Recent extremes of flood and drought across Australia have raised questions about the recurrence of such rare events and highlighted the importance of understanding multi-decadal climate variability. ...However, instrumental records over the past century are too short to adequately characterise climate variability on multi-decadal and longer timescales or robustly determine extreme event frequencies and their duration. Palaeoclimate reconstructions can provide much-needed information to help address this problem. Here, we use the 600-year hydroclimate record captured in the eastern Australian and New Zealand Drought Atlas (ANZDA) to analyse drought and pluvial frequency trends for East Australian Natural Resource Management (NRM) clusters. This partitioning of the drought atlas grid points into recognised biophysical areas (i.e. NRM clusters) revealed their differences and similarities in drought intensity and pluvial events over time. We find sustained multi-decadal periods of a wet–dry geographic 'seesaw' between eastern to central and southern NRMs (e.g. 1550–1600 CE and 1700–1750 CE). In contrast, other periods reveal spatially consistent wetting (e.g. 1500–1550 CE) or drying (e.g. 1750–1800 CE). Emerging hot spot analysis further shows that some areas that appear naturally buffered from severe drought during the instrumental period have a greater exposure risk when the longer 600-year record is considered. These findings are particularly relevant to management plans when dealing with the impacts of climate extremes developed at regional scales. Our results demonstrate that integrating and extending instrumental records with palaeoclimate datasets will become increasingly important for developing robust and locally specific extreme event frequency information for managing water resources.
This research investigates two factors influencing the ability of tree-ring data to provide accurate 14C calibration information: the fitness and rigor of the statistical model used to combine the ...data into a curve; and the accuracy, precision and reproducibility of the component 14C data sets. It presents a new Bayesian spline method for calibration curve construction and tests it on extant and new Southern Hemisphere (SH) data sets (also examining their dendrochronology and pretreatment) for the post-Little Ice Age (LIA) interval AD 1500–1950. The new method of construction allows calculation of component data offsets, permitting identification of laboratory and geographic biases. Application of the new method to the 10 suitable SH 14C data sets suggests that individual offset ranges for component data sets appear to be in the region of ± 10 yr. Data sets with individual offsets larger than this need to be carefully assessed before selection for calibration purposes. We identify a potential geographical offset associated with the Southern Ocean (high latitude) Campbell Island data. We test the new methodology for wiggle-matching short tree-ring sequences and use an OxCal simulation to assess the likely precision obtainable by wiggle-matching in the post-LIA interval.
Much of our knowledge about the impacts of volcanic eruptions on climate comes from proxy records. However, little is known about their impact on
the low to mid-latitudes of the Southern Hemisphere. ...Using superposed epoch analysis, we investigated whether volcanic signals could be identified
in annual tree-ring series from eight New Zealand dendrochronological species. We found that most species are reliable recorders of volcanic cooling
and that the magnitude and persistence of the post-event response can be broadly linked to plant life history traits. Across species, site-based
factors, particularly altitude and exposure to prevailing conditions, are more important determinants of the strength of the volcanic response than
species. We then investigated whether chronology selection impacts the magnitude of post-volcanic cooling in tree-ring-based temperature
reconstructions by developing two new multispecies reconstructions of New Zealand summer (December–February) temperature with one reconstruction
from the pool of all available chronologies, and the other from a selected subset shown to be sensitive to volcanic eruptions. Both reconstructions
record temperature anomalies that are remarkably consistent with studies based on instrumental temperature and the ensemble mean response of climate
models, demonstrating that New Zealand ring widths are reliable indicators of regional volcanic climate response. However, we also found that
volcanic response can be complex, with positive, negative, and neutral responses identified – sometimes within the same species group. Species-wide
composites thus tend to underestimate the volcanic response. This has important implications for the development of future tree-ring and multiproxy
temperature reconstructions from the Southern Hemisphere.
A recent article in this journal presented a US perspective regarding the modernization of clozapine prescription and proposed an escape from the long shadow cast by agranulocytosis.
Here, an ...international group of collaborators discusses a point of view complementary to the US view by focusing on worldwide outcomes of clozapine usage that may be uneven in terms of frequency of clozapine adverse drug reactions.
