Report on the CCT Supplementary comparison S2 on thermal conductivity measurements of insulating materials by guarded hot plate.

Seven National Metrology Institutes (NMIs) from France, United States, United Kingdom, Russia, Mexico, China and Germany participated in an inter-laboratory comparison on thermal conductivity measurements by the Guarded Hot Plate method. This action was part of a series of supplementary inter-laboratory comparisons (including infrared spectral emittance and thermal diffusivity) sponsored by the Consultative Committee on Thermometry (CCT) Task Group on Thermophysical Quantities (TG-ThQ). The objective of this collaborative work was to strengthen the consistency of thermal conductivity measurements carried out worldwide on low conductive materials. Measurements were conducted successively by all participants on the same sets of specimens of insulating materials (mineral wool and expanded polystyrene) at temperatures ranging from 10 °C to 40 °C, according to the International Standard ISO 8302. This protocol aimed to minimize issues of material variability by circulating the same pairs of specimens among the laboratories following the strict format of a round-robin test program. More than 120 data points (combinations of material, thickness and temperature) were compared. 92 % of the data points were in agreement, with differences to weighted mean values less than the expanded uncertainties calculated from the individual NMI uncertainties and uncertainties related to the comparison process.

Calibration of thermocouple-based scanning thermal microscope in active mode (2ω method).

We present a procedure dedicated to the calibration of a scanning thermal microscopy probe operated in an active mode and a modulated regime especially for the measurement of solid material thermal conductivities. The probe used is a microthermocouple wire mounted on a quartz tuning fork. Measurements on reference samples are performed successively in vacuum and ambient air conditions revealing a clear difference in the dependence of the thermal interaction between the probe and the sample on the sample properties. Analytical modeling based on the resolution of the heat equation in the wire probe and a description of the thermal interaction using a network of thermal conductances are used to fit experimental data and analyze this difference. We have experimentally verified that the effective thermal contact radius of the probe tip depends on the sample thermal conductivity in ambient conditions, whereas it remains constant in vacuum. We have defined the measurement range of the technique based on the decrease in the probe sensitivity at high thermal conductivities. Considering the experimental noise of our electrical device, it is shown that the maximum measurable value of thermal conductivity is near 23 W m-1 K-1 in vacuum and 37 W m-1 K-1 in ambient air conditions. Moreover, the lowest uncertainties are obtained for thermal conductivities below 5 W m-1 K-1 typically.

Development of an air flow calorimeter prototype for the measurement of thermal power released by large radioactive waste packages.

The estimation and control of the thermal power released by the radioactive waste packages are a key parameter in the management of radioactive waste geological repository sites. In the framework of the European project "Metrology for decommissioning nuclear facilities," the French National Agency of Radioactive Waste Management (ANDRA) collaborates with Laboratoire National de Métrologie et D'essais in order to measure the thermal power up to 500 W of typical real size radioactive waste packages (of at least 0.175 m3) with an uncertainty better than 5% by using a measurement method traceable to the international system of units. One of the selected metrological approaches is based on the principles of air flow calorimetry. This paper describes in detail the development of the air flow calorimeter prototype as well as the design of a radioactive waste package simulator used for its calibration. Results obtained from the calibration of the calorimeter and from the determination of thermal powers are presented here with an investigation of the measurement uncertainties.

[Neurodevelopmental outcome of very low birth weight infants born at the Perinatal Centre in Ulm, Germany]. / Entwicklungsneurologische Nachuntersuchung von sehr unreifen Frühgeborenen im Perinatalzentrum Ulm.

BACKGROUND: Since 2006 an assessment of the neurodevelopmental outcome of very low birth weight infants (VLBWI) at a corrected age of 2 years is mandatory for every perinatal centre in Germany. The aim of our study was to check how complete these assessments were performed in our population of infants born at our perinatal centre and receiving treatment within our local neonatal network. Furthermore, the data obtained will be used for prenatal consultations. Another objective was to identify risk factors for adverse neurodevelopmental outcomes. METHODS: All VLBWI were invited for a follow-up exam using the Bayley Scales of Infant Development II (BSID-II) or III (BSID-III), or Griffiths Mental Developmental Scales) at 2 years corrected age. The results of children assessed by other institutions were collected. RESULTS: 142 (69.3%) of the 205 VLBWI, born and finally discharged alive at the perinatal centre in Ulm were assessed at a median (minimum - maximum) corrected age of 23 (18-27) months. The BSID-II Psychomotor Development Index (PDI) 91 was (< 50-128) (n=115), the BSID-II Mental Development Index (MDI) was 87 (< 50-134) (n=96), BSID-III MDI 95 (60-112) (n=29) and the Griffiths Score was 93 (67-140) (n=17). Severe disability was diagnosed in 36 (25.4%) of the children studied. Gestational age and higher grade intraventricular haemorrhage were associated independently with severe disability. CONCLUSIONS: It is very difficult to achieve a high rate of follow-up examinations in preterm infants <1,500 g in a neonatal network. Severe impairment in VLBWI is not rare. Improving neurodevelopmental outcome remains a challenge.

