional status, cognitive function, receipt of therapies, interim renal and cardiovascular events, electrocardiography and urinalysis.</p> <p>Conclusions</p> <p>ASSESS-AKI will characterize the short-term and long-term natural history of AKI, evaluate the incremental utility of novel blood and urine biomarkers to refine the diagnosis and prognosis of AKI, and identify a subset of high-risk patients who could be targeted for future clinical trials to improve outcomes after AKI.</p

The first global deep-sea stable isotope assessment reveals the unique trophic ecology of Vampire Squid Vampyroteuthis infernalis (Cephalopoda)

Vampyroteuthis infernalis Chun, 1903, is a widely distributed deepwater cephalopod with unique morphology and phylogenetic position. We assessed its habitat and trophic ecology on a global scale via stable isotope analyses of a unique collection of beaks from 104 specimens from the Atlantic, Pacific and Indian Oceans. Cephalopods typically are active predators occupying a high trophic level (TL) and exhibit an ontogenetic increase in δ15N and TL. Our results, presenting the first global comparison for a deep-sea invertebrate, demonstrate that V. infernalis has an ontogenetic decrease in δ15N and TL, coupled with niche broadening. Juveniles are mobile zooplanktivores, while larger Vampyroteuthis are slow-swimming opportunistic consumers and ingest particulate organic matter. Vampyroteuthis infernalis occupies the same TL (3.0–4.3) over its global range and has a unique niche in deep-sea ecosystems. These traits have enabled the success and abundance of this relict species inhabiting the largest ecological realm on the planet.Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. The attached file is the published pdf