Deaths in Incorrectly Identified Low-Surgical-Risk Patients.

BACKGROUND: The American Society of Anesthesiologists (ASA) physical classification system was developed for assessing anaesthetic risk, but is often also used to estimate surgical death risk. Patients with low ASA grades (ASA 1 or 2) are expected to have better surgical outcomes than patients with higher ASA grades (ASA ≥ 4). This study examined the course to death in patients classified as ASA 1 or 2 was examined, to investigate possible factors in unexpected deaths, in addition to evaluating the use of ASA grades by clinicians. METHODS: Patient data from the national surgical mortality audit of Australian hospitals were examined. The patient group was listed as ASA grade 1 or 2 by surgeons. Patients over 60 or under 20 were excluded in the final analysis, as were cases from New South Wales due to data not being available. A total of 357 cases were examined. Assessor summaries of the cases were examined, and ASA score reassessed to determine accuracy. RESULTS: More than 95% (n = 339) of cases listed as ASA 1 or 2 were found to have an incorrectly low grade, with 17.6% (n = 63) of cases listed as "expected" deaths. CONCLUSION: ASA grades appear to be misunderstood in the reporting of patient surgical risk. Many patient summaries list patients with severe systemic disease or expected deaths as ASA 1 or 2, contrary to the intended use of this classification system. Improved education on the use of the ASA grading system would be beneficial to clinicians.

Subtle temperature-induced changes in small molecule conformer dynamics - observed and quantified by NOE spectroscopy.

NOE-distance relationships are shown to be sufficiently accurate to monitor very small changes in conformer populations in response to temperature (<0.5%/10 °C) - in good agreement with Boltzmann-predictions, illustrating the effectiveness of accurate NOE-distance measurements in obtaining high quality dynamics as well as structural information for small molecules.

Investigating public perceptions of carbon dioxide utilisation (CDU) technology: a mixed methods study.

Carbon dioxide utilisation (CDU) technologies hold promise for helping to limit atmospheric releases of CO2 while generating saleable products. However, while there is growing investment in the research and development required to bring CDU to the market, to date there has been very little systematic research into public perceptions of the technology. The current research reports upon the findings of a series of six qualitative focus groups (and an associated questionnaire) held with members of the UK public in order to discuss the perceived benefits and risks of CDU technology. The findings reveal that public awareness of CDU is currently very low and that there is a desire to learn more about the technology. While our participants did, on average, appear to develop an overall positive attitude towards CDU, this attitude was tentative and was associated with a number of caveats. The implications for the findings in terms of the development of communication and broader strategies of public engagements are outlined.

Performance of the LHCb RICH detector at the LHC.

The LHCb experiment has been taking data at the Large Hadron Collider (LHC) at CERN since the end of 2009. One of its key detector components is the Ring-Imaging Cherenkov (RICH) system. This provides charged particle identification over a wide momentum range, from 2-100 GeV/c. The operation and control, software, and online monitoring of the RICH system are described. The particle identification performance is presented, as measured using data from the LHC. Excellent separation of hadronic particle types (π, K, p) is achieved.

Defining the cognitive phenotype of autism.

Although much progress has been made in determining the cognitive profile of strengths and weaknesses that characterise individuals with autism spectrum disorders (ASDs), there remain a number of outstanding questions. These include how universal strengths and deficits are; whether cognitive subgroups exist; and how cognition is associated with core autistic behaviours, as well as associated psychopathology. Several methodological factors have contributed to these limitations in our knowledge, including: small sample sizes, a focus on single domains of cognition, and an absence of comprehensive behavioural phenotypic information. To attempt to overcome some of these limitations, we assessed a wide range of cognitive domains in a large sample (N=100) of 14- to 16-year-old adolescents with ASDs who had been rigorously behaviourally characterised. In this review, we will use examples of some initial findings in the domains of perceptual processing, emotion processing and memory, both to outline different approaches we have taken to data analysis and to highlight the considerable challenges to better defining the cognitive phenotype(s) of ASDs. Enhanced knowledge of the cognitive phenotype may contribute to our understanding of the complex links between genes, brain and behaviour, as well as inform approaches to remediation.

Acute sport-related stressors, coping, and emotion among professional rugby union players during training and matches.

