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Differences in cell sizes used in beekeeping are often proposed to be one of the factors regulating Varroa population growth. An in-depth research of the relationship between these factors was undertaken using the ‘Carnica Singer population’. The acceptance of foundation with a specific cell size appears to underlay selection. Smaller cell size (4.9 mm) foundation/combs reduce the Varroa population growth compared to 5.5 mm. This reduction is also dependent on the presence of the VSH (= Varroa sensitive hygienic) – behaviour trait in the worker bee population within the colony. Smaller cell size combs in combination with breeding for the ‘right genetics’ (cell size and VSH) can be one part of an integrated sustainable treatment concept for Varroa control.

•Breast cancer risk analyzed after reestimation of radiation exposure at infant age.•Risk estimates, after new dose calculations, increased compared to previous analyses.•Models of genomic instability were developed and applied to the cohort data.•A radiation-induced transition towards genomic instability was highly significant.

This review describes the PARTRAC suite of comprehensive Monte Carlo simulation tools for calculations of track structures of a variety of ionizing radiation qualities and their biological effects. A multi-scale target model characterizes essential structures of the whole genomic DNA within human fibroblasts and lymphocytes in atomic resolution. Calculation methods and essential results are recapitulated regarding the physical, physico-chemical and chemical stage of track structure development of radiation damage induction. Recent model extension towards DNA repair processes extends the time dimension by about 12 orders of magnitude and paves the way for superior predictions of radiation risks.

Recent publications on the integration of radiobiological effects in the two-step clonal expansion (TSCE) model of carcinogenesis and applications to radioepidemiological data are reviewed and updated. First, a model version with radiation-induced genomic instability was shown to be a possible explanation for the age dependence of the radiation-induced cancer mortality in the Techa River Cohort. Second, it is demonstrated that inclusion of a bystander effect with a dose threshold allows an improved description of the lung cancer mortality risk for the Mayak workers cohort due to incorporation of plutonium. The threshold for the annual lung dose is estimated to 12 (90%CI: 4; 14)mGy/year. This threshold applies to the initiation of preneoplastic cells and to hyperplastic growth. There is, however, no evidence for a threshold for the effects of gamma radiation. Third, models with radiation-induced cell inactivation tend to predict lower cancer risks among the atomic bomb survivors with exposure at young age than conventionally used empirical models. Also, risks after exposures with doses in the order of 100mGy are predicted to be higher in models with low-dose hypersensitivity than in models with conventional cell survival curves. In the reviewed literature, models of carcinogenesis tend to describe radioepidemiological data better than conventionally used empirical models.

Breast cancer incidence among 17,158 female Swedish hemangioma patients was analyzed with empirical excess relative risk models and with a biologically-based model of carcinogenesis. The patients were treated in infancy mainly by external application of radium-226. The mean and median absorbed doses to the breast were 0.29 and 0.04Gy, and a total of 678 breast cancer cases have been observed. Both models agree very well in the risk estimates with an excess relative risk and excess absolute risk at the age of 50 years, about the mean age of breast cancer incidence, of 0.25Gy−1(95% CI 0.14; 0.37) and 30.7 (105BYRGy)−1 (95% CI 16.9; 42.8), respectively. Models incorporating effects of radiation-induced genomic instability were developed and applied to the hemangioma cohort. The biologically-based description of the radiation risk was significantly improved with a model of genomic instability at an early stage of carcinogenesis.

26 April 2006 marks the 20th anniversary of the Chernobyl accident. On this occasion, the World Health Organization (WHO), within the UN Chernobyl Forum initiative, convened an Expert Group to evaluate the health impacts of Chernobyl. This paper summarises the findings relating to cancer. A dramatic increase in the incidence of thyroid cancer has been observed among those exposed to radioactive iodines in childhood and adolescence in the most contaminated territories. Iodine deficiency may have increased the risk of developing thyroid cancer following exposure to radioactive iodines, while prolonged stable iodine supplementation in the years after exposure may reduce this risk. Although increases in rates of other cancers have been reported, much of these increases appear to be due to other factors, including improvements in registration, reporting and diagnosis. Studies are few, however, and have methodological limitations. Further, because most radiation-related solid cancers continue to occur decades after exposure and because only 20 years have passed since the accident, it is too early to evaluate the full radiological impact of the accident. Apart from the large increase in thyroid cancer incidence in young people, there are at present no clearly demonstrated radiation-related increases in cancer risk. This should not, however, be interpreted to mean that no increase has in fact occurred: based on the experience of other populations exposed to ionising radiation, a small increase in the relative risk of cancer is expected, even at the low to moderate doses received. Although it is expected that epidemiological studies will have difficulty identifying such a risk, it may nevertheless translate into a substantial number of radiation-related cancer cases in the future, given the very large number of individuals exposed.

