The Cheshire & Merseyside Collaborative trainee-led on-call service: a review of safety and efficiency.

AIM: To assess safety and efficiency of the Cheshire & Merseyside Collaborative, the largest trainee led on-call service in the UK, based on discrepancy rates and time taken to issue reports. MATERIALS & METHODS: All studies reported by the collaborative in a 4-week period were evaluated for discrepancy and the time taken to issue a report. These figures were compared against the Royal College of Radiologists (RCR) guidelines and a recent national audit of discrepancy rates. The time taken to report was measured against the National Institute of Health and Clinical Excellence (NICE) and Trauma Audit Research Network (TARN) guidelines. RESULTS: The overall discrepancy rates for the collaborative were 2.5% for minor discrepancies and 2% for major discrepancies, which is within the RCR standard. The median time taken to issue a report was 30 min, which is within the NICE and TARN 1-h targets. CONCLUSIONS: The Cheshire & Merseyside Collaborative can be deemed a safe and efficient way of delivering an out-of-hours radiology service.

The dietary form of choline during lactation affects maternal immune function in rats.

PURPOSE: The present study was designed to determine the effects of both choline form and availability on maternal immune function during lactation. METHODS: Sprague-Dawley rats were randomized to one of the three diets 24-48 h before parturition and fed ad libitum until 21 days postnatal: 1 g/kg choline as free choline (C, n = 11), the current form, and amount of choline in commercial diets; 1 g/kg choline as phosphatidylcholine (PC1, n = 11); or 2.5 g/kg choline as PC (PC2.5, n = 8). Choline metabolites in offspring stomach contents were quantified. At 21 days, lymphocytes from mothers' mesenteric lymph nodes and spleens were isolated and phenotypes and ex vivo cytokine production after mitogen exposure were determined. RESULTS: There was a higher proportion of choline and a lower proportion of lyso-PC in stomach contents (representing dam's milk) of C pups compared to PC1. In the mesenteric lymph nodes, feeding PC1 compared to C led to a higher IL-2 production after Concanavalin A (ConA) stimulation and a higher proportion of T cells (CD3+) and a lower proportion of B cells [immunoglobulin (Ig)κ, CD45RA+, and IgM+; P < 0.05]. Splenocytes from the PC1 group produced more IL-6 and TNF-α after lipopolysaccharides stimulation compared to C (P < 0.05). Splenocytes from the PC2.5 group produced more IL-2 and IL-6 after ConA stimulation compared to PC1 (P < 0.05). CONCLUSIONS: Feeding choline as PC in the maternal diet improved the ability of immune cells to respond ex vivo to mitogens and increasing the amount of PC in the diet further improved T cell proliferation.

Life history and ecology of the elusive European short-snouted seahorse Hippocampus hippocampus.

To improve the understanding of the life history and ecology of one of Europe's most elusive fishes, the short-snouted seahorse Hippocampus hippocampus, data from wild populations in a shallow coastal lagoon in southern Portugal were analysed. The data were collected from 17 tagged seahorses on a focal-study grid as well as from >350 seahorses encountered during underwater visual surveys and a fishery-independent study using beach seines. These populations of settled juveniles and adults had a mean population density of 0·009 m-2 . During the study period (2000-2004), reproduction peaked in July and August. Juveniles recruited to the lagoon at c. 66 mm standard length (LS ) and 0·5 years of age and established small home ranges (0·8 to 18·2 m2 ). First reproduction was estimated at 100 mm and 1 year of age. Based on a fitted von Bertalanffy model, H. hippocampus grew quickly (growth coefficient K = 0·93) to a maximum theoretical size L∞ = 150 mm and have a maximum lifespan of c. 3·2 years. Courtship behaviours were consistent with the maintenance of pair bonds and males brooded multiple batches of young per year. Estimated annual reproductive output averaged 871 young (±632). Together these analyses provide the first life-history parameters for this species and indicate that H. hippocampus bears characteristics of opportunist and intermediate strategists. Such populations are predicted to exhibit large fluctuations in abundance, making them vulnerable to extended periods of poor recruitment.

Feeding a diet devoid of choline to lactating rodents restricts growth and lymphocyte development in offspring.

