Determination of antimony and barium in UK air quality samples as indicators of non-exhaust traffic emissions.

The aim of this study was to determine concentrations of antimony and barium in air quality samples and assess the potential suitability of these metals as tracer elements for non-exhaust traffic emissions sources. Air quality filters sampled at monitoring sites around the UK for the purposes of the UK Heavy Metals Monitoring Network were subjected to microwave digestion in hydrogen peroxide and nitric acid, then analysed by ICP-MS for a suite of metals including antimony and barium. The average antimony concentration found across all the network sites was 1.84 ng m-3; the average barium concentration was 6.33 ng m-3. The range of antimony concentrations observed was 0.13-8.02 ng m-3; barium concentrations ranged from levels below the detection limit of 0.18 to 39.9 ng m-3. There are no legislative limits for antimony and barium in ambient air, but the maximum concentrations found are well below the Workplace Exposure Limits specified by the UK Health and Safety Executive. The highest concentrations were found at roadside sites situated to monitor traffic environments, supporting the suitability of antimony and barium to be considered tracer elements for traffic emissions sources. Strong correlations were observed between antimony, barium and copper, indicating they share a common traffic-related source. Based on the strong correlation with copper at urban and traffic locations, indicative annual UK atmospheric emission estimates for antimony and barium in brake and tyre wear were calculated as 6 and 19 tonnes respectively.

Adductor canal versus femoral triangle anatomical locations for continuous catheter analgesia after total knee arthroplasty: a multicentre randomised controlled study.

BACKGROUND: Adductor canal (AC) catheters are being used to provide continuous postoperative analgesia after total knee arthroplasty (TKA) surgery. There are anatomical arguments that most AC catheters are being inserted into the femoral triangle (FT) compartment of the thigh rather than the AC compartment. The clinical relevance of this is unknown with respect to motor weakness, quality of analgesia, and opioid consumption. We hypothesised that AC catheters provide superior functional mobilisation on postoperative Day 1 after TKA as measured using the Timed Up and Go (TUG) test. METHODS: In this multinational, multicentre, double-blinded RCT, catheters were inserted under ultrasound guidance into the anatomical AC and FT compartments. The standardised protocol included spinal anaesthesia without intrathecal morphine, fixed catheter infusion rates, and oral analgesia. RESULTS: Of 151 subjects recruited, 75 were in the AC group and 76 in the FT group. There was no statistically significant difference in TUG on postoperative Day 1 between AC (38 [29-55] s) and FT subjects (44 [32-64] s) (median [inter-quartile range]); P=0.11). There was no difference in TUG Day 2, AC (38 [27-53] s) vs FT (42 [31-59] s); P=0.66. There were no statistically significant differences for secondary endpoints of pain level, effectiveness of pain relief, interference of functional activities and interpersonal relationships by pain, and opioid consumption between groups. CONCLUSIONS: There were no differences in immediate postoperative functional mobility, analgesia, and opioid consumption provided by catheters inserted into the AC vs FT locations for TKA surgery. CLINICAL TRIAL REGISTRATION: ANZCTR12617001421325.

Association of anal symptoms with anal high grade squamous intraepithelial lesions (HSIL) among men who have sex with men: Baseline data from the study of the prevention of anal cancer (SPANC).

BACKGROUND: The association between anal high-grade squamous intraepithelial lesion (HSIL) and anal symptoms has not been systematically investigated. METHODS: The Study of Prevention of Anal Cancer is a prospective cohort study of men who have sex with men (MSM) ≥ 35 years old in Sydney, Australia. Self-reported symptoms were collected. Anal cytology and high-resolution anoscopy were undertaken. Using baseline visit data, men negative for squamous intra-epithelial lesion (SIL) were compared with men diagnosed with composite-HSIL (cytology and/or histology). Logistic regression analyses were performed to assess the association of symptoms with HSIL. RESULTS: Among 414 MSM included (composite-HSIL (n = 231); negative for SIL (n = 183)), 306 (73.9%) reported symptom(s) within the last 6 months. There was no association between any symptom and composite-HSIL. A significant association between anal lump and a larger burden of HSIL (at least 2 intra-anal octants) (anal lump within last month: p = 0.014; anal lump within last 6 months: p = 0.010) became non-significant after adjusting for HIV-status and recent anal warts (anal lump within last month: p = 0.057; anal lump within last 6 months: p = 0.182). CONCLUSIONS: Among MSM age 35 years and older, most anal symptoms are not a useful marker of anal HSIL.

