Security and Privacy in Machine Learning for Health Systems: Strategies and Challenges.

OBJECTIVES: Machine learning (ML) is a powerful asset to support physicians in decision-making procedures, providing timely answers. However, ML for health systems can suffer from security attacks and privacy violations. This paper investigates studies of security and privacy in ML for health. METHODS: We examine attacks, defenses, and privacy-preserving strategies, discussing their challenges. We conducted the following research protocol: starting a manual search, defining the search string, removing duplicated papers, filtering papers by title and abstract, then their full texts, and analyzing their contributions, including strategies and challenges. Finally, we collected and discussed 40 papers on attacks, defense, and privacy. RESULTS: Our findings identified the most employed strategies for each domain. We found trends in attacks, including universal adversarial perturbation (UAPs), generative adversarial network (GAN)-based attacks, and DeepFakes to generate malicious examples. Trends in defense are adversarial training, GAN-based strategies, and out-of-distribution (OOD) to identify and mitigate adversarial examples (AE). We found privacy-preserving strategies such as federated learning (FL), differential privacy, and combinations of strategies to enhance the FL. Challenges in privacy comprehend the development of attacks that bypass fine-tuning, defenses to calibrate models to improve their robustness, and privacy methods to enhance the FL strategy. CONCLUSIONS: In conclusion, it is critical to explore security and privacy in ML for health, because it has grown risks and open vulnerabilities. Our study presents strategies and challenges to guide research to investigate issues about security and privacy in ML applied to health systems.

Screen time impairs the relationship between physical fitness and academic attainment in children / O tempo de tela prejudica a relação entre a forma física e o sucesso acadêmico em crianças

OBJECTIVE: The purpose of this study was twofold: to analyze the association between physical fitness and academic attainment, and to determine the influence of screen time on the association between physical fitness and academic attainment.METHODS: A cross-sectional study including 395 schoolchildren from seven schools of the Maule Region, Chile (mean age 12.1 years; 50.4% boys) participated in the autumn of 2014 (March to June). Self-reported physical activity and screen time were evaluated. The study measured academic achievement (mean of the grades obtained in several core subjects), physical fitness (cardiorespiratory fitness and muscular strength), weight, height, parental education, and socioeconomic status. Linear regression analysis was used to analyze the relationships between physical fitness and academic attainment after adjusting for potential confounders by gender. Analysis of variance was used to analyze the differences in academic attainment according to fitness and screen time categories (< 2 hours/day and ≥ 2 hours/day).RESULTS: In both genders good cardiorespiratory fitness levels were associated with high language (ß = 0.272-0.153) and mean academic attainment (ß = 0.192-0.156) grades; however, after adjusting for screen time and other potential confounders, these associations disappear. Similarly, no relationship was observed after analyzing those children who spend more hours of screen time (≥ 2 hours/day).CONCLUSIONS: Academic attainment is associated with higher cardiorespiratory fitness levels; however, it was weakly impaired by screen time. These findings seem to suggest that parents and policymakers should minimize the negative effects of screen time on children's lives to maximize the beneficial effect of healthy habits on academic attainment.

OBJETIVO: Analisar a relação entre a forma física e o sucesso acadêmico e determinar a influência do tempo de tela sobre a relação entre a forma física e o sucesso acadêmico.MÉTODO: Estudo transversal que incluiu 395 crianças em idade escolar de sete escolas da região de Maule, Chile (com idade média de 12,1 anos; 50,4% de meninos), foi feito no outono de 2014 (março a junho). A atividade física e o tempo de tela autorrelatados foram avaliados. Mensuramos o desempenho escolar (média das notas obtidas em diversas matérias principais), a forma física (aptidão cardiorrespiratória e força muscular), o peso, a estatura, a escolaridade dos pais e a condição socioeconômica. A análise de regressão linear foi usada para avaliar as relações entre a forma física e o sucesso acadêmico após o ajuste pelas possíveis variáveis de confusão por sexo. A análise de variância foi usada para avaliar as diferenças no sucesso escolar de acordo com as categorias de forma física e tempo de tela (< 2 horas/dia e ≥ 2 horas/dia).RESULTADOS: Em ambos os sexos, os bons níveis de aptidão cardiorrespiratória foram associados às maiores notas em línguas (ß = 0,272-0,153) e à média de sucesso acadêmico (ß = 0,192-0,156); contudo, após ajustar o tempo de tela e outras possíveis variáveis de confusão, essas associações desaparecem. Da mesma forma, não foi observada relação após analisar as crianças com mais horas de tempo de tela (≥ 2 horas/dia).CONCLUSÕES: O sucesso acadêmico está associado a maiores níveis de aptidão cardiorrespiratória; contudo, foi pouco prejudicado pelo tempo de tela. Esses achados parecem sugerir que os pais e órgãos reguladores devem minimizar os efeitos negativos do tempo de tela sobre as vidas das crianças para maximizar o efeito benéfico de hábitos saudáveis sobre o sucesso acadêmico.

