Search

This study presents an approach to provide seamless climate information by concatenating decadal climate predictions and climate projections in time. Results for near‐surface air temperature over 29 regions indicate that such an approach has potential to provide meaningful information but can also introduce significant inconsistencies. Inconsistencies are often most pronounced for relatively extreme quantiles of the CMIP6 multi‐model ensemble distribution, whereas they are generally smaller and mostly insignificant for quantiles close to the median. The regions most affected are the North Atlantic, Greenland and Northern Europe. Two potential ways to reduce inconsistencies are discussed, including a simple calibration method and a weighting approach based on model performance. Calibration generally reduces inconsistencies but does not eliminate all of them. The impact of model weighting is minor, which is found to be linked to the small size of the decadal climate prediction ensemble, which in turn limits the applicability of that method. Plain Language Summary: Continuous and consistent information about the evolution of climate in next 1–40 years is crucial for the development of mitigation and adaptation strategies. Historically, scientific products providing weather and climate information have been designed for specific time scales, for example, seasonal or decadal climate predictions (1–10 years), or long‐term climate projections (1–100 + years). As a consequence, currently only climate projections can be used to provide continuous information beyond the 10 years time scale. However, as climate projections are not initialized using observations, they are likely – depending on the variable and region – less skillful than initialized predictions for shorter lead times. In this study we assess if meaningful continuous climate information can be obtained by concatenating decadal climate predictions and climate projections in time. Results suggest that significant inconsistencies (materialized in jumps in the resulting time series) can be introduced by this approach, however, for some regions temporal concatenation might provide meaningful climate information beyond decadal time scales. Furthermore, potential ways to reduce inconsistencies when concatenating are discussed. Key Points: Concatenating climate predictions and projections can introduce inconsistenciesConcatenation is less problematic for quantiles close to the median compared to more extreme quantiles of the ensemble distributionA simple calibration method reduces but does not eliminate inconsistencies [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are a heterogeneous population of multipotent cells that are capable of differentiating into osteocytes, chondrocytes and adipocytes. Recently, MSCs have been found to home to the tumour site and engraft in the tumour stroma. However, it is not yet known whether they have a tumour promoting or suppressive function. We investigated the interaction between prostate cancer cell lines 22Rv1, DU145 and PC3, and bone marrow‐derived MSCs. MSCs were ‘educated’ for extended periods in prostate cancer cell conditioned media and PC3‐educated MSCs were found to be the most responsive with a secretory profile rich in pro‐inflammatory cytokines. PC3‐educated MSCs secreted increased osteopontin (OPN), interleukin‐8 (IL‐8) and fibroblast growth factor‐2 (FGF‐2) and decreased soluble fms‐like tyrosine kinase‐1 (sFlt‐1) compared to untreated MSCs. PC3‐educated MSCs showed a reduced migration and proliferation capacity that was dependent on exposure to PC3‐conditioned medium. Vimentin and α‐smooth muscle actin (αSMA) expression was decreased in PC3‐educated MSCs compared to untreated MSCs. PC3 and DU145 education of healthy donor and prostate cancer patient‐derived MSCs led to a reduced proportion of FAP+ αSMA+ cells contrary to characteristics commonly associated with cancer associated fibroblasts (CAFs). The migration of PC3 cells was increased toward both PC3‐educated and DU145‐educated MSCs compared to untreated MSCs, while DU145 migration was only enhanced toward patient‐derived MSCs. In summary, MSCs developed an altered phenotype in response to prostate cancer conditioned medium which resulted in increased secretion of pro‐inflammatory cytokines, modified functional activity and the chemoattraction of prostate cancer cells. [ABSTRACT FROM AUTHOR]