[Maintenance of health and relief for caregivers of elderly with dementia by using "initial case management": experiences from the Lighthouse Project on Dementia, Ulm, ULTDEM-study]. / Gesunderhaltung und Entlastung pflegender Angehöriger von Demenzkranken durch ein "initiales Case Management": Erfahrungen aus dem Ulmer Leuchtturmprojekt Demenz (ULTDEM-Studie).

BACKGROUND: When facing the well-known demographic development with an increasing number of people suffering from dementia, there is a need of programmes to support nursing relatives and care at home. Many support services have been established in the past few years but they are rarely used by the relatives and the patients. The purpose of the Lighthouse Project Ulm (ULTDEM Study) was to prove the effectiveness of a single advisory approach in order to provide support services after care level classification and to relieve the burden placed on relatives caring for family members suffering from dementia ("initial case management"). METHODS: The ULTDEM Study is a prospective, open, randomized, controlled, interventional study with different parallel outcome measures (burden of caring, quality of life and mood). After the randomization, the interventional group was given comprehensive, individual advice about available treatment possibilities for dementia patients. Control group participants received standard treatment. Inclusion criteria were application of a care level (0 or 1) as well as dementia diagnosis. All participants (patients/relatives) underwent an initial and a 6 month comprehensive assessment. RESULTS: Our results show that a single advisory approach does not lead to a significant difference in outcome measures in interventional and control groups. Those tendencies described have to be interpreted as clinically not relevant. Although utilization of support services increases, it remains similar in both study groups. A confirmatory interpretation has not been possible due to a lack of adjustment to the findings regarding multiple testing and an insufficient degree of recruitment. Possible causes will be discussed such as premature intervention during the course of the disease, a lack of intervention blinding, recruitment bias and lack of an influence on adherence with regard to the use of support services. IMPLICATIONS: The study demonstrates that there is a substantial information deficit for persons affected by dementia and their relatives. Innovative ways still have to be developed to ensure that this information actually reaches the target audience.

Chromosome 4q31 locus in COPD is also associated with lung cancer.

Chronic obstructive pulmonary disease (COPD) is the single greatest risk factor for lung cancer in smokers and is found in 50-90% of lung cancer cases. The link between COPD and lung cancer may stem in part from the matrix remodelling and repair processes underlying COPD, and the development of epithelial-mesenchymal transition (EMT) that underlies lung carcinogenesis. The Hedgehog-interacting protein (HHIP), which mediates the epithelial response (EMT) to smoking, has been implicated in COPD and lung cancer. Recent genome-wide and candidate gene studies of COPD implicate genetic variants on the chromosomal 4q31 (HHIP/glycophorin A (GYPA)) locus. In a case-control study of smokers with normal lung function, COPD and lung cancer (subphenotyped for COPD), we show the GG genotype of the rs 1489759 HHIP single-nucleotide polymorphism (SNP) and the CC genotype of the rs 2202507 GYPA SNP confers a "protective" effect on COPD (OR 0.59, p = 0.006 for HHIP and OR = 0.65, p = 0.006 for GYPA) and lung cancer (OR = 0.70 (p = 0.05) for HHIP and OR 0.70 (p = 0.02) for GYPA). This study suggests that, in smokers, genetic variants of the 4q31 locus conferring a protective effect for COPD are also protective in lung cancer. We conclude that genetic susceptibility to lung cancer includes COPD-related gene variants.

A gene-based risk score for lung cancer susceptibility in smokers and ex-smokers.

BACKGROUND: Epidemiological and family studies suggest that lung cancer results from the combined effects of age, smoking and genetic factors. Chronic obstructive pulmonary disease (COPD) is also an independent risk factor for lung cancer and coexists in 40-60% of lung cancer cases. METHODS: In a two-stage case-control association study, genetic markers associated with either susceptibility or protection against lung cancer were identified. In a test cohort of 439 Caucasian smokers or ex-smokers, consisting of healthy smokers and lung cancer cases, 157 candidate single nucleotide polymorphisms (SNPs) were screened. From this, 30 SNPs were identified, the genotypes (codominant or recessive model) of which were associated with either the healthy smokers (protective) or lung cancer (susceptibility) phenotype. After genotyping of this 30-SNP panel in a second validation cohort of 491 subjects and using the same protective and susceptibility genotypes from our test cohort, a 20-SNP panel was selected on the basis of independent univariate analyses. RESULTS: Using multivariate logistic regression, including the 20 SNPs, it was also found that age, history of COPD, family history of lung cancer and gender were significantly and independently associated with lung cancer. CONCLUSIONS: When numeric scores were assigned to both the SNP and demographic data, and sequentially combined by a simple algorithm in a risk model, the composite score was found to be linearly related to lung cancer risk with a bimodal distribution. Genetic data may therefore be combined with other risk variables from smokers or ex-smokers to identify individuals who are most susceptible to developing lung cancer.

