Worldwide reduction in MERS cases and deaths since 2016

Since 2012, Middle East respiratory syndrome (MERS) coronavirus has infected 2,442 persons worldwide. Case-based data analysis suggests that since 2016, as many as 1,465 cases and 293–520 deaths might have been averted. Efforts to reduce the global MERS threat are working, but countries must maintain vigilance to prevent further infections

Assessment of non-invasive ICP during CSF infusion test: an approach with transcranial Doppler.

BACKGROUND: This study aimed to compare four non-invasive intracranial pressure (nICP) methods in a prospective cohort of hydrocephalus patients whose cerebrospinal fluid dynamics was investigated using infusion tests involving controllable test-rise of ICP. METHOD: Cerebral blood flow velocity (FV), ICP and non-invasive arterial blood pressure (ABP) were recorded in 53 patients diagnosed for hydrocephalus. Non-invasive ICP methods were based on: (1) interaction between FV and ABP using black-box model (nICP_BB); (2) diastolic FV (nICP_FVd); (3) critical closing pressure (nICP_CrCP); (4) transcranial Doppler-derived pulsatility index (nICP_PI). Correlation between rise in ICP (∆ICP) and ∆nICP and averaged correlations for changes in time between ICP and nICP during infusion test were investigated. RESULTS: From baseline to plateau, all nICP estimators increased significantly. Correlations between ∆ICP and ∆nICP were better represented by nICP_PI and nICP_BB: 0.45 and 0.30 (p < 0.05). nICP_FVd and nICP_CrCP presented non-significant correlations: -0.17 (p = 0.21), 0.21 (p = 0.13). For changes in ICP during individual infusion test nICP_PI, nICP_BB and nICP_FVd presented similar correlations with ICP: 0.39 ± 0.40, 0.39 ± 0.43 and 0.35 ± 0.41 respectively. However, nICP_CrCP presented a weaker correlation (R = 0.29 ± 0.24). CONCLUSIONS: Out of the four methods, nICP_PI was the one with best performance for predicting changes in ∆ICP during infusion test, followed by nICP_BB. Unreliable correlations were shown by nICP_FVd and nICP_CrCP. Changes of ICP observed during the test were expressed by nICP values with only moderate correlations.DC is supported by a Cambridge Commonwealth, European & International Trust Scholarship, University of Cambridge. JD is supported by a Woolf Fisher Trust Scholarship. XL is supported by a Gates Cambridge Trust Scholarship. BCTC is supported by CNPQ (Research Project 203792/2014-9). DC and MC are partially supported by NIHR Brain Injury Healthcare Technology Co-operative, Cambridge, UK.This is the final version of the article. It was first available from Springer via http://dx.doi.org/10.1007/s00701-015-2661-

Quantised Vortices in an Exciton-Polariton Fluid

One of the most striking quantum effects in a low temperature interacting Bose gas is superfluidity. First observed in liquid 4He, this phenomenon has been intensively studied in a variety of systems for its amazing features such as the persistence of superflows and the quantization of the angular momentum of vortices. The achievement of Bose-Einstein condensation (BEC) in dilute atomic gases provided an exceptional opportunity to observe and study superfluidity in an extremely clean and controlled environment. In the solid state, Bose-Einstein condensation of exciton polaritons has now been reported several times. Polaritons are strongly interacting light-matter quasi-particles, naturally occurring in semiconductor microcavities in the strong coupling regime and constitute a very interesting example of composite bosons. Even though pioneering experiments have recently addressed the propagation of a fluid of coherent polaritons, still no conclusive evidence is yet available of its superfluid nature. In the present Letter, we report the observation of spontaneous formation of pinned quantised vortices in the Bose-condensed phase of a polariton fluid by means of phase and amplitude imaging. Theoretical insight into the possible origin of such vortices is presented in terms of a generalised Gross-Pitaevskii equation. The implications of our observations concerning the superfluid nature of the non-equilibrium polariton fluid are finally discussed.Comment: 14 pages, 4 figure