A new concept for continuous measurements on microchips is presented. A PMMA polymethylmethacrylate based capillary electrophoresis chip with integrated conductivity detection is combined with a second chip, which undertakes the task of fluid handling and electrical connections. The combination of electrokinetic and hydrodynamic flows allows long-term continuous stable analyses with good reproducibilities of migration time and peak heights of analytes. The two-chip system is characterized in terms of stability and reproducibility of separation and detection of small ions. Relative standard deviations of <1 and 3 respectively for retention times and peak heights during long-term measurements can be achieved. The new system combines simple handling and automated analysis without the need for refilling, cleaning or removal of the separation chip after one or several measurements.

Within the track structure code PARTRAC, DNA strand break induction by direct and indirect radiation action was calculated for the E. coli catabolite gene activator protein (CAP) DNA complex with 125I located at the position of the H 5 atom of the cytosine near the center. The shape of the resulting DNA fragment size distributions was found to be in reasonable agreement with corresponding experimental results. However, the calculated yield was considerably lower than the measured one. To study possible reasons for this, recently published experimental data on DNA strand breaks in a 41-mer synthetic oligodeoxynucleotide (oligoDNA) with incorporated 125I were analyzed aiming at an evaluation of the non-radiation-related component due to the neutralization of the initially highly charged 125mTe daughter ion. This was done by assuming that the differences between simulated radiation-induced distribution and the measured total fragment size distributions were due to the neutralization process. The neutralization effect defined in this way was found to dominate the strand breakage frequency within a range of 5–7 base pairs around the 125I decay site on both strands. After implementing this neutralization effect derived from the oligoDNA analysis into the PARTRAC simulation for the CAP-DNA complex, the agreement of the calculated DNA fragment distributions with the corresponding experimental data was considerably improved. The results indicate that DNA conformation may be explored by incorporation of 125I into the DNA, measurement of fragment size distributions, and comparison with simulation calculation for various hypothetical DNA models.

Lung cancer incidence among the atomic bomb survivors from Hiroshima and Nagasaki was analysed with the two-step clonal expansion (TSCE) model of carcinogenesis. For the baseline incidence, a new set of model parameters is introduced, which can be determined with a higher precision than the parameter sets previously used. The effect of temporal changes in the smoking behaviour on the lung cancer incidence is modelled by allowing initiation, inactivation and division rates of intermediate cells to depend on the year of birth. The TSCE model is further developed by implementing low-dose hypersensitivity in the survival of lung epithelial cells. According to the model fit to the data, the acute gamma exposure of the atomic bomb survivors does not only result in the conventional initiating effect, but also in a promoting effect for lung cancer. Compared to the model in which radiation acts merely on initiation, the new model is in better agreement with the age-at-exposure dependence in the data, and it does not predict an unexpected increase of the excess relative risk (ERR) at 40 years after exposure. According to the new model, the ERR at low doses increases non-linearly with dose, especially during the first 10 years after exposure to older persons.

Increased radioresistance for exposures to low-LET radiation with doses exceeding a few hundred milligray is a well established fact for cell inactivation in vitro and in vivo. Cell inactivation and the subsequent replacement by intermediate cells is a possible mechanism for a radiation-induced increase of the number of intermediate cells in carcinogenesis in an irradiated organ. In the present work this mechanism has been implemented in the two-step clonal expansion model for carcinogenesis in the lung in addition to the conventionally assumed radiation-induced initiation. Compared with the original TSCE model, the new model has the same number of parameters and fits the lung cancer incidence data for the atomic bomb survivors slightly better. The resulting estimate of the lung cancer risk after low-dose exposures of persons with an age of 20 or 40 years is similar in the two models; however, it is higher by about an order of magnitude in the new model for an age-at-exposure of 60 years. Age-at-exposure dependence and risk estimates at low dose turn out to be closer to best estimates obtained with a constant-excess-relative-risk model for different age-at-exposure subgroups.

