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ES‐62, a protein secreted by Acanthocheilonema viteae, is anti‐inflammatory by virtue of covalently attached phosphorylcholine (PC) residues and thus a library of drug‐like small molecule analogues (SMAs) based on its PC moieties has been designed for therapeutic purposes. Two members, SMAs 11a and 12b, were previously found to suppress production of pro‐inflammatory cytokines by mouse bone marrow‐derived macrophages (BMMs) exposed to cytosine‐phosphate‐guanosine oligodeoxynucleotides (CpG), agonists for Toll‐like receptor 9. In order to explore the mechanism of action underlying such activities, an untargeted mass spectrometry‐based metabolomics screen was undertaken. Stimulation of BMMs with CpG produced significant metabolic changes relating to glycolysis and the TCA cycle but the SMAs had little impact on this. Also, the SMAs did not promote alterations in metabolites known to be associated with macrophage M1/M2 polarization. Rather, BMMs exposed to SMAs 11a or 12b prior to CpG treatment, or even alone, revealed downregulation of metabolites of creatine, a molecule whose major role is in the transport of high energy phosphate from the mitochondria to the cytosol. These data therefore provide insight into a possible mechanism of action of molecules with significant therapeutic potential that has not previously been described for parasitic worm products. [ABSTRACT FROM AUTHOR]

Background: The medical profession has been slow in embracing email as a means of improving communication with patients. Aims: To explore the attitudes, practices and experiences of senior medical specialists towards email communication with their patients. Methods: A cross‐sectional qualitative interview of 30 medical staff specialists employed by Canberra Health Services, administered through one‐on‐one interviews conducted between June and August 2020 (several months into the COVID‐19 pandemic). Main outcome measures are the comments extracted from the interviews that were categorised into five domains: (i) integration of email use with patients; (ii) issues addressed through email; (iii) benefits of email communication; (iv) concerns and barriers to email communication; and (v) practice pointers for email use with patients. Results: Regular email correspondence with patients was not widespread. The main benefits identified were improved efficiency and flexibility, especially in the context of managing chronic disease and patient follow up. Participants also identified barriers, including time commitments, privacy and confidentiality, patient expectations and potential for misuse. Most participants were hesitant to endorse email with patients in their practices, citing concerns over the utility and safety of the medium and lack of established protocols and recommendations for email usage. Conclusions: There is a want and need for comprehensive and accessible professional guidance on email use with patients. Our results indicate opportunities to inform good clinical practice in respect of doctor–patient relationships, clinical workloads and risk management. There is also a need for formal guidelines on emailing with patients. The COVID‐19 pandemic has heightened the need for such guidelines. [ABSTRACT FROM AUTHOR]

Objectives: To assess stability and degradation over time, of methadone alone, and mixed with lidocaine and ketamine, using various diluents and storage conditions. Materials and Methods: Solutions of methadone diluted in 0.9% NaCl, and methadone–lidocaine–ketamine diluted in 0.9% NaCl or Hartmann's solution, and stored at room temperature with exposure to light, or refrigerated at 4°C and protected from light, were maintained over 10 days. Chemical stability was determined using liquid chromatography immediately after preparation and following 4, 24, 48, 96 and 240 hours of storage. Physical stability of the solutions was evaluated by visual examination and absorbance of ultraviolet/visible light. A linear model assessed the impact of different diluent solutions and storage conditions on drug degradation over time. Results: There was no evidence of physicochemical incompatibility for any solution. Methadone concentration, when diluted alone or in methadone–lidocaine–ketamine with Hartmann's solution at 4°C, did not decline over time. Ketamine and lidocaine decreased to a similar extent over time, regardless of the diluent used or storage method, while methadone in methadone–lidocaine–ketamine diluted with 0.9% NaCl or with Hartmann's solution at room temperature exposed to light, also declined over time; however, all three methadone–lidocaine–ketamine components retained acceptable stability (<10% degradation) for at least 48 hours following preparation, irrespective of diluent or storage conditions. Clinical Significance: Regardless of the diluent or storage method, methadone–lidocaine–ketamine solutions degrade over time, but this only becomes clinically significant after 48 hours. Solutions of 1 mg/ml methadone in 0.9% NaCl are stable for at least 10 days under storage conditions likely to be encountered in general practice. [ABSTRACT FROM AUTHOR]

The Conservation Reserve Program (CRP) is a primary tool for restoring grassland in the United States, in part as wildlife habitat, which has benefited declining grassland bird populations. Among potential mid‐contract management practices used to maintain early‐successional CRP grasslands, cattle grazing had been prohibited and is currently disincentivized during the primary nesting season for birds (much of the growing season), despite the important role that large herbivores historically played in structuring grassland ecosystems. Conservative grazing of CRP grasslands could increase spatial heterogeneity in vegetation structure and plant diversity, potentially supporting higher densities of some grassland bird species and higher bird diversity. Our objective was to determine the effect of experimental cattle grazing on species‐specific relative abundance and occupancy, species diversity, and community dissimilarity of grassland birds on CRP grasslands across the longitudinal extent of Kansas, USA (a 63.5‐cm precipitation gradient) during the 2017–2019 avian breeding seasons. Fifty‐three of 108 fields were grazed by cattle during the growing seasons of 2017 and 2018 and all fields were rested from grazing in 2019. For all analyses, we examined separate model sets for semiarid western versus more mesic eastern Kansas. Using data from line transect surveys, we modeled relative abundances of 5 songbird species: grasshopper sparrow (Ammodramus savannarum), dickcissel (Spiza americana), eastern meadowlark (Sturnella magna), western meadowlark (Sturnella neglecta), and brown‐headed cowbird (Molothrus ater). Grazing had delayed yet positive effects on abundances of grasshopper sparrow in western Kansas, and eastern meadowlark in eastern Kansas, but negative effects on dickcissel abundance in western Kansas and especially on burned fields in eastern Kansas. Somewhat counterintuitively, brown‐headed cowbirds in western Kansas were more abundant on ungrazed versus grazed fields in the years after grazing began. In addition, we modeled multi‐season occupancy of 3 gamebird species (ring‐necked pheasant [Phasianus colcicus], northern bobwhite [Colinus virginianus], mourning dove [Zenaida macroura]) and Henslow's sparrow (Centronyx henslowii); grazing did not affect occupancy of these species. In eastern Kansas, species diversity was highest in grazed, unburned fields. In western Kansas, bird communities in grazed and ungrazed fields were dissimilar, as determined from multivariate analysis. Though regionally variable, conservative stocking of cattle on CRP grasslands during the nesting season as a mid‐contract management tool might increase bird species diversity by restructuring habitat that accommodates a greater variety of species and decreasing abundances of species associated with taller, denser stands of vegetation. [ABSTRACT FROM AUTHOR]

