Extended spectrum β-lactamase-and AmpC β-lactamase-producing Enterobacterales associated with urinary tract infections in the New Zealand community: A case-control study.

(c) The Author/sOBJECTIVES: To assess whether having a pet in the home is a risk factor for community-acquired urinary tract infections associated with extended spectrum β-lactamase (ESBL)- or AmpC β-lactamase (ACBL)- producing Enterobacterales. METHODS: An unmatched case-control study was conducted between August 2015 and September 2017. Cases (n=141) were people with community-acquired urinary tract infection (UTI) caused by ESBL- or ACBL- producing Enterobacterales. Controls (n=525) were recruited from the community. A telephone questionnaire on pet ownership, and other factors was administered, and associations were assessed using logistic regression. RESULTS: Pet ownership was not associated with ESBL- or ACBL-producing Enterobacterales related human UTIs. A positive association was observed for recent antimicrobial treatment, travel to Asia in the previous year, and a doctor's visit in the previous six months. Among isolates with an ESBL-/ACBL-producing phenotype 126/134 (94%) were Escherichia coli, with sequence type (ST) 131 being the most common (47/126). CONCLUSIONS: Companion animals in the home were not found to be associated with ESBL- or ACBL-producing Enterobacterales related community-acquired UTI in New Zealand. Risk factors included overseas travel, recent antibiotic use, and doctor visits.Published onlin

Effective theories of single field inflation when heavy fields matter

We compute the low energy effective field theory (EFT) expansion for single-field inflationary models that descend from a parent theory containing multiple other scalar fields. By assuming that all other degrees of freedom in the parent theory are sufficiently massive relative to the inflaton, it is possible to derive an EFT valid to arbitrary order in perturbations, provided certain generalized adiabaticity conditions are respected. These conditions permit a consistent low energy EFT description even when the inflaton deviates off its adiabatic minimum along its slowly rolling trajectory. By generalizing the formalism that identifies the adiabatic mode with the Goldstone boson of this spontaneously broken time translational symmetry prior to the integration of the heavy fields, we show that this invariance of the parent theory dictates the entire non-perturbative structure of the descendent EFT. The couplings of this theory can be written entirely in terms of the reduced speed of sound of adiabatic perturbations. The resulting operator expansion is distinguishable from that of other scenarios, such as standard single inflation or DBI inflation. In particular, we re-derive how certain operators can become transiently strongly coupled along the inflaton trajectory, consistent with slow-roll and the validity of the EFT expansion, imprinting features in the primordial power spectrum, and we deduce the relevant cubic operators that imply distinct signatures in the primordial bispectrum which may soon be constrained by observations.Comment: (v1) 25 pages, 1 figure; (v2) references added and typos corrected, to appear in Journal of High Energy Physic

Assessment of ecological status in UK lakes using benthic diatoms

The European Union’s Water Framework Directive (WFD) requires that all water bodies in Europe achieve good ecological status (GES) by 2015. We developed an ecological classification tool for UK lakes based on benthic diatoms, a key component of the biological-quality element macrophytes and phytobenthos. A database of 1079 epilithic and epiphytic diatom samples and matching environmental data was assembled from 228 UK lakes. The data set was divided into 3 lake types: low, medium, and high alkalinity. A lake trophic diatom index (LTDI) was developed based on modification of the trophic diatom index (TDI) for rivers, and ecological quality ratios (EQRs) were generated for each lake type. The high/good status boundary was defined as the 25th percentile of EQRs of all reference sites (identified based on independent sedimentary-diatom-assemblage data or catchment point-source and landuse data), whereas the good/moderate boundary was set at the point at which nutrient-sensitive and nutrient-tolerant taxa were present in equal relative abundance. The moderate/poor and poor/bad boundaries were defined by equal division of the remaining EQR gradient. Samples from reference sites were used to predict the expected LTDI value for each sample, and these values were compared with the classifications derived from the LTDI. For lakes identified as reference sites, 68% were classified as having high status and 32% as having good. The model predicted 81% of nonreference lakes to have good or worse status. The model was applied to 17 English lakes (10 low- and 7 medium-alkalinity) for which classification based on other WFD tools was available. The classifications based on LTDI gave the same status (within 1 class) as other biological elements for 11 of the 17 lakes (65%). Thus, the LTDI gives a reliable assessment of the condition of the littoral biofilm and is a key component of a WFD-compliant tool kit for classifying UK standing waters

