Perceptions of Justice in Clinical Learning Environments: Development and Validation of an Organizational Justice Measure for Medical Trainees.

PURPOSE: This study aimed to develop an instrument to measure medical trainees' perceptions of justice in clinical learning environments. METHOD: Between 2019 and 2023, the authors conducted a multiyear, multi-institutional, multiphase study to develop a 16-item justice measure with 4 dimensions: interpersonal, informational, procedural, and distributive. The authors gathered validity evidence based on test content, internal structure, and relationships with other variables across 3 phases. Phase 1 involved drafting items and gathering evidence that items measured intended dimensions. Phase 2 involved analyzing relevance of items for target groups, examining interitem correlations and factor loadings in a preliminary analysis, and obtaining reliability estimates. Phase 3 involved a confirmatory factor analysis and collecting convergent and discriminant validity evidence. RESULTS: In phase 1, 63 of 91 draft items were retained following a content validation exercise gauging how well items measured targeted dimensions (mean [SD] item ratings within dimensions, 4.16 [0.36] to 4.39 [0.34]) on a 5-point Likert scale (with 1 indicating not at all well and 5 indicating extremely well). In phase 2, 30 items were removed due to low factor loadings (i.e., < 0.40), and 4 items per dimension were selected (factor loadings, 0.42-0.89). In phase 3, a confirmatory factor analysis supported the 4-dimension model (χ2 = 610.14, P < .001; comparative fit index = 0.90, Tucker-Lewis Index = 0.87, root mean squared error of approximation = 0.11, standardized root mean squared residual = 0.06), with convergent and discriminant validity evidence showing hypothesized positive correlations with a justice measure (r = 0.93, P < .001), trait positive affect (r = 0.46, P < .001), and emotional stability (r = 0.33, P < .001) and negative correlations with trait negative affect (r = -0.39, P < .001). CONCLUSIONS: Results indicate the measure's potential utility in understanding justice perceptions and designing targeted interventions.

Adverse Childhood Experiences, Household Income, and Mentorship Among Interns Who Are Underrepresented in Medicine.

Background: Underrepresented in medicine (UIM) interns have unique lived experiences that affect their paths to medicine, and more information is needed for medical residency and fellowship programs to better support them. Objective: We describe self-reported differences between UIM and White physician interns in key demographic areas, including household income growing up, physician mentorship, and adverse childhood experiences (ACEs). Methods: Between 2019 and 2021, we administered a diversity survey to incoming medical interns at the University of Minnesota-Twin Cities. Response rates across the 3 years were 51.2% (167 of 326), 93.9% (310 of 330), and 98.9% (354 of 358), respectively. We conducted analyses to compare UIM and White groups across demographic variables of interest. Results: A total of 831 of 1014 interns (81.9%) completed the survey. Relative to White interns, UIM interns had lower household incomes growing up, lower rates of mentorship, and higher rates of experiencing 4 or more ACEs. The odds of experiencing the cumulative burden of having a childhood household income of $29,999 or less, no physician mentor, and 4 or more ACEs was approximately 10 times higher among UIM (6.41%) than White (0.66%) interns (OR=10.38, 95% CI 1.97-54.55). Conclusions: Childhood household income, prior mentorship experiences, and number of ACEs differed between UIM and White interns.

Differences in Trainee Evaluations of Faculty by Rater and Ratee Gender.

PURPOSE: To examine whether gender differences exist in medical trainees' (residents' and fellows') evaluations of faculty at a number of clinical departments. METHOD: The authors conducted a single-institution (University of Minnesota Medical School) retrospective cohort analysis of 5,071 trainee evaluations of 447 faculty (for which trainee and faculty gender information was available) completed between July 1, 2019, and June 30, 2022. The authors developed and employed a 17-item measure of clinical teaching effectiveness, with 4 dimensions: overall teaching effectiveness, role modeling, facilitating knowledge acquisition, and teaching procedures. Using both between- and within-subject samples, they conducted analyses to examine gender differences among the trainees making ratings (rater effects), the faculty receiving ratings (ratee effects), and whether faculty ratings differed by trainee gender (interaction effects). RESULTS: There was a statistically significant rater effect for the overall teaching effectiveness and facilitating knowledge acquisition dimensions (B = -0.28 and -0.14, 95% CI: [-0.35, -0.21] and [-0.20, -0.09], respectively, P < .001, medium corrected effect sizes between -0.34 and -0.54); female trainees rated male and female faculty lower than male trainees on both dimensions. There also was a statistically significant ratee effect for the overall teaching effectiveness and role modeling dimensions (B = -0.09 and -0.08, 95% CI: [-0.16, -0.02] and [-0.13, -0.04], P = .01 and < .001, respectively, small to medium corrected effect sizes between -0.16 and -0.44); female faculty were rated lower than male faculty on both dimensions. There was not a statistically significant interaction effect. CONCLUSIONS: Female trainees rated faculty lower than male trainees and female faculty were rated lower than male faculty on 2 teaching dimensions each. The authors encourage researchers to continue to examine the reasons for the evaluation differences observed and how implicit bias interventions might help to address them.

