Protocol for studying cough frequency in people with pulmonary tuberculosis.

INTRODUCTION: Cough is a key symptom of tuberculosis (TB) as well as the main cause of transmission. However, a recent literature review found that cough frequency (number of coughs per hour) in patients with TB has only been studied once, in 1969. The main aim of this study is to describe cough frequency patterns before and after the start of TB treatment and to determine baseline factors that affect cough frequency in these patients. Secondarily, we will evaluate the correlation between cough frequency and TB microbiological resolution. METHODS: This study will select participants with culture confirmed TB from 2 tertiary hospitals in Lima, Peru. We estimated that a sample size of 107 patients was sufficient to detect clinically significant changes in cough frequency. Participants will initially be evaluated through questionnaires, radiology, microscopic observation drug susceptibility broth TB-culture, auramine smear microscopy and cough recordings. This cohort will be followed for the initial 60 days of anti-TB treatment, and throughout the study several microbiological samples as well as 24 h recordings will be collected. We will describe the variability of cough episodes and determine its association with baseline laboratory parameters of pulmonary TB. In addition, we will analyse the reduction of cough frequency in predicting TB cure, adjusted for potential confounders. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the ethics committees at each participating hospital in Lima, Peru, Asociación Benéfica PRISMA in Lima, Peru, the Universidad Peruana Cayetano Heredia in Lima, Peru and Johns Hopkins University in Baltimore, USA. We aim to publish and disseminate our findings in peer-reviewed journals. We also expect to create and maintain an online repository for TB cough sounds as well as the statistical analysis employed

Using neuroevolution for predicting mobile marketing conversion

This paper addresses user Conversion Rate (CVR) prediction within the context of Mobile Performance Marketing. Specifically, we adapt two main neuroevolution methods: Neuroevolution of Augmenting Topologies (NEAT) and Hypercube-based NEAT (HyperNEAT). First, we discuss two mechanisms for increasing execution speed (parallelism and data sampling); a strategy for preventing excessive network complexity with NEAT; and a rolling window scheme for performing an online learning. Then, we present experimental results, using distinct datasets and testing both offline and online learning environments.ThisarticleisaresultoftheprojectNORTE-01-0247-FEDER-017497,supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This work was also supported by FCT – Fundação para a Ciência e Tecnologia within the Project Scope: UID/CEC/00319/2019

El brocado de estaño en relieve aplicado. Evolución histórica y material en la Europa medieval con atención al arte español (siglos XV-XVI)

The term applied tin-relief brocade (commonly called applied brocade) refers to painted decoration that simulates the velvet and silk brocades made of gold and silver threads commonly used in Europe in the fifteenth and sixteenth centuries. This technique uses a mould, tin leaf, and filling mass to reproduce in a mechanical way the relief motifs of textile brocades. Once cut, they are applied to artwork, and then sometimes gilded or painted. The discovery of many examples of this type of decoration in northern Spain has led us to the study of the documentary sources, especially Spanish ones, with the purpose of improving our understanding of the technique, its historic and material development, and the typology of standardized patterns. Furthermore, this study has provided us with an important glossary of the relief painting additive techniques that culminated in applied tinrelief brocade.El término brocado de estaño en relieve aplicado (comúnmente conocido como brocado aplicado) se refiere a una decoración polícroma que imita los brocados de terciopelo y seda hechos con hilos de oro y plata, los cuales dominan el mundo de la moda de Europa en los siglos XV y XVI. Esta técnica reproduce mecánicamente a través de una matriz, lámina de estaño y masa de relleno motivos en relieve de brocados textiles, que, una vez recortados, son aplicados sobre la obra, pudiendo estar en ocasiones dorados y pintados. El hallazgo de más ejemplos de esta decoración en el Norte de España nos ha conducido a analizar las fuentes documentales, especialmente las españolas, con el objetivo de ampliar nuestro conocimiento sobre la técnica en cuestión, su evolución histórica y material y sus diferentes tipologías. Asimismo, dicho estudio nos ha proporcionado un importante glosario de técnicas pictóricas en relieve por adición precursoras del brocado de estaño en relieve aplicado