Genotype-Dependent Tumor Regression in Marek’s Disease Mediated at the Level of Tumor Immunity

Marek’s disease (MD) of chickens is a unique natural model of Hodgkin’s and Non Hodgkin’s lymphomas in which the neoplastically-transformed cells over-express CD30 (CD30hi) antigen. All chicken genotypes can be infected with MD virus and develop microscopic lymphomas. From 21 days post infection (dpi) microscopic lymphomas regress in resistant chickens but, in contrast, they progress to gross lymphomas in susceptible chickens. Here we test our hypothesis that in resistant chickens at 21 dpi the tissue microenvironment is pro T-helper (Th)-1 and compatible with cytotoxic T lymphocyte (CTL) immunity but in susceptible lines it is pro Th-2 or pro T-regulatory (T-reg) and antagonistic to CTL immunity. We used the B2, non-MHC-associated, MD resistance/susceptibility system (line [L]61/line [L]72) and quantified the levels of key mRNAs that can be used to define Th-1 (IL-2, IL-12, IL-18, IFNγ), Th-2 (IL-4, IL-10) and T-reg (TGFβ, GPR-83, CTLA-4, SMAD-7) lymphocyte phenotypes. We measured gene expression in both whole tissues (represents tissue microenvironment and tumor microenvironment) and in the lymphoma lesions (tumor microenvironment) themselves. Gene ontology-based modeling of our results shows that the dominant phenotype in whole tissue as well as in microscopic lymphoma lesions, is pro T-reg in both L61 and L72 but a minor pro Th-1 and anti Th-2 tissue microenvironment exists in L61 whereas there is an anti Th-1 and pro Th-2 tissue microenvironment in L72. The tumor microenvironment per se is pro T-reg, anti Th-1 and pro Th-2 in both L61 and L72. Together our data suggests that the neoplastic transformation is essentially the same in both L61 and L72 and that resistance/susceptibility is mediated at the level of tumor immunity in the tissues

Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance.

INTRODUCTION: 2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance. METHODS: This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009-2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence). RESULTS: Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60-1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14-2.28) when Hr genotype was included, but this analysis lacked power (p=0.42). CONCLUSIONS: In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations

Chiral perturbation theory in a magnetic background - finite-temperature effects

We consider chiral perturbation theory for SU(2) at finite temperature $T$ in a constant magnetic background $B$. We compute the thermal mass of the pions and the pion decay constant to leading order in chiral perturbation theory in the presence of the magnetic field. The magnetic field gives rise to a splitting between $M_{\pi^0}$ and $M_{\pi^{\pm}}$ as well as between $F_{\pi^0}$ and $F_{\pi^{\pm}}$. We also calculate the free energy and the quark condensate to next-to-leading order in chiral perturbation theory. Both the pion decay constants and the quark condensate are decreasing slower as a function of temperature as compared to the case with vanishing magnetic field. The latter result suggests that the critical temperature $T_c$ for the chiral transition is larger in the presence of a constant magnetic field. The increase of $T_c$ as a function of $B$ is in agreement with most model calculations but in disagreement with recent lattice calculations.Comment: 24 pages and 9 fig

Risk factors for acute chemical releases with public health consequences: Hazardous Substances Emergency Events Surveillance in the U.S., 1996–2001

BACKGROUND: Releases of hazardous materials can cause substantial morbidity and mortality. To reduce and prevent the public health consequences (victims or evacuations) from uncontrolled or illegally released hazardous substances, a more comprehensive analysis is needed to determine risk factors for hazardous materials incidents. METHODS: Hazardous Substances Emergency Events Surveillance (HSEES) data from 1996 through 2001 were analyzed using bivariate and multiple logistic regression. Fixed-facility and transportation-related events were analyzed separately. RESULTS: For fixed-facility events, 2,327 (8%) resulted in at least one victim and 2,844 (10%) involved ordered evacuations. For transportation-related events, 759 (8%) resulted in at least one victim, and 405 (4%) caused evacuation orders. Fire and/or explosion were the strongest risk factors for events involving either victims or evacuations. Stratified analysis of fixed-facility events involving victims showed a strong association for acid releases in the agriculture, forestry, and fisheries industry. Chlorine releases in fixed-facility events resulted in victims and evacuations in more industry categories than any other substance. CONCLUSIONS: Outreach efforts should focus on preventing and preparing for fires and explosions, acid releases in the agricultural industry, and chlorine releases in fixed facilities