The nutrient choline is necessary for membrane synthesis and methyl donation, with increased requirements during lactation. The majority of immune development occurs postnatally, but the importance of choline supply for immune development during this critical period is unknown. The objective of this study was to determine the importance of maternal supply of choline during suckling on immune function in their offspring among rodents. At parturition, Sprague-Dawley dams were randomised to either a choline-devoid (ChD; n 7) or choline-sufficient (ChS, 1 g/kg choline; n 10) diet with their offspring euthanised at 3 weeks of age. In a second experiment, offspring were weaned to a ChS diet until 10 weeks of age (ChD-ChS, n 5 and ChS-ChS, n 9). Splenocytes were isolated, and parameters of immune function were measured. The ChD offspring received less choline in breast milk and had lower final body and organ weight compared with ChS offspring (P<0·05), but this effect disappeared by week 10 with choline supplementation from weaning. ChD offspring had a higher proportion of T cells expressing activation markers (CD71 or CD28) and a lower proportion of total B cells (CD45RA+) and responded less to T cell stimulation (lower stimulation index and less IFN-γ production) ex vivo (P<0·05). ChD-ChS offspring had a lower proportion of total and activated CD4+ T cells, and produced less IL-6 after mitogen stimulation compared with cells from ChS-ChS (P<0·05). Our study suggests that choline is required in the suckling diet to facilitate immune development, and choline deprivation during this critical period has lasting effects on T cell function later in life.

Resistance to Leishmania major is linked to the H2 region on chromosome 17 and to chromosome 9.

In Leishmaniasis, as in many infectious diseases, clinical manifestations are determined by the interaction between the genetics of the host and of the parasite. Here we describe studies mapping two loci controlling resistance to murine cutaneous leishmaniasis. Mice infected with L. major show marked genetic differences in disease manifestations: BALB/c mice are susceptible, exhibiting enlarging lesions that progress to systemic disease and death, whereas C57BL/6 are resistant, developing small, self-healing lesions. F2 animals from a C57BL/6 X BALB/c cross showed a continuous distribution of lesion score. Quantitative trait loci (QTL) have been mapped after a non-parametric QTL analysis on a genome-wide scan on 199 animals. QTLs identified were confirmed in a second cross of 271 animals. Linkage was confirmed to a chromosome 9 locus (D9Mit67-D9Mit71) and to a region including the H2 locus on chromosome 17. These have been named Imr2 and Imr1, respectively.

The impact of disadvantage on the development and progression of diabetic kidney disease.

BACKGROUND: Disadvantaged people include those experiencing economic, social or educational deprivation and, in some cases, those undergoing rapid transition from subsistence to industrial economies. Disadvantaged people worldwide are affected disproportionately by the global epidemic of diabetes. They are also at increased risk of kidney disease attributable to diabetes, and for many, the cost of managing their kidney disease far exceeds their available resources. METHODS: We review factors associated with disadvantage that may increase the risk of diabetic kidney disease, and the barriers to care that hinder attempts to provide an adequate therapeutic response. RESULTS AND CONCLUSIONS: A rapidly rising prevalence and magnitude of obesity among children and adults, increasing frequency of intrauterine exposure to diabetes, and inadequate access to healthcare are responsible, in part, for a surge in the frequency of diabetes and, in turn, diabetic kidney disease among disadvantaged people. These factors may also predispose to an earlier onset of diabetes and kidney disease, thereby perpetuating the disadvantage by reducing the earning potential of those affected through illness and disability.

Effect of a lifestyle intervention on change in cardiorespiratory fitness in adults with type 2 diabetes: results from the Look AHEAD Study.