Screen time impairs the relationship between physical fitness and academic attainment in children.

OBJECTIVE: The purpose of this study was twofold: to analyze the association between physical fitness and academic attainment, and to determine the influence of screen time on the association between physical fitness and academic attainment. METHODS: A cross-sectional study including 395 schoolchildren from seven schools of the Maule Region, Chile (mean age 12.1 years; 50.4% boys) participated in the autumn of 2014 (March to June). Self-reported physical activity and screen time were evaluated. The study measured academic achievement (mean of the grades obtained in several core subjects), physical fitness (cardiorespiratory fitness and muscular strength), weight, height, parental education, and socioeconomic status. Linear regression analysis was used to analyze the relationships between physical fitness and academic attainment after adjusting for potential confounders by gender. Analysis of variance was used to analyze the differences in academic attainment according to fitness and screen time categories (< 2 hours/day and ≥ 2 hours/day). RESULTS: In both genders good cardiorespiratory fitness levels were associated with high language (ß=0.272-0.153) and mean academic attainment (ß=0.192-0.156) grades; however, after adjusting for screen time and other potential confounders, these associations disappear. Similarly, no relationship was observed after analyzing those children who spend more hours of screen time (≥ 2 hours/day). CONCLUSIONS: Academic attainment is associated with higher cardiorespiratory fitness levels; however, it was weakly impaired by screen time. These findings seem to suggest that parents and policymakers should minimize the negative effects of screen time on children's lives to maximize the beneficial effect of healthy habits on academic attainment.

Effects of the thyromimetic agent diiodothyropropionic acid on body weight, body mass index, and serum lipoproteins: a pilot prospective, randomized, controlled study.

CONTEXT: Widespread thyroid hormone actions offer the possibility of developing selective thyromimetic analogs with salutary metabolic properties. Consequently, effects of diiodothyropropionic acid (DITPA) on body weight, serum lipoproteins, and bone metabolism markers were studied in a prospective, controlled, double-blind 24-wk trial, which was primarily designed to assess treatment of stable chronic heart failure. DESIGN: Eighty-six patients (aged 66 +/- 11 yr, mean +/- sd) were randomized (1:2) to placebo or an escalating DITPA dose (90 to 180, 270, and 360 mg/d) over 8 wk until serum TSH was less than 0.02 mU/liter. Patients were studied at 2, 4, 6, 8, 16, and 24 wk and after 4 wk off study drug. Only 21 DITPA-treated and 27 placebo patients completed the full 24 wk of therapy. RESULTS: DITPA therapy lowered serum TSH levels and, to a lesser extent, serum T(3) and T(4), but there were no differences in clinical manifestations of thyrotoxicosis or hypothyroidism. Serum total and low-density lipoprotein cholesterol levels both decreased on DITPA; there was a transient decrease in triglycerides and no change in high-density lipoprotein cholesterol. DITPA therapy was associated with significant reduction in body weight, 12.5 lb at 24 wk. Increases in serum osteocalcin, N-telopeptide, and deoxypyridinoline levels were consistent with increased bone turnover on DITPA. CONCLUSION: This investigation of DITPA actions demonstrated its efficacy in reducing body weight and lowering total and low-density lipoprotein cholesterol levels. However, DITPA's adverse effects at doses used resulted in a high dropout rate and potentially dangerous skeletal actions were observed.

