S-(2-Succinyl)cysteine:a novel chemical modification of tissue proteins by a Krebs cycle intermediate

S-(2-Succinyl)cysteine (2SC) has been identified as a chemical modification in plasma proteins, in the non-mercaptalbumin fraction of human plasma albumin, in human skin collagen, and in rat skeletal muscle proteins and urine. 2SC increases in human skin collagen with age and is increased in muscle protein of diabetic vs. control rats. The concentration of 2SC in skin collagen and muscle protein correlated strongly with that of the advanced glycation/lipoxidation end-product (AGE/ALE), N(epsilon)-(carboxymethyl)lysine (CML). 2SC is formed by a Michael addition reaction of cysteine sulfhydryl groups with fumarate at physiological pH. Fumarate, but not succinate, inactivates the sulfhydryl enzyme, glyceraldehyde-3-phosphate dehydrogenase in vitro, in concert with formation of 2SC. 2SC is the first example of spontaneous chemical modification of protein by a metabolic intermediate in the Krebs cycle. These observations identify fumarate as an endogenous electrophile and suggest a role for fumarate in regulation of metabolism.

3D Analysis of Seepage under Hydraulic Structures with Intermediate Filters

Seepage flow under hydraulic structures provided with intermediate filters has been investigated. The flow through the banks of the canal has been included in the model. Different combinations of intermediate filter and canal width were studied. Different lengths of the floor, differential heads, and depths of the sheet pile driven beneath the floor were also investigated. The introduction of an intermediate filter to the floor of hydraulic structures reduced the uplift force acting on the downstream floor by up to 72%. The maximum uplift reduction occurred when the ratio of the distance of filter location downstream from the cutoff to the differential head was 1. Introducing a second filter in the downstream side resulted in a further reduction in the exit hydraulic gradient and in the uplift force, which reached 90%. The optimum locations of the two filters occurred when the first filter was placed just downstream of the cutoff wall and the second filter was placed nearly at the middistance between the cutoff and the end toe of the floor. The results showed significant differences between the three-dimensional (3D) and the two-dimensional (2D) analyses.

Fortune favours the bold: a higher predator reduces the impact of a native but not an invasive intermediate predator

Emergent multiple predator effects (MPEs) might radically alter predictions of predatory impact that are based solely on the impact of individuals. In the context of biological invasions, determining if and how the individual-level impacts of invasive predators relates to their impacts in multiple-individual situations will inform understanding of how such impacts might propagate through recipient communities. Here, we use functional responses (the relationship between prey consumption rate and prey density) to compare the impacts of the invasive freshwater mysid crustacean Hemimysis anomala with a native counterpart Mysis salemaai when feeding on basal cladoceran prey (i) as individuals, (ii) in conspecific groups and (iii) in conspecific groups in the presence of a higher fish predator, Gasterosteus aculeatus. In the absence of the higher predator, the invader consumed significantly more basal prey than the native, and consumption was additive for both mysid species - that is, group consumption was predictable from individual-level consumption. Invaders and natives were themselves equally susceptible to predation when feeding with the higher fish predator, but an MPE occurred only between the natives and higher predator, where consumption of basal prey was significantly reduced. In contrast, consumption by the invaders and higher predator remained additive. The presence of a higher predator serves to exacerbate the existing difference in individual-level consumption between invasive and native mysids. We attribute the mechanism responsible for the MPE associated with the native to a trait-mediated indirect interaction, and further suggest that the relative indifference to predator threat on the part of the invader contributes to its success and impacts within invaded communities.