OBJECTIVE: To examine the effect of an intensive lifestyle weight loss intervention (ILI) compared to diabetes support and education (DSE) on changes in fitness and physical activity in the Look AHEAD trial. DESIGN: Randomized clinical trial to compare a lifestyle intervention for weight loss with a DSE condition in individuals with type 2 diabetes. SUBJECTS: Data from 4376 overweight or obese adults with type 2 diabetes (age=58.7+/-6.8 years, body mass index (BMI)=35.8+/-5.8 kg/m(2)) who completed 1 year of the Look AHEAD trial and had available fitness data were analyzed. INTERVENTION: Subjects were randomly assigned to DSE or ILI. DSE received standard care plus three education sessions over the 1-year period. ILI included individual and group contact throughout the year, restriction in energy intake and 175 min per week of prescribed physical activity. MEASUREMENTS: Fitness was assessed using a submaximal graded exercise test. Physical activity was assessed by questionnaire in a subset of 2221 subjects. RESULTS: Change in fitness was statistically greater in ILI vs DSE after adjustment for baseline fitness (20.9 vs 5.7%; P<0.0001). Multivariate analysis showed that change in fitness was greater in overweight vs obese Class II and III (P<0.05). Physical activity increased by 892+/-1694 kcal per week in ILI vs 108+/-1254 kcal per week in DSE (P<0.01). Changes in fitness (r=0.41) and physical activity (r=0.42) were significantly correlated with weight loss (P<0.0001). CONCLUSIONS: The ILI was effective in increasing physical activity and improving cardiorespiratory fitness in overweight and obese individuals with type 2 diabetes. This effect may add to weight loss in improving metabolic control in patients in lifestyle intervention programs.

Early CD44(hi)CD4+ and CD44(hi)CD8+ T cell numbers and the absence of mannose-rich glycoconjugates determine the protective outcome of anti-leishmanial immunity.

Vaccination remains the best hope for control of all forms of leishmaniasis, and the development of a safe and effective vaccine is a critical global public-health priority. Our previous work showed that immunization with non-persistent phosphomannomutase-deficient (DeltaPMM) Leishmania major parasites confers significant protection in susceptible BALB/c mice due to increased T-cell numbers and suppression of IL-10 and IL-13 early during infection. Here, we complemented the DeltaPMM L. major parasites with human PMM2 to determine whether we could further improve the protection. Complemented DeltaPMM parasites have restored glycoconjugate biosynthesis, while retaining avirulence of the parental knockout strain. Immunization with hPMM2 add-back parasites showed similar Th1/Th2 cytokine profiles to that observed in DeltaPMM-vaccinated mice. However, the numbers of the activated CD4+CD44(hi) and CD8+CD44(hi) T cells recruited to the draining lymph nodes early after Leishmania infection were reduced, leading to decreased protection following hPMM2-immunization. Thus, the magnitude of T-cell responses early in the infection and the absence of mannose-rich glycoconjugates determine the protective outcome of anti-leishmanial immunity.

Sensitivity of population viability to spatial and nonspatial parameters using GRIP.

Metapopulation dynamics are influenced by spatial parameters including the amount and arrangement of suitable habitat, yet these parameters may be uncertain when deciding how to manage species or their habitats. Sensitivity analyses of population viability analysis (PVA) models can help measure relative parameter influences on predictions, identify research priorities for reducing uncertainty, and evaluate management strategies. Few spatial PVAs, however, include sensitivity analyses of both spatial and nonspatial parameters, perhaps because computationally efficient tools for such analyses are lacking or inaccessible. We developed GRIP, a program to facilitate sensitivity analysis of spatial and nonspatial input parameters for PVAs created in RAMAS Metapop, a widely applied software program. GRIP creates random sets of input files by varying parameters specified in the PVA model including vital rates and their correlations among populations, the number and configuration of populations, dispersal rates, dispersal survival, initial population abundances, carrying capacities, and the probability, intensity, and spatial extent of catastrophes, while drawing on specified parameter distributions. We evaluated GRIP's performance as a tool for sensitivity analysis of spatial PVAs and explored the consequences of varying spatial input parameters for predictions of a published PVA model of the sand lizard (Lacerta agilis). We used GRIP output to generate standardized regression coefficients (SRCs) and nonparametric correlation coefficients as indices of the relative sensitivity of predicted conservation status to input parameters. GRIP performed well; with a single analysis we were able to rank the relative influence of input parameters identified as influential by the PVA's original author, S. A. Berglind, who used three separate forms of sensitivity analysis. Our analysis, however, also underscored the value of exploring the relative influence of spatial parameters on PVA predictions; both SRCs and correlation coefficients indicated that the most influential parameters in the sand lizard model were spatial in nature. We provide annotated code so that GRIP may be modified to reflect particular species biology, customized for more complex spatial PVA models, upgraded to incorporate features added in newer versions of RAMAS Metapop, used as a template to develop similar programs, or used as it is for computationally efficient sensitivity analyses in support of conservation planning.

