Pattern and Prognostic Impact of Regional Wall Motion Abnormalities in 255 697 Men and 236 641 Women Investigated with Echocardiography

Background Regional wall motion abnormalities (WMAs) after myocardial infarction are associated with adverse remodeling and increased mortality in the short to medium term. Their long‐term prognostic impact is less well understood. Methods and Results Via the National Echo Database of Australia (2000–2019), we identified normal wall motion versus WMA for each left ventricular wall among 492 338 individuals aged 61.9±17.9 years. The wall motion score index was also calculated. We then examined actual 1‐ and 5‐year mortality, plus adjusted risk of long‐term mortality according to WMA status. Overall, 39 346/255 697 men (15.4%) and 17 834/236 641 women (7.5%) had a WMA. The likelihood of a WMA was associated with increasing age and greater systolic/diastolic dysfunction. A defect in the inferior versus anterior wall was the most and least common WMA in men (8.0% and 2.5%) and women (3.3% and 1.1%), respectively. Any WMA increased 5‐year mortality from 17.5% to 29.7% in men and from 14.9% to 30.8% in women. Known myocardial infarction (hazard ratio [HR], 0.86 [95% CI, 0.80–0.93]) or revascularization (HR, 0.87 [95% CI, 0.82–0.92]) was independently associated with a better prognosis, whereas men (1.22‐fold increase) and those with greater systolic/diastolic dysfunction had a worse prognosis. Among those with any WMA, apical (HR, 1.08 [95% CI, 1.02–1.13]) or inferior (HR, 1.09 [95% CI, 1.04–1.15]) akinesis, dyskinesis or aneurysm, or a wall motion score index >3.0 conveyed the worst prognosis. Conclusions In a large real‐world clinical cohort, twice as many men as women have a WMA, with inferior WMA the most common. Any WMA confers a poor prognosis, especially inferoapical akinesis/dyskinesis/aneurysm

The Papua New Guinea national health and HIV research agenda.

Contains fulltext : 136960.pdf (publisher's version ) (Open Access

Dependence of antibody gene diversification on uracil excision

Activation-induced deaminase (AID) catalyses deamination of deoxycytidine to deoxyuridine within immunoglobulin loci, triggering pathways of antibody diversification that are largely dependent on uracil-DNA glycosylase (uracil-N-glycolase [UNG]). Surprisingly efficient class switch recombination is restored to ung−/− B cells through retroviral delivery of active-site mutants of UNG, stimulating discussion about the need for UNG's uracil-excision activity. In this study, however, we find that even with the overexpression achieved through retroviral delivery, switching is only mediated by UNG mutants that retain detectable excision activity, with this switching being especially dependent on MSH2. In contrast to their potentiation of switching, low-activity UNGs are relatively ineffective in restoring transversion mutations at C:G pairs during hypermutation, or in restoring gene conversion in stably transfected DT40 cells. The results indicate that UNG does, indeed, act through uracil excision, but suggest that, in the presence of MSH2, efficient switch recombination requires base excision at only a small proportion of the AID-generated uracils in the S region. Interestingly, enforced expression of thymine-DNA glycosylase (which can excise U from U:G mispairs) does not (unlike enforced UNG or SMUG1 expression) potentiate efficient switching, which is consistent with a need either for specific recruitment of the uracil-excision enzyme or for it to be active on single-stranded DNA

H0LiCOW XII. Lens mass model of WFI2033-4723 and blind measurement of its time-delay distance and H0H_0

We present the lens mass model of the quadruply-imaged gravitationally lensed quasar WFI2033-4723, and perform a blind cosmographical analysis based on this system. Our analysis combines (1) time-delay measurements from 14 years of data obtained by the COSmological MOnitoring of GRAvItational Lenses (COSMOGRAIL) collaboration, (2) high-resolution $\textit{Hubble Space Telescope}$ imaging, (3) a measurement of the velocity dispersion of the lens galaxy based on ESO-MUSE data, and (4) multi-band, wide-field imaging and spectroscopy characterizing the lens environment. We account for all known sources of systematics, including the influence of nearby perturbers and complex line-of-sight structure, as well as the parametrization of the light and mass profiles of the lensing galaxy. After unblinding, we determine the effective time-delay distance to be $4784_{-248}^{+399}~\mathrm{Mpc}$, an average precision of $6.6\%$. This translates to a Hubble constant $H_{0} = 71.6_{-4.9}^{+3.8}~\mathrm{km~s^{-1}~Mpc^{-1}}$, assuming a flat $\Lambda$CDM cosmology with a uniform prior on $\Omega_\mathrm{m}$ in the range [0.05, 0.5]. This work is part of the $H_0$ Lenses in COSMOGRAIL's Wellspring (H0LiCOW) collaboration, and the full time-delay cosmography results from a total of six strongly lensed systems are presented in a companion paper (H0LiCOW XIII).Comment: Version accepted by MNRAS. 29 pages including appendix, 17 figures, 6 tables. arXiv admin note: text overlap with arXiv:1607.0140