Inactivation and elimination of human enteric viruses by Pacific oysters.

AIMS: To investigate the comparative elimination of three different human enterically transmitted viruses [i.e. hepatitis A virus (HAV), norovirus (NoV) and poliovirus (PV)] and inactivation of HAV and PV by Pacific oysters. METHODS AND RESULTS: New Zealand grown Pacific oysters (Crassostrea gigas) were allowed to bioaccumulate HAV, NoV and PV. Samples of oyster gut, faeces and pseudofaeces were then analysed by using real-time RT-PCR to determine the amount of viral RNA and cell culture methods to identify changes in the number of plaque forming units. The results suggest that the majority of the PV present in the oyster gut and oyster faeces is noninfectious, while in contrast, most of the HAV detected in the oyster gut are infectious. Depuration experiments identified a large drop in the count of PV in the gut over a 23-h cleansing period, whereas the levels of HAV and NoV did not significantly decrease. CONCLUSIONS: Human enterically transmitted viruses are eliminated and inactivated at different rates by Pacific oysters. SIGNIFICANCE AND IMPACT OF STUDY: The research presented in this article has implications for risk management techniques that are used to improve the removal of infectious human enteric viruses from bivalve molluscs.

Localization of norovirus and poliovirus in Pacific oysters.

AIMS: To examine the uptake and tissue distribution of norovirus (NoV) and poliovirus (PV) experimentally bioaccumulated in feeding Pacific oysters (Crassostrea gigas). METHODS AND RESULTS: Pacific oysters were allowed to bioaccumulated either PV or NoV under tidally synchronized feeding conditions in laboratory tanks. Oysters were then either fixed and paraffin wax embedded prior to localizing virus within tissues by immunohistochemistry (IHC), or they were dissected into digestive tract (stomach, intestine and digestive diverticula), gill and labial palp tissues, and the viral load determined by quantitative RT-PCR. Both PV and NoV immunoreactivities were predominantly found in the lumen and within cells of the digestive tract tissues; however, PV was also found within cells of nondigestive tract tissues, and in the gills and labial palp. Quantitative RT-PCR of tissue extracts corroborate the immunohistochemical data in that the major site for virus localization is the gut, but significant amounts of viral RNA were identified in the gills and labial palp. CONCLUSIONS: The human enteric viruses, PV and NoV, are readily bioaccumulated by feeding Pacific oysters and that some of the virus is internalized within cells of both digestive and nondigestive tissues. SIGNIFICANCE AND IMPACT OF THE STUDY: Oysters that have been virally contaminated even after depuration (cleaning) in uncontaminated seawater could pose a human health risk if consumed.

Lung cancer gene associated with COPD: triple whammy or possible confounding effect?

Recently, several large genome-wide association studies have identified a putative "lung cancer" locus in the nicotinic acetylcholine receptor subunit genes (nAChR) on 15q25. However, these findings may be confounded by the presence of chronic obstructive pulmonary disease (COPD), which is also strongly associated with smoking exposure and lung cancer. This is likely as the prevalence of COPD in lung cancer cohorts is as much as two-fold greater than that reported in smoking control populations (50 versus 20%). The present authors compared the genotype frequencies of the most strongly associated single nucleotide polymorphism (rs16969968) in the alpha5 subunit of the nAChR gene cluster between three matched smoking cohorts. The AA genotype was found to be more frequent and was seen in 437 (16%) lung cancer cases and 445 (14%) COPD cases compared with 475 (9%) healthy smoking controls. More importantly, when 429 lung cancer cases were divided according to spirometry results (performed within 3 months of diagnosis, prior to surgery and in the absence of effusions or collapse), the AA genotype was present in 19 and 11% of cases with and without COPD, respectively. These findings suggest that the association between the alpha5 subunit nicotinic acetylcholine receptor single nucleotide polymorphism and lung cancer may, in part, be confounded by chronic obstructive pulmonary disease.

