Integrating sample similarities into latent class analysis: a tree-structured shrinkage approach

This paper is concerned with using multivariate binary observations to estimate the probabilities of unobserved classes with scientific meanings. We focus on the setting where additional information about sample similarities is available and represented by a rooted weighted tree. Every leaf in the given tree contains multiple samples. Shorter distances over the tree between the leaves indicate a priori higher similarity in class probability vectors. We propose a novel data integrative extension to classical latent class models with tree-structured shrinkage. The proposed approach enables (1) borrowing of information across leaves, (2) estimating data-driven leaf groups with distinct vectors of class probabilities, and (3) individual-level probabilistic class assignment given the observed multivariate binary measurements. We derive and implement a scalable posterior inference algorithm in a variational Bayes framework. Extensive simulations show more accurate estimation of class probabilities than alternatives that suboptimally use the additional sample similarity information. A zoonotic infectious disease application is used to illustrate the proposed approach. The paper concludes by a brief discussion on model limitations and extensions.     

Twenty‐Four‐Hour and Annual Variation in Onset of Epistaxis in Osler Disease

Osler disease is an autosomal dominant disorder of the fibrovascular tissue characterized by arteriovenous malformations with multi‐systemic haemorrhages. Recurrent epistaxis is the predominant symptom in more than 90% of patients. Recent studies showed circadian and seasonal patterns in the onset of nosebleeds, similar to acute cardiovascular events, such as myocardial infarction and stroke. The aim of this study was to determine whether such patterns would also apply to the onset of epistaxis in patients with Osler disease. In all, 110 patients with Osler disease who were under treatment for recurrent epistaxis at the University Hospital of Mannheim were requested to complete a questionnaire addressing the intensity and frequency of epistaxis according to the classification of Bergler et al., as well as circadian and circannual rhythmicity in the occurrence of epistaxis according to visual analogue scales (VAS). More than half of the patients claimed to experience daily to weekly episodes of recurrent epistaxis. The occurrence of epistaxis showed a biphasic 24 h pattern, with a primary peak in the morning (05∶00–8∶00 h) and smaller secondary peaks in the evening (17∶00–20∶00 h and 21∶00–00∶00 h). No significant seasonal variation was found in the onset of epistaxis. However, a slight tendency, with a peak in winter months, was observed. Similar to other chronobiological studies on nosebleeds, this study showed that the 24 h pattern and seasonal tendency in the onset of epistaxis even applied to patients with Osler disease. Further investigations are necessary to determine the pathological mechanism underlying this phenomenon.     

Exploring Managers’ Perspectives on MNCH Program in Pakistan: A Qualitative Study

Background

Pakistan’s Maternal, Newborn and Child Health (MNCH) Program is faced with multiple challenges in service delivery, financial and logistic management, training and deployment of human resources, and integration within the existing health system. There is a lack of evidence on managerial aspects of the MNCH program management and implementation.

Methods and Findings

This study used qualitative methods to explore the challenges national, provincial and district program managers have faced in implementing a community midwifery program in province of Punjab while also exploring future directions for the program under a devolved health system. While the program had been designed in earnest, the planning lacked critical elements of involving relevant stakeholders in design and implementation, socio-demographic context and capacity of the existing health system. Financial limitations, weak leadership and lack of a political commitment to the problem of maternal health have also had an impact on program implementation.

Conclusions

Our study results suggest that there is a need to re-structure the program while ensuring sustainability and collaboration within the health sector to increase uptake of skilled birth attendance and improve maternal health care in Pakistan.     

Heavy metal uptake capacity of fresh water algae (Oedogonium westti) from aqueous solution: A mesocosm research

The green macroalgae present in freshwater ecosystems have attracted a great attention of the world scientists for removal of heavy metals from wastewater. In this mesocosm study, the uptake rates of heavy metals such as cadmium (Cd), nickel (Ni), chromium (Cr), and lead (Pb) by Oedogonium westi (O. westti) were measured. The equilibrium adsorption capabilities of O. westti were different for Cd, Ni, Cr, and Pb (0.974, 0.418, 0.620, and 0.261 mgg^–1, respectively) at 18°C and pH 5.0. Furthermore, the removal efficiencies for Cd, Cr, Ni and Pb were observed from 55–95%, 61–93%, 59–89%, and 61–96%, respectively. The highest removal efficiency was observed for Cd and Cr from aqueous solution at acidic pH and low initial metal concentrations. However, the removal efficiencies of Ni and Pb were higher at high pH and high concentrations of metals in aqueous solution. The results summarized that O. westti is a suitable candidate for removal of selected toxic heavy metals from the aqueous solutions.     