Large ensemble simulations for water resources planning

The UK has experienced recurring periods of hydrological droughts in the past, including the recent 2022 drought. Different types of large ensemble simulations such as single model initial condition climate model simulations or weather hindcasts provide a large sample of seasonal to decadal simulations. They can help overcome challenges in understanding extreme droughts presented by limited observations, the multivariate nature of individual drought events and internal variability of the climate system. Here, we demonstrate how weather reforecasts can be used to create physical climate storylines to assist water resources planning and understand plausible worst cases. Using the 2022 drought as a case study, event-based storylines of how the drought could unfold over winter 2022/23 and beyond can be created by using the SEAS5 hindcast dataset which consists of 2850 physically plausible winters since 1982 across three lead times and 25 ensemble members. Storylines were defined based on the possible combinations of ENSO, the North Atlantic Oscillation (NAO) and the East Atlantic Pattern (EA) (e.g. La Nina/NAO+/EA-). Storylines constructed in this way provide outlooks of ongoing events and supplement traditional weather forecasts to explore a wider range of plauasible outcomes. Circulation storylines can be used in hydrological/groundwater models to explore the possible ranges of river flow, groundwater and reservoir levels. Outlooks can be periodically updated as certain storylines may become implausible over time

Storylines of UK drought based on the 2010–2012 event

Spatially extensive multi-year hydrological droughts cause significant environmental stress. The UK is expected to remain vulnerable to future multi-year droughts under climate change. Existing approaches to quantify hydrological impacts of climate change often rely solely on global climate model (GCM) projections following different emission scenarios. This may miss out low-probability events with significant impacts. As a means of exploring such events, physical climate storyline approaches aim to quantify physically coherent articulations of how observed events could hypothetically have unfolded in alternative ways. This study uses the 2010–2012 drought, the most recent period of severe hydrological drought in the UK, as a basis and analyses storylines based on changes to (1) precondition severity, (2) temporal drought sequence, and (3) climate change. Evidence from multiple storylines shows that the maximum intensity, mean deficit, and duration of the 2010–2012 drought were highly influenced by its meteorological preconditions prior to drought inception, particularly for northern catchments at shorter timescales. The influence of progressively drier preconditions reflects both the spatial variation in drought preconditions and the role of physical catchment characteristics, particularly hydrogeology in the propagation of multi-year droughts. There are two plausible storylines of an additional dry year with dry winter conditions repeated either before the observed drought or replacing the observed dramatic drought termination confirm the vulnerability of UK catchments to a “third dry winter” storyline. Applying the UKCP18 climate projections, we find that drought conditions worsen with global warming with a mitigation of drought conditions by wetter winters in northern catchments at high warming levels. Comparison of the storylines with a benchmark drought (1975–1976) and a protracted multi-year drought (1989–1993) shows that, for each storyline (including the climate change storylines), drought conditions could have matched and exceeded those experienced during the past droughts at catchments across the UK, particularly for southern catchments. The construction of storylines based on observed events can complement existing methods to stress test UK catchments against plausible unrealised droughts

Added value of seasonal hindcasts to create UK hydrological drought storylines

The UK has experienced recurring periods of hydrological droughts in the past, including the drought declared in summer 2022. Seasonal hindcasts, consisting of a large sample of plausible weather sequences, can be used to create drought storylines and add value to existing approaches to water resources planning. In this study, the drivers of winter rainfall in the Anglian region in England are investigated using the ECMWF SEAS5 hindcast dataset, which includes 2850 plausible winters across 25 ensemble members and 3 lead times. Four winter clusters are defined using the hindcast winters based on possible combinations of various atmospheric circulation indices (such as the North Atlantic Oscillation, NAO; East Atlantic, EA, pattern; and El Niño–Southern Oscillation). Using the 2022 drought as a case study, we demonstrate how storylines representing alternative ways the event could have unfolded can be used to explore plausible worst-case scenarios over winter 2022/23 and beyond. The winter clusters span a range of temperature and rainfall response in the study region and represent circulation storylines that could have happened over winter 2022/23. River flow and groundwater level simulations with the large sample of plausible hindcast winters show that drier-than-average winters characterised by predominantly NAO−/EA− and NAO+/EA− circulation patterns could have resulted in the continuation of the drought with a high likelihood of below-normal to low river flows across all selected catchments and boreholes by spring and summer 2023. Catchments in Norfolk were particularly vulnerable to a dry summer in 2023 as river flows were not estimated to recover to normal levels even with wet winters characterised predominantly by NAO−/EA+ and NAO+/EA+ circulation patterns, due to insufficient rainfall to overcome previous dry conditions and the slow response nature of groundwater-dominated catchments. Through this analysis, we aim to demonstrate the added value of this approach to create drought storylines during an ongoing event. Storylines constructed in this way supplement traditional weather forecasts and hydrological outlooks, in order to explore a wider range of plausible outcomes

