A High-End Estimate of Sea Level Rise for Practitioners.

Sea level rise (SLR) is a long-lasting consequence of climate change because global anthropogenic warming takes centuries to millennia to equilibrate for the deep ocean and ice sheets. SLR projections based on climate models support policy analysis, risk assessment and adaptation planning today, despite their large uncertainties. The central range of the SLR distribution is estimated by process-based models. However, risk-averse practitioners often require information about plausible future conditions that lie in the tails of the SLR distribution, which are poorly defined by existing models. Here, a community effort combining scientists and practitioners builds on a framework of discussing physical evidence to quantify high-end global SLR for practitioners. The approach is complementary to the IPCC AR6 report and provides further physically plausible high-end scenarios. High-end estimates for the different SLR components are developed for two climate scenarios at two timescales. For global warming of +2°C in 2100 (RCP2.6/SSP1-2.6) relative to pre-industrial values our high-end global SLR estimates are up to 0.9 m in 2100 and 2.5 m in 2300. Similarly, for a (RCP8.5/SSP5-8.5), we estimate up to 1.6 m in 2100 and up to 10.4 m in 2300. The large and growing differences between the scenarios beyond 2100 emphasize the long-term benefits of mitigation. However, even a modest 2°C warming may cause multi-meter SLR on centennial time scales with profound consequences for coastal areas. Earlier high-end assessments focused on instability mechanisms in Antarctica, while here we emphasize the importance of the timing of ice shelf collapse around Antarctica. This is highly uncertain due to low understanding of the driving processes. Hence both process understanding and emission scenario control high-end SLR.

Evaluation of vegetable protein in canine diets: Assessment of performance and apparent ileal amino acid digestibility using a broiler model.

Recent technological advances in the human food industry with respect to meat processing have decreased the availability of animal proteins to the pet food industry which typically formulates diets with an excess of animal protein. In the long term, this is not sustainable; thus, alternative protein sources need to be investigated. This study examined three canine diets, comparing a typical animal protein-based diet (control) with two experimental diets where the animal protein was substituted in part with vegetable protein (formulated based either on total protein or amino acid content) using a broiler model. Each diet was fed to six cages each containing two birds from day 15, 18 cages in total (36 birds). Excreta were collected from days 19 to 21. On day 23, birds were euthanized and weighed, and their ileal digesta were collected and pooled for each cage. In addition, one leg per cage was collected for evaluation of muscle mass. Results showed no significant difference in animal performance (feed intake or live weight gain) or muscle to leg proportion across the diets. Birds fed the control diet and the diet balanced for amino acid content exhibited the greatest coefficients of apparent metabolizability for nitrogen (p < .001). Birds fed the diets that contained partial replacement of animal with vegetable protein generally had greater ileal digestibility of amino acids compared to birds fed the control (animal protein) diet. Analysis of excreta showed no dietary difference in terms of dry matter content; however, birds fed the diet balanced for total protein and the diet balanced for amino acid content had significantly greater excreta nitrogen than the control (p = .038). Overall, the study suggests vegetable proteins when formulated based on amino acid content are a viable alternative to animal proteins in canine diets.

Modelling the increased frequency of extreme sea levels in the Ganges-Brahmaputra-Meghna delta due to sea level rise and other effects of climate change.

Coastal flooding due to storm surge and high tides is a serious risk for inhabitants of the Ganges-Brahmaputra-Meghna (GBM) delta, as much of the land is close to sea level. Climate change could lead to large areas of land being subject to increased flooding, salinization and ultimate abandonment in West Bengal, India, and Bangladesh. IPCC 5th assessment modelling of sea level rise and estimates of subsidence rates from the EU IMPACT2C project suggest that sea level in the GBM delta region may rise by 0.63 to 0.88 m by 2090, with some studies suggesting this could be up to 0.5 m higher if potential substantial melting of the West Antarctic ice sheet is included. These sea level rise scenarios lead to increased frequency of high water coastal events. Any effect of climate change on the frequency and severity of storms can also have an effect on extreme sea levels. A shelf-sea model of the Bay of Bengal has been used to investigate how the combined effect of sea level rise and changes in other environmental conditions under climate change may alter the frequency of extreme sea level events for the period 1971 to 2099. The model was forced using atmospheric and oceanic boundary conditions derived from climate model projections and the future scenario increase in sea level was applied at its ocean boundary. The model results show an increased likelihood of extreme sea level events through the 21st century, with the frequency of events increasing greatly in the second half of the century: water levels that occurred at decadal time intervals under present-day model conditions occurred in most years by the middle of the 21st century and 3-15 times per year by 2100. The heights of the most extreme events tend to increase more in the first half of the century than the second. The modelled scenarios provide a case study of how sea level rise and other effects of climate change may combine to produce a greatly increased threat to life and property in the GBM delta by the end of this century.

