Clinical Physician Assistant Students' Perceptions of Evidence-Based Medicine Resources: A Cross-Sectional Examination.

Evidence-based medicine (EBM) instruction is required for physician assistant (PA) students. As a follow-up to an initial didactic year survey, this study seeks to understand which attributes of EBM resources clinical PA students find most and least useful, their self-efficacy utilizing medical literature, and their usage of EBM tools in the clinic. Results indicate that students preferred UpToDate and PubMed. PA students valued ease of use, which can inform instructors and librarians. Respondents utilized EBM tools daily or a few days a week, underscoring the importance of EBM tools in real-world scenarios. After their clinical year, students felt moderately confident utilizing the medical literature, emphasizing EBM training.

The Influence of Patient Care, Shadowing, and Volunteer Experience on Diverse Applicant Matriculation Into Physician Assistant/Associate Programs.

PURPOSE: To better understand factors contributing to low matriculation rates for health professions students from backgrounds underrepresented in medicine (URiM), this study examined the influence of healthcare-releated preadmission experiences on physician assistant/associate (PA) program matriculation. METHODS: We analyzed data from the Centralized Application Service for PAs 2018 to 2019 admissions cycle to compare characteristics of non-URiM and URiM PA program applicants and matriculants. The primary focus was on preadmission healthcare-releated experiences. To control for the strong influence of grade point average (GPA) on the likelihood of matriculation, we divided applicants into 2 groups: those with GPA < 3.6 (the median GPA for matriculants) and those with GPA ≥ 3.6. Analyses consisted of descriptive statistics and logistic regressions. RESULTS: Our sample consisted of 25,880 PA program applicants. Higher proportions of URiM compared with non-URiM applicants identified as first-generation college students (39.3% vs. 19.9%) or indicated economic disadvantage (32.3% vs. 12.5%). Overall, higher proportions of URiM compared with non-URiM applicants reported no patient care experience (24.3% vs. 17.9%), no shadowing (31.7% vs. 21.7%), or no volunteering (32.2% vs. 26.9%). Among all applicants with GPA < 3.6, reporting any type of experience was associated with increased odds of matriculation. Among URiM applicants with GPA ≥ 3.6, patient care experience did not influence odds of matriculation (odds ratio [OR] = 1.22, P = .23), whereas shadowing was associated with twice the odds (OR = 2.01, P < .001). CONCLUSIONS: Although academic metrics are known to predict PA program matriculation, we found that preadmission experiences also play a role. The study findings suggest that lack of experience hours may hinder URiM student access to PA education.

Central Application Service for Physician Assistants Fifteen-Year Data Report 2002-2016.

PURPOSE: This study highlights trends in available physician assistant (PA) applicant and matriculant data over the first 15 years of the Central Application Service for Physician Assistants (CASPA) service (2002-2016). This study expands knowledge identified in the CASPA 10-year data report. METHODS: This was a retrospective analysis of CASPA data from all CASPA-participating PA programs between 2002 and 2016. Central Application Service for Physician Assistants staff verified all applicant academic information. In addition, beginning in 2007, the online CASPA admissions portal linked matriculant data with applicant data. RESULTS: During the first 15 years of the CASPA service, there was a 194% increase in the number of CASPA-participating programs (from 68 to 200) and a 409% increase in the number of total applicants. Several trends identified in the CASPA 10-year report persisted, including increasing grade point averages among applicants and matriculants and lower matriculation rates among underrepresented minority applicants and applicants who reported economic disadvantage. CONCLUSION: This 15-year comprehensive analysis of the CASPA data will benefit the profession by providing historical information that faculty and policymakers can use as a basis for developing and evaluating future admissions policies and practices.

Effects of supplementing milk replacer with essential amino acids on blood metabolites, immune response, and nitrogen metabolism of Holstein calves exposed to an endotoxin.

