STOPP/START criteria for potentially inappropriate prescribing in older people: version 2

Purpose: screening tool of older people’s prescriptions (STOPP) and screening tool to alert to right treatment (START) criteria were first published in 2008. Due to an expanding therapeutics evidence base, updating of the criteria was required. Methods: we reviewed the 2008 STOPP/START criteria to add new evidence-based criteria and remove any obsolete criteria. A thorough literature review was performed to reassess the evidence base of the 2008 criteria and the proposed new criteria. Nineteen experts from 13 European countries reviewed a new draft of STOPP & START criteria including proposed new criteria. These experts were also asked to propose additional criteria they considered important to include in the revised STOPP & START criteria and to highlight any criteria from the 2008 list they considered less important or lacking an evidence base. The revised list of criteria was then validated using the Delphi consensus methodology. Results: the expert panel agreed a final list of 114 criteria after two Delphi validation rounds, i.e. 80 STOPP criteria and 34 START criteria. This represents an overall 31% increase in STOPP/START criteria compared with version 1. Several new STOPP categories were created in version 2, namely antiplatelet/anticoagulant drugs, drugs affecting, or affected by, renal function and drugs that increase anticholinergic burden; new START categories include urogenital system drugs, analgesics and vaccines. Conclusion: STOPP/START version 2 criteria have been expanded and updated for the purpose of minimizing inappropriate prescribing in older people. These criteria are based on an up-to-date literature review and consensus validation among a European panel of experts

Comparison of proteomic profiles of serum, plasma, and modified media supplements used for cell culture and expansion

BACKGROUND: The culture and expansion of human cells for clinical use requires the presence of human serum or plasma in culture media. Although these supplements have been extensively characterized in their chemical composition, only recently it has been possible to provide by high throughput protein analysis, a comprehensive profile of the soluble factors contributing to cell survival. This study analyzed and compared the presence of 100 proteins including chemokines, cytokines and soluble factors in six different types of media supplements: serum, plasma, recalcified plasma, heat inactivated serum, heat inactivated plasma and heat inactivated recalcified plasma. METHODS: Serum, plasma, recalcified plasma, and heat inactivated supplements were prepared from ten healthy subjects. The levels of 100 soluble factors were measured in each sample using a multiplexed ELISA assay and compared by Eisen hierarchical clustering analysis. RESULTS: A comparison of serum and plasma levels of soluble factors found that 2 were greater in plasma but 18 factors were greater in serum including 11 chemokines. The levels of only four factors differed between recalcified plasma and plasma. Heat inactivation had the greatest effect on soluble factors. Supervised Eisen hierarchical clustering indicated that the differences between heat inactivated supplements and those that were not were greater than the differences within these two groups. The levels of 36 factors differed between heat inactivated plasma and plasma. Thirty one of these factors had a lower concentration in heat inactivated plasma including 12 chemokines, 4 growth factors, 4 matrix metalloproteases, and 3 adhesion molecules. Heat inactivated decalcified plasma is often used in place of heat inactivated serum and the levels of 19 soluble factors differed between these two supplements. CONCLUSION: Our report provides a comprehensive protein profile of serum, plasma recalcified plasma, and heat inactivated supplements. This profile represents a qualitative and quantitative database that can aid in the selection of the appropriate blood derived supplement for human cell cultures with special requirements

Analysis of the MOST light curve of the heavily spotted K2IV component of the single-line spectroscopic binary II Pegasi

Continuous photometric observations of the visible component of the single-line, K2IV spectroscopic binary II Peg carried out by the MOST satellite during 31 consecutive days in 2008 have been analyzed. On top of spot-induced brightness modulation, eleven flares were detected of three distinct types characterized by different values of rise, decay and duration times. The flares showed a preference for occurrence at rotation phases when the most spotted hemisphere is directed to the observer, confirming previous similar reports. An attempt to detect a grazing primary minimum caused by the secondary component transiting in front of the visible star gave a negative result. The brightness variability caused by spots has been interpreted within a cold spot model. An assumption of differential rotation of the primary component gave a better fit to the light curve than a solid-body rotation model.Comment: Accepteed to MNRA

Diminished Left Ventricular Dyssynchrony and Impact of Resynchronization in Failing Hearts With Right Versus Left Bundle Branch Block

ObjectivesWe compared mechanical dyssynchrony and the impact of cardiac resynchronization therapy (CRT) in failing hearts with a pure right (RBBB) versus left bundle branch block (LBBB).BackgroundCardiac resynchronization therapy is effective for treating failing hearts with conduction delay and discoordinate contraction. Most data pertain to LBBB delays. With RBBB, the lateral wall contracts early so that biventricular (BiV) pre-excitation may not be needed. Furthermore, the magnitude of dyssynchrony and impact of CRT in pure RBBB versus LBBB remains largely unknown.MethodsDogs with tachypacing-induced heart failure combined with right or left bundle branch radiofrequency ablation were studied. Basal dyssynchrony and effects of single and BiV CRT on left ventricular (LV) function were assessed by pressure-volume catheter and tagged magnetic resonance imaging, respectively.ResultsLeft bundle branch block and RBBB induced similar QRS widening, and LV function (ejection fraction, maximum time derivative of LV pressure [dP/dtmax]) was similarly depressed in failing hearts with both conduction delays. Despite this, mechanical dyssynchrony was less in RBBB (circumferential uniformity ratio estimate [CURE] index: 0.80 ± 0.03 vs. 0.58 ± 0.09 for LBBB, p < 0.04; CURE 0→1 is dyssynchronous→synchronous). Cardiac resynchronization therapy had correspondingly less effect on hearts with RBBB than those with LBBB (i.e., 5.5 ± 1.1% vs. 29.5 ± 5.0% increase in dP/dtmax, p < 0.005), despite similar baselines. Furthermore, right ventricular-only pacing enhanced function and synchrony in RBBB as well or better than did BiV, whereas LV-only pacing worsened function.ConclusionsLess mechanical dyssynchrony is induced by RBBB than LBBB in failing hearts, and the corresponding impact of CRT on the former is reduced. Right ventricular-only pacing may be equally efficacious as BiV CRT in hearts with pure right bundle branch conduction delay

