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Results from the fully and biogeochemically coupled simulations in which CO2 increases at a rate of 1%yr-1 (1pctCO2) from its preindustrial value are analyzed to quantify the magnitude of carbon-concentration and carbon-climate feedback parameters which measure the response of ocean and terrestrial carbon pools to changes in atmospheric CO2 concentration and the resulting change in global climate, respectively. The results are based on 11 comprehensive Earth system models from the most recent uncertain over land than over ocean as has been seen in existing studies. These values and their spread from 11 CMIP6 models have not changed significantly compared to CMIP5 models. The absolute values of feedback parameters are lower for land with models that include a representation of nitrogen cycle. The transient climate response to cumulative emissions (TCRE) from the 11 CMIP6 models considered here is 1.77±0.37 ° C EgC-1 and is similar to that found in CMIP5 models (1.63±0.48 °C EgC-1) but with somewhat reduced model spread. The expressions for feedback parameters based on the fully and biogeochemically coupled configurations of the 1pctCO2 simulation are simplified when the small temperature change in the biogeochemically coupled simulation is ignored. Decomposition of the terms of these simplified expressions for the feedback parameters is used to gain insight into the reasons for differing responses among ocean and land carbon cycle models.

BACKGROUND: Working knowledge of physicians manifests as a combination of diagnostic pattern recognition and clinical data interpretation (analytic fact checking). PURPOSE: The purpose was to study medical student acquisition of these abilities as a function of years of medical training/experience. METHODS: A cross-sectional study involving students who had completed 0, 1, 2, and 3 years of medical school. All students at all levels of training took the same tests of diagnostic pattern recognition and clinical data interpretation. Percent correct scores were calculated and used to estimate learning curves. A cohort of family physicians also took the test to provide a benchmark. RESULTS: Student diagnostic pattern recognition and clinical data interpretation ability demonstrated a steady upward growth curve but leveled off in Year 3. Diagnostic pattern recognition performance was consistently higher than clinical data interpretation performance. The rate of diagnostic performance gain with training and experience was also higher. CONCLUSIONS: Medical students acquired diagnostic pattern recognition ability and all years of medical training contributed. The rate of clinical data interpretation performance improvement was slower, and the absolute performance level was lower. What was surprising was the lower rate of improvement in diagnostic pattern recognition and clinical data interpretation performance for students during their 1st year of clinical training. Students' understanding of findings and their relationships to disease processes may be affected by their limited patient experience. [ABSTRACT FROM AUTHOR]

This paper explores the core teaching beliefs of medical school faculty and establishes whether these beliefs differ among basic science, clinical, and instruction specialist faculty. One hundred and twenty-five medical school teachers who were members of professional organizations dedicated to the improvement of medical school teaching completed a Q-sort of 56 statements reflecting their core teaching beliefs. The statements described beliefs about motivation, knowledge and skill acquisition, retention, feedback, transfer, teacher characteristics, and teaching strategies. Q-sorts were completed by 37 basic scientists (30% of respondents), 59 clinicians (47%) and 29 instruction specialists (23%) working in medical schools. Fifty-two participants were classroom teachers (42%), 66 were classroom and clinical teachers (53%), and seven reported that they do not teach (6%). The Q-sort results indicate how medical school faculty members differ in their core beliefs about teaching and learning. Thirty-two respondents (26%) focused on the student as a person first. Eight (6%) were content oriented. Thirty-four (27%) were performance oriented; their focus was on having students learn and apply knowledge and skills to accomplish clinical tasks. Fifty-one respondents (41%) were found to have a blend of these viewpoints. Respondents' type of training or type of teaching did not provide a reliable indication of core teaching beliefs classification. [ABSTRACT FROM AUTHOR]

BACKGROUND: Global ratings based on observing convenience samples of clinical performance form the primary basis for appraising the clinical competence of medical students, residents, and practicing physicians. This review explores cognitive, social, and environmental factors that contribute unwanted sources of score variation (bias) to clinical performance evaluations. SUMMARY: Raters have a 1 or 2-dimensional conception of clinical performance and do not recall details. Good news is reported more quickly and fully than bad news, leading to overly generous performance evaluations. Training has little impact on accuracy and reproducibility of clinical performance ratings. CONCLUSIONS: Clinical performance evaluation systems should assure broad, systematic sampling of clinical situations; keep rating instruments short; encourage immediate feedback for teaching and learning purposes; encourage maintenance of written performance notes to support delayed clinical performance ratings; give raters feedback about their ratings; supplement formal with unobtrusive observation; make promotion decisions via group review; supplement traditional observation with other clinical skills measures (e.g., Objective Structured Clinical Examination); encourage rating of specific performances rather than global ratings; and establish the meaning of ratings in the manner used to set normal limits for clinical diagnostic investigations. [ABSTRACT FROM AUTHOR]

