Do pre-transplant cultural factors predict health-related quality of life after kidney transplantation?

BACKGROUND: Post-transplant health-related quality of life (HRQOL) is associated with health outcomes for kidney transplant (KT) recipients. However, pretransplant predictors of improvements in post-transplant HRQOL remain incompletely understood. Namely, important pretransplant cultural factors, such as experience of discrimination, perceived racism in healthcare, or mistrust of the healthcare system, have not been examined as potential HRQOL predictors. Also, few have examined predictors of decline in HRQOL post-transplant. METHODS: Using data from a prospective cohort study, we examined HRQOL change pre- to post-transplant, and novel cultural predictors of the change. We measured physical, mental, and kidney-specific HRQOL as outcomes, and used cultural factors as predictors, controlling for demographic, clinical, psychosocial, and transplant knowledge covariates. RESULTS: Among 166 KT recipients (57% male; mean age 50.6 years; 61.4% > high school graduates; 80% non-Hispanic White), we found mental and physical, but not kidney-specific, HRQOL significantly improved post-transplant. No culturally related factors outside of medical mistrust significantly predicted change in any HRQOL outcome. Instead, demographic, knowledge, and clinical factors significantly predicted decline in each HRQOL domain: physical HRQOL-older age, more post-KT complications, higher pre-KT physical HRQOL; mental HRQOL-having less information pre-KT, greater pre-KT mental HRQOL; and, kidney-specific HRQOL-poorer kidney functioning post-KT, lower expectations for physical condition to improve, and higher pre-KT kidney-specific HRQOL. CONCLUSIONS: Instead of cultural factors, predictors of HRQOL decline included demographic, knowledge, and clinical factors. These findings are useful for identifying patient groups that may be at greater risk of poorer post-transplant outcomes, in order to target individualized support to patients.

A Closed Form Model for Molecular Ratchet-Type Chemically Induced Dimerization Modules.

Chemical-induced dimerization (CID) modules enable users to implement ligand-controlled cellular and biochemical functions for a number of problems in basic and applied biology. A special class of CID modules occur naturally in plants and involve a hormone receptor that binds a hormone, triggering a conformational change in the receptor that enables recognition by a second binding protein. Two recent reports show that such hormone receptors can be engineered to sense dozens of structurally diverse compounds. As a closed form model for molecular ratchets would be of immense utility in forward engineering of biological systems, here we have developed a closed form model for these distinct CID modules. These modules, which we call molecular ratchets, are distinct from more common CID modules called molecular glues in that they engage in saturable binding kinetics and are characterized well by a Hill equation. A defining characteristic of molecular ratchets is that the sensitivity of the response can be tuned by increasing the molar ratio of the hormone receptor to the binding protein. Thus, the same molecular ratchet can have a pico- or micromolar EC50 depending on the concentration of the different receptor and binding proteins. Closed form models are derived for a base elementary reaction rate model, for ligand-independent complexation of the receptor and binding protein, and for homodimerization of the hormone receptor. Useful governing equations for a variety of in vitro and in vivo applications are derived, including enzyme-linked immunosorbent assay-like microplate assays, transcriptional activation in prokaryotes and eukaryotes, and ligand-induced split protein complementation.

Are cultural or psychosocial factors associated with patient-reported outcomes at the conclusion of kidney transplant evaluation?

BACKGROUND: Kidney transplant evaluation (KTE) is a period marked by many stressors for patients, which may lead to poorer patient-reported outcomes (PROs). Research on the association of cultural and psychosocial factors with PROs during KTE is lacking, even though cultural and psychosocial variables may mitigate the relationship between acceptance status and PROs. METHODS: Using a prospective cohort study of 955 adults referred for KTE, we examined whether cultural factors and psychosocial characteristics, assessed at the initiation of KTE, are associated with PROs at KTE completion, controlling for demographics and medical factors. Also, we analyzed whether these factors moderate the relationship between transplant acceptance status and PROs. RESULTS: In multivariable regression models, a stronger sense of mastery was associated with higher physical and mental QOL. A stronger sense of self-esteem was associated with higher kidney-specific QOL. Depression was associated with a lower mental QOL, but only in those who were accepted for transplant. Having low levels of external locus of control was associated with better mental QOL in those who were not accepted for transplant. Higher anxiety was associated with poorer kidney-specific QOL among those who were not accepted for KT, but trust in physician was only associated with greater satisfaction in transplant clinic service for those who were accepted for KT. CONCLUSIONS: Targeting interventions to increase patient mastery and external locus of control, and reduce depression and anxiety in patients undergoing kidney transplant evaluation may be useful approaches to improve their experience during this stressful period.

