Flagellar membrane association via interaction with lipid rafts

The eukaryotic flagellar membrane has a distinct composition from other domains of the plasmalemma. Our work shows that the specialized composition of the trypanosome flagellar membrane reflects increased concentrations of sterols and saturated fatty acids, correlating with direct observation of high liquid order by laurdan fluorescence microscopy. These findings indicate that the trypanosome flagellar membrane possesses high concentrations of lipid rafts: discrete regions of lateral heterogeneity in plasma membranes that serve to sequester and organize specialized protein complexes. Consistent with this, a dually acylated Ca(2+) sensor that is concentrated in the flagellum is found in detergent-resistant membranes and mislocalizes if the lipid rafts are disrupted. Detergent-extracted cells have discrete membrane patches localized on the surface of the flagellar axoneme, suggestive of intraflagellar transport particles. Together, these results provide biophysical and biochemical evidence to indicate that lipid rafts are enriched in the trypanosome flagellar membrane, providing a unique mechanism for flagellar protein localization and illustrating a novel means by which specialized cellular functions may be partitioned to discrete membrane domains

Patterns, predictors, variations, and temporal trends in emergency medical service hospital prenotification for acute ischemic stroke.

BACKGROUND#ENTITYSTARTX02014;: Emergency medical services (EMS) hospital prenotification of an incoming stroke patient is guideline recommended as a means of increasing the timeliness with which stroke patients are evaluated and treated. Still, data are limited with regard to national use of, variations in, and temporal trends in EMS prenotification and associated predictors of its use. METHODS AND RESULTS#ENTITYSTARTX02014;: We examined 371 988 patients with acute ischemic stroke who were transported by EMS and enrolled in 1585 hospitals participating in Get With The Guidelines-Stroke from April 1, 2003, through March 31, 2011. Prenotification occurred in 249 197 EMS-transported patients (67.0%) and varied widely by hospital (range, 0% to 100%). Substantial variations by geographic regions and by state, ranging from 19.7% in Washington, DC, to 93.4% in Montana, also were noted. Patient factors associated with lower use of prenotification included older age, diabetes mellitus, and peripheral vascular disease. Prenotification was less likely for black patients than for white patients (adjusted odds ratio 0.94, 95% confidence interval 0.92-0.97, P<0.0001). Hospital factors associated with greater EMS prenotification use were absence of academic affiliation, higher annual volume of tissue plasminogen activator administration, and geographic location outside the Northeast. Temporal improvements in prenotification rates showed a modest general increase, from 58.0% in 2003 to 67.3% in 2011 (P temporal trend <0.0001). CONCLUSIONS#ENTITYSTARTX02014;: EMS hospital prenotification is guideline recommended, yet among patients transported to Get With The Guidelines-Stroke hospitals it is not provided for 1 in 3 EMS-arriving patients with acute ischemic stroke and varies substantially by hospital, state, and region. These results support the need for enhanced implementation of stroke systems of care. (J Am Heart Assoc. 2012;1:e002345 doi: 10.1161/JAHA.112.002345.)

Market-Driven Innovation

A new method for starting the iterative innovation process from the market side based on a sociological trend has been developed. It eliminates the traditional difference between the innovators and the sociological group that carries this trend, which can only be achieved by combining real-world innovation with innovation education. The method for market need discovery is presented as a step-by-step process with detailed reasoning, followed by a real-world example that details the outcomes at every step along the way. The example concludes with a detailed description of the outcome after the first innovation iteration cycle. The richness of the resulting concept demonstrates that an innovation process can be successfully started from the market side via the proposed method

The Lantern Vol. 39, No. 2, Spring 1973

• Days of Rain • Reflections On Clifton, New Jersey • Interlude • Window Scene • Eh! • Odyssey of Malcolm • Tuna on Toast • The Second Avenue Bus • Salutation of the Dawn • So Say Something • Mood • Moriarty\u27s Lament • I\u27ve Been a Lonely Gypsy • Change • Cool Ray • The Thinker • A Southern Sunsethttps://digitalcommons.ursinus.edu/lantern/1102/thumbnail.jp