Objectives: To provide an overview and draw lessons from the establishment of a local oral health promotion programme for preschool children in Leicester, England (2013–2017). The article provides information on the strategic approach taken in Leicester, one of the most ethnically diverse cities in England, and also one of the most deprived. Over a third of children aged 3 years, and half of those aged 5 years, have experience of obvious dental decay. Methods: A description of the evolution and development of the programme is provided along with commentary by the authors. This includes the origins, design and evaluation of the programme. Results: Progress so far has been promising. There has been a statistically significant 8% decrease in the proportion of 5‐year‐old children in Leicester with dental decay from 2011/2012 to 2014/2015. This will need to be sustained and further developed to deliver the 10% reduction required within the strategy. Conclusions: The successful implementation of a local oral health improvement programme in Leicester has required leadership to coordinate a multiagency partnership approach to embedding effective concepts and realising opportunities collaboratively. However, longer term sustainability remains a concern. [ABSTRACT FROM AUTHOR]

Current guidelines in the setting of exposures to potentially rabid bats established by the Advisory Committee on Immunization Practices (ACIP) address post-exposure prophylaxis ( PEP) administration in situations where a person may not be aware that a bite or direct contact has occurred and the bat is not available for diagnostic testing. These include instances when a bat is discovered in a room where a person awakens from sleep, is a child without an adult witness, has a mental disability or is intoxicated. The current ACIP guidelines, however, do not address PEP in the setting of multiple persons exposed to a bat or a bat colony, otherwise known as mass bat exposure ( MBE) events. Due to a dearth of recommendations for response to these events, the reported reactions by public health agencies have varied widely. To address this perceived limitation, a survey of 45 state public health agencies was conducted to characterize prior experiences with MBE and practices to mitigate the public health risks. In general, most states (69% of the respondents) felt current ACIP guidelines were unclear in MBE scenarios. Thirty-three of the 45 states reported prior experience with MBE, receiving an average of 16.9 MBE calls per year and an investment of 106.7 person-hours annually on MBE investigations. PEP criteria, investigation methods and the experts recruited in MBE investigations varied between states. These dissimilarities could reflect differences in experience, scenario and resources. The lack of consistency in state responses to potential mass exposures to a highly fatal disease along with the large contingent of states dissatisfied with current ACIP guidance warrants the development of national guidelines in MBE settings. [ABSTRACT FROM AUTHOR]

Demonstrating the effect that climate change is having on regional weather is a subject which occupies climate scientists, government policy makers and the media. After an extreme weather event occurs, the question is often posed, 'Was the event caused by anthropogenic climate change?' Recently, a new branch of climate science (known as attribution) has sought to quantify how much the risk of extreme events occurring has increased or decreased due to climate change. One method of attribution uses very large ensembles of climate models computed via volunteer distributed computing. A recent advancement is the ability to run both a global climate model and a higher resolution regional climate model on a volunteer's home computer. Such a set-up allows the simulation of weather on a scale that is of most use to studies of the attribution of extreme events. This article introduces a global climate model that has been developed to simulate the climatology of all major land regions with reasonable accuracy. This then provides the boundary conditions to a regional climate model (which uses the same formulation but at higher resolution) to ensure that it can produce realistic climate and weather over any region of choice. The development process is documented and a comparison to previous coupled climate models and atmosphere-only climate models is made. The system (known as weather@home) by which the global model is coupled to a regional climate model and run on volunteers' home computers is then detailed. Finally, a validation of the whole system is performed, with a particular emphasis on how accurately the distributions of daily mean temperature and daily mean precipitation are modelled in a particular application over Europe. This builds confidence in the applicability of the weather@home system for event attribution studies. [ABSTRACT FROM AUTHOR]