Intermediate Care: The Role of Medicines Management

Healthcare systems worldwide are facing an unprecedented demographic change as globally, the number of older people will triple to 2 billion by the year 2050. The resulting pressures on acute services have been instrumental in the development of intermediate care (IC) as a new healthcare model, which has its origins in the National Health Service in the UK. IC is an umbrella term for patient services that do not require the resources of a general hospital but are beyond the scope of a traditional primary care team. IC aims to promote timely discharge from hospital, prevent unnecessary hospital admissions and reduce the need for long-term residential care by optimizing functional independence. Various healthcare providers around the world have adopted similar models of care to manage changing healthcare needs. Polypharmacy, along with age-related changes, places older people at an increased risk of adverse drug events, including inappropriate prescribing, which has been shown to be prevalent in this population in other healthcare settings. Medicines management (the practice of maximizing health through optimal use of medicines) of older people has been discussed in the literature in a variety of settings; however, its place within IC is largely unknown. Despite IC being a multidisciplinary healthcare model, there is a lack of evidence to suggest that enhanced pharmaceutical involvement is core to the service provided within IC. This review article highlights the gap in the literature surrounding medicines management within IC and identifies potential solutions aimed at improving patient outcomes in this setting.

Large- and small-scale structure of the intermediate- and high-velocity clouds towards the LMC and SMC.

We employ Ca II K and Na I D interstellar absorption-line spectroscopy of early-type stars in the Large and Small Magellanic Clouds (LMC, SMC) to investigate the large- and small-scale structure in foreground intermediate- and high-velocity clouds (I/HVCs). Data include FLAMES-GIRAFFE Ca II K observations of 403 stars in four open clusters, plus FEROS or UVES spectra of 156 stars in the LMC and SMC. The FLAMES observations are amongst the most extensive probes to date of Ca II structures on ∼20 arcsec scales in Magellanic I/HVCs. From the FLAMES data within a 0 ∘.∘.∘.5 field of view, the Ca II K equivalent width in the I/HVC components towards three clusters varies by factors of ≥10. There are no detections of molecular gas in absorption at intermediate or high velocities, although molecular absorption is present at LMC and Galactic velocities towards some sightlines. The FEROS/UVES data show Ca II K I/HVC absorption in ∼60 per cent of sightlines. The range in the Ca II/Na I ratio in I/HVCs is from –0.45 to +1.5 dex, similar to previous measurements for I/HVCs. In 10 sightlines we find Ca II/O I ratios in I/HVC gas ranging from 0.2 to 1.5 dex below the solar value, indicating either dust or ionization effects. In nine sightlines I/HVC gas is detected in both H I and Ca II at similar velocities, implying that the two elements form part of the same structure.

“It’s very complicated”: a qualitative study of medicines management in intermediate care facilities in Northern Ireland

Background: Intermediate care (IC) describes a range of services targeted at older people, aimed at preventing unnecessary hospitalisation, promoting faster recovery from illness and maximising independence. Older people are at increased risk of medication-related adverse events, but little is known about the provision of medicines management services in IC facilities. This study aimed to describe the current provision of medicines management services in IC facilities in Northern Ireland (NI) and to explore healthcare workers' (HCWs) and patients' views of, and attitudes towards these services and the IC concept. 

Methods: Semi-structured interviews were conducted, recorded, transcribed verbatim and analysed using a constant comparative approach with HCWs and patients from IC facilities in NI. 

Results: Interviews were conducted with 25 HCWs and 18 patients from 12 IC facilities in NI. Three themes were identified: 'concept and reality', 'setting and supply' and 'responsibility and review'. A mismatch between the concept of IC and the reality was evident. The IC facility setting dictated prescribing responsibilities and the supply of medicines, presenting challenges for HCWs. A lack of a standardised approach to responsibility for the provision of medicines management services including clinical review was identified. Whilst pharmacists were not considered part of the multidisciplinary team, most HCWs recognised a need for their input. Medicines management was not a concern for the majority of IC patients. 

Conclusions: Medicines management services are not integral to IC and medicine-related challenges are frequently encountered. Integration of pharmacists into the multidisciplinary team could potentially improve medicines management in IC.

A qualitative study of community pharmacists’ awareness of and involvement with intermediate care facilities

Rationale, aims and objectives: Intermediate care (IC) describes a range of services targeted at older people, aimed at preventing unnecessary hospitalisation, promoting faster recovery and maximising independence. The introduction of IC has created a new interface between primary and secondary care. Older people are known to be at an increased risk of medication-related problems when transferring between healthcare settings and pharmacists are often not included as part of IC multidisciplinary teams. This study aimed to explore community pharmacists’ (CPs) awareness of IC services and to investigate their views of and attitudes towards the medicines management aspects of such services, including the transfer of medication information.