An animal tissue simulation assessing three directional displacement forces on five common tracheostomy securing techniques.

Introduction Several methods of securing a tracheostomy tube have been described in the literature including using ties or tapes around the neck and suturing the plastic flange to the neck in various ways. However, there are no wet lab-based studies to objectively determine the force required to displace the tracheostomy tube using different securing techniques. Ours is the first animal tissue simulation study published in the literature. Methods A simulated tracheostomy stoma was created on a sheep neck model. A tracheostomy tube was inserted into the stoma and secured using various methods. Tension tests were conducted to significantly displace the tube from the stoma. Each technique was repeated six times on different sheep necks. All results were analysed using SPSS®. Results Repeat measurements indicated that the largest displacement forces come from an oblique direction while the lowest force values were found at the lateral angle. Averages of displacement showed that medially placed sutures required the largest forces in comparison with other securing methods. Wilcoxon signed-rank testing indicated that medial and continuous suture security resists displacement at forces that otherwise displace flange and interrupted sutures. Conclusions This study has shown that any type of securing suture requires a greater displacement force than the strap of the tracheostomy tube holder alone. Medially placed sutures require a greater displacement force than those placed laterally. Displacement in the lateral direction requires the least force in comparison with movement at perpendicular or oblique angles.

Novel genomic microsatellite markers for genetic population and diversity studies of tropical scalloped spiny lobster (Panulirus homarus) and their potential application in related Panulirus species.

Fourteen polymorphic microsatellites with perfect di-, tri-, and tetra-nucleotide repeats were identified for Panulirus homarus using Roche 454 whole-genome sequencing method. Microsatellites were efficiently co-amplified in four multiplexes and a singleplex, providing consistent and easily interpretable genotypes. The number of alleles per locus ranged from 2 to 11 with the observed and expected heterozygosity ranging between 0.000-0.532 and 0.031-0.836, respectively. A significant deviation from Hardy-Weinberg equilibrium was observed for majority of the loci, probably due to homozygote excess. Genetic linkage disequilibrium analysis between all the possible pairs of the loci showed significant departure from the null hypothesis in the loci pairs Pho-G11-Pho-G33 and Pho-G33-Pho-G57. High success in primer cross-species amplification of these microsatellite markers indicates their utility for genetic studies of different Panulirus species.

Isolation, characterization, and multiplexing of novel microsatellite markers for the tropical scalloped spiny lobster (Panulirus homarus).

Of the various spiny lobster species in the tropical and subtropical Indo-West Pacific region, the tropical scalloped spiny lobster (Panulirus homarus) supports one of the most commercially valuable fishery resources in many coastal African and Asian countries. The last decade has witnessed a serious decline in the wild populations of this species. Knowledge of the genetic basis of spiny lobster population structure is a prerequisite to achieve a sustainable fisheries management for this species. Here, we describe 13 novel polymorphic microsatellite markers developed for P. homarus, using a cross-species primer design strategy based on P. ornatus Roche 454 shot-gun generated sequencing. Microsatellite polymorphisms were assessed in 96 unrelated P. homarus individuals of a natural population, with the number of alleles per locus varying from 2 to 14, the observed and expected heterozygosity from 0.00 to 0.78 and from 0.03 to 0.79, respectively, and with only four loci (Pho-G27, Pho-G32, Pho-G36, and Pho-G58) deviating from Hardy- Weinberg equilibrium. Genetic linkage disequilibrium analysis between all pairs of the loci showed significant departure from the null hypothesis between loci Pho-G22 - Pho-G30, and Pho-G30 - Pho-G35. The successful cross amplification of these microsatellites highlights the potential of the developed microsatellites for future population genetic research within the different Panulirus species.

Proteomic identification of galectin-3 binding ligands and characterization of galectin-3 proteolytic cleavage in human prostasomes.