When you hear a murmur in a young patient, retrace your steps. A careful history review and physical examination can distinguish most innocent murmurs from those that need further investigation. [ABSTRACT FROM AUTHOR]

A child with a long standing history of cyanotic breath holding attacks presented with acute respiratory distress. Subsequent investigation established that her clinical condition was caused by tracheomalacia. We hypothesise that tracheomalacia might be an under recognised contributor to cyanotic breath holding attacks, the pathogenesis of which is poorly understood. [ABSTRACT FROM AUTHOR]

The maintenance of antigen-specific CD8 + T cells underlies the efficacy of vaccines and immunotherapies. Pathways contributing to CD8 + T cell loss are not completely understood. Uncovering the pathways underlying the limited persistence of CD8 + T cells would be of significant benefit for developing novel strategies of promoting T cell persistence. Here, we demonstrate that murine CD8 + T cells experience endoplasmic reticulum (ER) stress following activation and that the ER-associated degradation (ERAD) adapter Sel1L is induced in activated CD8 + T cells. Sel1L loss limits CD8 + T cell function and memory formation following acute viral infection. Mechanistically, Sel1L is required for optimal bioenergetics and c-Myc expression. Finally, we demonstrate that human CD8 + T cells experience ER stress upon activation and that ER stress is negatively associated with improved T cell functionality in T cell-redirecting therapies. Together, these results demonstrate that ER stress and ERAD are important regulators of T cell function and persistence., Competing Interests: Declaration of interests In the past three years, C.A.L. has consulted for Astellas Pharmaceuticals, Odyssey Therapeutics, Third Rock Ventures, and T-Knife Therapeutics and is an inventor on patents pertaining to Kras-regulated metabolic pathways, redox control pathways in pancreatic cancer, and therapeutically targeting the GOT1-ME1 pathway (US Patent no. 2015126580-A1, 05/07/2015; US Patent no. 20190136238, 05/09/2019; International Patent no. WO2013177426-A2, 04/23/2015)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Despite advances in systemic care, diabetic disease of the eye (DDE) remains the leading cause of blindness worldwide. There is a critical gap of up-to-date, evidence-based guidance for ophthalmologists in Canada that includes evidence from recent randomized controlled trials. Previous guidance has not always given special consideration to applying treatments and managing DDE in the context of the healthcare system. This consensus statement aims to assist practitioners in the field by providing a spectrum of acceptable opinions on DDE treatment and management from recognized experts in the field. In compiling evidence and generating consensus, a working group of retinal specialists in Canada addressed clinical questions surrounding the four themes of disease, patient, management, and collaboration. The working group reviewed literature representing the highest level of evidence on DDE and shared their opinions on topics surrounding the epidemiology and pathophysiology of diabetic retinopathy and diabetic macular edema; diagnosis and monitoring; considerations around diabetes medication use; strategic considerations for management given systemic comorbidities, ocular comorbidities, and pregnancy; treatment goals and modalities for diabetic macular edema, non-proliferative and proliferative diabetic retinopathy, and retinal detachment; and interdisciplinary collaboration. Ultimately, this work highlighted that the retinal examination in DDE not only informs the treating ophthalmologist but can serve as a global index for disease progression across many tissues of the body. It highlighted further that DDE can be treated regardless of diabetic control, that a systemic approach to patient care will result in the best health outcomes, and prevention of visual complications requires a multidisciplinary management approach. Ophthalmologists must tailor their clinical approach to the needs and circumstances of individual patients and work within the realities of their healthcare setting., (© 2024. The Author(s).)

The effect of the Southern Ocean on global climate change is assessed using Earth system model projections following an idealized 1% annual rise in atmospheric CO 2 . For this scenario, the Southern Ocean plays a significant role in sequestering heat and anthropogenic carbon, accounting for 40% ± 5% of heat uptake and 44% ± 2% of anthropogenic carbon uptake over the global ocean (with the Southern Ocean defined as south of 36°S). This Southern Ocean fraction of global heat uptake is however less than in historical scenarios with marked hemispheric contrasts in radiative forcing. For this idealized scenario, inter-model differences in global and Southern Ocean heat uptake are strongly affected by physical feedbacks, especially cloud feedbacks over the globe and surface albedo feedbacks from sea-ice loss in high latitudes, through the top-of-the-atmosphere energy balance. The ocean carbon response is similar in most models with carbon storage increasing from rising atmospheric CO 2 , but weakly decreasing from climate change with competing ventilation and biological contributions over the Southern Ocean. The Southern Ocean affects a global climate metric, the transient climate response to emissions, accounting for 28% of its thermal contribution through its physical climate feedbacks and heat uptake, and so affects inter-model differences in meeting warming targets. This article is part of a discussion meeting issue 'Heat and carbon uptake in the Southern Ocean: the state of the art and future priorities'.

