Prospective cohort study to investigate the burden and transmission of acute gastroenteritis in care homes: a study protocol.

INTRODUCTION: Noroviruses are the leading cause of acute gastroenteritis in all age groups, but illness is more severe and causes excess mortality in the elderly, particularly those in long-term care. The total burden of norovirus disease in the elderly in the UK is poorly defined; no current surveillance programmes systematically or accurately quantify norovirus infection in those living in care homes. The aim of this study is to evaluate an enhanced surveillance system for acute gastroenteritis among the elderly in care homes. METHODS AND ANALYSIS: We will conduct this prospective cohort study in care homes in North West England; residents and staff at study care homes will be asked to participate. We will prospectively enrol a cohort of participants in an enhanced surveillance system to capture the incidence of acute gastroenteritis and use multiplex PCR to detect pathogens. We will sample symptomatic and non-symptomatic participants to understand characteristics of norovirus disease and susceptibility to infection. We will generate novel data on transmission dynamics by collecting data on the pattern of interactions within care homes using electronic proximity sensors. Comparisons of outbreak and non-outbreak periods will be used to quantify the impact of norovirus outbreaks on care homes. ETHICS AND DISSEMINATION: The study has been approved by the North West-Greater Manchester South NHS Research Ethics Committee (REC Reference: 16/NW/0541). Study outputs will be disseminated through scientific conferences and peer-reviewed publications. This study will provide detailed insight on the burden and aetiology of acute gastroenteritis in care homes, in addition to generating novel data on transmission dynamics and risks. The study will identify areas for improving infection control practice and allow more accurate modelling of the introduction of interventions such as vaccination

Fluorescence spectrum of a two-level atom driven by a multiple modulated field

We investigate the fluorescence spectrum of a two-level atom driven by a multiple amplitude-modulated field. The driving held is modeled as a polychromatic field composed of a strong central (resonant) component and a large number of symmetrically detuned sideband fields displaced from the central component by integer multiples of a constant detuning. Spectra obtained here differ qualitatively from those observed for a single pair of modulating fields [B. Blind, P.R. Fontana, and P. Thomann, J. Phys. B 13, 2717 (1980)]. In the case of a small number of the modulating fields, a multipeaked spectrum is obtained with the spectral features located at fixed frequencies that are independent of the number of modulating fields and their Rabi frequencies. As the number of the modulating fields increases, the spectrum ultimately evolves to the well-known Mellow triplet with the sidebands shifted from the central component by an effective Rabi frequency whose magnitude depends on the initial relative phases of the components of the driving held. For equal relative phases, the effective Rabi frequency of the driving field can be reduced to zero resulting in the disappearance of fluorescence spectrum, i.e., the atom can stop interacting with the field. When the central component and the modulating fields are 180 degrees out of phase, the spectrum retains its triplet structure with the sidebands located at frequencies equal to the sum of the Rabi frequencies of the component of the driving field. Moreover, we shaw that the frequency of spontaneous emission can be controlled and switched from one frequency to another when the Rabi frequency or initial phase of the modulating fields are varied

Hydrogenation Properties of the Ti45Zr38 xYxNi17 5 lt; x lt; 10 and the Ti45 zYzZr38Ni17 5 lt; z lt; 15 Mechanically Alloyed Materials

The amorphous materials of the Ti45Zr38Ni17 composition synthesized by mechanical alloying are widely recognized for their ability to store hydrogen with gravimetric densities above 2 wt. . It is also known that those alloys can form a quasicrystalline state after thermal treatment and their structural and hydrogen sorption properties can be altered by doping with various elements. Therefore, in this paper, the results of the studies on the Ti45Zr38Ni17 system with yttrium substituted for titanium and zirconium are presented. We demonstrate that these alloys are able to absorb hydrogen with a concentration of up to 2.7 wt. while retaining their amorphous structure and they transform into the unique glassy quasicrystal phase upon annealing. Furthermore, we demonstrate that the in situ hydrogenation of those new materials is an effortless procedure in which the decomposition of the alloy can be avoided. Moreover, we prove that, in that process, hydrogen does not bind to any specific component of the alloy, which would otherwise cause the formation of simple hydrides or nanocluster