Galectin-3 is a multifunctional carbohydrate-binding protein that was previously characterized as a proteolytic substrate for prostate-specific antigen (PSA) and was shown to be associated with prostasomes in human semen. Prostasomes are exosome-like vesicles that are secreted by the prostatic epithelium and have multiple proposed functions in normal reproduction and prostate cancer. In the current study, galectin-3 binding ligands in human prostasomes were identified and characterized with the goal to investigate galectin-3 function in prostasomes. Galectin-3 binding proteins were isolated by affinity column chromatography. Candidate ligands identified by MS/MS were PSA, prostatic acid phosphatase (PAP), zinc alpha-2-glycoprotein (ZAG), dipeptidyl peptidase-4 (CD26), aminopeptidase N (CD13), neprilysin, clusterin, antibacterial protein (FALL-39) and alpha-1-acid glycoprotein (ORM1). Biochemical methods were used to characterize the ability of galectin-3 to bind to selected ligands, and galectin-3 cleavage assays were utilized to investigate the protease(s) in prostasomes that cleaves galectin-3. CD26, CD13, PSA, PAP and ZAG immunoreactivity were detected in extracts of purified prostasomes. One-dimensional electroblot analysis of prostasomes demonstrated that CD26, PAP and CD13 immunoreactivity co-migrated with galectin-3-reactive protein bands. PSA and ZAG were found to be associated with the surface of prostasomes. Both intact and cleaved galectin-3 were detected in prostate and prostasome extracts. Cleavage and inhibition assays indicated that PSA in prostasomes proteolytically cleaves galectin-3. The identification of these glycoproteins as galectin-3 ligands lays the groundwork for future studies of galectin-3 and prostasome function in reproduction and prostate cancer.

The new VARSKIN 4 photon skin dosimetry model.

A new photon skin dosimetry model, described here, was developed as the basis for the enhanced VARSKIN 4 thin tissue dosimetry code. The model employs a point-kernel method that accounts for charged particle build-up, photon attenuation and off-axis scatter. Early comparisons of the new model against Monte Carlo particle transport simulations show that VARSKIN 4 is highly accurate for very small sources on the skin surface, although accuracy at shallow depths is compromised for radiation sources that are on clothing or otherwise elevated from the skin surface. Comparison results are provided for a one-dimensional point source, a two-dimensional disc source and three-dimensional sphere, cylinder and slab sources. For very small source dimensions and sources in contact with the skin, comparisons reveal that the model is highly predictive. With larger source dimensions, air gaps or the addition of clothing between the source and skin; however, VARSKIN 4 yields over-predictions of dose by as much as a factor of 2 to 3. These cursory Monte Carlo comparisons confirm that significant accuracy improvements beyond the previous version were achieved for all geometries. Improvements were obtained while retaining the VARSKIN characteristic user convenience and rapid performance.

The WIMAT colonoscopy suitcase model: a novel porcine polypectomy trainer.

AIM: Simulation allows the acquisition of complex skills within a safe environment. Endoscopic polypectomy has a long learning curve. Our novel polypectomy simulator may be a useful adjunct for training. The aim of this study was to assess its content validity. METHOD: The Welsh Institute for Minimal Access Therapy (WIMAT) endoscopy suitcase was designed to simulate colonic polypectomy. Participants from regional and national courses were recruited into the study. Each undertook a standardized simulated polypectomy and completed a seven-point Likert scale questionnaire examining its realism. RESULTS: In all, 17 participants completed the questionnaire: 15 (88.2%) gastroenterologists, one (5.9%) colorectal surgeon and one (5.9%) experienced endoscopic nurse specialist. Of the gastroenterologists, seven (46.7%) were consultants and eight (53.3%) were senior trainees or Post CCT (Certificate of Completion of Training) fellows. The mean number of real-life polypectomies performed by the cohort was 156 (95% CI 35-355). The highest scores were for 'mucosal realism' (median score 6.0, P=0.001), 'endoscopic snare control' (median score 6.0, P=0.001), 'handling the polyp' (median score 6.0, P=0.001) and 'raising mucosa' (median score 6.0, P<0.001). Of the 15 parameters examined only three were not statistically significant in favour of the simulator. These were 'anatomical realism of sessile polyps', 'resistance of scope movement' and 'paradoxical motion'. The overall score for the simulation was 6.0 (P < 0.001). There was no significant difference between the level of difficulty of the simulator compared with real life (median score 4.0, P = 0.559). CONCLUSION: The WIMAT colonoscopy suitcase model has excellent content validity for several parameters. This may have potential applications in medical training and assessment.

Retrospective case series analysis of penicillin allergy testing in a UK specialist regional allergy clinic.

