Pharmacology and Toxicology of Metiamide, a Histamine H2 - Receptor Antagonist

A brief review of the pharmacology and toxicology of metiamide, a histamine H2-receptor antagonist, is given, and evidence is presented to support the view that it inhibits gastric acid secretion by virtue of its H2-receptor antagonist activity. Studies are also reported which show that metiamide given either intravenously or intraduodenally inhibits histamine- or pentagastrin-stimulated acid secretion in human subjects

Theory and numerical modeling of electrical self-potential signatures of unsaturated flow in melting snow

We have developed a new theory and numerical model of electrical self-potential (SP) signals associated with unsaturated flow in melting snow. The model is applicable to continuous natural-melt and transient-flow phenomena such as melt-water pulses, and is tested using laboratory column experiments. SP signals fundamentally depend on the temporal evolution of snow porosity and melt-water flux, electrical conductivity (EC) and pH. We infer a reversal of the sign of the zeta potential (a fundamental electrical property of grain surfaces in porous media), consistent with well-known elution sequences of ions that cause progressive increases and decreases in melt-water pH and EC respectively. Injection of fully-melted snow samples, containing the entire natural range of ions, into melting snow columns caused additional temporary reversals of the sign of the zeta potential. Widely-used empirical relationships between effective saturation, melt-water fraction, EC and pH, as well as snow porosity, grain size and permeability are found to be robust for modelling purposes. Thus, non-intrusive SP measurements can serve as proxies for snow melt-water fluxes and the temporal evolution of fundamental snow textural, hydraulic or water-quality parameters. Adaptation of automated multi-sensor SP acquisition technology from other environmental applications thus promises to bridge the widely acknowledged gap in spatial scale between satellite remote sensing and point measurements of snow properties. SP measurements and modelling may therefore contribute to solving a wide range of problems related to the assessment of water resource availability, avalanche or flood risk, or amplification of climatic forcing of ice-shelf, ice-sheet or glacier dynamics

A Study into the Effect of the Presence of Moisture at the Wheel/Rail Interface during Dew and Damp Conditions

Incidents involving low levels of adhesion between the wheel and rail are a recurrent issue in the rail industry. The problem has been mitigated using friction modifiers and traction enhancers, but a significant number of incidents still occur throughout the year. The following work looks at the environmental conditions that surround periods of low adhesion in order to provide an insight into why low adhesion events occur. Network Rail Autumn data, which provided details on the time and location of low adhesion incidents, was compared against weather data on a national and then local scale. Low adhesion incidents have often been attributed to contamination on the rail, such as organic leaf matter, but other incidents occur when no contamination is visible. The time, date and location of incidents were linked to local weather data to establish any specific weather conditions that could lead to these events. The effects of precipitation, temperature and humidity on the rail were analysed in order to further the understanding of low adhesion in the wheel-rail contact, which will lead to better methods of mitigating this problem

Variability of atmospheric dimethylsulphide over the southern Indian Ocean due to changes in ultraviolet radiation

Dimethylsulphide (DMS) is a climatically important component of global biogeochemical cycles, through its role in the sulphur cycle. Changes in ultraviolet radiation (UV) exhibit both positive and negative forcings on the dynamics of production and turnover of DMS and its precursor dimethylsulphoniopropionate (DMSP). In this study we investigate the net forcing of UV on atmospheric DMS. The work is based on a 10-year record of observed DMS at Amsterdam Island in the southern Indian Ocean, and satellite-based retrievals of surface UV and photosynthetically active radiation (PAR). The results show an inverse relationship between UV radiation and atmospheric DMS associated with extreme changes (defined as the greatest 5%) in daily UV, independent of changes in wind speed, sea surface temperature, and PAR

Stores healthy options project in remote indigenous communities (SHOP@RIC): a protocol of a randomised trial promoting healthy food and beverage purchases through price discounts and in-store nutrition education

