The eye lens dose of the interventionalist: Measurement in practice.

OBJECTIVE: Early 2018, the new eye lens dose limit of 20 mSv per year for occupational exposure to ionising radiation was implemented in the European Union. Dutch guidelines state that monitoring is compulsory above an expected eye lens dose of 15 mSv/year. In this study we propose a method to investigate whether the eye lens dose of interventionalists would exceed 15 mSv/year and to determine if the eye lens dose can be derived from the regular personal dosimeter measurements. METHODS: The eye lens dose, Hp(3), of interventional radiologists (n = 2), cardiologists (n = 2) and vascular surgeons (n = 3) in the Máxima Medical Centre, The Netherlands, was measured during six months, using thermoluminescence dosimeters on the forehead. Simultaneously, the surface dose, Hp(0,07), and whole body dose, Hp(10), were measured using regular dosimeters outside the lead skirt at chest level. The dosimeters were simultaneously refreshed every four weeks. The eye lens dose was compared to both the body-worn dosimeter values. Measurements were performed in the angiography suite, Cath lab and hybrid OR. RESULTS: A clear relation was observed between the two dosimeters: Hp(3) ≈ 0,25 Hp(0,07). The extrapolated year dose for the eye lens did not exceed 15 mSv for any of the interventionalists (average 3 to 10 studies/month). CONCLUSIONS: The eye lens dose can be monitored indirectly through the regular dosimeter at chest level. Additionally, based on the measurements we conclude that all monitored interventionalists remain below the dose limit and compulsory monitoring limit for the eye lens dose.

A multiscale modelling approach to elucidate the mechanism of the oxygen evolution reaction at the hematite-water interface.

Photoelectrochemical (PEC) splitting of water to make hydrogen is a promising clean-energy technology. The oxygen evolution reaction (OER) largely determines the energy efficiency in PEC water-splitting. Hematite, which is a cheap and sustainable semiconductor material with excellent chemical properties, a favourable band gap (2.1 eV) and composed of earth abundant elements is a suitable model photoanode material for studying OER. To understand the design of energy efficient anodes, it is highly desirable to have mechanistic insight into OER at an atomistic level which can be directly connected to experimentally measured quantities. We present a multiscale computational model of OER which connects the thermodynamics and kinetics of elementary charge transfer reactions in OER to kinetics of OER at laboratory length and time scales. We couple density functional theory (DFT) and DFT based molecular dynamics (DFT-MD) simulations with solvent effects at an atomistic level with kinetic Monte Carlo (kMC) simulations at a coarse-grained level in our multiscale model. The time and applied bias potential dependent surface coverage, which are experimentally not known, and the O2 evolution rate during OER at the hematite-water interface are calculated by the multiscale model. Furthermore, the multiscale model demonstrates the effect of explicitly modelling the interaction of water with the electrode surface via direct adsorption.

Interhemispheric connectivity estimated from EEG time-correlation analysis in preterm infants with normal follow-up at age of five.

Brain connectivity is associated with axonal connections between brain structures. Our goal was to quantify the interhemispheric neuronal connectivity in healthy preterm infants by automated quantitative EEG time-correlation analysis. As with advancing postmenstrual age (PMA, gestational age + postnatal age) the neuronal connectivity between left and right hemisphere increases, we expect to observe changes in EEG time-correlation with age. Thirty-six appropriate-for-gestational age preterm infants (PMA between 27-37 weeks) and normal neurodevelopmental follow-up at 5 years of age were included. Of these, 22 infants underwent 3-8 repeated EEG recordings at weekly intervals. The reduced 10-20 EEG electrode system for newborns was used with five sets of bipolar channels: central-temporal, frontal polar-temporal, frontal polar-central, temporal-occipital and central-occipital. We performed EEG time-correlation analysis between homologous channels of the brain hemispheres to identify interhemispheric similarity in EEG signal shape. For each 8 s epoch of the EEG the time-correlation values and the corresponding lag times were calculated for homologous channels on both hemispheres. In all channels, the median correlation value decreased significantly (between -40% and -60% decrease) from 27 to 37 weeks PMA, for gestational maturation. For the postnatal maturation only the central-temporal channel showed a significantly decreasing trend. In contrast, the median lag time showed no uniform change with PMA. The decreasing median correlation values in all homologous channels indicate a decrease in similarity in signal shape with advancing PMA. This finding may reflect greater functional differentiation of cortical areas in the developing preterm brain and may be explained by the increase of complex neural networks with excitatory and inhibitory circuitries.

Functional connectivity in preterm infants derived from EEG coherence analysis.

