Molecular characterisation and epidemiological investigation of an outbreak of blaOXA-181 carbapenemase-producing isolates of Klebsiella pneumoniae in South Africa

BACKGROUND : Klebsiella pneumoniae is an opportunistic pathogen often associated with nosocomial infections. A suspected outbreak of K. pneumoniae isolates, exhibiting reduced susceptibility to carbapenem antibiotics, was detected during the month of May 2012 among patients admitted to a haematology unit of a tertiary academic hospital in Cape Town, South Africa (SA). OBJECTIVES : An investigation was done to determine possible epidemiological links between the case patients and to describe the mechanisms of carbapenem resistance of these bacterial isolates. Methods. Relevant demographic, clinical and laboratory information was extracted from hospital records and an observational review of infection prevention and control practices in the affected unit was performed. Antimicrobial susceptibility testing including phenotypic testing and genotypic detection of the most commonly described carbapenemase genes was done. The phylogenetic relationship of all isolates containing the blaOXA-181 carbapenemase gene was determined by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. Results. Polymerase chain reaction analysis identified a total of seven blaOXA-181-positive, carbapenem-resistant K. pneumoniae isolates obtained from seven patients, all from a single unit. These isolates were indistinguishable using PFGE analysis and belonged to sequence type ST-14. No other carbapenemase enzymes were detected. CONCLUSION : This is the first documented laboratory-confirmed outbreak of OXA-181-producing K. pneumoniae in SA, and highlights the importance of enforcing strict adherence to infection control procedures and the need for ongoing surveillance of antibiotic-resistant pathogens in local hospitals.Global Disease and Detection Funding, Centre for Opportunistic Tropical and Hospital Infections,National Institute for Communicable Diseases and the National Health Laboratory Service, Johannesburg.http://www.sama.co.zahb201

Corrections to flat-space particle dynamics arising from space granularity

The construction of effective Hamiltonians describing corrections to flat space particle dynamics arising from the granularity of space at very short distances is discussed in the framework of an heuristic approach to the semiclassical limit of loop quantum gravity. After some general motivation of the subject, a brief non-specialist introduction to the basic tools employed in the loop approach is presented. The heuristical semiclassical limit is subsequently defined and the application to the case of photons and spin 1/2 fermions is described. The resulting modified Maxwell and Dirac Hamiltonians, leading in particular to Planck scale corrections in the energy-momentum relations, are presented. Alternative interpretations of the results and their limitations, together with other approaches are briefly discussed along the text. Three topics related to the above methods are reviewed: (1) The determination of bounds to the Lorentz violating parameters in the fermionic sector, obtained from clock comparison experiments.(2) The calculation of radiative corrections in preferred frames associated to space granularity in the framework of a Yukawa model for the interactions and (3) The calculation of synchrotron radiation in the framework of the Myers-Pospelov effective theories describing Lorentz invariance violations, as well as a generalized approach to radiation in Planck scale modified electrodynamics. The above exploratory results show that quantum gravity phenomenology provides observational guidance in the construction of quantum gravity theories and opens up the possibility of probing Planck scale physics.Comment: 49 pages, 6 figures and 4 tables. Extended version of the talk given at the 339-th WE-Heraeus-Seminar: Special Relativity, will it survive the next 100 years?, Potsdam, february 200

The remarkable outburst of the highly-evolved post period-minimum dwarf nova SSS J122221.7−311525

We report extensive 3-yr multiwavelength observations of the WZ Sge-type dwarf nova SSS J122221.7−311525 during its unusual double superoutburst, the following decline and in quiescence. The second segment of the superoutburst had a long duration of 33 d and a very gentle decline with a rate of 0.02 mag d−1, and it displayed an extended post-outburst decline lasting at least 500 d. Simultaneously with the start of the rapid fading from the superoutburst plateau, the system showed the appearance of a strong near-infrared excess resulting in very red colours, which reached extreme values (B − I ≃ 1.4) about 20 d later. The colours then became bluer again, but it took at least 250 d to acquire a stable level. Superhumps were clearly visible in the light curve from our very first time-resolved observations until at least 420 d after the rapid fading from the superoutburst. The spectroscopic and photometric data revealed an orbital period of 109.80 min and a fractional superhump period excess ≲0.8 per cent, indicating a very low mass ratio q ≲ 0.045. With such a small mass ratio the donor mass should be below the hydrogen-burning minimum mass limit. The observed infrared flux in quiescence is indeed much lower than is expected from a cataclysmic variable with a near-main-sequence donor star. This strongly suggests a brown-dwarf-like nature for the donor and that SSS J122221.7−311525 has already evolved away from the period minimum towards longer periods, with the donor now extremely dim

