DNA origami signposts for identifying proteins on cell membranes by electron cryotomography.

Electron cryotomography (cryoET), an electron cryomicroscopy (cryoEM) modality, has changed our understanding of biological function by revealing the native molecular details of membranes, viruses, and cells. However, identification of individual molecules within tomograms from cryoET is challenging because of sample crowding and low signal-to-noise ratios. Here, we present a tagging strategy for cryoET that precisely identifies individual protein complexes in tomograms without relying on metal clusters. Our method makes use of DNA origami to produce "molecular signposts" that target molecules of interest, here via fluorescent fusion proteins, providing a platform generally applicable to biological surfaces. We demonstrate the specificity of signpost origami tags (SPOTs) in vitro as well as their suitability for cryoET of membrane vesicles, enveloped viruses, and the exterior of intact mammalian cells.

Uncovering the Role of N-Glycan Occupancy on the Cooperative Assembly of Spike and Angiotensin Converting Enzyme 2 Complexes: Insights from Glycoengineering and Native Mass Spectrometry.

Interactions between the SARS-CoV-2 Spike protein and ACE2 are one of the most scrutinized reactions of our time. Yet, questions remain as to the impact of glycans on mediating ACE2 dimerization and downstream interactions with Spike. Here, we address these unanswered questions by combining a glycoengineering strategy with high-resolution native mass spectrometry (MS) to investigate the impact of N-glycan occupancy on the assembly of multiple Spike-ACE2 complexes. We confirmed that intact Spike trimers have all 66 N-linked sites occupied. For monomeric ACE2, all seven N-linked glycan sites are occupied to various degrees; six sites have >90% occupancy, while the seventh site (Asn690) is only partially occupied (∼30%). By resolving the glycoforms on ACE2, we deciphered the influence of each N-glycan on ACE2 dimerization. Unexpectedly, we found that Asn432 plays a role in mediating dimerization, a result confirmed by site-directed mutagenesis. We also found that glycosylated dimeric ACE2 and Spike trimers form complexes with multiple stoichiometries (Spike-ACE2 and Spike2-ACE2) with dissociation constants (Kds) of ∼500 and <100 nM, respectively. Comparing these values indicates that positive cooperativity may drive ACE2 dimers to complex with multiple Spike trimers. Overall, our results show that occupancy has a key regulatory role in mediating interactions between ACE2 dimers and Spike trimers. More generally, since soluble ACE2 (sACE2) retains an intact SARS-CoV-2 interaction site, the importance of glycosylation in ACE2 dimerization and the propensity for Spike and ACE2 to assemble into higher oligomers are molecular details important for developing strategies for neutralizing the virus.

Regional and time course differences in sweat cortisol, glucose, and select cytokine concentrations during exercise.

INTRODUCTION: The use of sweat as a biofluid for non-invasive sampling and diagnostics is a popular area of research. However, concentrations of cortisol, glucose, and cytokines have not been described across anatomical regions or as time progresses throughout exercise. PURPOSE: To determine regional and time course differences in sweat cortisol, glucose, and select cytokines (EGF, IFN-γ, IL-1ß, IL-1α, IL-1ra, TNF-α, IL-6, IL-8, and IL-10). METHODS: Sweat was collected with absorbent patches from eight subjects (24-44 y; 80.2 ± 10.2 kg) on the forehead (FH), right dorsal forearm (RDF), right scapula (RS), and right triceps (RT) at 0-25 min, 30-55 min, and 60-85 min during 90 min of cycling (~ 82% HRmax) in a heated chamber (32 °C, 50% rh). ANOVA was used to determine the effect of site and time on outcomes. Data are reported as LS means ± SE. RESULTS: There was a significant effect of location on sweat analyte concentrations with FH having higher values than most other regions for cortisol (FH: 1.15 ± 0.08 ng/mL > RDF: 0.62 ± 0.09 ng/mL and RT: 0.65 ± 0.12 ng/mL, P = 0.02), IL-1ra (P < 0.0001), and IL-8 (P < 0.0001), but lower concentrations for glucose (P = 0.01), IL-1α (P < 0.0001), and IL-10 (P = 0.02). Sweat IL-1ß concentration was higher on the RS than RT (P < 0.0001). Sweat cortisol concentration increased (25 min: 0.34 ± 0.10 ng/mL < 55 min: 0.89 ± 0.07 ng/mL < 85 min: 1.27 ± 0.07 ng/mL; P < 0.0001), while EGF (P < 0.0001), IL-1ra (P < 0.0001), and IL-6 (P = 0.02) concentrations decreased over time. CONCLUSION: Sweat analyte concentrations varied with time of sampling and anatomical region, which is essential information to consider when conducting future work in this area. CLINICAL TRIAL IDENTIFIER: NCT04240951 registered January 27, 2020.

