Complex interplay between intrinsic and extrinsic drivers of long-term survival trends in southern elephant seals

BACKGROUND: Determining the relative contribution of intrinsic and extrinsic factors to fluctuations in population size, trends and demographic composition is analytically complex. It is often only possible to examine the combined effects of these factors through measurements made over long periods, spanning an array of population densities or levels of food availability. Using age-structured mark-recapture models and datasets spanning five decades (1950–1999), and two periods of differing relative population density, we estimated age-specific probabilities of survival and examined the combined effects of population density and environmental conditions on juvenile survival of southern elephant seals at Macquarie Island. RESULTS: First-year survival decreased with density during the period of highest population size, and survival increased during years when the Southern Oscillation Index (SOI) anomaly (deviation from a 50-year mean) during the mother's previous foraging trip to sea was positive (i.e., El Niño). However, when environmental stochasticity and density were considered together, the effect of density on first-year survival effectively disappeared. Ignoring density effects also leads to models placing too much emphasis on the environmental conditions prevailing during the naïve pup's first year at sea. CONCLUSION: Our analyses revealed that both the state of the environment and population density combine to modify juvenile survival, but that the degree to which these processes contributed to the variation observed was interactive and complex. This underlines the importance of evaluating the relative contribution of both the intrinsic and extrinsic factors that regulate animal populations because false conclusions regarding the importance of population regulation may be reached if they are examined in isolation

The ‘Blueprint’ framework for career management skills: a critical exploration

This article examines the Blueprint framework for career management skills as it has been revealed across sequential implementations in the USA, Canada and Australia. It is argued that despite its lack of an empirical basis, the framework forms a useful and innovative means through which career theory, practice and policy can be connected. The framework comprises both core elements (learning areas, learning model and levels) and contextual elements (resources, community of practice, service delivery approach and policy connection). Each of these elements is explored

Robustness of MEK-ERK Dynamics and Origins of Cell-to-Cell Variability in MAPK Signaling.

Cellular signaling processes can exhibit pronounced cell-to-cell variability in genetically identical cells. This affects how individual cells respond differentially to the same environmental stimulus. However, the origins of cell-to-cell variability in cellular signaling systems remain poorly understood. Here, we measure the dynamics of phosphorylated MEK and ERK across cell populations and quantify the levels of population heterogeneity over time using high-throughput image cytometry. We use a statistical modeling framework to show that extrinsic noise, particularly that from upstream MEK, is the dominant factor causing cell-to-cell variability in ERK phosphorylation, rather than stochasticity in the phosphorylation/dephosphorylation of ERK. We furthermore show that without extrinsic noise in the core module, variable (including noisy) signals would be faithfully reproduced downstream, but the within-module extrinsic variability distorts these signals and leads to a drastic reduction in the mutual information between incoming signal and ERK activity

Intranasal fentanyl versus intravenous morphine in the emergency department treatment of severe painful sickle cell crises in children: study protocol for a randomised controlled trial.

BACKGROUND: Children with sickle cell disease (SCD) frequently and unpredictably present to the emergency department (ED) with pain. The painful event is the hallmark acute clinical manifestation of SCD, characterised by sudden onset and is usually bony in origin. This study aims to establish if 1.5mcg/kg of intranasal fentanyl (INF; administered via a Mucosal Atomiser Device, MAD™) is non-inferior to intravenous morphine 0.1 mg/kg in severe SCD-associated pain. METHODS/DESIGN: This study is a randomised,double-blind, double-dummy active control trial of children (weighing more than 10 kg) between 1 year and 21 years of age with severe painful sickle cell crisis. Severe pain is defined as rated seven or greater on a 0 to 10 age-appropriate numeric pain scale or equivalent. The trial will be conducted in a single tertiary urban paediatric ED in Dublin, Ireland. Each patient will receive a single active agent and a single placebo via the intravenous and intranasal routes. All clinical and research staff, patients and parents will be blinded to the treatment allocation. The primary endpoint is severity of pain scored at 10 min from administration of the study medications. Secondary endpoints include pain severity measured at 0, 5, 15, 20, 30, 60 and 120 min after the administration of analgesia, proportion of patients requiring rescue analgesia and incidence of adverse events. The trial ends at 120 min after the administration of the study drugs. A clinically meaningful difference in validated pain scores has been defined as 13 mm. Setting the permitted threshold to 50% of this limit (6 mm) and assuming both treatments are on average equal, a sample size of 30 patients (15 per group) will provide at least 80% power to demonstrate that INF is non-inferior to IV morphine with a level of significance of 0.05. DISCUSSION: This clinical trial will inform of the role of INF 1.5mcg/kg via MAD in the acute treatment of severe painful sickle cell crisis in children in the ED setting. TRIAL REGISTRATION: Current Controlled Trials ISRCTN67469672 and EudraCT no. 2011-005161-20

