Applying a mechanistic model to predict interacting effects of chemical exposure and food availability on fish populations.

The potential environmental impacts of chemical exposures on wildlife are of growing concern. Freshwater ecosystems are vulnerable to chemical effects and wildlife populations, including fish, can be exposed to concentrations known to cause adverse effects at the individual level. Wild fish populations are also often subjected to numerous other stressors simultaneously which in temperate climates often include sustained periods of food limitation. The potential interactive effects of chemical exposures and food limitation on fish populations are however difficult to establish in the field. Mechanistic modelling approaches can be employed to help predict how the physiological effects of chemicals and food limitation on individuals may translate to population-level effects. Here an energy budget-individual-based model was developed and the control (no chemical) model was validated for the three-spined stickleback. Findings from two endocrine active chemical (EAC) case studies, (ethinyloestradiol and trenbolone) were then used to investigate how effects on individual fecundity translated into predicted population-level effects for environmentally relevant exposures. The cumulative effects of chemical exposure and food limitation were included in these analyses. Results show that effects of each EAC on the population were dependent on energy availability, and effects on population abundance were exacerbated by food limitation. Findings suggest that chemical effects and density dependent food competition interact to determine population responses to chemical exposures. Our study illustrates how mechanistic modelling approaches might usefully be applied to account for specific chemical effects, energy budgets and density-dependent competition, to provide a more integrated evaluation of population outcomes in chemical risk assessments.

Progress on the BL2 beam measurement of the neutron lifetime.

A precise value of the neutron lifetime is important in several areas of physics, including determinations of the quark-mixing matrix element │V ud│, related tests of the Standard Model, and predictions of light element abundances in Big Bang Nucleosynthesis models. We report the progress on a new measurement of the neutron lifetime utilizing the cold neutron beam technique. Several experimental improvements in both neutron and proton counting that have been developed over the last decade are presented. This new effort should yield a final uncertainty on the lifetime of 1 s with an improved understanding of the systematic effects.

HbA1c for Diabetes Screening in Acute Coronary Syndrome: time for a reappraisal of the guidelines?

OBJECTIVE: Diabetes is highly prevalent in individuals with acute coronary syndrome (ACS). Current NICE guidelines recommend diabetes screening of hyperglycaemic patients using a fasting plasma glucose after 4 days from admission. In 2012 the World Health Organisation (WHO) approved the use of HbA1c in the diagnosis and targeted screening for type 2 diabetes. We introduced a service improvement project using HbA1c for diabetes screening in patients with no previous diagnosis of diabetes admitted with ACS regardless of glycaemic state. METHOD: An initial retrospective audit utilised 21 months of data from the MINAP database to identify patients meeting current NICE criteria for diabetes screening. A prospective service improvement project was undertaken over a 4 month period using HbA1c as a universal screening test to categorise ACS patients based on WHO criteria. RESULTS: The retrospective audit identified 93 of 420 (22%) patients with pre-existing diabetes and 8 of the remaining 327 (2.4%) were hyperglycaemic, thus meeting NICE criteria for diabetes screening. In the service improvement project 2/49 patients (4%) met NICE criteria for diabetes screening. Twenty six of these 49 patients had a HbA1c test on admission and 17/26 (65.4%) were classified as probable diabetes or high risk. CONCLUSION: A significant proportion of ACS patients have diabetes, which may be undetected by current NICE criteria. Universal HbA1c testing offers utility as a simple and effective screening test for diabetes in the ACS population.

Associations of subjective vitality with DNA damage, cardiovascular risk factors and physical performance.

