Functional Outcomes and Satisfaction Rates in Patients Aged 80 Years or Older are Not Clinically Different From Their Younger (65 to 75 Years) Counterparts Following Total Hip Arthroplasty.

Background: As the population ages, the proportion of elderly patients requiring total hip arthroplasty (THA) increases, but it is not clear whether older age independently influences outcome. The aim was to assess function, quality of life, and satisfaction after THA in patients ≥ 80 years compared with those aged between 65 and 75 years when adjusting for confounding factors.

Methods: A single-center retrospective cohort study was performed between 2010 and 2019.

Activation of the integrated stress response by inhibitors of its kinases.

Phosphorylation of the translation initiation factor eIF2α to initiate the integrated stress response (ISR) is a vital signalling event. Protein kinases activating the ISR, including PERK and GCN2, have attracted considerable attention for drug development. Here we find that the widely used ATP-competitive inhibitors of PERK, GSK2656157, GSK2606414 and AMG44, inhibit PERK in the nanomolar range, but surprisingly activate the ISR via GCN2 at micromolar concentrations.

Risky Business: Factors That Increase Risk of Falls Among Older Adult In-Patients.

In hospitals, older patients are at increased risk of falling multiple times. This study incorporated an epidemiologic cross-sectional design consisting of 4,348 older patients (≥65-year-old). Eight hundred eighty five (20.

GYY4137, a hydrogen sulfide donor, protects against endothelial dysfunction in porcine coronary arteries exposed to myeloperoxidase and hypochlorous acid.

Background And Aims: Myeloperoxidase (MPO) and its principal reaction product hypochlorous acid (HOCl) are part of the innate immune response but are also associated with endothelial dysfunction, thought to involve a reduction in nitric oxide (NO) bioavailability. We aimed to investigate the effect of MPO and HOCl on vasorelaxation of coronary arteries and to assess directly the involvement of NO. In addition, we hypothesised that the slow release hydrogen sulfide (HS) donor GYY4137 would salvage coronary artery endothelial function in the presence of MPO and HOCl.

Improved imaging and preservation of lysosome dynamics using silver nanoparticle-enhanced fluorescence.

The dynamics of living cells can be studied by live-cell fluorescence microscopy. However, this requires the use of excessive light energy to obtain good signal-to-noise ratio, which can then photobleach fluorochromes, and more worrisomely, lead to phototoxicity. Upon light excitation, noble metal nanoparticles such as silver nanoparticles (AgNPs) generate plasmons, which can then amplify excitation in direct proximity of the nanoparticle's surface and couple to the oscillating dipole of nearby radiating fluorophores, modifying their rate of emission and thus, enhancing their fluorescence.

Targeting RARA overexpression with tamibarotene, a potent and selective RARα agonist, is a novel approach in AML.

A superenhancer at the retinoic acid receptor alpha (RARA) gene is associated with RARA mRNA overexpression in ∼30% of non-acute promyelocytic leukemia acute myeloid leukemia (AML) and in ∼50% of myelodysplastic syndromes (MDS). RARA overexpression is an actionable target for treatment with tamibarotene, an oral potent and selective RARα agonist. Sensitivity to the RARα agonist tamibarotene was demonstrated in RARA-high but not RARA-low preclinical AML models.

Do statisticians count? A prior and posterior viewpoint.

In this article we look back over the last few decades and consider the progress made against the barriers that Andy Grieve has identified that may be holding statisticians back. We highlight some examples from his career where he leads the way in showing how we may overcome obstacles to enable statisticians to 'count' and assess whether anything has now changed for pharmaceutical statisticians.

Present and future bright and dark spots for coral reefs through climate change.

Marine heatwaves can cause coral bleaching and reduce coral cover on reefs, yet few studies have identified "bright spots," where corals have recently shown a capacity to survive such pressures. We analyzed 7714 worldwide surveys from 1997 to 2018 along with 14 environmental and temperature metrics in a hierarchical Bayesian model to identify conditions that contribute to present-day coral cover. We also identified locations with significantly higher (i.

Substrate recognition determinants of human eIF2α phosphatases.

Phosphorylation of the translation initiation factor eIF2α is a rapid and vital cellular defence against many forms of stress. In mammals, the levels of eIF2α phosphorylation are set through the antagonistic action of four protein kinases and two heterodimeric protein phosphatases. The phosphatases are composed of the catalytic subunit PP1 and one of two related non-catalytic subunits, PPP1R15A or PPP1R15B (R15A or R15B).

Optimization of an Imidazo[1,2-]pyridine Series to Afford Highly Selective Type I1/2 Dual Mer/Axl Kinase Inhibitors with Efficacy.

Inhibition of Mer and Axl kinases has been implicated as a potential way to improve the efficacy of current immuno-oncology therapeutics by restoring the innate immune response in the tumor microenvironment. Highly selective dual Mer/Axl kinase inhibitors are required to validate this hypothesis. Starting from hits from a DNA-encoded library screen, we optimized an imidazo[1,2-]pyridine series using structure-based compound design to improve potency and reduce lipophilicity, resulting in a highly selective probe compound .

Local conditions magnify coral loss after marine heatwaves.

