Toll-like receptor-4 299Gly allele is associated with Guillain-Barre syndrome in Bangladesh

Objective: TLR4 plays an important role in the pathogenesis of Guillain-Barre syndrome (GBS). The relationships between TLR4 polymorphisms and susceptibility to GBS are poorly understood. We investigated the frequency and assessed the association of two single nucleotide polymorphisms (SNPs) in the extracellular domain of TLR4 (Asp299Gly and Thr399Ile) with disease susceptibility and the clinical features of GBS in a Bangladeshi cohort. Methods: A total of 290 subjects were included in this study: 141 patients with GBS and 149 unrelated healthy controls. The TLR4 polymorphisms Asp299Gly and Thr399Ile were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Results: The minor 299Gly allele was significantly associated with GBS susceptibility (P = 0.0137, OR = 1.97, 95% CI = 1.17–3.31), and was present at a significantly higher frequency in patients with the acute motor axonal neuropathy (AMAN) subtype of GBS (P = 0.0120, OR = 2.37, 95% CI = 1.26–4.47) than acute inflammatory demyelinating polyneuropathy (AIDP) subtype (P = 0.961, OR = 1.15, 95% CI = 0.38–3.48); when compared to healthy controls. The genotype frequency of the Asp299Gly polymorphism was not significantly different between patients with GBS and healthy controls. The Asp299-Thr399 haplotype was associated with a significantly lower risk of developing GBS (P = 0.0451, OR = 0.63, 95% CI = 0.40– 0.99). No association was observed between the Thr399Ile polymorphism and GBS disease susceptibility. Interpretation: The TLR4 minor 299Gly allele was associated with increased susceptibility to GBS and the axonal GBS subtype in the Bangladeshi population. However, no associations were observed between the genotypes of the Asp299Gly and Thr399Ile SNPs and antecedent C. jejuni infection or disease severity in Bangladeshi patients with GBS

Automated Reconstruction of Neuronal Morphology Based on Local Geometrical and Global Structural Models

Digital reconstruction of neurons from microscope images is an important and challenging problem in neuroscience. In this paper, we propose a model-based method to tackle this problem. We first formulate a model structure, then develop an algorithm for computing it by carefully taking into account morphological characteristics of neurons, as well as the image properties under typical imaging protocols. The method has been tested on the data sets used in the DIADEM competition and produced promising results for four out of the five data sets

Increased waterborne blaNDM-1 resistance gene abundances associated with seasonal human pilgrimages to the Upper Ganges River

Antibiotic resistance (AR) is often rooted in inappropriate antibiotic use, but poor water quality and inadequate sanitation exacerbate the problem, especially in emerging countries. An example is increasing multi-AR due to mobile carbapenemases, such as NDM-1 protein (coded by blaNDM-1 genes), which can produce extreme drug-resistant phenotypes. In 2010, NDM-1 positive isolates and blaNDM-1 genes were detected in surface waters across Delhi and have since been detected across the urban world. However, little is known about blaNDM-1 levels in more pristine locations, such as the headwaters of the Upper Ganges River. This area is of particular interest because it receives massive numbers of visitors during seasonal pilgrimages in May/June, including visitors from urban India. Here we quantified blaNDM-1 abundances, other AR genes (ARG) and coliform bacteria in sediments and water column samples from seven sites in the Rishikesh-Haridwar region of the Upper Ganges and five sites on the Yamuna River in Delhi to contrast blaNDM-1 levels and water quality conditions between season and region. Water quality in the Yamuna was very poor (e.g., anoxia at all sites), and blaNDM-1 abundances were high across sites in water (5.4 ± 0.4 log(blaNDM-1·mL-1); 95% confidence interval) and sediment (6.3 ± 0.7 log(blaNDM-1·mg-1)) samples from both seasons. In contrast, water column blaNDM-1 abundances were very low across all sites (2.1 ± 0.6 log(blaNDM-1·mL-1)) in February in the Upper Ganges and water quality was good (e.g., near saturation oxygen). However, per capita blaNDM-1 levels were 20 times greater in June in the Ganges water column relative to February and blaNDM-1 levels significantly correlated with fecal coliform levels (r=0.61; p=0.007). Given waste management infrastructure is limited in Rishikesh-Haridwar; data imply blaNDM-1 levels are higher in visitor's wastes than local residents, which results in seasonally higher blaNDM-1 levels in the river. Pilgrimage areas without adequate waste treatment are possible "hot spots" for AR transmission, and waste treatment must be improved to reduce broader AR dissemination via exposed returning visitors

Changing perspectives on the internationalization of R&D and innovation by multinational enterprises: a review of the literature