AIM: To examine associations of DNA damage, cardiovascular risk factors and physical performance with vitality, in middle-aged men. We also sought to elucidate underlying factors of physical performance by comparing physical performance parameters to DNA damage parameters and cardiovascular risk factors. METHODS: We studied 2487 participants from the Metropolit cohort of 11 532 men born in 1953 in the Copenhagen Metropolitan area. The vitality level was estimated using the SF-36 vitality scale. Cardiovascular risk factors were determined by body mass index (BMI), and haematological biochemistry tests obtained from non-fasting participants. DNA damage parameters were measured in peripheral blood mononuclear cells (PBMCs) from as many participants as possible from a representative subset of 207 participants. RESULTS: Vitality was inversely associated with spontaneous DNA breaks (measured by comet assay) (P = 0.046) and BMI (P = 0.002), and positively associated with all of the physical performance parameters (all P < 0.001). Also, we found several associations between physical performance parameters and cardiovascular risk factors. In addition, the load of short telomeres was inversely associated with maximum jump force (P = 0.018), with lowered significance after exclusion of either arthritis sufferers (P = 0.035) or smokers (P = 0.031). CONCLUSION: Here, we show that self-reported vitality is associated with DNA breaks, BMI and objective (measured) physical performance in a cohort of middle-aged men. Several other associations in this study verify clinical observations in medical practice. In addition, the load of short telomeres may be linked to peak performance in certain musculoskeletal activities.

Point of care testing provides an accurate measurement of creatinine, anion gap, and osmolal gap in ex-vivo whole blood samples with nitromethane.

CONTEXT: Nitromethane interferes with Jaffé measurements of creatinine, potentially mimicking acute kidney injury. OBJECTIVES: We determined the proportional contribution of nitromethane in blood samples to creatinine measured by the Jaffé colorimetric and the point-of-care (POC) reactions and determined whether the difference can reliably estimate the concentration of nitromethane. Additionally, we determined whether the presence of nitromethane interferes with anion/osmolal gaps and ascertained the stability of nitromethane in serum after 7 days. METHODS: Nitromethane was added to whole blood from four healthy volunteers to achieve concentrations of 0, 0.25, 0.5, 1, and 2 mmol/L. The following tests were performed: creatinine (Jaffé and POC), electrolytes (associated with Jaffé and POC), osmolality and nitromethane concentration (gas chromatography [GC]). Remaining samples were refrigerated and reanalyzed using GC at 7 days. Anion and osmolal gaps were calculated. Proportional recovery and degradation of nitromethane were measured using GC. Data were analyzed for agreement with single-factor ANOVA (p = 0.05). RESULTS: Mean creatinine for POC and Jaff methods were 0.93 vs. 0.76 mg/dL, respectively. Jaff creatinine concentrations increased linearly with increasing nitromethane concentrations (R(2) = 1, p = 0.01): measured creatinine (mg/dL) = 7.1*nitromethane (mmol/L) = 0.79. POC creatinine remained unchanged across the range of nitromethane concentrations (p = 0.99). Anion and osmolal gaps also remained unchanged. Nitromethane was reliably identified in all sample concentrations using GC on Day 0. Detection of 0.25 mmol/L nitromethane was not consistently recovered on Day 7. Nitromethane degradation was most pronounced at 2 mmol/L concentrations (81% recovery). CONCLUSIONS: Nitromethane alters apparent concentration of creatinine using the Jaffé reaction in a linear fashion but not when using the POC reaction. Measured difference between Jaffé and POC creatinine may identify the presence and estimate concentration of nitromethane. Presence of nitromethane did not alter the anion or osmolal gap; thus it would not potentially interfere with the diagnosis of co-exposure to a toxic alcohol.

Quantitative X-ray microradiography for high-throughput phenotyping of osteoarthritis in mice.