Studies from the Scandinavian national registries (Finland and Denmark) did not find increased mortality in clozapine patients or any clear evidence of the alleged toxicity of clozapine. Data on clozapine-associated fatal outcomes were obtained from 2 recently published pharmacovigilance studies and from the UK pharmacovigilance database. A pharmacovigilance study focused on physician reports to assess worldwide lethality of drugs from 2010 to 2019 found 968 clozapine-associated fatal outcomes in the United Kingdom. Moreover, the United Kingdom accounted for 55% (968 of 1761) of worldwide and 90% (968 of 1073) of European fatal clozapine-associated outcomes. In a pharmacovigilance study from the UK database (from 2008 to 2017), clozapine was associated with 383 fatal outcomes/year including all reports from physicians and nonphysicians. From 2018 to 2021, UK clozapine-associated fatal outcomes increased to 440/year.
The interpretation of fatal outcomes in each country using pharmacovigilance databases is limited and only allows gross comparisons; even with those limitations, the UK data seem concerning. Pneumonia and myocarditis may be more important than agranulocytosis in explaining the uneven distribution of fatal outcomes in clozapine patients across countries.
Objectives
Fetal 2D and 3D fractional limb volume (FLV) measurements by ultrasound can detect fetal lean and subcutaneous mass and possibly percent body fat. Our objectives were to 1) compare FLV ...measurements in fetuses with fetal growth restriction (FGR) versus small for gestational age (SGA) defined by the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG)‐supported international Delphi consensus and 2) correlate FLV findings with birth metrics. We hypothesize that FLV measurements will be significantly smaller in FGR versus SGA fetuses and will correlate closer with Ponderal index (PIx) in the neonate than abdominal circumference (AC).
Methods
Patients were categorized as FGR or SGA as defined by ISUOG. Total thigh volume (TTV), volumes of lean mass (LMV), and fat mass volume (FMV) were calculated from 3D acquisitions. Measurements were compared between groups and correlated with birthweight (BW) and PIx (BW/crown‐heal length).
Results
The FGR group (n = 37) delivered earlier (37/2 versus 38/0; P = .0847), were lighter (2.2 kg versus 2.6 kg; P = .0003) and had lower PIx (0.023 versus 0.025; P = .0013) than SGAs (n = 22). FGRs had reduced TTV (40.6 versus 48.4 cm3; P = .0164), FMV (20.8 versus 25.3 cm3; P = .0413), and LMV (19.8 versus 23.1 cm3; P = .0387). AC had the highest area under the curve (0.69) for FGR. FMV was more strongly associated with PIx than the AC (P = .0032).
Conclusions
The AC and FLV measurements were significantly reduced in FGR fetuses compared to SGAs. While the AC outperformed FLV in predicting FGR, the FLV correlated best with PIx, which holds investigative promise.
Interspecific variation in tree growth rate and maximum age is central to understanding and predicting the dynamics of forest ecosystems. While there are abundant sources of this information for ...economically important New Zealand timber species and other common tree species, data for trees from subantarctic environments are almost entirely lacking. Here we present measurements of growth from Auckland and Campbell Islands for three species: Metrosideros umbellata (southern rata; Myrtaceae, n = 1 site), a canopy dominant; Dracophyllum sp. (inaka; Ericaceae, n = 5 sites), a widespread small tree; and Olearia lyallii (tupare, subantarctic tree daisy; Asteraceae, n = 2 sites), a species native to Snares Island that has naturalised on the Auckland Islands. Our data showed large differences in tree growth rates among and within species across islands. Growth rates varied eight-fold (i.e. from 0.34 mm yr-1 to 2.78 mm yr-1), being greatest in Olearia lyallii, least in Dracophyllum sp. and intermediate in Metrosideros umbellata. Comparisons of the five Dracophyllum sites suggest that these trees experience reduced growth rates and reach older ages when in competition with the bigger southern rata (M. umbellata) trees, possibly due to the larger southern rata providing protection from wind-throw. Measurements of resprouted southern rata trees showed a variable juvenile-phase radial growth rate, highlighting the need for caution in extrapolating the likely ages of bigger trees. Remeasured individuals of Olearia lyallii growing among taller southern rata trees showed slow growth rates compared to much faster rates seen in a nearby monospecific stand. Overall, the variability in growth seen by all three species illustrates that tree size cannot be used to indicate age in these subantarctic islands.
