Nicotine and cannabis use during adolescence has the potential to induce long lasting changes on affective and cognitive function. Here, we examined whether adolescent exposure to nicotine, the ...cannabinoid agonist WIN55-212,2 (WIN), or co-exposure to both would alter operant learning, locomotion, and anxiety- and reward-related behaviors in male and female mice during adulthood. Males exposed to a moderate dose of WIN (2 mg/kg) or co-exposed to nicotine and the moderate dose of WIN exhibited decreased anxiety-associated behaviors and increased cognitive flexibility, but did not differ in operant learning or generalized locomotion. In contrast, differences were not found among the females in these measures at the moderate WIN dose or in both sexes with exposure to a low WIN dose (0.2 mg/kg). Furthermore, a sex-dependent dissociative effect was found in natural reward consumption. Males exposed to the moderate dose of WIN or co-exposed to nicotine and the moderate dose of WIN demonstrated increased sucrose consumption. In contrast, females exposed to the moderate dose of WIN exhibited a decrease in sucrose consumption, which was ameliorated with co-administration of nicotine. Together, these novel findings demonstrate that adolescent exposure to cannabinoids in the presence or absence of nicotine results in altered affective and reward-related behaviors during adulthood.
This paper presents the Modular Assessment of Rainfall–Runoff Models Toolbox (MARRMoT): a modular open-source toolbox containing documentation and model code based on 46 existing conceptual ...hydrologic models. The toolbox is developed in MATLAB and works with Octave. MARRMoT models are based solely on traceable published material and model documentation, not on already-existing computer code. Models are implemented following several good practices of model development: the definition of model equations (the mathematical model) is kept separate from the numerical methods used to solve these equations (the numerical model) to generate clean code that is easy to adjust and debug; the implicit Euler time-stepping scheme is provided as the default option to numerically approximate each model's ordinary differential equations in a more robust way than (common) explicit schemes would; threshold equations are smoothed to avoid discontinuities in the model's objective function space; and the model equations are solved simultaneously, avoiding the physically unrealistic sequential solving of fluxes. Generalized parameter ranges are provided to assist with model inter-comparison studies. In addition to this paper and its Supplement, a user manual is provided together with several workflow scripts that show basic example applications of the toolbox. The toolbox and user manual are available from https://github.com/wknoben/MARRMoT (last access: 30 May 2019; https://doi.org/10.5281/zenodo.3235664). Our main scientific objective in developing this toolbox is to facilitate the inter-comparison of conceptual hydrological model structures which are in widespread use in order to ultimately reduce the uncertainty in model structure selection.
The choice of hydrological model structure, that is, a model's selection of states and fluxes and the equations used to describe them, strongly controls model performance and realism. This work ...investigates differences in performance of 36 lumped conceptual model structures calibrated to and evaluated on daily streamflow data in 559 catchments across the United States. Model performance is compared against a benchmark that accounts for the seasonality of flows in each catchment. We find that our model ensemble struggles to beat the benchmark in snow‐dominated catchments. In most other catchments model structure equifinality (i.e., cases where different models achieve similar high efficiency scores) can be very high. We find no relation between the number of model parameters and performance during either calibration or evaluation periods nor evidence of increased risk of overfitting for models with more parameters. Instead, the choice of model parametrization (i.e., which equations are used and how parameters are used within them) dictates the model's strengths and weaknesses. Results suggest that certain model structures are inherently better suited for certain objective functions and thus for certain study purposes. We find no clear relationships between the catchments where any model performs well and descriptors of those catchments' geology, topography, soil, and vegetation characteristics. Instead, model suitability seems to relate strongest to the streamflow regime each catchment generates, and we have formulated several tentative hypotheses that relate commonalities in model structure to similarities in model performance. Modeling results are made publicly available for further investigation.
