Screening families of patients with premature coronary heart disease to identify avoidable cardiovascular risk: a cross-sectional study of family members and a general population comparison group

<b>Background:</b> Primary prevention should be targeted at individuals with high global cardiovascular risk, but research is lacking on how best to identify such individuals in the general population. Family history is a good proxy measure of global risk and may provide an efficient mechanism for identifying high risk individuals. The aim was to test the feasibility of using patients with premature cardiovascular disease to recruit family members as a means of identifying and screening high-risk individuals. <b>Findings:</b> We recruited family members of 50 patients attending a cardiology clinic for premature coronary heart disease (CHD). We compared their cardiovascular risk with a general population control group, and determined their perception of their risk and current level of screening. 103 (36%) family members attended screening (27 siblings, 48 adult offspring and 28 partners). Five (5%) had prevalent CHD. A significantly higher percentage had an ASSIGN risk score >20% compared with the general population (13% versus 2%, p < 0.001). Only 37% of family members were aware they were at increased risk and only 50% had had their blood pressure and serum cholesterol level checked in the previous three years. <b>Conclusions:</b> Patients attending hospital for premature CHD provide a mechanism to contact family members and this can identify individuals with a high global risk who are not currently screened

Leave entitlements, time off work and the household financial impacts of quarantine compliance during an H1N1 outbreak

The Australian state of Victoria, with 5.2 million residents, enforced home quarantine during a H1N1 pandemic in 2009. The strategy was targeted at school children. The objective of this study was to investigate the extent to which parents’ access to paid sick leave or paid carer’s leave was associated with (a) time taken off work to care for quarantined children, (b) household finances, and (c) compliance with quarantine recommendations.This project was funded by two NHMRC Strategic Awards: “Call for research on H1N1 influenza 09 to inform public policy” (#628962) and “Changing patterns of work: Impacts on physical and mental health and the mediating role of resilience and social capital” (#375196). JM is supported by a NHMRC Career Development Award; DS is funded by an ARC Federation Fellowship

'This is what democracy looks like' : New Labour's blind spot and peripheral vision

New Labour in government since 1997 has been roundly criticized for not possessing a clear, coherent and consistent democratic vision. The absence of such a grand vision has resulted, from this critical perspective, in an absence of 'joined-up' thinking about democracy in an evolving multi-level state. Tensions have been all too apparent between the government's desire to exert central direction - manifested in its most pathological form as 'control freakery' - and its democratising initiatives derived from 'third-way' obsessions with 'decentralising', 'empowering' and 'enabling'. The purpose of this article is to examine why New Labour displayed such apparently impaired democratic vision and why it appeared incapable of conceiving of democratic reform 'in the round'. This article seeks to explain these apparent paradoxes, however, through utilising the notion of 'macular degeneration'. In this analysis, the perceived democratic blind spot of New Labour at Westminster is connected to a democratic peripheral vision, which has envisaged innovative participatory and decentred initiatives in governance beyond Westminster

The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes

Organisms have evolved to survive rigorous environments and are not prepared to thrive in a world of caloric excess and sedentary behavior. A realization that physical exercise (or lack of it) plays a pivotal role in both the pathogenesis and therapy of type 2 diabetes mellitus (t2DM) has led to the provocative concept of therapeutic exercise mimetics. A decade ago, we attempted to simulate the beneficial effects of exercise by treating t2DM patients with 3 weeks of daily hyperthermia, induced by hot tub immersion. The short-term intervention had remarkable success, with a 1 % drop in HbA1, a trend toward weight loss, and improvement in diabetic neuropathic symptoms. An explanation for the beneficial effects of exercise and hyperthermia centers upon their ability to induce the cellular stress response (the heat shock response) and restore cellular homeostasis. Impaired stress response precedes major metabolic defects associated with t2DM and may be a near seminal event in the pathogenesis of the disease, tipping the balance from health into disease. Heat shock protein inducers share metabolic pathways associated with exercise with activation of AMPK, PGC1-a, and sirtuins. Diabetic therapies that induce the stress response, whether via heat, bioactive compounds, or genetic manipulation, improve or prevent all of the morbidities and comorbidities associated with the disease. The agents reduce insulin resistance, inflammatory cytokines, visceral adiposity, and body weight while increasing mitochondrial activity, normalizing membrane structure and lipid composition, and preserving organ function. Therapies restoring the stress response can re-tip the balance from disease into health and address the multifaceted defects associated with the disease