A Highly Magnified Gravitationally Lensed Red QSO at z = 2.5 with a Significant Flux Ratio Anomaly

We present the discovery of a gravitationally lensed dust-reddened QSO at z = 2.517, identified in a survey for QSOs by infrared selection. Hubble Space Telescope imaging reveals a quadruply lensed system in a cusp configuration, with a maximum image separation of ~1.8\arcsec. We find that compared to the central image of the cusp, the neighboring brightest image is anomalous by a factor of ~ 7 - 10, which is the largest flux anomaly measured to date in a lensed QSO. Incorporating high-resolution Jansky Very Large Array radio imaging and sub-mm imaging with the Atacama Large (sub-)Millimetre Array, we conclude that a low-mass perturber is the most likely explanation for the anomaly. The optical through near-infrared spectrum reveals that the QSO is moderately reddened with E(B - V) = 0.7 - 0.9. We see an upturn in the ultraviolet spectrum due to ~ 1% of the intrinsic emission being leaked back into the line of sight, which suggests that the reddening is intrinsic and not due to the lens. The QSO may have an Eddington ratio as high as L/L_Edd ~ 0.2. Consistent with previous red QSO samples, this source exhibits outflows in its spectrum as well as morphological properties suggestive of it being in a merger-driven transitional phase. We find a host-galaxy stellar mass of log M_*/M_Sun = 11.4, which is higher than the local M_BH vs. M_* relation, but consistent with other high redshift QSOs. When de-magnified, this QSO is at the knee of the luminosity function, allowing for the detailed study of a more typical moderate-luminosity infrared-selected QSO at high redshift.Comment: Accepted for publication in ApJ; 29 pages, 18 figures, 8 tables. arXiv admin note: text overlap with arXiv:1807.0543

Comparison of magnetic resonance imaging and computed tomography for breast target volume delineation in prone and supine positions

Purpose To\ua0determine whether T2-weighted MRI improves seroma cavity (SC) and whole breast (WB) interobserver conformity for radiation therapy purposes, compared with the gold standard of CT, both in the prone and supine positions. Methods and Materials Eleven observers (2 radiologists and 9 radiation oncologists) delineated SC and WB clinical target volumes (CTVs) on T2-weighted MRI and CT supine and prone scans (4 scans per patient) for 33 patient datasets. Individual observer's volumes were compared using the Dice similarity coefficient, volume overlap index, center of mass shift, and Hausdorff distances. An average cavity visualization score was also determined. Results Imaging modality did not affect interobserver variation for WB CTVs. Prone WB CTVs were larger in volume and more conformal than supine CTVs (on both MRI and CT). Seroma cavity volumes were larger on CT than on MRI. Seroma cavity volumes proved to be comparable in interobserver conformity in both modalities (volume overlap index of 0.57\ua0(95% Confidence Interval (CI) 0.54-0.60) for CT supine and 0.52\ua0(95% CI 0.48-0.56) for MRI supine, 0.56\ua0(95% CI 0.53-0.59) for CT prone and 0.55\ua0(95% CI 0.51-0.59) for MRI prone); however, after registering modalities together the intermodality variation (Dice similarity coefficient of 0.41\ua0(95% CI 0.36-0.46) for supine and 0.38\ua0(0.34-0.42) for prone) was larger than the interobserver variability for SC, despite the location typically remaining constant. Conclusions Magnetic resonance imaging interobserver variation was comparable to CT for the WB CTV and SC delineation, in both prone and supine positions. Although the cavity visualization score and interobserver concordance was not significantly higher for MRI than for CT, the SCs were smaller on MRI, potentially owing to clearer SC definition, especially on T2-weighted MR images