Interannual variations in distribution, size, indices of feeding and condition of juvenile Bristol Bay sockeye salmon Oncorhynchus nerka collected in August to September (2000–2003) during Bering–Aleutian Salmon International Surveys were examined to test possible mechanisms influencing their early marine growth and survival. Juvenile sockeye salmon were mainly distributed within the southern region of the eastern Bering Sea, south of 57°0′ N during 2000 and 2001 and farther offshore, south of 58°0′ N during 2002 and 2003. In general, juvenile sockeye salmon were significantly larger ( P < 0·05) and had significantly higher indices of condition ( P < 0·05) during 2002 and 2003 than during 2000 and 2001. The feeding index was generally higher for age 1.0 year sockeye salmon than age 2.0 year during all years. Among-year comparisons suggested that Pacific sand lance Ammodytes hexapterus were important components of the juvenile sockeye salmon diet during 2000 and 2001 (20 to 50% of the mean wet mass) and age 0 year walleye pollock Theragra chalcogramma were important components during 2002 and 2003 (50 to 60% of the mean wet mass). Warmer sea temperatures during spring and summer of 2002 and 2003 probably increased productivity on the eastern Bering Sea shelf, enhancing juvenile sockeye salmon growth. [ABSTRACT FROM AUTHOR]

Background: The behavioral effects of neuropeptide Y (NPY) attributed to its actions in the hypothalamus are complex and include effects on feeding, sedation, and the hypothalamic-pituitary-adrenal axis. NPY infused into the paraventricular nucleus (PVN) increases ethanol intake in unselected rats. High-alcohol-drinking (HAD1) and low-alcohol-drinking (LAD1) rats differ in basal NPY levels in the PVN, and HAD1, but not LAD1, rats exhibit decreases in ethanol intake after infusion of NPY into the ventricles. This study examined whether NPY infused into the PVN alters ethanol intake in HAD1 and LAD1 rats. Methods: Female HAD1 (n = 14) and LAD1 (n = 18) rats were given 24-hr free-choice continuous access to 15% (v/v) ethanol and water for 6 weeks and then implanted bilaterally with cannulas aimed at the PVN. Two weeks later, rats received a series of microinfusions, each separated by 1 week, that included four doses of NPY (0.0,0.25, 0.5, and 1.0 μg). Ethanol, water, and food were available ad libitum after infusions. All rats received a final microinfusion of 1.0 μg of NPY, after which ethanol and water, but no food, were made available for 2 hr. Results: During the 2 hr after infusion, NPY yielded dose-dependent increases in both water and food consumption. With food concurrently available, the 0.25- and 1.0-μg doses of NPY did not alter baseline ethanol intake, whereas the 0.5-μg dose increased ethanol intake. Infusion of 1.0 μg of NPY in the absence of food yielded a decrease in water intake and an increase in ethanol intake relative to the same dose in the presence of food. Twenty-four hours after infusion, there were no effects of NPY on water and food intake, and increases in ethanol intake were no longer apparent. Conclusions: Increases in ethanol intake after infusion of NPY into the PVN may depend on NPY dose and whether food is concurrently available. [ABSTRACT FROM AUTHOR]

Murphy JM, Horton NJ, Laird NM, Monson RR, Sobol AM, Leighton AH. Anxiety and depression: a 40-year perspective on relationships regarding prevalence, distribution, and comorbidity. Acta Psychiatr Scand 2004: 109: 355–375. © Blackwell Munksgaard 2004. Building on a report about the prevalence of depression over time, this paper examines historical trends regarding anxiety in terms of its prevalence, its distribution by age and gender, and its comorbidity with depression. Methods for conducting such time trend analysis are reviewed. Representative samples of adults were selected and interviewed in 1952, 1970, and 1992. Logistic regressions were used for statistical analysis. Although twice as common as depression, the prevalence of anxiety was equally stable. Anxiety was consistently and significantly more characteristic of women than men. A re-distribution of rates in 1992 indicated that depression but not anxiety had significantly increased among younger women ( P = 0.03). Throughout the study, approximately half of the cases of anxiety also suffered depression. The relationships between anxiety and depression remained similar over time with the exception that depression came to resemble anxiety as a disorder to which women were significantly more vulnerable than men. Social and historical factors should be investigated to assess their relevance to this change. [ABSTRACT FROM AUTHOR]

