Preequilibrium Asymmetries in the

The physical properties of neutrons emitted from neutron-induced fission are fundamental to our understanding of nuclear fission. However, while state-of-the-art fission models still incorporate isotropic fission neutron spectra, it is believed that the preequilibrium prefission component of these spectra is strongly anisotropic. The lack of experimental guidance on this feature has not motivated incorporation of anisotropic neutron spectra in fission models, though any significant anisotropy would impact descriptions of a fissioning system. In the present work, an excess of counts at high energies in the fission neutron spectrum of ^{239}Pu is clearly observed and identified as an excess of the preequilibrium prefission distribution above the postfission neutron spectrum. This excess is separated from the underlying postfission neutron spectrum, and its angular distribution is determined as a function in incident neutron energy and outgoing neutron detection angle. Comparison with neutron scattering models provides the first experimental evidence that the preequilibrium angular distribution is uncorrelated with the fission axis. The results presented here also impact the interpretation of several influential prompt fission neutron spectrum measurements.

Implementation and evaluation of nationwide scale-up of the Surgical Safety Checklist.

BACKGROUND: The WHO Surgical Safety Checklist improves surgical outcomes, but evidence and theoretical frameworks for successful implementation in low-income countries remain lacking. Based on previous research in Madagascar, a nationwide checklist implementation in Benin was designed and evaluated longitudinally. METHODS: This study had a longitudinal embedded mixed-methods design. The well validated Consolidated Framework for Implementation Research (CFIR) was used to structure the approach and evaluate the implementation. Thirty-six hospitals received 3-day multidisciplinary training and 4-month follow-up. Seventeen hospitals were sampled purposively for evaluation at 12-18 months. The primary outcome was sustainability of checklist use at 12-18 months measured by questionnaire. Secondary outcomes were CFIR-derived implementation outcomes, measured using the WHO Behaviourally Anchored Rating Scale (WHOBARS), safety questionnaires and focus groups. RESULTS: At 12-18 months, 86·0 per cent of participants (86 of 100) reported checklist use compared with 31·1 per cent (169 of 543) before training and 88·8 per cent (158 of 178) at 4 months. There was high-fidelity use (median WHOBARS score 5·0 of 7; use of basic safety processes ranged from 85·0 to 99·0 per cent), and high penetration shown by a significant improvement in hospital safety culture (adapted Human Factors Attitude Questionnaire scores of 76·7, 81·1 and 82·2 per cent before, and at 4 and 12-18 months after training respectively; P < 0·001). Acceptability, adoption, appropriateness and feasibility scored 9·6-9·8 of 10. This approach incorporated 31 of 36 CFIR implementation constructs successfully. CONCLUSION: This study shows successfully sustained nationwide checklist implementation using a validated implementation framework.

Skeletal muscle morphology in sarcopenia defined using the EWGSOP criteria: findings from the Hertfordshire Sarcopenia Study (HSS).

BACKGROUND: Sarcopenia is defined as the loss of muscle mass and function with age and is associated with decline in mobility, frailty, falls and mortality. There is considerable interest in understanding the underlying mechanisms. Our aim was to characterise muscle morphology changes associated with sarcopenia among community dwelling older men. METHODS: One hundred and five men aged 68-76 years were recruited to the Hertfordshire Sarcopenia Study (HSS) for detailed characterisation of muscle including measures of muscle mass, strength and function. Muscle tissue was obtained from a biopsy of the vastus lateralis for 99 men and was processed for immunohistochemical studies to determine myofibre distribution and area, capillarisation and satellite cell (SC) density. RESULTS: Six (6 %) men had sarcopenia as defined by the European Working Group on Sarcopenia in Older People (EWGSOP) criteria. These men had lower SC density (1.7 cells/mm(2) vs 3.8 cells/mm(2), p = 0.06) and lower SC/fibre ratio (0.02 vs 0.06, p = 0.06) than men without sarcopenia. Although men with sarcopenia tended to have smaller myofibres and lower capillary to fibre ratio, these relationships were not statistically significant. CONCLUSION: We have shown that there may be altered muscle morphology parameters in older men with sarcopenia. These results have the potential to help identify cell and molecular targets for therapeutic intervention. This work now requires extension to larger studies which also include women.