Informing investment to reduce inequalities: a modelling approach

Background: Reducing health inequalities is an important policy objective but there is limited quantitative information about the impact of specific interventions. Objectives: To provide estimates of the impact of a range of interventions on health and health inequalities. Materials and methods: Literature reviews were conducted to identify the best evidence linking interventions to mortality and hospital admissions. We examined interventions across the determinants of health: a ‘living wage’; changes to benefits, taxation and employment; active travel; tobacco taxation; smoking cessation, alcohol brief interventions, and weight management services. A model was developed to estimate mortality and years of life lost (YLL) in intervention and comparison populations over a 20-year time period following interventions delivered only in the first year. We estimated changes in inequalities using the relative index of inequality (RII). Results: Introduction of a ‘living wage’ generated the largest beneficial health impact, with modest reductions in health inequalities. Benefits increases had modest positive impacts on health and health inequalities. Income tax increases had negative impacts on population health but reduced inequalities, while council tax increases worsened both health and health inequalities. Active travel increases had minimally positive effects on population health but widened health inequalities. Increases in employment reduced inequalities only when targeted to the most deprived groups. Tobacco taxation had modestly positive impacts on health but little impact on health inequalities. Alcohol brief interventions had modestly positive impacts on health and health inequalities only when strongly socially targeted, while smoking cessation and weight-reduction programmes had minimal impacts on health and health inequalities even when socially targeted. Conclusions: Interventions have markedly different effects on mortality, hospitalisations and inequalities. The most effective (and likely cost-effective) interventions for reducing inequalities were regulatory and tax options. Interventions focused on individual agency were much less likely to impact on inequalities, even when targeted at the most deprived communities

Bringing Habits and Emotions into Food Waste Behaviour

This study examined consumer food waste behaviour using a comprehensive model integrating the theory of planned behaviour (TPB), the theory of interpersonal behaviour, and the comprehensive model of environmental behaviour. Using a temporally lagged design, one hundred and seventy-two respondents answered four questionnaires over a period of 14 months. Questionnaires measured emotions in relation to food waste, habits, the TPB variables, intention to reduce food waste, and self-reported food waste behaviour. Results showed that the less well-studied variables of habits and emotions were important determinants of participants’ intentions to reduce food waste and their current food waste behaviour. As expected, we found that negative emotions were associated with greater intentions to reduce food waste, but contrary to our predictions they were also associated with higher levels of food waste behaviour. In other words, participants who experienced more negative emotion when thinking about food waste intended to reduce their waste but actually ended up wasting more food. Results also show that participants with a greater sense of control, and more normative support for reducing food waste also had stronger intentions to engage in the behaviour. Our findings extend existing understanding and underscore the importance of the non-cognitive determinants of behaviour, namely emotions and habits. The implications for research and practice are discussed

Using decision analysis to support proactive management of emerging infectious wildlife diseases

Despite calls for improved responses to emerging infectious diseases in wildlife, management is seldom considered until a disease has been detected in affected populations. Reactive approaches may limit the potential for control and increase total response costs. An alternative, proactive management framework can identify immediate actions that reduce future impacts even before a disease is detected, and plan subsequent actions that are conditional on disease emergence. We identify four main obstacles to developing proactive management strategies for the newly discovered salamander pathogen Batrachochytrium salamandrivorans (Bsal). Given that uncertainty is a hallmark of wildlife disease management and that associated decisions are often complicated by multiple competing objectives, we advocate using decision analysis to create and evaluate trade-offs between proactive (pre-emergence) and reactive (post-emergence) management options. Policy makers and natural resource agency personnel can apply principles from decision analysis to improve strategies for countering emerging infectious diseases

Increasing physical activity in postpartum multiethnic women in Hawaii: results from a pilot study