Can a Situational Judgment Test Identify Trainees at Risk of Professionalism Issues? A Multi-Institutional, Prospective Cohort Study.

PURPOSE: To determine whether overall situational judgment test (SJT) scores are associated with programs' clinical competency committee (CCC) ratings of trainee professionalism, any concerning behavior, and concerning behavior requiring active remediation at 2 time periods. METHOD: In fall 2019, trainees from 17 U.S. programs (16 residency, 1 fellowship) took an online 15-scenario SJT developed to measure 7 dimensions of professionalism. CCC midyear and year-end (6 months and 1 year following SJT completion, respectively) professionalism scores and concern ratings were gathered for academic year 2019-2020. Analyses were conducted to determine whether overall SJT scores related to overall professionalism ratings, trainees displaying any concerns, and trainees requiring active remediation at both time periods. RESULTS: Overall SJT scores correlated positively with midyear and year-end overall professionalism ratings ( r = .21 and .14, P < .001 and = .03, respectively). Holding gender and race/ethnicity constant, a 1 standard deviation (SD) increase in overall SJT score was associated with a .20 SD increase in overall professionalism ratings at midyear ( P = .005) and a .22 SD increase at year-end ( P = .001). Holding gender and race/ethnicity constant, a 1 SD increase in overall SJT score decreased the odds of a trainee displaying any concerns by 37% (odds ratio [OR] 95% confidence interval [CI]: [.44, .87], P = .006) at midyear and 34% (OR 95% CI: [.46, .95], P = .025) at year-end and decreased the odds of a trainee requiring active remediation by 51% (OR 95% CI: [.25, .90], P = .02) at midyear. CONCLUSIONS: Overall SJT scores correlated positively with midyear and year-end overall professionalism ratings and were associated with whether trainees exhibited any concerning behavior at midyear and year-end and whether trainees needed active remediation at midyear. Future research should investigate whether other potential professionalism measures are associated with concerning trainee behavior.

Improving Mental Health Support, Career Transitions and Access to Health Care for Surgical Residents.

OBJECTIVE: To increase access to mental health support, assist with career transitions, and improve access to health care. DESIGN: Retrospective survey data. SETTING: General surgery residency program. PARTICIPANTS: Surgical residents. RESULTS: We developed three programs to address the issues above. The "Fifth Tuesday of the Month" program allows residents to take time off during the first Tuesday morning of any month with five Tuesdays. The Physician Wellness Collaborative provides confidential, affordable, and easy-to-access counseling resources for residents. Residents are automatically signed up for a session to establish care. The Peer Resident Mentorship Program matches a fourth-year resident with a first-year resident based on personal and professional interests to help ease the transition and improve career satisfaction. All programs were associated with improvement in related outcome measures on our institution's annual program evaluation survey. CONCLUSIONS: At our institution, we introduced three simple and accessible programs aimed at increasing access to mental health support, assisting with career transitions, and improving work-life balance. These programs have improved related outcomes in our residents and can be easily implemented at any program.

Meta-analysis finds recurrent infection is more common after endovascular than after open repair of infected abdominal aortic aneurysm.

