Circular Silhouette and a Fast Algorithm.

Circular data clustering has recently been solved exactly in sub-quadratic time. However, the solution requires a given number of clusters; methods for choosing this number on linear data are inapplicable to circular data. To fill this gap, we introduce the circular silhouette to measure cluster quality and a fast algorithm to calculate the average silhouette width. The algorithm runs in linear time to the number of points on sorted data, instead of quadratic time by the silhouette definition. Empirically, it is over 3000 times faster than by silhouette definition on 1,000,000 circular data points in five clusters. On simulated datasets, the algorithm returned correct numbers of clusters. We identified clusters on round genomes of human mitochondria and bacteria. On sunspot activity data, we found changed solar-cycle patterns over the past two centuries. Using the circular silhouette not only eliminates the subjective selection of number of clusters, but is also scalable to big circular and periodic data abundant in science, engineering, and medicine.

ST2 in patients with severe aortic stenosis and heart failure.

BACKGROUND: ST2 is a circulating biomarker that is well established for predicting outcome in heart failure (HF). This is the first study to look at ST2 concentrations in optimally treated patients with stable but significant left ventricular systolic dysfunction (LVSD) compared to patients with severe aortic stenosis (AS). METHODS: Two cohorts were retrospectively studied: 94 patients undergoing transcatheter aortic valve implantation for severe AS (63 with normal ejection fraction [EF] and 31 with reduced EF), and 50 patients with severe LVSD from non-valvular causes. ST2 pre-procedural samples were taken, and repeated again at 3 and 6 months. Patients were followed-up for 2 years. Data was analyzed using SPSS software. RESULTS: Baseline concentrations of soluble ST2 did not differ significantly between the HF group and AS group with normal EF (EF ≥ 50%). However, in the AS group with a low EF (EF < 50%) ST2 concentrations were significantly higher that the HF group (p = 0.009). New York Heart Association class IV HF, baseline N-terminal pro-B-type natriuretic peptide and gender were all independent predictors of soluble ST2 (sST2) baseline concentrations. CONCLUSIONS: Raised ST2 concentrations in the context of severe AS may be a marker for subclinical or clinical left ventricular dysfunction. More research is required to assess its use for assessment of prognosis and response to treatment.

Association of high-density lipoprotein levels with baseline coronary plaque volumes by coronary CTA in the EVAPORATE trial.

BACKGROUND AND AIMS: Dyslipidemia with elevated triglycerides (TGL) and low high-density lipoprotein cholesterol (HDL-C) predicts residual cardiovascular risk, despite goal LDL-C levels and optimal statin therapy. Coronary plaque characterization by CCTA can provide mechanistic understanding of coronary artery disease and associated prognosis. The role of HDL-C in the pathogenesis of atherosclerosis is not well understood in statin-treated patients with elevated TGL. We sought to examine the association of HDL-C levels with baseline coronary plaque volumes, namely total plaque (TP) and total non-calcified plaque (TNCP) volumes by CCTA in participants enrolled in the EVAPORATE trial. METHODS: We analyzed 80 participants who were enrolled in the trial. Linear regression analysis as a univariate and multivariate model adjusted for significant cardiovascular risk factors was performed to evaluate independent association of HDL-C and baseline coronary plaque volumes. In an exploratory analysis, stratified by sex, we compared the association of serum HDL-C levels with baseline coronary plaque volumes in males and females. RESULTS: Mean (SD) age of participants (n = 80) was 57.1 (8.6) years and 43% were male. Median (Inter Quartile Range/IQR) log-TNCP volume was 83.0 (0.1-7.3) mm3 and median (IQR) log-TP volume was 144.8 (0.1-7.1) mm3. After adjustment for relevant clinical covariates including age, gender, BMI, hypertension, diabetes, past smoking and baseline TGL levels, increasing levels of HDL-C remain independently associated with lower baseline log-TNCP volumes (ß: 0.043 ± 0.021, p = 0.042) and baseline log-TP volumes (ß: 0.046 ± 0.022, p = 0.035) on CCTA. On stratifying by sex in a multivariable regression analysis, HDL-C levels were inversely associated with baseline log-TNCP volumes (ß: 0.066 ± 0.026, p = 0.018) and log-TP volumes (ß: 0.077 ± 0.025, p = 0.004) in females, but not in males (log-TNCP volumes ß: 0.038 ± 0.034, p = 0.282) and log-TP volumes (ß: -0.033 ± 0.036, p = 0.364). CONCLUSIONS: In a cohort of statin treated patients with known atherosclerosis and residually elevated TGL, there was a significant inverse relationship between HDL-C levels and baseline coronary plaque, TP and TNCP volumes on CCTA. Our findings provide more detailed mechanistic evidence regarding the protective role of HDL-C in coronary atherosclerosis in a high-risk cohort. Further investigation to evaluate the interaction of HDL-C levels and coronary plaque volumes on differential CVD risk in statin-treated patients with elevated TGL levels is warranted.

Black ethnicity predicts better survival on dialysis despite greater deprivation and co-morbidity: a UK study.

BACKGROUND: Observational studies from the United States have identified black race as conferring a survival advantage on dialysis. This study represents the first large single-center study from a UK dialysis unit examining the outcome of ethnic minorities on renal replacement therapy (RRT). METHODS: A retrospective analysis of all patients of white or black race initiating RRT at King's College Hospital Renal Unit, London, between 1996 and 2008 was performed. A total of 1,340 patients were studied, of which 952 (71%) were of white race, and 388 (29%) were of black race. Kaplan-Meier survival curves, the log rank test and Cox's proportional hazard models were used to compare survival between groups. RESULTS: The results revealed black ethnicity to be associated with a significant survival benefit on dialysis. This was the case even after adjustment for age, gender, diabetes, transplantation, and deprivation. In those patients not transplanted, black race conferred a hazard ratio (HR) of 0.51 (95% CI 0.41 - 0.63) over 5 years. CONCLUSIONS: This study provides evidence for a lower mortality rate amongst black patients on dialysis in comparison with their white counterparts in the UK. The reasons behind this remain poorly understood but a lower incidence of cardiovascular disease in black patients and more kidney-limited disease may be important.

