Increased prevalence of precancerous changes in relatives of gastric cancer patients: critical role of H. pylori

Background & Aims:Helicobacter pylori is believed to predispose to gastric cancer by inducing gastric atrophy and hypochlorhydria. First-degree relatives of patients with gastric cancer have an increased risk of developing gastric cancer. The aim of this study was to determine the prevalence of atrophy and hypochlorhydria and their association with H. pylori infection in first-degree relatives of patients with gastric cancer. Methods:H. pylori status, gastric secretory function, and gastric histology were studied in 100 first-degree relatives of patients with noncardia gastric cancer and compared with those of controls with no family history of this cancer. Results: Compared with healthy controls, relatives of patients with gastric cancer had a higher prevalence of hypochlorhydria (27% vs. 3%) but a similar prevalence of H. pylori infection (63% vs. 64%). Relatives of cancer patients also had a higher prevalence of atrophy (34%) than patients with nonulcer dyspepsia (5%) matched for H. pylori prevalence. Among the relatives of cancer patients, the prevalence of atrophy and hypochlorhydria was increased only in those with evidence of H. pylori infection, was greater in relatives of patients with familial cancer than in relatives of sporadic cancer index patients, and increased with age. Eradication of H. pylori infection produced resolution of the gastric inflammation in each subject and resolution of hypochlorhydria and atrophy in 50% of the subjects. Conclusions: Relatives of patients with gastric cancer have an increased prevalence of precancerous gastric abnormalities, but this increase is confined to those with H. pylori infection. Consequently, prophylactic eradication of the infection should be offered to such subjects

Eimeria species occurrence varies between geographic regions and poultry production systems and may influence parasite genetic diversity

Coccidiosis is one of the biggest challenges faced by the global poultry industry. Recent studies have highlighted the ubiquitous distribution of all Eimeria species which can cause this disease in chickens, but intriguingly revealed a regional divide in genetic diversity and population structure for at least one species, Eimeria tenella. The drivers associated with such distinct geographic variation are unclear, but may impact on the occurrence and extent of resistance to anticoccidial drugs and future subunit vaccines. India is one of the largest poultry producers in the world and includes a transition between E. tenella populations defined by high and low genetic diversity. The aim of this study was to identify risk factors associated with the prevalence of Eimeria species defined by high and low pathogenicity in northern and southern states of India, and seek to understand factors which vary between the regions as possible drivers for differential genetic variation. Faecal samples and data relating to farm characteristics and management were collected from 107 farms from northern India and 133 farms from southern India. Faecal samples were analysed using microscopy and PCR to identify Eimeria occurrence. Multiple correspondence analysis was applied to transform correlated putative risk factors into a smaller number of synthetic uncorrelated factors. Hierarchical cluster analysis was used to identify poultry farm typologies, revealing three distinct clusters in the studied regions. The association between clusters and presence of Eimeria species was assessed by logistic regression. The study found that large-scale broiler farms in the north were at greatest risk of harbouring any Eimeria species and a larger proportion of such farms were positive for E. necatrix, the most pathogenic species. Comparison revealed a more even distribution for E. tenella across production systems in south India, but with a lower overall occurrence. Such a polarised region- and system-specific distribution may contribute to the different levels of genetic diversity observed previously in India and may influence parasite population structure across much of Asia and Africa. The findings of the study can be used to prioritise target farms to launch and optimise appropriate anticoccidial strategies for long-term control

Scattering of light and atoms in a Fermi-Dirac gas with BCS pairing

We theoretically study the optical properties of a Fermi-Dirac gas in the presence of a superfluid state. We calculate the leading quantum-statistical corrections to the standard column density result of the electric susceptibility. We also consider the Bragg diffraction of atoms by means of light-stimulated transitions of photons between two intersecting laser beams. Bardeen-Cooper-Schrieffer pairing between atoms in different internal levels magnifies incoherent scattering processes. The absorption linewidth of a Fermi-Dirac gas is broadened and shifted. Bardeen-Cooper-Schrieffer pairing introduces a collisional local-field shift that may dramatically dominate the Lorentz-Lorenz shift. For the case of the Bragg spectroscopy the static structure function may be significantly increased due to superfluidity in the nearforward scattering.Comment: 13 pages, 6 figures; to appear in PR

Cyclotrimerisation of isocyanates catalysed by low-coordinate Mn(II) and Fe(II) m-terphenyl complexes

Two- and three-coordinate m-terphenyl complexes of manganese and iron are efficient catalysts for the selective cyclotrimerisation of primary aliphatic isocyanates affording isocyanurates in short reaction times and under mild conditions