OBJECTIVE: To quantify the neuronal connectivity in preterm infants between homologous channels of both hemispheres. METHODS: EEG coherence analysis was performed on serial EEG recordings collected from preterm infants with normal neurological follow-up. The coherence spectrum was divided in frequency bands: δnewborn(0-2 Hz), θnewborn(2-6 Hz), αnewborn(6-13 Hz), ßnewborn(13-30 Hz). Coherence values were evaluated as a function of gestational age (GA) and postnatal maturation. RESULTS: All spectra show two clear peaks in the δnewborn and θnewborn-band, corresponding to the delta and theta EEG waves observed in preterm infants. In the δnewborn-band the peak magnitude coherence decreases with GA and postnatal maturation for all channels. In the θnewborn-band, the peak magnitude coherence decreases with GA for all channels, but increases with postnatal maturation for the frontal polar channels. In the ßnewborn-band a modest magnitude coherence peak was observed in the occipital channels, which decreases with GA. CONCLUSIONS: Interhemispherical connectivity develops analogously with electrocortical maturation: signal intensities at low frequencies decrease with GA and postnatal maturation, but increase at high frequencies with postnatal maturation. In addition, peak magnitude coherence is a clear trend indicator for brain maturation. SIGNIFICANCE: Coherence analysis can aid in the clinical assessment of the functional connectivity of the infant brain with maturation.

The principles of abdominal wound closure.

BACKGROUND: Incisional hernia (IH) is a common complication of abdominal surgery. Its incidence has been reported as high as 39.9%. Many factors influence IH rates. Of these, surgical technique is the only factor directly controlled by the surgeon. There is much evidence in the literature on the optimal midline laparotomy closure technique. Despite the high level of evidence, this optimal closure technique has not met wide acceptance in the surgical community. In preparation of a clinical trial, the PRINCIPLES trial, a literature review was conducted to find the best evidence based technique for abdominal wall closure after midline laparotomy. METHODS: An Embase search was performed. Articles describing closure of the fascia after midline laparotomy by different suture techniques and/or suture materials were selected. RESULTS: Fifteen studies were identified, including five meta-analyses. Analysis of the literature showed significant lower IH rates with single layer closure, using a continuous technique with slowly absorbable suture material. No significant difference in IH incidence was found comparing slowly absorbable and non absorbable sutures. Furthermore, a suture length to wound length ratio of four or more and short stitch length significantly decreased IH rates. CONCLUSIONS: Careful analysis of the literature indicates that an evidenced based optimal midline laparotomy closure technique can be identified. This technique involves single layer closure with a running suture, using a slowly absorbable suture with a suture length to wound length ratio of four or more and a short stitch length. We adopt this technique as the PRINCIPLES technique.

Local structure of liquid carbon controls diamond nucleation.

Diamonds melt at temperatures above 4000 K. There are no measurements of the steady-state rate of the reverse process, i.e., diamond nucleation from the melt, because experiments are difficult at these extreme temperatures and pressures. Using numerical simulations, we estimate the diamond nucleation rate and find that it increases by many orders of magnitude when the pressure is increased at constant supersaturation. The reason is that by increasing the pressure the local coordination of the liquid changes from threefold to fourfold, and we show that the free-energy cost to create a diamond-liquid interface is lower in the fourfold than in the threefold liquid. We speculate that this mechanism for nucleation control is relevant for crystallization in many network-forming liquids. We conclude that homogeneous diamond nucleation is likely in carbon-rich stars and unlikely in gaseous planets.

A density functional theory based study of the microscopic structure and dynamics of aqueous HCl solutions.

The aqueous solvation of hydrochloric acid is studied using density functional theory based molecular dynamics simulations at two concentrations. The large simulation boxes that we use allow us to investigate larger-scale structures such as the water-bridged chloride ion network. We find a strong concentration dependence for almost all structural and dynamical properties. Excess protons are mostly present both as Eigen and Zundel structures, either as a direct hydronium-chloride contact-ion pair or a solvent-separated ion pair. Increasing the concentration has a detrimental effect on the natural hydrogen bonded network of water molecules. This effect is visible in our studies as a decrease in the persistence time of the solvation shells around the chloride ions. Also the number of proton hops, determined by a new and well defined identification procedure, suffers from the breakdown of the natural hydrogen bond network.

Common pathological mechanisms in mouse models for muscular dystrophies.

Duchenne/Becker and limb-girdle muscular dystrophies share clinical symptoms like muscle weakness and wasting but differ in clinical presentation and severity. To get a closer view on the differentiating molecular events responsible for the muscular dystrophies, we have carried out a comparative gene expression profiling of hindlimb muscles of the following mouse models: dystrophin-deficient (mdx, mdx(3cv)), sarcoglycan-deficient (Sgca null, Sgcb null, Sgcg null, Sgcd null), dysferlin-deficient (Dysf null, SJL(Dysf)), sarcospan-deficient (Sspn null), and wild-type (C57Bl/6, C57Bl/10) mice. The expression profiles clearly discriminated between severely affected (dystrophinopathies and sarcoglycanopathies) and mildly or nonaffected models (dysferlinopathies, sarcospan-deficiency, wild-type). Dystrophin-deficient and sarcoglycan-deficient profiles were remarkably similar, sharing inflammatory and structural remodeling processes. These processes were also ongoing in dysferlin-deficient animals, albeit at lower levels, in agreement with the later age of onset of this muscular dystrophy. The inflammatory proteins Spp1 and S100a9 were up-regulated in all models, including sarcospan-deficient mice, which points, for the first time, at a subtle phenotype for Sspn null mice. In conclusion, we identified biomarker genes for which expression correlates with the severity of the disease, which can be used for monitoring disease progression. This comparative study is an integrating step toward the development of an expression profiling-based diagnostic approach for muscular dystrophies in humans.