Comparative Natural History of Visual Function From Patients With Biallelic Variants in BBS1 and BBS10.

The purpose of this study was to compare the natural history of visual function change in cohorts of patients affected with retinal degeneration due to biallelic variants in Bardet-Biedl syndrome genes: BBS1 and BBS10. Patients were recruited from nine academic centers from six countries (Belgium, Canada, France, New Zealand, Switzerland, and the United States). Inclusion criteria were: (1) female or male patients with a clinical diagnosis of retinal dystrophy, (2) biallelic disease-causing variants in BBS1 or BBS10, and (3) measures of visual function for at least one visit. Retrospective data collected included genotypes, age, onset of symptoms, and best corrected visual acuity (VA). When possible, data on refractive error, fundus images and autofluorescence (FAF), optical coherence tomography (OCT), Goldmann kinetic perimetry (VF), electroretinography (ERG), and the systemic phenotype were collected. Sixty-seven individuals had variants in BBS1 (n = 38; 20 female patients and 18 male patients); or BBS10 (n = 29; 14 female patients and 15 male patients). Missense variants were the most common type of variants for patients with BBS1, whereas frameshift variants were most common for BBS10. When ERGs were recordable, rod-cone dystrophy (RCD) was observed in 82% (23/28) of patients with BBS1 and 73% (8/11) of patients with BBS10; cone-rod dystrophy (CORD) was seen in 18% of patients with BBS1 only, and cone dystrophy (COD) was only seen in 3 patients with BBS10 (27%). ERGs were nondetectable earlier in patients with BBS10 than in patients with BBS1. Similarly, VA and VF declined more rapidly in patients with BBS10 compared to patients with BBS1. Retinal degeneration appears earlier and is more severe in BBS10 cases as compared to those with BBS1 variants. The course of change of visual function appears to relate to genetic subtypes of BBS

Extrinsic CPT Violation in Neutrino Oscillations in Matter

We investigate matter-induced (or extrinsic) CPT violation effects in neutrino oscillations in matter. Especially, we present approximate analytical formulas for the CPT-violating probability differences for three flavor neutrino oscillations in matter with an arbitrary matter density profile. Note that we assume that the CPT invariance theorem holds, which means that the CPT violation effects arise entirely because of the presence of matter. As special cases of matter density profiles, we consider constant and step-function matter density profiles, which are relevant for neutrino oscillation physics in accelerator and reactor long baseline experiments as well as neutrino factories. Finally, the implications of extrinsic CPT violation on neutrino oscillations in matter for several past, present, and future long baseline experiments are estimated.Comment: 47 pages, 7 figures, RevTeX4. Final version to be published in Phys. Rev.

Incidence of AIDS-Defining Opportunistic Infections in a Multicohort Analysis of HIV-infected Persons in the United States and Canada, 2000–2010

Background. There are few recent data on the rates of AIDS-defining opportunistic infections (OIs) among human immunodeficiency virus (HIV)–infected patients in care in the United States and Canada

Wnt signalling and cancer stem cells

[Abstract] Intracellular signalling mediated by secreted Wnt proteins is essential for the establishment of cell fates and proper tissue patterning during embryo development and for the regulation of tissue homeostasis and stem cell function in adult tissues. Aberrant activation of Wnt signalling pathways has been directly linked to the genesis of different tumours. Here, the components and molecular mechanisms implicated in the transduction of Wnt signal, along with important results supporting a central role for this signalling pathway in stem cell function regulation and carcinogenesis will be briefly reviewed.Ministerio de Ciencia e Innovación; SAF2008-0060

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362