The Procalcitonin Antibiotic Consensus Trial (ProACT) found provision of a procalcitonin antibiotic prescribing guideline to hospital-based clinicians did not reduce antibiotic use. Possible reasons ...include clinician reluctance to follow the guideline, with an observed 64.8% adherence rate. In this study we sought to determine the threshold adherence rate for reduction in antibiotic use, and to explore opportunities to increase adherence.
This study is a retrospective analysis of ProACT data. ProACT randomized 1656 patients presenting to 14 U.S. hospitals with suspected lower respiratory tract infection to usual care or provision of procalcitonin assay results and an antibiotic prescribing guideline to the treating clinicians. We simulated varying adherence to guideline recommendations for low procalcitonin levels and determined which threshold adherence rate could have resulted in rejection of the null hypothesis of no difference between groups at alpha = 0.05. We also performed sensitivity analyses within specific clinical settings and grouped patients initially prescribed antibiotics despite low procalcitonin into low, medium, and high risk of illness severity or bacterial infection.
Our primary outcome was number of antibiotic-days by day 30 using an intention-to-treat approach and a null hypothesis of no difference in antibiotic use. We determined that an 84% adherence rate in the hospital setting (emergency department and inpatient) for low procalcitonin could have allowed rejection of the null hypothesis (3.7 vs 4.3 antibiotic-days, p = 0.048). The threshold adherence rate was 76% for continued guideline adherence after discharge. Even 100% adherence in the emergency department alone failed to reduce antibiotic-days. Of the 218 patients prescribed antibiotics in the emergency department despite low procalcitonin, 153 (70.2%) were categorized as low or medium risk.
High adherence in the hospital setting to a procalcitonin antibiotic prescribing guideline is necessary to reduce antibiotic use in suspected lower respiratory tract infection. Continued guideline adherence after discharge and withholding of antibiotics in low and medium risk patients with low procalcitonin may offer impactful potential opportunities for antibiotic reduction. Trial registration Procalcitonin Antibiotic Consensus Trial (ProACT), ClinicalTrials.gov Identifier: NCT02130986. First posted May 6, 2014.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IntroductionIdiopathic pulmonary fibrosis (IPF) and non-IPF, progressive fibrotic interstitial lung diseases (PF-ILD), are associated with a progressive loss of lung function and a poor prognosis. ...Treatment with antifibrotic agents can slow, but not halt, disease progression, and treatment discontinuation because of adverse events is common. Fibrotic diseases such as these can be mediated by lysophosphatidic acid (LPA), which signals via six LPA receptors (LPA1–6). Signalling via LPA1 appears to be fundamental in the pathogenesis of fibrotic diseases. BMS-986278, a second-generation LPA1 antagonist, is currently in phase 2 development as a therapy for IPF and PF-ILD.Methods and analysisThis phase 2, randomised, double-blind, placebo-controlled, parallel-group, international trial will include adults with IPF or PF-ILD. The trial will consist of a 42-day screening period, a 26-week placebo-controlled treatment period, an optional 26-week active-treatment extension period, and a 28-day post-treatment follow-up. Patients in both the IPF (n=240) and PF-ILD (n=120) cohorts will be randomised 1:1:1 to receive 30 mg or 60 mg BMS-986278, or placebo, administered orally two times per day for 26 weeks in the placebo-controlled treatment period. The primary endpoint is rate of change in per cent predicted forced vital capacity from baseline to week 26 in the IPF cohort.Ethics and disseminationThis study will be conducted in accordance with Good Clinical Practice guidelines, Declaration of Helsinki principles, and local ethical and legal requirements. Results will be reported in a peer-reviewed publication.Trial registration numberNCT04308681.
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