The roles of child temperament, parent stress, and parenting style in family mealtimes.

Family mealtimes are associated with benefits for children, including healthy eating, fewer behavior problems, and healthy psychological well-being. However, the interactions during family mealtimes, and the parent and child characteristics, which may affect both the family mealtime environment and the associated benefits in children are not fully understood. The goal of this study was to examine the role of child and parent characteristics on the family mealtime environment. We tested several mediation models to explain how child temperament (negative affectivity), parent stress, and the dimensions of parent feeding style (responsiveness and demandingness) interact and influence each other to impact the structure and quality of the mealtime environment. Parents (68 mothers; 82 fathers) of children between 2 and 6 years completed an online survey. Measures included the Children's Behavior Questionnaire, Perceived Stress Scale, Caregiver's Feeding Styles Questionnaire, and The Meals in Our Household Questionnaire. Child negative affectivity was associated with poorer mealtime quality and structure. These associations were mediated through parent responsiveness, but not demandingness. The role of demandingness in family mealtimes may depend on parent responsiveness. When examined together in a serial mediation model, child negative affectivity increased parent stress, which reduced responsiveness, and led to poorer mealtime quality and structure. These results emphasize the complex relationships between child temperament, parent stress, and the dimensions of parenting styles that occur within the mealtime context. This line of research is essential for understanding family mealtime dynamics and informing future studies aimed at creating positive interactions between parents and children during mealtimes.

Multiple regression analyses to determine the effect of sweating rate and tattoo characteristics on sweat outcome measures during exercise.

PURPOSE: To compare local sweating rate (LSR) and local sweat sodium ([Na+]), chloride ([Cl-]), and potassium ([K+]) concentrations of tattooed skin and contralateral non-tattooed skin during exercise. METHODS: Thirty-three recreational exercisers (17 men, 16 women) with ≥ 1 unilateral permanent tattoo on the torso/arms were tested during cycling, running, or fitness sessions (26 ± 4 °C and 54 ± 13% relative humidity). Forty-eight tattoos with a range of ink colors, ages (3 weeks to 20 years), and densities (10-100%) were included. Before exercise, the skin was cleaned with alcohol and patches (3 M Tegaderm + Pad) were placed on the tattooed and contralateral non-tattooed skin. LSR was calculated from sweat mass (0.80 ± 0.31 g), patch surface area (11.9 cm2), and duration (62 ± 14 min). Sweat [Na+], [Cl-], and [K+] were measured via ion chromatography. RESULTS: Based on the analysis of variance results, there were no differences between tattooed and non-tattooed skin for LSR (1.16 ± 0.52 vs. 1.12 ± 0.53 mg/cm2/min; p = 0.51), sweat [Na+] (60.2 ± 23.5 vs. 58.5 ± 22.7 mmol/L; p = 0.27), sweat [Cl-] (52.1 ± 22.4 vs. 50.6 ± 22.0 mmol/L; p = 0.31), or sweat [K+] (5.8 ± 1.6 vs. 5.9 ± 1.4 mmol/L; p = 0.31). Multiple regression analyses suggested that younger tattoos were associated with higher sweat [Na+] (p = 0.045) and colorful tattoos were associated with higher sweat [Cl-] (p = 0.04) compared with contralateral non-tattooed skin. Otherwise, there were no effects of LSR or tattoo characteristics on regression models for LSR or sweat electrolyte concentrations. CONCLUSION: There were no effects of tattoos on LSR and sweat [K+] during exercise-induced sweating, but tattoo age and color had small effects on sweat [Na+] and sweat [Cl-], respectively. CLINICAL TRIAL IDENTIFIERS: NCT04240951 was registered on January 27, 2020 and NCT04920266 was registered on June 9, 2021.

Cryo-SOFI enabling low-dose super-resolution correlative light and electron cryo-microscopy.