Effect of Brahman genetic influence on collagen enzymatic crosslinking gene expression and meat tenderness.

The objective of the study was to examine the effect of Brahman genetics on collagen enzymatic crosslinking gene expression and meat tenderness. Steers were randomly selected to represent a high percentage Brahman genetics (n = 13), Half-Blood genetics (n = 13), Brangus genetics (n = 13), and a high percentage Angus genetics (n = 13). Muscle samples from the Longissimus lumborum muscle were collected at weaning and harvest and reverse transcription quantitative PCR (qPCR) analysis was conducted to measure the mRNA expression of lysyl oxidase (LOX), bone morphogenetic protein 1 (BMP1), and cystatin C (CYS). Steaks from subject animals were collected at harvest, aged for 14 d and subjected to collagen analysis, Warner-Bratzler Shear Force (WBS) and trained sensory panel analysis (tenderness, juiciness, and connective tissue). Data indicated that Half-Blood and Brahman steers had greater (P<0.05) WBS values and tended to receive decreased (P < 0.06) panel tenderness scores than Angus and Brangus steers. Panelists tended to detect more connective tissue in Brahman and Half-Blood steaks when compared to Angus and Brangus steaks (P < 0.07). Crosslinking gene expression data revealed that at weaning Half-Blood steers had more (P < 0.05) mRNA expression of CYS and LOX than Angus and Brangus steers. At weaning and harvest, all genetic groups had similar mRNA expression of BMP1 (P > 0.10). At harvest, Brangus and Angus steers had greater LOX mRNA expression than Brahman cattle (P < 0.05). Pearson's correlation coefficients indicated that only weaning CYS mRNA expression was correlated to WBS, panel tenderness and connective tissue scores (P < 0.05). Expression of LOX was only correlated to these measures at harvest, and BMP1 was correlated to these traits at both time periods (P < 0.05). These results indicate that collagen crosslinking enzyme activity, as indicated by mRNA levels, early in an animal's life may account for some of the variation seen in steak tenderness due to Brahman genetic influence.

The histone deacetylase inhibitor valproic acid enhances equine herpesvirus type 1 (EHV-1)-mediated oncolysis of human glioma cells.

Histone deacetylase (HDAC) inhibitors represent a promising new therapy against malignant glioma. When used in conjunction with oncolytic viral vectors, these compounds have been shown to augment virotherapy. In the current study, we examined the antitumor effect of combining the lytic animal virus equine herpesvirus type 1 (EHV-1) with the HDAC inhibitor valproic acid (VPA). Pretreatment of two human glioblastoma cell lines (U251 and SNB19) with VPA resulted in a significant increase in virus entry, replication, cell to cell spread and cell lysis. Overall, these data indicate that VPA significantly improves EHV-1-mediated oncolysis of human glioma cells that are only moderately killed by EHV-1 alone.

Sulindac sulfide inhibits sarcoendoplasmic reticulum Ca2+ ATPase, induces endoplasmic reticulum stress response, and exerts toxicity in glioma cells: relevant similarities to and important differences from celecoxib.