Bird populations in grasslands have experienced declines coinciding with loss and fragmentation of prairies. The United States Department of Agriculture (USDA)‐administered Conservation Reserve Program (CRP) is the most extensive grassland restoration program in North America and it has especially benefitted grassland birds. Grazing by domestic cattle has been restricted in CRP during avian nesting seasons despite the potential improvements in structuring habitat for a greater diversity of grassland bird species. Potential negative consequences of grazing in CRP grasslands include trampling of nests by cattle, reductions in nest concealment from predators, and attraction of brood‐parasitic brown‐headed cowbirds (Molothrus ater). We designed an experiment to test for effects of cattle grazing in CRP fields during the nesting season on nest survival and brood parasitism of 5 bird species that commonly nest in CRP grasslands: mourning dove (Zenaida macroura), grasshopper sparrow (Ammodramus savannarum), dickcissel (Spiza americana), and eastern (Sturnella magna) and western (S. neglecta) meadowlarks. Grazing was implemented during summers 2017 and 2018 on 17 of 36 fields followed by a year of rest on all fields in 2019. Of the 879 nests on grazed fields, only 4 were likely trampled by cattle (vs. 54% of all nests estimated as failing because of depredation). Experimental grazing (grazed vs. ungrazed fields) had variable effects on nest survival and cowbird parasitism among the bird species analyzed. Negative effects of grazing on daily nest survival of dickcissel and meadowlarks were apparent, at least in some years. We found no direct effects of grazing on nest survival of mourning dove or grasshopper sparrow. Probability and intensity (cowbird offspring/nest) of cowbird parasitism in dickcissel nests was higher on grazed versus ungrazed sites but only in conservation practice (CP) CP2 (vs. CP25 fields). Parasitism probability of grasshopper sparrow nests by cowbirds was higher on grazed fields in the 2 years after introduction of cattle in 2017. Greater vegetative concealment around nest sites was associated with reduced cowbird parasitism of meadowlark and grasshopper sparrow nests and higher nest survival for grasshopper sparrows. Reductions in vegetative height caused by longer‐term or high‐intensity grazing might therefore have negative consequences for some grassland birds by increasing nest site visibility and exposure to cowbird parasitism. Our results indicate that cattle grazing in CRP fields during the nesting season might have some negative effects on reproductive success of some grassland bird species, at least in the short term; however, the potential improvements of structuring habitat to accommodate more grassland bird species and increasing landowner participation in the CRP are considerable. [ABSTRACT FROM AUTHOR]

Identifying how plant species diversity varies across environmental gradients remains a controversial topic in plant community ecology because of complex interactions among putative factors. This is especially true for grasslands where habitat loss has limited opportunities for systematic study across broad spatial scales. Here we overcome these limitations by examining restored plant community responses to a large‐scale precipitation gradient under two common Conservation Reserve Program (CRP) restoration approaches. The two restoration strategies examined were CP2, which seeds a relatively low number of species, and CP25, which seeds a higher number of species. We sampled plant communities on 55 CRP fields distributed along a broad precipitation gradient (410–1,170 mm mean annual precipitation) spanning 650 km within the grassland biome of North America. Mean annual precipitation (MAP) was the most important predicator of plant species richness and had a positive, linear response across the gradient. To a lesser degree, restoration practices also played a role in determining community diversity. The linear increase in species richness across the precipitation gradient reflects the species pool increase from short to tallgrass prairie communities and explained most of the richness variation. These findings provide insight into the diversity constraints and fundamental drivers of change across a large‐scale gradient representing a wide variety of grassland habitats. Across a broad environmental gradient, initial planting differences between restoration practices had lower effects on plant diversity than expected. This suggests that new strategies are needed to effectively establish diverse plant communities on large‐scale restorations such as these. [ABSTRACT FROM AUTHOR]

Filth flies are of medical and veterinary importance because of the transfer of disease organisms to animals and humans. The traditional control methods include the use of chemical insecticides. A novel mechanical insecticide made from volcanic glass and originally developed to control mosquitoes (Imergard™ WP; ImG) was investigated for control of adult grey flesh flies, Sarcophaga bullata (Parker), secondary screwworms, Cochliomyia macellaria (F.), and house flies, Musca domestica L. In a modified WHO cone test device, the time to 50% mortality (LT50) when applied at 5 g/m2 (tested at 30 °C and 50% relative humidity (rH)) was 7.1, 4.3 and 3.2 h, respectively. When knockdown was included, the LT50s were 5.5, 1.5 and 2.8 h, respectively. Application rates of 1.25 and greater g/m2 had the shortest LT50s. The time to the LT50 increased for M. domestica as rH increased, but ImG was still active at the highest rH tested of 70%. Scanning electron micrographs showed ImG was present on all body parts, unlike that for mosquitoes where it was found mostly on the lower legs. These first studies on the use of Imergard WP against flies suggest this could be an alternative method for filth fly control. [ABSTRACT FROM AUTHOR]

Summary: Missense variants are associated with various phenotypic traits and disorders in dogs. The canine P2RX7 gene, coding the ATP‐gated P2X7 receptor ion channel, contains four known missense variants. The current study aimed to examine the presence of these variants in a random sample of pedigree and mixed‐pedigree dogs. Exons 3, 8, 11 and 13 of the P2RX7 gene, encoding these four respective variants, in 65 dogs were assessed by Sanger sequencing and combined with existing sequencing data from another 69 dogs. The distribution of these variants was then evaluated in all 134 dogs combined and separately within individual breeds including 35 different pure breeds. The rs23314713 (p.Phe103Leu) and rs23315462 (p.Pro452Ser) variants were present in 47 and 40% of all dogs studied respectively, with the rs23314713 variant associated with brachycephalic breeds. Among pedigree dogs, the rs23314713 and rs23315462 variants were associated with brachycephalic and non‐brachycephalic breeds respectively. The rs851148233 (p.Arg270Cys) and rs850760787 (p.Arg365Gln) variants were present only in dogs of Cocker Spaniel and Labrador Retriever pedigrees respectively. No other missense variants were found in exons 3, 8, 11 and 13 of the P2RX7 gene within the dogs. In conclusion, the rs23314713 and rs23315462 missense variants of the P2RX7 gene are present in a large proportion of dogs, with the rs23314713 variant associated with a number of brachycephalic breeds. However, the association of this variant with dogs of bulldog ancestry, not brachycephaly per se, cannot be excluded. [ABSTRACT FROM AUTHOR]

Objectives: The congenital lung malformation volume ratio (CVR) is a prenatal ultrasound measurement that parameterizes congenital lung malformation (CLM) size. The aims of this study were to use serial measurements to create estimated growth curves of fetal CVR for asymptomatic and symptomatic neonates with CLM and to investigate whether a discriminant prognostic model based on these measurements could predict accurately which fetuses with CLM will require invasive respiratory support at delivery and should therefore be delivered at a tertiary-care facility.Methods: This was a retrospective study of fetuses diagnosed prenatally with CLM at three tertiary-care children's hospitals between 2009 and 2016. Those with two or more sonographic measurements of CVR were included. Serial fetal CVR measurements were used to create estimated growth curves for neonates with and those without respiratory symptoms at delivery, defined as requiring invasive respiratory support for the first 24 h after delivery. A discriminant model based on serial CVR measurements was used to calculate the dynamic probability of the need for invasive respiratory support. The performance of this model overall and in preterm and term neonates was compared with those using maximum CVR thresholds of 1.0 and 1.6.Results: Of the 147 neonates meeting the inclusion criteria, 16 (10.9%) required postnatal invasive respiratory support. The estimated CVR growth curve models showed different growth trajectories for asymptomatic and symptomatic neonates, with significantly higher CVR in symptomatic neonates, and values peaking late in the second trimester at around 25 weeks' gestation in asymptomatic neonates. All prognostic methods had high accuracy for the prediction of the need for invasive respiratory support in term neonates, but the discriminant model had the best performance overall (area under the receiver-operating characteristics curve (AUC) = 0.88) and in the preterm population (AUC = 0.85).Conclusions: The estimated CVR growth curves showed different growth patterns in asymptomatic and symptomatic neonates with CLM. The dynamic discriminant model performed well overall and particularly in neonates that were carried to term. Development of an externally validated clinical tool based on this analysis could be useful in determining the site of delivery for fetuses with CLM. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background: Flatulence is known to be a common side effect of laparoscopic fundoplication, yet the true incidence is unclear and its impact on patients' quality of life not well understood. This study aimed to assess the long-term incidence of flatulence, and its effect on quality of life, following fundoplication. Methods: All patients who underwent primary laparoscopic fundoplication between 1999 and 2009 were identified from a prospectively maintained institutional database. A cross-sectional analysis of post-operative gastrointestinal symptoms and quality of life was performed using a symptom-specific questionnaire. Statistical analysis of outcomes stratified by sex and type of fundoplication was performed. Results: 462 eligible patients were identified from the database, with follow-up obtained in 265 (57%). Median age at surgery was 53 (22–78) years. 137 patients (52%) were female. 138 (52%) underwent a 360° fundoplication, the remainder a partial fundoplication. At median follow-up of 11 (8–15) years, excessive flatulence was reported by 85%. Only 12% reported an adverse impact on social life, and 11% an adverse impact on quality of life. Flatulence was worse following a total than partial fundoplication, women reported more gas-related symptoms than men, yet neither sex nor wrap type had a significant impact on social life or quality of life. Conclusions: The majority of patients report excessive flatulence at long-term follow-up after anti-reflux surgery, yet the impact on social life and quality life was small. There was no evidence to support tailoring of wrap type by sex to avoid gas-related symptoms. The authors advocate that all patients understand the inevitable side effects of fundoplication to help manage expectations from surgery. [ABSTRACT FROM AUTHOR]