OBJECTIVE: Controversy has continued regarding the use of endovascular aneurysm repair (EVAR) vs open aneurysm repair (OAR) for infected abdominal aortic aneurysms (AAAs). In the present study, we investigated the comparative outcomes of EVAR and OAR for the treatment of infected AAAs. METHODS: We conducted a systematic review and meta-analysis using the MEDLINE and EMBASE databases through May 2021. We included studies that had described both EVAR and OAR for the treatment of infected AAAs. The primary endpoints were the rates of recurrent infection and related rupture and/or death. Perioperative and 1-year mortality and readmissions and reinterventions were also analyzed. RESULTS: Fourteen observational studies describing a total of 1203 patients (EVAR, 359 [29.8%]; OAR, 844 [70.2%]) were eligible for qualitative analysis. The baseline characteristics included diabetes mellitus (33.2%), fever at presentation (71.6%), rupture at diagnosis (26.1%), and positive blood cultures (52.5%). The mean follow-up period ranged from 12 to 40 months. The use of EVAR became more prevalent in recent years (2016-2020, 32.4%) compared with the former period (2010-2015, 13.8%; P < .0001). Fenestrated, branched, or concomitant visceral debranching EVAR was performed in 6.1% of cases. In OAR, surgical debridement was consistently performed, and in situ reconstruction was applied in 82.2% and an omental flap in 51.5%. In nine studies considered for quantitative analysis, the patients' background (EVAR, n = 264; OAR, n = 274) were statistically balanced. The crude rates of recurrent infection and related rupture or death were 13.6% (95% confidence interval [CI], 8.8%-18.5%) and 4.9% (95% CI 1.8%-8.0%), respectively. The pooled analyses depicted significantly higher rates of recurrent infection after EVAR than after OAR (relative risk [RR], 2.42; 95% CI, 1.80-3.27; P < .0001; I2 = 0%). Recurrent infection-related rupture or death (RR, 1.51; 95% CI, 0.70-3.23; P = .29; I2 = 0%), perioperative death (RR, 0.80; 95% CI, 0.39-1.65; P = .55; I2 = 35%), 1-year mortality (hazard ratio, 1.12; 95% CI, 0.97-1.28; P =.13; I2 = 0%), and readmission or reintervention (RR, 1.16; 95% CI, 0.74-1.82; P =.52; I2 = 0%) were not significantly different statistically between the two groups. Funnel plots showed no evidence of publication bias. Sensitivity analyses of leave-one-out meta-analysis confirmed higher rates of recurrent infection after EVAR. CONCLUSIONS: EVAR has become more prevalent as the initial treatment of infected AAAs. Although operative and 1-year survival were similar between OAR and EVAR groups, recurrent infection was more frequent after EVAR. This limitation should be weighed in selecting patients for EVAR in infected AAAs. Postoperative graft and infection surveillance are critical, especially after EVAR.

Development of an Abbreviated Longitudinal Approach for Medical Student Learning in Perioperative Medicine: Teaching the Perioperative Surgical Home.

INTRODUCTION: Leaders in anesthesiology are promoting increased involvement of anesthesiologists in perioperative medicine (POM). Academic leaders are calling for a corresponding increase in resident and medical student education in this evolving medical discipline. Formalized POM programs are new to most academic anesthesiology programs, and very little has been written about development of these programs for anesthesiology residents or medical students. We describe the creation of a longitudinal medical student clerkship in POM using established curriculum design methods with minimal capital resources. METHODS: This is a descriptive account of the process of clerkship design. It includes a qualitative analysis of participants' satisfaction with the novel clerkship. RESULTS: Design and implementation of a new, advanced medical student clerkship in POM using no additional capital resources was successful. Medical students indicated appreciation for the unique longitudinal design. Students also demonstrated understanding of the expanding role of anesthesiology in perioperative care of patients, a primary goal of the educational process. CONCLUSIONS: The principles of the American Society of Anesthesiology's Perioperative Surgical Home can be taught systematically and successfully to advanced medical students with little additional expenditure of departmental resources.

The Minnesota Method: A Learner-Driven, Entrustable Professional Activity-Based Comprehensive Program of Assessment for Medical Students.

PROBLEM: Assessment has been the Achilles heel of competency-based medical education. It requires a program of assessment in which outcomes are clearly defined, students know where they are in the development of the competencies, and what the next steps are to attaining them. Achieving this goal in a feasible manner has been elusive with traditional assessment methods alone. The Education in Pediatrics Across the Continuum (EPAC) program at the University of Minnesota developed a robust program of assessment that has utility and recognizes when students are ready for the undergraduate to graduate medical education transition. APPROACH: The authors developed a learner-driven program of assessment in the foundational clinical training of medical students in the EPAC program based on the Core Entrustable Professional Activities for Entering Residency (Core EPAs). Frequent workplace-based assessments, coupled with summative assessments, informed a quarterly clinical competency committee and individualized learning plans. The data were displayed on real time dashboards for the students to review. OUTCOMES: Over 4 cohorts from 2015 to 2019, students (n = 13) averaged approximately 200 discrete Core EPA workplace-based assessments during their foundational clinical training year. Assessments were completed by an average of 9 different preceptors each month across 8 different specialties. The data were displayed in a way students and faculty could monitor development and inform a clinical competency committee's ability to determine readiness to transition to advanced clinical rotations and residency. NEXT STEPS: The next steps include continuing to scale the program of assessment to a larger cohort of students.

