Measurements of the BKCa Channel's High-Affinity Ca2+ Binding Constants: Effects of Membrane Voltage

It has been established that the large conductance Ca2+-activated K+ channel contains two types of high-affinity Ca2+ binding sites, termed the Ca2+ bowl and the RCK1 site. The affinities of these sites, and how they change as the channel opens, is still a subject of some debate. Previous estimates of these affinities have relied on fitting a series of conductance–voltage relations determined over a series of Ca2+ concentrations with models of channel gating that include both voltage sensing and Ca2+ binding. This approach requires that some model of voltage sensing be chosen, and differences in the choice of voltage-sensing model may underlie the different estimates that have been produced. Here, to better determine these affinities we have measured Ca2+ dose–response curves of channel activity at constant voltage for the wild-type mSlo channel (minus its low-affinity Ca2+ binding site) and for channels that have had one or the other Ca2+ binding site disabled via mutation. To accurately determine these dose–response curves we have used a series of 22 Ca2+ concentrations, and we have used unitary current recordings, coupled with changes in channel expression level, to measure open probability over five orders of magnitude. Our results indicate that at −80 mV the Ca2+ bowl has higher affinity for Ca2+ than does the RCK1 site in both the opened and closed conformations of the channel, and that the binding of Ca2+ to the RCK1 site is voltage dependent, whereas at the Ca2+ bowl it is not

Unmet care needs in people living with advanced cancer: a systematic review

Purpose: The support needs of cancer patients vary according to the phase of their cancer journey. Recent developments in healthcare are such that the advanced cancer phase is increasingly experienced as a chronic illness phase, with consequent changes in patient support needs. Understanding these needs, and identifying areas of unmet need, can enable us to develop services that are more adequate to the task of supporting this population. Methods: We conducted a systematic search of four electronic databases to identify studies examining the unmet needs of people living with advanced cancer. Relevant data were extracted and synthesised; meta-analyses were conducted to obtain pooled estimates for prevalence of needs. Results: We identified 23 studies (4 qualitative) for inclusion. Unmet needs were identified across a broad range of domains, with greatest prevalence in informational (30–55 %), psychological (18–42 %), physical (17–48 %), and functional (17–37 %) domains. There was considerable heterogeneity amongst studies in terms of methods of assessment, coding and reporting of needs, respondent characteristics, and appraised study quality. Conclusions: Heterogeneity made it difficult to compare across studies and inflated confidence intervals for pooled estimates of prevalence—we need standardised and comprehensive approaches to assessment and reporting of unmet needs to further our understanding. Nonetheless, the review identified prominent needs across a range of (interacting) experiential domains. Moreover, by focussing on unmet needs for support, we were able to extrapolate potential implications for service development

Information security, compliance and the grant life cycle

These slides support the oral presentation by Beth Chancellor, Jeremy Cox, Jennifer Duncan, Jennifer May, and Michelle Wisdom on October 10, 2013 at Cyberinfrastructure Day 2013 on the University of Missouri campus

Profiling the Audience for Self-Transcendent Media: A National Survey

This article reports the findings from a national survey of self-transcendent (or inspiring) media audience members in the United States. Exposure to self-transcendent content is socially significant because, theoretically, it can orient users towards matters beyond themselves, ultimately promoting connections with others and altruistic behaviors. However, to date, little is known about the daily audiences for such fare. Four primary questions guided the investigation: (1) What are the media sources and contents identified as “inspiring” by the audience?, (2) Who makes up the current U.S. audience for self-transcendent media content?, (3) What personality traits and viewer characteristics are associated with self-transcendent media consumption?, and (4) What prosocial and altruistic behaviors are associated with self-transcendent media consumption? To address these questions, a nationally representative survey (n = 3,006) was conducted. The findings are discussed in relation to the growing body of scholarship on positive media psychology

Exploring the Spirit in U.S. Audiences: The Role of the Virtue of Transcendence in Inspiring Media Consumption

Little is yet known about audiences who routinely seek out media content that is inspirational in nature. The current study expands the research on inspirational media by utilizing a nationally representative sample of U.S. audiences (n = 2,016) to explore relationships between inspiring media exposure, trait transcendence, and self-transcendent emotions. Results show that media content is a reliable source for everyday self-transcendent emotional experiences in U.S. audiences. These experiences are most frequently encountered by persons with high levels of trait spirituality and gratitude. The profile of U.S. audiences that seek out inspiring media is discussed

Natural Observation of Alcohol Price and Promotions at Bars: Implications for Alcohol Misuse Prevention

