Deep sr-DDL: Deep structurally regularized dynamic dictionary learning to integrate multimodal and dynamic functional connectomics data for multidimensional clinical characterizations.

We propose a novel integrated framework that jointly models complementary information from resting-state functional MRI (rs-fMRI) connectivity and diffusion tensor imaging (DTI) tractography to extract biomarkers of brain connectivity predictive of behavior. Our framework couples a generative model of the connectomics data with a deep network that predicts behavioral scores. The generative component is a structurally-regularized Dynamic Dictionary Learning (sr-DDL) model that decomposes the dynamic rs-fMRI correlation matrices into a collection of shared basis networks and time varying subject-specific loadings. We use the DTI tractography to regularize this matrix factorization and learn anatomically informed functional connectivity profiles. The deep component of our framework is an LSTM-ANN block, which uses the temporal evolution of the subject-specific sr-DDL loadings to predict multidimensional clinical characterizations. Our joint optimization strategy collectively estimates the basis networks, the subject-specific time-varying loadings, and the neural network weights. We validate our framework on a dataset of neurotypical individuals from the Human Connectome Project (HCP) database to map to cognition and on a separate multi-score prediction task on individuals diagnosed with Autism Spectrum Disorder (ASD) in a five-fold cross validation setting. Our hybrid model outperforms several state-of-the-art approaches at clinical outcome prediction and learns interpretable multimodal neural signatures of brain organization.

A joint network optimization framework to predict clinical severity from resting state functional MRI data.

We propose a novel optimization framework to predict clinical severity from resting state fMRI (rs-fMRI) data. Our model consists of two coupled terms. The first term decomposes the correlation matrices into a sparse set of representative subnetworks that define a network manifold. These subnetworks are modeled as rank-one outer-products which correspond to the elemental patterns of co-activation across the brain; the subnetworks are combined via patient-specific non-negative coefficients. The second term is a linear regression model that uses the patient-specific coefficients to predict a measure of clinical severity. We validate our framework on two separate datasets in a ten fold cross validation setting. The first is a cohort of fifty-eight patients diagnosed with Autism Spectrum Disorder (ASD). The second dataset consists of sixty three patients from a publicly available ASD database. Our method outperforms standard semi-supervised frameworks, which employ conventional graph theoretic and statistical representation learning techniques to relate the rs-fMRI correlations to behavior. In contrast, our joint network optimization framework exploits the structure of the rs-fMRI correlation matrices to simultaneously capture group level effects and patient heterogeneity. Finally, we demonstrate that our proposed framework robustly identifies clinically relevant networks characteristic of ASD.

Photo-irradiated biosynthesis of silver nanoparticles using edible mushroom pleurotus Florida and their antibacterial activity studies.

This is a report on photo-irradiated extracellular synthesis of silver nanoparticles using the aqueous extract of edible oyster mushroom (Pleurotus florida) as a reducing agent. The appearance, size, and shape of the silver nanoparticles are understood by UV-visible spectroscopy, field emission scanning electron microscopy, transmission electron microscopy, and atomic force microscopy. The X-ray diffraction studies, energy dispersive X-ray analysis indicate that particles are crystalline in nature. Fourier transform infrared spectroscopy analysis revealed that the nanoparticles are covered with biomoieties on their surface. As can be seen from our studies, the biofunctionalized silver nanoparticles thus produced have shown admirable antimicrobial effects, and the synthetic procedure involved is eco-friendly and simple, and hence high range production of the same can be considered for using them in many pharmaceutical applications.

Validation of the Clinical COPD Questionnaire as a psychophysical outcome measure in adult laryngotracheal stenosis.