Method: Semi-structured interviews were conducted, recorded, transcribed verbatim and analysed using a constant comparative approach with CPs practising in the vicinity of IC facilities in Northern Ireland, UK.

Results: Interviews were conducted with 16 CPs. Three themes were identified and named ‘left out of the loop’, ‘chasing things up’ and ‘closing the loop’. CPs felt that they were often ‘left out of the loop’ with regards to both their involvement with local IC services and communication across the healthcare interfaces. As a result, CPs resorted to ‘chasing things up’ as they had to proactively try to obtain information relating to patients’ medications. CPs viewed themselves as ideally placed to facilitate medicines management across the healthcare interfaces (i.e., ‘closing the loop’), but several barriers to potential services were identified.

Conclusion: CPs have limited involvement with IC services. There is a need for improvement of effective communication of patients’ medication information between secondary care, IC and community pharmacy. Increasing CP involvement may contribute to improving continuity of care across such healthcare interfaces, thereby increasing the person-centeredness of service provision.

Investigation into the effect of molybdenum-site substitution on the performance of Sr2Fe1.5Mo0.5O6-δ for intermediate temperature solid oxide fuel cells

In this paper, niobium doping is evaluated as a means of enhancing the electrochemical performance of a Sr₂Fe_1.5Mo_0.5O_6-δ (SFM) perovskite structure cathode material for intermediate temperature solid oxide fuel cells (IT-SOFCs) applications. As the radius of Nb approximates that of Mo and exhibits +4/+5 mixed valences, its substitution is expected to improve material performance. A series of Sr₂Fe_1.5Mo_0.5-xNb_xO_6-δ (x = 0.05, 0.10, 0.15, 0.20) cathode materials are prepared and the phase structure, chemical compatibility, microstructure, electrical conductivity, polarization resistance and power generation are systematically characterized. Among the series of samples, Sr₂Fe_1.5Mo_0.4Nb_0.10O_6-δ (SFMNb_0.10) exhibits the highest conductivity value of 30 S cm^-1 at 550°C, and the lowest area specific resistance of 0.068 Ω cm² at 800°C. Furthermore, an anode-supported single cell incorporating a SFMNb_0.10 cathode presents a maximum power density of 1102 mW cm^-2 at 800°C. Furthermore no obvious performance degradation is observed over 15 h at 750°C with wet H₂(3% H₂O) as fuel and ambient air as the oxidant. These results demonstrate that SFMNb shows great promise as a novel cathode material for IT-SOFCs.

Development and testing of an intermediate temperature glass sealant for use in mixed ionic and electronic conducting membrane reactors

High temperature ceramic membranes have interesting possibilities for application in areas of new and developing technologies such as hydrocarbon combustion with carbon dioxide capture and electrochemical promotion of catalysis (EPOC). However, membrane module sealing remains a significant technical challenge. In this work a borosilicate glass sealant (50SiO₂·25B₂O₃·25Na₂O, mol%) was developed to fit the requirements of sealing an air separation membrane system at intermediate temperatures (300-600 °C). The seal was assessed by testing the leak rates under a range of conditions. The parameters tested included the effect of flowrate on the leak rate, the heating and cooling rates of the reactor and the range of temperatures under which the system could operate. Tests for durability and reliability were also performed. It was found that the most favourable reactor configuration employed a reactor with the ceramic pellet placed underneath the inner chamber alumina tube (inverted configuration), using a quartz wool support to keep the membrane in place prior to sealing. Using this configuration the new glass-based seal was found to be a more suitable sealant than traditional alternatives; it produced lower leak rates at all desirable flowrates, with the potential for rapid heating and cooling and multiple cycling, allowing for prolonged usage. © 2010 Elsevier B.V. All rights reserved.