Validity Evidence for Assessing Entrustable Professional Activities During Undergraduate Medical Education.

PURPOSE: To explore validity evidence for the use of entrustable professional activities (EPAs) as an assessment framework in medical education. METHOD: Formative assessments on the 13 Core EPAs for entering residency were collected for 4 cohorts of students over a 9- to 12-month longitudinal integrated clerkship as part of the Education in Pediatrics Across the Continuum pilot at the University of Minnesota Medical School. The students requested assessments from clinical supervisors based on direct observation while engaging in patient care together. Based on each observation, the faculty member rated the student on a 9-point scale corresponding to levels of supervision required. Six EPAs were included in the present analyses. Student ratings were depicted as curves describing their performance over time; regression models were employed to fit the curves. The unit of analyses for the learning curves was observations rather than individual students. RESULTS: (1) Frequent assessments on EPAs provided a developmental picture of competence consistent with the negative exponential learning curve theory; (2) This finding was true across a variety of EPAs and across students; and (3) The time to attain the threshold level of performance on the EPA for entrustment varied by student and EPA. CONCLUSIONS: The results provide validity evidence for an EPA-based program of assessment. Students assessed using multiple observations performing the Core EPAs for entering residency demonstrate classic developmental progression toward the desired level of competence resulting in entrustment decisions. Future work with larger data samples will allow further psychometric analyses of assessment of EPAs.

Development of a taxonomy of unprofessional behavior in clinical learning environments using learner-generated critical incidents.

PURPOSE: Few studies have examined medical residents' and fellows' (trainees) direct experience of unprofessional behavior in clinical learning environments (CLE). The purpose of this study was to create a taxonomy of unprofessional behavior in CLEs using critical incidents gathered from trainees. METHOD: In step 1 (data collection), the authors collected 382 critical incidents from trainees at more than a dozen CLEs over a six-year period (2013-2019). In step 2 (model generation), nine subject matter experts (SMEs) sorted the incidents into homogenous clusters and this structure was tested with principal components analysis (PCA). In step 3 (model evaluation), two new groups of SMEs each re-sorted half of the incidents into the PCA-derived categories. RESULTS: A 13-component solution accounted for 62.46% of the variance in the critical incidents collected. The SMEs who re-sorted the critical incidents demonstrated good agreement with each other and with the 13-component PCA solution. The resulting taxonomy included 13 dimensions, with 48.7% of behaviors focused on displays of aggression or discriminatory conduct. CONCLUSIONS: Critical incident methodology can provide unique insights into the dimensionality of unprofessional behavior in the CLE. Future research should leverage the taxonomy created to inform professionalism assessment development in the CLE.

Improving Our Ability to Predict Resident Applicant Performance: Validity Evidence for a Situational Judgment Test.