The climate feedback determines how Earth's climate responds to anthropogenic forcing. It is thought to have been more negative in recent decades due to a sea surface temperature "pattern effect," whereby warming is concentrated in the western tropical Pacific, where nonlocal radiative feedbacks are very negative. This phenomenon has however primarily been studied within climate models. We diagnose a pattern effect from historical records as an evolution of the climate feedback over the past five decades. Our analysis assumes a constant rate of change of the climate feedback, which is justified post hoc. We find a decrease in climate feedback by 0.8 ± 0.5 W m -2 K -1 over the past 50 years, corresponding to a reduction in climate sensitivity. Earth system models' climate feedbacks instead increase over this period. Understanding and simulating this historical trend and its future evolution are critical for reliable climate projections.

Optical coherence tomography of the eye suggests the retina thins in normal pregnancy. Our objectives were to confirm and extend these observations to women with hypertensive disorders of pregnancy (HDP). Maternal demographics, clinical/laboratory findings and measurements of macular thickness were repeatedly collected at gestational ages <20 weeks, 20-weeks to delivery, at delivery and postpartum. The primary outcome was the change in macular thickness from non-pregnant dimensions in women with incident HDP compared to non-hypertensive pregnant controls. Secondary outcomes were the relationship(s) between mean arterial pressure (MAP) and macular response. Data show macular thicknesses diminished at <20 weeks gestation in each of 27 pregnancies ending in HDP (mean 3.94 µm; 95% CI 4.66, 3.21) and 11 controls (mean 3.92 µm; 5.05, 2.79; P < 0.001 versus non-pregnant dimensions in both; P = 0.983 HDP versus controls). This thinning response continued to delivery in all controls and in 7 women with HDP superimposed on chronic hypertension. Macular thinning was lost after 20 weeks gestation in the other 20 women with HDP. MAP at loss of macular thinning in women without prior hypertension (n = 12) was identical to MAP at enrollment. However, mean MAP subsequently rose 19 mmHg (15, 22) leading to de novo HDP in all 12 women. Loss of thinning leading to a rise in MAP was also observed in 8 of 15 women with HDP superimposed on chronic hypertension. We conclude the macula thins in most women in early pregnancy. Those who lose this early macular thinning response often develop blood pressure elevations leading to HDP., (© 2021. The Author(s).)

The expansive gyres of the subtropical ocean account for a significant fraction of global organic carbon export from the upper ocean. In the gyre interior, vertical mixing and the heaving of nutrient-rich waters into the euphotic layer sustain local productivity, in turn depleting the layers below. However, the nutrient pathways by which these subeuphotic layers are themselves replenished remain unclear. Using a global, eddy-permitting simulation of ocean physics and biogeochemistry, we quantify nutrient resupply mechanisms along and across density surfaces, including the contribution of eddy-scale motions that are challenging to observe. We find that mesoscale eddies (10 to 100 km) flux nutrients from the shallow flanks of the gyre into the recirculating interior, through time-varying motions along density surfaces. The subeuphotic layers are ultimately replenished in approximately equal contributions by this mesoscale eddy transport and the remineralization of sinking particles. The mesoscale eddy resupply is most important in the lower thermocline for the whole subtropical region but is dominant at all depths within the gyre interior. Subtropical gyre productivity may therefore be sustained by a nutrient relay, where the lateral transport resupplies nutrients to the thermocline and allows vertical exchanges to maintain surface biological production and carbon export.