Associations of sodium and potassium intake with chronic kidney disease in a prospective cohort study: findings from the Hispanic Community Health Study/Study of Latinos, 2008-2017.

BACKGROUND: According to dietary recommendations, reduction of sodium intake has potential to reduce Chronic Kidney Disease (CKD) risk; however the role of dietary potassium and the sodium -to- potassium ratio in the development of CKD is unclear. METHODS: We studied 9778 participants of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) from four US urban communities. Participants were aged 18-74 yrs., free from CKD at baseline in 2008-2011 and re-examined between 2014 and - 2017. Dietary intake of sodium, potassium and the ratio of dietary sodium -to- potassium were measured from two baseline 24-h dietary recalls. Incident CKD was defined as: 1) estimated glomerular filtration rate (eGFR) decline of 1 unit per year and eGFR < 60 ml/min/1.73m2 or 2) albumin to creatinine ratio ≥ 30 mg/g at the follow-up visit. We used multivariable survey weighted Poisson regression to estimate adjusted incident rates of incident CKD. RESULTS: At baseline, mean age was 41 years. Average follow up time was 6.2 years. From fully adjusted Poisson regression analyses, self-reported sodium intake was not associated with incident CKD. However, for each 500 mg decrement in potassium intake, there was an 11% increase risk of incident CKD (IRR = 1.11, 95% CI = 1.00, 1.24). Additionally, every 1 M ratio increment of sodium -to -potassium ratio was associated with a 21% increased risk of incident CKD (IRR = 1.21, 95% CI = 1.02, 1.45), p < 0.05). CONCLUSIONS: We conclude that diets low in potassium and high in sodium are associated with increased risk of developing chronic kidney disease among healthy US Hispanic/Latino adults.

Associations of Income Volatility With Incident Cardiovascular Disease and All-Cause Mortality in a US Cohort.

BACKGROUND: Income volatility is on the rise and presents a growing public health problem. Because in many epidemiological studies income is measured at a single point in time, the association of long-term income volatility with incident cardiovascular disease (CVD) and mortality has not been adequately explored. The goal of this study was to examine associations of income volatility from 1990 to 2005 with incident CVD and all-cause mortality in the subsequent 10 years. METHODS: The Coronary Artery Risk Development in Young Adults Study is an ongoing prospective cohort study conducted within urban field centers in Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA. We studied 3937 black and white participants 23 to 35 years of age in 1990 (our study baseline). Income volatility was defined as the intraindividual SD of the percent change in income across 5 assessments from 1990 to 2005. An income drop was defined as a decrease of ≥25% from the previous visit and less than the participant's average income from 1990 to 2005. CVD events (fatal and nonfatal) and all-cause mortality between 2005 and 2015 were adjudicated with the use of medical records and death certificates. CVD included primarily acute events related to heart disease and stroke. RESULTS: A total of 106 CVD events and 164 deaths occurred between 2005 and 2015 (incident rate, 2.76 and 3.66 per 1000 person-years, respectively). From Cox models adjusted for sociodemographic, behavioral, and CVD risk factors, higher income volatility and more income drops were associated with greater CVD risk (high versus low volatility: hazard ratio, 2.07; 95% CI, 1.10-3.90; ≥2 versus 0 income drops: hazard ratio, 2.54; 95% CI, 1.24-5.19) and all-cause mortality (high versus low volatility: hazard ratio, 1.78; 95% CI,1.03-3.09; ≥2 versus 0 income drops: hazard ratio, 1.92; 95% CI, 1.07-3.44). CONCLUSIONS: In a cohort of relatively young adults, income volatility and drops during a 15-year period of formative earning years were independently associated with a nearly 2-fold risk of CVD and all-cause mortality.