<p>Abstract</p> <p>Background</p> <p>Mothers of an infant are much less likely to exercise regularly compared to other women. This study tested the efficacy of a brief tailored intervention to increase physical activity (PA) in women 3–12 months after childbirth. The study used a pretest-posttest design. Sedentary women (n = 20) were recruited from a parenting organization. Half the participants were ethnic minorities, mean age was 33 ± 3.8, infants' mean age was 6.9 ± 2.4 months, 50% were primiparas, and mean body mass index was 23.6 ± 4.2.</p> <p>Methods</p> <p>The two-month intervention included telephone counseling, pedometers, referral to community PA resources, social support, email advice on PA/pedometer goals, and newsletters.</p> <p>The primary outcome of the study was minutes per week of moderate and vigorous leisure-time physical activity measured by the Godin physical activity instrument.</p> <p>Results</p> <p>All women (100%) returned for post-test measures; thus, paired t-tests were used for pre-post increase in minutes of moderate and vigorous leisure-time physical activity and comparisons of moderate and vigorous leisure-time physical activity increases among ethnic groups. At baseline participants' reported a mean of 3 ± 13.4 minutes per week moderate and vigorous leisure-time physical activity. At post-test this significantly increased to 85.5 ± 76.4 minutes per week of moderate and vigorous leisure-time physical activity (p < .001, Cohen's d = 2.2; effect size r = 0.7). There were no differences in pre to post increases in minutes of moderate and vigorous leisure-time physical activity among races.</p> <p>Conclusion</p> <p>A telephone/email intervention tailored to meet the needs of postpartum women was effective in increasing physical activity levels. However, randomized trials comparing tailored telephone and email interventions to standard care and including long-term follow-up to determine maintenance of physical activity are warranted.</p

Genome Scan of M. tuberculosis Infection and Disease in Ugandans

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is an enduring public health problem globally, particularly in sub-Saharan Africa. Several studies have suggested a role for host genetic susceptibility in increased risk for TB but results across studies have been equivocal. As part of a household contact study of Mtb infection and disease in Kampala, Uganda, we have taken a unique approach to the study of genetic susceptibility to TB, by studying three phenotypes. First, we analyzed culture confirmed TB disease compared to latent Mtb infection (LTBI) or lack of Mtb infection. Second, we analyzed resistance to Mtb infection in the face of continuous exposure, defined by a persistently negative tuberculin skin test (PTST-); this outcome was contrasted to LTBI. Third, we analyzed an intermediate phenotype, tumor necrosis factor-alpha (TNFα) expression in response to soluble Mtb ligands enriched with molecules secreted from Mtb (culture filtrate). We conducted a full microsatellite genome scan, using genotypes generated by the Center for Medical Genetics at Marshfield. Multipoint model-free linkage analysis was conducted using an extension of the Haseman-Elston regression model that includes half sibling pairs, and HIV status was included as a covariate in the model. The analysis included 803 individuals from 193 pedigrees, comprising 258 full sibling pairs and 175 half sibling pairs. Suggestive linkage (p<10−3) was observed on chromosomes 2q21-2q24 and 5p13-5q22 for PTST-, and on chromosome 7p22-7p21 for TB; these findings for PTST- are novel and the chromosome 7 region contains the IL6 gene. In addition, we replicated recent linkage findings on chromosome 20q13 for TB (p = 0.002). We also observed linkage at the nominal α = 0.05 threshold to a number of promising candidate genes, SLC11A1 (PTST- p = 0.02), IL-1 complex (TB p = 0.01), IL12BR2 (TNFα p = 0.006), IL12A (TB p = 0.02) and IFNGR2 (TNFα p = 0.002). These results confirm not only that genetic factors influence the interaction between humans and Mtb but more importantly that they differ according to the outcome of that interaction: exposure but no infection, infection without progression to disease, or progression of infection to disease. Many of the genetic factors for each of these stages are part of the innate immune system