Child sexual abuse and social identity loss: a qualitative analysis of survivors' public accounts

Emerging evidence suggests that social identities are an important determinant of adaptation following traumatic life experiences. In this paper we analyse accounts of people who experienced child sexual abuse. Using publicly available talk of people who waived their right to anonymity following successful conviction of perpetrators, we conducted a thematic analysis focusing on trauma related changes in their social identities. Analysis of these accounts highlighted two themes. The first highlights the acquisition in these accounts of unwanted and damaging identity labels. The second presents child sexual abuse as a key destructive force in terms of important identity work during childhood. Discussion of this analysis centres on the pathological consequences of social identity change. Both the loss of valued identities and the acquisition of aberrant and isolating identities are experienced and constructed as devastating by those affected by child sexual abuse. This has important implications, not only for those impacted by child sexual abuse, but for how abuse is discussed in society, and how it is approached by policy makers, educators and individuals working with survivors and their families

Sexual violence and traumatic identity change: evidence of collective post-traumatic growth

Recent research indicates that social identities play a crucial role in the connection between adversity, post-traumatic stress, and overall psychological well-being. Understanding of how trauma influences collective dimensions of the self, positively or negatively, is limited. This study focuses on analysing publicly accessible narratives of four women who chose to waive their anonymity after the conviction of the men who had attacked and sexually assaulted them in Ireland. Thematic analysis highlighted two themes that signal (i) collective dimensions to this personal trauma, (ii) attempts to reconstruct social identities in the aftermath of trauma. Women presented their experiences as having the potential to amplify positive connections with others despite the wider embedded sociocultural understanding of sexual assault. These changes were associated with redefinition of social identities. Discussion highlights the potential for personal and intimate trauma to result in positive social identity change; a phenomenon that we label collective post-traumatic growth

Effect of increasing intraperitoneal infusion rates on bupropion hydrochloride-induced seizures in mice

<p>Abstract</p> <p>Background</p> <p>It is not known if there is a relationship between input rate and incidence of bupropion-induced seizures. This is important, since different controlled release formulations of bupropion release the active drug at different rates.</p> <p>Methods</p> <p>We investigated the effect of varying the intraperitoneal infusion rates of bupropion HCl 120 mg/kg, a known convulsive dose₅₀(CD₅₀), on the incidence and severity of bupropion-induced convulsions in the Swiss albino mice. A total of 69 mice, approximately 7 weeks of age, and weighing 21.0 to 29.1 g were randomly assigned to bupropion HCl 120 mg/kg treatment by intraperitoneal (IP) administration in 7 groups (9 to 10 animals per group). Bupropion HCl was infused through a surgically implanted IP dosing catheter with infusions in each group of 0 min, 15 min, 30 min, 60 min, 90 min, 120 min, and 240 min. The number, time of onset, duration and the intensity of the convulsions or absence of convulsions were recorded.</p> <p>Results</p> <p>The results showed that IP administration of bupropion HCl 120 mg/kg by bolus injection induced convulsions in 6 out of 10 mice (60% of convulsing mice) in group 1. Logistic regression analysis revealed that infusion time was significant (p = 0.0004; odds ratio = 0.974) and increasing the IP infusion time of bupropion HCl 120 mg/kg was associated with a 91% reduced odds of convulsions at infusion times of 15 to 90 min compared to bolus injection. Further increase in infusion time resulted in further reduction in the odds of convulsions to 99.8% reduction at 240 min.</p> <p>Conclusion</p> <p>In conclusion, the demonstration of an inverse relationship between infusion time of a fixed and convulsive dose of bupropion and the risk of convulsions in a prospective study is novel.</p

A Design Exploration of Health-Related Community Displays

The global population is ageing, leading to shifts in healthcare needs. It is well established that increased physical activity can improve the health and wellbeing of many older adults. However, motivation remains a prime concern. We report findings from a series of focus groups where we explored the concept of using community displays to promote physical activity to a local neighborhood. In doing so, we contribute both an understanding of the design space for community displays, as well as a discussion of the implications of our work for the broader CSCW community. We conclude that our work demonstrates the potential for developing community displays for increasing physical activity amongst older adults