Construct: We investigated whether a situational judgment test (SJT) designed to measure professionalism in physicians predicts residents' performance on (a) Accreditation Council for Graduate Medical Education (ACGME) competencies and (b) a multisource professionalism assessment (MPA). Background: There is a consensus regarding the importance of assessing professionalism and interpersonal and communication skills in medical students, residents, and practicing physicians. Nonetheless, these noncognitive competencies are not well measured during medical education selection processes. One promising method for measuring these noncognitive competencies is the SJT. In a typical SJT, respondents are presented with written or video-based scenarios and asked to make choices from a set of alternative courses of action. Interpersonally oriented SJTs are commonly used for selection to medical schools in the United Kingdom and Belgium and for postgraduate selection of trainees to medical practice in Belgium, Singapore, Canada, and Australia. However, despite international evidence suggesting that SJTs are useful predictors of in-training performance, end-of-training performance, supervisory ratings of performance, and clinical skills licensing objective structured clinical examinations, the use of interpersonally oriented SJTs in residency settings in the United States has been infrequently investigated. The purpose of this study was to investigate whether residents' performance on an SJT designed to measure professionalism-related competencies-conscientiousness, integrity, accountability, aspiring to excellence, teamwork, stress tolerance, and patient-centered care-predicts both their current and future performance as residents on two important but conceptually distinct criteria: ACGME competencies and the MPA. Approach: We developed an SJT to measure seven dimensions of professionalism. During calendar year 2017, 21 residency programs from 2 institutions administered the SJT. We conducted analyses to determine the validity of SJT and USMLE scores in predicting milestone performance in ACGME core competency domains and the MPA in June 2017 and 3 months later in September 2017 for the MPA and 1 year later, in June 2018, for ACGME domains. Results: At both periods, the SJT score predicted overall ACGME milestone performance (r = .13 and .17, respectively; p < .05) and MPA performance (r = .19 and .21, respectively; p < .05). In addition, the SJT predicted ACGME patient care, systems-based practice, practice-based learning and improvement, interpersonal and communication skills, and professionalism competencies (r = .16, .15, .15, .17, and .16, respectively; p < .05) 1 year later. The SJT score contributed incremental validity over USMLE scores in predicting overall ACGME milestone performance (ΔR = .07) 1 year later and MPA performance (ΔR = .05) 3 months later. Conclusions: SJTs show promise as a method for assessing noncognitive attributes in residency program applicants. The SJT's incremental validity to the USMLE series in this study underscores the importance of moving beyond these standardized tests to a more holistic review of candidates that includes both cognitive and noncognitive measures.

See No Evil, Hear No Evil, Stop No Evil: Institutional-Level Tracking to Combat Mistreatment of Residents and Fellows.

BACKGROUND: Mistreatment of trainees, including discrimination and harassment, is a problem in graduate medical education. Current tools to assess the prevalence of mistreatment often are not administered institutionally and may not account for multiple sources of mistreatment, limiting an institution's ability to respond and intervene. OBJECTIVE: We describe the utility of a brief questionnaire, embedded within longer institutional program evaluations, measuring the prevalence of different types of trainee mistreatment from multiple sources, including supervisors, team members, colleagues, and patients. METHODS: In 2018, we administered a modified version of the mistreatment questions in the Association of American Medical Colleges Graduation Questionnaire to investigate the prevalence and sources of mistreatment in graduating residents and fellows. We conducted analyses to determine the prevalence, types, and sources of mistreatment of trainees at the institutional level across graduate medical education programs. RESULTS: A total of 234 graduating trainees (77%) from the University of Minnesota-Twin Cities completed the questions. Patients were cited as the primary source of mistreatment in 5 of 6 categories, including both direct and indirect offensive remarks, microaggressions, sexual harassment, and physical threats (paired t test comparisons from t = 3.92 to t = 9.71, all P < .001). The only category of mistreatment in which patients were not the most significant source was humiliation and shaming. CONCLUSIONS: Six questions concerning types and sources of trainee mistreatment, embedded within an institutional survey, generated new information for institutional-, departmental- and program-based future interventions. Patients were the greatest source for all types of mistreatment except humiliation and shaming.

Predicting Performance of First-Year Residents: Correlations Between Structured Interview, Licensure Exam, and Competency Scores in a Multi-Institutional Study.

PURPOSE: To determine whether scores on structured interview (SI) questions designed to measure noncognitive competencies in physicians (1) predict subsequent first-year resident performance on Accreditation Council for Graduate Medical Education (ACGME) milestones and (2) add incremental validity over United States Medical Licensing Examination (USMLE) Step 1 and Step 2 Clinical Knowledge scores in predicting performance. METHOD: The authors developed 18 behavioral description questions to measure key noncognitive competencies (e.g., teamwork). In 2013-2015, 14 programs (13 residency, 1 fellowship) from 6 institutions used subsets of these questions in their selection processes. The authors conducted analyses to determine the validity of SI and USMLE scores in predicting first-year resident milestone performance in the ACGME's core competency domains and overall. RESULTS: SI scores predicted midyear and year-end overall performance (r = 0.18 and 0.19, respectively, P < .05) and year-end performance on patient care, interpersonal and communication skills, and professionalism competencies (r = 0.23, r = 0.22, and r = 0.20, respectively, P < .05). SI scores contributed incremental validity over USMLE scores in predicting year-end performance on patient care (ΔR = 0.05), interpersonal and communication skills (ΔR = 0.09), and professionalism (ΔR = 0.09; all P < .05). USMLE scores contributed incremental validity over SI scores in predicting year-end performance overall and on patient care and medical knowledge. CONCLUSIONS: SI scores predict first-year resident year-end performance in the interpersonal and communication skills, patient care, and professionalism competency domains. Future research should investigate whether SIs predict a range of clinically relevant outcomes.