Internationalization of R&D and innovation by Multinational Enterprises (MNEs) has undergone a gradual and comprehensive change in perspective over the past 50 years. From sporadic works in the late 1950s and in the 1960s, it became a systematically analysed topic in the 1970s, starting with pioneering reports and “foundation texts”. Our review unfolds the theoretical and empirical evolution of the literature from dyadic interpretations of centralization versus decentralization of R&D by MNEs to more comprehensive frameworks, wherein established MNEs from Advanced Economies still play a pivotal role, but new players and places also emerge in the global generation and diffusion of knowledge. Hence views of R&D internationalization increasingly rely on concepts, ideas and methods from IB and other related disciplines such as industrial organization, international economics and economic geography. Two main findings are highlighted. First, scholarly research pays an increasing attention to the network-like characteristics of international R&D activities. Second, different streams of literature have emphasized the role of location- specific factors in R&D internationalization. The increasing emphasis on these aspects has created new research opportunities in some key areas, including inter alia: cross-border knowledge sourcing strategies, changes in the geography of R&D and innovation, and the international fragmentation of production and R&D activities

Hybrid microalgae-activated sludge system for carbon-efficient wastewater treatment

Engineered microalgae-bacteria systems can play a key role in the realisation of energy-efficient carbon-neutral wastewater treatment technologies. An attempt was made to develop a hybrid microalgae-activated sludge (HMAS) system coupling carbon capture with domestic wastewater treatment. Photobioreactors internally illuminated with red light-emitting diodes (LEDs), and inoculated with mixed microbial culture, resulted in substantial savings in operational cost. System performance was evaluated at about 600 μmol/m2 s LED irradiance while treating synthetic municipal wastewater in a chemostat for about 2 months, containing about 250 mg/L soluble chemical oxygen demand (SCOD), 90 mg/L NH3-N and 10 mg/L orthophosphate. Carbon dioxide was supplied into the HMAS at 25 mL/min, 25% v/v. SCOD was efficiently removed from the wastewater (up to 70%) and bacterial oxygen requirement of >2 mg/L was met through microalgal photosynthesis. The system demonstrated its potential in achieving carbon-efficient wastewater treatment. HIGHLIGHTS A hybrid microalgae-activated sludge (HMAS) system coupling carbon capture with wastewater treatment.; Up to 75% soluble chemical oxygen demand removal achieved.; Ammonium removal efficiencies greater than 90% were achieved in all the bioreactors.; Need for external aeration was eliminated by satisfying bacterial oxygen requirements.; Need for further studies with other types of wastewater.

Hospital Wastewater Releases of Carbapenem-Resistance Pathogens and Genes in Urban India

Increasing antibiotic resistant hospital-acquired infections and limited new antibiotic discovery are jeopardizing human health at global scales, although how hospitals themselves fuel antimicrobial resistance (AMR) in the wider environment is largely unknown. Antibiotic resistance (AR) in hospitals in countries such as India is potentially problematic because of high antibiotic use, overcrowding, and inadequate wastewater containment. Here we quantified fecal coliforms (FC), carbapenem-resistant Enterobacteriaceae (CRE), <i>bla</i>_{<i>NDM‑1</i>}, and selected extended-spectrum β-lactam (ESBL) resistant bacteria and genes in 12 hospital wastewater outfalls and five background sewer drains across New Delhi over two seasons. Hospital wastewaters had up to 9 orders of magnitude greater concentrations of CRE bacteria and <i>bla</i>_NDM‑1 than local sewers (depending on the hospital), implying hospitals contribute high concentrations of AR relative to community sources in Delhi, especially during the winter. Significant correlations were found between FC levels (a fecal indictor), and CRE (<i>r</i> = 0.924; <i>p</i> = 0.005), <i>bla</i>_NDM‑1 (<i>r</i> = 0.934, <i>p</i> = 0.009), and ESBL-resistant bacteria (<i>r</i> = 0.913, <i>p</i> = 0.010) levels across hospital wastewaters, respectively, implying that elevated CRE and <i>bla</i>_NDM‑1 are of patient origin. However, of greater importance to global health, microbial culturing found 18 to 41% of wastewater CRE isolates (<i>n</i> = 1447) were on the WHO “critical pathogen” list in urgent need of new antibiotics, and 55% of CRE isolates from larger hospitals carried at least one <i>bla</i>_NDM‑1 gene. Wastewater releases from New Delhi hospitals may pose a greater AR exposure risk to residents than believed, implying in-hospital antibiotic use must be better controlled and more effective waste treatment is needed for hospital wastewaters