Climate change threatens coral reefs by causing heat stress events that lead to widespread coral bleaching and mortality. Given the global nature of these mass coral mortality events, recent studies argue that mitigating climate change is the only path to conserve coral reefs. Using a global analysis of 223 sites, we show that local stressors act synergistically with climate change to kill corals.

Frequency of use of household products containing VOCs and indoor atmospheric concentrations in homes.

Volatile organic compounds (VOCs) are a key class of atmospheric emission released from highly complex petrochemical, transport and solvent sources both outdoors and indoors. This study established the concentrations and speciation of VOCs in 60 homes (204 individuals, 360 × 72 h samples, 40 species) in summer and winter, along with outdoor controls. Self-reported daily statistics were collected in each home on the use of cleaning, household and personal care products, all of which are known to release VOCs.

Optical writing and single molecule reading of photoactivatable and silver nanoparticle-enhanced fluorescence.

We designed a hybrid nanoparticle-molecular system composed of silver nanostructures (AgNP) and a fluorogenic boron dipyrromethene (BODIPY) that can be selectively activated by UVA or UVC light in the presence of an appropriate photoacid generator (PAG). Light irradiation of the PAG encourages the release of -toluenesulfonic, triflic or hydrobromic acid, any of which facilitate optical 'writing' by promoting the formation of a fluorescent species. Metal-enhanced fluorescence (MEF) by AgNP was achieved through rational design of the nano-molecular system in accordance with the principles of radiative decay engineering.

A global analysis of coral bleaching over the past two decades.

Thermal-stress events associated with climate change cause coral bleaching and mortality that threatens coral reefs globally. Yet coral bleaching patterns vary spatially and temporally. Here we synthesize field observations of coral bleaching at 3351 sites in 81 countries from 1998 to 2017 and use a suite of environmental covariates and temperature metrics to analyze bleaching patterns.

High profile backing for GS1 drive.

At the 2016 GS1 UK Healthcare Conference in London, delegates heard from speakers including Pat Mills, the Department of Health's commercial director, on the ongoing work to embed GS1 standards throughout the NHS in England in line with the DH's eProcurement Strategy, published in April 2014. This mandated that any service or product procured by an English NHS acute Trust comply with the standards--one of the most obvious representations of which is on barcodes--'to enable Trusts to manage their non-pay spending by adopting master procurement data, automating the exchange of such data, and benchmarking their procurement against other Trusts and healthcare providers'. One of six 'demonstrator site' Trusts to provide a speaker at the 2016 GS1 UK national conference to report on their progress to date was Leeds Teaching Hospitals NHS Trust.

Two-Photon Excitation of a Plasmonic Nanoswitch Monitored by Single-Molecule Fluorescence Microscopy.

Visible-light excitation of the surface plasmon band of silver nanoplates can effectively localize and concentrate the incident electromagnetic field enhancing the photochemical performance of organic molecules. Herein, the first single-molecule study of the plasmon-assisted isomerization of a photochrome-fluorophore dyad, designed to switch between a nonfluorescent and a fluorescent state in response to the photochromic transformation, is reported. The photochemistry of the switchable assembly, consisting of a photochromic benzooxazine chemically conjugated to a coumarin moiety, is examined in real time with total internal reflection fluorescence microscopy in the presence of silver nanoplates excited with a 633 nm laser.

Dye synthesis in the Pechmann reaction: catalytic behaviour of samarium oxide nanoparticles studied using single molecule fluorescence microscopy.

Photochemically prepared samarium oxide nanoparticles (SmONP) efficiently catalyze the formation of coumarin 153 the Pechmann trans-esterification and condensation process. The formation of the fluorescent coumarin allowed the catalytic process to be monitored in real time at the single molecule level using Total Internal Reflection Fluorescence Microscopy (TIRFM). Benchtop experiments conducted in parallel demonstrated that the observed catalysis occurred in solution rather than by pure heterogeneous catalysis and is due to a mobile population of small SmONP released from a polydisperse original sample containing larger particles.

A case study using the PrOACT-URL and BRAT frameworks for structured benefit risk assessment.

While benefit-risk assessment is a key component of the drug development and maintenance process, it is often described in a narrative. In contrast, structured benefit-risk assessment builds on established ideas from decision analysis and comprises a qualitative framework and quantitative methodology. We compare two such frameworks, applying multi-criteria decision-analysis (MCDA) within the PrOACT-URL framework and weighted net clinical benefit (wNCB), within the BRAT framework.

Drainage discharge impacts on hydrology and water quality of receiving streams in the wheatbelt of Western Australia.

The use of surface and subsurface drainage to manage waterlogging and salinity in dryland (rainfed) and irrigated agricultural systems is common throughout the world. The drainage systems often discharge into natural streams. The same is true for the wheatbelt drainage systems in south-western Australia, where 11,000 km (ABS 2003) of artificial drains have been constructed within the last two decades.

Hourly rounding in a high dependency unit.

The Leeds Teaching Hospitals NHS Trust is one of the many organisations that have signed up to Safety Express, a pilot programme of the Department of Health's Quality, Innovation, Productivity and Prevention safe care coalition. Its aim is to reduce avoidable harm to patients in four areas: trips and falls, pressure ulcers, catheter-associated urinary tract infections and venous thromboembolism. Hourly rounding (hourly checks on patients) has been identified as a means of reducing harm to patients.