Not all unprofessional behaviors are equal: The creation of a checklist of bad behaviors.

INTRODUCTION: Professionalism is a key component of medical education and training. However, there are few tools to aid educators in diagnosing unprofessional behavior at an early stage. The purpose of this study was to employ policy capturing methodology to develop two empirically validated checklists for identifying professionalism issues in early-career physicians. METHOD: In a series of workshops, a professionalism competency model containing 74 positive and 70 negative professionalism behaviors was developed and validated. Subsequently, 23 subject matter experts indicated their level of concern if each negative behavior occurred 1, 2, 3, 4, or 5 or more times during a six-month period. These ratings were used to create a "brief" and "extended" professionalism checklist for monitoring physician misconduct. RESULTS: This study confirmed the subjective impression that some unprofessional behaviors are more egregious than others. Fourteen negative behaviors (e.g. displaying obvious signs of substance abuse) were judged to be concerning if they occurred only once, whereas many others (e.g. arriving late for conferences) were judged to be concerning only when they occurred repeatedly. DISCUSSION: Medical educators can use the professionalism checklists developed in this study to aid in the early identification and subsequent remediation of unprofessional behavior in medical students and residents.

Racial/ethnic subgroup differences in cognitive ability test range restriction: implications for differential validity.

Recent meta-analyses demonstrated that the observed correlation between cognitive ability test scores and performance criteria was lower for Black and Hispanic subgroups than for Asian and White subgroups in college admissions, civilian employment, and military domains (i.e., differential validity). Given mean score differences between racial/ethnic subgroups, these observed validities may have been confounded by subgroup differences in range restriction. The present study draws on data from hundreds of cognitive ability test validity studies including more than 1 million persons to investigate whether Asian, Black, Hispanic, and White subgroups have differed in amounts of range restriction. We first replicated observed differential validity results and also extended them by presenting the first meta-analytic evidence that observed cognitive ability test validity is lower for the Hispanic subgroup in civilian employment settings. All subgroups were approximately equivalently restricted in range in college admissions and civilian employment domains, but the Black subgroup was more restricted in range than the White subgroup in military studies. In all 3 domains, any differences in range restriction could not account for observed validity differences between subgroups. We also provide estimates of range-restriction-corrected validities; Black and Hispanic subgroups' corrected validities were 11.3-18.0% lower than White corrected validities across domains.

Diagnosis of boundary-layer circulations.

Diagnoses of circulations in the vertical plane provide valuable insights into aspects of the dynamics of the climate system. Dynamical theories based on geostrophic balance have proved useful in deriving diagnostic equations for these circulations. For example, semi-geostrophic theory gives rise to the Sawyer-Eliassen equation (SEE) that predicts, among other things, circulations around mid-latitude fronts. A limitation of the SEE is the absence of a realistic boundary layer. However, the coupling provided by the boundary layer between the atmosphere and the surface is fundamental to the climate system. Here, we use a theory based on Ekman momentum balance to derive an SEE that includes a boundary layer (SEEBL). We consider a case study of a baroclinic low-level jet. The SEEBL solution shows significant benefits over Ekman pumping, including accommodating a boundary-layer depth that varies in space and structure, which accounts for buoyancy and momentum advection. The diagnosed low-level jet is stronger than that determined by Ekman balance. This is due to the inclusion of momentum advection. Momentum advection provides an additional mechanism for enhancement of the low-level jet that is distinct from inertial oscillations.

Mathematics applied to the climate system: outstanding challenges and recent progress.

The societal need for reliable climate predictions and a proper assessment of their uncertainties is pressing. Uncertainties arise not only from initial conditions and forcing scenarios, but also from model formulation. Here, we identify and document three broad classes of problems, each representing what we regard to be an outstanding challenge in the area of mathematics applied to the climate system. First, there is the problem of the development and evaluation of simple physically based models of the global climate. Second, there is the problem of the development and evaluation of the components of complex models such as general circulation models. Third, there is the problem of the development and evaluation of appropriate statistical frameworks. We discuss these problems in turn, emphasizing the recent progress made by the papers presented in this Theme Issue. Many pressing challenges in climate science require closer collaboration between climate scientists, mathematicians and statisticians. We hope the papers contained in this Theme Issue will act as inspiration for such collaborations and for setting future research directions.