The effects of climate change on storm surges around the United Kingdom.

Coastal flooding is often caused by extreme events, such as storm surges. In this study, improved physical models have been used to simulate the climate system and storm surges, and to predict the effect of increased atmospheric concentrations of greenhouse gases on the surges. In agreement with previous studies, this work indicates that the changes in atmospheric storminess and the higher time-average sea-level predicted for the end of the twenty-first century will lead to changes in the height of water levels measured relative to the present day tide. However, the details of these projections differ somewhat from earlier assessments. Uncertainty in projections of future extreme water levels arise from uncertainty in the amount and timing of future greenhouse gas emissions, uncertainty in the physical models used to simulate the climate system and from the natural variability of the system. The total uncertainty has not yet been reliably quantified and achieving this should be a priority for future research.

Predictions of extreme precipitation and sea-level rise under climate change.

Two aspects of global climate change are particularly relevant to river and coastal flooding: changes in extreme precipitation and changes in sea level. In this paper we summarize the relevant findings of the IPCC Third Assessment Report and illustrate some of the common results found by the current generation of coupled atmosphere-ocean general circulation models (AOGCMs), using the Hadley Centre models. Projections of changes in extreme precipitation, sea-level rise and storm surges affecting the UK will be shown from the Hadley Centre regional models and the Proudman Oceanographic Laboratory storm-surge model. A common finding from AOGCMs is that in a warmer climate the intensity of precipitation will increase due to a more intense hydrological cycle. This leads to reduced return periods (i.e. more frequent occurrences) of extreme precipitation in many locations. The Hadley Centre regional model simulates reduced return periods of extreme precipitation in a number of flood-sensitive areas of the UK. In addition, simulated changes in storminess and a rise in average sea level around the UK lead to reduced return periods of extreme high coastal water events. The confidence in all these results is limited by poor spatial resolution in global coupled models and by uncertainties in the physical processes in both global and regional models, and is specific to the climate change scenario used.

A new class of selective and potent inhibitors of neuronal nitric oxide synthase.

The synthesis and SAR of a series of 6-(4-(substituted)phenyl)-2-aminopyridines as inhibitors of nitric oxide synthase are described. Compound 3a from this series shows potent and selective inhibition of the human nNOS isoform, with pharmacokinetics sufficient to provide in vivo inhibition of nNOS activity.

The scope of unmet maternal health needs in pediatric settings.

OBJECTIVE: Previous work has focused attention on the prevalence of specific maternal health problems known to affect children, such as smoking or depression. However, the cumulative health burden experienced by mothers and the potential for a practical pediatric health services response have not been examined. The aims of this study were to characterize: 1) the prevalence and cumulative burden of maternal health behaviors and conditions, 2) maternal access to a source of comprehensive adult primary care, and 3) maternal perceptions of a pediatric role in screening and referral. METHODS: We surveyed 559 consecutive women bringing a child 18 months of age or less to one of four pediatric primary care sites between July 1996 and May 1997. The pediatric sites included one outpatient program in an academic hospital, one in a community health center, and two in-staff model practices of a managed care organization (these last two were combined for analysis). The self-administered questionnaire contained previously validated questions to assess health behaviors and conditions (smoking, alcohol abuse, depression, violence, risk for unintended pregnancy, serious illness, self-reported health) and access to care (regular source, regular provider, health insurance, care delayed or not received). Maternal attitudes toward a pediatric role in screening and referral were also elicited. RESULTS: In the three settings, response rates ranged from 75% to 84%. The average age of the women ranged from 25.1 to 32. 1 years and the average age of the children ranged from 6.5 to 8.0 months. Across the settings, the percentage of women reporting at least one health condition (66%-74%) was similarly high, despite significant demographic differences among sites. Many women reported more than one condition (31%-37%); among all women who smoked, 33% also screened positive for alcohol abuse, 31% for emotional or physical abuse, and 48% for depression. Access to comprehensive adult primary care was variable with 23% to 58% of women reporting one or more barriers depending on the site. Across all sites, >85% of mothers reported they would "not mind" or "would welcome" a pediatric role in screening and referral. CONCLUSIONS: Two-thirds of women bringing their children for pediatric care had health problems regardless of the site of care. Many women also reported substantial barriers to comprehensive health care. Most women reported acceptance of a pediatric role in screening and referral. Given the range and depth of maternal health needs, strategies to connect or reconnect mothers to comprehensive adult primary care from a variety of pediatric settings should be explored.