Ankle sprains and instability.

Ankle injuries are among the most common injuries presenting to primary care providers and emergency departments and may cause considerable time lost to injury and long-term disability. Inversion injuries about the ankle involve about 25% of all injuries of the musculoskeletal system and 50% of all sports-related injuries. Medial-sided ankle sprains occur less frequently than those on the lateral side. High ankle sprains occur less frequently in the general population, but do occur commonly in collision sports. Providers should apply the Ottawa ankle rules when radiography is indicated and refer fractures and more severe injuries to orthopedic surgery as needed.

Calpain mediates epithelial cell microvillar effacement by enterohemorrhagic Escherichia coli.

A member of the attaching and effacing (AE) family of pathogens, enterohemorrhagic Escherichia coli (EHEC) induces dramatic changes to the intestinal cell cytoskeleton, including effacement of microvilli. Effacement by the related pathogen enteropathogenic E. coli (EPEC) requires the activity of the Ca(+2)-dependent host protease, calpain, which participates in a variety of cellular processes, including cell adhesion and motility. We found that EHEC infection results in an increase in epithelial (CaCo-2a) cell calpain activity and that EHEC-induced microvillar effacement was blocked by ectopic expression of calpastatin, an endogenous calpain inhibitor, or by pretreatment of intestinal cells with a cell-penetrating version of calpastatin. In addition, ezrin, a known calpain substrate that links the plasma membrane to axial actin filaments in microvilli, was cleaved in a calpain-dependent manner during EHEC infection and lost from its normal locale within microvilli. Calpain may be a central conduit through which EHEC and other AE pathogens induce enterocyte cytoskeletal remodeling and exert their pathogenic effects.

Elevated intracellular calcium causes distinct mitochondrial remodelling and calcineurin-dependent fission in astrocytes.

Disruptions of mitochondrial dynamics have been implicated in the pathogenesis of neurodegenerative diseases. The regulation mechanisms of mitochondrial dynamics have not been fully elucidated; however, calcium has been suggested to play a role. In the present study, we examined the role of intracellular calcium in regulating mitochondrial morphology and motility in cortical astrocytes employing different concentrations of a calcium ionophore. High levels of calcium caused a dramatic reduction in mitochondrial length, the result of two distinct phenomena: mitochondrial remodelling (or "rounding") and fission. Quantitative analysis revealed that mitochondrial remodelling/rounding was the predominant process. In addition, mitochondrial motility was reduced, as reported previously in neurons. By contrast, prolonged, more modest levels of intracellular calcium resulted in a reduction in mitochondrial length without significant effects upon mitochondrial motility. This calcium-induced reduction in mitochondrial length was not affected by the presence of calcineurin inhibitors; however, when mitochondrial fission events were specifically examined, calcineurin inhibitors had a significant inhibitory effect. This suggests that changes in mitochondrial length were primarily due to mitochondrial remodelling as opposed to fission. In the present study, we have therefore dissected the effects of calcium on mitochondrial motility, remodelling and fission. Our results suggest independent mechanisms for regulating these processes.

Non-arteritic ischaemic optic neuropathy after first return to haemodialysis.

The authors present an interesting case of non-arteritic anterior ischaemic optic neuropathy (NAION) after 2 h of haemodialysis, in a 42-year-old Caucasian woman with anaemia (haemoglobin 7.1 g/dl) uraemia (56.3 mmol/l), spurious hypotension (42/26 mm Hg) and previous history of anterior ischaemic optic neuropathy (AION) in the other eye. Thirteen cases of haemodialysis related NAION in adults have been reported to date. NAION is produced when oxygen delivery to the optic nerve is compromised resulting in hypoxic swelling, nerve compression in the optic canal and ischaemia of the optic nerve head. It typically presents as a sudden, unilateral and painless inferior visual field defect with a fixed unreactive pupil after a period of relative hypotension. Clinicians should be aware of this unusual complication when considering and explaining dialysis options, particularly in patients with other risk factors such as hypotension, anaemia, significant uraemia and previous history of AION.

Appearance of anti-NMDAR antibodies after plasma exchange and total removal of malignant ovarian teratoma in a patient with paraneoplastic limbic encephalopathy.

A 29-year-old female was admitted under section 2 of the mental health act with an acute psychosis. Her condition deteriorated as she developed a fever and worsening hallucinations. Brain imaging was normal but a lumbar puncture revealed a reactive cerebrospinal fluid. A transvaginal ultrasound revealed a left ovarian mass suggestive of a teratoma. A diagnosis of anti-N-methyl-D-aspartic acid receptor (NMDAR) limbic encephalitis was made but the anti-NMDAR antibody was found to be negative. The patient proceeded to a laparoscopic oopherectomy and a 5-day course of plasma exchange. The patient has made a gradual improvement and the anti-NMDAR antibody has since become positive.

Acute Chest Presentation following a Laparoscopic Nissen Fundoplication.

We describe a case of an acute paraoesophageal hernia in the early post-operative period following a laparoscopic Nissen fundoplication. Patient developed intraoperative tension pneumothorax requiring an immediate chest drain and subsequently needed respiratory support of a continuous positive airway pressure (CPAP) ventilation. A short discussion of this rare but deleterious complication and the difficulty of making a prompt diagnosis are included as delayed revision surgery can be technically challenging with a poor outcome.