Refractile superficial retinal crystals and chronic retinal detachment: Case report

BACKGROUND: Few previous reports have described the presence of retinal refractile opacities at the macular area in patients presenting with longstanding peripheral retinal detachment. The exact nature of these opacities is unknown. CASE PRESENTATION: Two patients were referred with an abnormal appearance of refractile opacities in the macular area noted during routine examination. Both were found to have longstanding peripheral retinal detachments. Subretinal fluid analysis of one patient revealed the presence of multiple birefringent crystals. We hypothesise that these crystals are the origin of the refractile macular opacities noted. CONCLUSION: This report describes the rare presentation of asymptomatic peripheral retinal detachment by the detection of refractile macular opacities on routine examination. It highlights the importance of meticulous peripheral retinal examination in these cases. The article also describes the findings of the subretinal fluid analysis and discusses the possible hypothesis behind their appearance

National CO\u3csub\u3e2\u3c/sub\u3e budgets (2015-2020) inferred from atmospheric CO\u3csub\u3e2\u3c/sub\u3e observations in support of the global stocktake

Accurate accounting of emissions and removals of CO2 is critical for the planning and verification of emission reduction targets in support of the Paris Agreement. Here, we present a pilot dataset of country-specific net carbon exchange (NCE; fossil plus terrestrial ecosystem fluxes) and terrestrial carbon stock changes aimed at informing countries\u27 carbon budgets. These estimates are based on top-down NCE outputs from the v10 Orbiting Carbon Observatory (OCO-2) modeling intercomparison project (MIP), wherein an ensemble of inverse modeling groups conducted standardized experiments assimilating OCO-2 column-Averaged dry-Air mole fraction (XCO2) retrievals (ACOS v10), in situ CO2 measurements or combinations of these data. The v10 OCO-2 MIP NCE estimates are combined with bottom-up estimates of fossil fuel emissions and lateral carbon fluxes to estimate changes in terrestrial carbon stocks, which are impacted by anthropogenic and natural drivers. These flux and stock change estimates are reported annually (2015-2020) as both a global 1gg×g1g gridded dataset and a country-level dataset and are available for download from the Committee on Earth Observation Satellites\u27 (CEOS) website: 10.48588/npf6-sw92 . Across the v10 OCO-2 MIP experiments, we obtain increases in the ensemble median terrestrial carbon stocks of 3.29-4.58gPgCO2yr-1 (0.90-1.25gPgCyr-1). This is a result of broad increases in terrestrial carbon stocks across the northern extratropics, while the tropics generally have stock losses but with considerable regional variability and differences between v10 OCO-2 MIP experiments. We discuss the state of the science for tracking emissions and removals using top-down methods, including current limitations and future developments towards top-down monitoring and verification systems

Gridded and direct Epoch of Reionisation bispectrum estimates using the Murchison Widefield Array

We apply two methods to estimate the 21~cm bispectrum from data taken within the Epoch of Reionisation (EoR) project of the Murchison Widefield Array (MWA). Using data acquired with the Phase II compact array allows a direct bispectrum estimate to be undertaken on the multiple redundantly-spaced triangles of antenna tiles, as well as an estimate based on data gridded to the $uv$-plane. The direct and gridded bispectrum estimators are applied to 21 hours of high-band (167--197~MHz; $z$=6.2--7.5) data from the 2016 and 2017 observing seasons. Analytic predictions for the bispectrum bias and variance for point source foregrounds are derived. We compare the output of these approaches, the foreground contribution to the signal, and future prospects for measuring the bispectra with redundant and non-redundant arrays. We find that some triangle configurations yield bispectrum estimates that are consistent with the expected noise level after 10 hours, while equilateral configurations are strongly foreground-dominated. Careful choice of triangle configurations may be made to reduce foreground bias that hinders power spectrum estimators, and the 21~cm bispectrum may be accessible in less time than the 21~cm power spectrum for some wave modes, with detections in hundreds of hours.Comment: 19 pages, 10 figures, accepted for publication in PAS

Real‐world conservation planning for evolutionary diversity in the Kimberley, Australia, sidesteps uncertain taxonomy

Targeting phylogenetic diversity (PD) in systematic conservation planning is an efficient way to minimize losses across the Tree of Life. Considering representation of genetic diversity below and above species level, also allows robust analyses within systems where taxonomy is in flux. We use dense sampling of phylogeographic diversity for 11 lizard genera, to demonstrate how PD can be applied to a policy‐ready conservation planning problem. Our analysis bypasses named taxa, using genetic data directly to inform conservation decisions. We highlight areas that should be prioritized for ecological management, and also areas that would provide the greatest benefit if added to the multisector conservation estate. We provide a rigorous and effective approach to represent the spectrum of genetic and species diversity in conservation planning.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145539/1/conl12438.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145539/2/conl12438-sup-0001-figureS1-S2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145539/3/conl12438_am.pd