An Eye to a Kill: Using Predatory Bacteria to Control Gram-Negative Pathogens Associated with Ocular Infections

Ocular infections are a leading cause of vision loss. It has been previously suggested that predatory prokaryotes might be used as live antibiotics to control infections. In this study, Pseudomonas aeruginosa and Serratia marcescens ocular isolates were exposed to the predatory bacteria Micavibrio aeruginosavorus and Bdellovibrio bacteriovorus. All tested S. marcescens isolates were susceptible to predation by B. bacteriovorus strains 109J and HD100. Seven of the 10 P. aeruginosa isolates were susceptible to predation by B. bacteriovorus 109J with 80% being attacked by M. aeruginosavorus. All of the 19 tested isolates were found to be sensitive to at least one predator. To further investigate the effect of the predators on eukaryotic cells, human corneal-limbal epithelial (HCLE) cells were exposed to high concentrations of the predators. Cytotoxicity assays demonstrated that predatory bacteria do not damage ocular surface cells in vitro whereas the P. aeruginosa used as a positive control was highly toxic. Furthermore, no increase in the production of the proinflammatory cytokines IL-8 and TNF-alpha was measured in HCLE cells after exposure to the predators. Finally, injection of high concentration of predatory bacteria into the hemocoel of Galleria mellonella, an established model system used to study microbial pathogenesis, did not result in any measurable negative effect to the host. Our results suggest that predatory bacteria could be considered in the near future as a safe topical bio-control agent to treat ocular infections. © 2013 Shanks et al

Reduced Diversity and High Sponge Abundance on a Sedimented Indo-Pacific Reef System: Implications for Future Changes in Environmental Quality

Although coral reef health across the globe is declining as a result of anthropogenic impacts, relatively little is known of how environmental variability influences reef organisms other than corals and fish. Sponges are an important component of coral reef fauna that perform many important functional roles and changes in their abundance and diversity as a result of environmental change has the potential to affect overall reef ecosystem functioning. In this study, we examined patterns of sponge biodiversity and abundance across a range of environments to assess the potential key drivers of differences in benthic community structure. We found that sponge assemblages were significantly different across the study sites, but were dominated by one species Lamellodysidea herbacea (42% of all sponges patches recorded) and that the differential rate of sediment deposition was the most important variable driving differences in abundance patterns. Lamellodysidea herbacea abundance was positively associated with sedimentation rates, while total sponge abundance excluding Lamellodysidea herbacea was negatively associated with rates of sedimentation. Overall variation in sponge assemblage composition was correlated with a number of variables although each variable explained only a small amount of the overall variation. Although sponge abundance remained similar across environments, diversity was negatively affected by sedimentation, with the most sedimented sites being dominated by a single sponge species. Our study shows how some sponge species are able to tolerate high levels of sediment and that any transition of coral reefs to more sedimented states may result in a shift to a low diversity sponge dominated system, which is likely to have subsequent effects on ecosystem functioning. © 2014 Powell et al

Phase 2 study of canfosfamide in combination with pegylated liposomal doxorubicin in platinum and paclitaxel refractory or resistant epithelial ovarian cancer

<p>Abstract</p> <p>Background</p> <p>Canfosfamide is a novel glutathione analog activated by glutathione S-transferase P1-1. This study evaluated the safety and efficacy of canfosfamide in combination with pegylated liposomal doxorubicin (PLD) in patients with platinum resistant ovarian cancer. Patients with platinum resistant ovarian carcinoma and measurable disease received canfosfamide at 960 mg/m²in combination with PLD at 50 mg/m², intravenously day 1 in every 28 day cycles until tumor progression or unacceptable toxicities. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS).</p> <p>Results</p> <p>Canfosfamide plus PLD combination therapy was administered at 960/50 mg/m², respectively. Thirty-nine patients received a median number of 4 cycles (range 1.0-18.0). The ORR was 27.8% (95% CI, 14.2-45.2) with a disease stabilization rate of 80.6% (95% CI, 64.0-91.8) in the evaluable population. The CA-125 marker responses correlated with the radiological findings of complete response or partial response. The median PFS was 6.0 months (95% CI, 4.2-7.9) and median survival was 17.8 months. The combination was well tolerated. Myelosuppression was managed with dose reductions and growth factor support. Grade 3 febrile neutropenia was observed in 2 patients (5.1%). Non-hematologic adverse events occurred at the expected frequency and grade for each drug alone, with no unexpected or cumulative toxicities.</p> <p>Conclusions</p> <p>Canfosfamide in combination with PLD is well tolerated and active in platinum and paclitaxel refractory or resistant ovarian cancer. A randomized phase 3 study was conducted based on this supportive phase 2 study.</p> <p>Trial Registration</p> <p>This study was registered at www.clinicaltrials.gov: NCT00052065.</p