Bidirectional lipid droplet velocities are controlled by differential binding strengths of HCV Core DII protein

Host cell lipid droplets (LD) are essential in the hepatitis C virus (HCV) life cycle and are targeted by the viral capsid core protein. Core-coated LDs accumulate in the perinuclear region and facilitate viral particle assembly, but it is unclear how mobility of these LDs is directed by core. Herein we used two-photon fluorescence, differential interference contrast imaging, and coherent anti-Stokes Raman scattering microscopies, to reveal novel core-mediated changes to LD dynamics. Expression of core protein’s lipid binding domain II (DII-core) induced slower LD speeds, but did not affect directionality of movement on microtubules. Modulating the LD binding strength of DII-core further impacted LD mobility, revealing the temporal effects of LD-bound DII-core. These results for DII-core coated LDs support a model for core-mediated LD localization that involves core slowing down the rate of movement of LDs until localization at the perinuclear region is accomplished where LD movement ceases. The guided localization of LDs by HCV core protein not only is essential to the viral life cycle but also poses an interesting target for the development of antiviral strategies against HCV

Development of a cDNA microarray for the measurement of gene expression in the sheep scab mite Psoroptes ovis

Background: Sheep scab is caused by the ectoparasitic mite Psoroptes ovis which initiates a profound cutaneous inflammatory response, leading to the development of the skin lesions which are characteristic of the disease. Existing control strategies rely upon injectable endectocides and acaricidal dips but concerns over residues, eco-toxicity and the development of acaricide resistance limit the sustainability of this approach. In order to identify alternative means of disease control, a deeper understanding of both the parasite and its interaction with the host are required. Methods: Herein we describe the development and utilisation of an annotated P. ovis cDNA microarray containing 3,456 elements for the measurement of gene expression in this economically important ectoparasite. The array consists of 981 P. ovis EST sequences printed in triplicate along with 513 control elements. Array performance was validated through the analysis of gene expression differences between fed and starved P. ovis mites. Results: Sequences represented on the array include homologues of major house dust mite allergens and tick salivary proteins, along with factors potentially involved in mite reproduction and xenobiotic metabolism. In order to validate the performance of this unique resource under biological conditions we used the array to analyse gene expression differences between fed and starved P. ovis mites. These analyses identified a number of house dust mite allergen homologues up-regulated in fed mites and P. ovis transcripts involved in stress responses, autophagy and chemosensory perception up-regulated in starved mites. Conclusion: The P. ovis cDNA microarray described here has been shown to be both robust and reproducible and will enable future studies to analyse gene expression in this important ectoparasite

Pediatric interventional radiography equipment: safety considerations

This paper discusses pediatric image quality and radiation dose considerations in state-of-the-art fluoroscopic imaging equipment. Although most fluoroscopes are capable of automatically providing good image quality on infants, toddlers, and small children, excessive radiation dose levels can result from design deficiencies of the imaging device or inappropriate configuration of the equipment’s capabilities when imaging small body parts. Important design features and setup choices at installation and during the clinical use of the imaging device can improve image quality and reduce radiation exposure levels in pediatric patients. Pediatric radiologists and cardiologists, with the help of medical physicists, need to understand the issues involved in creating good image quality at reasonable pediatric patient doses. The control of radiographic technique factors by the generator of the imaging device must provide a large dynamic range of mAs values per exposure pulse during both fluoroscopy and image recording as a function of patient girth, which is the thickness of the patient in the posterior–anterior projection at the umbilicus (less than 10 cm to greater than 30 cm). The range of pulse widths must be limited to less than 10 ms in children to properly freeze patient motion. Variable rate pulsed fluoroscopy can be leveraged to reduce radiation dose to the patient and improve image quality. Three focal spots with nominal sizes of 0.3 mm to 1 mm are necessary on the pediatric unit. A second, lateral imaging plane might be necessary because of the child’s limited tolerance of contrast medium. Spectral and spatial beam shaping can improve image quality while reducing the radiation dose. Finally, the level of entrance exposure to the image receptor of the fluoroscope as a function of operator choices, of added filter thickness, of selected pulse rate, of the selected field-of-view and of the patient girth all must be addressed at installation