Force distributions in three-dimensional compressible granular packs.

We present an experimental investigation of the probability distribution of normal contact forces, P(F), at the bottom boundary of static three-dimensional packings of compressible granular materials. We find that the degree of deformation of individual grains plays a large role in determining the form of this distribution. For small amounts of deformation we find a small peak in P(F) below the mean force with an exponential tail for forces larger than the mean force. As the degree of deformation is increased the peak at the mean force grows in height and the slope of the exponential tail increases.

Signaling through TNF receptor p55 in TNF-alpha-deficient mice alters the CXCL13/CCL19/CCL21 ratio in the spleen and induces maturation and migration of anergic B cells into the B cell follicle.

The organization of secondary lymphoid tissues into distinct T and B cell compartments supports proper regulation of an immune response to foreign Ags. In the splenic white pulp, this compartmentalization is also thought to be important in the maintenance of B cell tolerance. Using lymphotoxin-alpha-(LT-alpha)-, TNF-alpha-, or TNFRp55-deficient mice, all with disrupted splenic architecture, we tested whether normal T/B segregation and/or intact follicular structure are necessary for the maintenance of anti-dsDNA B cell anergy. This study demonstrates that anti-dsDNA B cells remain tolerant in LT-alpha(-/-), TNF-alpha(-/-), and TNFRp55(-/-) mice; however, TNF-alpha or a TNF-alpha-dependent factor is required for their characteristic positioning to the T/B interface. Providing a TNF-alpha signal in TNF-alpha(-/-) mice by systemic administration of an agonist anti-TNFRp55 mAb induces the maturation of the anti-dsDNA B cells and their movement away from the T cell area toward the B cell area. Additionally, the agonist Ab induces changes in the follicular environment, including FDC clustering, up-regulation of the CXC chemokine ligand CXCL13, and down-regulation of the CC chemokine ligands CCL19 and CCL21. Therefore, this study suggests that a balance between B and T cell tropic chemokine signals may be an important mechanism for positioning anergic B cells at the T/B interface of the splenic white pulp.

Fas/Fas ligand deficiency results in altered localization of anti-double-stranded DNA B cells and dendritic cells.

Autoantibodies directed against dsDNA are found in patients with systemic lupus erythematosus as well as in mice functionally deficient in either Fas or Fas ligand (FasL) (lpr/lpr or gld/gld mice). Previously, an IgH chain transgene has been used to track anti-dsDNA B cells in both nonautoimmune BALB/c mice, in which autoreactive B cells are held in check, and MRL-lpr/lpr mice, in which autoantibodies are produced. In this study, we have isolated the Fas/FasL mutations away from the autoimmune-prone MRL background, and we show that anti-dsDNA B cells in Fas/FasL-deficient BALB/c mice are no longer follicularly excluded, and they produce autoantibodies. Strikingly, this is accompanied by alterations in the frequency and localization of dendritic cells as well as a global increase in CD4 T cell activation. Notably, as opposed to MRL-lpr/lpr mice, BALB-lpr/lpr mice show no appreciable kidney pathology. Thus, while some aspects of autoimmune pathology (e.g., nephritis) rely on the interaction of the MRL background with the lpr mutation, mutations in Fas/FasL alone are sufficient to alter the fate of anti-dsDNA B cells, dendritic cells, and T cells.

Novel roles for Lyn in B cell migration and lipopolysaccharide responsiveness revealed using anti-double-stranded DNA Ig transgenic mice.