The purpose of this study was to examine acute sport-related stressors, coping, and emotion among a sample of professional rugby union players during training and matches. Five professional rugby union players maintained diaries for 31 days. The diaries consisted of a stressor checklist and an open-ended stressor response section, an open-ended coping response section, a Likert-type evaluation of coping effectiveness, a best-of-fit emotional response section, and a Likert-type evaluation of emotional intensity. Six out of the 10 stressors reported had a higher mean frequency in training compared with matches. Blocking was the most frequently cited coping strategy on match days, whereas increased concentration was the most frequently cited coping strategy on training days. Coping effectiveness was significantly higher during training compared with matches. Additionally, higher levels of emotional intensity were significantly associated with lower levels of coping effectiveness. Significant individual differences were found for both coping effectiveness and emotional intensity.

Urinary metabolites and health effects in workers exposed chronically to chloronitrobenzene.

For workers exposed to 4-chloronitrobenzene (4CNB), the major metabolites were determined. Urine were analysed before and after acid hydrolysis to qualify the free and conjugated metabolites of 4CNB. Three conjugated metabolites were identified in exposed workers: the mercapturic acid N-acetyl-S-(4-nitrophenyl)-L-cysteine (NANPC) was the only metabolite detected in non-hydrolysed urine, and accounted for approximately 51% of the total metabolites detected. The two remaining metabolites 4-chloroaniline (4CA) and 2-chloro-5-nitrophenol (CNP) were identified as cleavage products in hydrolysed urine, and accounted for approximately 18 and 30% of the total metabolites detected, respectively. No metabolites were found in factory controls within the limits of quantitation (LOQ) of the assay. There is a moderate correlation between NANPC and both 4CA and CNP. The correlation between 4CA and CNP is minor. The correlation between the total metabolites and both 4CA and CNP are good. The best correlation was found between the total metabolites and NANPC. There is a moderate inverse correlation between age and the creatinine levels. The raw metabolite levels CNP and NANPC decrease with age. The urine metabolites increase and correlate significantly with the creatinine levels. 4CA, NANPC and the total metabolite levels correlate with the haemoglobin adduct levels. NANPC is the most appropriate biomarker in the urine for a recent absorbed dose of 4CNB, since NANPC reflects the levels of 4CA and CNP and is the most prevalent metabolite detected in all the exposed workers.

A randomised trial of two methods of issuing prenatal test results: the ARIA (Amniocentesis Results: Investigation of Anxiety) trial.

BACKGROUND: Many pregnant women experience anxiety while waiting for the results of diagnostic tests. Policies and practices intended to reduce this anxiety require evaluation. OBJECTIVES: To test the following two hypotheses: * That giving amniocentesis results out on a fixed date alters maternal anxiety during the waiting period, compared with a policy of telling parents that the result will be issued "when available" (i.e. variable date). * That issuing early results from a rapid molecular test alters maternal anxiety during the waiting period, compared with not receiving any results prior to the karyotype. The effects of the two interventions on anxiety 1 month after receiving karyotype results were also examined. DESIGN: A multicentre, randomised, controlled, open fixed sample, 2 x 2 factorial design trial, with equal randomisation. SETTING: The prenatal diagnosis clinics in 12 hospitals in England offering amniocentesis as a diagnostic test for Down's syndrome. SAMPLE: Two hundred and twenty-six women who had had an amniocentesis were randomised between June 2002 and July 2004. Eight women with abnormal results or test failure were excluded post-randomisation. INTERVENTIONS: Issuing karyotype results on a prespecified fixed date, rather than issuing them as soon as they became available. Issuing karyotype results alone, or subsequent to issuing results from a rapid molecular test for the most common chromosomal abnormalities. MAIN OUTCOME MEASURES: Average anxiety during the waiting period, calculated using daily scores from the short version of the Spielberger State-Trait Anxiety Inventory (STAI). Anxiety 1 month after receiving karyotype results, measured using the short form STAI. RESULTS: Issuing early results from a partial but rapid test reduced maternal anxiety by a clinically significant amount during the waiting period (mean daily score 12.5 versus 14.8; scale score difference -2.36, 95% CI -1.2, -3.6), compared with receiving only the full karyotype results. There was no evidence that giving out karyotype results on a fixed or on a variable date altered maternal anxiety during the waiting period (mean daily score 13.2 versus 14.2; scale score difference -1.02, 95% CI -2.2, 0.2). One month after receiving normal karyotype results, anxiety was low in all groups, but women who had been given rapid test results tended to be more anxious than those who had not (mean single day score 9.2 versus 8.3; mean scale score difference 0.95, 95% CI -0.03, 1.9). This small to moderate effect did not reach conventional levels of statistical significance. CONCLUSIONS: Rapid testing was a beneficial addition to karyotyping, at least in the short term. This does not necessarily imply that early results would be preferred to comprehensive ones if women had to choose between them. Because there are no clear advantages in anxiety terms of issuing karyotype results as soon as they become available, or on a fixed date, women could be given a choice between them.