Background: Transthoracic esophagectomy for cancer triggers a massive inflammatory reaction. The data whether a minimally invasive esophagectomy (MIE) leads to less pronounced inflammatory response compared to open right-sided transthoracic esophagectomy (OE) are scarce. The aim of this study was to evaluate the extent of the inflammatory reaction, represented by levels of the pro-inflammatory interleukins IL-6 and IL-8, the anti-inflammatory IL-1 RA and the chemokines CINC-1 and MCP-1 in the right pleural fluid and the blood from patients undergoing standard OE or MIE. Methods: Pleural drainage fluid and blood was collected at five different time points during the first 72 h following surgery, and the concentrations of IL-6, IL-8, IL-1 RA, CINC-1 and MCP-1 were analyzed using enzyme-linked immune-sorbent assays in 24 patients undergoing MIE or OE. Results: The groups were matched for cancer stage and comorbidities. Pro- and anti-inflammatory mediator levels in the pleural fluid were markedly increased at the end of surgery and on postoperative days 1–3. The pleural inflammatory response of all cyto- and chemokines was lower in the MIE group, reaching significance at some time points. Cyto- and chemokine response levels measured in the blood were overall lower compared to those in the pleural fluid. The chemokines CINC-1 and MCP-1 reacted less pronounced or not at all. Preoperative pulmonary comorbidity, postoperative pulmonary morbidity and length of surgery were associated with an increased reaction in selected mediators. Conclusions: The minimally invasive technique attenuates the inflammatory response, especially locally in the thoracic compartment. Length of procedure, preoperative pulmonary comorbidity and postoperative pulmonary complications are mirrored in an increase in individual inflammatory markers in the pleural fluid. The value of the chemokines CINC-1 and MCP-1 as markers of inflammation in the setting of esophagectomy is unclear. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect of maternal sildenafil therapy on fetal growth in pregnancies with early-onset fetal growth restriction.Design: A randomised placebo-controlled trial.Setting: Thirteen maternal-fetal medicine units across New Zealand and Australia.Population: Women with singleton pregnancies affected by fetal growth restriction at 22+0 to 29+6 weeks.Methods: Women were randomised to oral administration of 25 mg sildenafil citrate or visually matching placebo three times daily until 32+0 weeks, birth or fetal death (whichever occurred first).Main Outcome Measures: The primary outcome was the proportion of pregnancies with an increase in fetal growth velocity. Secondary outcomes included live birth, survival to hospital discharge free of major neonatal morbidity and pre-eclampsia.Results: Sildenafil did not affect the proportion of pregnancies with an increase in fetal growth velocity; 32/61 (52.5%) sildenafil-treated, 39/57 (68.4%) placebo-treated [adjusted odds ratio (OR) 0.49, 95% CI 0.23-1.05] and had no effect on abdominal circumference Z-scores (P = 0.61). Sildenafil use was associated with a lower mean uterine artery pulsatility index after 48 hours of treatment (1.56 versus 1.81; P = 0.02). The live birth rate was 56/63 (88.9%) for sildenafil-treated and 47/59 (79.7%) for placebo-treated (adjusted OR 2.50, 95% CI 0.80-7.79); survival to hospital discharge free of major neonatal morbidity was 42/63 (66.7%) for sildenafil-treated and 33/59 (55.9%) for placebo-treated (adjusted OR 1.93, 95% CI 0.84-4.45); and new-onset pre-eclampsia was 9/51 (17.7%) for sildenafil-treated and 14/55 (25.5%) for placebo-treated (OR 0.67, 95% CI 0.26-1.75).Conclusions: Maternal sildenafil use had no effect on fetal growth velocity. Prospectively planned meta-analyses will determine whether sildenafil exerts other effects on maternal and fetal/neonatal wellbeing.Tweetable Abstract: Maternal sildenafil use has no beneficial effect on growth in early-onset FGR, but also no evidence of harm. [ABSTRACT FROM AUTHOR]

Background: A lack of consensus exists amongst national guidelines regarding who should be investigated for haematuria. Type of haematuria and age-specific thresholds are frequently used to guide referral for the investigation of haematuria.Objectives: To develop and externally validate the haematuria cancer risk score (HCRS) to improve patient selection for the investigation of haematuria.Methods: Development cohort comprise of 3539 prospectively recruited patients recruited at 40 UK hospitals (DETECT 1; ClinicalTrials.gov: NCT02676180) and validation cohort comprise of 656 Swiss patients. All patients were aged >18 years and referred to hospital for the evaluation of visible and nonvisible haematuria. Sensitivity and specificity of the HCRS in the validation cohort were derived from a cut-off identified from the discovery cohort.Results: Patient age, gender, type of haematuria and smoking history were used to develop the HCRS. HCRS validation achieves good discrimination (AUC 0.835; 95% CI: 0.789-0.880) and calibration (calibration slope = 1.215) with no significant overfitting (P = 0.151). The HCRS detected 11.4% (n = 8) more cancers which would be missed by UK National Institute for Health and Clinical Excellence guidelines. The American Urological Association guidelines would identify all cancers with a specificity of 12.6% compared to 30.5% achieved by the HCRS. All patients with upper tract cancers would have been identified.Conclusion: The HCRS offers good discriminatory accuracy which is superior to existing guidelines. The simplicity of the model would facilitate adoption and improve patient and physician decision-making. [ABSTRACT FROM AUTHOR]

Objective: To identify laryngeal mRNA gene changes in patients with laryngopharyngeal reflux (LPR). Method: Laryngeal biopsies from non‐smoking LPR patients (n=10; Reflux Symptom Index (RSI) >12 and a Reflux Finding Score (RFS) >6) and controls (n=9; RSI <12 and RFS <6) were collected from four subsites (true vocal cord, false vocal cord, medial arytenoid and posterior commissure) of the larynx. qRT‐PCR analyses were conducted on 20 reflux‐ and inflammation‐related genes, including interleukins 6 and 8, cytokeratins 8 and 14, mucin genes MUC1, MUC2, MUC3B, MUC4, MUC5B, MUC6 and MUC7 and carbonic anhydrase III. Statistical analysis (Mann‐Whitney U test) compared gene expression levels between LPR and control groups at each subsite. Results: Site‐specific differences in squamous metaplasia and gene expression were noted in LPR patients, with the majority present in the medial arytenoid region. Significant.differences were noted in genes related to mucosal defence and inflammation, including CRNN, CD1d, TGFβ‐1, MUC2, MUC5B and CDH1. Conclusion: Whilst the posterior commissure is commonly identified as the area demonstrating the most significant macroscopic change in LPR, the histological changes and genes assessed here showed more pronounced LPR associated differences in the medial arytenoid. We identified differences in expression of mucin genes, cytokeratin‐14 and molecular markers of inflammation. Whilst some of these changes may be metaplasia‐related, further evaluation of the mRNA expression of these genes may provide a useful biomarker panel for diagnosis and therapeutic monitoring of LPR. [ABSTRACT FROM AUTHOR]