Association of traumatic brain injury with dementia and memory decline in older adults in the United States.

INTRODUCTION: To examine associations of history of traumatic brain injuries (TBIs) with loss of consciousness (LOC) with dementia incidence and memory decline. METHODS: We studied 2718 participants from the 1992 enrollment cohort of the Health and Retirement Study (HRS) aged 65 years or older in 2000. History of TBI with LOC was self-reported in 1992. Dementia was assessed using four algorithms established in HRS. Participants were followed from 2000 to 2014 with repeated measures of dementia and memory performance. Cox models and linear mixed-effects models were used. RESULTS: In 1992, 11.9% of the participants reported a history of TBI with LOC. In fully adjusted models for all four algorithms, participants with a history of TBI with LOC had no statistically significant difference in dementia incidence nor in memory decline, compared to participants without TBI history. DISCUSSION: Our study did not find evidence of a long-term association between history of TBI with LOC (of unknown frequency and severity) and dementia incidence or memory decline.

Sociodemographic Disparities in Long-Term Mortality Among Stroke Survivors in the United States.

Background and Purpose- It is unclear whether disparities in mortality among stroke survivors exist long term. Therefore, the purpose of the current study is to describe rates of longer term mortality among stroke survivors (ie, beyond 30 days) and to determine whether socioeconomic disparities exist. Methods- This analysis included 1329 black and white participants, aged ≥45 years, enrolled between 2003 and 2007 in the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) who suffered a first stroke and survived at least 30 days after the event. Long-term mortality among stroke survivors was defined in person-years as time from 30 days after a first stroke to date of death or censoring. Mortality rate ratios (MRRs) were used to compare rates of poststroke mortality by demographic and socioeconomic characteristics. Results- Among adults who survived ≥30 days poststroke, the age-adjusted rate of mortality was 82.3 per 1000 person-years (95% CI, 75.4-89.2). Long-term mortality among stroke survivors was higher in older individuals (MRR for 75+ versus <65, 3.2; 95% CI, 2.6-4.1) and among men than women (MRR, 1.3; 95% CI, 1.1-1.6). It was also higher among those with less educational attainment (MRR for less than high-school versus college graduate, 1.5; 95% CI, 1.1-1.9), lower income (MRR for <$20k versus >50k, 1.4; 95% CI, 1.1-1.9), and lower neighborhood socioeconomic status (SES; MRR for low versus high neighborhood SES, 1.4; 95% CI, 1.1-1.7). There were no differences in age-adjusted rates of long-term poststroke mortality by race, rurality, or US region. Conclusions- Rates of long-term mortality among stroke survivors were higher among individuals with lower SES and among those residing in neighborhoods of lower SES. These results emphasize the need for improvements in long-term care poststroke, especially among individuals of lower SES.

Zinc-binding triggers a conformational-switch in the cullin-3 substrate adaptor protein KEAP1 that controls transcription factor NRF2.

Kelch-like ECH-associated protein 1 (Keap1) is a cullin-3 (Cul3)-RING ubiquitin ligase (CRL) adaptor/scaffold protein that enables cells to adapt to environmental stressors because modification of certain of its Cys residues initiates de-repression of the NF-E2 p45-related factor-2 (Nrf2) transcription factor. Thus, in normal unstressed cells, the cytoprotective Nrf2 is continuously ubiquitylated by CRLKeap1, thereby ensuring that Nrf2 is efficiently degraded by the proteasome and expression of Nrf2 target genes restricted. By contrast, this process is attenuated in stressed cells, allowing Nrf2 protein to accumulate in the nucleus and induce genes that promote cell survival. It remains unclear how Keap1 senses stress. Previously, we suggested that release of free Zn2+ from damaged proteins represents an endogenous 'danger' signal recognized by Keap1. However, the existence of a Zn2+ sensor in Keap1 is not widely acknowledged. We now present data that support the hypothesis that Keap1 directly senses Zn2+ through a cluster of amino-acids that include His-225, Cys-226, and Cys-613. We show that this mechanism does not require p62/sequestosome-1, an autophagy adaptor protein implicated in metal(loid) sensing by Keap1. Moreover, using a genetically-encoded FRET reporter, we present evidence that binding of Zn2+ triggers a conformational switch in Keap1. The altered conformation of Keap1 is envisaged to perturb the architecture of CRLKeap1, such that bound Nrf2 becomes mis-aligned with respect to the ubiquitin-charged E2 enzyme. These data are consistent with the notion that Keap1 possesses a Zn2+ sensor whose triggering distorts its structure in a fashion that inhibits ubiquitylation of Nrf2 upon CRLKeap1.