Stoichiometric determination of moisture in edible oils by Mid-FTIR spectroscopy.

A simple and accurate method for the determination of moisture in edible oils by differential FTIR spectroscopy has been devised based on the stoichiometric reaction of the moisture in oil with toluenesulfonyl isocyanate (TSI) to produce CO2. Calibration standards were devised by gravimetrically spiking dry dioxane with water, followed by the addition of neat TSI and examination of the differential spectra relative to the dry dioxane. In the method, CO2 peak area changes are measured at 2335 cm(-1) and were shown to be related to the amount of moisture added, with any CO2 inherent to residual moisture in the dry dioxane subtracted ratioed out. CO2 volatility issues were determined to be minimal, with the overall SD of dioxane calibrations being ∼18 ppm over a range of 0-1000 ppm. Gravimetrically blended dry and water-saturated oils analysed in a similar manner produced linear CO2 responses with SD's of <15 ppm on average. One set of dry-wet blends was analysed in duplicate by FTIR and by two independent laboratories using coulometric Karl Fischer (KF) procedures. All 3 methods produced highly linear moisture relationships with SD's of 7, 16 and 28 ppm, respectively over a range of 200-1500 ppm. Although the absolute moisture values obtained by each method did not exactly coincide, each tracked the expected moisture changes proportionately. The FTIRTSI-H2O method provides a simple and accurate instrumental means of determining moisture in oils rivaling the accuracy and specificity of standard KF procedures and has the potential to be automated. It could also be applied to other hydrophobic matrices and possibly evolve into a more generalized method, if combined with polar aprotic solvent extraction.

Lysosomotropic agents selectively target chronic lymphocytic leukemia cells due to altered sphingolipid metabolism.

Lysosome membrane permeabilization (LMP) mediates cell death in a variety of cancer cells. However, little is known about lysosomes and LMP in chronic lymphocytic leukemia (CLL). Owing to drug resistance and toxicity in CLL patients, better treatment strategies are required. Our results show that CLL cells were sensitive to the lysosomotropic agent siramesine. Furthermore, this drug was more effective in CLL cells, regardless of prognostic factors, compared with normal B cells. Siramesine caused LMP, lipid peroxidation and transcription factor EB nuclear translocation followed by mitochondrial membrane potential loss and reactive oxygen species release. Siramesine-induced cell death was blocked by lipid antioxidants, but not by soluble antioxidants or protease inhibitors. To determine whether CLL cells had altered lysosomes, we investigated sphingolipid metabolism as the lysosome is a hub for lipid metabolism. We found that CLL cells had more lysosomes, increased sphingosine-1-phosphate phosphatase 1 (SPP1) expression, and increased levels of sphingosine compared with normal B cells. Raising sphingosine levels increased LMP and cell death in CLL cells, but not in normal B cells. Together, these results show that excess sphingosine in CLL cells could contribute to their sensitivity toward LMP. Thus, targeting the lysosome could be a novel therapeutic strategy in CLL.

Epitope mapping of monoclonal antibodies directed against lipophosphoglycan of Leishmania major promastigotes.