CB1 receptor antagonist precipitates withdrawal in mice exposed to Delta9-tetrahydrocannabinol.

Although tolerance to cannabinoids has been well established, the question of cannabinoid dependence had been very controversial until the discovery of a cannabinoid antagonist, SR141716A. The objective of this study was to develop and characterize a mouse model of precipitated withdrawal indicative of cannabinoid dependence. Using a dosing regimen known to produce pharmacological and behavioral tolerance, mice were treated with Delta9-tetrahydrocannabinol (Delta9-THC) twice a day for 1 wk. SR141716A administration after the last Delta9-THC injection promptly precipitated a profound withdrawal syndrome. Typical withdrawal behavior was an increase in paw tremors and head shakes that was accompanied with a decrease in normal behavior such as grooming and scratching. Of the three Delta9-THC regimens tested, daily Delta9-THC injections of 10 and 30 mg/kg produced the greatest number of paw tremors and head shakes and the least number of grooms after challenge with SR141716A. Precipitated withdrawal was apparent after 2, 3, 7 and 14 days of treatment based on an increase in paw tremors in Delta9-THC-treated mice as compared with vehicle-treated mice. These findings are consistent with SR141716A-precipitated withdrawal in rats. Moreover, these results suggest that mice are a viable model for investigating dependence to cannabinoids.

Synthesis and structure-activity relationships of CP-122,721, a second-generation NK-1 receptor antagonist.

The synthesis and SAR of benzylamine side chain analogs of the NK-1 receptor antagonist CP-99,994 are described. The 5-trifluoromethoxy analog, CP-122,721, shows superior in vivo blockade of NK-1 receptor mediated responses.

Characterization of non-peptide antagonist and peptide agonist binding sites of the NK1 receptor with fluorescent ligands.

Ligand recognition of the NK1 receptor (substance P receptor) by peptide agonist and non-peptide antagonist has been investigated and compared by the use of fluorescent ligands and spectrofluorometric methods. Analogues of substance P (SP) labeled with the environment-sensitive fluorescent group 5-dimethylaminonaphthalene-1-sulfonyl (dansyl) at either position 3, 8, or 11 or with fluorescein at the Nalpha position were synthesized and characterized. Peptides modified at the alpha-amino group or at positions 3 or 11 conserved a relatively good affinity for NK1 and agonistic properties. Modification at position 8 resulted in an 18, 000-fold decrease in affinity. A fluorescent dansyl analogue of the non-peptide antagonist CP96,345 was prepared and characterized. The quantum yield of fluorescence for dansyl-CP96,345 was much higher than for any of the dansyl-labeled peptides indicating that the micro-environment of the binding site is more hydrophobic for the non-peptide antagonist than for the peptide agonists. Comparison of collisional quenching of fluorescence by the water-soluble hydroxy-Tempo compound showed that dansyl-CP96,345 is buried and virtually inaccessible to aqueous quenchers, whereas dansyl- or fluoresceinyl-labeled peptides were exposed to the solvent. Anisotropy of all fluorescent ligands increased upon binding to NK1 indicating a restricted motional freedom. However, this increase in anisotropy was more pronounced for the dansyl attached to the non-peptide antagonist CP96,345 than for the fluorescent probes attached to different positions of SP. In conclusion, our data indicate that the environment surrounding non-peptide antagonist and peptide agonists are vastly different when bound to the NK1 receptor. These results support recent observations by mutagenesis and cross-linking work suggesting that peptide agonists have their major interaction points in the N-terminal extension and the loops forming the extracellular face of the NK1 receptor. Our data also suggest that neither the C terminus nor the N terminus of SP appears to penetrate deeply below the extracellular surface in the transmembrane domain of the receptor.

The ameliorating effect of Yucca schidigera extract on canine and feline faecal aroma.

Addition of Yucca schidigera extract (YSE) products to canine or feline diets improved the character and reduced the intensity of faecal aroma as monitored by a human panel. The general condition of the animals was not adversely affected as monitored by faecal pH, food retention time, and blood cell counts. Blood urea increased significantly in YSE-treated cats, possibly due to the saponins of YSE affecting gut wall permeability. This finding contrasts with previously published reports of a reduction in blood urea on the addition of sarsaponin (from YSE) to rat diets and of YSE products to poultry and cattle diets.