OBJECTIVES: To validate the Clinical Chronic Obstructive Pulmonary Disease Questionnaire (CCQ), a patient-administered instrument developed for bronchopulmonary disease as a disease-specific psychophysical outcome measure for adult laryngotracheal stenosis. DESIGN: Prospective observational study. SETTINGS: Tertiary/National referral airway reconstruction centre. PARTICIPANTS: Thirty-three tracheostomy-free patients undergoing endoscopic laryngotracheoplasty. MAIN OUTCOME MEASURES: CCQ and the Medical Research Council (MRC) Dyspnoea scale, a previously validated but more limited scale, were administered to patients 2 weeks before surgery, preoperatively, and 2 weeks after endoscopic laryngotracheoplasty. Pulmonary function was assessed preoperatively. Internal consistency was assessed with Cronbach alpha statistics and test-retest reliability was determined using intraclass correlation. Correlations between CCQ and MRC scale, and pulmonary function were used to assess convergent and divergent validity respectively. Instrument responsiveness was assessed by correlating total and domain-specific CCQ scores with anatomical disease severity and post-treatment effect size. RESULTS: There were 12 males and 21 females. Mean age was 44 +/- 15 years. Cronbach alpha coefficient and intraclass correlation coefficient were 0.88 and 0.95 respectively. Total and domain-specific CCQ scores significantly correlated with the MRC scores (P < 0.001) and significant correlations between CCQ and peak expiratory flow rate and FEV(1) were identified (P < 0.03). There were statistically significant changes in total and domain-specific CCQ scores when different stenosis severities were compared. Clinical COPD Questionnaire scores also changed significantly and congruently following surgery (P < 0.05 in both cases). DISCUSSION: Clinical COPD Questionnaire is a valid and sensitive instrument for assessing symptom severity and levels of function and well-being in adult patients with laryngotracheal stenosis and can be used as a patient-centred disease-specific outcome measure for this condition.

Use of material decomposition in the context of neurovascular intervention using standard flat panel and a high-resolution CMOS detector.

The imaging of endovascular devices during neurovascular procedures such as the coiling of aneurysms guided with CBCT imaging may be challenging due to the presence of highly attenuating materials such as platinum in the coil and stent marker, nickel-titanium in the stent, iodine in the contrast agent, and tantalum in the embolization agent. The use of dual-energy imaging followed by a basis material decomposition image processing-scheme may improve the feature separation and recognition. Two sets of testing were performed to validate this concept. The first trial was the acquisition of dual-energy micro-CBCT data of a 3D-printed simple aneurysm model using a 49.5 µm pixel size CMOS detector (Teledyne DALSA, Waterloo, ON.). Two sets of projection data were acquired using beam energies of 35 kVp and 70 kVp. Axial slices were reconstructed and used to carry out the material decomposition processing. The second trial was the acquisition of dual-energy CBCT images of a RS-240T angiographic head phantom (Radiology Support Devices Inc., CA.) with an iodine vascular insert using a Toshiba Infinix BiPlane C-arm system coupled to a flat panel detector. Two sets of image data were acquired using beam energies of 80 kVp and 120 kVp. Following image reconstruction, slices of the phantom were decomposed using the same processing as previously. The resulting image data over both trials indicate that the decomposition process was successful in separating the kinds of materials commonly used during a neurovascular intervention, such as platinum, cobalt-chromium, and iodine. The normalized root mean square error metric was used to quantitatively assess this. This indicates a basis for future more clinically relevant testing of our methods.

Beware Cold Agglutinins in Organ Donors! Ex Vivo Lung Perfusion From an Uncontrolled Donation After Circulatory-Determination-of-Death Donor With a Cold Agglutinin: A Case Report.

BACKGROUND: We began to recover lungs from uncontrolled donation after circulatory determination of death to assess for transplant suitability by means of ex vivo lung perfusion (EVLP) and computerized tomographic (CT) scan. Our first case had a cold agglutinin with an interesting outcome. CASE REPORT: A 60-year-old man collapsed at home and was pronounced dead by Emergency Medical Services personnel. Next-of-kin consented to lung retrieval, and the decedent was ventilated and transported. Lungs were flushed with cold Perfadex, removed, and stored cold. The lungs did not flush well. Medical history revealed a recent hemolytic anemia and a known cold agglutinin. Warm nonventilated ischemia time was 51 minutes. O2-ventilated ischemia time was 141 minutes. Total cold ischemia time was 6.5 hours. At cannulation for EVLP, established clots were retrieved from both pulmonary arteries. At initiation of EVLP with Steen solution, tiny red aggregates were observed initially. With warming, the aggregates disappeared and the perfusate became red. After 1 hour, EVLP was stopped because of florid pulmonary edema. The lungs were cooled to 20°C; tiny red aggregates formed again in the perfusate. Ex vivo CT scan showed areas of pulmonary edema and a pyramidal right middle lobe opacity. Dissection showed multiple pulmonary emboli-the likely cause of death. However, histology showed agglutinated red blood cells in the microvasculature in pre- and post-EVLP biopsies, which may have contributed to inadequate parenchymal preservation. CONCLUSIONS: Organ donors with cold agglutinins may not be suitable owing to the impact of hypothermic preservation.