Monoclonal antibodies (MAbs) were generated against Leishmania major promastigote lipophosphoglycan (LPG) to use as tools in defining functional epitopes of this major cell surface glycoconjugate. Epitope mapping of four MAbs, designated 4A2-A2, 2G11-A3, 5E6-D10 and 5E10-F2, revealed that the phosphorylated oligosaccharide repeat unit PO4-6[Gal(beta 1-3)]Gal(beta 1-4)Man alpha 1-, P3, is a highly immunogenic epitope which has previously been demonstrated, by chemical analyses, to be a repeat unit specific to L. major. Two antibodies, 4A2-A2 and 5E10-F2, also recognised the repeat unit PO4-6[Ara(beta 1-2)Gal(beta 1-3)]Gal(beta 1-4)Man alpha 1-, 4Pa, with less affinity than P3, while 2G11-A3 recognised P4a with greater affinity than for P3. The L. major metacyclic-specific antibody 3F12 only recognised repeat units terminating with arabinose residues. In particular, 3F12 recognised P4a, which is upregulated in metacyclic LPG compared to the procyclic form of the molecule. The oligosaccharides P3, P4a and P5a are specific to L. major LPG. The epitopes of 4A2-A2, 2G11-A3, 5E6-D10 and 5E10-F2 were found on the cell surface and in the flagellar pocket of both procyclic and metacyclic V121 promastigotes, but were only detected at very low levels on amastigotes. The repeat unit P3 is able to inhibit attachment of procyclic promastigotes to the midgut of the sandfly vector, but neither Fab fragments of the four antibodies nor purified P3 could inhibit attachment of metacyclic promastigotes to the macrophage cell line J774. It was also shown that human sera from patients with cutaneous leishmaniasis recognised purified P3. The data suggests that while P3 is an immunogen in the natural course of infection of the human host, P3 plays no role in attachment and internalisation of promastigotes into the macrophages of the mammalian host.

Electron ionization-tandem mass spectrometry of glycosphingolipids. I: The identiftcation of compound-specific sequence ions in the collision-induced dissociation spectra of the immonium ions of two isomeric hexaglycosylceramides.

A permethylated-reduced hexaglycosylceramide in a complex glycolipid mixture isolated from a unique human tissue has been identified by using tandem mass spectrometry (MS/MS). The mass spectrum of this glycolipid mixture, obtained by using in-beam electron ionization, is very complex, and fragment ions derived from the hexaglycosylceramide cannot be distinguished from other ions. Tandem mass spectrometry using a four-sector mass spectrometer gave the mass spectrum of the immonium ion of the permethylated-reduced hexaglycosykeramide (m / z 1645.8), which is characteristic of its structure. Comparison of this MS/MS spectrum with those of two similarly derivatized blood group hexaglycosylceramide isomers permitted identification of the unknown glycolipid structure.

Effects of ionization mode on charge-site-remote and related fragmentation reactions of long-chain quaternary ammonium ions.

Comparison of collisionally activated fragment spectra of long-chain quaternary ammonium ions, formed by liquid-assisted secondary ion mass spectrometry (LSIMS) and electrospray ionization (ESI), shows the latter are dominated by radical cations while the former yield mainly even-electron charge-site-remote (CSR) fragments, similar to the report for different precursors by Cheng et al., J. Am. Soc. Mass Spectrom. 1998, 9, 840. Here, mixed-site fragmentation products (formal loss of a radical directly bonded to the nitrogen plus a radical derived from the long chain) are of comparable importance for both ionization techniques. These observations are difficult to understand if the CSR ions are formed by a concerted rearrangement-elimination reaction, since precollision internal energies of the ESI ions are much lower than those of the ions from LSIMS. Alternatively, if one discards the concerted mechanism for high-energy CA, and assumes that the even-electron fragments are predominantly formed via homolytic bond cleavage, the colder radical cations from ESI survive to the detector while the more energized counterparts from LSIMS preferentially lose a hydrogen atom to yield the CSR ions, as proposed by Wysocki and Ross (Int. J. Mass Spectrom. Ion Processes 1991, 104, 179). The present work also attempts to reconcile discrepancies involving critical energies and known structures for neutral fragments.

Endobronchial tumours in childhood.

Endobronchial tumours are rare in childhood and are not often considered in the differential diagnosis of persistent pneumonitis and atelectasis. We present the clinical and radiological features of seven cases of childhood bronchial 'adenoma' seen at our hospital over a 16-year period. Because they are relatively slow growing, prompt diagnosis and early surgical treatment offer the best chance of cure in these patients. A review of the literature is given.

The use of nicotinates and sulfoquinovosyl monoacylglycerols in the analysis of monounsaturated n-3 fatty acids by mass spectrometry.