Correlative light and electron cryo-microscopy (cryo-CLEM) combines information from the specific labeling of fluorescence cryo-microscopy (cryo-FM) with the high resolution in environmental context of electron cryo-microscopy (cryo-EM). Exploiting super-resolution methods for cryo-FM is advantageous, as it enables the identification of rare events within the environmental background of cryo-EM at a sensitivity and resolution beyond that of conventional methods. However, due to the need for relatively high laser intensities, current super-resolution cryo-CLEM methods require cryo-protectants or support films which can severely reduce image quality in cryo-EM and are not compatible with many samples, such as mammalian cells. Here, we introduce cryogenic super-resolution optical fluctuation imaging (cryo-SOFI), a low-dose super-resolution imaging scheme based on the SOFI principle. As cryo-SOFI does not require special sample preparation, it is fully compatible with conventional cryo-EM specimens, and importantly, it does not affect the quality of cryo-EM imaging. By applying cryo-SOFI to a variety of biological application examples, we demonstrate resolutions up to ∼135 nm, an improvement of up to three times compared with conventional cryo-FM, while maintaining the specimen in a vitrified state for subsequent cryo-EM. Cryo-SOFI presents a general solution to the problem of specimen devitrification in super-resolution cryo-CLEM. It does not require a complex optical setup and can easily be implemented in any existing cryo-FM system.

Sweating Rate and Sweat Chloride Concentration of Elite Male Basketball Players Measured With a Wearable Microfluidic Device Versus the Standard Absorbent Patch Method.

The purpose of this study was to compare a wearable microfluidic device and standard absorbent patch in measuring local sweating rate (LSR) and sweat chloride concentration ([Cl-]) in elite basketball players. Participants were 53 male basketball players (25 ± 3 years, 92.2 ± 10.4 kg) in the National Basketball Association's development league. Players were tested during a moderate-intensity, coach-led practice (98 ± 30 min, 21.0 ± 1.2 °C). From the right ventral forearm, sweat was collected using an absorbent patch (3M Tegaderm™ + Pad). Subsequently, LSR and local sweat [Cl-] were determined via gravimetry and ion chromatography. From the left ventral forearm, LSR and local sweat [Cl-] were measured using a wearable microfluidic device and associated smartphone application-based algorithms. Whole-body sweating rate (WBSR) was determined from pre- to postexercise change in body mass corrected for fluid/food intake (ad libitum), urine loss, and estimated respiratory water and metabolic mass loss. The WBSR values predicted by the algorithms in the smartphone application were also recorded. There were no differences between the absorbent patch and microfluidic patch for LSR (1.25 ± 0.91 mg·cm-2·min-1 vs. 1.14 ±0.78 mg·cm-2·min-1, p = .34) or local sweat [Cl-] (30.6 ± 17.3 mmol/L vs. 29.6 ± 19.4 mmol/L, p = .55). There was no difference between measured and predicted WBSR (0.97 ± 0.41 L/hr vs. 0.89 ± 0.35 L/hr, p = .22; 95% limits of agreement = 0.61 L/hr). The wearable microfluidic device provides similar LSR, local sweat [Cl-], and WBSR results compared with standard field-based methods in elite male basketball players during moderate-intensity practices.

Re-envisioning paradigms of education: towards awareness, alignment, and pluralism.

In this article we introduce a synthesis of education "paradigms," adapted from a multi-disciplinary body of literature and tailored to health professions education (HPE). Each paradigm involves a particular perspective on the purpose of education, the nature of knowledge, what knowledge is valued and included in the curriculum, what it means to learn and how learning is assessed, and the roles of teachers and learners in the learning process. We aim to foster awareness of how these different paradigms look in practice and to illustrate the importance of alignment between teaching, learning and assessment practices with paradigmatic values and assumptions. Finally, we advocate for a pluralistic approach that purposefully and meaningfully integrates paradigms of education, enhancing our ability to drive quality in HPE.

Predicted sweat rates for group water planning in sport: accuracy and application.

