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.

Hidden Markov Models (HMM) are statistical models used very successfully and effectively in speech processing. The model is however a general model for stochastic processes and may thus be applied to a large variety of biomedical signals. The paper provides an in depth tutorial on HMM and its applications to biomedical signal processing. Discrete Density (DD-HMM) and Continuous Density HMM (CD-HMM) are presented. The various algorithms required for training the model, for estimating the optimal state sequence and the observation probabilities are discussed. The HMMs have not been widely applied to biomedical signal processing. The paper reviews some of the applications, and discusses potential applications.

Hidden Markov models in biomedical signal processing

BACKGROUND: Multiple miliary osteoma cutis of the face represents primary extra-skeletal bone formation that arises within the skin of the face. METHODS: A 60-year-old woman with multiple miliary osteoma cutis of the face was treated by application of 0.05% tretinoin (all- trans -retinoic acid) cream nightly. RESULTS: After 3 months of therapy there were fewer papules and a decrease in size of remaining lesions. In a literature search, it was found that local application of tretinoin was successful and achieved a decrease in the number of papules over the face in all patients with multiple miliary osteoma cutis of the face; however, the length of time to achieve response varied from a few weeks to 6 months. CONCLUSION: It is suggested that local application of tretinoin cream should be considered in the therapy of multiple miliary osteoma cutis of the face, particularly when the lesions are small and superficial.

Treatment of multiple miliary osteoma cutis of the face with local application of tretinoin (all-trans-retinoic acid): a case report and review of the literature.

The association of dipeptidyl peptidase-4 inhibitors (DPP4is) with autoimmune diseases is controversial. While these agents were proposed as a novel therapeutic approach for several inflammatory diseases by blocking T cell proliferation and cytokine production, they were found to trigger inflammatroy bowel disease, inflammatory arthritis and bullous pemphigoid. Our objective is to examine the association between DPP4i and autoimmune diseases. This study was conducted as a cross-sectional study utilizing the database of Clalit Health Services. The prevalence of 15 autoimmune-/immune-mediated diseases was compared between patients on DPP4i treatment and age-, sex-, and ethnicity-matched controls. Univariate analysis was performed using chi-square and the Student t test and multivariate analysis was performed using a logistic regression model. The study included 283 patients treated with DPP4i agents and 5660 age-, sex-, and ethnicity-matched diabetic control subjects. The prevalence of Crohn’s disease (1.1 vs. 0.3%; odds ratios (OR), 3.56; 95% CI, 1.04–12.21, P = 0.031), psoriasis (2.5 vs. 1.2%; OR, 2.12; 95% CI, 0.99–4.66; P = 0.050), and Hashimoto’s thyroiditis (16.6 vs. 12.6%; OR, 1.38; 95% CI, 1.00–1.91; P = 0.049) was significantly higher in patients on DPP4i treatment than in controls. The prevalence of the remaining autoimmune diseases did not differ significantly between DPP4i-treated patients and their matched control subjects. In conclusion, this population-based study demonstrates an association of DPP4i intake with three autoimmune and inflammatory diseases noted to be part of a distinct autoimmune cluster that includes multiple sclerosis, psoriasis, thyroiditis, bullous pemphigoid, and inflammatory bowel disease. Experimental studies are required to define the role of DPP4i in this autoimmune cluster.

Is there an association between dipeptidyl peptidase-4 inhibitors and autoimmune disease? A population-based study.

The authors introduce a new ECG compression algorithm, and a new distortion measure. The distortion measure, called the Weighted Diagnostic Distortion (WDD), is based on comparing PQRST complex features (such as: RR interval, QT interval, ST elevation, etc.) of the original ECG signal and the reconstructed one. The compression algorithm is based on analysis by synthesis coding. It consists of a beat codebook, long and short term predictors, and an adaptive residual quantizer. The compression algorithm uses the WDD measure in order to encode, by means of analysis by synthesis, every beat of the original ECG signal. The compression algorithm has been applied to the MIT-BIH Arrhythmia Database. A rate of approximately 100 bits per second has been achieved with a very good quality (WDD below 4%, and PRD below 8%).

Analysis by synthesis ECG signal compression

Comorbidities associated with psoriatic arthritis (PsA) include cardiovascular diseases, diabetes mellitus, and obesity. This study evaluated the association between PsA and common gastrointestinal (GI) diseases. A retrospective study was performed in Israel’s largest health care provider database between 2002 and 2013. 3161 PsA patients were matched for age and sex with 31610 randomly selected patients. We searched these patients’ records for the presence of peptic ulcer disease (PUD), reflux esophagitis, Crohn’s disease, ulcerative colitis, irritable bowel syndrome (IBS) and celiac disease. T-test was used to compare continuous variables and a Chi-square test was used for categorical variables. Multivariate logistic regression models were used to assess the association between PsA and GI comorbidities. PsA was associated with Crohn’s disease (OR 2.4, 95 %CI: 1.75–3.32, p < 0.0001), ulcerative colitis (OR 2.1, 95 %CI: 1.33–3.26, p = 0.001), reflux esophagitis (OR 1.6, 95 %CI: 1.44–1.78, p < 0.0001), PUD (OR 1.5, 95 %CI: 1.31–1.63, p < 0.0001) and IBS (OR 1.4, 95 %CI: 1.01–1.86, p = 0.045). After controlling for known risk factors, the association remained significant between PsA and Crohn’s disease (OR 2.2, 95 %CI: 1.59–3.03, p < 0.0001), ulcerative colitis (OR 1.9, 95 %CI: 1.21–3.00, p = 0.005), reflux esophagitis (OR 1.5, 95 %CI: 1.31–1.63, p < 0.0001), and PUD (OR 1.3, 95 %CI: 1.12–1.47, p < 0.0001). No significant association was found between PsA and celiac disease. In the current study PsA was associated with gastrointestinal morbidities including Crohn’s disease, ulcerative colitis, PUD and IBS. Physicians treating patients with PsA should be aware of these associations.

Arnon D. Cohen

Papers

Hidden Markov models in biomedical signal processing

Treatment of multiple miliary osteoma cutis of the face with local application of tretinoin (all-trans-retinoic acid): a case report and review of the literature.

Is there an association between dipeptidyl peptidase-4 inhibitors and autoimmune disease? A population-based study.

Analysis by synthesis ECG signal compression

Gastrointestinal comorbidities in patients with psoriatic arthritis