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Purpose: To evaluate the impact of a digital whiteboard system integrated with data from the oncology information system (OIS) on the urgency of physics quality assurance (QA) tasks in the radiation oncology department. Methods: Quality check list (QCL) items in the Mosaiq OIS corresponding to eight discrete, sequential steps in the treatment planning process were created. A whiteboard to graphically display active QCLs automatically and in real time was implemented in March 2020 using R shiny. QCL data with completion status were collected in two 12‐month time periods before and after whiteboard implementation: January 2019–December 2019 and July 2020–June 2021. For all plans requiring patient‐specific QA, we recorded when each plan was available for physics QA and which treatments started the following day. We further classified those plans into four categories (urgency levels 1–4 with 4 being the most urgent) depending on how much time was available to perform QA. We compared the proportion of these next‐day QAs in each category between time periods accounting for plan type, day of the week, and time of year. Results: Overall QA numbers were similar between time periods with 797 and 765 QAs total. The total proportion of next‐day QA decreased by 27% and the proportions of urgency levels 1 and 4 both showed significant decreases after whiteboard implementation of 29.2% and 54.9%, respectively (p<0.05$p<0.05$). All plan types had reduced proportions of next‐day QAs, especially nonstereotactic body radiation therapy (non‐SBRT) (30.3% decrease, p<0.05$p < 0.05$). Fridays and the months of October–December had the highest proportion of next‐day QAs but showed significant reductions of 19.1% and 40.6% in the proportion of next‐day QAs, respectively (p<0.05$p<0.05$). Conclusions: The integrated whiteboard system significantly reduced the proportion of last‐minute physics work, increasing patient safety. Advantages of the integrated whiteboard were low cost, low overhead with automatic interface to the OIS, and concurrent user support. [ABSTRACT FROM AUTHOR]

Introduction: A novel approach of in-advance preparatory respiratory training and practice for deep inspiration breath holding (DIBH) has been shown to further reduce cardiac dose in breast cancer radiotherapy patients, enabled by deeper (extended) DIBH. Here we investigated the consistency and stability of such training-induced extended DIBH after training completion and throughout the daily radiotherapy course.Methods: Daily chestwall motion from real-time surface tracking transponder data was analysed in 67 left breast radiotherapy patients treated in DIBH. Twenty-seven received preparatory DIBH training/practice (prep Trn) 1-2 weeks prior to CT simulation, resulting in an extended DIBH (ext DIBH) and reduced cardiac dose at simulation. Forty had only conventional immediate pre-procedure DIBH instruction without prep Trn and without extended DIBH (non-Trn group). Day-to-day variability in chestwall excursion pattern during radiotherapy was compared among the groups.Results: The average of daily maximum chestwall excursions was overall similar, 2.5 ± 0.6 mm for prep Trn/ext DIBH vs. 2.9 ± 0.8 mm for non-Trn patients (P = 0.24). Chestwall excursions beyond the 3-mm tolerance threshold were less common in the prep Trn/ext DIBH group (18.8% vs. 37.5% of all fractions within the respective groups, P = 0.038). Among patients with cardiopulmonary disease those with prep Trn/ext DIBH had fewer chestwall excursions beyond 3 mm (9.4% vs. 46.7%, P = 0.023) and smaller average maximum excursions than non-Trn patients (2.4 ± 0.3 vs. 3.0 ± 0.6 mm, P = 0.047, respectively).Conclusion: Similar stability of daily DIBH among patients with and without preparatory training/practice suggests that the training-induced extended DIBH and cardiac dose reductions were effectively sustained throughout the radiotherapy course. Training further reduced beyond-tolerance chestwall excursions, particularly in patients with cardiopulmonary disease. [ABSTRACT FROM AUTHOR]