This study tested the accuracy of a novel, limited-availability web application (H2Q™) for predicting sweat rates in a variety of sports using estimates of energy expenditure and air temperature only. The application of predictions for group water planning was investigated for soccer match play. Fourteen open literature studies were identified where group sweat rates were reported (n = 20 group means comprising 230 individual observations from 179 athletes) with fidelity. Sports represented included: walking, cycling, swimming, and soccer match play. The accuracy of H2Q™ sweat rates was tested by comparing to measured group sweat rates using the concordance correlation coefficient (CCC) with 95% confidence interval [CI]. The relative absolute error (RAE) with 95% [CI] was also assessed, whereby the mean absolute error was expressed relative to an acceptance limit of 0.250 L/h. The CCC was 0.98 [0.95, 0.99] and the RAE was 0.449 [0.279, 0.620], indicating that the prediction error was on average 0.112 L/h. The RAE was < 1.0 for 19/20 observations (95%). Drink volumes modeled as a proxy for sweat losses during soccer match play prevented dehydration (< 1% loss of body mass). The H2Q™ web application demonstrated high group sweat prediction accuracy for the variety of sports activities tested. Water planning for soccer match play suggests the feasibility of easily and accurately predicting sweat rates to plan group water needs and promote optimal hydration in training and/or competition.

Nusinersen for older patients with spinal muscular atrophy: A real-world clinical setting experience.

INTRODUCTION: Clinical trials data concerning use of nusinersen in older spinal muscular atrophy (SMA) patients is lacking. We describe our center's experience in using intrathecal nusinersen for older patients in the clinical setting. METHODS: Retrospective study. RESULTS: Twelve patients (12-52 years old) were treated with nusinersen. Mean follow-up duration was 17.4 months (range, 4-26 months). All patients had scoliosis; 10 had spinal fusion/instrumentation. All procedures (30 cervical and 57 lumbar punctures) were technically successful. The only side effects were postprocedural headache (9%) and site pain (5.7%). Functional assessments showed stability in 6/9 patients and improvement in 3/9 patients. Subjective improvements in endurance, hand strength, and bulbar functioning critical for activities of daily living were reported in 8/12 patients. None of the patients has discontinued treatment so far. DISCUSSION: Intrathecal nusinersen can be safely delivered in older SMA patients. Available functional outcome measures are not adequate to capture meaningful subjective improvements.

Physiological mechanisms determining eccrine sweat composition.

PURPOSE: The purpose of this paper is to review the physiological mechanisms determining eccrine sweat composition to assess the utility of sweat as a proxy for blood or as a potential biomarker of human health or nutritional/physiological status. METHODS: This narrative review includes the major sweat electrolytes (sodium, chloride, and potassium), other micronutrients (e.g., calcium, magnesium, iron, copper, zinc, vitamins), metabolites (e.g., glucose, lactate, ammonia, urea, bicarbonate, amino acids, ethanol), and other compounds (e.g., cytokines and cortisol). RESULTS: Ion membrane transport mechanisms for sodium and chloride are well established, but the mechanisms of secretion and/or reabsorption for most other sweat solutes are still equivocal. Correlations between sweat and blood have not been established for most constituents, with perhaps the exception of ethanol. With respect to sweat diagnostics, it is well accepted that elevated sweat sodium and chloride is a useful screening tool for cystic fibrosis. However, sweat electrolyte concentrations are not predictive of hydration status or sweating rate. Sweat metabolite concentrations are not a reliable biomarker for exercise intensity or other physiological stressors. To date, glucose, cytokine, and cortisol research is too limited to suggest that sweat is a useful surrogate for blood. CONCLUSION: Final sweat composition is not only influenced by extracellular solute concentrations, but also mechanisms of secretion and/or reabsorption, sweat flow rate, byproducts of sweat gland metabolism, skin surface contamination, and sebum secretions, among other factors related to methodology. Future research that accounts for these confounding factors is needed to address the existing gaps in the literature.

Permanent tattooing has no impact on local sweat rate, sweat sodium concentration and skin temperature or prediction of whole-body sweat sodium concentration during moderate-intensity cycling in a warm environment.