Revealing the higher-order spin nature of the Hall effect in non-collinear antiferromagnet Mn3Ni0.35Cu0.65N\mathrm{Mn_3Ni_{0.35}Cu_{0.65}N}

Ferromagnets generate an anomalous Hall effect even without the presence of a magnetic field, something that conventional antiferromagnets cannot replicate but noncollinear antiferromagnets can. The anomalous Hall effect governed by the resistivity tensor plays a crucial role in determining the presence of time reversal symmetry and the topology present in the system. In this work we reveal the complex origin of the anomalous Hall effect arising in noncollinear antiferromagnets by performing Hall measurements with fields applied in selected directions in space with respect to the crystalline axes. Our coplanar magnetic field geometry goes beyond the conventional perpendicular field geometry used for ferromagnets and allows us to suppress any magnetic dipole contribution. It allows us to map the in-plane anomalous Hall contribution and we demonstrate a 120$^\circ$ symmetry which we find to be governed by the octupole moment at high fields. At low fields we subsequently discover a surprising topological Hall-like signature and, from a combination of theoretical techniques, we show that the spins can be recast into dipole, emergent octupole and noncoplanar effective magnetic moments. These co-existing orders enable magnetization dynamics unachievable in either ferromagnetic or conventional collinear antiferromagnetic materials

High Diversity of vacA and cagA Helicobacter pylori Genotypes in Patients with and without Gastric Cancer

BACKGROUND: Helicobacter pylori is associated with chronic gastritis, peptic ulcers, and gastric cancer. The aim of this study was to assess the topographical distribution of H. pylori in the stomach as well as the vacA and cagA genotypes in patients with and without gastric cancer. METHODOLOGY/PRINCIPAL FINDINGS: Three gastric biopsies, from predetermined regions, were evaluated in 16 patients with gastric cancer and 14 patients with dyspeptic symptoms. From cancer patients, additional biopsy specimens were obtained from tumor centers and margins; among these samples, the presence of H. pylori vacA and cagA genotypes was evaluated. Positive H. pylori was 38% and 26% in biopsies obtained from the gastric cancer and non-cancer groups, respectively (p = 0.008), and 36% in tumor sites. In cancer patients, we found a preferential distribution of H. pylori in the fundus and corpus, whereas, in the non-cancer group, the distribution was uniform (p = 0.003). A majority of the biopsies were simultaneously cagA gene-positive and -negative. The fundus and corpus demonstrated a higher positivity rate for the cagA gene in the non-cancer group (p = 0.036). A mixture of cagA gene sizes was also significantly more frequent in this group (p = 0.003). Ninety-two percent of all the subjects showed more than one vacA gene genotype; s1b and m1 vacA genotypes were predominantly found in the gastric cancer group. The highest vacA-genotype signal-sequence diversity was found in the corpus and 5 cm from tumor margins. CONCLUSION/SIGNIFICANCE: High H. pylori colonization diversity, along with the cagA gene, was found predominantly in the fundus and corpus of patients with gastric cancer. The genotype diversity observed across systematic whole-organ and tumor sampling was remarkable. We find that there is insufficient evidence to support the association of one isolate with a specific disease, due to the multistrain nature of H. pylori infection shown in this work

Exclusion of NFAT5 from Mitotic Chromatin Resets Its Nucleo-Cytoplasmic Distribution in Interphase