Lyn-deficient mice produce Abs against dsDNA, yet exhibit exaggerated tolerance to the model Ag hen-egg lysozyme. To investigate this apparent contradiction, and to further examine the function of Lyn in Ag-engaged cells, we have used an anti-dsDNA Ig transgenic model. Previously, looking at these anti-dsDNA B cells in Lyn-sufficient BALB/c mice, we showed that they are regulated by functional inactivation (anergy). In the absence of Lyn, these anti-dsDNA B cells remain unable to secrete Ab. This suggests that functional inactivation of anti-dsDNA B cells does not depend on Lyn, and that the anti-dsDNA Abs that are produced in lyn(-/-) mice arise from a defect in another mechanism of B cell tolerance. Although the anti-dsDNA B cells remain anergic, Lyn deficiency does restore their ability to proliferate to LPS. This reveals a novel role for Lyn in mediating the LPS unresponsiveness that normally follows surface Ig engagement. Furthermore, Lyn deficiency leads to an altered splenic localization and EBV-induced molecule 1 ligand chemokine responsiveness of anti-dsDNA B cells, as well as an absence of marginal zone B cells, suggesting additional roles for Lyn in controlling the migration and development of specific B cell populations.

Validation of a mouse conductance system to determine LV volume: comparison to echocardiography and crystals.

The application of left ventricular pressure-volume analysis to transgenic mice to characterize the cardiac phenotype has been problematic due to the small size of the mouse heart and the rapid heartbeat. Conductance technology has been miniaturized for the mouse and can solve this problem. However, there has been no validation of this technique. Accordingly, we performed echocardiography followed by simultaneous ultrasonic crystals, flow probe, and conductance studies in 18 CD-1 mice. Raw conductance volumes were corrected for an inhomogenous electrical field (alpha) and parallel conductance (G(pi)) yielding a stroke volume of 14.1 +/- 3.7 microliter/beat, end-diastolic volume of 20.8 +/- 6.5 microliter, and end-systolic volume of 9.0 +/- 5.8 microliter. The mean conductance volumes were no different from those derived by flow probe and echocardiography but did differ from ultrasonic crystals. G(pi) was determined to be 14.9 +/- 8.7 microliter. However, hypertonic saline altered dimension and pressure in the mouse left ventricle. Although G(pi) can be determined by the hypertonic saline method, saline altered hemodynamics, questioning its validity in the mouse. Although mean measures of absolute volume may be similar among different techniques, individual values did not correlate.

Alterations in splenic architecture and the localization of anti-double-stranded DNA B cells in aged mice.

Aging is characterized by a decline in humoral immunity and a concommitant increased incidence of anti-DNA and other autoantibodies. To define how the regulation of autoreactive B cells is altered with age, we have used BALB/c mice with an Ig heavy H chain transgene to track the fate of anti-double-stranded (ds) DNA B cells in vivo. In young adult mice, anti-dsDNA B cells are developmentally arrested and excluded from the splenic B cell follicle, whereas in most aged mice they are mature and localize within the B cell follicle. Furthermore, we have detailed global changes in lymphoid architecture that accompany aging: CD4(+) T cells are found not only in the periarteriolar lymphoid sheath, but also in the B cell follicles. Strikingly, these disruptions are similar to those that precede serum anti-dsDNA antibody expression in autoimmune MRL-lpr/lpr mice.

The origin of anti-nuclear antibodies in bcl-2 transgenic mice.

bcl-2 transgenic mice develop anti-double-stranded (ds) DNA antibodies similar to those present in systemic lupus erythematosus. To begin to understand where a breakdown in the regulation of autoreactive lymphocytes is occurring, we have used a bcl-2 transgene (Tg) in conjunction with an Ig Tg that allows us to identify and track anti-dsDNA B cells. Previously, we have shown that anti-dsDNA B cells are actively tolerized in BALB/c mice as manifested by their developmental arrest, follicular exclusion, increased in vivo turnover rate and lack of their antibody in the serum. The bcl-2 Tg mice increased the lifespan of anti-dsDNA B cells, but did not alter the other features of tolerance, indicating that the anergy of the anti-dsDNA B cells is independent of their reduced lifespan. Furthermore, these data suggest that the serum anti-dsDNA antibodies in bcl-2 transgenic mice are not due to a breakdown in the induction or maintenance of B cell anergy; rather they may originate from B cells that have transited through a germinal center.

Interleukin-8 as an autocrine growth factor for human colon carcinoma cells in vitro.