Malignant gliomas have low survival expectations regardless of current treatments. Nonsteroidal anti-inflammatory drugs (NSAIDs) prevent cell transformation and slow cancer cell growth by mechanisms independent of cyclooxygenase (COX) inhibition. Certain NSAIDs trigger the endoplasmic reticulum stress response (ERSR), as revealed by upregulation of molecular chaperones such as GRP78 and C/EBP homologous protein (CHOP). Although celecoxib (CELE) inhibits the sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA), an effect known to induce ERSR, sulindac sulfide (SS) has not been reported to affect SERCA. Here, we investigated these two drugs for their effects on Ca(2+) homeostasis, ERSR, and glioma cell survival. Our findings indicate that SS is a reversible inhibitor of SERCA and that both SS and CELE bind SERCA at its cyclopiazonic acid binding site. Furthermore, CELE releases additional Ca(2+) from the mitochondria. In glioma cells, both NSAIDS upregulate GRP78 and activate ER-associated caspase-4 and caspase-3. Although only CELE upregulates the expression of CHOP, it appears that CHOP induction could be associated with mitochondrial poisoning. In addition, CHOP induction appears to be uncorrelated with the gliotoxicity of these NSAIDS in our experiments. Our data suggest that activation of ERSR is primarily responsible for the gliotoxic effect of these NSAIDS. Because SS has good brain bioavailability, has lower COX-2 inhibition, and has no mitochondrial effects, it represents a more appealing molecular candidate than CELE to achieve gliotoxicity via activation of ERSR.

Changes in characteristics of inmates with latent tuberculosis infection.

OBJECTIVES: Health and social characteristics place prisoners at high risk for progression from latent tuberculosis infection (LTBI) to tuberculosis (TB), but completion of LTBI therapy is low with many patients lost to follow-up after release. Despite decreases in active TB, demographic characteristics of active cases have remained relatively unchanged. This study investigated whether characteristics have changed in inmates diagnosed with LTBI in San Francisco, CA, USA. STUDY DESIGN: Cross-sectional. METHODS: Data from baseline interviews of randomized trials conducted in 1998-1999 and 2004-2007 were compared. RESULTS: In both time periods, most subjects with LTBI (>60%) were Latinos, while the proportion in both the jail and San Francisco remained at 15-20%. Overall, the prisoners interviewed in 2004-2007 were less likely to have been on medication for LTBI previously, and expressed more likelihood of finishing their medication compared with those interviewed in 1998-1999. In 2004-2007, the foreign-born subjects were more likely to prefer English to Spanish, to have been in stable housing and to have been employed before jail compared with 1998-1999, while no such changes were seen between the two time periods for US-born subjects. CONCLUSIONS: The pool of TB-infected individuals coming from a jail is not static, and understanding the changes over time is of importance for targeted programmes. Given the high infection rate and the predominance of foreign-born individuals who may have received bacillus Calmette-Guérin vaccination, screening with interferon-gamma release assay may be beneficial to identify those with true infection.

A randomised, controlled trial comparing the Airtraq™ optical laryngoscope with conventional laryngoscopy in infants and children.

The Airtraq(™) optical laryngoscope became available in paediatric sizes in the UK in May 2008. We conducted a randomised, controlled trial comparing the Airtraq with conventional laryngoscopy during routine anaesthesia in children. We hypothesised that the Airtraq laryngoscope would perform as well as conventional laryngoscopy. Sixty patients (20 infants and 40 children) were recruited. The mean (SD) intubation time using the Airtraq was longer than conventional laryngoscopy overall (47.3 (32.6) vs 26.3 (11.5) s; p=0.002), though the difference was only significant for children (p=0.003) and not for infants (p=0.29). The Airtraq provided a better view of the larynx compared with conventional laryngoscopy (in infants (percentage of glottic opening scores 100 (95-100 [90-100]) vs 77 (50-90 [40-100]), respectively; p=0.001; visual analogue scores for field of view 9.2 (9.2-9.5 [8.2-10.0]) vs 6.8 (5.1-8.0 [4.7-10.0]), respectively; p=0.001). In children, the Airtraq provided a similar view of the larynx (percentage of glottic opening scores 100 (100-100 [40-100]) vs 100 (90-100 [50-100]), respectively; visual analogue scores for field of view 9.2 (8.6-10.0 [7.0-10.0]) vs 9.2 (8.6-10.0 [5.6-10.0]), respectively; both p>0.05), compared with conventional laryngoscopy.