Two methods of retrospective dosimetry for external exposures are reviewed. First, electron paramagnetic resonance (EPR or electron spin resonance, ESR) with teeth has its strengths in the determination of individual exposures, acute or protracted, that may have occurred several decades ago. The method is best studied for photon fields. The current detection limit is 100 mGy. Due to a higher sensitivity to photons with energies in the range of 30-100 keV, information of this spectral component is necessary to achieve a high accuracy. Second, luminescence methods including thermoluminescence (TL) and optical stimulated luminescence (OSL) have their strengths in determining absorbed dose in bricks or porcelain. A detection limit in the order of several tens of mGy is achieved if the mineral fraction of the brick is well suited for luminescence measurements. By measuring depth profiles of absorbed dose in a brick or height profiles over a wall, information on effective source geometry and photon energy may be obtained. Future perspectives of the methods include: (i) conversion of dose quantities measured as absorbed dose in enamel or bricks to absorbed dose in air and human organ doses; (ii) EPR measurements with milk teeth; (iii) in situ EPR measurements of teeth in the human mouth; and (iv) exploration of new materials for the luminescence method, especially those which are worn by people allowing to come closer to an individual dosimetry.

The goal of this study was to compare stapes prostheses of different materials with respect to their surface structures and to discuss their suitability for their use in stapes surgery.

A tailor-designed acoustic trap has been built and tested as a sample handling device for use in laser spectroscopy. It is based on a piezoelectric vibrator that sets up a standing acoustic wave with several nodes into which liquid or solid samples may be placed and held in a levitated position. The usefulness of such a system to hold samples without the need for sample cells was demonstrated for various experiments involving direct spectroscopic measurements on the suspended sample. Changes in the UV spectrum of bromocresol green dye during a simple pH titration on a drop of the levitated solution were followed by dual dye laser spectrometry. A chemical actinometry spectrochemistry experiment was conducted on Aberchrome 540 fulgide dissolved in DMSO in the levitated state by following changes in the molecular structure of the fulgide by Raman spectroscopy. Finally, crystallization experiments were carried out on droplets and bubbles of tris-(hydroxymethyl)-amino-methane and l-cystein.

Introduction:AV nodal re-entry tachycardia (AVNRT) is the most common type of paroxysmal supraventricular tachycardia. At present, the underlying etiology of AVNRT is unclear.Hypothesis:In a genome-wide association study (GWAS), we aimed to identify common genetic variants associated with AVNRT.Methods:We performed a GWAS meta-analysis of Danish patients diagnosed with AVNRT verified by invasive electrophysiological study. An Icelandic population of AVNRT patients was used for replication. We performed conditional analysis by adjusting our analysis for atrial fibrillation (AF) genetics and transcriptome-wide analyses (TWAS) to assess associations between gene expression and AVNRT. Electrophysiological consequences were investigated in CRISPR-Cas9 modified zebrafish.Results:A total of 1,515 AVNRT patients and 38,428 controls were available for meta-analysis. Two genetic loci associated with AVNRT; at chromosome 5q35.1, close to the NKX2-5gene (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.38-1.58, P = 2.6 х 10-13), and at 14q11.2 in the MYH6gene (OR 1.26, 95% CI 1.18-1.34, P = 2.3 х 10-8). We found similar effect sizes and direction of effect for both loci in the Icelandic AVNRT cohort. Using conditional analyses, we found that these loci were associated with AVNRT independent of AF. Analyses of loss of Nkx2-5 zebrafish showed no difference with regards to electrocardiographic parameters and transmission electron microscopy of atrial tissue compared with wildtype.Conclusion:This is, to our knowledge, the first GWAS on AVNRT. We identified two genetic loci that associated with AVNRT.

Abstract: The Monte Carlo track structure code PARTRAC has been further improved by implementing electron scattering cross-sections for liquid water and by explicitly modelling the interaction of water radicals with DNA. The model of the genome inside a human cell nucleus in its interphase is based on the atomic coordinates of the DNA double helix with an additional volume for the water shell. The DNA helix is wound around histone complexes, and these nucleosomes are folded into chromatin fibres and further to fibre loops, which are interconnected to build chromosomes with a territorial organisation. Simulations have been performed for the irradiation of human fibroblast cells with carbon K and aluminium K ultrasoft x-rays, 220 kVp x-rays and 60Co γ-rays. The ratio single-strand breaks to double-strand breaks (ssb/dsb) for both types of ultrasoft x-rays is lower than for γ-rays by a factor of 2. The contributions of direct and indirect effects to strand break induction are almost independent of photon energy. Strand break patterns from indirect effects reflect differences in the susceptibility of the DNA helix to OH• attack inside the chromatin fibre. Distributions of small DNA fragments (<3 kbp) are determined by the chromatin fibre structure irrespective of whether direct or indirect effects are causing the breaks. In the calculated fragment size distributions for larger DNA fragments (>30 kbp), a substantial deviation from random breakage is found only for carbon K irradiation, and is attributed to its inhomogeneous dose distribution inside the cell nucleus. For the other radiation qualities, the results for larger fragments can be approximated by random breakage distributions calculated for a yield of dsb which is about 10% lower than the average for the whole genome. The excess of DNA fragments detected experimentally in the 8–300 kbp region after x-ray irradiation is not seen in our simulation results.