Background: Previous studies indicated that, under continuous access conditions, the 5-HT3 antagonist MDL 72222 (MDL) effectively reduced ethanol drinking of alcohol-preferring P rats. However, MDL was without effect when similar doses were tested under scheduled access conditions, unless the ethanol access period was randomly presented. This study examined the effects of MDL on operant responding for ethanol and water by adult male alcohol-preferring P rats. Methods: During the dark cycle, subjects in the first experiment were trained to respond concurrently for 15% ethanol and water on a fixed-ratio 5 (FR-5) and FR-1 schedule of reinforcement, respectively. Approximately 30 min before the 4-hr operant session, rats were injected subcutaneously (sc) with saline or MDL (1,3, or 5 mg/kg). A second experiment tested the effects of 1 mg/kg MDL on operant responding for 15% ethanol in 1-hr sessions when operant access was given at a fixed time each day (fixed scheduled access, FSA group) or at variable time periods throughout the dark cycle (variable scheduled access, VSA group). Results: In the first experiment, only the 5 mg/kg dose of MDL decreased responding for ethanol (approximately 20%) during the first 30 min of the 4-hr session. This dose also reduced total 4-hr responding for ethanol and water. In the second experiment, the 1 mg/kg dose of MDL had no effect on operant responding by the FSA group, but significantly reduced ethanol responding by the VSA group. Conclusions: These results suggest that 5-HT3 receptors may be involved in mediating the reinforcing effects of ethanol, and that temporal-environmental cues associated with the presentation of ethanol may be one factor involved in reducing the effectiveness of 5-HT3 antagonists to attenuate ethanol intake. [ABSTRACT FROM AUTHOR]

Background: The ventral tegmental area (VTA) dopamine (DA) system is considered to be involved in mediating the actions of ethanol (EtOH). The objective of the present study was to examine the role of VTA DA D2 receptors in regulating EtOH intake of alcohol-preferring P rats. Methods: EtOH (10% v/v) and saccharin (SACC, 0.0125% g/v) intake during 2 hr of limited access was assessed after microinjections of the D2 agonist quinpirole and the D2 antagonist sulpiride into the anterior VTA (AVTA) of female P rats. Both EtOH-SACC alternate-day-access conditions and daily availability of EtOH and SACC solutions to separate groups of subjects were used. A second D2 agonist, quinelorane, and coadministration of 2.0 μg sulpiride with 2.0 μg quinpirole were tested in animals given limited access to EtOH. Finally, the effects of quinpirole injected 2 mm dorsal to the VTA and within the posterior VTA (PVTA) were assessed under EtOH-SACC alternate-day-access conditions. Results: Microinjections of 2.0-6.0 μg quinpirole into the AVTA dose dependently decreased EtOH intake 40-80% during the first 30 min of the limited access sessions but did not alter SACC intake. Injections of 2.0-4.0 μg quinelorane into the AVTA also reduced EtOH intake in the first 30 min. Administration of 0.5-2.0 μg sulpiride into the AVTA had no effect on either EtOH or SACC intakes but did attenuate the effects of quinpirole on reducing EtOH intake. Injections of 2.0-4.0 quinpirole 2 mm dorsal to the VTA did not alter EtOH or SACC intakes. Posterior VTA injections of quinpirole decreased EtOH and SACC intakes approximately 25-30% and 60-70%, respectively, in the first 30 min. None of the treatments altered intakes during the 30-120 min period. Conclusions: The data suggest that DA neuronal activity within the AVTA may be important for maintaining EtOH drinking in P rats, whereas DA neuronal activity within the PVTA may be involved in regulating general drinking and/or motivational behaviors. Overall, the results confirm the involvement of mesolimbic DA in EtOH self-administration and suggest that there is functional heterogeneity within the VTA regulating drinking behavior of the P rat. [ABSTRACT FROM AUTHOR]