The cell culture is the central piece of a biotechnological industrial process. It includes upstream (e.g. media preparation, fixed costs, etc.) and downstream steps (e.g. product purification, waste disposal, etc.). In the continuous mode of cell culture, a constant flow of fresh media replaces culture fluid until the system reaches a steady state. This steady state is the standard operation mode which, under very general conditions, is a function of the ratio between the cell density and the dilution rate and depends on the media supplied to the culture. To optimize the production process it is widely accepted that the concentration of the metabolites in this media should be carefully tuned. A poor media may not provide enough nutrients to the culture, while a media too rich in nutrients may be a waste of resources because, either the cells do not use all of the available nutrients, or worse, they over‐consume them producing toxic byproducts. In this study, we show how an in‐silico study of a genome scale metabolic network coupled to the dynamics of a chemostat could guide the strategy to optimize the media to be used in a continuous process. Given a known media we model the concentrations of the cells in a chemostat as a function of the dilution rate. Then, we cast the problem of optimizing the production process within a linear programming framework in which the goal is to minimize the cost of the media keeping fixed the cell concentration for a given dilution rate in the chemostat. We evaluate our results in two metabolic models: first a simplified model of mammalian cell metabolism, and then in a realistic genome‐scale metabolic network of mammalian cells, the Chinese hamster ovary cell line. We explore the latter in more detail given specific meaning to the predictions of the concentrations of several metabolites. [ABSTRACT FROM AUTHOR]

Activation of T cells triggers the expression of regulatory molecules like the programmed cell death 1 (PD1) protein. The association of PD1 with the natural ligands PDL1 and PDL2 induces an inhibitory signal that prevents T cells from proliferating and exerting effector functions. However, little is known about how the binding of the ligands induce the PD1 inhibitory signal over T cells effector functions. Here, we explore the dynamics of PD1 free, and in complex with different PDL1 variants as well as the therapeutic antibodies nivolumab and pembrolizumab in order to assess the conformational changes in PD1 related to the signaling process. Our simulations suggest a pre‐conformational selection mechanism for the binding of the different PDL1 variants, while an induced‐fit model fits better for the molecular recognition process of the therapeutic antibodies. A deep analysis of the changes on PD1 movement upon the binding to different ligands revealed that as larger is the difference in the conformation adopted by loop C′D with respect to the complex with PDL1 is higher the ligand ability to reduce the PD1 inhibitory signaling. This behavior suggests that targeting specific conformations of this loop can be useful for designing therapies able to recover T cells effector functions. [ABSTRACT FROM AUTHOR]

The recent explosion in machine learning efforts in the quality assurance (QA) space has produced a variety of proofs‐of‐concept many with promising results. Expected outcomes of model implementation include improvements in planning time, plan quality, advanced dosimetric QA, predictive machine maintenance, increased safety checks, and developments key for new QA paradigms driven by adaptive planning. In this article, we outline several areas of research and discuss some of the unique challenges each area presents. [ABSTRACT FROM AUTHOR]

Purpose: Surface‐guided radiation therapy (SGRT) is a nonionizing imaging approach for patient setup guidance, intra‐fraction monitoring, and automated breath‐hold gating of radiation treatments. SGRT employs the premise that the external patient surface correlates to the internal anatomy, to infer the treatment isocenter position at time of treatment delivery. Deformations and posture variations are known to impact the correlation between external and internal anatomy. However, the degree, magnitude, and algorithm dependence of this impact are not intuitive and currently no methods exist to assess this relationship. The primary aim of this work was to develop a framework to investigate and understand how a commercial optical surface imaging system (C‐RAD, Uppsala, Sweden), which uses a nonrigid registration algorithm, handles rotations and surface deformations. Methods: A workflow consisting of a female torso phantom and software‐introduced transformations to the corresponding digital reference surface was developed. To benchmark and validate the approach, known rigid translations and rotations were first applied. Relevant breast radiotherapy deformations related to breast size, hunching/arching back, distended/deflated abdomen, and an irregular surface to mimic a cover sheet over the lower part of the torso were investigated. The difference between rigid and deformed surfaces was evaluated as a function of isocenter location. Results: For all introduced rigid body transformations, C‐RAD computed isocenter shifts were determined within 1 mm and 1˚. Additional translational shifts to correct for rotations as a function of isocenter location were determined with the same accuracy. For yaw setup errors, the difference in shift corrections between a plan with an isocenter placed in the center of the breast (BrstIso) and one located 12 cm superiorly (SCFIso) was 2.3 mm/1˚ in lateral direction. Pitch setup errors resulted in a difference of 2.1 mm/1˚ in vertical direction. For some of the deformation scenarios, much larger differences up to 16 mm and 7˚ in the calculated shifts between BrstIso and SCFIso were observed that could lead to large unintended gaps or overlap between adjacent matched fields if uncorrected. Conclusions: The methodology developed lends itself well for quality assurance (QA) of SGRT systems. The deformable C‐RAD algorithm determined accurate shifts for rigid transformations, and this was independent of isocenter location. For surface deformations, the position of the isocenter had considerable impact on the registration result. It is recommended to avoid off‐axis isocenters during treatment planning to optimally utilize the capabilities of the deformable image registration algorithm, especially when multiple isocenters are used with fields that share a field edge. [ABSTRACT FROM AUTHOR]