DNA replication initiation in Bacillus subtilis: Structural and functional characterization of the essential DnaA-DnaD interaction

© 2018 The Author(s). The homotetrameric DnaD protein is essential in low G+C content gram positive bacteria and is involved in replication initiation at oriC and re-start of collapsed replication forks. It interacts with the ubiquitously conserved bacterial master replication initiation protein DnaA at the oriC but structural and functional details of this interaction are lacking, thus contributing to our incomplete understanding of the molecular details that underpin replication initiation in bacteria. DnaD comprises N-terminal (DDBH1) and C-terminal (DDBH2) domains, with contradicting bacterial two-hybrid and yeast two-hybrid studies suggesting that either the former or the latter interact with DnaA, respectively. Using Nuclear Magnetic Resonance (NMR) we showed that both DDBH1 and DDBH2 interact with the N-terminal domain I of DnaA and studied the DDBH2 interaction in structural detail. We revealed two families of conformations for the DDBH2-DnaA domain I complex and showed that the DnaA-interaction patch of DnaD is distinct from the DNA-interaction patch, suggesting that DnaD can bind simultaneously DNA and DnaA. Using sensitive single-molecule FRET techniques we revealed that DnaD remodels DnaA-DNA filaments consistent with stretching and/or untwisting. Furthermore, the DNA binding activity of DnaD is redundant for this filament remodelling. This in turn suggests that DnaA and DnaD are working collaboratively in the oriC to locally melt the DNA duplex during replication initiation

Implementing the global plan to stop TB, 2011-2015 - optimizing allocations and the global fund's contribution: A scenario projections study

Background: The Global Plan to Stop TB estimates funding required in low- and middle-income countries to achieve TB control targets set by the Stop TB Partnership within the context of the Millennium Development Goals. We estimate the contribution and impact of Global Fund investments under various scenarios of allocations across interventions and regions. Methodology/Principal Findings: Using Global Plan assumptions on expected cases and mortality, we estimate treatment costs and mortality impact for diagnosis and treatment for drug-sensitive and multidrug-resistant TB (MDR-TB), including antiretroviral treatment (ART) during DOTS for HIV-co-infected patients, for four country groups, overall and for the Global Fund investments. In 2015, China and India account for 24% of funding need, Eastern Europe and Central Asia (EECA) for 33%, sub-Saharan Africa (SSA) for 20%, and other low- and middle-income countries for 24%. Scale-up of MDR-TB treatment, especially in EECA, drives an increasing global TB funding need - an essential investment to contain the mortality burden associated with MDR-TB and future disease costs. Funding needs rise fastest in SSA, reflecting increasing coverage need of improved TB/HIV management, which saves most lives per dollar spent in the short term. The Global Fund is expected to finance 8-12% of Global Plan implementation costs annually. Lives saved through Global Fund TB support within the available funding envelope could increase 37% if allocations shifted from current regional demand patterns to a prioritized scale-up of improved TB/HIV treatment and secondly DOTS, both mainly in Africa - with EECA region, which has disproportionately high per-patient costs, funded from alternative resources. Conclusions/Significance: These findings, alongside country funding gaps, domestic funding and implementation capacity and equity considerations, should inform strategies and policies for international donors, national governments and disease control programs to implement a more optimal investment approach focusing on highest-impact populations and interventions