Cell lines derived from human colon carcinomas secrete interleukin 8 (IL-8) in vitro and this chemokine has also been detected immunohistochemically in human colon carcinoma specimens, in which it is tumour cell associated. In these experiments, IL-8 was shown to comprise an important component of the angiogenic activity of colon carcinoma cell line supernatants. The effect of modulating IL-8 activity upon the growth of the colon carcinoma cell lines HCT116A, HT29 and CaCo2 was investigated. Supplementing endogenously produced IL-8 by recombinant chemokine led to stimulation of cell growth. Neutralization of the effect of endogenously produced IL-8, either with the specific antagonist peptide AcRRWWCR or with blocking anti-IL-8 antibody, resulted in around 50% inhibition of cell growth (P<0.05). All of the colon carcinoma cell lines tested expressed mRNA for both IL-8RA and RB when grown at confluence. At the protein level, all cell lines expressed IL-8RA. Expression of IL-8RB was weak, although increased expression was seen in HCT116A cells as they approached confluence. Antibodies to IL-8RA and RB did not affect proliferation at low cell density but were strongly inhibitory when cells were cultured at a higher density. These data suggest that IL-8 acts as an autocrine growth factor for colon carcinoma cell lines and would support the concept that a similar autocrine loop operates in vivo.

Functional consequences of the developmental arrest and follicular exclusion of anti-double-stranded DNA B cells.

Anti-dsDNA B cells are actively tolerized in nonautoimmune BALB/c mice, as manifested by their developmental arrest, follicular exclusion, and rapid turnover rate. Previously, we have documented changes in the maturation status and follicular localization of anti-dsDNA B cells in autoimmune-prone MRL (+/+ and lpr/lpr) mice. To determine whether these differences in developmental status and follicular localization affect the functional capacity of anti-dsDNA B cells, we have now compared their in vivo life spans and their responses to in vitro stimuli. Our study shows that although anti-dsDNA B cells from both BALB/c and MRL-+/+ mice are localized to the T/B interface, only those in BALB/c mice have a rapid turnover rate. Therefore, the immature status and not the exclusion from the B cell follicle correlates with a shortened life span. Interestingly, apoptotic anti-dsDNA B cells were not detected at the T/B interface in BALB/c mice, suggesting that they are not dying there. This study also demonstrates that anti-dsDNA B cells, regardless of maturation status or follicular localization, are able to proliferate and up-regulate the costimulatory molecule B7-2 in response to CD40 ligand and IL-4. Therefore, one of the critical in vivo differences between anti-dsDNA B cells in BALB/c and MRL-+/+ mice compared with MRL-lpr/lpr mice may be the availability of T cell help.

Polarized expression of immunoglobulin, spectrin, and protein kinase C beta II occurs in B cells from normal BALB/c, autoimmune lpr, and anti-ssDNA transgenic, tolerant mice.

The rapid redistribution of B cell surface immunoglobulin to a cap upon cross-linking treatment is a well-described phenomenon, the physiological significance of which is unknown. We describe the observation that splenic B cells from unimmunized normal, autoimmune, and tolerant mice express naturally occurring capped immunoglobulin in the absence of exogenous stimulation. The percentage of capped B cells increases to 20% of B cells by age 16 weeks in the progressive autoimmune lpr mouse. Transgenic, tolerant mice expressing lpr-derived genes for ssDNA-binding antibody also demonstrate a large percentage (35-75%) of immunoglobulin-capped splenic B cells. In these capped B cells, protein kinase C beta II, the cytoskeletal proteins spectrin and ankyrin, and the lipophilic probe diI are enriched beneath the site of the immunoglobulin cap. These data suggest that polarization of surface receptors, signaling molecules, anionic phospholipid domains, and cytoskeletal proteins may be an important part of the B cell immune response in vivo.

Expression in transgenic mice of dominant interfering Fas mutations: a model for human autoimmune lymphoproliferative syndrome.