Background: NeuroEPO (NeuralCIM®) is a variant of EPO, which contains low sialic acid. NeuralCIM® is devoid of hematopoietic effects and produces clinical benefits in subjects with mild‐to‐moderate Alzheimer's clinical syndrome. NeuralCIM® has received accelerated approval as a treatment for mild‐moderate AD, from the Cuban Regulatory Authority (CECMED). Method: NeuralCIM® 0.5 mg was evaluated in patients who, after completing the clinical trial, continued to be treated with the drug, whether they had been included in the NeuralCIM® or placebo arm during trial. They were compared with subjects who did not request to continue treatment or who never received it, because they were included in the placebo group during the clinical study. Result: After the clinical trial, the patients who continue to be treated with NeuralCIM® for two years from their inclusion in the clinical study, stabilized the disease. On the other hand, the subjects who did not continue the treatment with the drug, present a cognitive impairment characteristic of the progression of the disease. No serious adverse events related with NeuralCIM® were reported. Conclusion: NeuralCIM® treatment, stabilized the progression of AD clinical syndrome, during two years of treatment. [ABSTRACT FROM AUTHOR]

Purpose: The current process for radiotherapy treatment plan quality assurance relies on human inspection of treatment plans, which is time‐consuming, error prone and oft reliant on inconsistently applied professional judgments. A previous proof‐of‐principle paper describes the use of a Bayesian network (BN) to aid in this process. This work studied how such a BN could be expanded and trained to better represent clinical practice. Methods: We obtained 51 540 unique radiotherapy cases including diagnostic, prescription, plan/beam, and therapy setup factors from a de‐identified Elekta oncology information system from the years 2010–2017 from a single institution. Using a knowledge base derived from clinical experience, factors were coordinated into a 29‐node, 40‐edge BN representing dependencies among the variables. Conditional probabilities were machine learned using expectation maximization module using all data except a subset of 500 patient cases withheld for testing. Different classes of errors that were obtained from incident learning systems were introduced to the testing set of cases which were withheld from the dataset used for building the BN. Different sizes of datasets were used to train the network. In addition, the BN was trained using data from different length epochs as well as different eras. Its performance under these different conditions was evaluated by means of Areas Under the receiver operating characteristic Curve (AUC). Results: Our performance analysis found AUCs of 0.82, 0.85, 0.89, and 0.88 in networks trained with 2‐yr, 3‐yr 4‐yr and 5‐yr windows. With a 4‐yr sliding window, we found AUC reduction of 3% per year when moving the window back in time in 1‐yr steps. Compared to the 4‐yr window moved back by 4 yrs (2010–2013 vs 2014–2017), the largest component of overall reduction in AUC over time was from the loss of detection performance in plan/beam error types. Conclusions: The expanded BN method demonstrates the ability to detect classes of errors commonly encountered in radiotherapy planning. The results suggest that a 4‐yr training dataset optimizes the performance of the network in this institutional dataset, and that yearly updates are sufficient to capture the evolution of clinical practice and maintain fidelity. [ABSTRACT FROM AUTHOR]