OBJECTIVES To assess and quantify medetomidine contamination of butorphanol multidose vials in small animal general practices and determine if practice policies and procedures regarding drug handling, as determined by questionnaire, impact upon contamination level. METHODS Samples of butorphanol were withdrawn from in-use vials in participating practices in June and July 2013. Samples were analysed using high-performance liquid chromatography and mass spectrometry. RESULTS Forty-one samples were obtained from 31 practices. Contamination was detected in 29 samples from 10 mL vials. The mean (αsd) contamination was 0 · 275 (α0 · 393) µg/ mL; maximum contamination in any vial was 2 · 034 µg/ mL. There was no correlation between volume of the vial used and the level of contamination. None of the survey factors predicted contamination levels of the vials. CLINICAL SIGNIFICANCE Contamination of butorphanol multidose vials with medetomidine was common but the level of contamination was insufficient to cause detrimental effects in dogs if butorphanol were to be administered alone. The potential for sporadic higher levels of contamination must be taken into account, especially when using 50 mL vials when sedating critically ill cases, because there is a risk of clinical side effects. [ABSTRACT FROM AUTHOR]

We measured total and free plasma concentrations of ropivacaine following high-volume, high-dose local infiltration analgesia in 28 patients aged 65 years or over undergoing unilateral total knee arthroplasty. Patients received infiltration of ropivacaine 400 mg followed by infusion at 20 mg.h(-1) through an intra-articular catheter. Total and free plasma levels of ropivacaine were measured at specified time intervals during a 24-h period after tourniquet release. Patients were monitored for symptoms and signs of local anaesthetic toxicity. Total levels of plasma ropivacaine varied from 0.147 to 3.093 μg.ml(-1) (mean (SD) 1.105 (0.518) μg.ml(-1) ). Free levels of plasma ropivaca-ine varied from 0.001 to 0.104 μg.ml(-1) (mean (SD) 0.037 (0.020) μg.ml(-1) ). Six samples had total plasma ropivacaine levels greater the toxic threshold of 2.2 μg.ml(-1) . No samples reached the toxic threshold for free venous ropivacaine concentration. We conclude that the use of high-dose ropivacaine infiltration and catheter infusion for total knee arthroplasty in an elderly population does not result in free plasma ropivacaine levels previously associated with toxicity but that raised total plasma levels may be observed. [ABSTRACT FROM AUTHOR]

SUMMARY Objectives To record the fate of transfused platelet doses in the North of England, and thereby assist with demand-planning and help target teaching on appropriate use. Background Platelet use has risen recently to the extent that donation practice has changed to meet demand. Two national comparative audits have shown inappropriate use and the 2010 audit concluded that current UK guidelines for platelet usage should be completely implemented at a local level. It is necessary to know how platelets are used and by whom in order to facilitate guideline concordance. Methods All hospital trusts in the North East and Cumbria recorded data on all platelet doses transfused in two separate 4-week periods in 2012. Data were entered onto an electronic survey tool. Results One thousand and five hundred and seventy-four reports were received, documenting 1937 transfused doses - 96% of total issues for the study periods. One thousand and forty-five platelet doses (54%) were given for haematological indications. The second commonest indication was cardiac surgery (201 doses, 10% of the total) followed by non-haematological oncology (127 doses, 6.5%), critical care (106 doses, 5%) and liver disease (50 doses, 2·5%). The commonest haematological indication was acute myeloid leukaemia, 310 doses, (16% of all platelet use), followed by stem cell transplantation, 271 doses (14%). Seventy-two percent of platelet doses were given prophylactically, the majority without any planned procedure. Conclusion The commonest indication for platelet use, where reinforcement of guidelines will be productive, is prophylaxis in haematological disease. Use of platelets in cardiac surgery is also worthy of close scrutiny. [ABSTRACT FROM AUTHOR]

We measured total and free plasma concentrations of ropivacaine following high-volume, high-dose local infiltration analgesia in 19 patients aged 65 years or over undergoing unilateral total hip arthroplasty. The patients received 180 ml ropivacaine 0.2% (360 mg), which was injected into the deep and peri-capsular tissues, the gluteal muscles and fascia lata, and the subcutaneous tissues and skin. Patients were monitored for clinical symptoms and signs of systemic local anaesthetic toxicity. Total levels of plasma ropivacaine varied from 0.081 to 1.707 μg.ml−1 (mean (SD) 0.953 (0.323) μg.ml−1). Free levels of plasma ropivacaine varied from 0.000 to 0.053 μg.ml−1 (mean (SD) 0.024 (0.011) μg.ml−1). No samples reached the toxic threshold for venous ropivacaine concentration, although four patients exhibited mild symptoms consistent with local anaesthetic toxicity. One patient had episodes of complete heart block on ECG monitoring, but plasma ropivacaine levels were below toxic levels. We conclude that plasma levels for ropivacaine associated with toxicity in a volunteer population (total 2.2 μg.ml−1, free 0.15 μg.ml−1) are not reached during local infiltration analgesia for hip arthroplasty in elderly patients. [ABSTRACT FROM AUTHOR]

Introduction Wrong blood in tube ( WBIT) describes a transfusion sample collected from one patient but labelled with the identification details of a different patient. These incidents have the potential to result in catastrophic harm to patients. In 2011, the Serious Hazards of Transfusion ( SHOT) organisation received 469 reports of WBIT across the UK. What this study adds This was a prospective study of WBIT which collected information not only on the frequency of WBIT but also risk factors. Method All hospitals in the North East region of England submitted details of known WBITs during a 12-month period starting from July 2011, including the time of day and location where samples were taken, the job title and competency of the sample taker, and how the WBIT was identified. Where possible, the sampler was interviewed to determine reasons for the WBIT. RESULTS There were 48 WBITs, giving a corrected incidence of 1 : 2717 repeat transfusion samples. Doctors were responsible for 24 of 45 WBITs where the identity of the sampler was known. The rate as a proportion of samples was highest in medicine and paediatric specialties. The commonest risk factor for WBIT was labelling away from the bedside (44%). Conclusions These findings support, and add to, the data collected by SHOT. If our figures are representative of the whole of the UK, then over 1160 WBITs will occur each year, justifying SHOT's concerns that WBITs are under reported. Interventions are needed to ensure labelling of transfusion samples is always carried out at the patient's side. [ABSTRACT FROM AUTHOR]

At the Oak Ridge Integrated Field Research Challenge (IFRC) site, Tennessee, the saprolitic aquifer was contaminated by leaks from the former S-3 disposal ponds between 1951 and 1983. The chemistry of the contaminant plume is also episodically impacted by fresh meteoritic water infiltrating vertically from a shallow variably saturated perched zone and the ditch surrounding the former S-3 ponds. We performed a column experiment using saprolite from the contaminated aquifer to understand the geochemical and complex electrical conductivity signatures associated with such events. The changes in the pH and pore water ionic strength are responsible for measurable changes in both the in-phase and quadrature conductivities. The pore water conductivity can be related to the nitrate concentration (the main ionic species in the plume) while the release of uranium is controlled by the pH. We developed a simple model to determine the pore water conductivity and pH from the recorded complex conductivity. This model is applied to time-lapse resistivity data at the IFRC site. Time-lapse inversion of resistivity data, performed with an active time constrain approach, shows the occurrence of an infiltration event during the winter of 2008-2009 with a dilution of the pore water chemistry and an increase of the pH. A simple numerical simulation of the infiltration of fresh water into the unconfined contaminated aquifer is consistent with this scenario. [ABSTRACT FROM AUTHOR]