Studies of instrumental responding often include the delivery of a cue that is coincident with the delivery of the reinforcer. One purpose of this is for the cue to be removed during extinction and then presented later to assess whether responding returns (cue-induced reinstatement). In two experiments, we examined the effects of having a cue associated with reinforcement present or absent during extinction. In Experiment 1, the cue was associated with fixed ratio responding for intravenous cocaine or food pellets in one context (Context A), followed by extinction in another context (Context B), where responding produced the cue in one group but did not produce the cue in the other group. Afterward, contextual renewal was assessed with and without the cue in Context A. During extinction, a cue previously associated with cocaine reinforcement caused an increase in responding initially (an extinction burst) and throughout 16 2-hr extinction sessions, as well as weakened contextual renewal when animals were tested with the cue in Context A. In contrast, there were few detectable effects of the cue on extinction and contextual renewal when food pellets were the reinforcer. In Experiment 2, effects of a cue during extinction of progressive ratio responding were revealed with food pellets when animals showed weakened responding on the initial trials of postextinction reacquisition sessions. These experiments demonstrate that the presence of a cue associated with reinforcement during extinction may prolong responding in the short term while creating a more persistent form of extinction that resists relapse. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The actions of corticotropin-releasing factor (CRF) in the core of the nucleus accumbens including increasing dopamine release and inducing conditioned place preference in stress-naïve animals. However, following two-day, repeated forced swim stress (rFSS), neither of these effects are present, indicating a stress-sensitive interaction between CRF and dopamine. To ascertain the degree to which this mechanism influences integrated, reward-based decision making, we used an operant concurrent-choice task where mice could choose between two liquid receptacles containing a sucrose solution or water delivery. Following initial training, either a CRF or dopamine antagonist, α-helical CRF (9-41) and flupenthixol, respectively, or vehicle was administered intracranially to the nucleus accumbens core. Next, the animals underwent rFSS, were reintroduced to the task, and were retested. Prior to stress, mice exhibited a significant preference for sucrose over water and made more total nose pokes into the sucrose receptacle than the water receptacle throughout the session. There were no observed sex differences. Stress did not robustly affect preference metrics but did increase the number of trial omissions compared to their stress-naïve, time-matched counterparts. Interestingly, flupenthixol administration did not affect sucrose choice but increased their nosepoke preference during the inter-trial interval, increased trial omissions, and decreased the total nosepokes during the ITI. In contrast, microinjections of α-helical CRF (9-41) did not affect omissions or ITI nosepokes but produced interactions with stress on choice metrics. These data indicate that dopamine and CRF both interact with stress to impact performance in the task but influence different behavioral aspects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Williams, Li and Phillips.)

Objective: The aim of this study was to propose an evidence-based blueprint for training, assessment, and certification of operative performance for surgical trainees., Summary Background Data: Operative skill is a critical aspect of surgical performance. High-quality assessment of operative skill therefore has profound implications for training, accreditation, certification, and the public trust of the profession. Current methods of operative skill assessment for surgeons rely heavily on global assessment strategies across a very broad domain of procedures. There is no mechanism to assure technical competence for individual procedures. The science and scalability of operative skill assessment has progressed significantly in recent decades, and can inform a much more meaningful strategy for competency-based assessment of operative skill than has been previously achieved., Methods: The present article reviews the current status and science of operative skill assessment and proposes a template for competency-based assessment which could be used to update training, accreditation, and certification processes. The proposal is made in reference to general surgery but is more generally applicable to other procedural specialties., Results: Streamlined, routine assessment of every procedure performed by surgical trainees is feasible and would enable a more competency-based educational paradigm. In light of the constraints imposed by both clinical volume and assessment bias, trainees should be expected to become proficient and be measured against a mastery learning standard only for the most important and highest-frequency procedures. For less frequently observed procedures, performance can be compared to a norm-referenced standard and, to provide an overall trajectory of performance, analyzed in aggregate. Key factors in implementing this approach are the number of evaluations, the number of raters, the timeliness of evaluation, and evaluation items., Conclusions: A competency-based operative skill assessment can be incorporated into surgical training, assessment, and certification. The time has come to develop a systematic approach to this issue as a means of demonstrating professional standards worthy of the public trust., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Our aim was to determine if end-stage liver disease (ESLD) is associated with an attenuated response to vasodilator-stress or dobutamine-stress using 82 Rb-PET MPI with blood flow quantification., Methods and Results: Pre-liver transplant patients who had a normal dipyridamole-stress (n = 27) or dobutamine-stress (n = 26) 82 Rb PET/CT MPI study with no identifiable coronary artery calcium were identified retrospectively and compared to a prospectively identified low-risk of liver disease dipyridamole-stress control group (n = 20). The dipyridamole-stress liver disease group had a lower myocardial flow reserve (MFR) (1.89 ± 0.79) than the control group (2.79 ± 0.96, P < .05). The dobutamine-stress group had a higher MFR than both other groups (3.69 ± 1.49, P < .05). A moderate negative correlation between MELD score and MFR was demonstrated for the dipyridamole-stress liver disease group (r = - 0.473, P < .05). This correlation was not observed for the dobutamine-stress liver disease group (r = - 0.253, P = .21). The liver failure group as a whole (n = 53) had a higher resting myocardial blood flow (0.97 ± 0.33 mL/min/g) than the control group (0.82 ± 0.26, P < .05)., Conclusion: Dipyridamole demonstrates an attenuated vasodilatory response in ESLD patients compared to a non-ESLD control group related to higher resting blood flow and comparatively reduced stress blood flow. Dobutamine does not demonstrate this effect implying it may be the preferred pharmacologic MPI stress agent for ESLD patients.