This study evaluated the effects of supplementing calf milk replacer with essential AA on immune responses, blood metabolites, and nitrogen metabolism of 32 Holstein bull calves [28 d of age, 44 ± 0.8 kg of body weight (BW)] exposed to lipopolysaccharide (LPS). Calves were bottle-fed a commercial milk replacer (20% crude protein and 20% fat, dry matter basis) twice daily along with a calf starter (19% crude protein, dry matter basis) for 45 d. The experiment was a randomized complete block design and treatments were a 2 × 2 factorial arrangement. Treatments were milk replacer (fed twice daily at 0.5 kg/d of powder) supplemented with or without 10 essential AA (+AA vs. -AA), and subcutaneous injection of sterile saline with or without LPS (+LPS vs. -LPS) at 3 h after the morning feeding on d 15 (4 µg LPS per kg of BW) and 17 (2 µg LPS per kg of BW). Calves also received a 2-mL subcutaneous injection of ovalbumin (6 mg of ovalbumin/mL) on d 16 and 30. Rectal temperature and blood samples were collected on d 15 before LPS injection and at h 4, 8, 12, and 24 thereafter. From d 15 to 19, total fecal and urinary output were collected, and feed refusals were documented. Rectal temperature was greater in +LPS than -LPS calves at h 4, 8, and 12 after LPS injection. Serum cortisol was greater for +LPS than -LPS at h 4 after LPS exposure. At d 28, serum antiovalbumin IgG level was greater in +LPS +AA calves compared with +LPS -AA. Serum glucose was lower for +LPS than -LPS at h 4 and 8. Serum insulin was greater in +LPS than -LPS calves. Plasma concentrations of Thr, Gly, Asn, Ser, and hydroxyproline were lower for +LPS versus -LPS calves. Plasma concentrations of Met, Leu, Phe, His, Ile, Trp, Thr, and Orn were greater in +AA calves than -AA calves. Plasma urea N and N retention were not different among LPS and AA treatments. The lower concentrations of AA in +LPS than -LPS calves indicate higher demand for AA in immuno-compromised calves fed milk replacer. Additionally, higher concentration of ovalbumin-specific IgG level in +LPS calves supplemented with +AA compared with +LPS calves with -AA suggests that supplementing AA to immune-compromised calves might improve immune status.

Reuniting the Three Sisters: collaborative science with Native growers to improve soil and community health.

Before Euro-American settlement, many Native American nations intercropped maize (Zea mays), beans (Phaseolus vulgaris), and squash (Cucurbita pepo) in what is colloquially called the "Three Sisters." Here we review the historic importance and consequences of rejuvenation of Three Sisters intercropping (3SI), outline a framework to engage Native growers in community science with positive feedbacks to university research, and present preliminary findings from ethnography and a randomized, replicated 3SI experiment. We developed mutually beneficial collaborative research agendas with four Midwestern US Native American nations. Ethnographic data highlighted a culturally based respect for 3SI as living beings, the importance it holds for all cultural facets of these Native nations, and the critical impact the practice has on environmental sustainability. One concern expressed by Native growers during ethnographic research was improving soil health-part of the rationale for establishing the 3SI agronomic experiment. To address this, we collaboratively designed a 3SI experiment. After 1 year, 3SI increased short-term soil respiration by 24%, decreased salt-extractable nitrate by 54%, had no effect on soil microbial biomass (but increased its carbon-to-nitrogen ratio by 32%) compared to the average of monoculture crops. The overarching purpose of this collaborative project is to develop a deeper understanding of 3SI, its cultural importance to Native communities, and how reinvigorating the practice-and intercropping in general-can make agroecosystems more sustainable for people and the environment.

Didactic Physician Assistant Students' Perceptions of Evidence-Based Medicine Resources: A Preliminary Investigation.

Evidence-Based Medicine (EBM) instruction is required for physician Assistant (PA) students. This pilot study surveyed didactic PA students at three geographically diverse PA programs at the end of their didactic EBM course to understand which attributes of EBM resources they find most and least useful, and their self-efficacy in searching and appraising medical literature. Thematic analysis identified the most important student-reported attributes of a resource. PA students in this sample preferred UpToDate and PubMed as their top EBM tools based on attribute ratings. However, each database included in this pilot study received positive feedback, despite a low usage rate across institutions. The most important attributes were ease of use/search, information presentation, and conclusion/critical appraisal skill. After one EBM course, on average, students rated their self-efficacy searching the literature and appraising the literature as "moderately confident." This suggests that instructors and librarians have an opportunity to expose students to more tools as well as encourage "the right tool for the right job."

Illicit drug use and self-reported vision loss among military service members or veterans.