Background Recent studies suggest an underlying three- or four-factor structure explains the conceptual overlap and distinctiveness of several negative emotionality and pain-related constructs. However, the validity of these latent factors for predicting pain has not been examined. Methods A cohort of 189 (99 female, 90 male) healthy volunteers completed eight self-report negative emotionality and pain-related measures ( Eysenck Personality Questionnaire - Revised, Positive and Negative Affect Schedule, State- Trait Anxiety Inventory, Pain Catastrophizing Scale, Fear of Pain Questionnaire; Somatosensory Amplification Scale, Anxiety Sensitivity Index and Whiteley Index). Using principal axis factoring, three primary latent factors were extracted: general distress, catastrophic thinking and pain-related fear. Using these factors, individuals clustered into three subgroups of high, moderate and low negative emotionality responses. Experimental pain was induced via intramuscular acidic infusion into the anterior tibialis muscle, producing local (infusion site) and/or referred (anterior ankle) pain and hyperalgesia. Results Pain outcomes differed between clusters (multivariate analysis of variance and multinomial regression), with individuals in the highest negative emotionality cluster reporting the greatest local pain ( p = 0.05), mechanical hyperalgesia (pressure pain thresholds; p = 0.009) and greater odds (2.21 odds ratio) of experiencing referred pain when compared to the lowest negative emotionality cluster. Conclusion Our results provide support for three latent psychological factors explaining the majority of the variance between several pain-related psychological measures, and that individuals in the high negative emotionality subgroup are at increased risk for (1) acute local muscle pain; (2) local hyperalgesia; and (3) referred pain using a standardized nociceptive input. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To investigate the association between dog hair nicotine concentration and owner-reported exposure to environmental tobacco smoke to establish whether dogs are exposed to significant, detectable amounts of environmental tobacco smoke in the home. METHODS: Hair was collected from 23 dogs exposed to environmental tobacco smoke and from 15 dogs reportedly not exposed to environmental tobacco smoke. Hair was washed to remove adhered nicotine, digested in 1 M NaOH and extracted using solid phase extraction. Nicotine concentration was measured by high-resolution mass spectrometry. Results were analysed using a Kruskall-Wallis test and post hoc pair-wise comparisons using a Mann-Whitney test to assess significance between exposure groups. RESULTS: The different exposure groups were significantly different (P<0·001) for both hair and surface nicotine. Pair-wise comparisons were significant at P<0·05 for all categories except unexposed and occasionally exposed groups (P=0·076). CLINICAL SIGNIFICANCE: Dog hair nicotine concentration appears to be strongly associated with reported exposure to environmental tobacco smoke. The range and median of hair nicotine concentration in dogs exposed to environmental tobacco smoke was similar to those reported in children. This suggests that dog hair could provide a useful method of determining the amount of environmental tobacco smoke exposure in all environments common to pets and children. [ABSTRACT FROM AUTHOR]

Objectives: (1) To show that extracellular matrix deposition in 3-dimensional culture of human septal chondrocytes cultured in a rotary bioreactor is comparable to the deposition achieved under static culture conditions. (2) To demonstrate that the biomechanical properties of human septal chondrocytes cultured in a bioreactor are enhanced with time and are analogous to beads cultured under static culture.Study Design: Prospective, basic science.Setting: Research laboratory.Methods: Human septal chondrocytes from 9 donors were expanded in monolayer and seeded in alginate beads. The beads were cultured in a rotary bioreactor for 21 days in media supplemented with growth factors and human serum, using static culture as the control. Biochemical and biomechanical properties of the beads were measured.Results: Glycosaminoglycan (GAG) accumulation significantly increased during 2 measured time intervals, 0 to 21 days and 10 to 21 days (P < .01). No significant difference was seen between the static and bioreactor conditions. Substantial type II collagen production was demonstrated in the beads terminated at day 21 of culture in both conditions. In addition, the biomechanical properties of the beads were significantly improved at 21 days in comparison to beads from day 0.Conclusion: Human septal chondrocytes cultured in alginate beads exhibit significant matrix deposition and improved biomechanical properties after 21 days. Alginate bead diameter and stiffness positively correlated with GAG and type II collagen accretion. Matrix production in beads is supported by the use of a rotary bioreactor. [ABSTRACT FROM AUTHOR]

Developing reliable, predictive animal models for complex psychiatric disorders, such as schizophrenia, is essential to increase our understanding of the neurobiological basis of the disorder and for the development of novel drugs with improved therapeutic efficacy. All available animal models of schizophrenia fit into four different induction categories: developmental, drug-induced, lesion or genetic manipulation, and the best characterized examples of each type are reviewed herein. Most rodent models have behavioural phenotype changes that resemble 'positive-like' symptoms of schizophrenia, probably reflecting altered mesolimbic dopamine function, but fewer models also show altered social interaction, and learning and memory impairment, analogous to negative and cognitive symptoms of schizophrenia respectively. The negative and cognitive impairments in schizophrenia are resistant to treatment with current antipsychotics, even after remission of the psychosis, which limits their therapeutic efficacy. The MATRICS initiative developed a consensus on the core cognitive deficits of schizophrenic patients, and recommended a standardized test battery to evaluate them. More recently, work has begun to identify specific rodent behavioural tasks with translational relevance to specific cognitive domains affected in schizophrenia, and where available this review focuses on reporting the effect of current and potential antipsychotics on these tasks. The review also highlights the need to develop more comprehensive animal models that more adequately replicate deficits in negative and cognitive symptoms. Increasing information on the neurochemical and structural CNS changes accompanying each model will also help assess treatments that prevent the development of schizophrenia rather than treating the symptoms, another pivotal change required to enable new more effective therapeutic strategies to be developed. [ABSTRACT FROM AUTHOR]

Issue Addressed: New Zealand's (NZ) smokefree legislation, implemented on 1 January 2004, requires that all school and early childhood centre buildings and grounds are 100% smokefree; one aim being to prevent young people being influenced by seeing people (including teachers) smoke there. This study, conducted in 2008, investigated teachers'smoking behaviour and perceived adherence to the legislation.Methods: A national NZ cross-sectional survey of 2,004 teachers (oversampling Māori), who were randomly selected from the electoral roll of registered voters and sent postal invitations to complete an anonymous survey.Results: The response rate was 70%. Current smokers numbered 7%, and proportionately more Maori and Pacific Island teachers (12% each) smoked than European/Other teachers (7%). Of current smokers, 37% smoked non-daily. Smokers smoked less on work than non-work days. Introducing smokefree legislation was associated with teachers changing when they smoked, cutting down, quitting or trying to quit. Perceived compliance with the legislation was high, although 30% of teachers reported seeing staff smoking. Proportionately, significantly more teachers from low than from high socioeconomic schools perceived poor compliance and staff visibly smoking.Conclusions: Smokefree legislation affects people's smoking behaviour. Smoking in NZ is becoming confined to population subgroups defined by socioeconomic status and ethnicity. Our findings argue for supporting cessation among those who work with children and young people, and for targeting support at school communities in areas of low socioeconomic status or with large populations of Māori or Pacific peoples. [ABSTRACT FROM AUTHOR]