Purpose: The review of a radiation therapy plan by a physicist prior to treatment is a standard tool for ensuring the quality of treatments. However, little is known about how well this task is performed in practice. The goal of this study is to present a novel method to measure the effectiveness of physics plan review by introducing simulated errors into computerized "mock" treatment charts and measuring the performance of plan review by physicists. Methods: We generated six simulated treatment charts containing multiple errors. To select errors, we compiled a list based on events from a departmental incident learning system and an international incident learning system (SAFRON). Seventeen errors with the highest scores for frequency and severity were included in the simulations included six mock treatment charts. Eight physicists reviewed the simulated charts as they would a normal pretreatment plan review, with each chart being reviewed by at least six physicists. There were 113 data points for evaluation. Observer bias was minimized using a simple error vs hidden error approach, using detectability scores for stratification. The confidence interval for the proportion of errors detected was computed using the Wilson score interval. Results: Simulated errors were detected in 67% of reviews [58–75%] (95% confidence interval [CI] in brackets). Of the errors included in the simulated plans, the following error scenarios had the highest detection rates: an incorrect isocenter in DRR (93% [70–99%]), a planned dose different from the prescribed dose (92% [67–99%]) and invalid QA (85% [58–96%]). Errors with low detection rates included incorrect CT dataset (0%, [0–39%]) and incorrect isocenter localization in planning system (38% [18–64%]). Detection rates of errors from simulated charts were compared against observed detection rates of errors from a departmental incident learning system. Conclusions: It has been notoriously difficult to quantify error and safety performance in oncology. This study uses a novel technique of simulated errors to quantify performance and suggests that the pretreatment physics plan review identifies some errors with high fidelity while other errors are more challenging to detect. These data will guide future work on standardization and automation. The example process studied here was physics plan review, but this approach of simulated errors may be applied in other contexts as well and may also be useful for training and education purposes. [ABSTRACT FROM AUTHOR]

Purpose Bayesian networks ( BNs) are graphical representations of probabilistic knowledge that offer normative reasoning under uncertainty and are well suited for use in medical domains. Traditional knowledge-based network development of BN topology requires that modeling experts establish relevant dependency links between domain concepts by searching and translating published literature, querying domain experts, or applying machine learning algorithms on data. For initial development these methods are time-intensive and this cost hinders the growth of BN applications in medical decision making. Further, this approach fails to utilize knowledge representation in medical fields to automate network development. Our research alleviates the challenges surrounding BN modeling in radiation oncology by leveraging an ontology based hub and spoke system for BN construction. Methods We implement a hub and spoke system by developing (a) an ontology of knowledge in radiation oncology (the hub) which includes dependency semantics similar to BN relations and (b) a software tool that operates on ontological semantics using deductive reasoning to create BN topologies (the spokes). We demonstrate that network topologies built using the software are terminologically consistent and form networks that are topologically compatible with existing ones. We do this first by merging two different BN models for prostate cancer radiotherapy prediction which contain domain cross terms. We then use the logic to perform discovery of new causal chains between radiation oncology concepts. Results From the radiation oncology ( RO) ontology we successfully reconstructed a previously published prostate cancer radiotherapy Bayes net using up-to-date domain knowledge. Merging this model with another similar prostate cancer model in the RO domain produced a larger, highly interconnected model representing the expanded scope of knowledge available regarding prostate cancer therapy parameters, complications, and outcomes. The causal discovery resulted in an automatically-built causal network model of all ontologized radiotherapy concepts between a 'Mucositis' complication and anatomic tumor location. Conclusions The proposed model building approach lowers barriers to developing probabilistic models relevant to real-world clinical decision making, and offers a solution to the consistency and compatibility problems. Further, the knowledge representation in this work demonstrates potential for broader radiation oncology applications outside of Bayes nets. [ABSTRACT FROM AUTHOR]

This study examined the direct and indirect effects of medical clerkship students' prior knowledge, self-regulation and motivation on learning performance in complex multimedia learning environments. The data from 386 medical clerkship students from six medical schools were analysed using structural equation modeling. The structural model revealed that medical students' prior knowledge directly positively affected their learning outcome, selfefficacy and performance approach goal orientation. The learners' self-regulation had a significant positive direct effect on learning outcome. The learners' mastery goal orientation directly affected their learning outcome. Interestingly, inconsistent with our hypothesis, the learners' performance approach goal orientation showed a significant negative direct effect on learning outcome, and performance avoidance goal orientation had a significant positive effect on learning outcome. These findings help develop a more comprehensive understanding of the role of individual characteristics on learning performance of complex tasks in multimedia learning environments. [ABSTRACT FROM AUTHOR]