INTRODUCTION: Little is known about differences in vision loss prevalence among service members or veterans (SMVs) and civilians; further, no study has compared vision loss risk factors in these two populations. As such, we seek to fill this gap in the literature. METHODS: In this cross sectional study, we obtained data on 106 SMVs and 1572 civilians from the 2013-2018 National Health and Nutrition Examination Surveys. We compared the prevalence of or mean values of vision loss risk factors between SMVs and civilians using the Wald χ2 statistic or Kruskal-Wallis test. Further, we examined the relative strength of 17 vision loss risk factors in predicting self-reported vision loss via Firth's logistic regression. RESULTS: SMVs had a significantly higher prevalence of illicit drug use (20.75% vs 13.62%) and HIV (1.89% vs 0.41%), while civilians had a higher prevalence of poor dietary habits (7.61% vs 13.21%). SMVs also had higher mean values of systolic blood pressure (125.85 vs 122.53 mmHg), pack years of cigarette smoking (8.29 vs 4.25), and sedentary minutes per day (379.15 vs 337.07 min). More SMVs (8.49%) self-reported vision loss than civilians (4.48%). After adjustment for covariates, illicit drug use (adjusted ß coefficient=0.72, p=0.02) was associated with self-reported vision loss. CONCLUSIONS: This study indicates that self-reported vision loss among SMVs is more prevalent than among civilians, and vision loss in SMVs is associated with severe or prolonged illicit drug use.

New Advances in Physician Assistant Admissions: The History of Situational Judgement Tests and the Development of CASPer.

ABSTRACT: During the first 50 years of the physician assistant (PA) profession, admission to PA programs was based primarily on cognitive domains such as academic performance and standardized test scores. Many programs also considered other measurable factors, including patient care experience, community service, and extracurricular activities. While interviews were frequently conducted by the programs, it was not until the applicants had been "pre-screened" for the previously identified qualifications. As the PA profession continued to expand, PA programs began to realize that potentially strong applicants were being excluded from the admissions process because of this emphasis on mostly cognitive factors. In an attempt to reduce this disparity, PA programs have begun to expand their assessment of applicants to include assessment of noncognitive characteristics. This article outlines the history surrounding this change in the approach to admissions in medical education, reviews the development of situational judgement tests and other tools used to assess these noncognitive characteristics, and explores the relationship of these noncognitive characteristics to the development of program-defined competencies.

Undergraduate Men's Self-Reports of Sexual Assault and Perceptions of College Campus Acquaintance Rape.

Acquaintance rape is distressingly common on college campuses. Differing models of the perpetration of sexual assault make diverging predictions regarding the degree to which individual differences may distinguish among such sexual offenders and nonoffenders. Much research investigating these issues has primarily sampled students from large, commuter colleges. Such data may not generalize to students in other university settings (e.g., private schools, students in university housing). The present study sought to examine the rate of self-reported sexual assault among college men at a private school at which most students live in university housing. Furthermore, we examined whether individual difference characteristics-namely, endorsement of masculine gender norms and endorsement of modern myths about sexual assault-predicted participants' perceptions of acquaintance rape. A total of 219 college men completed a survey consisting of the Male Role Norm Inventory (MRNI), followed by the Acceptance of Modern Myths About Sexual Aggression (AMMSA) and the Sexual Experiences Survey (SES). They then read a hypothetical acquaintance rape scenario and provided several ratings regarding their attributions of blame. Approximately, 4.6% of men self-reported having committed sexual assault. A Bayesian analysis indicated that self-reported offenders did not score differently on MRNI and AMMSA than self-reported nonoffenders, nor did they view the hypothetical scenario differently. Overall, men who endorsed male role norms tended to accept modern myths about rape and tended to attribute more blame to the victim and less blame to the perpetrator in the acquaintance rape scenario. We discuss methodological difficulties in conducting this type of research and identify several directions for future research.

Charting the Course for Online Physician Assistant Education.

The move to online learning has become one of the most challenging events in physician assistant (PA) education; however, new advances in online technology now make it possible to deliver an entire PA didactic curriculum online. The blending of the latest innovations in online technology with a problem-based learning (PBL) curriculum enables programs to engage students using the Socratic method online while providing feedback in real time. While this novel approach to learning is still being evaluated as data is continually collected, preliminary results indicate online technology can be successfully implemented in a blended PA education curriculum.

Innovative Strategies for Clinical Microscopy Instruction: Virtual Versus Light Microscopy.