PURPOSES: This study investigated the impact of permanently tattooed skin on local sweat rate, sweat sodium concentration and skin temperature and determined whether tattoos alter the relationship between local and whole-body sweat sodium concentration. METHODS: Thirteen tattooed men (27 ± 6 years) completed a 1 h (66 ± 4% of [Formula: see text]) cycling trial at 32 °C, 35% relative humidity. Sweat rate and sweat sodium concentration were measured using the whole-body washdown and local absorbent patch techniques. Patches and skin-temperature probes were applied over the right/left thighs and tattooed/non-tattooed (contralateral) regions. RESULTS: Local sweat rates did not differ (p > 0.05) between the right (1.11 ± 0.38) and left (1.21 ± 0.37) thighs and the permanently tattooed (1.93 ± 0.82) and non-tattooed (1.72 ± 0.81 mg cm-2 min-1) regions. There were no differences in local sweat sodium concentration between the right (58.2 ± 19.4) and left (55.4 ± 20.3) thighs and the permanently tattooed (73.0 ± 22.9) and non-tattooed (70.2 ± 18.9 mmol L-1) regions. Difference in local skin temperature between the right and left thighs (- 0.043) was similar to that between the permanently tattooed and non-tattooed (- 0.023 °C) regions. Prediction of whole-body sweat sodium concentration for the permanently tattooed (41.0 ± 6.7) and the non-tattooed (40.2 ± 5.3 mmol L-1) regions did not differ. CONCLUSION: Permanent tattoos do not alter local sweat rate, sweat sodium concentration or local skin temperature during moderate-intensity cycling exercise in a warm environment. Results from a patch placed over a tattooed surface correctly predicts whole-body sweat sodium concentration from an equation developed from a non-tattooed region.

Reducing Pediatric Tracheostomy Wound Complications: An Evidence-Based Literature Review.

OBJECTIVE: To discuss prevention strategies that can mitigate the frequency of tracheostomy-related wound complications. DATA SOURCES: A systematic literature review of PubMed between 2010 and 2019. STUDY SELECTION: Full-text articles written in English language and studying human participants younger than 18 years. DATA EXTRACTION: The primary outcome was the rate of tracheostomy-related skin complications after implementation of a given intervention. Secondary outcomes included rates of accidental decannulation or other complications. DATA SYNTHESIS: A total of 348 studies were identified and 6 met inclusion criteria. There were 1,607 children included with interventions designed to reduce peristomal and cervical wound complications in 1,174 (73.1%). Strategies considered safe and effective included protective skin barriers, reducing prolonged pressure, and early wound identification protocols. CONCLUSIONS: Wound complications after pediatric tracheostomy can be reduced using a multifaceted approach by providers committed to making skin care a priority.

Exercise intensity effects on total sweat electrolyte losses and regional vs. whole-body sweat [Na+], [Cl-], and [K+].

PURPOSE: To quantify total sweat electrolyte losses at two relative exercise intensities and determine the effect of workload on the relation between regional (REG) and whole body (WB) sweat electrolyte concentrations. METHODS: Eleven recreational athletes (7 men, 4 women; 71.5 ± 8.4 kg) completed two randomized trials cycling (30 °C, 44% rh) for 90 min at 45% (LOW) and 65% (MOD) of VO2max in a plastic isolation chamber to determine WB sweat [Na+] and [Cl-] using the washdown technique. REG sweat [Na+] and [Cl-] were measured at 11 REG sites using absorbent patches. Total sweat electrolyte losses were the product of WB sweat loss (WBSL) and WB sweat electrolyte concentrations. RESULTS: WBSL (0.86 ± 0.15 vs. 1.27 ± 0.24 L), WB sweat [Na+] (32.6 ± 14.3 vs. 52.7 ± 14.6 mmol/L), WB sweat [Cl-] (29.8 ± 13.6 vs. 52.5 ± 15.6 mmol/L), total sweat Na+ loss (659 ± 340 vs. 1565 ± 590 mg), and total sweat Cl- loss (931 ± 494 vs. 2378 ± 853 mg) increased significantly (p < 0.05) from LOW to MOD. REG sweat [Na+] and [Cl-] increased from LOW to MOD at all sites except thigh and calf. Intensity had a significant effect on the regression model predicting WB from REG at the ventral wrist, lower back, thigh, and calf for sweat [Na+] and [Cl-]. CONCLUSION: Total sweat Na+ and Cl- losses increased by ~ 150% with increased exercise intensity. Regression equations can be used to predict WB sweat [Na+] and [Cl-] from some REG sites (e.g., dorsal forearm) irrespective of intensity (between 45 and 65% VO2max), but other sites (especially ventral wrist, lower back, thigh, and calf) require separate prediction equations accounting for workload.

Normative data for sweating rate, sweat sodium concentration, and sweat sodium loss in athletes: An update and analysis by sport.