Purpose: Complex treatments in radiation therapy require robust verification in order to prevent errors that can adversely affect the patient. For this purpose, the authors estimate the effectiveness of detecting errors with a "defense in depth" system composed of electronic portal imaging device (EPID) based dosimetry and a software-based system composed of rules-based and Bayesian network verifications. Methods: The authors analyzed incidents with a high potential severity score, scored as a 3 or 4 on a 4 point scale, recorded in an in-house voluntary incident reporting system, collected from February 2012 to August 2014. The incidents were categorized into different failure modes. The detectability, defined as the number of incidents that are detectable divided total number of incidents, was calculated for each failure mode. Results: In total, 343 incidents were used in this study. Of the incidents 67% were related to photon external beam therapy (EBRT). The majority of the EBRT incidents were related to patient positioning and only a small number of these could be detected by EPID dosimetry when performed prior to treatment (6%). A large fraction could be detected by in vivo dosimetry performed during the first fraction (74%). Rules-based and Bayesian network verifications were found to be complimentary to EPID dosimetry, able to detect errors related to patient prescriptions and documentation, and errors unrelated to photon EBRT. Combining all of the verification steps together, 91% of all EBRT incidents could be detected. Conclusions: This study shows that the defense in depth system is potentially able to detect a large majority of incidents. The most effective EPID-based dosimetry verification is in vivo measurements during the first fraction and is complemented by rules-based and Bayesian network plan checking. [ABSTRACT FROM AUTHOR]

A mutein with stronger antitumor activity and lower toxicity than wild-type human interleukin-2 (IL-2) has been recently described. The rationale behind its design was to reinforce the immunostimulatory potential through the introduction of four mutations that would selectively disrupt the interaction with the IL-2 receptor alpha chain (thought to be critical for both IL-2-driven expansion of T regulatory cells and IL-2-mediated toxic effects). Despite the successful results of the mutein in several tumor models, characterization of its interactions was still to be performed. The current work, based on phage display of IL-2-derived variants, showed the individual contribution of each mutation to the impairment of alpha chain binding. A more sensitive assay, based on the ability of phage-displayed IL-2 variants to induce proliferation of the IL-2-dependent CTLL-2 cell line, revealed differences between the mutated variants. The results validated the mutein design, highlighting the importance of the combined effects of the four mutations. The developed phage display-based platform is robust and sensitive, allows a fast comparative evaluation of multiple variants, and could be broadly used to engineer IL-2 and related cytokines, accelerating the development of cytokine-derived therapeutics. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives Most medical procedures have a time element. It is uncommon, however, to explicitly use chronometry, the measurement of time, in the learning of these procedures. This study considered whether instructional designs that include chronometry could improve deliberate practice and be used in meaningful formative assessments. Methods A selective review of the medical education literature was undertaken to identify how chronometry was used in a broad sampling of medical education research in the learning of medical procedures. We identified prior publications in which time measurement was used either directly as a pedagogic intervention or as an assessment method in a medical school programme. Results Our review suggests a number of desirable features of chronometry. For the individual learner, procedural time measurements can demonstrate both improving ability and increasing consistency. Chronometry can enhance instructional designs involving deliberate practice by facilitating overlearning (i.e. learning that goes beyond minimum competence), increasing the challenge level and enhancing self-regulation of learning (e.g. self-competition). Breaking down chronometric data into meaningful interval or split times might further inform instructional designs. Conclusions Chronometry has the potential to contribute to instructional designs and assessment methods in medical procedures training. However, more research is needed to elucidate its full potential and describe possible negative consequences of this widely available but underutilised educational tool. [ABSTRACT FROM AUTHOR]

