Growth in fossil and extant deer and implications for body size and life history evolution

© Kolb et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The attached file is the published version of the article

Sexual Size Dimorphism and Body Condition in the Australasian Gannet

Funding: The research was financially supported by the Holsworth Wildlife Research Endowment. Acknowledgments We thank the Victorian Marine Science Consortium, Sea All Dolphin Swim, Parks Victoria, and the Point Danger Management Committee for logistical support. We are grateful for the assistance of the many field volunteers involved in the study.Peer reviewedPublisher PD

Russian roulette with unlicensed fat-burner drug 2,4-dinitrophenol (DNP) : evidence from a multidisciplinary study of the internet, bodybuilding supplements and DNP users

BACKGROUND: 2,4-Dinitrophenol (DNP) poses serious health-risks to humans. The aims of this three-stage multidisciplinary project were, for the first time, to assess the risks to the general public from fraudulent sale of or adulteration/contamination with DNP; and to investigate motives, reasons and risk-management among DNP-user bodybuilders and avid exercisers. METHODS: Using multiple search-engines and guidance for Internet research, online retailers and bodybuilding forums/blogs were systematically explored for availability of DNP, advice offered on DNP use and user profiles. Ninety-eight pre-workout and weight-loss supplements were purchased and analysed for DNP using liquid-chromatography-mass-spectrometry. Psychosocial variables were captured in an international sample of 35 DNP users (26.06 ± 6.10 years, 94.3 % male) with an anonymous, semi-qualitative self-reported survey. RESULTS: Although an industrial chemical, evidence from the Internet showed that DNP is sold 'as is', in capsules or tablets to suit human consumption, and is used 'uncut'. Analytical results confirmed that DNP is not on the supplement market disguised under fictitious supplement names, but infrequently was present as contaminant in some supplements (14/98) at low concentration (<100mcg/kg). Users make conscious and 'informed' decisions about DNP; are well-prepared for the side-effects and show nonchalant attitude toward self-experimentation with DNP. Steps are often taken to ensure that DNP is genuine. Personal experience with performance- and appearance enhancing substances appears to be a gateway to DNP. Advice on DNP and experiences are shared online. The significant discrepancy between the normative perception and the actual visibility suggests that DNP use is-contrary to the Internet accounts-a highly concealed and lonesome activity in real life. Positive experiences with the expected weight-loss prevail over the negative experiences from side effects (all but two users considered using DNP again) and help with using DNP safely is considered preferable over scare-tactics. CONCLUSION: Legislation banning DNP sale for human consumption protects the general public but DNP is sold 'as is' and used 'uncut' by determined users who are not dissuaded from experimenting with DNP based on health threats. Further research with stakeholders' active participation is imperative for targeted, proactive public health policies and harm-reduction measures for DNP, and other illicit supplements

BLISS: an artificial language for learnability studies

To explore neurocognitive mechanisms underlying the human language faculty, cognitive scientists use artificial languages to control more precisely the language learning environment and to study selected aspects of natural languages. Artificial languages applied in cognitive studies are usually designed ad hoc, to only probe a specific hypothesis, and they include a miniature grammar and a very small vocabulary. The aim of the present study is the construction of an artificial language incorporating both syntax and semantics, BLISS. Of intermediate complexity, BLISS mimics natural languages by having a vocabulary, syntax, and some semantics, as defined by a degree of non-syntactic statistical dependence between words. We quantify, using information theoretical measures, dependencies between words in BLISS sentences as well as differences between the distinct models we introduce for semantics. While modeling English syntax in its basic version, BLISS can be easily varied in its internal parametric structure, thus allowing studies of the relative learnability of different parameter sets

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Correction : Transcriptome analysis of pigeon milk production - role of cornification and triglyceride synthesis genes