Susceptibility of Pigs and Chickens to SARS Coronavirus

An outbreak of severe acute respiratory syndrome (SARS) in humans, associated with a new coronavirus, was reported in Southeast Asia, Europe, and North America in early 2003. To address speculations that the virus originated in domesticated animals, or that domestic species were susceptible to the virus, we inoculated 6-week-old pigs and chickens intravenously, intranasally, ocularly, and orally with 106 PFU of SARS-associated coronavirus (SARS-CoV). Clinical signs did not develop in any animal, nor were gross pathologic changes evident on postmortem examinations. Attempts at virus isolation were unsuccessful; however, viral RNA was detected by reverse transcriptase-polymerase chain reaction in blood of both species during the first week after inoculation, and in chicken organs at 2 weeks after inoculation. Virus-neutralizing antibodies developed in the pigs. Our results indicate that these animals do not play a role as amplifying hosts for SARS-CoV

Commercial Arctic shipping through the Northeast Passage:routes, resources, governance, technology, and infrastructure

The Russian and Norwegian Arctic are gaining notoriety as an alternative maritime route connecting the Atlantic and Pacific Oceans and as sources of natural resources. The renewed interest in the Northeast Passage or the Northern Sea Route is fueled by a recession of Arctic sea ice coupled with the discovery of new natural resources at a time when emerging and global markets are in growing demand for them. Driven by the expectation of potential future economic importance of the region, political interest and governance has been rapidly developing, mostly within the Arctic Council. However, this paper argues that optimism regarding the potential of Arctic routes as an alternative to the Suez Canal is overstated. The route involves many challenges: jurisdictional disputes create political uncertainties; shallow waters limit ship size; lack of modern deepwater ports and search and rescue (SAR) capabilities requires ships to have higher standards of autonomy and safety; harsh weather conditions and free-floating ice make navigation more difficult and schedules more variable; and more expensive ship construction and operation costs lessen the economic viability of the route. Technological advances and infrastructure investments may ameliorate navigational challenges, enabling increased shipping of natural resources from the Arctic to global markets.Albert Buixadé Farré, Scott R. Stephenson, Linling Chen, Michael Czub, Ying Dai, Denis Demchev, Yaroslav Efimov, Piotr Graczyk, Henrik Grythe, Kathrin Keil, Niku Kivekäs, Naresh Kumar, Nengye Liu, Igor Matelenok, Mari Myksvoll, Derek O'Leary, Julia Olsen, Sachin Pavithran.A.P., Edward Petersen, Andreas Raspotnik, Ivan Ryzhov, Jan Solski, Lingling Suo, Caroline Troein, Vilena Valeeva, Jaap van Rijckevorsel and Jonathan Wightin

Discovery of inhibitory fragments that selectively target Spire2−FMN2 interaction

Here, we report the fragment-based drug discovery of potent and selective fragments that disrupt the Spire2–FMN2 but not the Spire1–FMN2 interaction. Hit fragments were identified in a differential scanning fluorimetry-based screen of an in-house library of 755 compounds and subsequently validated in multiple orthogonal biophysical assays, including fluorescence polarization, microscale thermophoresis, and 1H–15N HSQC nuclear magnetic resonance. Extensive structure–activity relationships combined with molecular docking followed by chemical optimization led to the discovery of compound 13, which exhibits micromolar potency and high ligand efficiency (LE = 0.38). Therefore, this fragment represents a validated starting point for the future development of selective chemical probes targeting the Spire2–FMN2 interaction

A Gcn5-Related N-Acetyltransferase (GNAT) Capable of Acetylating Polymyxin B and Colistin Antibiotics in Vitro