Psychological strategies for winning a geopolitical forecasting tournament.

Five university-based research groups competed to recruit forecasters, elicit their predictions, and aggregate those predictions to assign the most accurate probabilities to events in a 2-year geopolitical forecasting tournament. Our group tested and found support for three psychological drivers of accuracy: training, teaming, and tracking. Probability training corrected cognitive biases, encouraged forecasters to use reference classes, and provided forecasters with heuristics, such as averaging when multiple estimates were available. Teaming allowed forecasters to share information and discuss the rationales behind their beliefs. Tracking placed the highest performers (top 2% from Year 1) in elite teams that worked together. Results showed that probability training, team collaboration, and tracking improved both calibration and resolution. Forecasting is often viewed as a statistical problem, but forecasts can be improved with behavioral interventions. Training, teaming, and tracking are psychological interventions that dramatically increased the accuracy of forecasts. Statistical algorithms (reported elsewhere) improved the accuracy of the aggregation. Putting both statistics and psychology to work produced the best forecasts 2 years in a row.

Associations between sodium, potassium, and blood pressure: results from the Hispanic Community Health Study/Study of Latinos, a prospective cohort study.

BACKGROUND: Although the subject of numerous studies, the associations between dietary sodium, potassium, and the ratio of dietary sodium to potassium with blood pressure are not clear-cut. In addition, there is a paucity of research on these relationships in prospective cohort studies with representation from diverse Hispanic/Latino adults. OBJECTIVES: To evaluate the associations between dietary intake of sodium, potassium, and the ratio of dietary sodium to potassium and blood pressure in a diverse sample of Hispanics living in the United States. METHODS: This analysis included 11,429 Hispanic/Latino participants of the prospective cohort Hispanic Community Health Study/Study of Latinos recruited between 2008 and 2011 in visit 1 who participated in a follow-up visit in 2014-2017. Dietary sodium and potassium intakes were averaged from 2 interviewer-administered 24-h diet recalls collected at visit 1. At both visits, blood pressure was measured 3 times in a seated position and averaged. We assessed the relationship between dietary sodium, potassium, and the sodium-to-potassium ratio with changes in systolic and diastolic blood pressure using survey-weighted multivariable-adjusted regression models. RESULTS: At visit 1, the mean age was 41 y, and the mean sodium intake was 3203 mg/d. Each 500 mg/d sodium increment in intake was associated with an increase in systolic blood pressure (ß: 0.35 [mmHg]; 95% confidence interval: 0.06, 0.63) and diastolic blood pressure (ß: 0.45 [mmHg]; 95% confidence interval: 0.08, 0.82). Dietary potassium and the molar ratio of dietary sodium to potassium were not associated with changes in systolic or diastolic blood pressure. CONCLUSIONS: Among a large sample of diverse United States Hispanic/Latino adults, higher sodium intake was associated with small increases in systolic blood pressure over 6 y. This research underscores the importance of dietary sodium reduction in maintaining lower blood pressure.

Diets high in subsidized foods and chronic kidney disease in Hispanic communities in the United States: the Hispanic Community Health Study/Study of Latinos.