Stanley, D ORCiD: 0000-0001-7019-4726Background The pigeon crop is specially adapted to produce milk that is fed to newly hatched young. The process of pigeon milk production begins when the germinal cell layer of the crop rapidly proliferates in response to prolactin, which results in a mass of epithelial cells that are sloughed from the crop and regurgitated to the young. We proposed that the evolution of pigeon milk built upon the ability of avian keratinocytes to accumulate intracellular neutral lipids during the cornification of the epidermis. However, this cornification process in the pigeon crop has not been characterised. Results We identified the epidermal differentiation complex in the draft pigeon genome scaffold and found that, like the chicken, it contained beta-keratin genes. These beta-keratin genes can be classified, based on sequence similarity, into several clusters including feather, scale and claw keratins. The cornified cells of the pigeon crop express several cornification-associated genes including cornulin, S100-A9 and A16-like, transglutaminase 6-like and the pigeon ‘lactating’ crop-specific annexin cp35. Beta-keratins play an important role in ‘lactating’ crop, with several claw and scale keratins up-regulated. Additionally, transglutaminase 5 and differential splice variants of transglutaminase 4 are up-regulated along with S100-A10. Conclusions This study of global gene expression in the crop has expanded our knowledge of pigeon milk production, in particular, the mechanism of cornification and lipid production. It is a highly specialised process that utilises the normal keratinocyte cellular processes to produce a targeted nutrient solution for the young at a very high turnover. Background Pigeon lactation was first noted in the literature in 1786 when John Hunter described pigeon milk as being like “..granulated white curd” [1]. This curd-like substance is produced in the crop of male and female pigeons and regurgitated to the young. Like the mammary gland, the pigeon crop undergoes significant changes to the tissue structure during lactation. Several histological studies have characterised these changes and determined that pigeon milk consists of desquamated, sloughed crop epithelial cells [2, 3]. The process of pigeon milk production begins when the germinal cell layer of the crop rapidly proliferates in response to prolactin [4, 5], and this results in a convoluted, highly folded epithelial structure that then coalesces as it out-grows the vasculature, to form the nutritive cell layer that is sloughed off to produce the milk. This nutritive cell layer contains lipid-filled vacuoles [2, 3, 5, 6]. The lipid content of pigeon milk consists mainly of triglycerides, along with phospholipids, cholesterol, free fatty acids, cholesterol esters and diglycerides [7]. The triglyceride content decreases across the lactation period, from 81.2% of total lipid at day one, to 62.7% at day 19, whereas the other lipids increase, which suggests the cellular lipid content decreases towards the end of the lactation period, but the cell membrane-associated lipids remain constant [7]. Several studies have investigated the differences in gene expression between ‘lactating’ pigeon crop tissue and non-‘lactating’ crop tissue [6, 8, 9]. Nearly three decades ago, Horseman and Pukac were the first to identify that mRNA species differ in response to prolactin injection in the crop [8]. Specifically, they identified and characterised gene expression and protein translation of the prolactin-responsive mRNA anxI cp35 and the non-prolactin-responsive isoform, anxI cp37 [9, 10]. In addition, a recent global gene expression study in our laboratory [6] showed that genes encoding products involved in triglyceride synthesis and tissue signalling were up-regulated in the ‘lactating’ crop. We proposed that the evolution of the processes that result in the production of pigeon milk has built upon the more general ability of avian keratinocytes to accumulate intracellular neutral lipids during the cornification of the epidermis [11] in order to produce a nutritive substance for their young [6]. The mechanism of avian epidermal cornification and lipid accumulation is not well-characterised. However, studies have shown that antibodies against mammalian cornification proteins, which are relatively well-characterised, can cross-react with avian and reptilian species [12, 13], which suggests similarities in cornification proteins amongst vertebrate species. Cultured chicken keratinocytes have been shown to express beta-keratins (feather, scale and claw keratins), alpha-keratins (type I and II cytokeratins) and the cornified envelope precursor genes envoplakin and periplakin, as well as accumulating neutral lipids [11]. Mammalian keratinocytes differ from avian keratinocytes in that they are unable to accumulate intracellular neutral lipids [11], and can express alpha-keratins (cytokeratins) but not beta-keratins, which expanded from early archosaurians [14]. There are many cornification-associated proteins characterised from mammalian epidermal tissues. The proteins that form the cornified envelope include keratins, S100 proteins, small proline-rich proteins (SPRRs), late cornified envelope (LCE) proteins, annexins, involucrin, loricrin, filaggrin, desmoplakin, envoplakin, periplakin, trichohyalin, cystatin A, elafin and repetin [15]. Trans-glutaminase enzymes, some of which require cleavage by proteases and an increase in intracellular calcium concentration to become active, cross-link the cornified envelope proteins to form a ceramide lipid-coated protective barrier to the epidermis [16]. Many of the cornified envelope genes are present in the “epidermal differentiation complex” (EDC) which was first identified on chromosome 1q21 in humans [17]. Interestingly, the EDC region has been identified in an avian species (chicken), and is linked to the genes for beta-keratins, but lacks the LCE proteins [18]. Here we present an analysis of the pigeon crop transcriptome to show that pigeon milk production involves a specialised cornification process and de novo synthesis of lipids that accumulate intracellularly

The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) Study: Trial Design and Baseline Characteristics