The purpose of this study was to expand our previously published sweat normative data/analysis (n = 506) to establish sport-specific normative data for whole-body sweating rate (WBSR), sweat [Na+], and rate of sweat Na+ loss (RSSL). Data from 1303 athletes were compiled from observational testing (2000-2017) using a standardized absorbent sweat patch technique to determine local sweat [Na+] and normalized to whole-body sweat [Na+]. WBSR was determined from change in exercise body mass, corrected for food/fluid intake and urine/stool loss. RSSL was the product of sweat [Na+] and WBSR. There were significant differences between sports for WBSR, with highest losses in American football (1.51 ± 0.70 L/h), then endurance (1.28 ± 0.57 L/h), followed by basketball (0.95 ± 0.42 L/h), soccer (0.94 ± 0.38 L/h) and baseball (0.83 ± 0.34 L/h). For RSSL, American football (55.9 ± 36.8 mmol/h) and endurance (51.7 ± 27.8 mmol/h) were greater than soccer (34.6 ± 19.2 mmol/h), basketball (34.5 ± 21.2 mmol/h), and baseball (27.2 ± 14.7 mmol/h). After ANCOVA, significant between-sport differences in adjusted means for WBSR and RSSL remained. In summary, due to the significant sport-specific variation in WBSR and RSSL, American football and endurance have the greatest need for deliberate hydration strategies. Abbreviations: WBSR: whole body sweating rate; SR: sweating rate; Na+: sodium; RSSL: rate of sweat sodium loss.

Facioscapulohumeral muscular dystrophy functional composite outcome measure.

INTRODUCTION: We developed an evaluator-administered functional facioscapulohumeral muscular dystrophy composite outcome measure (FSHD-COM) comprising patient-identified areas of functional burden for future clinical trials. METHODS: We performed a prospective observational study of 41 patients with FSHD at 2 sites. The FSHD-COM includes functional assessment of the legs, shoulders and arms, trunk, hands, and balance/mobility. We determined the test-retest reliability and convergent validity compared to established FSHD disease metrics. RESULTS: The FSHD-COM demonstrated excellent test-retest reliability (intraclass correlation coefficient [ICC] 0.96; subscale ICC range, 0.90-0.94). Cross-sectional associations between the FSHD-COM and disease duration, clinical severity, and strength were moderate to strong (Pearson correlation coefficient range |0.51-0.92|). DISCUSSION: The FSHD-COM is a disease-relevant, functional composite outcome measure suitable for future FSHD clinical trials that shows excellent test-retest reliability and cross-sectional associations to disease measures. Future directions include determining multisite reliability, sensitivity to change, and the minimal clinically important change in the FSHD-COM. Muscle Nerve, 2018.

Sweat Sodium, Potassium, and Chloride Concentrations Analyzed Same Day as Collection Versus After 7 Days Storage in a Range of Temperatures.

The purpose of this study was to determine the effect of storage temperature on sodium ([Na+]), potassium ([K+]), and chloride ([Cl-]) concentrations of sweat samples analyzed 7 days after collection. Using the absorbent patch technique, 845 sweat samples were collected from 39 subjects (32 ± 7 years, 72.9 ± 10.5 kg) during exercise. On the same day as collection (PRESTORAGE), 609 samples were analyzed for [Na+], [Cl-], and [K+] by ion chromatography (IC) and 236 samples were analyzed for [Na+] using a compact ion-selective electrode (ISE). Samples were stored at one of the four conditions: -20 °C (IC, n = 138; ISE, n = 60), 8 °C (IC, n = 144; ISE, n = 59), 23 °C (IC, n = 159; ISE, n = 59), or alternating between 8 °C and 23 °C (IC, n = 168; ISE, n = 58). After 7 days in storage (POSTSTORAGE), samples were reanalyzed using the same technique as PRESTORAGE. PRESTORAGE sweat electrolyte concentrations were highly related to that of POSTSTORAGE (intraclass correlation coefficient: .945-.989, p < .001). Mean differences (95% confidence intervals) between PRESTORAGE and POSTSTORAGE were statistically, but not practically, significant for most comparisons: IC [Na+]: -0.5(0.9) to -2.1(0.9) mmol/L; IC [K+]: -0.1(0.1) to -0.2(0.1) mmol/L; IC [Cl-]: -0.4(1.4) to -1.3(1.3) mmol/L; ISE [Na+]: -2.0(1.1) to 1.3(1.1) mmol/L. Based on typical error of measurement results, 95% of the time PRESTORAGE and POSTSTORAGE sweat [Na+], [K+], and [Cl-] by IC analysis fell within ±7-9, ±0.6-0.7, and ±9-13 mmol/L, respectively, while sweat [Na+] by ISE was ±6 mmol/L. All conditions produced high reliability and acceptable levels of agreement in electrolyte concentrations of sweat samples analyzed on the day of collection versus after 7 days in storage.