DNAH6 and Its Interactions with PCD Genes in Heterotaxy and Primary Ciliary Dyskinesia

Heterotaxy, a birth defect involving left-right patterning defects, and primary ciliary dyskinesia (PCD), a sinopulmonary disease with dyskinetic/immotile cilia in the airway are seemingly disparate diseases. However, they have an overlapping genetic etiology involving mutations in cilia genes, a reflection of the common requirement for motile cilia in left-right patterning and airway clearance. While PCD is a monogenic recessive disorder, heterotaxy has a more complex, largely non-monogenic etiology. In this study, we show mutations in the novel dynein gene DNAH6 can cause heterotaxy and ciliary dysfunction similar to PCD. We provide the first evidence that trans-heterozygous interactions between DNAH6 and other PCD genes potentially can cause heterotaxy. DNAH6 was initially identified as a candidate heterotaxy/PCD gene by filtering exome-sequencing data from 25 heterotaxy patients stratified by whether they have airway motile cilia defects. dnah6 morpholino knockdown in zebrafish disrupted motile cilia in Kupffer’s vesicle required for left-right patterning and caused heterotaxy with abnormal cardiac/gut looping. Similarly DNAH6 shRNA knockdown disrupted motile cilia in human and mouse respiratory epithelia. Notably a heterotaxy patient harboring heterozygous DNAH6 mutation was identified to also carry a rare heterozygous PCD-causing DNAI1 mutation, suggesting a DNAH6/DNAI1 trans-heterozygous interaction. Furthermore, sequencing of 149 additional heterotaxy patients showed 5 of 6 patients with heterozygous DNAH6 mutations also had heterozygous mutations in DNAH5 or other PCD genes. We functionally assayed for DNAH6/DNAH5 and DNAH6/DNAI1 trans-heterozygous interactions using subthreshold double-morpholino knockdown in zebrafish and showed this caused heterotaxy. Similarly, subthreshold siRNA knockdown of Dnah6 in heterozygous Dnah5 or Dnai1 mutant mouse respiratory epithelia disrupted motile cilia function. Together, these findings support an oligogenic disease model with broad relevance for further interrogating the genetic etiology of human ciliopathies.     

Concentration dependent growth/non-growth linked kinetics of endosulfan biodegradation by <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis>

The rates of biodegradation of endosulfan by P. aeruginosa were determined with different initial endosulfan concentrations (10, 50, 100, 150, 200 and 250 mg l⁻¹) and different growth linked kinetic models were fitted at these concentrations. At 10 mg endosulfan l⁻¹, Monod no growth model was well fitted. Monod with growth model described the biodegradation pattern at an initial concentration of 50, 100 and 150 mg endosulfan l⁻¹. Significant increases of P. aeruginosa MN2B14 density in broth culture during incubation further support this result. Conversely, zero order kinetic model was well fitted into the biodegradation data if initial endosulfan concentration was ≥200 mg endosulfan l⁻¹. The kinetics of endosulfan biodegradation by P. aeruginosa MN2B14 in liquid broth was highly dependent upon its initial concentration. The results of this study could be employed for predicting the persistence of endosulfan in water environment containing P. aeruginosa as an endosulfan degrading bacterium.     

Lipoxygenase inhibiting and antioxidant oligostilbene and monoterpene galactoside from Paeonia emodi

Paeoninol and paeonin C, oligostilbene and monoterpene galactoside, have been isolated from the methanolic extract of the fruits of Paeonia emodi. Their structures have been assigned on the basis of spectral analysis including 1D and 2D NMR techniques. In addition, 4-hydroxybenzoic acid 3, gallic acid 4 and methyl gallate 5 have also been reported for the first time from this species. Compounds 1 and 2 have displayed potent inhibitory potential against enzyme lipoxygenase in a concentration-dependent fashion with the IC(50) values 0.77 and 99.5 microM, along with ABTS(.+) radical quenching activity with IC(50) values of 147.5 and 498.2 microM, respectively.