Two new field bioassay methods were developed to compare the repellent activity of BioUD (containing 7.75% 2-undecanone), 98.1% DEET and 0.5% permethrin against natural populations of nymphal Amblyomma americanum (L.) (Acari: Ixodidae). In a cloth sheet assay, pieces of material measuring 41 × 58 cm, separately treated with one of the test materials or the appropriate solvent carrier, were placed at random on the ground and baited with dry ice for 1 h. Mean numbers of ticks on repellent-treated sheets were significantly lower than on control sheets. There was no significant difference in the number of ticks collected between sheets treated with BioUD and those treated with DEET. However, significantly fewer ticks were found on sheets treated with BioUD or DEET than on permethrin-treated sheets. In a sock test, over-the-calf tube socks were treated with one of the test materials or the appropriate solvent carrier. Human volunteers wore a repellent-treated and a corresponding carrier-treated sock on either leg and walked randomly over an area of approximately 4000 m for 15 min. Significantly fewer ticks were collected from socks treated with BioUD or DEET than from socks treated with the carrier and there was no significant difference in repellency between these two agents. No difference in the mean number of ticks collected was found between permethrin-treated and corresponding carrier-treated socks. To examine the mechanism of repellency of BioUD, a four-choice olfactometer was used to assess spatial repellency against adult A. americanum. As expected in the absence of a repellent, when all choices were represented by water-treated filter paper, ticks were equally distributed among the choices. When one choice consisted of BioUD-treated filter paper and the remaining choices of water-treated paper, the distribution of ticks on the repellent-treated paper was significantly lower than might be expected to occur by chance, suggesting that repellency is at least partly achieved by an olfactory mechanism. [ABSTRACT FROM AUTHOR]

It is known that 20-30% of fresh frozen plasma (FFP) is used in intensive care units (ICUs), but little is known about variations in decision making between clinicians in relation to coagulopathy management. Our aim was to describe ICU clinicians' beliefs and practice in relation to FFP treatment of non-bleeding coagulopathic critically ill patients. Two patient-based scenarios were developed and sent to 2700 members of two UK intensive care professional societies. Scenario 1 was a non-bleeding septic patient with coagulopathy; scenario 2 was a non-bleeding critically ill patient with hepatic cirrhosis and coagulopathy. Responses were sought in relation to FFP prophylaxis, and prior to central venous cannulation. A supplementary question asked clinicians' view of prophylaxis in relation to other ICU procedures. Two-thousand-and-seven-hundred clinicians were surveyed from whom 601 responses were received (22·3% response rate). For scenario 1 52% of respondents stated that they would never routinely administer prophylactic FFP, but this decreased to 9% when central venous cannulation was planned ( P < 0·01). There was wide variation in the 'trigger' INR (international normalised ratio) value used prior to central vein cannulation, the most common range being 2·0-2·4. For scenario 2, responses were very similar. More than 80% of clinicians stated that they would routinely treat coagulopathy prior to lumbar puncture, epidural catheterisation, intracranial pressure monitoring and tracheostomy; and 54% prior to chest drain insertion. Our survey demonstrated a wide range of responses consistent with important variations in clinical practice and substantial clinical uncertainty in relation to FFP treatment for non-bleeding ICU patients. [ABSTRACT FROM AUTHOR]

A generalized, efficient, and practical approach based on the travel-time modeling framework is developed to estimate in situ reaction rate coefficients for groundwater remediation in heterogeneous aquifers. The required information for this approach can be obtained by conducting tracer tests with injection of a mixture of conservative and reactive tracers and measurements of both breakthrough curves (BTCs). The conservative BTC is used to infer the travel-time distribution from the injection point to the observation point. For advection-dominant reactive transport with well-mixed reactive species and a constant travel-time distribution, the reactive BTC is obtained by integrating the solutions to advective-reactive transport over the entire travel-time distribution, and then is used in optimization to determine the in situ reaction rate coefficients. By directly working on the conservative and reactive BTCs, this approach avoids costly aquifer characterization and improves the estimation for transport in heterogeneous aquifers which may not be sufficiently described by traditional mechanistic transport models with constant transport parameters. Simplified schemes are proposed for reactive transport with zero-, first-, nth-order, and Michaelis-Menten reactions. The proposed approach is validated by a reactive transport case in a two-dimensional synthetic heterogeneous aquifer and a field-scale bioremediation experiment conducted at Oak Ridge, Tennessee. The field application indicates that ethanol degradation for U(VI)-bioremediation is better approximated by zero-order reaction kinetics than first-order reaction kinetics. [ABSTRACT FROM AUTHOR]

The application of geophysical methods, in particular, electrical resistivity measurements, may be useful for monitoring subsurface contamination. However, interpreting geophysical data without additional data and without considering the associated hydrogeochemical processes is challenging since the geophysical response is sensitive to not only heterogeneity in rock properties but also to the saturation and chemical composition of pore fluids. We present an inverse modeling framework that incorporates the simulation of hydrogeochemical processes and time-lapse electrical resistivity data and apply it to various borehole and cross-borehole data sets collected in 2008 near the S-3 Ponds at the U.S. Department of Energy's Oak Ridge Integrated Field Research Challenge site, where efforts are underway to better understand freshwater recharge and associated contaminant dilution. Our goal is to show that the coupled hydrogeochemical-geophysical modeling framework can be used to (1) develop a model that honors all the available data sets, (2) help understand the response of the geophysical data to subsurface properties and processes at the site, and (3) allow for the estimation of petrophysical parameters needed for interpreting the geophysical data. We present a series of cases involving different data sets and increasingly complex models and find that the approach provides useful information about soil properties, recharge-related transport processes, and the geophysical response. Spatial heterogeneity of the petrophysical model can be described sufficiently with two layers, and its parameters can be estimated concurrently with the hydrogeochemical parameters. For successful application of the approach, the parameters of interest must be sensitive to the available data, and the experimental conditions must be carefully modeled. [ABSTRACT FROM AUTHOR]

Background and Objectives This study was undertaken to provide data relating to the timing of laboratory crossmatch procedures, and the source of requests for out of hours crossmatch, to support interpretation of error reports originating in the transfusion laboratory, received by the Serious Hazards of Transfusion haemovigilance scheme. Materials and Methods Data on the timing, origin and urgency of all crossmatch requests were collected in 34 hospitals in northern England over a 7-day period in 2008. Additional data on clinical urgency were collected on crossmatches that were performed out of hours. Results Data were obtained on 2423 crossmatches, including 610 (25·2%) performed outside core hours. 30·3% of out of hours crossmatch requests were for transfusions that were set up outside 4 h of completion of the crossmatch. Conclusion 2008 Serious Hazards of Transfusion data showed that 29/39 (74%) of laboratory errors resulting in ‘wrong blood’ occurred out of hours whilst our audit shows that only 25% of crossmatch requests are made in that time period, suggesting that crossmatching performed outside core hours carries increased risks. The reason for increased risk of error needs further research, but 25 laboratories had only one member of staff working out of hours, often combining blood transfusion, haematology and coagulation work. A total of 25% of out of hours requests were not clinically urgent. Hospitals should develop policies to define indications for out of hours transfusion testing, empower laboratory staff to challenge inappropriate requests and ensure that staffing and expertise is appropriate for the workload at all times. [ABSTRACT FROM AUTHOR]