BackgroundIndigenous Australians suffer a disproportionate burden of preventable chronic disease compared to their non-Indigenous counterparts – much of it diet-related. Increasing fruit and vegetable intakes and reducing sugar-sweetened soft-drink consumption can reduce the risk of preventable chronic disease. There is evidence from some general population studies that subsidising healthier foods can modify dietary behaviour. There is little such evidence relating specifically to socio-economically disadvantaged populations, even though dietary behaviour in such populations is arguably more likely to be susceptible to such interventions.This study aims to assess the impact and cost-effectiveness of a price discount intervention with or without an in-store nutrition education intervention on purchases of fruit, vegetables, water and diet soft-drinks among remote Indigenous communities.Methods/DesignWe will utilise a randomised multiple baseline (stepped wedge) design involving 20 communities in remote Indigenous Australia. The study will be conducted in partnership with two store associations and twenty Indigenous store boards. Communities will be randomised to either i) a 20% price discount on fruit, vegetables, water and diet soft-drinks; or ii) a combined price discount and in-store nutrition education strategy. These interventions will be initiated, at one of five possible time-points, spaced two-months apart. Weekly point-of-sale data will be collected from each community store before, during, and for six months after the six-month intervention period to measure impact on purchasing of discounted food and drinks. Data on physical, social and economic factors influencing weekly store sales will be collected in order to identify important covariates. Intervention fidelity and mediators of behaviour change will also be assessed.DiscussionThis study will provide original evidence on the effectiveness and cost-effectiveness of price discounts with or without an in-store nutrition education intervention on food and drink purchasing among a socio-economically disadvantaged population in a real-life setting

Nitrate stable isotopes and major ions in snow and ice samples from four Svalbard sites

Increasing reactive nitrogen (N-r) deposition in the Arctic may adversely impact N-limited ecosystems. To investigate atmospheric transport of N-r to Svalbard, Norwegian Arctic, snow and firn samples were collected from glaciers and analysed to define spatial and temporal variations (1 10 years) in major ion concentrations and the stable isotope composition (delta N-15 and delta O-18) of nitrate (NO3-) across the archipelago. The delta N-15(NO3-) and delta O-18(NO3-) averaged -4 parts per thousand and 67 parts per thousand in seasonal snow (2010-11) and -9 parts per thousand and 74 parts per thousand in firn accumulated over the decade 2001-2011. East-west zonal gradients were observed across the archipelago for some major ions (non-sea salt sulphate and magnesium) and also for delta N-15(NO3-) and delta O-18(NO3-) in snow, which suggests a different origin for air masses arriving in different sectors of Svalbard. We propose that snowfall associated with long-distance air mass transport over the Arctic Ocean inherits relatively low delta N-15(NO3-) due to in-transport N isotope fractionation. In contrast, faster air mass transport from the north-west Atlantic or northern Europe results in snowfall with higher delta N-15(NO3-) because in-transport fractionation of N is then time-limited

Striatal Dopamine Transporter Function Is Facilitated by Converging Biology of α-Synuclein and Cholesterol

Striatal dopamine transporters (DAT) powerfully regulate dopamine signaling, and can contribute risk to degeneration in Parkinson’s disease (PD). DATs can interact with the neuronal protein α-synuclein, which is associated with the etiology and molecular pathology of idiopathic and familial PD. Here, we tested whether DAT function in governing dopamine (DA) uptake and release is modified in a human-α-synuclein-overexpressing (SNCA-OVX) transgenic mouse model of early PD. Using fast-scan cyclic voltammetry (FCV) in ex vivo acute striatal slices to detect DA release, and biochemical assays, we show that several aspects of DAT function are promoted in SNCA-OVX mice. Compared to background control α-synuclein-null mice (Snca-null), the SNCA-OVX mice have elevated DA uptake rates, and more pronounced effects of DAT inhibitors on evoked extracellular DA concentrations ([DA] ) and on short-term plasticity (STP) in DA release, indicating DATs play a greater role in limiting DA release and in driving STP. We found that DAT membrane levels and radioligand binding sites correlated with α-synuclein level. Furthermore, DAT function in Snca-null and SNCA-OVX mice could also be promoted by applying cholesterol, and using Tof-SIMS we found genotype-differences in striatal lipids, with lower striatal cholesterol in SNCA-OVX mice. An inhibitor of cholesterol efflux transporter ABCA1 or a cholesterol chelator in SNCA-OVX mice reduced the effects of DAT-inhibitors on evoked [DA] . Together these data indicate that human α-synuclein in a mouse model of PD promotes striatal DAT function, in a manner supported by extracellular cholesterol, suggesting converging biology of α-synuclein and cholesterol that regulates DAT function and could impact DA function and PD pathophysiology