The effects of 250 mg/100 ml ethanol on the efflux of 3,4-dihydrox-yphenylacetic acid (DOPAC) and the 35 nw K+-stimulated, Ca2+-dependent release of norepinephrine (NE), dopamine (DA), serotonin (5-HT), γ-aminobutyric acid (GABA), glutamate, and aspartate from cerebral cortical slices of the alcohol-preferring P line of rats and stock Wistar rats were studied. The K+-stimuiated, Ca2+-dependent release of GABA for the P rats was 35% lower, while the release of glutamate was almost twice that of the stock animals. The release of the other compounds was similar for the two groups. Addition of 250 mg/100 ml ethanol to the superfusion media did not after the release of NE, DA, and 5-HT nor the efflux of DOPAC from cortical slices of either group of rats. However, the K+-stimulated, Ca2+-dependent release of GABA, glutamate, and aspartate was significantly enhanced by ethanol for both the P and stock group of rats. These in vitro data do not support a direct action of ethanol on DA, NE, and 5-HT release or on DOPAC efflux, but suggest a direct action on the transmitter release process for GABA, glutamate, and aspartate in the cerebral cortex. [ABSTRACT FROM AUTHOR]

A characteristic of heritable alcoholism is an early onset of alcohol abuse, which may begin at or before the age of adolescence. The objective of the present study was to determine the ontogeny of alcohol drinking behavior before and during puberty in the selectively bred alcohol-preferring (P), alcohol-nonpreferring (NP), high alcohol drinking (HAD), and low alcohol drinking (LAD) lines of rats. In addition, the effects of postweaning housing conditions (single- or pair-housed) and initiation procedure (4 days forced ethanol or free-choice) were evaluated in male and female P rats. Results indicate that high alcohol drinking in P and HAD (replicate line 2) rats, as well as low alcohol drinking behavior in NP and LAD (replicate line 2) rats, is present as early as 3 to 4 weeks of age. Ethanol intakes in juvenile P and HAD rats reached levels of ∼4 to 5 g/kg/day by 38 to 41 days of age and were comparable with levels observed in adults. Neither housing conditions nor ethanol initiation procedure significantly altered the acquisition or magnitude of alcohol intake levels in juvenile male and female P rats. These results suggest that the neural substrates underlying divergent ethanol drinking behavior in P/NP and HAD/LAD lines of rats are present early in life. [ABSTRACT FROM AUTHOR]

The alcohol-deprivation effect (ADE) was examined under 4-hr operant and 24-hr free-choice alcohol access in the alcohol-preferring (P) rat after deprivation intervals from 2 to 4 weeks. Results indicated that adult male P rats responding for 6 weeks on a concurrent FR-5/ FR-1 schedule of reinforcement for alcohol and water, respectively, and then deprived of alcohol for 2 weeks, demonstrated a 40% increase in alcohol responding during the first 60 min of alcohol reinstatement. The alcohol deprivation effect was temporary, however, as responding did not differ from baseline levels on the second day of reinstatement. In a second experiment, weanling male and female P rats received 7 weeks of continuous access to alcohol, beginning at 21 days of age, and were then deprived of alcohol for 4 weeks. On the first day of alcohol reinstatement, P rats exhibited a 40% to 45% increase from baseline alcohol drinking levels, with alcohol intake returning to baseline levels by the 3rd day of reinstatement. Although alcohol intake was higher in females than in males when adjustment was made for body weight, there were no gender differences in the magnitude of the alcohol deprivation effect. Taken together, these results indicate that the ADE is a long-lasting phenomenon that occurs under both operant and continuous access conditions in the P rat, and thus these rats may be useful models for the study of factors involved in relapse of alcohol drinking. [ABSTRACT FROM AUTHOR]