INTRODUCTION: Penicillin allergy is the most common drug allergy. Skin testing for the major (PPL) and minor determinants (MDMs) of penicillin offers increased sensitivity and specificity over in vitro testing alone. Following a worldwide absence of reagents, a new kit was licensed in the UK in 2008 (Diater, Spain) and this report evaluates its use in a UK specialist allergy clinic. METHODS: Prospective data on 50 consecutive patients tested with the new reagents were collected. The departmental protocol is adapted from the 2003 EAACI position paper. RESULTS: 14% (7/50) and 12% (6/50) of patients were diagnosed with immediate and non-immediate reactions respectively. The negative predictive value of the PPL and MDM reagents at the neat concentration for an immediate reaction was 93% (true negatives 37, false negatives 3). Two patients experienced systemic reactions to DPT in the absence of demonstrable specific IgE. None of the patients were diagnosed using skin prick testing alone or at lower concentrations of IDT. Five patients were diagnosed at the IDT stage and two at the DPT stage in the absence of demonstrable specific IgE. Six patients were diagnosed with non-immediate reactions, two on IDT alone and four following IDT and DPT. CONCLUSION: The new PPL and MDM determinants offer enhanced sensitivity when evaluating ß-lactam hypersensitivity; however, there are limitations to the current testing regimens. The UK would benefit from local guidelines, which incorporate the new reagents and acknowledge the high amoxicillin prescription rate and the relatively lower specialist-to-patient ratio in this country.

Wheat dependent exercise induced anaphylaxis: is this an appropriate terminology?

BACKGROUND: The presentation of wheat dependent exercise induced anaphylaxis (WDEIA) can be variable. A high index of clinical suspicion is required to initiate the investigation pathway. Double blind placebo controlled food-exercise challenge is the gold standard investigation but the practicality of this test limits its application. AIM: To critically analyse the symptoms of WDEIA and their correlation with serum specific IgE (sIgE) to romega-5-gliadin. METHODS: 17 patients were tested for serum sIgE to romega-5-gliadin. The clinical response to a diet/exercise intervention protocol was used to assess specificity of a positive sIgE to romega-5-gliadin. Length of time to diagnosis, clinical likelihood scores, exercise intensity involved and the severity of allergic reactions were examined retrospectively. RESULT: 8/10 patients with positive sIgE to romega-5-gliadin had a confirmed diagnosis of WDEIA. Half of the WDEIA patients had a prolonged time lag to diagnosis (32-62 months) and were initially diagnosed with idiopathic anaphylaxis or chronic idiopathic urticaria and angioedema. Only three patients had experienced life threatening symptoms (Mueller grading 4). A close association was observed between requirements of lower exercise intensity to provoke a reaction and diagnostic delay. CONCLUSION: Specific IgE to romega-5-gliadin can provide supportive evidence for WDEIA without the need of a food-exercise challenge. The wheat-exercise association is not obvious in many patients, highlighting the need to consider WDEIA in the differential diagnosis of all patients presenting with idiopathic systemic reactions. The term anaphylaxis may be inappropriate and it is therefore worth considering an alternative terminology such as 'activity dependent wheat allergy' to describe this condition.

Prognostic value of Dicer expression in human breast cancers and association with the mesenchymal phenotype.

BACKGROUND: Dicer, a ribonuclease, is the key enzyme required for the biogenesis of microRNAs and small interfering RNAs and is essential for both mammalian development and cell differentiation. Recent evidence indicates that Dicer may also be involved in tumourigenesis. However, no studies have examined the clinical significance of Dicer at both the RNA and the protein levels in breast cancer. METHODS: In this study, the biological and prognostic value of Dicer expression was assessed in breast cancer cell lines, breast cancer progression cellular models, and in two well-characterised sets of breast carcinoma samples obtained from patients with long-term follow-up using tissue microarrays and quantitative reverse transcription-PCR. RESULTS: We have found that Dicer protein expression is significantly associated with hormone receptor status and cancer subtype in breast tumours (ER P=0.008; PR P=0.019; cancer subtype P=0.023, luminal A P=0.0174). Dicer mRNA expression appeared to have an independent prognostic impact in metastatic disease (hazard ratio=3.36, P=0.0032). In the breast cancer cell lines, lower Dicer expression was found in cells harbouring a mesenchymal phenotype and in metastatic bone derivatives of a breast cancer cell line. These findings suggest that the downregulation of Dicer expression may be related to the metastatic spread of tumours. CONCLUSION: Assessment of Dicer expression may facilitate prediction of distant metastases for patients suffering from breast cancer.