Context Conducting research in real life settings (effectiveness studies) can introduce many confounding factors. Efficacy studies seek to control for researcher bias and data quality rather than considering how the efficacy of an intervention is changed by the contexts in which it is used. Relatively little is known about the impact of context on educational interventions, in particular on multimedia learning. Methods An effectiveness study to understand implementation variance of online educational modules in surgery clerkships was conducted in six US medical schools participating in an efficacy trial of different multimedia designs. Student and teacher experiences were captured through focus groups and one-to-one interviews with trial participants and their teachers. Audio-recordings of these sessions were transcribed and analysed using grounded theory techniques. Results Differences were identified in student and teacher perceptions of how the educational intervention had been implemented and how its uptake had been influenced by context-dependent factors: (i) the intervention was implemented in different ways to suit different educational contexts and this influenced how students and teachers responded to it; (ii) the ways students and teachers interacted with, and behaved around, the intervention influenced its uptake; (iii) the way the intervention was perceived by students and teachers influenced its uptake; and (iv) the medium and design of the intervention had a directing influence on its uptake. Conclusions It was observed that each institutional context formed a complex educational ecology. The intervention became interwoven with different educational ecologies so that it could no longer be considered a stable variable across the study. We suggest that researchers should conduct implementation-profiling studies in advance of any intervention-based research to account for the constructing nature of educational ecologies on their interventions and in doing so to more clearly differentiate between efficacy and effectiveness studies. [ABSTRACT FROM AUTHOR]

Objective: It is unclear whether training physicians to counsel obese patients leads to weight loss. This study assessed whether a 5-h multimodal longitudinal obesity curriculum for residents on the basis of the 5As (assess, advise, agree, assist, and arrange) was associated with weight loss in their obese patients. Design and Methods: Twenty-three primary care internal medicine residents were assigned by rotation schedule to intervention (curriculum) or control groups. We then conducted follow-up chart reviews to determine weight change at up to 12 months following the index visit. 158 obese patients (76 in the intervention group and 82 in the control group) completed exit interviews; 22 patients who presented for acute care at the index visit were excluded. Chart reviews were conducted on the 46 patients in the intervention group and 41 patients in the control group who were seen again within 12 months of the index visit and had follow-up weight measurements. Results: The main outcome of interest was mean change in weight at 12 months compared between the intervention and control groups. Patients of residents in the intervention group had a mean weight loss of −1.53 kg (s.d. = 3.72) although the patients of those in the control group had a mean weight gain of 0.30 kg (s.d. = 3.60), P = 0.03. Six (15.8%) patients in the intervention group and 2 (5.4%) patients in the control group lost >5% body weight ( P = 0.14). Conclusions: Although the magnitude of weight loss was small, this study shows that training physicians to counsel patients can produce measurable patient outcomes. [ABSTRACT FROM AUTHOR]

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Objectives: The authors piloted unannounced standardized patients (USPs) in an emergency medicine (EM) residency to test feasibility, acceptability, and performance assessment of professionalism and communication skills. Methods: Fifteen postgraduate year (PGY)-2 EM residents were scheduled to be visited by two USPs while working in the emergency department (ED). Multidisciplinary support was utilized to ensure successful USP introduction. Scores (% well done) were calculated for communication and professionalism skills using a 26-item, behaviorally anchored checklist. Residents’ attitudes toward USPs and USP detection were also surveyed. Results: Of 27 USP encounters attempted, 17 (62%) were successfully completed. The detection rate was 44%. Eighty-three percent of residents who encountered a USP felt that the encounter did not hinder daily practice and did not make them uncomfortable (86%) or suspicious of patients (71%). Overall, residents received a mean score of 60% for communication items rated “well done” (SD ± 28%, range = 23%–100%) and 53% of professionalism items “well done” (SD ± 20%, range = 23%-85%). Residents’ communication skills were weakest for patient education and counseling (mean = 43%, SD ± 31%), compared with information gathering (68%, SD ± 36% and relationship development (62%, SD ± 32%). Scores of residents who detected USPs did not differ from those who had not. Conclusions: Implementing USPs in the ED is feasible and acceptable to staff. The unpredictability of the ED, specifically resident schedules, accounted for most incomplete encounters. USPs may represent a new way to assess real-time resident physician performance without the need for faculty resources or the bias introduced by direct observation. [ABSTRACT FROM AUTHOR]