Experiments were undertaken to compare the selectively bred, alcohol-preferring (P) and alcohol-nonpreferring (NP) rat lines for differences in the locomotor activity (LMA) response to intracerebroventricular infusions of muscarinic- and nicotinic-cholinergic agents. Scopolamine, a nonselective muscarinic antagonist (40 to 120 μg/0.5 μl), dose-dependently increased LMA in both P and NP rats (up to 90 to 100% above baseline; p < 0.05). On the other hand, pirenzepine, a selective M1 muscarinic antagonist (10 to 80 μg/0.5 μl), decreased LMA in P and NP rats (as much as 35 to 40% below control values; p < 0.05). Mecamylamine, a nicotinic antagonist (20 to 120 μg/0.5 μl), also decreased LMA in P and NP rats (as much as 30 to 40% below baseline; p < 0.05). The agonist nicotine (20 to 80 μg/0.5 μl) dose-dependently decreased LMA in both P and NP rats (to a maximum of ˜60 to 65% below control values; p < 0.05). Based on standardized z-scores, NP rats were more sensitive ( p < 0.05) to the locomotor depressant effects of nicotine than P rats, whereas no differences were observed for standardized z-scores between the P and NP lines on the effects of scopolamine, pirenzepine, or mecamylamine on LMA. The results suggest that subtypes of muscarinic and nicotinic receptors are involved in regulating LMA in a complex manner, with the M 1 subtype possibly mediating behavioral activation, and that P and NP rats may possess innate differences in CNS nicotinic receptors regulating LMA. [ABSTRACT FROM AUTHOR]

Early alcohol drinking has been hypothesized to cause alcohol-related problems in adulthood. In addition, a potential role for genetic factors exist in the etiology of some types of alcoholism. The objective of the present study was to determine if taste aversion training to ethanol during adolescence in previously ethanol-naive, alcohol-preferring P and high-alcohol drinking HAD-1 lines of rats would retard or prevent the onset of high alcohol drinking. Taste aversion training began at 30 days of age. Male and female rat pups were fluid-deprived for 24 hr before 30 min access to a 10% (v/v) ethanol solution, followed by an intraperitoneal injection of either saline or 0.15 M LiCl (10 ml/kg). A total of five training sessions were administered every other day with unrestricted access to water on intervening training days. Twenty-four hours after the last training trial, rats were given continuous free-choice between water and 10% ethanol for 4 weeks with food available ad libitum. There were no obvious gender or line differences to the effects of taste aversion training. All LiCl-treated subjects avoided the usually preferred ethanol solution for the entire 4-week test period, whereas saline-treated rats steadily increased their alcohol intake to over 6.0 g/kg/day by week 4. Rats in the saline and LiCl-treated groups gained weight at comparable rates, and the groups did not differ in total fluid intake. The findings demonstrate that early environmental intervention can prevent the onset of high alcohol drinking in the selectively bred alcohol-preferring P and high-alcohol drinking HAD-1 lines of rats. [ABSTRACT FROM AUTHOR]

Experiments were undertaken to determine if CNS muscarinic- and nicotinic-cholinergic receptors are involved in regulating alcohol drinking of rats from the selectively-bred alcohol-preferring P line. Intracerebroventricular (i.c.v.) drug infusions were administered into the lateral ventricle of female P rats 15 minutes before ethanol access. The muscarinic antagonists pirenzepine and scopolamine were tested on limited access (4 hours/day) to a 10% (v/v) ethanol solution. Food and water were available ad libitum. Nicotine and the nicotinic antagonist mecamylamine were tested on limited access (4 hours/day) to 10% (v/v) ethanol and 0.0125% saccharin solutions. Food was available ad libitum and water was available during the remaining 20 hours. The baseline ethanol intakes ranged between an average of 3.0 ± 0.3 g/kg/4 hours and 3.4 ± 0.3 g/kg/4 hours. Administration of 40-100 m g pirenzepine (M1-selective antagonist) had no effect on ethanol, food or water consumption. However, 20-80 m g scopolamine, a non-selective muscarinic antagonist, dosedependently decreased ethanol intake as much as 60% (p < 0.05) without altering food or water consumption. The nicotinic antagonist mecamylamine (20-120 m g) did not alter ethanol intake, but nicotine (40-80 m g) dose-dependently decreased ethanol drinking as much as 60% within the first 30 minutes (p < 0.05) without an effect on saccharin intake. The results suggest that: (a), muscarinic receptors, with the possible exception of the M1 subtype, are involved in regulating alcohol drinking and (b), activation of nicotinic receptors can reduce alcohol drinking of the P line of rats. [ABSTRACT FROM AUTHOR]