The molecular causes of low ATM protein expression in breast carcinoma; promoter methylation and levels of the catalytic subunit of DNA-dependent protein kinase.

AIMS: To investigate whether aberrant methylation of the ATM promoter or loss of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) may be the underlying causes of reduced ATM protein levels often seen in breast tumours. METHODS AND RESULTS: Methylation-specific polymerase chain reaction was used to determine the ATM promoter status and DNA-PKcs levels were measured by immunohistochemistry. None of the 74 invasive carcinomas (ICs) studied showed ATM promoter hypermethylation, whereas promoter methylation of CDKN2A/p16 (1.8%) and GSTP1 (15.8%) was detected. Of 92 ICs examined, 68 had reduced DNA-PKcs levels, supporting previous findings that alterations in double-strand break repair are associated with breast cancer pathogenesis. Although no association was found between the DNA-PKcs and ATM scores for the series of 92 tissues and 22/24 tissues with normal DNA-PKcs had reduced ATM, 29 tumours showed low expression of both DNA-PKcs and ATM compared with normal tissues. CONCLUSIONS: No evidence was found that the reduction in ATM protein levels seen in breast carcinoma is the result of epigenetic silencing. However, cross-regulation between DNA-PKcs and ATM may be a possible cause in a subset of tumours and warrants further investigation.

An audit of imaging test utilization for the management of lymphoma in an oncology hospital: implications for resource planning?

The purpose of this study was to assist with resource planning by examining the pattern of physician utilization of imaging procedures for lymphoma patients in a dedicated oncology hospital. The proportion of imaging tests ordered for routine follow up with no specific clinical indication was quantified, with specific attention to CT scans. A 3-month audit was performed. The reasons for ordering all imaging procedures (X-rays, CT scans, ultrasound, nuclear scan and MRI) were determined through a retrospective chart review. 411 lymphoma patients had 686 assessments (sets of imaging tests) and 981 procedures (individual imaging tests). Most procedures were CT scans (52%) and chest radiographs (30%). The most common reasons for ordering imaging were assessing response (23%), and investigating new symptoms (19%). Routine follow up constituted 21% of the assessments (142/686), and of these, 82% were chest radiographs (116/142), while 24% (34/142) were CT scans. With analysis restricted to CT scans (296 assessments in 248 patients), the most common reason for ordering CT scans were response evaluation (40%), and suspicion of recurrence and/or new symptom (23%). Follow-up CT scans done with no clinical indication comprised 8% (25/296) of all CT assessments. Staging CT scans were under-represented at 6% of all assessments. Imaging with CT scans for follow up of asymptomatic patients is infrequent. However, scans done for staging new lymphoma patients were unexpectedly low in frequency, due to scans done elsewhere prior to referral. This analysis uncovered utilization patterns, helped resource planning and provided data to reduce unnecessary imaging procedures.

An evaluation of Cidex OPA (0.55% ortho-phthalaldehyde) as an alternative to 2% glutaraldehyde for high-level disinfection of endoscopes.

Cidex OPA (0.55% ortho-phthalaldehyde) is marketed as a safer alternative to 2% glutaraldehyde for endoscope decontamination. As clinical experience is limited, an evaluation was undertaken in a busy endoscopy unit. Cidex OPA cycle dilution was monitored by manufacturer's test strips and high-pressure liquid chromatography (HPLC). Eight endoscopy staff completed daily occupational health questionnaires before and after its introduction. Patient throughput times were assessed in view of Cidex OPAs reduced disinfection time. HPLC confirmed that Cidex OPA levels are maintained above 0.3% for at least 50 cycles. Indicator strips proved generally reliable when tested by pharmacy staff. However, busy endoscopy staff found the indicator strips difficult to interpret, with 28 out of 223 (12.5%) test results being inappropriately recorded as 'fails'. Two hundred and two questionnaires were completed and no short-term health problems were noted. Apart from bronchoscopy lists, patient turnaround times were not improved. The increased cost of changing to Cidex OPA was estimated as pound 7691 per annum. Staining of washer-disinfectors was of concern as it proved very difficult to remove.