Prior research shows that diets high in government subsidized foods may be associated with cardiometabolic disease risk factors. Our aim was to evaluate the relationship between diets high in subsidized foods and the development of chronic kidney disease (CKD) and other cardiometabolic risk factors in United States (US) Hispanics/Latinos. Using data from 16,172 Hispanics/Latino's living in the United States, we used the Cochran-Armitage test to assess the relationship between subsidized foods in the diets of participants and baseline characteristics. We used survey-weighted Poisson regression models to examine whether intake of subsidized foods was associated with incident CKD or cardiometabolic risk factors. Several baseline characteristics were associated with higher subsidized food scores. Higher subsidized food scores were not associated with incident CKD or cardiometabolic risk factors. These findings may be useful for future researchers, clinicians, and nutritional policy advocates who are interested in the way Hispanic and Latinos consume foods subsidized by the US government and the structural factors that may shape observed dietary and disease patterns.

Associations of Food Insecurity and Memory Function Among Middle to Older-Aged Adults in the Health and Retirement Study.

Importance: Food insecurity is a leading public health issue in the US. Research on food insecurity and cognitive aging is scarce, and is mostly cross-sectional. Food insecurity status and cognition both can change over the life course, but their longitudinal relationship remains unexplored. Objective: To examine the longitudinal association between food insecurity and changes in memory function during a period of 18 years among middle to older-aged adults in the US. Design, Setting, and Participants: The Health and Retirement Study is an ongoing population-based cohort study of individuals aged 50 years or older. Participants with nonmissing information on their food insecurity in 1998 who contributed information on memory function at least once over the study period (1998-2016) were included. To account for time-varying confounding and censoring, marginal structural models were created, using inverse probability weighting. Data analyses were conducted between May 9 and November 30, 2022. Main outcomes and Measures: In each biennial interview, food insecurity status (yes/no) was assessed by asking respondents whether they had enough money to buy food or ate less than they felt they should. Memory function was a composite score based on self-completed immediate and delayed word recall task of a 10-word list and proxy-assessed validated instruments. Results: The analytic sample included 12 609 respondents (mean [SD] age, 67.7 [11.0] years, 8146 [64.60%] women, 10 277 [81.51%] non-Hispanic White), including 11 951 food-secure and 658 food-insecure individuals in 1998. Over time, the memory function of the food-secure respondents decreased by 0.045 SD units annually (ß for time, -0.045; 95% CI, -0.046 to -0.045 SD units). The memory decline rate was faster among food-insecure respondents than food-secure respondents, although the magnitude of the coefficient was small (ß for food insecurity × time, -0.0030; 95% CI, -0.0062 to -0.00018 SD units), which translates to an estimated 0.67 additional (ie, excess) years of memory aging over a 10-year period for food-insecure respondents compared with food-secure respondents. Conclusions and Relevance: In this cohort study of middle to older-aged individuals, food insecurity was associated with slightly faster memory decline, suggesting possible long-term negative cognitive function outcomes associated with exposure to food insecurity in older age.

Associations Between Albuminuria and Mortality Among US Adults by Demographic and Comorbidity Factors.

Background Albuminuria is a known marker of mortality risk. Whether the association between albuminuria and mortality differs by demographic and comorbidity factors remains unclear. Therefore, we sought to determine whether albuminuria is differentially associated with mortality. Methods and Results This study included 49 640 participants from the National Health and Nutrition Examination Survey (1999-2018). All-cause mortality through 2019 was linked from the National Death Index. Multivariable-adjusted Poisson regression models were used to determine whether levels of urine albumin-to-creatinine ratio (ACR) were associated with mortality. Models were adjusted for demographic, socioeconomic, behavioral, and clinical factors. Mean age in the population was 46 years, with 51.3% female, and 30.3% with an ACR ≥10 mg/g. Over a median follow-up of 9.5 years, 6813 deaths occurred. Compared with ACR <10, ACR ≥300 was associated with increased risk of mortality by 132% overall (95% CI, 2.01-2.68), 124% among men (95% CI, 1.84-2.73), 158% among women (95% CI, 2.14-3.11), 130% among non-Hispanic White adults (95% CI: 1.89-2.79), 135% among non-Hispanic Black adults (95% CI, 1.82-3.04), and 114% among Hispanic adults (95% CI, 1.55-2.94). Compared with ACR <10, ACR ≥300 was associated with increased risk of mortality by 148% among individuals with neither hypertension nor hypercholesterolemia (95% CI, 1.69-3.64), 128% among individuals with hypertension alone (95% CI, 1.86-2.79), and 166% among individuals with both hypertension and hypercholesterolemia (95% CI, 2.18-3.26). Conclusions We found strong associations between albuminuria and mortality risk, even at mildly increased levels of albuminuria. Associations persisted across categories of sex, race or ethnicity, and comorbid conditions, with subtle differences.