A cohort evaluation of the paediatric i-gel(™) airway during anaesthesia in 120 children.

We studied the i-gel™ in 120 anaesthetised children (92 boys, 28 girls; median (IQR [range]) age (3 -7 [0.4 -13]) years and weight 19 (15-26 [7-35]) kg) to assess efficacy and usability. Insertion was successful on the first/second/third attempt in 110/8/1 children and failed in one child. Median (IQR [range]) insertion time was 14 (9-16 [6-200]) s. Manual ventilation was possible in all cases, although excess leak precluded a tidal volume above 7 ml.kg(-1) in three children. Fibreoptic inspection through the i-gel revealed a clear view of the vocal cords in 40 out of 46 cases (87%). Median (IQR [range]) leak pressure was 20 (16-26 [8-30]) cmH(2) O. During maintenance of anaesthesia, 16 manipulations were required in 11 children to improve the airway. One child regurgitated without aspirating. Other complications and side effects were infrequent. The i-gel was inserted without complications, establishing a clear airway and enabling spontaneous and controlled ventilation, in 113 (94%) children.

A comparison of the Glidescope and Karl Storz DCI videolaryngoscopes in a paediatric manikin.

A new paediatric Glidescope (Cobalt GVL Stat) has recently become available. This varies in design from the Karl Storz DCI videolaryngoscope, as it possesses a short curved disposable blade compared with the narrower straighter blade of the Storz. We compared the time taken for tracheal intubation under normal and difficult intubation conditions in a paediatric manikin. A total of 32 anaesthetists completed four intubations in a random order, with each participant blinded to the airway condition. We hypothesised there would be no difference between the devices. The results showed no difference in tracheal intubation time between the Glidescope and the Storz videolaryngoscope. The mean (SD) times under normal conditions were 18.8 (5.2) s vs 19.9 (6.1) s, (p = 0.16), respectively. Under difficult conditions the times were 22.6 (10.5) vs 27.0 (14.2) s, (p = 0.13), respectively. There were no differences in the visual analogue scores for field of view, ease of use, willingness to use in an emergency, and overall satisfaction.

Anaesthesia for acute intestinal obstruction associated with cerebral arteriovenous malformation in a child.

This case report describes the perioperative management of a child presenting with acute intestinal obstruction secondary to bowel malrotation after a recent intracranial haemorrhage associated with an intracranial arteriovenous malformation. We discuss the anaesthesia planning for this case, where the 'optimal' management strategies for the two conditions present are potentially conflicting. Issues include rapid sequence induction in the presence of a ruptured arteriovenous malformation, maintenance of cerebral perfusion pressure in the face of bowel ischaemia, and the use of epidural anaesthesia in a child with recent intracranial haemorrhage. Written consent was obtained from the patient and parents to publish this case.

Audit of performance of size 1.5 ProSeal laryngeal mask airways in infants less than six months undergoing inguinal herniotomy.

Many anaesthetists have found the size 1.5 classic Laryngeal Mask Airway unsuitable for use in children under 10 kg, whereas recent studies evaluating the ProSeal Laryngeal Mask Airway (PLMA) show high success rates, even during laparoscopic surgery. Our routine practice has been to use tracheal intubation for inguinal herniotomy in children weighing less than 10 kg. Following the introduction of the PLMA to our hospital, we decided to audit our use of the PLMA 1.5 in this group of patients. We included 20 consecutive infants, aged less than six months and weighing 5 to 10 kg. We recorded patient, anaesthetic and insertion details, device performance data and complications. No aspect of anaesthetic practice was changed by involvement in this audit. The PLMA was inserted successfully at the first attempt in 85% (17/20) of infants. Overall successful insertion occurred in 90% (18/20) and satisfactory airway maintenance was provided for the duration of anaesthesia in 90% (18/20). The mean leak pressure was 24 cmH2O (range 15 to 30 cmH2O). We found the 1.5 PLMA provided a satisfactory airway in 90% of infants. This report adds to the evidence that the PLMA 1.5 can provide a satisfactory alternative to intubation in selected infants.

