The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

An overview of the self-organizing map algorithm, on which the papers in this issue are based, is presented in this article.

The Self-Organizing Map

In this paper we develop new Newton and conjugate gradient algorithms on the Grassmann and Stiefel manifolds. These manifolds represent the constraints that arise in such areas as the symmetric eigenvalue problem, nonlinear eigenvalue problems, electronic structures computations, and signal processing. In addition to the new algorithms, we show how the geometrical framework gives penetrating new insights allowing us to create, understand, and compare algorithms. The theory proposed here provides a taxonomy for numerical linear algebra algorithms that provide a top level mathematical view of previously unrelated algorithms. It is our hope that developers of new algorithms and perturbation theories will benefit from the theory, methods, and examples in this paper.

http://www-math.mit.edu/~edelman/publications/geometry_of_algorithms.pdf

The Geometry of Algorithms with Orthogonality Constraints

结节病易误诊,据王洪武等~([1])收集国内18篇关于此病误诊的文献,误诊率高达63.2%,当然有误诊就会有误治,如孙永昌等~([2])报道26例结节病在影像学检查诊断的第一印象中拟诊结核5例,其中就有2例完成规范的抗结核治疗,为此应引起临床对本病诊治的重视。

Sarcoidosis

Type 2 diabetes mellitus (T2DM) is an expanding global health problem, closely linked to the epidemic of obesity. Individuals with T2DM are at high risk for both microvascular complications (including retinopathy, nephropathy and neuropathy) and macrovascular complications (such as cardiovascular comorbidities), owing to hyperglycaemia and individual components of the insulin resistance (metabolic) syndrome. Environmental factors (for example, obesity, an unhealthy diet and physical inactivity) and genetic factors contribute to the multiple pathophysiological disturbances that are responsible for impaired glucose homeostasis in T2DM. Insulin resistance and impaired insulin secretion remain the core defects in T2DM, but at least six other pathophysiological abnormalities contribute to the dysregulation of glucose metabolism. The multiple pathogenetic disturbances present in T2DM dictate that multiple antidiabetic agents, used in combination, will be required to maintain normoglycaemia. The treatment must not only be effective and safe but also improve the quality of life. Several novel medications are in development, but the greatest need is for agents that enhance insulin sensitivity, halt the progressive pancreatic β-cell failure that is characteristic of T2DM and prevent or reverse the microvascular complications. For an illustrated summary of this Primer, visit: http://go.nature.com/V2eGfN.

Type 2 diabetes mellitus.

AIMS
Anti-Ro/La autoantibodies are especially prevalent in autoimmune diseases but are also relatively frequent in healthy adults. Their arrhythmogenic effect on the immature cardiac conductive system is well established, with substantial evidence demonstrating an increased risk for congenital atrioventricular block in neonates of seropositive mothers. Despite their wide distribution and their arrhythmogenic potential effect, there are no large population studies conducted in seropositive adults. Thus, this is the first large population-based study to examine the association of anti-Ro/La seropositivity with cardiac rhythm and conduction disturbances.


METHODS AND RESULTS
This cross-sectional designed study involved the electronic health records of the largest health maintenance organization in Israel. All subjects that were tested positive for anti-Ro/anti-La antibodies between the years 2002 and 2019 were included and were matched by age, gender, and place of residence, with controls. Rates of different cardiac rhythm and conduction disturbances were compared between groups. Sensitivity analyses were performed using propensity score matching. The study population included 17 231 anti-Ro/La seropositive subjects and 84 368 controls. Anti-Ro seropositive patients had higher rates of conduction disturbances (3.0 vs. 1.7%, P < 0.001) and rhythm disturbances (10.5 vs. 7.0%, P < 0.001). Patients who tested positive for anti-La alone did not demonstrate a significant association with arrhythmias. Multivariate logistic regression analysis, controlling for possible confounders, showed an increased risk for cardiac conduction disturbances [odds ratio (OR) 1.44, 95% confidence interval (CI) 1.25-1.66, P < 0.001], as well as for cardiac rhythm disturbances (OR 1.21, 95% CI 1.11-1.31, P < 0.001) among anti-Ro seropositive patients. However, the association with rhythm disturbances was more robust in certain subgroup analyses.


CONCLUSIONS
Anti-Ro seropositivity is positively associated with adult cardiac conduction disturbances and, to a lesser extent, cardiac rhythm disturbances, regardless of the presence of concurrent autoimmune disease.

Association of anti-Ro seropositivity with cardiac rhythm and conduction disturbances.

Several types of Semi-Continuous HMM (SCHMM) have been compared with the Continuous Density HMM (CD-HMM) in the context of Speaker Independent Isolated Words Recognition (SI-IWR). It is demonstrated that for the ten-digit vocabulary (TIDIGITS), the SC-HMM outperforms the CD-HMM when memory constraints are imposed on the system. SC-HMMs demonstrate recognition rate of about 95% with a total of 59 Gaussians, while under similar conditions the CDHMM yield recognition rates of well below 80%. An algorithm for optimal selection of Gaussian functions for SC-HMM is presented.

Comparison of continuous-density and semi-continuous HMM in isolated words recognition systems.

Objective To assess the prevalence of lupus (SLE) in a psoriatic arthritis (PsA) cohort and to compare it to the general population using the database of a large health care provider. Methods We analyzed the database of the PsA cohort (2002-2017) matched for age and sex with randomly selected controls for demographics, clinical and laboratory manifestations and dispensed medications. Statistical analysis used student’s t-test, Chi square test, as appropriate. In the PsA group, incidence density sampling was performed matching PsA patients without SLE as controls to each case of PsA with SLE by age and follow-up time. Univariable and multivariable conditional logistic regression analysis were used to assess factors affecting SLE development. Results The PsA and control groups consisted of 4836 and 24180 subjects, respectively, median age of 56±15 years, 53.8% of whom were female. Eighteen patients (0.37%) in the PsA group and 36 patients (0.15%) in the control group were diagnosed with SLE (p=0.001). SLE patients without PsA had higher anti-dsDNA and anti-cardiolipin antibodies. Usage of drugs with known potential to induce SLE was higher in the PsA than in the control group. Older age at PsA diagnosis, shorter PsA duration and statin treatment were associated with SLE in PsA patients. Conclusion A 2.3fold increase in the prevalence of SLE in PsA relative to control group was found. Risk factors for SLE development included older age at PsA diagnosis, shorter PsA duration, and statin treatment. The association between PsA and SLE may affect treatment choices and medication development.

https://www.jrheum.org/content/jrheum/48/2/207.full.pdf

Arnon D. Cohen

Papers

Association of anti-Ro seropositivity with cardiac rhythm and conduction disturbances.

Comparison of continuous-density and semi-continuous HMM in isolated words recognition systems.

Increased Prevalence of Systemic Lupus Erythematosus Comorbidity in Patients With Psoriatic Arthritis: A Population-based Case-control Study.

A microcomputer-controlled system for stimulation and acquisition of evoked potentials.

Bullous pemphigoid and neuropsychiatric medications: An influence of drugs or of underlying conditions?