Association of negative financial shocks during the Great Recession with depressive symptoms and substance use in the USA: the CARDIA study.

BACKGROUND: The Great Recession of 2008 was marked by large increases in unemployment and decreases in the household wealth of many Americans. In the 21st century, there have also been increases in depressive symptoms, alcohol use and drug use among some groups in the USA. The objective of this analysis is to evaluate the influence of negative financial shocks incurred during the Great Recession on depressive symptoms, alcohol and drug use. METHODS: We employed a quasi-experimental fixed-effects design, using data from adults enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Our financial shock predictors were within-person change in employment status, income and debt to asset ratio between 2005 and 2010. Our outcomes were within-person change in depressive symptoms score, alcohol use and past 30-day drug use. RESULTS: In adjusted models, we found that becoming unemployed and experiencing a drop in income and were associated with an increase in depressive symptoms. Incurring more debts than assets was also associated with an increase in depressive symptoms and a slight decrease in daily alcohol consumption (mL). CONCLUSION: Our findings suggest that multiple types of financial shocks incurred during an economic recession negatively influence depressive symptoms among black and white adults in the USA, and highlight the need for future research on how economic recessions are associated with health.

Relation between 20-year income volatility and brain health in midlife: The CARDIA study.

OBJECTIVE: Income volatility presents a growing public health threat. To our knowledge, no previous study examined the relationship among income volatility, cognitive function, and brain integrity. METHODS: We studied 3,287 participants aged 23-35 years in 1990 from the Coronary Artery Risk Development in Young Adults prospective cohort study. Income volatility data were created using income data collected from 1990 to 2010 and defined as SD of percent change in income and number of income drops ≥25% (categorized as 0, 1, or 2+). In 2010, cognitive tests (n = 3,287) and brain scans (n = 716) were obtained. RESULTS: After covariate adjustment, higher income volatility was associated with worse performance on processing speed (ß = -1.09, 95% confidence interval [CI] -1.73 to -0.44) and executive functioning (ß = 2.53, 95% CI 0.60-4.50) but not on verbal memory (ß = -0.02, 95% CI -0.16 to 0.11). Similarly, additional income drops were associated with worse performance on processing speed and executive functioning. Higher income volatility and more income drops were also associated with worse microstructural integrity of total brain and total white matter. All findings were similar when restricted to those with high education, suggesting reverse causation may not explain these findings. CONCLUSION: Income volatility over a 20-year period of formative earning years was associated with worse cognitive function and brain integrity in midlife.

Racial discrimination in medical care settings and opioid pain reliever misuse in a U.S. cohort: 1992 to 2015.

BACKGROUND: In the United States whites are more likely to misuse opioid pain relievers (OPRs) than blacks, and blacks are less likely to be prescribed OPRs than whites. Our objective is to determine whether racial discrimination in medical settings is protective for blacks against OPR misuse, thus mediating the black-white disparities in OPR misuse. METHODS: We used data from 3528 black and white adults in the Coronary Artery Risk Development in Young Adults (CARDIA) study, an ongoing multi-site cohort. We employ causal mediation methods, with race (black vs white) as the exposure, lifetime discrimination in medical settings prior to year 2000 as the mediator, and OPR misuse after 2000 as the outcome. RESULTS: We found black participants were more likely to report discrimination in a medical setting (20.3% vs 0.9%) and less likely to report OPR misuse (5.8% vs 8.0%, OR = 0.71, 95% CI = 0.55, 0.93, adjusted for covariates). Our mediation models suggest that when everyone is not discriminated against, the disparity is wider with black persons having even lower odds of reporting OPR misuse (OR = 0.63, 95% CI = 0.45, 0.89) compared to their white counterparts, suggesting racial discrimination in medical settings is a risk factor for OPR misuse rather than protective. CONCLUSIONS: These results suggest that racial discrimination in a medical setting is a risk factor for OPR misuse rather than being protective, and thus could not explain the seen black-white disparity in OPR misuse.