A mandala of faculty development: using theory-based evaluation to explore contexts, mechanisms and outcomes.

Demonstrating the impact of faculty development, is an increasingly mandated and ever elusive goal. Questions have been raised about the adequacy of current approaches. Here, we integrate realist and theory-driven evaluation approaches, to evaluate an intensive longitudinal program. Our aim is to elucidate how faculty development can work to support a range of outcomes among individuals and sub-systems in the academic health sciences. We conducted retrospective framework analysis of qualitative focus group data gathered from 79 program participants (5 cohorts) over a 10-year period. Additionally, we conducted follow-up interviews with 15 alumni. We represent the interactive relationships among contexts, mechanisms, and outcomes as a "mandala" of faculty development. The mandala illustrates the relationship between the immediate program context, and the broader institutional context of academic health sciences, and identifies relevant change mechanisms. Four primary mechanisms were collaborative-reflection, self-reflection and self-regulation, relationship building, and pedagogical knowledge acquisition. Individual outcomes, including changed teaching practices, are described. Perhaps most interestingly, secondary mechanisms-psychological and structural empowerment-contributed to institutional outcomes through participants' engagement in change leadership in their local contexts. Our theoretically informed evaluation approach models how faculty development, situated in appropriate institutional contexts, can trigger mechanisms that yield a range of benefits for faculty and their institutions. The adopted methods hold potential as a way to demonstrate the often difficult-to-measure outcomes of educational programs, and allow for critical examination as to how and whether faculty development programs can accomplish their espoused goals.

Sweat Sodium Concentration: Inter-Unit Variability of a Low Cost, Portable, and Battery Operated Sodium Analyzer.

The B-722 Laqua Twin is a low cost, portable, and battery operated sodium analyzer, which can be used for the assessment of sweat sodium concentration. The Laqua Twin is reliable and provides a degree of accuracy similar to more expensive analyzers; however, its interunit measurement error remains unknown. The purpose of this study was to compare the sodium concentration values of 70 sweat samples measured using three different Laqua Twin units. Mean absolute errors, random errors and constant errors among the different Laqua Twins ranged respectively between 1.7 mmol/L to 3.5 mmol/L, 2.5 mmol/L to 3.7 mmol/L and -0.6 mmol/L to 3.9 mmol/L. Proportional errors among Laqua Twins were all < 2%. Based on a within-subject biological variability in sweat sodium concentration of ± 12%, the maximal allowable imprecision among instruments was considered to be £ 6%. In that respect, the within (2.9%), between (4.5%), and total (5.4%) measurement error coefficient of variations were all < 6%. For a given sweat sodium concentration value, the largest observed difference in mean and lower and upper bound error of measurements among instruments were, respectively, 4.7 mmol/L, 2.3 mmol/L, and 7.0 mmol/L. In conclusion, our findings show that the interunit measurement error of the B-722 Laqua Twin is low and methodologically acceptable.

Evidence for curricular and instructional design approaches in undergraduate medical education: An umbrella review.

INTRODUCTION: An umbrella review compiles evidence from multiple reviews into a single accessible document. This umbrella review synthesizes evidence from systematic reviews on curricular and instructional design approaches in undergraduate medical education, focusing on learning outcomes. METHODS: We conducted bibliographic database searches in Medline, EMBASE and ERIC from database inception to May 2013 inclusive, and digital keyword searches of leading medical education journals. We identified 18,470 abstracts; 467 underwent duplicate full-text scrutiny. RESULTS: Thirty-six articles met all eligibility criteria. Articles were abstracted independently by three authors, using a modified Kirkpatrick model for evaluating learning outcomes. Evidence for the effectiveness of diverse educational approaches is reported. DISCUSSION: This review maps out empirical knowledge on the efficacy of a broad range of educational approaches in medical education. Critical knowledge gaps, and lapses in methodological rigour, are discussed, providing valuable insight for future research. The findings call attention to the need for adopting evaluative strategies that explore how contextual variabilities and individual (teacher/learner) differences influence efficacy of educational interventions. Additionally, the results underscore that extant empirical evidence does not always provide unequivocal answers about what approaches are most effective. Educators should incorporate best available empirical knowledge with experiential and contextual knowledge.