High dimethylsulfide photolysis rates in nitrate-rich Antarctic waters

Author Posting. © American Geophysical Union, 2004. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 31 (2004): L11307, doi:10.1029/2004GL019863.The photochemistry of dimethylsulfide (DMS) was examined in the Southern Ocean to assess its impact on the biogeochemical dynamics of DMS in Antarctic waters. Very high DMS photolysis rate constants (0.16–0.23 h−1) were observed in surface waters exposed to full sunlight. DMS photolysis rates increased linearly with added nitrate concentrations, and 35% of the DMS loss in unamended samples was attributed to the photochemistry of ambient nitrate (29 μM). Experiments with optical filters showed that the UV-A band of sunlight (320–400 nm) accounted for ~65% of DMS photolysis suggesting that dissolved organic matter was the main photosensitizer for DMS photolysis. During the austral spring, DMS photolysis was the dominant loss mechanism under non-bloom and non-ice cover conditions owing to the high doses and deep penetration of UV radiation in the water column, low observed microbial consumption rates, and high in situ nitrate concentrations.This work was supported by NSF (OPP- 0230499, DJK; OPP-0230497, RPK)

Admission decisions following contact with an emergency mental health assessment and intervention service.

AIMS: To define the demographic and clinical profile of individuals referred to an emergency mental health assessment team. To identify factors associated with being admitted to inpatient psychiatric services or not admitted following an emergency assessment. BACKGROUND: Crisis resolution and home treatment services are being developed across the UK, targeted towards people with severe mental health problems, who would otherwise require hospitalization. Further information about people presenting to an emergency mental health assessment service may clarify the skills that are required to deliver effective crisis resolution and home treatment services. METHOD: Over a six-month period referrals to, and admission decisions by, an emergency mental health assessment team were recorded. Measures used were the Health of the Nation Outcome Scale and the Crisis Triage Rating Scale. Age, sex and postcode data were recorded. Postcode data were used to identify the Townsend Deprivation Index for each individual. Reasons given for the referral were categorized. A preliminary descriptive analysis was performed for all people referred. The Demographic and clinical characteristics of referrals admitted and not admitted were then compared. A multivariate logistic regression was performed in order to investigate the possible impact of demographic and clinical characteristics on admission status. RESULTS: A total of 375 individuals were referred. Forty-eight (12.8%) were admitted. Higher referral rates were significantly associated with more deprived areas of the city. Referrers most frequently identified suicide risk as the reason for referral, followed by deterioration of an existing serious mental health problem. The mean Health of the Nation Outcome Scale score of all people referred was 10.5. Those admitted had a significantly greater mean Health of the Nation Outcome Scale score than those not admitted. The mean Crisis Triage Rating Scale score of all people referred was 11.0. Those admitted had a significantly lower (worse) mean Crisis Triage Rating Scale score than those not admitted. Individuals with lower Crisis Triage Rating Scale scores tended to have a higher (more deprived) Townsend index scores. Crisis Triage Rating Scale and Health of the Nation Outcome Scale scores were significantly negatively correlated. Conclusions. Crisis resolution and home treatments need to target areas of greatest deprivation. Social interventions will be important. Presentations related to suicide risk are likely to be common. The Crisis Triage Rating Scale may be a useful brief alternative to Health of the Nation Outcome Scale. RELEVANCE TO CLINICAL PRACTICE: This study highlights the valuable role of mental health nurses in frontline emergency mental health care in particular mental health nurses skills in conducting a risk assessment in an emergency

A cohort study of the impact of COVID-19 on the quality of life of people newly diagnosed with dementia and their family carers

Introduction COVID-19 has impacted people with dementia and their family carers, yet little is known about effects on overall quality of life. Methods In a UK cohort study, pre- and post-pandemic data were collected from 114 carers and 93 recently diagnosed people with dementia. Latent growth curve modeling examined change in quality of life. Results Carers reported significant decline in quality of life, although no change was demonstrated by people with dementia. In multivariable analyses, higher levels of cognitive impairment, deprivation, study site, and lower number of memory clinic contacts were associated with greater decline in carer quality of life. Discussion Maintaining life quality for people with dementia during the pandemic appears to have come at the expense of their family carers. This inequity has fallen hardest on those caring for people with more severe dementia, in deprived areas, and with least support from memory services. These effects may be prevented or reversed by post-diagnostic care