A review of the Sentusidinium complex of dinoflagellate cysts

The Jurassic to Neogene (Miocene) dinoflagellate cyst genus Sentusidinium has a relatively simple overall morphology. This genus, together with Batiacasphaera, Kallosphaeridium and Pentafidia, comprises the Sentusidinium complex. This is distinct from the superficially similar laterally asymmetrical and subspheroidal/lenticular Cyclonephelium complex. The genus Sentusidinium is an acavate, subcircular, proximate to proximochorate, sexiform gonyaulacacean genus with an apical archaeopyle and typically low relief ornamentation. Since the erection of Sentusidinium in 1978, three similar genera have been established, which we consider to be taxonomic junior synonyms of that genus: Barbatacysta, Escharisphaeridia and Pilosidinium. However, we deem the Early Cretaceous to Miocene genera Batiacasphaera, Kallosphaeridium and Pentafidia are deemed to be separate from Sentusidinium. We refine the definition of the Early Cretaceous to Miocene genus Batiacasphaera to circumscribe cysts with a reticulate to rugulate autophragm and an apical archaeopyle with a free operculum. By contrast, Kallosphaeridium has a ventrally attached apical archaeopyle with five plates that can be interpreted as type (4A1I)@ or type (5A)@; it also has a small operculum relative to the overall cyst diameter. The six accepted Kallosphaeridium species are confined to the Palaeogene. The Australian genus Pentafidia is unusual in appearing to only have five precingular plates; this comprises two species from the Jurassic–Cretaceous transition of Western Australia. Therefore, we emend Sentusidinium to restrict it to acavate, proximate or proximochorate dinoflagellate cysts with an autophragm devoid of, or covered with, highly variable, non-linear ornamentation and a type (tA) apical archaeopyle. Occasionally the elements of ornamentation may be connected, but rarely is a cingulum indicated, and the tabulation is never clearly evident. A kalyptra may be occasionally present. The operculum is free. Following a comprehensive literature review, we accept 17 species in Batiacasphaera. In Kallosphaeridium we accept six species confidently and consider six species to be problematical. We list 38 (34 accepted and four problematical) species of Sentusidinium. Kallosphaeridium? helbyi is here transferred to Cyclonephelium without question. The species Batiacasphaera angularis is occasionally tabulate and hence we transfer it, with question, to Meiourgonyaulax. The Sentusidinium complex is clearly polyphyletic, and all genera considered herein belong to the order Gonyaulacales. Batiacasphaera, Kallosphaeridium and Pentafidia cannot be confidently assigned to a family, whereas Sentusidinium belongs to the Gonyaulacaceae. The number of species within the complex has been reduced from 137 to 68; furthermore, all infraspecific taxa have been eliminated

Scalar field exact solutions for non-flat FLRW cosmology: A technique from non-linear Schr\"odinger-type formulation

We report a method of solving for canonical scalar field exact solution in a non-flat FLRW universe with barotropic fluid using non-linear Schr\"{o}dinger (NLS)-type formulation in comparison to the method in the standard Friedmann framework. We consider phantom and non-phantom scalar field cases with exponential and power-law accelerating expansion. Analysis on effective equation of state to both cases of expansion is also performed. We speculate and comment on some advantage and disadvantage of using the NLS formulation in solving for the exact solution.Comment: 12 pages, GERG format, Reference added. accepted by Gen. Relativ. and Gra

Quantitative analysis of breast cancer tissue composition and associations with tumor subtype

The tumor microenvironment is an important determinant of breast cancer progression, but standard methods for describing the tumor microenvironment are lacking. Measures of microenvironment composition such as stromal area and immune infiltrate are labor-intensive and few large studies have systematically collected this data. However, digital histologic approaches are becoming more widely available, allowing high-throughput, quantitative estimation. We applied such methods to tissue microarrays of tumors from 1687 women (mean 4 cores per case) in the Carolina Breast Cancer Study Phase 3. Tumor composition was quantified as percentage of epithelium, stroma, adipose, and lymphocytic infiltrate (with the latter as presence/absence using a ≥1% cutoff). Composition proportions and presence/absence were evaluated in association with clinical and molecular features of breast cancer (intrinsic subtype and RNA-based risk of recurrence [ROR] scores) using multivariable linear and logistic regression. Lower stromal content was associated with aggressive tumor phenotypes, including triple-negative (31.1% vs. 41.6% in HR+/HER2-; RFD [95% CI]: −10.5%, [-13.1, −7.9]), Basal-like subtypes (29.0% vs. 44.0% in Luminal A; RFD [95% CI]: −14.9%, [-17.8, −12.0]), and high RNA-based PAM50 ROR scores (27.6% vs. 48.1% in ROR low; RFD [95% CI]: −20.5%, [24.3, 16.7]), after adjusting for age and race. HER2+ tumors also had lower stromal content, particularly among RNA-based HER2-enriched (35.2% vs. 44.0% in Luminal A; RFD [95% CI]: −8.8%, [-13.8, −3.8]). Similar associations were observed between immune infiltrate and tumor phenotypes. Quantitative digital image analysis of the breast cancer microenvironment showed significant associations with demographic characteristics and biological indicators of aggressive behavior

Stability of Negative Image Equilibria in Spike-Timing Dependent Plasticity

We investigate the stability of negative image equilibria in mean synaptic weight dynamics governed by spike-timing dependent plasticity (STDP). The neural architecture of the model is based on the electrosensory lateral line lobe (ELL) of mormyrid electric fish, which forms a negative image of the reafferent signal from the fish's own electric discharge to optimize detection of external electric fields. We derive a necessary and sufficient condition for stability, for arbitrary postsynaptic potential functions and arbitrary learning rules. We then apply the general result to several examples of biological interest.Comment: 13 pages, revtex4; uses packages: graphicx, subfigure; 9 figures, 16 subfigure