The relationship between cerebral and somatic oxygenation and superior and inferior vena cava flow, arterial oxygenation and pressure in infants during cardiopulmonary bypass.

We investigated blood flow and regional oxygenation (rSO(2)) during cardiopulmonary bypass (CPB). Twenty infants (mean (SD) age 5 (3) months, weight 5.4 (1.6) kg) were prospectively studied. Total CPB and superior vena cava (SVC) flow were measured using Transonic Bypass Flowmeters, inferior vena cava (IVC) flow derived arithmetically and rSO(2) measured using Near Infra-Red Spectroscopy. Mean SVC flow was 51.3 (14.8) ml.kg(-1).min(-1) and mean IVC flow 62.5 (19.0) ml.kg(-1).min(-1). Mean cerebral rSO(2) was 71 (11)% and somatic rSO(2) 55 (13)%. Cerebral and somatic rSO(2) showed no correlation with SVC and IVC flow. Cerebral rSO(2) showed a positive correlation with P(a)co(2), mean arterial pressure (MAP) and haematocrit (p < 0.0001). Somatic rSO(2) showed a positive correlation with MAP and haematocrit (p = 0.01, p = 0.02). In conclusion, the distribution of blood flow during CPB varies. The most important factor affecting this is P(a)CO(2). Cerebral and somatic oxygenation are unaffected by flow but significantly influenced by MAP, haematocrit and P(a)CO(2).

A prevalence survey for smear-positive tuberculosis in Thai prisons.

SETTINGS: Twenty-seven prisons in Thailand. OBJECTIVES: To measure the prevalence of smear-positive tuberculosis (TB) and to compare its detection using the World Health Organization (WHO) guidelines for prisons or the International Standards for Tuberculosis Care (ISTC) criteria. METHOD: Prisoners who were not on TB medications and who had not been treated for TB in the previous 6 months were enrolled in the survey. Prison nurses conducted a one-time mass screening using the WHO questionnaire, with follow-up sputum collection in TB suspects. RESULTS: Of 71594 prisoners, 22132 (30.9%) were identified as TB suspects, and 254 were confirmed by sputum smear, for a prevalence of 354.8/100000. Males were most likely to be diagnosed with TB disease (OR 2.6), as were those transferring in from another prison versus new prisoners (OR 3.0). The positive predictive value of the WHO criteria was 1.2%, and that of the ISTC standard was 5.9%. CONCLUSION: TB prevalence in this survey remained high. WHO guidelines, recognised as a standard, require health workers to question prisoners and measure height and weight. The ISTC standard, a single question about cough >or=2 weeks, is simple, may be asked by non-health personnel and may be a better alternative.

The therapeutic potential of phospholipase A2 inhibitors in cardiovascular disease.

Leukocyte recruitment and the expression of pro-inflammatory cytokines are prevalent characteristics of early atherogenesis. Recently, several inflammatory mediators have been linked to atheroma formation and inflammatory pathways have been shown to promote thrombosis. The discovery of mast cells, activated T lymphocytes and macrophages in atherosclerotic lesions, the detection of human leukocyte antigen class II expression, and the finding of local secretion of several cytokines all suggest the involvement of immune and inflammatory mechanisms in the pathogenesis of atherosclerosis. Recent research suggests activation of protease activated receptors (PAR) on the surface of endothelial cells may play a role in general mechanisms of inflammation. In previous studies, our laboratory has demonstrated that thrombin (which activates PAR-1) and tryptase (which activates PAR-2) stimulation of endothelial cells results in activation of calcium-independent phospholipase A(2) (iPLA(2)). iPLA(2) plays a critical role in the synthesis of membrane phospholipid-derived inflammatory mediators such as arachidonic acid, platelet activating factor (PAF), and prostaglandins, all demonstrated to be central in both the initiation and propagation of the inflammatory response. Activation of iPLA(2) results in release of choline lysophospholipids from endothelial cells, these metabolites may contribute to the initiation of ventricular arrhythmias following myocardial ischemia as a direct result of incorporation into the myocyte sarcolemma. This biochemical event represents a direct link between occlusion of a coronary vessel and the nearly immediate initiation of arrhythmogenesis often seen in myocardial ischemia.