The organ doses for γ rays from typical environmental sources were determined with Monte Carlo calculations using anthropomorphic phantoms having different body sizes. It has been suggested that body weight is the predominant factor influencing organ doses for environmental γ rays, regardless of sex and age. A weight function expressing organ doses for environmental γ rays was introduced. This function fitted well with the organ doses calculated using the different phantoms. The function coefficients were determined mathematically with the least squares method. On the assumption that this function was applicable to organ doses for human bodies with diverse characteristics, the variances in organ doses due to race, sex, age and difference in body weight of adults were investigated. The variations of organ doses due to race and sex were not significant. Differences in body weight were found to alter organ doses by a maximum of 10% for γ rays over 100 keV, and 20% for low-energy γ rays. The doses for organs located deep inside a body, such as ovaries, differed between a newborn baby and an adult by a maximum factor of 2 to 3. For y rays over 100 keV, the variation was within a factor of 2 for all organs. The organ doses for adolescents more than 12 years agreed within 15% with those of the average adult.

• OBJECTIVE. —To describe a family in whom fluorescence in situ hybridization allowed for accurate diagnosis of Miller-Dieker syndrome in an at-risk pregnancy and determination of parental carrier status. DESIGN. —Restrospective case analysis and application of a new molecular tool to evaluate the family. SETTING. —Health maintenance organization. The family was followed up by the Departments of Medical Genetics, Pediatrics, and Obstetrics and Gynecology, Kaiser Permanente Medical Center, Panorama City, Calif. PARTICIPANTS. —Members of a single family. INTERVENTIONS. —Clinical evaluation and neuroimaging studies of the proband. Prenatal diagnosis via ultrasonography and amniocentesis. Chromosomal evaluation of the couple and their offspring. In situ hybridization studies in both parents and an affected fetus. MEASUREMENTS/MAIN RESULTS. —We describe a family in whom fluorescence in situ hybridization detected a submicroscopic deletion of the Miller-Dieker syndrome critical region 17p13.3 arising from a cryptic translocation in one of the parents. The proband was determined at birth owing to the presence of multiple congenital anomalies, including low birth weight, microcephaly, agenesis of the corpus callosum, lissencephaly, cerebral atrophy, unilateral ptosis, polydactyly, and omphalocele. High-resolution chromosome-banding analysis findings were normal in the parents and proband, who died at age 4 years. There were four subsequent pregnancies: two ended in first-trimester spontaneous abortion, and in the other two, large omphaloceles were detected in fetuses at 15 and 13 weeks' gestation. Both pregnancies were terminated. Fluorescence in situ hybridization probes for 17p13.3 had become available before the most recent pregnancy and were used to study parental and fetal cells. As a result, a balanced cryptic translocation between chromosome 17 and chromosome 19 was identified in the father: 46,XY,t(17;19)(p13.3;q13.33). An unbalanced form of the translocation, involving a deletion of 17p13.3, was detected with fluorescence in situ hybridization in the fetus. This finding was in accordance with a clinical diagnosis of Miller-Dieker syndrome. CONCLUSIONS. —Molecular cytogenetic technology should be used in cases of suspected Miller-Dieker syndrome when high-resolution cytogenetic analysis fails to detect del(17) (p13.3). Positive findings should be followed up with parental studies. In addition, omphalocele should be included among the list of malformations that make up the Miller-Dieker syndrome.(AJDC. 1993;147:1291-1294)

The described investigations are focused on peroxides occurring as products in atmospheric chemical processes, namely, hydrogen peroxide, methylhydroperoxide, hydroxymethylhydroperoxide, bis-(hydroxymethyl)peroxide, 1-hydroxyethylhydroperoxide, bis-(hydroxyethyl)peroxide, and hydroxymethylmethylperoxide. The compounds are identified and determined through the position and intensity of their characteristic O–O stretching bands in the range between 767 and 878 cm−1. Time-resolved Raman spectroscopy of peroxide solutions permits the in situinvestigation of pathways and kinetics of reactions between peroxides and aldehydes.

Photolysis of alkyl-substituted 2-(2-oxa-3-butenyl)cyclopent-2-enones gives rise to derivatives of bicyclo[2.1.1]hexanes (“rule of five” product), and α-methylenecyclopentanones(photo-Claisen rearrangement). Methyl substitution remote from the bond forming centers produces a regioselective reaction yielding only the “rule of five” product.