PURPOSE: The purpose of the study was to compare virtual microscopy with light microscopy to determine differences in learning outcomes and learner attitudes in teaching clinical microscopy to physician assistant (PA) students. METHODS: A prospective, randomized, crossover design study was conducted with a convenience sample of 67 first-year PA students randomized to 2 groups. One group used light microscopes to find microscopic structures, whereas the other group used instructor-directed video streaming of microscopic elements. At the midpoint of the study, the groups switched instructional strategies. Learning outcomes were assessed via posttest after each section of the study, with comparison of final practical examination results to previous cohorts. Attitudes about the 2 educational strategies were assessed through a postcourse questionnaire with a Likert scale. RESULTS: Analysis of the first posttest demonstrated that students in the video-streamed group had significantly better learning outcomes than those in the light microscopy group (P = .004; Cohen's d = 0.74). Analysis of the posttest after crossover showed no differences between the 2 groups (P = .48). Between the 2 posttests, students first assigned to the light microscopy group scored a 6.6 mean point increase (±10.4 SD; p = .0011), whereas students first assigned to the virtual microscopy group scored a 1.3 mean point increase (±7.1 SD; p = .29). The light microscopy group improved more than the virtual microscopy group (P = .019). Analysis of practical examination data revealed higher scores for the study group compared with 5 previous cohorts of first-year students (P < .0001; Cohen's d = 0.66). Students preferred virtual microscopy to traditional light microscopy. CONCLUSION: Virtual microscopy is an effective educational strategy, and students prefer this method when learning to interpret images of clinical specimens.

Physician Assistant Applicant Pool: The First 50 Years.

The physician assistant (PA) profession's first attempt to characterize the applicant pool for PA education began with publication of the first Annual Report on Physician Assistant Educational Programs in the United States in 1985. The methodology used in the report was limited, however, in identifying the number of unique applicants to PA programs. Collecting accurate and reliable data on the profession's applicant pool was the primary motivator leading to initiation of the Central Application Service for Physician Assistants (CASPA) in 2001. In the past 15 years, CASPA has provided increasingly valuable data on the profession's applicant pool, allowing for accurate tracking and analysis of trends in the growth and changing demographics of those applying to PA educational programs. This special report presents a unique analysis of CASPA data that relates the competitiveness of entry into PA programs with that experienced by our colleagues in medicine, for both Doctor of Medicine (MD) and Doctor or Osteopathic Medicine (DO) schools. We present data reflecting the most notable changing demographics of the profession's applicant and matriculant pools in sex, age, grade point average, and health care experience. We use aggregate data of self-identified race descriptors to compare the contributions of PA, medical, and osteopathic medicine schools to the improvement of diversity within the health professions. To date, the applicant pool of PA programs seems to have kept pace with the expansion of existing programs and the development of new programs. This article poses serious questions for the profession to ponder, as the demographics of those entering PA education change and the number of PA graduates continues to grow.

Central Application Service for Physician Assistants Ten-Year Data Report, 2002 to 2011.

PURPOSE: This study highlights the trends and data points of interest in physician assistant (PA) applicant data over the first 10 years of the Central Application Service for Physician Assistants (CASPA) (2002-2011) and PA matriculant data over the last 5 years of that 10-year period (2007-2011). METHODS: A retrospective study of data provided by applicants to all CASPA-participating PA programs between 2002 and 2011 was conducted. Applicant data analyzed over the 10-year period were provided by applicants and collected through an online CASPA applicant portal. Academic information was verified by CASPA staff through official transcript review. Matriculant data were obtained from CASPA-participating programs through the online CASPA admissions portal, which linked to applicant data in the CASPA applicant portal. RESULTS: During the first 10 years of the CASPA service, the Physician Assistant Education Association experienced a 93% increase in the number of CASPA-participating programs and a 255% increase in the number of unique applicants identified through CASPA. Relatively constant trends were identified in the major demographic features (age, gender, ethnic composition, and disadvantaged status) and the academic data of applicants. Major demographic features of matriculants (2007-2011) also remained relatively constant, whereas trends in academic data of matriculants revealed an increasing total grade point average. CONCLUSION: This 10-year comprehensive analysis of the CASPA data will benefit the profession by establishing a baseline of applicant characteristics. Ultimately, these data will help redefine recruitment strategies at program, state, and national levels by providing programs and national organizations with data needed to target applicants not previously included in recruitment activities.

Crop rotational diversity enhances belowground communities and functions in an agroecosystem.

Biodiversity loss, an important consequence of agricultural intensification, can lead to reductions in agroecosystem functions and services. Increasing crop diversity through rotation may alleviate these negative consequences by restoring positive aboveground-belowground interactions. Positive impacts of aboveground biodiversity on belowground communities and processes have primarily been observed in natural systems. Here, we test for the effects of increased diversity in an agroecosystem, where plant diversity is increased over time through crop rotation. As crop diversity increased from one to five species, distinct soil microbial communities were related to increases in soil aggregation, organic carbon, total nitrogen, microbial activity and decreases in the carbon-to-nitrogen acquiring enzyme activity ratio. This study indicates positive biodiversity-function relationships in agroecosystems, driven by interactions between rotational and microbial diversity. By increasing the quantity, quality and chemical diversity of residues, high diversity rotations can sustain soil biological communities, with positive effects on soil organic matter and soil fertility.