The geography of recent genetic ancestry across Europe

The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (the POPRES dataset) to conduct one of the first surveys of recent genealogical ancestry over the past three thousand years at a continental scale. We detected 1.9 million shared genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 10-50 genetic common ancestors from the last 1500 years, and upwards of 500 genetic ancestors from the previous 1000 years. These numbers drop off exponentially with geographic distance, but since genetic ancestry is rare, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1000 years. There is substantial regional variation in the number of shared genetic ancestors: especially high numbers of common ancestors between many eastern populations likely date to the Slavic and/or Hunnic expansions, while much lower levels of common ancestry in the Italian and Iberian peninsulas may indicate weaker demographic effects of Germanic expansions into these areas and/or more stably structured populations. Recent shared ancestry in modern Europeans is ubiquitous, and clearly shows the impact of both small-scale migration and large historical events. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world.Comment: Full size figures available from http://www.eve.ucdavis.edu/~plralph/research.html; or html version at http://ralphlab.usc.edu/ibd/ibd-paper/ibd-writeup.xhtm

People of the British Isles: preliminary analysis of genotypes and surnames in a UK control population

There is a great deal of interest in fine scale population structure in the UK, both as a signature of historical immigration events and because of the effect population structure may have on disease association studies. Although population structure appears to have a minor impact on the current generation of genome-wide association studies, it is likely to play a significant part in the next generation of studies designed to search for rare variants. A powerful way of detecting such structure is to control and document carefully the provenance of the samples involved. Here we describe the collection of a cohort of rural UK samples (The People of the British Isles), aimed at providing a well-characterised UK control population that can be used as a resource by the research community as well as providing fine scale genetic information on the British population. So far, some 4,000 samples have been collected, the majority of which fit the criteria of coming from a rural area and having all four grandparents from approximately the same area. Analysis of the first 3,865 samples that have been geocoded indicates that 75% have a mean distance between grandparental places of birth of 37.3km, and that about 70% of grandparental places of birth can be classed as rural. Preliminary genotyping of 1,057 samples demonstrates the value of these samples for investigating fine scale population structure within the UK, and shows how this can be enhanced by the use of surnames

Microneedles: A New Frontier in Nanomedicine Delivery

This review aims to concisely chart the development of two individual research fields, namely nanomedicines, with specific emphasis on nanoparticles (NP) and microparticles (MP), and microneedle (MN) technologies, which have, in the recent past, been exploited in combinatorial approaches for the efficient delivery of a variety of medicinal agents across the skin. This is an emerging and exciting area of pharmaceutical sciences research within the remit of transdermal drug delivery and as such will undoubtedly continue to grow with the emergence of new formulation and fabrication methodologies for particles and MN. Firstly, the fundamental aspects of skin architecture and structure are outlined, with particular reference to their influence on NP and MP penetration. Following on from this, a variety of different particles are described, as are the diverse range of MN modalities currently under development. The review concludes by highlighting some of the novel delivery systems which have been described in the literature exploiting these two approaches and directs the reader towards emerging uses for nanomedicines in combination with MN

Development of an evidence-based checklist for the detection of drug related problems in type 2 diabetes

Objective To develop an evidence-based checklist to identify potential drug related problems (PDRP) in patients with type 2 diabetes. Setting The evidence based checklist was applied to records of ambulatory type 2 diabetes patients in New South Wales, Australia. Method After comprehensive review of the literature, relevant medication groups and potential drug related problems in type 2 diabetes were identified. All the relevant information was then structured in the form of a checklist. To test the utility of the evidence-based checklist a cross-sectional retrospective study was conducted. The PDRP checklist was applied to the data of 148 patients with established type 2 diabetes and poor glycaemic control. The range and extent of DRPs in this population were identified, which were categorized using the PCNE classification. In addition, the relationship between the total as well as each category of DRPs and several of the patients’ clinical parameters was investigated. Main outcome measure: Number and category of DRPs per patient. Results The PDRP checklist was successfully developed and consisted of six main sections. 682 potential DRPs were identified using the checklist, an average of 4.6 (SD = 1.7) per patient. Metabolic and blood pressure control in the study subjects was generally poor: with a mean HbA1c of 8.7% (SD = 1.5) and mean blood pressure of 139.8 mmHg (SD = 18.1)/81.7 mmHg (SD = 11.1). The majority of DRPs was recorded in the categories ‘therapy failure’ (n = 264) and ‘drug choice problem’ (n = 206). Potentially non-adherent patients had a significantly higher HbA1c than patients who adhered to therapy (HbA1c of 9.4% vs. 8.5%; P = 0.01). Conclusion This is the first tool developed specifically to detect potential DRPs in patients with type 2 diabetes. It was used to identify DRPs in a sample of type 2 diabetes patients and demonstrated the high prevalence of DRPs per patient. The checklist may assist pharmacists and other health care professionals to systematically identify issues in therapy and management of their type 2 diabetes patients and enable earlier intervention to improve metabolic control