Fatty acyl groups (16:1 and 16:0) liberated from purified sulfoquinovosyl diacylglycerols produced by the unicellular marine microalga, Heterosigma carterae (formerly H. akashiwo), were converted to either the corresponding alcohols or methyl esters. Nicotinate derivatives of the alcohols were examined by combined gas chromatography/mass spectrometry, and the methyl esters were examined by nuclear magnetic resonance (NMR) spectroscopy after separation by high-performance liquid chromatography. Three different hexadecenoyl fatty acyl groups were identified, one of which was cis 13-hexadecenoyl (16:1n-3). Both the configuration and the n-3 position of the double bond in the cis 13-hexadecenoyl moiety were unequivocally established by NMR analysis of the corresponding methyl ester. The nicotinate derived from the alcohol of the 16:1n-3 fatty acyl moiety gave a characteristic fragmentation series in the electron impact mass spectrum which, by careful interpretation, was consistent with, but not unambiguous for, the assigned location of the double bond. Tandem mass spectrometry experiments on a sulfoquinovosyl monoacylglycerol containing the cis 13-hexadecenoyl group in the sn-2 position, using negative-ion liquid secondary ion mass spectrometry, also gave a fragmentation pattern which was consistent with the positional assignment of the double bond.

Sulfoquinovosyl diacylglycerols from the alga Heterosigma carterae.

An extract of the chloromonad Heterosigma carterae (Raphidophyceae), cultivated in natural seawater, contained a complex mixture of sulfoquinovosyl diacylglycerols. Palmitoyl (16:0), three isomers of hexadecenoyl (16:1 cis delta 9, delta 11, delta 13), and eicosapentenoyl (20:5) were found to be the main fatty acyl substituents. Exact double-bond sites were determined by mass spectrometry analysis of the corresponding nicotinyl derivatives. Four major sulfoquinovosyl diacylglycerol components were partially purified and identified as 1-4 by interpretation of their nuclear magnetic resonance and mass spectral data. In addition, complete analysis of the H. carterae sulfoquinovosyl diacylglycerols was performed using high-performance liquid chromatography combined with electrospray tandem mass spectrometry.

In-line Kevlar filters for microfiltration of transuranic-containing liquid streams.

The Department of Energy Rocky Flats Plant has numerous ongoing efforts to minimize the generation of residue and waste and to improve safety and health. Spent polypropylene liquid filters held for plutonium recovery, known as "residue," or as transuranic mixed waste contribute to storage capacity problems and create radiation safety and health considerations. An in-line process-liquid filter made of Kevlar polymer fiber has been evaluated for its potential to: (1) minimize filter residue, (2) recover economically viable quantities of plutonium, (3) minimize liquid storage tank and process-stream radioactivity, and (4) reduce potential personnel radiation exposure associated with these sources. Kevlar filters were rated to less than or equal to 1 mu nominal filtration and are capable of reducing undissolved plutonium particles to more than 10 times below the economic discard limit, however produced high back-pressures and are not yet acid resistant. Kevlar filters performed independent of loaded particles serving as a sieve. Polypropylene filters removed molybdenum particles at efficiencies equal to Kevlar filters only after loading molybdenum during recirculation events. Kevlars' high-efficiency microfiltration of process-liquid streams for the removal of actinides has the potential to reduce personnel radiation exposure by a factor of 6 or greater, while simultaneously achieving a reduction in the generation of filter residue and waste by a factor of 7. Insoluble plutonium may be recoverable from Kevlar filters by incineration.

Elements of critical incident debriefing.

The present paper lists a number of specific therapeutic steps involved in critical incident debriefing. These therapeutic suggestions, while by no means exhaustive, include (a) identification, (b) labeling, (c) articulation, (d) expression, (e) externalization, (f) ventilation, (g) validation, and (h) acceptance. More careful attention to these specific elements--regardless of debriefers' training and backgrounds--might improve therapeutic consistency for trauma victims afflicted with stress-related symptoms. Further applications of these therapeutic steps were also suggested for other types of behavioral problems.

Elements of behavioral health intervention in geriatric long-term care settings.

The somewhat alarming incidence of mental disorders among institutionalized elderly persons has necessitated improved ways of dealing with their behavioral health needs. Because conventional psychotherapy has not been feasible with this population, alternative types of behavioral health interventions have been suggested. The present paper lists a number of elements which may be helpful in delivering focused behavioral health services to residents in long-term care facilities.