OBJECTIVE: To investigate and validate digital X-ray microradiography as a novel, high-throughput and cost-effective screening approach to identify abnormal joint phenotypes in mice. METHOD: Digital X-ray microradiography was used to quantify the subchondral bone mineral content (BMC) in the medial tibial plateau. Accuracy and reproducibility of the method were determined in 22 samples from C57BL/6(B6Brd;B6Dnk;B6N-Tyr(c-Brd)) wild-type mice. The method was then validated in wild-type mice that had undergone surgical destabilisation of medial meniscus (DMM) and in a genetically modified mouse strain with an established increase in trabecular bone mass. RESULTS: The measurement of subchondral BMC by digital X-ray microradiography had a coefficient of variation of 3.6%. Digital X-ray microradiography was able to demonstrate significantly increased subchondral BMC in the medial tibial plateau of male mice 4 and 8 weeks after DMM surgery and in female mice 8 weeks after surgery. Furthermore, digital X-ray microradiography also detected the increase in subchondral BMC in a genetically modified mouse strain with high trabecular bone mass. CONCLUSION: Quantitation of subchondral BMC by digital X-ray microradiography is a rapid, sensitive and cost-effective method to identify abnormal joint phenotypes in mice of both genders at several ages.

Follow-up of adult patients with repaired esophageal atresia: how, when, and for how long?

Esophageal atresia (EA) is the most common congenital anomaly of the esophagus. With the progress of surgical and anesthetic techniques, the survival is now more than 90% and the majority of children survives and eventually reaches adulthood. However, even if the continuity of the esophagus is anatomically replaced by the surgery, there are some new pieces of evidence that suggest considerable long-term morbidity. In this paper, we will illustrate how symptomatic gastroesophageal reflux, dysphagia, and esophageal motility disturbances, as well as columnar epithelial metaplasia, are common in adults with repaired EA. The ideal follow-up for adult patients born with EA has not been clearly defined, and routine endoscopic assessment has not been widely advocated. It is well known that the patient's symptoms have a poor correlation with histological findings. However, routine follow-up may be expensive and time consuming. With the growing number of children reaching adulthood, it is now essential to know and understand the natural history of this condition to improve the management of these patients.

Novel splice variants of sFlt1 are upregulated in preeclampsia.

Soluble fms-like tyrosine kinase-1 (sFlt1) is a truncated splice variant of Flt1, which is upregulated in preeclampsia. In this study we sought to characterize the unique C-terminus of sFlt. Through bioinformatic analyses, we identified two novel sFlt1 splice variants and two previously described sFlt1 splice variants. The novel variants are identical to the previously described sFlt1_v1 through exon 13, but then diverge to unique 3' termini consisting of a novel exon 15 (sFlt1_v2 and sFlt1_v3) or an extension of exon 14 (sFlt1_v4). Quantitative PCR showed that three out of four sFlt variants were upregulated in placenta of women with preeclampsia. Mass spectrometry analysis of sFlt1 purified from placental serum confirmed the presence of sFlt1_v1 protein, and an additional variant which includes sequence derived from exon 14. siRNA experiments targeting each variant confirmed that three of the four variants contribute significantly to total sFlt1 expression by cytotrophoblasts in vitro. These findings provide evidence that human placenta expresses a family of sFlt1 splice variants, at least three of which are expressed as proteins, and which appear to be globally upregulated in preeclampsia.

The potential of financial incentives to enhance householders' kerbside recycling behaviour.

Although the successful enhancement of householders' participation in kerbside recycling schemes is essential for household waste recycling schemes to reach their desired levels of achievement, our understanding of householders' responses to the various incentives available to waste managers is incomplete. In particular, whether and how the recycling behaviour of householders may be favourably altered through imposition of financial penalties or rewards is not fully understood. Surveys of householders' attitudes in the London Borough of Havering, served by a kerbside co-mingled survival bag recycling scheme, showed they might be better encouraged to recycle more through improvements to structural and promotional aspects of the recycling scheme than through imposition of financial incentives. If financial incentives were to be imposed to enhance kerbside recycling, householders preferred: (1) rewards to penalties, and (2) community-based rewards and local taxation rebates to other or individual rewards. Given the attitudes of householders and the resources that would be needed to monitor their recycling behaviour as a basis for delivering financial incentives, it is suggested that the priority for enhancing recycling should be to make appropriate improvements in the infrastructure and support of the kerbside scheme and service.

High-dose radiotherapy in the management of chordoma and chondrosarcoma of the skull base and cervical spine: Part 1--Clinical outcomes.