Maintaining competency: a qualitative study of clinical supervision and mentorship as a framework for specialist paramedics.

INTRODUCTION: The aim of this study was to explore the factors influencing the maintenance of clinical competence and the effectiveness of the specialist paramedic in the context of mentorship, from the specialist paramedic's own perspective. METHODS: Semi-structured interviews were conducted with eight specialist paramedics in four regions of one ambulance service. Thematic analysis and coding were used to explore the data and identify emergent themes. RESULTS: The study identified three key themes: appropriate clinical exposure; support and development; and opportunity for reflection. A tailored clinical leadership and mentorship model is required to maintain competency and effectiveness of specialist paramedics. Participants valued a model that delivered support, development and role clarity. Experienced advanced practitioners as mentors and organisational commitment were highlighted as essential components. CONCLUSIONS: Mentorship is an essential training requirement in extended roles to maximise efficacy of complex care out of hospital, to maintain clinical competence and as a source of motivation and psychological support.

Time-lapse imaging of nuclear bodies.

Fluorescence microscopy is a powerful technique that has become central in the study of the structure and function of biological specimens. This is due in large part to its specificity and versatility. Although an understanding of structure-typically through high-resolution imaging of fixed material-has proved an important tool to understanding function, fluorescence microscopy also offers a mechanism to interrogate cells in the living state, providing a means to explore dynamic process within the specimen over long time periods at high temporal resolution. The cell nucleus is a highly compartmented environment whose components are often highly motile and in a constant state of flux. The ability to monitor the dynamic behavior of nuclear bodies by live-cell imaging provides the researcher with important information regarding underlying mechanistic processes relating to their formation and maintenance. Two techniques have proved particularly valuable to our study of cellular dynamics and molecular mobility, namely, time-lapse imaging and fluorescence recovery after photobleaching (FRAP). Time-lapse microscopy allows for qualitative and quantitative analysis of a wide range of events at the cellular and subcellular level. FRAP provides a mechanism to study the mobility of a population of proteins in a range of conditions within discrete areas of the biological specimen. Therefore, fluorescence microscopy is unique in its ability to provide data at high temporal resolution and in such exquisite detail.

Inflated applicants: attribution errors in performance evaluation by professionals.

When explaining others' behaviors, achievements, and failures, it is common for people to attribute too much influence to disposition and too little influence to structural and situational factors. We examine whether this tendency leads even experienced professionals to make systematic mistakes in their selection decisions, favoring alumni from academic institutions with high grade distributions and employees from forgiving business environments. We find that candidates benefiting from favorable situations are more likely to be admitted and promoted than their equivalently skilled peers. The results suggest that decision-makers take high nominal performance as evidence of high ability and do not discount it by the ease with which it was achieved. These results clarify our understanding of the correspondence bias using evidence from both archival studies and experiments with experienced professionals. We discuss implications for both admissions and personnel selection practices.

Correspondence bias in performance evaluation: why grade inflation works.

Performance (such as a course grade) is a joint function of an individual's ability (such as intelligence) and the situation (such as the instructor's grading leniency). Prior research has documented a human bias toward dispositional inference, which ascribes performance to individual ability, even when it is better explained through situational influences on performance. It is hypothesized here that this tendency leads admissions decisions to favor students coming from institutions with lenient grading because those students have their high grades mistaken for evidence of high ability. Three experiments show that those who obtain high scores simply because of lenient grading are favored in selection. These results have implications for research on attribution because they provide a more stringent test of the correspondence bias and allow for a more precise measure of its size. Implications for university admissions and personnel selection decisions are also discussed.