Alcohol misuse among young adults remains a primary public health concern given the wide range of short- and longterm physical, social, and societal consequences of the behavior. On-premise drinking establishments, which allow alcohol consumption on site (i.e., bars), are frequent locations for young adult alcohol use. Risks for alcohol misuse within the bar setting are key factors to identify for prevention. Notably, alcohol price and promotions are associated with alcohol consumption among young adults. This study sought to develop and pilot test an observational protocol to assess the alcohol environment at on-premise drinking establishments. Following qualitative exploration of salient risk factors in these settings through focus groups with young adults, an observational tool was adapted and tested in a feasibility study. The refined tool was then pilot tested with two independent data collectors conducting natural observation at 13 establishments in the downtown nightlife district of a small, southeastern city. High interrater reliability was noted. Descriptive summary statistics of bar characteristics demonstrate low alcohol prices with variability across types of alcohol (e.g., beer, wine, and liquor), greater numbers of alcohol promotions inside rather than outside the building, and higher rates of manual versus electronic age verification procedures. Observational assessment of alcohol price and marketing at on-premise drinking establishments as described in this study is needed to inform prevention policy and programs to reduce harms associated with young adult alcohol misuse

Severe anomalies associated with ring chromosome 7

A newborn infant with the polyasplenia sequence, intrauterine growth retardation, cutaneous nevi, and minor anomalies was found to have mosaicism for ring chromosome 7. This patient's anomalies are markedly different from those of previous patients reported with this cytogenetic anomaly.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38256/1/1320400410_ftp.pd

Implementation of the LANS-alpha turbulence model in a primitive equation ocean model

This paper presents the first numerical implementation and tests of the Lagrangian-averaged Navier-Stokes-alpha (LANS-alpha) turbulence model in a primitive equation ocean model. The ocean model in which we work is the Los Alamos Parallel Ocean Program (POP); we refer to POP and our implementation of LANS-alpha as POP-alpha. Two versions of POP-alpha are presented: the full POP-alpha algorithm is derived from the LANS-alpha primitive equations, but requires a nested iteration that makes it too slow for practical simulations; a reduced POP-alpha algorithm is proposed, which lacks the nested iteration and is two to three times faster than the full algorithm. The reduced algorithm does not follow from a formal derivation of the LANS-alpha model equations. Despite this, simulations of the reduced algorithm are nearly identical to the full algorithm, as judged by globally averaged temperature and kinetic energy, and snapshots of temperature and velocity fields. Both POP-alpha algorithms can run stably with longer timesteps than standard POP. Comparison of implementations of full and reduced POP-alpha algorithms are made within an idealized test problem that captures some aspects of the Antarctic Circumpolar Current, a problem in which baroclinic instability is prominent. Both POP-alpha algorithms produce statistics that resemble higher-resolution simulations of standard POP. A linear stability analysis shows that both the full and reduced POP-alpha algorithms benefit from the way the LANS-alpha equations take into account the effects of the small scales on the large. Both algorithms (1) are stable; (2) make the Rossby Radius effectively larger; and (3) slow down Rossby and gravity waves.Comment: Submitted to J. Computational Physics March 21, 200

Utilization of the propensity score method: an exploratory comparison of proxy-completed to self-completed responses in the Medicare Health Outcomes Survey

BACKGROUND: This research examined the use of the propensity score method to compare proxy-completed responses to self-completed responses in the first three baseline cohorts of the Medicare Health Outcomes Survey, administered in 1998, 1999, and 2000, respectively. A proxy is someone other than the respondent who completes the survey for the respondent. METHODS: The propensity score method of matched sampling was used to compare proxy and self-completed responses. A propensity score is a value that equals the estimated probability of a given individual belonging to a treatment group given the observed background characteristics of that individual. Proxy and self-completed responses were compared on demographics, the SF-36, chronic conditions, activities of daily living, and depression-screening questions. For each individual survey respondent, logistic regression was used to calculate the probability that this individual belonged to the proxy respondent group (propensity score). Pre and post adjustment comparisons were tested by calculating effect sizes. RESULTS: Differences between self and proxy-completed responses were substantially reduced with the use of the propensity score method. However, differences were still found in the SF-36, several demographics, several impaired activities of daily living, several chronic conditions, and one depression-screening question. CONCLUSION: The propensity score method helped to reduce differences between proxy-completed and self-completed survey responses, thereby providing an approximation to a randomized controlled experiment of proxy-completed versus self-completed survey responses