Convulsive liability of bupropion hydrochloride metabolites in Swiss albino mice

<p>Abstract</p> <p>Background</p> <p>It is known that following chronic dosing with bupropion HCl active metabolites are present in plasma at levels that are several times higher than that of the parent drug, but the possible convulsive effects of the major metabolites are not known.</p> <p>Methods</p> <p>We investigated the convulsive liability and dose-response of the three major bupropion metabolites following intraperitoneal administration of single doses in female Swiss albino mice, namely erythrohydrobupropion HCl, threohydrobupropion HCl, and hydroxybupropion HCl. We compared these to bupropion HCl. The actual doses of the metabolites administered to mice (n = 120; 10 per dose group) were equimolar equivalents of bupropion HCl 25, 50 and 75 mg/kg. Post treatment, all animals were observed continuously for 2 h during which the number, time of onset, duration and intensity of convulsions were recorded. The primary outcome variable was the percentage of mice in each group who had a convulsion at each dose. Other outcome measures were the time to onset of convulsions, mean convulsions per mouse, and the duration and intensity of convulsions.</p> <p>Results</p> <p>All metabolites were associated with a greater percentage of seizures compared to bupropion, but the percentage of convulsions differed between metabolites. Hydroxybupropion HCl treatment induced the largest percentage of convulsing mice (100% at both 50 and 75 mg/kg) followed by threohydrobupropion HCl (50% and 100%), and then erythrohydrobupropion HCl (10% and 90%), compared to bupropion HCl (0% and 10%). Probit analysis also revealed the dose-response curves were significantly different (p < 0.0001) with CD₅₀values of 35, 50, 61 and 82 mg/kg, respectively for the four different treatments. Cox proportional hazards model results showed that bupropion HCl, erythrohydrobupropion HCl, and threohydrobupropion HCl were significantly less likely to induce convulsions within the 2-h post treatment observation period compared to hydroxybupropion HCl. The mean convulsions per mouse also showed the same dose-dependent and metabolite-dependent trends.</p> <p>Conclusion</p> <p>The demonstration of the dose-dependent and metabolite-dependent convulsive effects of bupropion metabolites is a novelty.</p

Alcohol significantly lowers the seizure threshold in mice when co-administered with bupropion hydrochloride

<p>Abstract</p> <p>Background</p> <p>Bupropion HCl is a widely used antidepressant that is known to cause seizures in a dose-dependent manner. Many patients taking antidepressants will consume alcohol, even when advised not to. Previous studies have not shown any interactions between bupropion HCl and alcohol. However, there have been no previous studies examining possible changes in seizure threshold induced by a combination of alcohol and bupropion HCl.</p> <p>Methods</p> <p>Experimentally naïve female Swiss albino mice (10 per group) received either single doses of bupropion HCl (ranging from 100 mg/kg to 120 mg/kg) or vehicle (0.9% NaCl) by intraperitoneal (IP) injection in a dose volume of 10 ml/kg, and single-dose ethanol alone (2.5 g/kg), or vehicle, 5 min prior to bupropion dosing. The presence or absence of seizures, the number of seizures, the onset, duration and the intensity of seizures were all recorded for 5 h following the administration of ethanol.</p> <p>Results</p> <p>The results show that administration of IP bupropion HCl alone induced seizures in mice in a dose-dependent manner, with the 120 mg/kg dose having the largest effect. The percentage of convulsing mice were 0%, 20%, 30% and 60% in the 0 (vehicle), 100, 110, and 120 mg/kg dose groups, respectively. Pretreatment with ethanol produced a larger bupropion HCl-induced convulsive effect at all the doses (70% each at 100, 110 and 120 mg/kg) and a 10% effect in the ethanol + vehicle only group. The convulsive dose of bupropion HCl required to induce seizures in 50% of mice (CD₅₀), was 116.72 mg/kg for bupropion HCl alone (CI: 107.95, 126.20) and 89.40 mg/kg for ethanol/bupropion HCl (CI: 64.92, 123.10).</p> <p>Conclusion</p> <p>These results show that in mice alcohol lowers the seizure threshold for bupropion-induced seizures. Clinical implications are firstly that there may be an increased risk of seizures in patients consuming alcohol, and secondly that formulations that can release bupropion more readily in alcohol may present additional risks to patients.</p