Introduction: Despite optimal current care, up to 30% of individuals suffering from immunoglobulin A nephropathy (IgAN) will develop kidney failure requiring dialysis or kidney transplantation. The Therapeutic Evaluation of STeroids in IgA Nephropathy Global (TESTING) study was designed to assess the benefits and risks of steroids in people with IgAN. We report the trial design as well as the baseline characteristics of study participants. Methods: It is an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized trial of individuals with kidney biopsy-confirmed IgAN, proteinuria ≥1 g/day, and an estimated GFR of 20-120 mL/min/1.73 m2, following at least 3 months of standard of care including maximum labelled (or tolerated) dose of renin-angiotensin system blockade. The original study design randomized participants 1:1 to oral methylprednisolone (0.6-0.8 mg/kg/day, maximum 48 mg/day) for 2 months, with subsequent weaning by 8 mg/day/month over 6-8 months, or matching placebo. The intervention was modified in 2016 (due to an excess of serious infection) to low-dose methylprednisolone (0.4 mg/kg/day, maximum 32 mg/day) for 2 months, followed by weaning by 4 mg/day/month over 6-9 months, or matching placebo. Participants recruited after 2016 also received prophylaxis against Pneumocystis jirovecii pneumonia during the first 12 weeks of treatment. Results: The study recruitment period extended from May 2012 to November 2019. By the time the excess of serious infections was observed, 262 participants had been randomized to the original full-dose treatment algorithm, and an interim analysis was reported in 2016. Subsequently, 241 additional participants were randomized to a revised low-dose protocol, for a total of 503 participants from China (373), India (78), Canada (24), Australia (18), and Malaysia (10). The mean age of randomized participants was 38, 39% were female, mean eGFR at randomization was 62.7 mL/min/1.73 m2, and mean 24-h urine protein 2.54 g. The primary endpoint is a composite of 40% eGFR decline from baseline or kidney failure (dialysis, transplantation, or death due to kidney disease), and participants will be followed until the primary outcome has been observed in at least 160 randomized participants. Analyses will also be made across predefined subgroups. Effects on eGFR slope and albuminuria will also be assessed overall, as well as by the steroid dosing regimen. Conclusions: The TESTING study (combined full and low dose) will define the benefits of corticosteroid use on major kidney outcomes, as well as the risks of therapy, and provide data on the relative effects of different doses, in individuals with high-risk IgAN

The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) Study: Trial Design and Baseline Characteristics

INTRODUCTION: Despite optimal current care, up to 30% of individuals suffering from immunoglobulin A nephropathy (IgAN) will develop kidney failure requiring dialysis or kidney transplantation. The Therapeutic Evaluation of STeroids in IgA Nephropathy Global (TESTING) study was designed to assess the benefits and risks of steroids in people with IgAN. We report the trial design as well as the baseline characteristics of study participants. METHODS: It is an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized trial of individuals with kidney biopsy-confirmed IgAN, proteinuria ≥1 g/day, and an estimated GFR of 20-120 mL/min/1.73 m2, following at least 3 months of standard of care including maximum labelled (or tolerated) dose of renin-angiotensin system blockade. The original study design randomized participants 1:1 to oral methylprednisolone (0.6-0.8 mg/kg/day, maximum 48 mg/day) for 2 months, with subsequent weaning by 8 mg/day/month over 6-8 months, or matching placebo. The intervention was modified in 2016 (due to an excess of serious infection) to low-dose methylprednisolone (0.4 mg/kg/day, maximum 32 mg/day) for 2 months, followed by weaning by 4 mg/day/month over 6-9 months, or matching placebo. Participants recruited after 2016 also received prophylaxis against Pneumocystis jirovecii pneumonia during the first 12 weeks of treatment. RESULTS: The study recruitment period extended from May 2012 to November 2019. By the time the excess of serious infections was observed, 262 participants had been randomized to the original full-dose treatment algorithm, and an interim analysis was reported in 2016. Subsequently, 241 additional participants were randomized to a revised low-dose protocol, for a total of 503 participants from China (373), India (78), Canada (24), Australia (18), and Malaysia (10). The mean age of randomized participants was 38, 39% were female, mean eGFR at randomization was 62.7 mL/min/1.73 m2, and mean 24-h urine protein 2.54 g. The primary endpoint is a composite of 40% eGFR decline from baseline or kidney failure (dialysis, transplantation, or death due to kidney disease), and participants will be followed until the primary outcome has been observed in at least 160 randomized participants. Analyses will also be made across predefined subgroups. Effects on eGFR slope and albuminuria will also be assessed overall, as well as by the steroid dosing regimen. CONCLUSIONS: The TESTING study (combined full and low dose) will define the benefits of corticosteroid use on major kidney outcomes, as well as the risks of therapy, and provide data on the relative effects of different doses, in individuals with high-risk IgAN

Treating frailty-a practical guide

Frailty is a common syndrome that is associated with vulnerability to poor health outcomes. Frail older people have increased risk of morbidity, institutionalization and death, resulting in burden to individuals, their families, health care services and society. Assessment and treatment of the frail individual provide many challenges to clinicians working with older people. Despite frailty being increasingly recognized in the literature, there is a paucity of direct evidence to guide interventions to reduce frailty. In this paper we review methods for identification of frailty in the clinical setting, propose a model for assessment of the frail older person and summarize the current best evidence for treating the frail older person. We provide an evidence-based framework that can be used to guide the diagnosis, assessment and treatment of frail older people