Regulatory CD4+ T cells, enriched in the CD25 pool of healthy individuals, mediate natural tolerance and prevent autoimmune diseases. Despite their fundamental and potential clinical significance, regulatory T (TR) cells have not yet been incorporated in a coherent theory of the immune system. This article reviews experimental evidence and theoretical arguments supporting a model of TR cell dynamics, uncovering some of its most relevant biological implications. According to this model, the persistence and expansion of TR cell populations depend strictly on specific interactions they make with antigen-presenting cells (APCs) and conventional effector T (TE) cells. This three-partner crossregulation imposes that TR cells feed on the specific autoimmune activities they suppress, with implications ranging from their interactions with other cells to their repertoire selection in the periphery and in the thymus, and to the relationship between these cells and the innate immune system. These implications stem from the basic prediction that the peripheral dynamics sort the CD4+ T-cell repertoire into two subsets: a less diverse set of small clones of autoreactive effector and regulatory cells that regulate each other’s growth, and a more diverse set of barely autoreactive TE cell clones, whose expansion is limited only by APC availability. It is argued that such partitioning of the repertoire sets the ground for self–non-self discrimination. [ABSTRACT FROM AUTHOR]

Background The human haptoglobin ( Hp) gene is polymorphic with two functional classes of alleles, denoted 1 and 2. We have demonstrated in three longitudinal studies and several cross-sectional studies that the Hp genotype is an independent risk factor for diabetic vascular disease. These studies have presented a compelling argument that diabetic individuals homozygous for the Hp 1 allele are at decreased risk of vascular complications as compared to diabetic individuals with the Hp 2 allele. Methods The naturally occurring (wild type) mouse Hp is a class 1 Hp allele. We examined renal hypertrophy in wild-type mice, Hp knockout mice (Hp 0), and in mice with the Hp 2 allele (Hp 2) with and without diabetes. Results In the absence of diabetes, we found that renal hypertrophy was significantly increased in Hp 0 mice and that this could be prevented with vitamin E. There was no difference between wild type and Hp 2 mice with regard to renal hypertrophy in the absence of diabetes. However, in the presence of diabetes, Hp 2 mice demonstrated a significant increase in renal hypertrophy as compared to wild-type mice. Conclusions These results support a direct linkage between diabetic vascular disease and the Hp genotype. These Hp-modified mice may serve as a platform on which to test a variety of pharmacological agents in order to decrease diabetic vascular disease. Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

An abstract of the article "Towards entrusting medical students: recognising safety behaviours," by Grace Ng and colleagues is presented.

Cites a study on the benefits of utilizing an Internet-based classroom in the teaching forums of traditional clinical clerkships, including small group teaching seminars. Enhancement of clinical reasoning; Collaboration of medical students with faculty facilitation in addressing certain issues; Progression from faculty-centered to student-centered discussions.

Reports on the implementation of a redesigned core surgery clerkship to address the educational deficiencies created by the rapidly changing training environment in the U.S. Confusion of medical students regarding their goals and roles; Views of faculty members on students as poorly motivated; Replacement by lectures by asynchronous, Web-based multimedia learning modules.

Reports on the growing array of constraints faced by teaching in the surgical clerkship as the breadth and depth of students' education is fragmented by changes in patient and doctor exposure in the U.S. Improvements in the teaching of clinical reasoning skills; Increase in student comfort and participation in the operating rooms; Advantages offered by the development of the Surgical Interactive Multimedia Modules.

An abstract of the study "Attracting Health Professional Students to Substance Abuse Research," by Adina Kalet, Colleen Gillespie, Madeline A. Naegle, and Frederick More is presented.

Informs that at New York University School of Medicine the Professionalism Committee was formed in response to dissatisfaction on part of both administration and students with the lack of clarity about expectations of medical students' standards of professionalism. Members of the committee; Approach of the committee during the orientation week; Preparation of case studies on unprofessional behavior.