Strains of Xanthomonas isolated in New Zealand from diseased endemic and introduced plants, investigated in a multi-locus sequence analysis (MLSA), were distributed primarily in two species. Strains from Dysoxylum, Hardenbergia, Liquidambar, Magnolia and Mahonia were members of Xanthomonas arboricola. Strains of Xanthomonas campestris pv. laureliae, X. campestris pv. eucalypti and strains from Aralia, Diospyros, Dysoxylum, Eriostemon, Eucalyptus, Metrosideros and Olea formed a population distinct from all known Xanthomonas spp. These latter strains have a unique fatty acid methyl ester profile and are considered to be members of a new Xanthomonas species, for which the name Xanthomonas dyei is proposed. Xanthomonas campestris pv. eucalypti and X. campestris pv. laureliae are considered to be pathovars of the new species and their reclassification as X. dyei pv. eucalypti and X. dyei pv. laureliae, respectively, is proposed. Strains previously identified as Pseudomonas syringae pv. dysoxyli from Dysoxylum spectabile, including the pathotype strain, were examined and found not to represent the pathogen originally described as P. dysoxyli. Other strains (proved to be pathogenic) from diseased D. spectabile, corresponding to the original description of P. dysoxyli, are members of X. dyei and the new combination X. dyei pv. dysoxyli is proposed. The geographic and evolutionary origins of X. dyei, apparently endemic to Australasia, and the adaptation of strains to the introduced host plants Aralia, Diospyros, Eriostemon, Metrosideros and Olea, are discussed. The origins of the X. arboricola strains isolated from Dysoxylum, Hardenbergia, Liquidambar, Magnolia and Mahonia pose a conundrum. [ABSTRACT FROM AUTHOR]

Title. Judging nursing information on the WWW: a theoretical understanding.Aim. This paper is a report of a study of the judgement processes nurses use when evaluating World Wide Web information related to nursing practice.Background. The World Wide Web has increased the global accessibility of online health information. However, the variable nature of the quality of World Wide Web information and its perceived level of reliability may lead to misinformation. This makes demands on healthcare professionals, and on nurses in particular, to ensure that health information of reliable quality is selected for use in practice.Method. A grounded theory approach was adopted. Semi-structured interviews and focus groups were used to collect data, between 2004 and 2005, from 20 nurses undertaking a postqualification graduate course at a university and 13 nurses from a local hospital in the United Kingdom.Findings. A theoretical framework emerged that gave insight into the judgement process nurses use when evaluating World Wide Web information. Participants broke the judgement process down into specific tasks. In addition, they used tacit, process and propositional knowledge and intuition, quasi-rational cognition and analysis to undertake these tasks. World Wide Web information cues, time available and nurses' critical skills were influencing factors in their judgement process.Conclusion. Addressing the issue of quality and reliability associated with World Wide Web information is a global challenge. This theoretical framework could contribute towards meeting this challenge. [ABSTRACT FROM AUTHOR]

Objectives: To compare pepsin, carbonic anhydrase III (CAIII), cyclooxygenase-2 (COX-2) and mucin 5AC (MUC5AC) expression in children with adenoid hypertrophy and normal controls. Design: A non-randomised, controlled prospective study. Setting: Two paediatric hospitals in Adelaide, South Australia. Participants: Children aged 2–10 years, 21 undergoing adenoidectomy and 12 controls undergoing routine dental surgery. Main outcome measures: We measured expression of pepsin, CAIII, COX-2 and MUC5AC levels by real-time RT-PCR, immunohistochemistry, and Western blot to determine any difference between children with hyperplastic adenoids and controls. Results: Pepsin was not detected in any study or control adenoid by immunohistochemistry or Western blot. Real-time RT-PCR analysis showed a statistically significant difference between groups with respect to COX-2 ( P = 0.027) and MUC5AC ( P = 0.02) but no difference in CAIII expression ( P = 0.414). A significant correlation was also found between COX-2 and MUC5AC expression (Kendall Tau = 0.4, P = 0.005). Conclusion: Our results suggest that the biochemical changes seen in adenoid hypertrophy are different to those seen in reflux-affected tissues. The decreased COX-2 and MUC5AC expression may be due to squamous metaplasia and other inflammatory changes associated with adenoid hypertrophy. Our findings infer there is little evidence of reflux being a major contributory factor in the pathophysiology of adenoidal hypertrophy. [ABSTRACT FROM AUTHOR]

There is a lack of consensus on the safety of the coadministration of drugs and red blood cells (RBCs). A systematic review was undertaken to establish the evidence base for this question and assess how the evidence may be translated into present clinical day practice. Comprehensive searches of MEDLINE, EMBASE, CINAHL, the Cochrane Library and hand searching of transfusion journals, guidelines and websites identified 12 relevant papers: 11 in-vitro experiments and 1 case report. Data on incidences of haemolysis and agglutination following coadministration were extracted and analysed. Overall findings suggest that iron chelators (two papers), antimicrobials (three papers) and lower doses of opioids (three papers) are safe to coadminister with RBCs. Haemolysis was observed with higher doses of opioids (three papers). Transposition of these findings to clinical practice is limited because of the lack of clinical applicability of in-vitro experiments and diversity in how, and what, clinical outcome measures were used. Further evidence from true clinical settings would be required to inform clinical practice on the efficacy and safety of the coadministration of drugs and RBCs. [ABSTRACT FROM AUTHOR]

The aim of this study was to describe current blood conservation practice during revision hip surgery in Scotland and document practice variation. Revision hip surgery is associated with a high likelihood of blood transfusion. A decrease in the proportion of patients requiring blood transfusion has been documented, but the reasons for this are unclear. Various blood conservation practices are available to clinicians, but the extent to which these are used in Scottish hospitals is not known. A cross-sectional postal survey was sent to all consultant orthopaedic surgeons and consultant anaesthetists participating in revision hip surgery in Scottish hospitals. Responses were received from 92 of 120 (77%) surgeons, and 174 of 216 (81%) anaesthetists (62/92). A total of 62 of 92 (67%) surgeons and 78 of 174 (45%) anaesthetists surveyed participated in revision hip surgery. Blood conservation practice varied widely: 34 of 78 (44%) anaesthetists routinely assessed revision hip patients ≥1 week prior to surgery; 10 of 62 (16%) surgeons and 24 of 78 (31%) anaesthetists routinely used cell salvage; 7 of 78 (9%) anaesthetists and 2 of 62 (3%) surgeons routinely used tranexamic acid; and 45 of 62 (73%) surgeons use a transfusion protocol. A wide variation in the use of blood conservation strategies exists during revision hip surgery in Scotland. [ABSTRACT FROM AUTHOR]

Previous reports describe a population of non-cardiac surgical patients at high risk of complications and death. Outcomes are sub-optimal for such patients, perhaps in part related to inadequate provision or ineffective utilisation of critical care resources. In this study, data describing 26 051 in-patient non-cardiac surgical procedures performed in a large NHS Trust between April 2002 and March 2005 were extracted from local databases. Of these procedures, 2 414 (9.3%) were high risk with an overall mortality rate of 12.2% and a prolonged hospital stay (high-risk population median (IQR) 16 (9–30) days vs standard risk 3 (2–6) days). Mortality rates for specific procedures were consistent with UK averages. However, only 852 (35.3%) high-risk patients were admitted to a critical care unit at any stage after surgery. Of 294 high-risk patients who died, only 144 (49.0%) were admitted to a critical care unit at any time and only 75 (25.6%) of these deaths occurred within a critical care area. Mortality rates were high amongst patients discharged and readmitted to critical care (37.7%) and amongst those admitted to critical care following initial postoperative care on a standard ward (29.9%). These data suggest that the outcome of high-risk general surgical patients could be improved by adequate provision and more effective utilisation of critical care resources. [ABSTRACT FROM AUTHOR]

Asplenic or hyposplenic patients are at risk of fulminant sepsis. This entity has a mortality of up to 50%. The spectrum of causative organisms is evolving as are recommended preventive strategies, which include education, prophylactic and standby antibiotics, preventive immunizations, optimal antimalarial advice when visiting endemic countries and early management of animal bites. However, there is evidence that adherence to these strategies is poor. Consensus-updated guidelines have been developed to help Australian and New Zealand clinicians and patients in the prevention of sepsis in asplenic and hyposplenic patients. [ABSTRACT FROM AUTHOR]