Modeling of a human circadian mutation yields insights into clock regulation by PER2.

Circadian rhythms are endogenous oscillations of physiological and behavioral phenomena with period length of approximately 24 hr. A mutation in human Period 2 (hPER2), a gene crucial for resetting the central clock in response to light, is associated with familial advanced sleep phase syndrome (FASPS), an autosomal dominant condition with early morning awakening and early sleep times. The FASPS hPER2 S662G mutation resulted in PER2 being hypophosphorylated by casein kinase I (CKI) in vitro. We generated transgenic mice carrying the FASPS hPER2 S662G mutation and faithfully recapitulate the human phenotype. We show that phosphorylation at S662 leads to increased PER2 transcription and suggest that phosphorylation at another site leads to PER2 degradation. Altering CKIdelta dosage modulates the S662 phenotype demonstrating that CKIdelta can regulate period through PER2 in vivo. Modeling a naturally occurring human variant in mice has yielded novel insights into PER2 regulation.

Novel insights from genetic and molecular characterization of the human clock.

Biological rhythms govern the ebb and flow of life on planet Earth. Animals have an internal timekeeping mechanism that precisely regulates 24-hour rhythms of body function and behavior and synchronizes them to the day/night cycle. Circadian pacemakers trigger behavioral and physiological processes that dictate our daily rhythms. Despite the importance of the circadian clock to all aspects of our physiology and behavior, the opportunity to probe the human circadian clock only recently became possible with the recognition of Mendelian circadian variants in people (familial advanced sleep phase syndrome, FASPS). We have now cloned several genes and identified mutations causing FASPS. Study of these genes and the proteins they encode and engineering of the human mutations into mouse models are allowing study of this fascinating phenotype and yielding novel insights into circadian regulation in humans. Ultimately, such work will allow us to understand the similarities and differences between the human clock and those of model organisms. In addition, recent studies have also linked disruption of the circadian clock with numerous ailments, including cancer, cardiovascular diseases, asthma, and learning disorders. Thus, studying the molecular mechanism of human circadian rhythmicity will have an enormous impact on our understanding of human health and disease. It should also lead to new strategies for pharmacological manipulation of the human clock to improve the treatment of jet lag, various clock-related sleep and psychiatric disorders, and other human diseases.

Urinary metabolites of workers exposed to nitrotoluenes.

Nitrotoluenes are important intermediates in the chemical industry. 2,6-Dinitrotoluene (26DNT), 2,4-dinitrotoluene (24DNT) and 2-nitrotoluene (2NT) are carcinogenic in animals and possibly carcinogenic in humans. Thus, it is important to develop methods to biomonitor workers exposed to such chemicals. The authors have monitored the air and urine metabolite levels for a group of workers in China exposed to 24DNT, 26DNT, 2NT and 4-nitrotoluene (4NT). The metabolites 2,4-dinitrobenzylalcohol (24DNBAlc), 2-amino-4-nitrobenzoic acid (2A4NBA), 4-amino-2-nitrobenzoic acid (4A2NBA) and 2,4-dinitrobenzoic acid (24DNBA) resulting from exposure to 24DNT were found in 89, 88, 91 and 78% of the exposed workers, respectively. The metabolites 2,6-dinitrobenzylalcohol (26DNBAlc) and 2,6-dinitrobenzoic acid resulting from 26DNT exposure were found in 99 and 86% of the exposed workers, respectively. Quantitatively, 2A4NBA, 4A2NBA and 26DNBAlc were the major metabolites. The nitrobenzoic acids were the major metabolites resulting from exposure to 2NT and 4NT and were present in 96 and 73% of the exposed workers, respectively. Air concentrations of DNT and 2NT did not correlate with the levels of metabolites in the urine. In conclusion, the dinitrobenzyl alcohols and aminonitrobenzoic acids determined in the urine provided a good marker for recently absorbed dose and were intrinsically related to the bioactivation and detoxification pathways of DNT. Air measurements were not a good measure to predict internal exposure.