Changing the culture of assessment: the dominance of the summative assessment paradigm

Background Despite growing evidence of the benefits of including assessment for learning strategies within programmes of assessment, practical implementation of these approaches is often problematical. Organisational culture change is often hindered by personal and collective beliefs which encourage adherence to the existing organisational paradigm. We aimed to explore how these beliefs influenced proposals to redesign a summative assessment culture in order to improve students’ use of assessment-related feedback. Methods Using the principles of participatory design, a mixed group comprising medical students, clinical teachers and senior faculty members was challenged to develop radical solutions to improve the use of post-assessment feedback. Follow-up interviews were conducted with individual members of the group to explore their personal beliefs about the proposed redesign. Data were analysed using a socio-cultural lens. Results Proposed changes were dominated by a shared belief in the primacy of the summative assessment paradigm, which prevented radical redesign solutions from being accepted by group members. Participants’ prior assessment experiences strongly influenced proposals for change. As participants had largely only experienced a summative assessment culture, they found it difficult to conceptualise radical change in the assessment culture. Although all group members participated, students were less successful at persuading the group to adopt their ideas. Faculty members and clinical teachers often used indirect techniques to close down discussions. The strength of individual beliefs became more apparent in the follow-up interviews. Conclusions Naïve epistemologies and prior personal experiences were influential in the assessment redesign but were usually not expressed explicitly in a group setting, perhaps because of cultural conventions of politeness. In order to successfully implement a change in assessment culture, firmly-held intuitive beliefs about summative assessment will need to be clearly understood as a first step

Does the level of expressed emotion (LEE) questionnaire have the same factor structure for adolescents as it has for adults?

Background The level of expressed emotion (LEE) is a four-factor questionnaire that measures expressed emotion (EE) as perceived by the recipient. These factors are: perceived lack of emotional support, perceived intrusiveness, perceived irritation, and perceive criticism. The four factors of the LEE has previously been found to be related to psychological disorders and has good psychometric properties for adults. However, it has not previously been studied in adolescent populations. Methods A total of 311 adolescents participated in this study. Using structural equation modeling, confirmatory factor analyses were conducted to examine if the LEE also had the same four-factor structure for adolescents as it does for adults. Results The confirmatory factor analyses demonstrated that the LEE's four-factor structure also applied to adolescents. The internal consistency of the scales were good and all the inter-correlations between the scales were significant. Additionally, the factors were significantly correlated to adolescent depressive and anxiety symptom score dimensions. Conclusion These findings seem to indicate that the LEE may be a good instrument in the measurement of adolescents perceived EE

A simple rule governs the evolution and development of hominin tooth size

The variation in molar tooth size in humans and our closest relatives (hominins) has strongly influenced our view of human evolution. The reduction in overall size and disproportionate decrease in third molar size have been noted for over a century, and have been attributed to reduced selection for large dentitions owing to changes in diet or the acquisition of cooking1, 2. The systematic pattern of size variation along the tooth row has been described as a ‘morphogenetic gradient’ in mammal, and more specifically hominin, teeth since Butler3 and Dahlberg4. However, the underlying controls of tooth size have not been well understood, with hypotheses ranging from morphogenetic fields3 to the clone theory5. In this study we address the following question: are there rules that govern how hominin tooth size evolves? Here we propose that the inhibitory cascade, an activator–inhibitor mechanism that affects relative tooth size in mammals6, produces the default pattern of tooth sizes for all lower primary postcanine teeth (deciduous premolars and permanent molars) in hominins. This configuration is also equivalent to a morphogenetic gradient, finally pointing to a mechanism that can generate this gradient. The pattern of tooth size remains constant with absolute size in australopiths (including Ardipithecus, Australopithecus and Paranthropus). However, in species of Homo, including modern humans, there is a tight link between tooth proportions and absolute size such that a single developmental parameter can explain both the relative and absolute sizes of primary postcanine teeth. On the basis of the relationship of inhibitory cascade patterning with size, we can use the size at one tooth position to predict the sizes of the remaining four primary postcanine teeth in the row for hominins. Our study provides a development-based expectation to examine the evolution of the unique proportions of human teeth