AIMS: Patients with chordoma and chondrosarcoma in the skull base present a complex multidisciplinary problem. These tumours are rare and occur in difficult anatomical regions. We reviewed the local control and survival of patients treated in our centre. MATERIALS AND METHODS: Between 1996 and 2005, 12 adult cases of chordoma (nine) and chondrosarcoma (three) in the skull base or cervical spine were treated in our centre. The median follow-up is currently 38 months. One patient was treated with palliative intent. In 10 cases the prescription dose was 65 Gy in 39 fractions. The target volumes were measured, and the target maximum and minimum doses and the equivalent uniform dose (EUD) for the phase I plans were recorded. RESULTS: Local control was achieved in 11 of 12 cases. One chordoma patient failed locally, and one other died of metastatic disease despite local control. The 3- and 5-year cause-specific survival for the series was 88 and 75%, respectively. The mean phase I planning target volume (PTV) was 120.4 cm(3). The median minimum dose in the phase I PTV was 81.0%. The median EUD (expressed as a percentage of the prescribed dose) for the phase I PTV, calculated using a value for the exponent a of -15, was 98.3%. The phase I EUD was below 80% in two of the 12 cases. CONCLUSIONS: Our results confirm a need for aggressive local surgery and high-dose radiotherapy, and endorse multidisciplinary working. Although charged particle therapy is accepted as providing optimal treatment plans, in eight of our patients travel abroad would not have been feasible. This series provides encouraging results for carefully planned photon conformal radiotherapy, carried out in close collaboration with a specialist surgical team.

On the relationship between set-out rates and participation ratios as a tool for enhancement of kerbside household waste recycling.

Although the use of kerbside recycling facilities by householders is often key to the reduction of materials disposed of to landfill, the quantitative assessment of householders' recycling behaviour is problematic. This study introduces a method to diagnose recycling behaviour by assessing kerbside scheme use in terms of the set-out of recyclate containers compared to the proportion of households participating in recycling (participation ratio). Application of numerical behaviour models demonstrated that kerbside recycling in sampled regions of the UK tends to be consistent with householders using kerbside schemes more frequently than would be observed with random patterns of use that are uniform amongst all householders. When aggregated to collection rounds, householders' modal recycling behaviour tended towards either non-participation or frequent participation. We propose that initiatives to enhance kerbside recycling should employ such quantitative assessments of recycling behavioural modes to inform and guide promotional and educational strategies. A conceptual model for prioritizing campaigns to promote recycling at the kerbside on the basis of identifiable and quantifiable patterns of householder recycling behaviour is presented.

Observation of the radiative decay mode of the free neutron.

The theory of quantum electrodynamics (QED) predicts that beta decay of the neutron into a proton, electron and antineutrino should be accompanied by a continuous spectrum of soft photons. While this inner bremsstrahlung branch has been previously measured in nuclear beta and electron capture decay, it has never been observed in free neutron decay. Recently, the photon energy spectrum and branching ratio for neutron radiative decay have been calculated using two approaches: a standard QED framework and heavy baryon chiral perturbation theory (an effective theory of hadrons based on the symmetries of quantum chromodynamics). The QED calculation treats the nucleons as point-like, whereas the latter approach includes the effect of nucleon structure in a systematic way. Here we observe the radiative decay mode of free neutrons, measuring photons in coincidence with both the emitted electron and proton. We determined a branching ratio of (3.13 +/- 0.34) x 10(-3) (68 per cent level of confidence) in the energy region between 15 and 340 keV, where the uncertainty is dominated by systematic effects. The value is consistent with the predictions of both theoretical approaches; the characteristic energy spectrum of the radiated photons, which differs from the uncorrelated background spectrum, is also consistent with the calculated spectrum. This result may provide opportunities for more detailed investigations of the weak interaction processes involved in neutron beta decay.

World Year of Physics: a direct test of E=mc2.