Variable responses of human microbiomes to dietary supplementation with resistant starch.

BACKGROUND: The fermentation of dietary fiber to various organic acids is a beneficial function provided by the microbiota in the human large intestine. In particular, butyric acid contributes to host health by facilitating maintenance of epithelial integrity, regulating inflammation, and influencing gene expression in colonocytes. We sought to increase the concentration of butyrate in 20 healthy young adults through dietary supplementation with resistant starch (unmodified potato starch-resistant starch (RS) type 2). METHODS: Fecal samples were collected from individuals to characterize butyrate concentration via liquid chromatography and composition of the microbiota via surveys of 16S rRNA-encoding gene sequences from the Illumina MiSeq platform. Random Forest and LEfSe analyses were used to associate responses in butyrate production to features of the microbiota. RESULTS: RS supplementation increased fecal butyrate concentrations in this cohort from 8 to 12 mmol/kg wet feces, but responses varied widely between individuals. Individuals could be categorized into three groups based upon butyrate concentrations before and during RS: enhanced, high, and low (n = 11, 3, and 6, respectively). Fecal butyrate increased by 67 % in the enhanced group (from 9 to 15 mmol/kg), while it remained ≥11 mmol/kg in the high group and ≤8 mmol/kg in the low group. Microbiota analyses revealed that the relative abundance of RS-degrading organisms-Bifidobacterium adolescentis or Ruminococcus bromii-increased from ~2 to 9 % in the enhanced and high groups, but remained at ~1.5 % in the low group. The lack of increase in RS-degrading bacteria in the low group may explain why there was no increase in fecal butyrate in response to RS. The microbiota of individuals in the high group were characterized by an elevated abundance of the butyrogenic microbe Eubacterium rectale (~6 % in high vs. 3 % in enhanced and low groups) throughout the study. CONCLUSIONS: We document the heterogeneous responses in butyrate concentrations upon RS supplementation and identify characteristic of the microbiota that appear to underlie this variation. This study complements and extends other studies that call for personalized approaches to manage beneficial functions provided by gut microbiomes.

Brain responses to biological motion predict treatment outcome in young children with autism.

Autism spectrum disorders (ASDs) are common yet complex neurodevelopmental disorders, characterized by social, communication and behavioral deficits. Behavioral interventions have shown favorable results-however, the promise of precision medicine in ASD is hampered by a lack of sensitive, objective neurobiological markers (neurobiomarkers) to identify subgroups of young children likely to respond to specific treatments. Such neurobiomarkers are essential because early childhood provides a sensitive window of opportunity for intervention, while unsuccessful intervention is costly to children, families and society. In young children with ASD, we show that functional magnetic resonance imaging-based stratification neurobiomarkers accurately predict responses to an evidence-based behavioral treatment-pivotal response treatment. Neural predictors were identified in the pretreatment levels of activity in response to biological vs scrambled motion in the neural circuits that support social information processing (superior temporal sulcus, fusiform gyrus, amygdala, inferior parietal cortex and superior parietal lobule) and social motivation/reward (orbitofrontal cortex, insula, putamen, pallidum and ventral striatum). The predictive value of our findings for individual children with ASD was supported by a multivariate pattern analysis with cross validation. Predicting who will respond to a particular treatment for ASD, we believe the current findings mark the very first evidence of prediction/stratification biomarkers in young children with ASD. The implications of the findings are far reaching and should greatly accelerate progress toward more precise and effective treatments for core deficits in ASD.

Characterization of non-membrane-damaging cytotoxin of non-toxigenic Vibrio cholerae O1 and its relevance to disease.