Comparative assessment of life cycle assessment methods used for personal computers.

This article begins with a summary of findings from commonly cited life cycle assessments (LCA) of Information and Communication Technology (ICT) products. While differing conclusions regarding environmental impact are expected across product segments (mobile phones, personal computers, servers, etc.) significant variation and conflicting conclusions are observed even within product segments such as the desktop Personal Computer (PC). This lack of consistent conclusions and accurate data limits the effectiveness of LCA to influence policy and product design decisions. From 1997 to 2010, the majority of published studies focused on the PC concluded that the use phase contributes most to the life cycle energy demand of PC products with a handful of studies suggesting that manufacturing phase of the PC has the largest impact. The purpose of this article is to critically review these studies in order to analyze sources of uncertainty, including factors that extend beyond data quality to the models and assumptions used. These findings suggest existing methods to combine process-based LCA data with product price data and remaining value adjustments are not reliable in conducting life cycle assessments for PC products. Recommendations are provided to assist future LCA work.

The role of mutant UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetylgalactosaminyltransferase 3 in regulating serum intact fibroblast growth factor 23 and matrix extracellular phosphoglycoprotein in heritable tumoral calcinosis.

CONTEXT: Familial tumoral calcinosis (TC) results from disruptions in phosphate metabolism and is characterized by high serum phosphate with normal or elevated 1,25 dihydroxyvitamin vitamin D concentrations and ectopic and vascular calcifications. Recessive loss-of-function mutations in UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) and fibroblast growth factor-23 (FGF23) result in TC. OBJECTIVE: The objective of the study was to determine the relationship between GALNT3 and FGF23 in familial TC. DESIGN, SETTING, AND PATIENTS: We assessed the major biochemical defects and potential genes involved in patients with TC. INTERVENTION: Combination therapy consisted of the phosphate binder Sevelamer and the carbonic anhydrase inhibitor acetazolamide. RESULTS: We report a patient homozygous for a GALNT3 exon 1 deletion, which is predicted to truncate the encoded protein. This patient had high serum FGF23 concentrations when assessed with a C-terminal FGF23 ELISA but low-normal FGF23 levels when tested with an ELISA for intact FGF23 concentrations. Matrix extracellular phosphoglycoprotein has been identified as a possible regulator of phosphate homeostasis. Serum matrix extracellular phosphoglycoprotein levels, however, were normal in the family with GALNT3-TC and a kindred with TC carrying the FGF23 S71G mutation. The tumoral masses of the patient with GALNT3-TC completely resolved after combination therapy. CONCLUSIONS: Our findings demonstrate that GALNT3 inactivation in patients with TC leads to inadequate production of biologically active FGF23 as the most likely cause of the hyperphosphatemic phenotype. Furthermore, combination therapy may be effective for reducing the tumoral burden associated with familial TC.

High-resolution en-face visualization of the cardiomyocyte plasma membrane reveals distinctive distributions of spectrin and dystrophin.

The actin-binding proteins, spectrin and dystrophin, are key components of the plasma membrane-associated cytoskeleton of the cardiac muscle cell. From confocal immunofluorescence studies, the distribution of spectrin appears to overlap with that of dystrophin, but the precise functional differentiation, molecular distributions and spatial relationship of these two cytoskeletal systems remain unclear. Freeze-fracture replica immuno-electron microscopy, in parallel with immunofluorescence/confocal microscopy, were applied to examine at high resolution the spatial relationships between the spectrin and dystrophin membrane-associated cytoskeleton systems in cardiac muscle. Application of freeze-fracture replica cytochemistry, with single and double immunogold labeling, permitted simultaneous examination of the organization of spectrin and dystrophin in en-face views of the plasma membrane at high resolution. In contrast to the close spatial relationship previously demonstrated for dystrophin and beta-dystroglycan, no association between the gold label marking dystrophin and that marking spectrin was observed. Our freeze-fracture cytochemical results suggest that the two membrane skeletal networks formed by dystrophin and spectrin in cardiac muscle are independently organized, implying that whatever overlap of function (e.g., in structural support to the plasma membrane) may exist between them, the two systems may each have additional distinctive roles.