One of the most striking predictions of Einstein's special theory of relativity is also perhaps the best known formula in all of science: E=mc(2). If this equation were found to be even slightly incorrect, the impact would be enormous--given the degree to which special relativity is woven into the theoretical fabric of modern physics and into everyday applications such as global positioning systems. Here we test this mass-energy relationship directly by combining very accurate measurements of atomic-mass difference, Delta(m), and of gamma-ray wavelengths to determine E, the nuclear binding energy, for isotopes of silicon and sulphur. Einstein's relationship is separately confirmed in two tests, which yield a combined result of 1-Delta(mc2)/E=(-1.4+/-4.4)x10(-7), indicating that it holds to a level of at least 0.00004%. To our knowledge, this is the most precise direct test of the famous equation yet described.

Body surface mapping improves early diagnosis of acute myocardial infarction in patients with chest pain and left bundle branch block.

OBJECTIVE: To test prospectively depolarisation and repolarisation body surface maps (BSMs) for mirror image reversal, which is less susceptible to artefact, in patients with acute ischaemic-type chest pain, and to compare these BSM criteria with previously published 12 lead ECG criteria. METHODS: An 80 lead portable BSM system was used to map patients presenting with acute ischaemic-type chest pain and a 12 lead ECG with left bundle branch block (LBBB). Acute myocardial infarction (AMI) was defined by serial cardiac enzymes. Each 12 lead ECG was assessed by the criteria of Sgarbossa et al and Hands et al for diagnosis of AMI. Depolarisation and repolarisation BSMs were assessed for loss of mirror image reversal of QRS with ST-T isointegral map patterns and a change in vector angle from QRS to ST-T outside 180+/-15 degrees -findings typically seen in LBBB with AMI. RESULTS: Of 56 patients with chest pain and LBBB, 18 had enzymatically confirmed AMI. Patients with loss of BSM image reversal were significantly more likely to have AMI (odds ratio 4.9, 95% confidence interval 1.5 to 16.4, p = 0.007). Loss of BSM image reversal was significantly more sensitive (67%) for AMI than either 12 lead ECG method (17%, 33%) albeit with some loss in specificity (BSM 71%, 12 lead ECG 87%, 97%). Patients with AMI compared with those without AMI had a greater mean change in vector angle outside the normal range (180+/-15 degrees ), particularly between QRS isointegral and ST60 isopotential (the potential 60 ms after the J point at each electrode site) BSMs (19 degrees v 9 degrees, p = 0.038). Loss of image reversal and QRS-ST60 vector change outside 180+/-15 degrees had 61% sensitivity and 82% specificity for AMI (odds ratio 7.0, 95% confidence interval 2.0 to 24.4, p = 0.001). CONCLUSIONS: BSM compared with the 12 lead ECG improved the early diagnosis of AMI in the presence of LBBB.

The constitutive activation of the CEF-4/9E3 chemokine gene depends on C/EBPbeta in v-src transformed chicken embryo fibroblasts.

The CEF-4/9E3 chemokine gene is expressed constitutively in chicken embryo fibroblasts (CEF) transformed by the Rous sarcoma virus (RSV). This aberrant induction is controlled at the transcriptional and post-transcriptional levels. Transcriptional activation depends on multiple elements of the CEF-4 promoter composing a Src-responsive-Unit or SRU. The SRU includes a TPA responsive element, a PRDII/kappaB domain and a CAAT box. In this report, we identify C/EBPbeta as a component of the trans-acting factor interacting with the CAAT box of the CEF-4 promoter. In addition, we show that C/EBPbeta binds to a second element located in proximity of the TRE. A mutation of this distal CAAT box impaired the activation of the CEF-4 promoter by pp60(v-src) indicating that this element is also part of the SRU. Using the RCASBP retroviral vector, we expressed a dominant negative mutant of C/EBPbeta (designated Delta184-C/EBPbeta) in RSV-transformed CEF. Delta184-C/EBPbeta decreased the accumulation of the CEF-4 mRNA and activation of the CEF-4 promoter by pp60(v-src). The induction of the Cox-2 gene (CEF-147) was also reduced by Delta184-C/EBPbeta. The effect of the dominant negative mutant was observed within 1 h of the activation of a thermolabile pp60(v-src) suggesting that C/EBPbeta is an early target of v-src transformation. The dominant negative mutant did not inhibit the transformation of CEF by RSV and in fact accentuated the transformed cell phenotype. Therefore, the activation of C/EBPbeta is important for the expression of v-src regulated genes but is not required for the in vitro transformation of CEF by pp60(v-src).