Validation of the Welch Allyn 'Vital Signs' blood pressure measurement device in pregnancy and pre-eclampsia.

OBJECTIVE: To establish the accuracy the Welch Allyn 'Vital Signs' blood pressure monitor in pregnancy and pre-eclampsia according to a modified British Hypertension Society protocol. DESIGN: Prospective observational study. SETTING: Maternity Unit/Obstetric Ward, Guy's and St Thomas' Hospital, London, UK. POPULATION: Forty-three pregnant women of whom 12 had pre-eclampsia. METHODS: Nine sequential same-arm measurements were taken from each woman by two trained observers, alternating between a mercury sphygmomanometer and the device. The last seven readings were analysed according to the British Hypertension Society protocol. The accuracy of the device was determined using the grading scale indicated by the British Hypertension Society protocol (grade A/B = pass, grade C/D = fail). MAIN OUTCOME MEASURES: Grading criteria of the British Hypertension Society Protocol. RESULTS: The Welch Allyn 'Vital Signs' monitor achieved a grade A for both systolic and diastolic pressures in pregnant women who did not have pre-eclampsia. In those women with pre-eclampsia, it achieved a grade D and B for systolic and diastolic pressures, respectively. The mean differences between the observers and the device in women without pre-eclampsia were -2.6 (6.4) and -1.5 (7.2) mmHg for systolic and diastolic pressures [and in pre-eclamptic women -7.8 (6.3) and -5.5 (6.5)mmHg]. It therefore fulfils criteria set by the Association for the Advancement of Medical Instrumentation (mean <5 mmHg and standard deviation <8 mmHg) in pregnancy, but not in pre-eclampsia. CONCLUSION: This is the first automated device suitable for robust clinical use that can be recommended for use in pregnancy. However, it should be borne in mind that-similar to other devices--it significantly under--recorded readings obtained in pre-eclamptic women.

A controlled study of cognitive deficits in children with chronic Lyme disease.

Although neurologic Lyme disease is known to cause cognitive dysfunction in adults, little is known about its long-term sequelae in children. Twenty children with a history of new-onset cognitive complaints after Lyme disease were compared with 20 matched healthy control subjects. Each child was assessed with measures of cognition and psychopathology. Children with Lyme disease had significantly more cognitive and psychiatric disturbances. Cognitive deficits were still found after controlling for anxiety, depression, and fatigue. Lyme disease in children may be accompanied by long-term neuropsychiatric disturbances, resulting in psychosocial and academic impairments. Areas for further study are discussed.

Validation of the Welch Allyn 'Vital Signs' oscillometric blood pressure monitor.

This study has determined the accuracy of the Welch Allyn 'Vital Signs' blood pressure (BP) monitoring device in an adult population, according to the criteria of the British Hypertension Society (British Hypertension Society, 1993). Validation was also classified by the American 'Association for the Advancement of Medical Instrumentation' (AAMI). The Welch Allyn 'Vital Signs' monitor achieved a BHS grade A for both systolic and diastolic BP. It also met the criteria for the AAMI protocol. The mean differences between trained observers using a mercury sphygmomanometer and the device were -1 +/- 5 mm Hg for systolic BP and -3 +/- 4 mm Hg for diastolic BP. The Welch Allyn 'Vital Signs' monitor can be recommended for clinical use in the adult population. This is one of the first oscillometric monitors designed for routine use in a hospital environment that has been found to provide an accurate assessment of BP by accepted validation procedures.

An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome.

Familial advanced sleep phase syndrome (FASPS) is an autosomal dominant circadian rhythm variant; affected individuals are "morning larks" with a 4-hour advance of the sleep, temperature, and melatonin rhythms. Here we report localization of the FASPS gene near the telomere of chromosome 2q. A strong candidate gene (hPer2), a human homolog of the period gene in Drosophila, maps to the same locus. Affected individuals have a serine to glycine mutation within the casein kinase Iepsilon (CKIepsilon) binding region of hPER2, which causes hypophosphorylation by CKIepsilon in vitro. Thus, a variant in human sleep behavior can be attributed to a missense mutation in a clock component, hPER2, which alters the circadian period.