Current recommendations vary with regard to the frequency of change of a red blood cell (RBC) administration set. A full review was undertaken to evaluate the recommendations for how often a RBC administration set should be changed while a patient is being transfused. Comprehensive searches of Medline, Embase, Cinahl, the Cochrane Library, handsearching of transfusion journals, guidelines and websites and contact with administration set manufacturers identified 32 relevant papers: 11 clinical updates; 11 guidelines; 5 manufacturer data sheets; 3 standards; 1 Department of Health report and 1 expert opinion. Recommendations varied widely across papers. There was no pattern in recommendation by paper type, date or country of origin. Recommendations were based on change of RBC administration set either after a given number of hours or number of RBC units. The recommendations varied widely and ranged from 4 to 48 h and from ‘every unit’ to ‘several units’. The most frequent recommendations were change of RBC administration set after 12 h or 4 units. Methodological quality of the included papers is poor. There is no formal evidence base on which to support current recommendations or challenge the current British Committee for Standards in Haematology guideline. Targeted research aimed at establishing an evidence base may be warranted and would need to document other variables that can impact frequency of change, including type of filter, age of blood and duration of RBC transfusion. [ABSTRACT FROM AUTHOR]

Objective Reports suggest that the rates of tuberculosis (TB) continue to rise in the UK and throughout the world. The spread of the disease is aided by poverty, overcrowding, co-infection with human immunodeficiency virus and drug resistance. Consistent with the overall trend, intra-abdominal and gastrointestinal (GI) TB rates are rising. Tuberculosis is a treatable disease, whether occurring in the lungs or at extra-pulmonary sites but the nonspecific features of the disease result in difficulty in establishing a diagnosis. In this report, we have concentrated on the benefits and potential pitfalls of diagnostic methods. Method A literature review was performed using the National Library of Medicine's Pubmed Database using the keywords diagnosis, management, abdominal and GI TB. Results Abdominal TB presents a particular challenge, as the diverse features of the disease do not readily suggest a particular diagnosis and diagnostic delays lead to significant morbidity and mortality. A number of investigative methods have been used to aid in the diagnosis of abdominal and GI TB. Conclusion The nonspecific presentation of abdominal and GI TB present challenges in the diagnosis of this increasingly common disease. A high index of suspicion is an important factor in early diagnosis. After a diagnosis has been established, prompt initiation of treatment helps prevent morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background Children with complex healthcare needs are often excluded, both from active involvement in research projects and from direct consultation in services. During a 3-year research study into multi-agency services for children with complex healthcare needs, the authors involved children in a number of innovative ways and endeavoured to discover what impact, if any, multi-agency working made to them. Methods The researchers ‘spent time’ with 18 children with complex healthcare needs. They used a variety of methods to engage with the children in a meaningful way. More than half of the children had no verbal communication, so it was necessary in some cases to work with an advocate, usually the parent, to aid the process. Results Children with complex healthcare needs can take part in research as long as the research is set up sensitively and flexibly. In terms of the impact of multi-agency working, the authors concluded significant advances had been achieved for this group: almost all the children were living at home and attending school. However, there were significant gaps in addressing children’s human rights in relation to communication, independence and relationships. In addition, many of the children had very little effective direct consultation with the multi-agency services. Conclusions There are significant advances in involving disabled children in research and in service delivery, but there is still some way to go in involving those with complex healthcare needs. The challenges are considerable, but the benefits far outweigh these, not least being the value that parents, carers and the children themselves place upon being listened to. [ABSTRACT FROM AUTHOR]

Little is known about the metabolism and mechanism of action of the trypanocide, isometamidium (ISM), the major drug used for prophylaxis of trypanosomiasis. We have investigated its metabolism and distribution in isolated rat hepatocytes using liquid chromatography-mass spectrometry and confocal laser scanning microscopy (CLSM). Two putative metabolites were formed, which were proposed to be a mono-acetyl derivative and an oxidized metabolite (SII). This is the first demonstration of the hepatic metabolism of ISM, as previous in vivo studies were hampered by dose-limiting toxicity and insensitive analytical methods. The intrinsic fluorescence of the drug enabled its intracellular uptake to be followed by CLSM. It is taken up rapidly into the nucleolus, nuclear membrane and endoplasmic reticulum within 5 min, and retained in the nucleus for at least 24 h. Persistent binding of ISM to cellular macromolecules may contribute to its prophylactic effect in vivo. Pretreatment of rats with 3-methylcholanthrene, phenobarbitone (PB) or the widely used pyrethroid pesticide, deltamethrin, resulted in an increase in metabolism of ISM to the proposed SII after 1 h incubation with hepatocytes. 3-methylcholanthrene was the most potent inducer, causing a maximal 19.5-fold induction of SII formation after exposure of hepatocytes to ISM for 1 h compared with formation by control hepatocytes. In comparison, at the 1 h timepoint deltamethrin pre-treatment caused a 10.2-fold induction, and PB only 8.2 fold. [ABSTRACT FROM AUTHOR]

Objective Surgery induces a catabolic response with stress hormone release and insulin resistance. The aim of this study was to assess the effect of pre-operative carbohydrate administration on grip strength, gastrointestinal function and hospital stay following elective colorectal surgery. Methods Thirty-six patients undergoing elective colonic resection were randomized into one of three groups. Group 1 were fasted; Group 2 were given pre-operative oral water, Group 3 received equivalent volumes of a Maltodextrin drink. Time to first flatus, first bowel movement and hospital stay were recorded. Muscle strength was measured pre-operatively, and on alternate days thereafter until discharge using a grip strength dynamometer. Results Patients in the carbohydrate group had a median postoperative hospital stay of 7.5 days compared with 13 days in the water group ( P > 0.01) and 10 days in the fasted group ( P = 0.06). The median time postsurgery to first flatus was 3 days for both the fasted and water groups compared with 1.5 days in the carbohydrate group ( P = 0.13). First bowel movement occurred on day 3 in the carbohydrate group, day 4 in the fasting group and day 5 in the water group. The fasted group showed a significant reduction in postoperative grip strength ( P < 0.05) with a median drop of 10% at discharge. Neither the water nor the carbohydrate groups showed significant reductions in muscle strength. Conclusion We found that pre-operative administration of oral carbohydrate leads to a significantly reduced postoperative hospital stay, and a trend towards earlier return of gut function when compared with fasting or supplementary water. [ABSTRACT FROM AUTHOR]

The article investigates the distribution of uranium contamination in weathered fractured saprolite, shale and groundwater by researchers from the U.S. The objective of this study was to determine how structure, stratigraphy and weathering influence fate and transport of contaminants in the ground water and geologic material. Several cores were collected, near four former unlined adjoining waste disposal ponds. The cores were collected, described, analyzed for uranium, and compared with ground water geochemistry from surrounding multilevel wells.

Propolis is a widely used natural remedy and a range of biological activities have been attributed to it. The chemical composition of propolis is highly variable and its quality is often controlled on the basis of one or two marker compounds. In order to progress towards a method for the quality control of this complex material, HPLC and 1H-NMR approaches as methods of quality control have been compared. HPLC analyses of 43 samples of propolis were carried out and six marker compounds were quantified in each sample. The same samples were analysed using 1H-NMR and the spectra were then converted into their first derivative forms and digitised using the software application MestRe-C. The digitised data were subjected to principal component analysis using the software application Simca-P. It was found that the chemical composition of propolis mapped well according to the geographical origins of the samples studied when the first three principal components were used to display them. In addition, each sample was assessed for anti-oxidant activity, and the results were then overlaid onto the sample groupings according to 1H-NMR data. It was observed that anti-oxidant properties also mapped quite well according to geographical origin. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]