The feasibility and accuracy of the sentinel lymph node biopsy for breast carcinoma.

As the procedure of sentinel lymph node biopsy for breast cancer becomes more widely available, the practicality of it in the hands of general surgeons should be assessed. This is a study of the accuracy and use of this procedure. A prospective study was conducted at two university-affiliated teaching hospitals. Ninety-one patients with invasive breast cancer were enrolled in the study. Twelve patients were excluded from analysis. The remaining 79 patients were injected peritumorally with technetium-99m-labeled sulfur colloid and isosulfan vital blue dye. The sentinel lymph node was located and excised using a gamma probe, and the definitive breast cancer operation was completed, including an axillary dissection. Histology of the sentinel lymph node specimen was compared with that of the axilla. Sentinel lymph nodes were located in 64 (81.0%) of the 79 patients. Sentinel lymph nodes and axillary nodes were benign in 44 (68.8%) of the 64 patients; these patients could potentially have been spared the axillary dissection. Fourteen (21.9%) patients had metastatic cancer to the sentinel nodes only, and five (7.8%) patients had axillary metastasis beyond the sentinel lymph node. Among the 64 patients, there was one false negative. Sensitivity and specificity when a sentinel lymph node was found were 95.0 per cent and 100 per cent, respectively. The sentinel lymph node accurately predicted the axillary contents 98.4 per cent of the time. This study demonstrates that the sentinel lymph node can be identified and is reliable in predicting axillary node status. This study also shows that the procedure has a notable learning curve, but can be used by general surgeons with a commitment to the care of breast cancer patients.

The therapeutic use of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes.

Acute coronary syndrome (ACS) embraces the clinical diagnoses of unstable angina and non-Q-wave myocardial infarction (NON-Q-MI). Conventional treatment for these conditions with aspirin, heparin and other anti-anginal drugs has its limitations. Treatment of acute symptoms with lytic therapy has not been beneficial. A large proportion of patients in this high-risk group will eventually need revascularisation due to ongoing symptoms. Platelet aggregation plays a crucial role in the pathogenesis of ACS and ischaemic complications of coronary intervention. The glycoprotein (GP) IIb/IIIa receptor, which belongs to a family of surface receptors called integrins, is the final step in this pathway. This has led to the development and use of GP IIb/IIIa inhibitors as potential therapeutic agents. Inhibitors developed so far include abciximab, a chimeric monoclonal antibody, and more recently, novel synthetic intravenous and orally administered competitive integrin blocking agents. To date, abciximab, tirofiban and eptifibatide are commercially available for clinical use. Completed clinical trials have looked at these agents as a primary treatment and as an adjunct to intervention for ACS; they have shown improvement over existing treatments, with reductions in the incidence of death, myocardial infarction (MI), refractory ischaemia and need for urgent revascularisation. Risk of bleeding and thrombocytopenia is low, and appears to be dose related and associated with concomitant treatment with high dose heparin. Cost benefit has been proven.

Growing up in an alcoholic family system: the effect on anxiety and differentiation of self.

Adults from alcoholic families of origin were compared to persons from non-alcoholic families on differentiation of self and state and trait anxiety. Data were collected from community college students, clients in a private psychotherapy practice, and individuals attending several community-based Al-anon/Adult Children of Alcoholics (ACOA) meetings. A total of 112 volunteers met the criteria for participation in the study. Offspring from alcoholic families experienced higher levels of state and trait anxiety and lower levels of differentiation of self than offspring from non-alcoholic families.