Key Points
Conceptual model structure uncertainty is high across different catchments and objective functions
There is no evidence of systematic overfitting for models with up to 15 calibrated parameters
Model performance relates more to streamflow signatures than to climate or catchment descriptors
Hydrologic models have potential to be useful tools in planning for future climate variability. However, recent literature suggests that the current generation of conceptual rainfall runoff models ...tend to underestimate the sensitivity of runoff to a given change in rainfall, leading to poor performance when evaluated over multiyear droughts. This research revisited this conclusion, investigating whether the observed poor performance could be due to insufficient model calibration and evaluation techniques. We applied an approach based on Pareto optimality to explore trade‐offs between model performance in different climatic conditions. Five conceptual rainfall runoff model structures were tested in 86 catchments in Australia, for a total of 430 Pareto analyses. The Pareto results were then compared with results from a commonly used model calibration and evaluation method, the Differential Split Sample Test. We found that the latter often missed potentially promising parameter sets within a given model structure, giving a false negative impression of the capabilities of the model. This suggests that models may be more capable under changing climatic conditions than previously thought. Of the 282347 cases of apparent model failure under the split sample test using the lower higher of two model performance criteria trialed, 155120 were false negatives. We discuss potential causes of remaining model failures, including the role of data errors. Although the Pareto approach proved useful, our aim was not to suggest an alternative calibration strategy, but to critically assess existing methods of model calibration and evaluation. We recommend caution when interpreting split sample results.
Key Points:
Models may be more capable under changing climatic conditions than previously thought
Common calibration methods often fail to identify parameter sets that are robust
Caution is needed when interpreting the results of split sample testing
Age of patients undergoing surgery Fowler, A. J.; Abbott, T. E. F.; Prowle, J. ...
British journal of surgery,
July 2019, 2019-07-00, 20190701, Letnik:
106, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Background
Advancing age is independently associated with poor postoperative outcomes. The ageing of the general population is a major concern for healthcare providers. Trends in age were studied ...among patients undergoing surgery in the National Health Service in England.
Methods
Time trend ecological analysis was undertaken of Hospital Episode Statistics and Office for National Statistics data for England from 1999 to 2015. The proportion of patients undergoing surgery in different age groupings, their pooled mean age, and change in age profile over time were calculated. Growth in the surgical population was estimated, with associated costs, to the year 2030 by use of linear regression modelling.
Results
Some 68 205 695 surgical patient episodes (31 220 341 men, 45·8 per cent) were identified. The mean duration of hospital stay was 5·3 days. The surgical population was older than the general population of England; this gap increased over time (1999: 47·5 versus 38·3 years; 2015: 54·2 versus 39·7 years). The number of people aged 75 years or more undergoing surgery increased from 544 998 (14·9 per cent of that age group) in 1999 to 1 012 517 (22·9 per cent) in 2015. By 2030, it is estimated that one‐fifth of the 75 years and older age category will undergo surgery each year (1·49 (95 per cent c.i. 1·43 to 1·55) million people), at a cost of €3·2 (3·1 to 3·5) billion.
Conclusion
The population having surgery in England is ageing at a faster rate than the general population. Healthcare policies must adapt to ensure that provision of surgical treatments remains safe and sustainable.
The surgical population of England is ageing more quickly than the general population. More than 1·4 million patients aged over 75 years will have surgery each year by 2030.
Worrying prediction
Despite evidence of high activity, the number of surgical procedures performed in UK hospitals, their cost and subsequent mortality remain unclear.
Time-trend ecological study using hospital episode ...data from England, Scotland, Wales and Northern Ireland. The primary outcome was the number of in-hospital procedures, grouped using three increasingly specific categories of surgery. Secondary outcomes were all-cause mortality, length of hospital stay and healthcare costs according to standard National Health Service tariffs.
Between April 1, 2009 and March 31, 2014, 39 631 801 surgical patient episodes were recorded. There was an annual average of 7 926 360 procedures (inclusive category), 5 104 165 procedures (intermediate category) and 1 526 421 procedures (restrictive category). This equates to 12 537, 8073 and 2414 procedures per 100 000 population per year, respectively. On average there were 85 181 deaths (1.1%) within 30 days of a procedure each year, rising to 178 040 deaths (2.3%) after 90 days. Approximately 62.8% of all procedures were day cases. Median length of stay for in-patient procedures was 1.7 (1.3–2.0) days. The total cost of surgery over the 5 yr period was £54.6 billion ($104.4 billion), representing an average annual cost of £10.9 billion (inclusive), £9.5 billion (intermediate) and £5.6 billion (restrictive). For each category, the number of procedures increased each year, while mortality decreased. One-third of all mortalities in national death registers occurred within 90 days of a procedure (inclusive category).
The number of surgical procedures in the UK varies widely according to definition. The number of procedures is slowly increasing whilst the number of deaths is decreasing.