The non-membrane-damaging cytotoxin which causes dramatic cell rounding of cultured HeLa cells was purified to homogeneity from a clinical strain (WO5) of non-toxigenic Vibrio cholerae O1 Inaba belonging to the E1 Tor biotype. The purified protein has a denatured molecular weight of 35 kDa and a native molecular weight of approximately 37 kDa indicating the monomeric nature of the protein. The 15 N-terminal amino acid sequence of non-membrane-damaging cytotoxin showed complete homology to the hemagglutinin protease previously purified and characterized from V. cholerae O1. Purified non-membrane-damaging cytotoxin from V. cholerae O1 was immunologically and biochemically identical to that previously purified from V. cholerae O26. Non-membrane-damaging cytotoxin was found to be enterotoxic in rabbit ileal loop assay inducing accumulation of non-hemorrhagic fluid at 100 micrograms and elicited a concentration dependent increase in short circuit current and tissue conductance of rabbit ileal mucosa mounted on Ussing chambers. A significant serum immunoglobulin G response against non-membrane-damaging cytotoxin was elicited by patients infected with V. cholerae O139 but not with V. cholerae O1. These properties make non-membrane-damaging cytotoxin a potential virulence factor of V. cholerae which should be taken into consideration while making live, attenuated recombinant vaccine strains against cholera.

Coronary ventricular fistula as a complication of PTCA: a case report and literature review.

A 58-year-old man with previous myocardial infarction and coronary bypass surgery underwent angioplasty to a totally occluded venous graft to the left anterior descending artery (LAD). The procedure resulted in a coronary-ventricular fistula. Prolonged inflation of the balloon in the proximal part of the graft resulted in obliteration of the fistula with little haemodynamic compromise.

An epidemic of diarrhoea in south India caused by enteroaggregative Escherichia coli.

A diarrhoeal epidemic in a village close to Vellore was investigated in January 1996. Faecal samples were obtained from 20 subjects with diarrhoea and from 11 individuals without diarrhoea (controls) and were examined for bacterial, viral and parasitic enteropathogens. Water samples from all sources in the village were analysed. The epidemic affected all age groups (overall attack rate 15%). The mean duration of diarrhoea was 11 days. Individuals who consumed water exclusively from a borewell had a lower relative risk (RR) of disease (0.14, 95% Cl 0.02-1.01) compared to users of two open wells (RR 6.93, Cl 0.99-48.66 and RR 7.81, Cl 1.02-59.79, respectively). No conventional bacterial enteropathogens were isolated from the stool samples. Enteroaggregative Escherichia coli (EAggEC) were identified in the stool of 11 of 20 subjects with diarrhoea, and in 1 of 11 control samples (P = 0.02). All the EAggEC isolates from the patients had identical antibiotic sensitivity patterns and produced a toxin in Ussing chamber studies. Serotyping indicated that all the EAggEC from individuals with diarrhoea belonged to one or other of two serotypes. All water samples had high coliform counts and E. coli were cultured from the two open wells but not from the borewell. The evidence suggests that EAggEC was responsible for this outbreak of diarrhoea. EAggEC should be considered as a possible pathogen in unexplained diarrhoeal outbreaks in developing countries.

The relative effect of dietary fats and carbohydrates on lipid metabolism in the albino rat.

This study is concerned with the effect of two carbohydrates, cane-sugar and corn starch, at four different levels in the presence of two dietary fats, on the serum and the tissue lipids (cholesterol, phospholipid and fatty acid patterns). Keeping the dietary fats (coconut safflower seed oil) at 20% level, diets containing (a) startch (54%) + cane sugar (0%), (b) starch (44%) + cane sugar 10%), (c) starch (10%) + cane sugar (44%) and (d) only cane sugar (54%) were administered to rats for 8 weeks. The lipid levels were determined at the end of the feeding period. The beneficial effect of the unsaturated fat in lowering the serum cholesterol level is nullified by an excess of cane sugar in the diet. In liver, there is an increase of 40-50% of cholesterol, as the cane sugar level in the diet is raised, irrespective of the type of dietary fat. The fatty acid pattern of the serum and tissue lipids is influenced by dietary fats as well as carbohydrates.