Since the reactor accident of Chernobyl, cesium depth profiles and nuclide-specific kerma rates in air have been determined for various grassland sites in south Bavaria and in Ukraine. The sites are described by soil characteristics, annual precipitation, distance from release point, mode of deposition, and activity per unit area. The effects of surface roughness and migration of cesium into the soil on the kerma rate in air over grasslands was determined by two methods. The kerma rates in air obtained by the evaluations of in situ gamma-ray spectrometry results and of measured activity distributions in the soil showed only negligible differences for the observation period of 6 years after deposition. For the sites in Ukraine the kerma rate in air per activity per unit area was found to be systematically 40% higher than in Bavaria. The results from Bavaria on the attenuation of the kerma rate and a data set, including experiences from the weapons test fallout, are analytically approximated as a function of time up to 25 years after deposition.

Reagents and preparative methods for the synthesis of oligonucleotides are the topic of this paper. The preparation of some highly reactive five-membered cyclic phosphorylating reagents, the 2-chloro-2-oxo-phospholes 3a-e, is described, as well as their behaviour as phosphorylating reagents. In addition, the 1,1-dianisyl-2,2,2-trichloroethyl (DATE) protective group, and the oxidation of P(III)-compounds by oxaziridines, including the destructively stereoselective oxidation of stereoisomeric P(III) compounds are presented.

Background: The effect of prior hypoglycaemia on cognitive function in type 1 diabetes is an important unresolved clinical question. In this systematic review, we aimed to summarize the studies exploring the impact of prior hypoglycaemia on any aspect of cognitive function in type 1 diabetes.Methods: We used a multidatabase search platform Healthcare Database Advanced Search to search Medline, PubMed, EMBASE, EMCARE, CINAHL, PsycINFO, BNI, HMIC, and AMED from inception until 1 May 2019. We included studies on type 1 diabetes of any age. The outcome measure was any aspect of cognitive function.Results: The 62 studies identified were grouped as severe hypoglycaemia (SH) in childhood (⩽18 years) and adult-onset (>18 years) diabetes, nonsevere hypoglycaemia (NSH) and nocturnal hypoglycaemia (NH). SH in early childhood-onset diabetes, especially seizures and coma, was associated with poorer memory (verbal and visuospatial), as well as verbal intelligence. Among adult-onset diabetes, SH was associated with poorer cognitive performance in the older age (>55 years) group only. Early versuslate exposure to SH had a significant association with cognitive dysfunction (CD). NSH and NH did not have any significant association with CD, while impaired awareness of hypoglycaemia was associated with poorer memory and cognitive-processing speeds.Conclusion: The effect of SH on cognitive function is age dependent. Exposure to SH in early childhood (<10 years) and older age groups (>55 years) was associated with a moderate effect on the decrease in cognitive function in type 1 diabetes [PROSPERO ID: CRD42019141321].

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An overview of existing approaches on assessing and evaluating the radiological situation in the late phase of a nuclear accident is given in this paper. Special attention is paid to the weak points of existing approaches and to problems to be solved in the future. Assessment of the radiological situation can be based on both monitoring data and model predictions. Approaches have been developed for many years in both categories and have meanwhile reached some kind of maturity and also operational applicability. Nevertheless, some areas exist where significant improvements could be achieved in the near future, e.g. by combining monitoring data and model predictions, by improving the modelling of urban areas or by improving existing radioecological models.

Clinical, neurophysiological and neuroimaging data suggest that chronic tinnitus resembles neuropsychiatric syndromes characterised by focal brain activation. Low frequency repetitive transcranial magnetic stimulation rTMS has been proposed as an efficient method in treating brain hyperexcitability disorders. In one patient suffering from chronic tinnitus, 18Fdeoxyglucose PET revealed increased metabolic activity in a circumscript area of the left primary auditory cortex PAC. The effect of MRI and PET guided neuronavigated IHz rTMS of this area was evaluated in a singleblind, shamcontrolled, crossover manner, followed by a 4week open treatment. Following active stimulation there was a remarkable effect, enduring several weeks, on tinnitus sensation, which was paralleled by altered cortical excitability. These findings suggest that neuronavigated rTMS of increased PAC activity might offer a new option for treating auditory phantom perceptions like chronic tinnitus. NeuroReport14977–980 © 2003 Lippincott Williams & Wilkins.

A letter to the editor is presented in response to articles published in the July 25, 2013 issue of the journal, which was devoted to the topic of architectural education in Great Britain.

A letter to the editor about the Royal Institute of British Architects (RIBA) Education Trust Fund is presented.