Thrombogenic side-effects of recombinant factor VIIa after use in coronary artery bypass surgery.

Recombinant activated factor VII (rFVIIa) has been used 'off licence' to successfully treat bleeding and reduce transfusion requirements in complex cardiac surgery. However; concerns over thrombogenic side-effects have limited but not excluded its use in patients undergoing coronary artery bypass surgery (CABG). We present two cases of CABG (one 'on pump' and one 'off pump') which were complicated by intraoperative aortic dissection and severe bleeding. In both cases the bleeding was successfully treated with rFVIIa. However the first case suffered from severe postoperative arrhythmias, myocardial infarction, cardiac arrest and worsening left ventricular dysfunction, suggesting graft patency may have been impaired, whereas the second case remained symptom-free suggesting graft patency was unaffected by the use of rFVIIa. If rFVIIa is needed to treat bleeding during CABG surgery, it may be more appropriate to administer smaller, repeated doses to minimize the risk of thrombosis and early graft failure.

Impact of the European Working Time Directive on the training of paediatric anaesthetists.

The European Working Time Directive and the New Deal have decreased the number of hours worked by anaesthetic trainees. We implemented the Working Time Directive in May 2004 and evaluated the effect of its implementation on training. During two 6-month periods, one before and one after the change, we determined the number of operating lists undertaken by each Specialist Registrar in Anaesthesia. After implementation of the Working Time Directive, the mean number of lists performed by Specialist Registrars decreased from 24 to 21 lists per registrar per month, a 13% decrease. Exposure to subspecialty lists was the same in both periods, but this was at the expense of general lists and those in remote locations. We conclude that the Working Time Directive has had a measurable impact on the training of paediatric anaesthetists, but that the significance of this change for clinical practice has not yet been measured.

Neuropathic pain following multilevel surgery in children with cerebral palsy: a case series and review.

Six children with cerebral palsy are presented who developed neuropathic pain following multilevel orthopedic surgery. This significant complication is previously unreported. The diagnosis and treatment options are reviewed. Treatment should be kept as simple and noninvasive as possible, and aim to enable physiotherapy to continue. Early recognition and interdisciplinary treatment is important to prevent a downward spiral of increasing pain and decreased function. A good outcome in respect of improved pain and functioning was achieved in five of these six children. It is our opinion that this complication should form part of informed consent for multilevel surgery and that anesthetists should be aware of this complication when managing postoperative pain control.

Improving tuberculosis therapy completion after jail: translation of research to practice.

Inmates have high rates of latent tuberculosis infection (LTBI), but inmates are often released early and do not complete therapy in the community. This study evaluated the translation of results from a randomized trial to improve therapy completion to usual care in a county jail using Rogers' Diffusion of Innovation theory. Inmates who received a single education in the randomized trial in 1998-1999 (study group) were compared to inmates educated by Jail Discharge Planners in 2002-2003 (usual care group). Outcomes were rates of completion of a visit to the TB clinic and completion of therapy. Subjects in the usual care group were significantly less likely to go to clinic in the 30-day period after release (relative risk 0.84, 95% confidence interval 0.75-0.95). The transfer of an educational protocol did not achieve results seen under study conditions, mostly because of implementation fidelity. The educational session in the usual care period for 81.0% of inmates took 5 min, as compared to 10-15 min during the randomized trial. Differences in personnel administering the protocol, training, high turnover and time available may also account for lower rates seen. Practical clinical trials should focus on the context of care as well as the intervention and should have participation by those who will be implementing results.