The effect of Yucca schidigera extract on canine and feline faecal volatiles occurring concurrently with faecal aroma amelioration.

Addition of Yucca schidigera extract (YSE) products to canine or feline diets improved faecal aroma as monitored by a human panel. Odour port-gas chromatography (GC) indicated different odour component types in dog faecal volatiles and, in particular, 'faecal'-type odours due to methyl sulfides. GC-mass spectrometry demonstrated several chemical compound classes present in faecal volatiles and quantitation in the cat indicated apparently significant changes in the concentrations of several compounds on YSE treatment, although these were not necessarily aroma components. The potential for direct YSE alteration of aroma perception in a mixture of volatiles, possibly by binding, was demonstrated.

Cardiovascular effects of cholecystokinin-4 are mediated by the cholecystokinin-B receptor subtype in the conscious guinea pig and dog.

Panicogenic effects in humans of the selective cholecystokinin (CCK(B)) receptor agonist, cholecystokinin tetrapeptide (CCK4), have been reported to correlate with increases in heart rate (HR) and mean arterial pressure (MAP). Previous investigators have demonstrated that the nonselective CCK(A) and CCK(B) receptor agonist, sulfated cholecystokinin octapeptide, also produces increases in HR and mean arterial pressure. The purpose of our study is to determine if the cardiovascular changes induced by CCK4 are mediated by the CCK(A) or CCK(B) receptor subtype using selective CCK antagonists for both receptor subtypes. The rank order of potency of the CCK receptor antagonists affecting CCK4-induced HR and mean arterial pressure changes in the guinea pig corresponded to the rank order of potency for blockade of the CCK(B) receptor binding in rat cortex, phosphatidyl inositol turnover in AR 4-2J rat pancreatoma cells and inhibition of pentagastrin-induced acid secretion in the rat. The changes induced by CCK4 on HR, but not mean arterial pressure, appear to be species dependent as reflected by a decrease in the HR in the guinea pig and an increase in the dog. Nonetheless, the results from the antagonist studies indicate that the cardiovascular responses to CCK4 in both the guinea pig and dog are mediated by the CCK(B) receptor subtype.

The concentration of creatine in meat, offal and commercial dog food.

The concentrations of creatine (Cr), phosphorylcreatine (PCr) and creatinine (Cn) were determined in a variety of meats, before and after cooking by boiling, in a range of commercially available canned dog foods, in rendered and dried meat products and in commercially available dry dog foods. None of the samples contained PCr. Uncooked chicken, beef and rabbit meat contained approximately 30 mmol kg-1 of Cr. Ox-heart and ox-liver had Cr concentrations of 22.5 and 2.3 mmol kg-1, respectively. Canned dog foods had Cr concentrations of 0.5 to 2 mmol kg-1. Dried meat samples had Cr concentrations of 90 to 100 mmol kg-1 dry weight. In contrast, the Cr concentration of dried rendered meat meal was 3 mmol kg-1 dry weight or less. Dry dog foods contained 0.5 to 4 mmol kg-1 dry weight of Cr. The results indicate that in the canned dog foods, the dried meat samples and the dried rendered meat meal creatine had been degraded to variable extents to creatinine.

Dependence on delta 9-tetrahydrocannabinol: studies on precipitated and abrupt withdrawal.

A cannabinoid antagonist, SR 141716A, dose dependently precipitated a behavioral withdrawal syndrome in rats continuously infused i.p. for only 4 days with relatively low-dose regimens of delta 9-tetrahydrocannabinol. The following dose regimens, expressed as mg/kg/24 hr, were used for days 1 through 4: high-12.5, 25, 50 and 100; medium-2.5, 5, 10 and 20; and low-0.5, 1, 2 and 4. The major withdrawal signs of the syndrome were scratching, rubbing face with paws, licking, wetdog shakes, arched back and ptosis (at least 50% closure of eyelids). At the highest dose regimen, other signs noted in fewer subjects were biting, tongue rolling, retropulsion, head shakes, extended limbs or high stepping, ataxia, myoclonic spasms and front paw treading. During abrupt withdrawal (delta 9 tetrahydrocannabinol was discontinued and vehicle substituted) abstinence signs were also noted; however, except during a 48-hr observation period, withdrawal was not sufficiently robust to achieve statistical significance. The results of this study provide evidence that a modest course of delta 9-tetrahydrocannabinol can produce physical dependence. Hence, the risk and incidence of marijuana dependence in humans may be greater than previously projected.