Molecular analysis of the Acinetobacter baumannii biofilm-associated protein

Acinetobacter baumannii is a multidrug-resistant pathogen associated with hospital outbreaks of infection across the globe, particularly in the intensive care unit. The ability of A. baumannii to survive in the hospital environment for long periods is linked to antibiotic resistance and its capacity to form biofilms. Here we studied the prevalence, expression, and function of the A. baumannii biofilm-associated protein (Bap) in 24 carbapenem-resistant A. baumannii ST92 strains isolated from a single institution over a 10-year period. The bap gene was highly prevalent, with 22/24 strains being positive for bap by PCR. Partial sequencing of bap was performed on the index case strain MS1968 and revealed it to be a large and highly repetitive gene approximately 16 kb in size. Phylogenetic analysis employing a 1,948-amino-acid region corresponding to the C terminus of Bap showed that Bap(MS1968) clusters with Bap sequences from clonal complex 2 (CC2) strains ACICU, TCDC-AB0715, and 1656-2 and is distinct from Bap in CC1 strains. By using overlapping PCR, the bap(MS1968) gene was cloned, and its expression in a recombinant Escherichia coli strain resulted in increased biofilm formation. A Bap-specific antibody was generated, and Western blot analysis showed that the majority of A. baumannii strains expressed an similar to 200-kDa Bap protein. Further analysis of three Bap-positive A. baumannii strains demonstrated that Bap is expressed at the cell surface and is associated with biofilm formation. Finally, biofilm formation by these Bap-positive strains could be inhibited by affinity-purified Bap antibodies, demonstrating the direct contribution of Bap to biofilm growth by A. baumannii clinical isolates

Therapeutic DNA vaccine induces broad T cell responses in the gut and sustained protection from viral rebound and AIDS in SIV-infected rhesus macaques.

Immunotherapies that induce durable immune control of chronic HIV infection may eliminate the need for life-long dependence on drugs. We investigated a DNA vaccine formulated with a novel genetic adjuvant that stimulates immune responses in the blood and gut for the ability to improve therapy in rhesus macaques chronically infected with SIV. Using the SIV-macaque model for AIDS, we show that epidermal co-delivery of plasmids expressing SIV Gag, RT, Nef and Env, and the mucosal adjuvant, heat-labile E. coli enterotoxin (LT), during antiretroviral therapy (ART) induced a substantial 2-4-log fold reduction in mean virus burden in both the gut and blood when compared to unvaccinated controls and provided durable protection from viral rebound and disease progression after the drug was discontinued. This effect was associated with significant increases in IFN-γ T cell responses in both the blood and gut and SIV-specific CD8+ T cells with dual TNF-α and cytolytic effector functions in the blood. Importantly, a broader specificity in the T cell response seen in the gut, but not the blood, significantly correlated with a reduction in virus production in mucosal tissues and a lower virus burden in plasma. We conclude that immunizing with vaccines that induce immune responses in mucosal gut tissue could reduce residual viral reservoirs during drug therapy and improve long-term treatment of HIV infection in humans

Anaesthetic considerations of adults with Morquio's syndrome - a case report

<p>Abstract</p> <p>Background</p> <p>The anaesthetic management of patients with Morquio syndrome is complicated by a number of factors including odontoid hypoplasia, atlantoaxial instability, thoracic kyphosis, and deposition of mucopolysaccharides in the soft tissue of the oropharnyx.</p> <p>Case presentation</p> <p>Herein we describe the anaesthetic considerations and management of a 26 year old adult with Morquio syndrome, who presented for an elective hip replacement.</p> <p>Conclusion</p> <p>This report details an awake fiberoptic intubation in an adult with Morquio syndrome. We recommend that this approach be considered in patients with Morquio syndrome undergoing general anaesthesia.</p