A validation of the Mobil O Graph (version 12) ambulatory blood pressure monitor.

OBJECTIVE: To assess the clinical accuracy of the Mobil O Graph (version 12) ambulatory blood pressure monitor in an adult population. METHODS: The accuracy of the device was assessed by predefined criteria (British Hypertension Society, BHS) in 85 subjects recruited from the patients and staff in a teaching hospital. A series of same-arm sequential blood pressure measurements were taken: first two observers taking simultaneous mercury readings, followed by a reading with the Mobil O Graph ambulatory monitor. A total of seven readings were taken from each subject in the sitting position. The data were then analysed according to the BHS protocol and the criteria of the Association for the Advancement of Medical Instrumentation (AAMI). RESULTS: The Mobil O Graph ambulatory monitor fulfilled the criteria of the BHS protocol, achieving a grade B for systolic blood pressure (SBP) and a grade A for diastolic blood pressure (DBP). The mean differences were -2+/-8 mmHg for SBP and -2+/-7 mmHg for DBP. The device therefore also passed the AAMI standard (the mean to be within 5+/-8 mmHg). CONCLUSION: The Mobil O Graph ambulatory monitor performed in a satisfactory manner according to the BHS and the AAMI criteria and can therefore be recommended for clinical use in the general population.

Coexistent coronary and cerebrovascular disease: results of simultaneous surgical management in specific patient groups.

OBJECTIVE: Results of synchronous combined revascularization were examined in specific patient groups with coexistent coronary and cerebrovascular diseases. METHODS: Between 1.1.1980 and 31.12.1998, 408 patients underwent a synchronous combined carotid endarterectomy (CEA)+myocardial revascularization (CABG). In 259 (63.5%) patients, carotid disease was asymptomatic. Remaining patients presented with a previous stroke (n=35) or a transient ischemic episode (TIA) (n=114). In 245 (60%) patients, carotid stenosis was bilateral (Group A: bilateral > or =80% stenosis, Group B: contralateral occlusion, Group C: contralateral subcritical disease). A synchronous ipsilateral CEA+CABG was performed in all patients with an unilateral disease (n=163) and also in all Group B (n=33) and Group C (n=142) patients with bilateral disease. A simultaneous bilateral CEA+CABG was performed in 12 high risk Group A patients. Remaining Group A patients (n=58), initially underwent an ipsilateral CEA for most dominant lesion+CABG, soon followed by the contralateral CEA. Results were examined in above specific patient Groups. RESULTS: Overall combined hospital mortality from stroke+myocardial infarction was 2.45%. No independent predictor of stroke was identified. In general, initial prophylactic CEA, subdued the risk of subsequent strokes for 7-8yr. Predictors of a late stroke were: progression of bilateral (P=0.007) and intracranial (P=0.04) cerebrovascular disease. Highest risk of an early stroke was recorded in Group A patients. A composite high risk group of patients with multiple risk factors (n=155) demonstrated a higher risk of both early and late strokes, as compared to the remaining patients (n=253) (P<0.04). Observed risk of early and late strokes, in specific patient groups was lower than standard predictions. CONCLUSIONS: A regular use of combined approach was justified in the above patient groups.

Iaterogenic injuries during retrograde delivery of cardioplegia.

During last eight years, retrograde delivery of cardioplegia was used on a regular basis, utilizing a DLP INC (Grand Rapids, MI) or a Research Medical INC (Salt Lake City UT) delivery systems, in almost an equal number of patients. This method resulted in a high pressure rupture, or perforation of the coronary sinus, its radicals or the right ventricle (RV) in 0.06% (5/7886) of patients. Intraoperative diagnosis of these injuries were confirmed on abnormal haemodynamic tracings and trans oesophageal echocardiography (TOE), and appearance of cardiac contusion or leakage of cardioplegia. A low incidence of these iaterogenic injuries may be attributed to: (1) a regular use of this method and (2) use of TOE guided manipulations in select high risk and reoperative patients. Repair of these injuries, as described, resulted in salvage of 4/5 (80%) patients.