Caring for patients with melanoma in the primary care setting.

The incidence of melanoma is steadily rising and mortality continues to increase. This article describes types of melanoma and the role of primary care providers in the long-term management and follow-up of patients diagnosed with melanoma.

Does agricultural crop diversity enhance soil microbial biomass and organic matter dynamics? A meta-analysis.

Our increasing dependence on a small number of agricultural crops, such as corn, is leading to reductions in agricultural biodiversity. Reductions in the number of crops in rotation or the replacement of rotations by monocultures are responsible for this loss of biodiversity. The belowground implications of simplifying agricultural plant communities remain unresolved; however, agroecosystem sustainability will be severely compromised if reductions in biodiversity reduce soil C and N concentrations, alter microbial communities, and degrade soil ecosystem functions as reported in natural communities. We conducted a meta-analysis of 122 studies to examine crop rotation effects on total soil C and N concentrations, and the faster cycling microbial biomass C and N pools that play key roles in soil nutrient cycling and physical processes such as aggregate formation. We specifically examined how rotation crop type and management practices influence C and N dynamics in different climates and soil types. We found that adding one or more crops in rotation to a monoculture increased total soil C by 3.6% and total N by 5.3%, but when rotations included a cover crop (i.e., crops that are not harvested but produced to enrich the soil and capture inorganic N), total C increased by 8.5% and total N 12.8%. Rotations substantially increased the soil microbial biomass C (20.7%) and N (26.1%) pools, and these overwhelming effects on microbial biomass were not moderated by crop type or management practices. Crop rotations, especially those that include cover crops, sustain soil quality and productivity by enhancing soil C, N, and microbial biomass, making them a cornerstone for sustainable agroecosystems.

Climate change interactions affect soil carbon dioxide efflux and microbial functioning in a post-harvest forest.

Forest disturbances, including whole-tree harvest, will increase with a growing human population and its rising affluence. Following harvest, forests become sources of C to the atmosphere, partly because wetter and warmer soils (relative to pre-harvest) increase soil CO2 efflux. This relationship between soil microclimate and CO2 suggests that climate changes predicted for the northeastern US may exacerbate post-harvest CO2 losses. We tested this hypothesis using a climate-manipulation experiment within a recently harvested northeastern US forest with warmed (H; +2.5 °C), wetted (W; +23% precipitation), warmed + wetted (H+W), and ambient (A) treatments. The cumulative soil CO2 effluxes from H and W were 35% (P = 0.01) and 22% (P = 0.07) greater than A. However, cumulative efflux in H+W was similar to A and W, and 24% lower than in H (P = 0.02). These findings suggest that with higher precipitation soil CO2 efflux attenuates rapidly to warming, perhaps due to changes in substrate availability or microbial communities. Microbial function measured as CO2 response to 15 C substrates in warmed soils was distinct from non-warmed soils (P < 0.001). Furthermore, wetting lowered catabolic evenness (P = 0.04) and fungi-to-bacteria ratios (P = 0.03) relative to non-wetted treatments. A reciprocal transplant incubation showed that H+W microorganisms had lower laboratory respiration on their home soils (i.e., home substrates) than on soils from other treatments (P < 0.01). We inferred that H+W microorganisms may use a constrained suite of C substrates that become depleted in their "home" soils, and that in some disturbed ecosystems, a precipitation-induced attenuation (or suppression) of soil CO2 efflux to warming may result from fine-tuned microbe-substrate linkages.

The use of noncognitive factors in physician assistant admissions.