It is currently unclear whether the GluN2 subtype influences NMDA receptor (NMDAR) excitotoxicity. We report that the toxicity of NMDAR-mediated Ca2+ influx is differentially controlled by the ...cytoplasmic C-terminal domains of GluN2B (CTD2B) and GluN2A (CTD2A). Studying the effects of acute expression of GluN2A/2B-based chimeric subunits with reciprocal exchanges of their CTDs revealed that CTD2B enhances NMDAR toxicity, compared to CTD2A. Furthermore, the vulnerability of forebrain neurons in vitro and in vivo to NMDAR-dependent Ca2+ influx is lowered by replacing the CTD of GluN2B with that of GluN2A by targeted exon exchange in a mouse knockin model. Mechanistically, CTD2B exhibits stronger physical/functional coupling to the PSD-95-nNOS pathway, which suppresses protective CREB activation. Dependence of NMDAR excitotoxicity on the GluN2 CTD subtype can be overcome by inducing high levels of NMDAR activity. Thus, the identity (2A versus 2B) of the GluN2 CTD controls the toxicity dose-response to episodes of NMDAR activity.
► The CTD of GluN2B promotes excitotoxicity better than that of GluN2A ► GluN2 CTD subtype differences are seen in both WT and chimeric 2A/2B subunits ► The GluN2B CTD couples to a prodeath PSD-95/nNOS-dependent CREB shut-off pathway
Martel et al. find that the two subtypes (2A versus 2B) of the GluN2 C-terminal domain differentially couple to the CREB shut-off pathway, causing distinct effects on NMDA receptor-mediated neuronal death both in vitro and in vivo.
Satellite‐derived estimates of sea‐ice age and thickness are combined to produce a proxy ice thickness record for 1982 to the present. These data show that in addition to the well‐documented loss of ...perennial ice cover as a whole, the amount of oldest and thickest ice within the remaining multiyear ice pack has declined significantly. The oldest ice types have essentially disappeared, and 58% of the multiyear ice now consists of relatively young 2‐ and 3‐year‐old ice compared to 35% in the mid‐1980s. Ice coverage in summer 2007 reached a record minimum, with ice extent declining by 42% compared to conditions in the 1980s. The much‐reduced extent of the oldest and thickest ice, in combination with other factors such as ice transport that assist the ice‐albedo feedback by exposing more open water, help explain this large and abrupt ice loss.
Though tree-ring chronologies are annually resolved, their dating has never been independently validated at the global scale. Moreover, it is unknown if atmospheric radiocarbon enrichment events of ...cosmogenic origin leave spatiotemporally consistent fingerprints. Here we measure the
C content in 484 individual tree rings formed in the periods 770-780 and 990-1000 CE. Distinct
C excursions starting in the boreal summer of 774 and the boreal spring of 993 ensure the precise dating of 44 tree-ring records from five continents. We also identify a meridional decline of 11-year mean atmospheric radiocarbon concentrations across both hemispheres. Corroborated by historical eye-witness accounts of red auroras, our results suggest a global exposure to strong solar proton radiation. To improve understanding of the return frequency and intensity of past cosmic events, which is particularly important for assessing the potential threat of space weather on our society, further annually resolved
C measurements are needed.
This paper presents the Australian edition of the Catchment Attributes and
Meteorology for Large-sample Studies (CAMELS) series of datasets. CAMELS-AUS (Australia) comprises data for 222 unregulated ...catchments, combining hydrometeorological
time series (streamflow and 18 climatic variables) with 134 attributes
related to geology, soil, topography, land cover, anthropogenic influence
and hydroclimatology. The CAMELS-AUS catchments have been monitored for
decades (more than 85 % have streamflow records longer than 40 years) and
are relatively free of large-scale changes, such as significant changes in
land use. Rating curve uncertainty estimates are provided for most (75 %)
of the catchments, and multiple atmospheric datasets are included, offering
insights into forcing uncertainty. This dataset allows users globally to
freely access catchment data drawn from Australia's unique hydroclimatology,
particularly notable for its large interannual variability. Combined with
arid catchment data from the CAMELS datasets for the USA and Chile,
CAMELS-AUS constitutes an unprecedented resource for the study of arid-zone
hydrology. CAMELS-AUS is freely downloadable from https://doi.org/10.1594/PANGAEA.921850 (Fowler et al., 2020a).
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