Most humans with autoimmune lymphoproliferative syndrome (ALPS) carry heterozygous dominant mutations in one allele of the gene encoding Fas/APO-1/CD95. ALPS patients, like Fas-deficient MRL lpr/lpr mice, have lymphoproliferation, autoimmunity, increased CD4(-)/CD8(-) T lymphocytes, and apoptosis defects. Consistent with the phenotypic variability of lpr/lpr mice of different background strains, human genetic studies indicate that a Fas mutation is insufficient to induce ALPS in all mutation carriers. To investigate the dominant function of human Fas mutations and the additional genetic factor(s) involved in the development of ALPS, we generated transgenic mice expressing, in addition to endogenous Fas, mouse Fas molecules bearing mutations in the intracellular death domain corresponding to mutations identified in ALPS patients. Transgenic mice developed mild features of ALPS, including hepatosplenomegaly, elevated proportions of lymphocytes in spleen and lymph nodes, apoptotic defects, and hepatic lymphocytic infiltrates. Therefore defective murine Fas proteins act in a dominant manner to impair apoptosis of activated lymphocytes and disrupt lymphocyte homeostasis. The influence of genetic background on phenotype was studied by comparing transgenic mice on FVB/N and (FVB/N x MRL) backgrounds with syngenetic control mice and with MRL and MRL lpr/lpr mice. While expression of transgenic mutant Fas contributed mainly to hepatosplenomegaly and accumulation of lymphocytes, MRL background genes played a major role in the production of autoantibodies and elevated serum immunoglobulin levels. Moreover, compared to FVB/N (+/+) mice, a substantial Fas-specific apoptotic defect was found in MRL (+/+) mice, suggesting a mechanism for the known tendency of this strain to develop autoimmunity.

MRL-lpr/lpr mice exhibit a defect in maintaining developmental arrest and follicular exclusion of anti-double-stranded DNA B cells.

A hallmark of systemic lupus erythematosus and the MRL murine model for lupus is the presence of anti-double-stranded (ds)DNA antibodies (Abs). To identify the steps leading to the production of these Abs in autoimmune mice, we have compared the phenotype and localization of anti-dsDNA B cells in autoimmune (MRL+/+ and lpr/lpr) mice with that in nonautoimmune (BALB/c) mice. Anti-dsDNA B cells are actively regulated in BALB/c mice as indicated by their developmental arrest and accumulation at the T-B interface of the splenic follicle. In the MRL genetic background, anti-dsDNA B cells are no longer developmentally arrested, suggesting an intrinsic B cell defect conferred by MRL background genes. With intact Fas, they continue to exhibit follicular exclusion; however, in the presence of the lpr/lpr mutation, anti-dsDNA B cells are now present in the follicle. Coincident with the altered localization of anti-dsDNA B cells is a follicular infiltration of CD4 T cells. Together, these data suggest that MRL mice are defective in maintaining the developmental arrest of autoreactive B cells and indicate a role for Fas in restricting entry into the follicle.

Characterization of anergic anti-DNA B cells: B cell anergy is a T cell-independent and potentially reversible process.

Anti-single stranded DNA (ssDNA) and anti-double stranded DNA (dsDNA) B cells are regulated in non-autoimmune mice. In this report we show that while both anti-ssDNA and anti-dsDNA B cells are blocked in their ability to differentiate into antibody-secreting cells, other phenotypic and functional characteristics distinguish them from one another. Splenic anti-ssDNA B cells are found distributed throughout the B cell follicle, and are phenotypically mature and long-lived. On the other hand, splenic anti-dsDNA B cells are short-lived, exhibit an immature and antigen-experienced phenotype, and localize to the T-B interface of the splenic follicle. Functionally, anti-ssDNA B cells proliferate, albeit suboptimally, in response to anti-IgM, lipopolysaccharide (LPS) and CD40L/IL-4 + anti-IgM stimulation, and tyrosine phosphorylate intracellular proteins upon mIgM cross-linking. Anti-dsDNA B cells, on the other hand, are functionally unresponsive to anti-IgM and LPS stimulation, and do not phosphorylate intracellular proteins, including Syk, upon mIg stimulation. Importantly, anti-DNA B cell anergy is maintained in the absence of T cells since both anti-ssDNA and anti-dsDNA B cells are as efficiently regulated in RAG2(-/-) mice as in their RAG2(+/+) counterparts. Interestingly, the severely anergic state of anti-dsDNA B cells is partially reversible upon stimulation with CD40 ligand and IL-4. In response to these signals, anti-dsDNA B cells remain viable, up-regulate cell surface expression of B7-2 and IgM, and restore their ability to proliferate and phosphorylate Syk upon mIg cross-linking. Collectively, these data suggest that anti-DNA B cell anergy encompasses distinct phenotypes which, even in its most severe form, may be reversible upon stimulation with T cell-derived factors.