PURPOSE: To identify the most influential noncognitive factors valued in admissions processes by physician assistant (PA) programs throughout the United States, as well as the motivators for and barriers to using these factors. METHODS: A literature search was performed using PubMed and the Journal of Physician Assistant Education to identify noncognitive factors that were reported to have an effect on admissions in various health professions. A survey was developed incorporating the most frequently identified factors and was electronically distributed to all program directors of the Physician Assistant Education Association (PAEA). Respondents were asked to rank the noncognitive factors that were most valued by their program's admissions process as well as to rate motivators and barriers for the use of these noncognitive factors in admissions. Survey responses were anonymous but respondents reported program location by geographic region as defined by PAEA. RESULTS: There were 94 respondents from 154 programs surveyed (61% response rate). The five most influential noncognitive factors were faculty/staff/interviewer interactions, career motivation, knowledge of profession, maturity, and professionalism. The most important motivators for using noncognitive factors were identified as academic success and career success. All aforementioned factors and motivators did not vary based on PA program region (P > .05). The factors identified with the highest level of regional variance were leadership experience (P = .014), self-awareness (P = .034), cultural sensitivity (P = .022), undergraduate institution (P = .010), and peer interaction (P = .035). CONCLUSION: These study results will assist PA applicants in becoming more competitive and provide programs with additional factors for consideration in current admissions practices. Further considerations for research include correlating results to academic success as well as success on the Physician Assistant National Certifying Exam (PANCE).

Treatment trends for haemophilia A and haemophilia B in the United States: results from the 2010 practice patterns survey.

Frequent evaluation of haemophilia treatment is necessary to improve patient care. The 2010 Practice Patterns Survey (PPS) investigated current trends in haemophilia treatment in the United States, as reported by nurses. The aim was to document practice patterns for haemophilia A and haemophilia B Survey questionnaires were sent to nurses at haemophilia treatment centres (HTCs) across the United States. Seventy-one of 126 HTCs (56%) responded to the survey. Factor dosage across treatment modalities ranged from 20 to 50 IU kg(-1) for severe haemophilia A. Dosage for severe haemophilia B was more variable (<40 to >100 IU kg(-1)). On-demand dosing regimens were inconsistent for haemophilia A and more so for haemophilia B. Rates of adherence to prescribed treatment were similar for both haemophilia types (∼80%). The main barrier to adherence was identified as inconvenience. More bleeding episodes occurred in adults (16.6 bleeding episodes per year) with severe haemophilia A than in younger patients (11.3 bleeding episodes per year) before switching patients to prophylaxis. For both haemophilia types, most patients who switched from prophylaxis to on-demand treatment were aged 13-24 years; these patients also had the lowest adherence (60-71%). More paediatric patients with severe haemophilia A and inhibitors (53%) received prophylactic bypassing therapy than their haemophilia B counterparts (38%). Adults with severe haemophilia A faced challenges in relation to co-morbidities and long-term care. This PPS provides insights into previously unexplored aspects of haemophilia care that will serve to increase awareness and promote discussion of current issues affecting haemophilia patient care.

Hyperinsulinism in mice with heterozygous loss of K(ATP) channels.

AIMS/HYPOTHESIS: ATP-sensitive K(+) (K(ATP)) channels couple glucose metabolism to insulin secretion in pancreatic beta cells. In humans, loss-of-function mutations of beta cell K(ATP) subunits (SUR1, encoded by the gene ABCC8, or Kir6.2, encoded by the gene KCNJ11) cause congenital hyperinsulinaemia. Mice with dominant-negative reduction of beta cell K(ATP) (Kir6.2[AAA]) exhibit hyperinsulinism, whereas mice with zero K(ATP) (Kir6.2(-/-)) show transient hyperinsulinaemia as neonates, but are glucose-intolerant as adults. Thus, we propose that partial loss of beta cell K(ATP) in vivo causes insulin hypersecretion, but complete absence may cause insulin secretory failure. MATERIALS AND METHODS: Heterozygous Kir6.2(+/-) and SUR1(+/-) animals were generated by backcrossing from knockout animals. Glucose tolerance in intact animals was determined following i.p. loading. Glucose-stimulated insulin secretion (GSIS), islet K(ATP) conductance and glucose dependence of intracellular Ca(2+) were assessed in isolated islets. RESULTS: In both of the mechanistically distinct models of reduced K(ATP) (Kir6.2(+/-) and SUR1(+/-)), K(ATP) density is reduced by approximately 60%. While both Kir6.2(-/-) and SUR1(-/-) mice are glucose-intolerant and have reduced glucose-stimulated insulin secretion, heterozygous Kir6.2(+/-) and SUR1(+/-) mice show enhanced glucose tolerance and increased GSIS, paralleled by a left-shift in glucose dependence of intracellular Ca(2+) oscillations. CONCLUSIONS/INTERPRETATION: The results confirm that incomplete loss of beta cell K(ATP) in vivo underlies a hyperinsulinaemic phenotype, whereas complete loss of K(ATP) underlies eventual secretory failure.