Antidepressant effects of augmentative transcranial magnetic stimulation: randomised multicentre trial.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a new treatment option for depression. Previous studies were performed with low sample sizes in single centres and reported heterogeneous results. AIMS: To investigate the efficacy of rTMS as augmentative treatment in depression. METHOD: In a randomised, double-blind, sham-controlled multicentre trial 127 patients with moderate to severe depressive episodes were randomly assigned to real or sham stimulation for 3 weeks in addition to simultaneously initiated antidepressant medication. RESULTS: We found no difference in the responder rates of the real and the sham treatment groups (31% in each) or in the decrease of the scores on the depression rating scales. CONCLUSIONS: The data do not support previous reports from smaller samples indicating an augmenting or accelerating antidepressant effect of rTMS. Further exploration of the possible efficacy of other stimulation protocols or within selected sub-populations of patients is necessary.

Type II diabetes mellitus and impaired glucose regulation in Caucasian children and adolescents with obesity living in Germany.

BACKGROUND: Recent studies reported an increased prevalence of type II diabetes mellitus in obese children and adolescents, especially in specific ethnic subgroups. The aim of this study was to determine the prevalence of type II diabetes mellitus and impaired glucose regulation in a large group of Caucasian children and adolescents with obesity living in Germany. PATIENTS AND METHODS: A total of 520 subjects (237 boys, 283 girls) (mean age: 14.0+/-2.0 y (range 8.9-20.4 y)) with a BMI>97th percentile, BMI-SDS: 2.7+/-0.5 (range 1.9-4.6), who were consecutively admitted to an in-patient obesity unit participated in the study. A 2-h oral glucose tolerance test (1.75 mg of glucose per kilogram of body weight) was performed before entering a weight-loss program and capillary blood glucose concentrations were measured. Patients were categorized into normal glucose regulation, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes. In addition, fasting venous blood was taken to determine the circulating insulin, C-peptide and lipids. Insulin resistance was estimated by homeostatic model assessment. RESULTS: Type II diabetes was present in 1.5% (n=8) of the patients, two patients were admitted with already diagnosed type II diabetes and six patients were identified with yet unknown diabetes. IFG was detected in 3.7% (n=19) and IGT in 2.1% (n=11) of the patients. All together, in 6.7% (n=35) (95% confidence interval: 4.7-9.2%) of the patients, impaired glucose regulation (IFG, IGT) or diabetes was identified. These patients had a higher BMI-SDS, higher levels of fasting insulin and C-peptide and a higher insulin resistance index than the patients with normal glucose regulation. Risk factors for the occurrence of impaired glucose regulation were a BMI-SDS>2.5 as well as a positive parents' history for diabetes. CONCLUSIONS: This is the first report on the prevalence of type II diabetes in a large cohort of Caucasian children and adolescents with obesity living in Europe. Impaired glucose regulation and type II diabetes were present in a substantial proportion of the patients studied. Screening for diabetes in severely obese children and adolescents (BMI-SDS>2.5) is therefore recommended. Patients identified with impaired glucose regulation need specific treatment programs in order to prevent progression to diabetes.

Tribenzo-18-crown-6 acetonitrile disolvate.

Tribenzo-18-crown-6 binds two acetonitrile ligands, i.e. C(24)H(24)O(6) x 2C(2)H(3)N, one to each face of the crown ring. The crown conformation is relatively low in energy, but does not appear optimized for cation binding. Few significant intermolecular interactions are observed.

Small molecule somatostatin receptor subtype-2 antagonists.

The first potent small molecule sst2 antagonists are reported. Altering known sst2 agonist molecules yielded compounds with high sst2 binding affinity and full antagonist activity. Compound 7a, for example, displaced somatostatin binding to the sst2 receptor with an IC(50)=2.9 nM and antagonized somatostatin action with an IC(50)=29nM.

Structural analysis of a functional DIAP1 fragment bound to grim and hid peptides.

The inhibitor of apoptosis protein DIAP1 suppresses apoptosis in Drosophila, with the second BIR domain (BIR2) playing an important role. Three proteins, Hid, Grim, and Reaper, promote apoptosis, in part by binding to DIAP1 through their conserved N-terminal sequences. The crystal structures of DIAP1-BIR2 by itself and in complex with the N-terminal peptides from Hid and Grim reveal that these peptides bind a surface groove on DIAP1, with the first four amino acids mimicking the binding of the Smac tetrapeptide to XIAP. The next 3 residues also contribute to binding through hydrophobic interactions. Interestingly, peptide binding induces the formation of an additional alpha helix in DIAP1. Our study reveals the structural conservation and diversity necessary for the binding of IAPs by the Drosophila Hid/Grim/Reaper and the mammalian Smac proteins.