Machine phenotyping of cluster headache and its response to verapamil

Cluster headache is characterized by recurrent, unilateral attacks of excruciating pain associated with ipsilateral cranial autonomic symptoms. Although a wide array of clinical, anatomical, physiological, and genetic data have informed multiple theories about the underlying pathophysiology, the lack of a comprehensive mechanistic understanding has inhibited, on the one hand, the development of new treatments and, on the other, the identification of features predictive of response to established ones. The first-line drug, verapamil, is found to be effective in only half of all patients, and after several weeks of dose escalation, rendering therapeutic selection both uncertain and slow. Here we use high-dimensional modelling of routinely acquired phenotypic and MRI data to quantify the predictability of verapamil responsiveness and to illuminate its neural dependants, across a cohort of 708 patients evaluated for cluster headache at the National Hospital for Neurology and Neurosurgery between 2007 and 2017. We derive a succinct latent representation of cluster headache from non-linear dimensionality reduction of structured clinical features, revealing novel phenotypic clusters. In a subset of patients, we show that individually predictive models based on gradient boosting machines can predict verapamil responsiveness from clinical (410 patients) and imaging (194 patients) features. Models combining clinical and imaging data establish the first benchmark for predicting verapamil responsiveness, with an area under the receiver operating characteristic curve of 0.689 on cross-validation (95% confidence interval: 0.651 to 0.710) and 0.621 on held-out data. In the imaged patients, voxel-based morphometry revealed a grey matter cluster in lobule VI of the cerebellum (–4, –66, –20) exhibiting enhanced grey matter concentrations in verapamil non-responders compared with responders (familywise error-corrected P = 0.008, 29 voxels). We propose a mechanism for the therapeutic effect of verapamil that draws on the neuroanatomy and neurochemistry of the identified region. Our results reveal previously unrecognized high-dimensional structure within the phenotypic landscape of cluster headache that enables prediction of treatment response with modest fidelity. An analogous approach applied to larger, globally representative datasets could facilitate data-driven redefinition of diagnostic criteria and stronger, more generalizable predictive models of treatment responsiveness

Phylogeny in Aid of the Present and Novel Microbial Lineages: Diversity in Bacillus

Bacillus represents microbes of high economic, medical and biodefense importance. Bacillus strain identification based on 16S rRNA sequence analyses is invariably limited to species level. Secondly, certain discrepancies exist in the segregation of Bacillus subtilis strains. In the RDP/NCBI databases, out of a total of 2611 individual 16S rDNA sequences belonging to the 175 different species of the genus Bacillus, only 1586 have been identified up to species level. 16S rRNA sequences of Bacillus anthracis (153 strains), B. cereus (211 strains), B. thuringiensis (108 strains), B. subtilis (271 strains), B. licheniformis (131 strains), B. pumilus (83 strains), B. megaterium (47 strains), B. sphaericus (42 strains), B. clausii (39 strains) and B. halodurans (36 strains) were considered for generating species-specific framework and probes as tools for their rapid identification. Phylogenetic segregation of 1121, 16S rDNA sequences of 10 different Bacillus species in to 89 clusters enabled us to develop a phylogenetic frame work of 34 representative sequences. Using this phylogenetic framework, 305 out of 1025, 16S rDNA sequences presently classified as Bacillus sp. could be identified up to species level. This identification was supported by 20 to 30 nucleotides long signature sequences and in silico restriction enzyme analysis specific to the 10 Bacillus species. This integrated approach resulted in identifying around 30% of Bacillus sp. up to species level and revealed that B. subtilis strains can be segregated into two phylogenetically distinct groups, such that one of them may be renamed

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

S

Evaluating the role of mosque as emergency shelter during natural disasters

Providing emergency shelter for the victims of natural disasters is part of disaster risk reduction (DRR) strategies. It is essential for the proper management of resources in the communities during emergency time. The approach toward providing emergency shelter to the victims varies in different contexts depending on the availability of suitable places. Organizations like IOM and FEMA have proposed a framework for appropriate planning and design of emergency shelters. These bodies also encourage local disaster management authorities in their guideline to utilize existing structures like schools, community centers, etc., as an emergency shelter for the victims. However, recent flood occurrence in India, UK, and Malaysia showed that the institution of the mosque is highly appropriate to be used as an emergency disaster shelter. This study analyzes the compatibility of mosque institution as a potential place for emergency shelter. The analysis follows the criteria set by IOM and FEMA to design properly functioning emergency shelter. Then, based on these criteria the design of common mosques is discussed considering different aspects such as location, capacity, and facilities. The institution of the mosque is also analyzed from the perspective of Islamic theology and how it is recommended for mosques to provide social and welfare services to the community. This paper recommends further study in this regard to proposing specific guidelines for the mosque so that it can be utilized as an existing structure for providing emergency shelter for disaster victims

Herat failure and chronic obstructive airway disease as combined comorbidities. Meta-analysis and Review

Background: The existence of COPD and heart failure in elderly population adds additional morbidity and mortality risk than if those with only one of the two comorbidities. The aim of the current metaanalysis was to explore the effect of COPD on heart failure patient in terms of all-cause mortality, cardiac mortality and recurrent heart failure hospitalization.Methods and results: A comprehensive search of PubMed, MEDLINE, Embase and Cochrane was conducted until August 2017. The total standardized mean difference, with 95% (CI), was estimated for&nbsp; fixed and random effects models to present “pooled effect” for continuous outcomes (mean ± standard deviation or median ± interquartile range) &amp; categorical outcomes (Odds risk OR). Statistical heterogeneity among studies was assessed with Cochran’s Q test and the I2 statistic.</p