Radial approach: a new concept in surgical treatment for atrial fibrillation. II. Electrophysiologic effects and atrial contribution to ventricular filling.

BACKGROUND: In a previous study the atrial incisions that follow the concept of the radial approach were designed according to the activation sequence during sinus rhythm and the atrial coronary artery anatomy in normal dogs. The purpose of the present study was to determine whether the radial approach provides a more physiologic activation sequence and atrial transport function than the maze procedure. METHODS: Ten dogs that had undergone the radial approach (n = 5) or the maze procedure (n = 5) were studied 6 weeks postoperatively. Sinus node function and inducibility of atrial fibrillation were examined before and after operation. The atria were mapped endocardially with 212 electrodes, and atrial activation sequences during sinus rhythm and right atrial pacing were examined. Atrial transport function was assessed by transepicardial Doppler echocardiography. RESULTS: No dogs developed sinus node dysfunction postoperatively. Both the radial approach and the maze procedure equally prevented sustained atrial fibrillation. The atrial activation sequence was more synchronous after the radial approach than after the maze procedure. There was no electrically isolated region after the radial approach. The total activation time of the left atrium was significantly shorter after the radial approach than after the maze procedure (53.6+/-9.8 versus 70.5+/-9.6 ms, p<0.05). The ratio of peak flow velocity of the E wave to the A wave (peak E/A) of the transmitral Doppler flow was significantly smaller after the radial approach than after the maze procedure (1.7+/-0.4 versus 3.5+/-1.7, p<0.05). The atrial filling fraction of the transmitral Doppler flow was significantly larger after the radial approach than after the maze procedure (29.9%+/-7.3% versus 14.8%+/-5.0%, p<0.01). There was no significant difference in peak E/A and atrial filling fraction of the transtricuspid Doppler flow between the two procedures. CONCLUSIONS: The radial approach provides a more synchronous activation sequence and atrial transport function, and thus may represent a more physiologic alternative to the maze procedure as a surgical treatment for atrial fibrillation.

Self-reactive B cells in nonautoimmune and autoimmune mice.

The defining feature of autoimmune disease is the presence of specific autoreactive lymphocytes. Systemic lupus erythematosus (SLE), for example, is characterized by a discrete set of antibodies directed to nuclear antigens; these include autoantibodies to DNA and snRNPs that are diagnostic for SLE. The murine model of SLE, the MRL-lpr/lpr mouse, likewise, has a similar autoantibody profile. To understand how SLE-associated autoantibodies are regulated in healthy individuals and to identify mechanisms underlying their expression in autoimmunity, we have developed a transgenic (tg) model system using multiple sets of tgs. The development of B cells bearing these tgs has been studied in BALB/c and MRL-lpr/lpr autoimmune backgrounds, and the relative fates of anti-ssDNA and anti-dsDNA tg B cells when they are a part of a diverse as well as monoclonal B cell repertoire have been evaluated.

The importance of play in adulthood. An interview with Joan M. Erikson. Interview by Daniel Benveniste.

Joan M. Erikson (1902-1997) was an artist, a writer, a mother, and the wife and collaborator of Erik H. Erikson (1902-1994), one of the most important and influential psychoanalysts in the world. The following is an edited dialogue on one of her favorite topics--The Importance of Play in Adulthood. It features her thoughts on the subject and reminiscences of the ways she played throughout her life. She muses on play in relation to humor, fun, the role of the fool, and more. The article was a project undertaken in the spirit of play and it will hopefully evoke further playful musings in the minds of readers.