Deeper exploration of uncharacterized Gcn5-related N-acetyltransferases has the potential to expand our knowledge of the types of molecules that can be acylated by this important superfamily of enzymes and may offer new opportunities for biotechnological applications. While determining native or biologically relevant in vivo functions of uncharacterized proteins is ideal, their alternative or promiscuous in vitro capabilities provide insight into key active site interactions. Additionally, this knowledge can be exploited to selectively modify complex molecules and reduce byproducts when synthetic routes become challenging. During our exploration of uncharacterized Gcn5-related N-acetyltransferases from Pseudomonas aeruginosa, we identified such an example. We found that the PA3944 enzyme acetylates both polymyxin B and colistin on a single diaminobutyric acid residue closest to the macrocyclic ring of the antimicrobial peptide and determined the PA3944 crystal structure. This finding is important for several reasons. (1) To the best of our knowledge, this is the first report of enzymatic acylation of polymyxins and thus reveals a new type of substrate that this enzyme family can use. (2) The enzymatic acetylation offers a controlled method for antibiotic modification compared to classical promiscuous chemical methods. (3) The site of acetylation would reduce the overall positive charge of the molecule, which is important for reducing nephrotoxic effects and may be a salvage strategy for this important class of antibiotics. While the physiological substrate for this enzyme remains unknown, our structural and functional characterization of PA3944 offers insight into its unique noncanonical substrate specificity

The ecology of chronic wasting disease in wildlife

This work is licensed under a Creative Commons Attribution 4.0 International License.Prions are misfolded infectious proteins responsible for a group of fatal neurodegenerative diseases termed transmissible spongiform encephalopathy or prion diseases. Chronic Wasting Disease (CWD) is the prion disease with the highest spillover potential, affecting at least seven Cervidae (deer) species. The zoonotic potential of CWD is inconclusive and cannot be ruled out. A risk of infection for other domestic and wildlife species is also plausible. Here, we review the current status of the knowledge with respect to CWD ecology in wildlife. Our current understanding of the geographic distribution of CWD lacks spatial and temporal detail, does not consider the biogeography of infectious diseases, and is largely biased by sampling based on hunters’ cooperation and funding available for each region. Limitations of the methods used for data collection suggest that the extent and prevalence of CWD in wildlife is underestimated. If the zoonotic potential of CWD is confirmed in the short term, as suggested by recent results obtained in experimental animal models, there will be limited accurate epidemiological data to inform public health. Research gaps in CWD prion ecology include the need to identify specific biological characteristics of potential CWD reservoir species that better explain susceptibility to spillover, landscape and climate configurations that are suitable for CWD transmission, and the magnitude of sampling bias in our current understanding of CWD distribution and risk. Addressing these research gaps will help anticipate novel areas and species where CWD spillover is expected, which will inform control strategies. From an ecological perspective, control strategies could include assessing restoration of natural predators of CWD reservoirs, ultrasensitive CWD detection in biotic and abiotic reservoirs, and deer density and landscape modification to reduce CWD spread and prevalence

Love and affectionate touch toward romantic partners all over the world

Touch is the primary way people communicate intimacy in romantic relationships, and affectionate touch behaviors such as stroking, hugging and kissing are universally observed in partnerships all over the world. Here, we explored the association of love and affectionate touch behaviors in romantic partnerships in two studies comprising 7880 participants. In the first study, we used a cross-cultural survey conducted in 37 countries to test whether love was universally associated with affectionate touch behaviors. In the second study, using a more fine-tuned touch behavior scale, we tested whether the frequency of affectionate touch behaviors was related to love in romantic partnerships. As hypothesized, love was significantly and positively associated with affectionate touch behaviors in both studies and this result was replicated regardless of the inclusion of potentially relevant factors as controls. Altogether, our data strongly suggest that affectionate touch is a relatively stable characteristic of human romantic relationships that is robustly and reliably related to the degree of reported love between partners.info:eu-repo/semantics/publishedVersio