The transcription factor NFAT5 is a major inducer of osmoprotective genes and is required to maintain the proliferative capacity of cells exposed to hypertonic stress. In response to hypertonicity, NFAT5 translocates to the nucleus, binds to regulatory regions of osmoprotective genes and activates their transcription. Besides stimulus-specific regulatory mechanisms, the activity of transcription factors in cycling cells is also regulated by the passage through mitosis, when most transcriptional processes are downregulated. It was not known whether mitosis could be a point of control for NFAT5.Using confocal microscopy we observed that NFAT5 was excluded from chromatin during mitosis in both isotonic and hypertonic conditions. Analysis of NFAT5 deletions showed that exclusion was mediated by the carboxy-terminal domain (CTD). NFAT5 mutants lacking this domain showed constitutive binding to mitotic chromatin independent of tonicity, which caused them to localize in the nucleus and remain bound to chromatin in the subsequent interphase without hypertonic stimulation. We analyzed the contribution of the CTD, DNA binding, and nuclear import and export signals to the subcellular localization of this factor. Our results indicated that cytoplasmic localization of NFAT5 in isotonic conditions required both the exclusion from mitotic DNA and active nuclear export in interphase. Finally, we identified several regions within the CTD of NFAT5, some of them overlapping with transactivation domains, which were separately capable of causing its exclusion from mitotic chromatin.Our results reveal a multipart mechanism regulating the subcellular localization of NFAT5. The transactivating module of NFAT5 switches its function from an stimulus-specific activator of transcription in interphase to an stimulus-independent repressor of binding to DNA in mitosis. This mechanism, together with export signals acting in interphase, resets the cytoplasmic localization of NFAT5 and prevents its nuclear accumulation and association with DNA in the absence of hypertonic stress

Cough Frequency During Treatment Associated With Baseline Cavitary Volume and Proximity to the Airway in Pulmonary TB.

BACKGROUND: Cough frequency, and its duration, is a biomarker that can be used in low-resource settings without the need of laboratory culture and has been associated with transmission and treatment response. Radiologic characteristics associated with increased cough frequency may be important in understanding transmission. The relationship between cough frequency and cavitary lung disease has not been studied. METHODS: We analyzed data in 41 adults who were HIV negative and had culture-confirmed, drug-susceptible pulmonary TB throughout treatment. Cough recordings were based on the Cayetano Cough Monitor, and sputum samples were evaluated using microscopic observation drug susceptibility broth culture; among culture-positive samples, bacillary burden was assessed by means of time to positivity. CT scans were analyzed by a US-board-certified radiologist and a computer-automated algorithm. The algorithm evaluated cavity volume and cavitary proximity to the airway. CT scans were obtained within 1 month of treatment initiation. We compared small cavities (≤ 7 mL) and large cavities (> 7 mL) and cavities located closer to (≤ 10 mm) and farther from (> 10 mm) the airway to cough frequency and cough cessation until treatment day 60. RESULTS: Cough frequency during treatment was twofold higher in participants with large cavity volumes (rate ratio [RR], 1.98; P = .01) and cavities located closer to the airway (RR, 2.44; P = .001). Comparably, cough ceased three times faster in participants with smaller cavities (adjusted hazard ratio [HR], 2.89; P = .06) and those farther from the airway (adjusted HR, 3.61;, P = .02). Similar results were found for bacillary burden and culture conversion during treatment. CONCLUSIONS: Cough frequency during treatment is greater and lasts longer in patients with larger cavities, especially those closer to the airway

tropiTree:an NGS-based EST-SSR resource for 24 tropical tree species

The development of genetic tools for non-model organisms has been hampered by cost, but advances in next-generation sequencing (NGS) have created new opportunities. In ecological research, this raises the prospect for developing molecular markers to simultaneously study important genetic processes such as gene flow in multiple non-model plant species within complex natural and anthropogenic landscapes. Here, we report the use of bar-coded multiplexed paired-end Illumina NGS for the de novo development of expressed sequence tag-derived simple sequence repeat (EST-SSR) markers at low cost for a range of 24 tree species. Each chosen tree species is important in complex tropical agroforestry systems where little is currently known about many genetic processes. An average of more than 5,000 EST-SSRs was identified for each of the 24 sequenced species, whereas prior to analysis 20 of the species had fewer than 100 nucleotide sequence citations. To make results available to potential users in a suitable format, we have developed an open-access, interactive online database, tropiTree (http://bioinf.hutton.ac.uk/tropiTree), which has a range of visualisation and search facilities, and which is a model for the efficient presentation and application of NGS data