Photo-bio-synthesis of irregular shaped functionalized gold nanoparticles using edible mushroom Pleurotus florida and its anticancer evaluation.

A green chemistry approach to the synthesis of gold nanoparticles using edible mushroom Pleurotus florida (Oyster mushroom) by photo-irradiation method has been attempted. The mixture containing the aqueous gold ions and the mushroom extract was exposed to sunlight; this resulted in the formation of biofunctionalized gold nanoparticles. These nanoparticles were characterized using various techniques like UV-visible spectroscopy; X-ray diffraction studies, Energy dispersive X-ray analysis, Field emission scanning electron microscopy, Atomic force microscopy, Transmission electron microscopy and Fourier transform infrared spectrometry. The obtained biofunctionalized gold nanoparticles showed effective anti-cancer property against four different cancer cell lines A-549 (Human lung carcinoma), K-562 (Human chronic myelogenous leukemia bone marrow), HeLa (Human cervix) and MDA-MB (Human adenocarcinoma mammary gland) and no lethal effect is observed in Vero (African green monkey kidney normal cell) cell lines.

Anti-cancer studies of noble metal nanoparticles synthesized using different plant extracts.

Biofunctionalized gold and silver nanoparticles synthesized using different plant extracts of guava and clove in vitro anti-cancer efficacy against four different cancer cell lines human colorectal adenocarcinoma, human kidney, human chronic myelogenous, leukemia, bone marrow, and human cervix have been studied and reported. The present experimental study suggests that flavonoids functionalized gold nanoparticles synthesized using aqueous clove buds extract are more potential than guava leaf extract towards anti-cancer activities. The microscopic and 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide (XTT) assay infer that the functionalized irregular shaped gold nanoparticles synthesized with aqueous clove bud extract showed a satisfactory anti-cancer effect on all the cell lines. The silver nanoparticles synthesized using same extracts are devoid of anti-cancer activity. The XTT assay revealed dose-dependent cytotoxicity to cancer cell lines. The study revealed that the free radicals generated by gold nanoparticles are responsible for anti-cancer effect. To confirm the free-radical scavenging efficacy of gold nanoparticle, nitric oxide assay is followed. We observed that the gold nanoparticles swabbed the free radicals in dose-dependent manner. With continued improvements, these nanoparticles may prove to be potential anti-cancer agents.

Rapid biosynthesis of irregular shaped gold nanoparticles from macerated aqueous extracellular dried clove buds (Syzygium aromaticum) solution.

In this paper, we stress upon rapid synthesis of irregular shape gold nanoparticles from a biological base. Treatment of macerated extracellular aqueous dried clove buds (Syzygium aromaticum) solution with the aqueous gold salt solution yielded irregular shaped stable gold nanoparticles in the range of 5-100 nm. The synthesis and morphology of these gold nanoparticles are understood by UV (UV-vis spectroscopy), FESEM (field emission scanning electron microscopy), TEM (transmission electron microscopy) and AFM (atomic force microscopy) techniques. The formation of these bio-adsorbed gold nanoparticles is rapid as the reaction process completes within few minutes. The XRD (X-ray diffraction studies) and EDAX (energy dispersive X-ray analysis) show that the particles are crystalline in nature. This clean-green method of synthesis is performed under ambient conditions. Probable biochemical pathway of the synthesis is studied using FTIR (Fourier transformed infrared spectroscopy). It is observed that the freely water soluble flavonoids of clove buds are responsible for bioreduction. The possible applications viz., catalysis, sensor, diagnostics, biomedical imaging and photo thermal therapy of these functionalized noble metal nanoparticles are envisaged.

Pulsar discovery by global volunteer computing.

Einstein@Home aggregates the computer power of hundreds of thousands of volunteers from 192 countries to mine large data sets. It has now found a 40.8-hertz isolated pulsar in radio survey data from the Arecibo Observatory taken in February 2007. Additional timing observations indicate that this pulsar is likely a disrupted recycled pulsar. PSR J2007+2722's pulse profile is remarkably wide with emission over almost the entire spin period; the pulsar likely has closely aligned magnetic and spin axes. The massive computing power provided by volunteers should enable many more such discoveries.