Density functional theory based molecular-dynamics study of aqueous iodide solvation.

We study the solvation of iodide in water using density functional theory based molecular-dynamics simulations. Detailed analysis of the structural and dynamical properties of the first solvation shell is presented, showing a disruptive influence of the ion on the local water structure. Iodide-water hydrogen bonding is weak, compared to water-water hydrogen bonds. This effective repulsive ion-water interaction leads to the formation of a quite unstructured solvation shell. The dynamics of water molecules surrounding the iodide is relatively fast. The intramolecular structural and electronical properties of water molecules around the ion are not affected.

Muscle regeneration in dystrophin-deficient mdx mice studied by gene expression profiling.

BACKGROUND: Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is lethal. In contrast, dystrophin-deficient mdx mice recover due to effective regeneration of affected muscle tissue. To characterize the molecular processes associated with regeneration, we compared gene expression levels in hindlimb muscle tissue of mdx and control mice at 9 timepoints, ranging from 1-20 weeks of age. RESULTS: Out of 7776 genes, 1735 were differentially expressed between mdx and control muscle at at least one timepoint (p < 0.05 after Bonferroni correction). We found that genes coding for components of the dystrophin-associated glycoprotein complex are generally downregulated in the mdx mouse. Based on functional characteristics such as membrane localization, signal transduction, and transcriptional activation, 166 differentially expressed genes with possible functions in regeneration were analyzed in more detail. The majority of these genes peak at the age of 8 weeks, where the regeneration activity is maximal. The following pathways are activated, as shown by upregulation of multiple members per signalling pathway: the Notch-Delta pathway that plays a role in the activation of satellite cells, and the Bmp15 and Neuregulin 3 signalling pathways that may regulate proliferation and differentiation of satellite cells. In DMD patients, only few of the identified regeneration-associated genes were found activated, indicating less efficient regeneration processes in humans. CONCLUSION: Based on the observed expression profiles, we describe a model for muscle regeneration in mdx mice, which may provide new leads for development of DMD therapies based on the improvement of muscle regeneration efficacy.

Density functional theory based molecular-dynamics study of aqueous fluoride solvation.

We use density functional theory based molecular-dynamics simulations to study the aqueous solvation of the fluoride anion. Our studies are focused on the first solvation shell and have resulted in detailed information on its structural and dynamical properties. The fluoride ion leads to the formation of a rigid solvation shell, qualitatively consistent with simulation and experimental studies, classifying fluoride as a "structure making" particle. However, quantitatively we find the solvation shell to be less structured and more mobile than predicted from empirical force-field simulation. The influence on the intramolecular electronical and structural properties of water is minimal, as observed for other halogens. We propose two distinct mechanisms for the exchange of bulk and first solvation shell water molecules.

Unification of the hole transport in polymeric field-effect transistors and light-emitting diodes.

A systematic study of the hole mobility in hole-only diodes and field-effect transistors based on poly(2-methoxy-5-(3('),7(')-dimethyloctyloxy)-p-phenylene vinylene) and on amorphous poly(3-hexyl thiophene) has been performed as a function of temperature and applied bias. The experimental hole mobilities extracted from both types of devices, although based on a single polymeric semiconductor, can differ by 3 orders of magnitude. We demonstrate that this apparent discrepancy originates from the strong dependence of the hole mobility on the charge carrier density in disordered semiconducting polymers.

Solution-processed ambipolar organic field-effect transistors and inverters.

There is ample evidence that organic field-effect transistors have reached a stage where they can be industrialized, analogous to standard metal oxide semiconductor (MOS) transistors. Monocrystalline silicon technology is largely based on complementary MOS (CMOS) structures that use both n-type and p-type transistor channels. This complementary technology has enabled the construction of digital circuits, which operate with a high robustness, low power dissipation and a good noise margin. For the design of efficient organic integrated circuits, there is an urgent need for complementary technology, where both n-type and p-type transistor operation is realized in a single layer, while maintaining the attractiveness of easy solution processing. We demonstrate, by using solution-processed field-effect transistors, that hole transport and electron transport are both generic properties of organic semiconductors. This ambipolar transport is observed in polymers based on interpenetrating networks as well as in narrow bandgap organic semiconductors. We combine the organic ambipolar transistors into functional CMOS-like inverters.

Lelystad virus belongs to a new virus family, comprising lactate dehydrogenase-elevating virus, equine arteritis virus, and simian hemorrhagic fever virus.

Lelystad virus (LV) is an enveloped positive-stranded RNA virus, which causes abortions and respiratory disease in pigs. The complete nucleotide sequence of the genome of LV has been determined. This sequence is 15.1 kb in length and contains a poly(A) tail at the 3' end. Open reading frames that might encode the viral replicases (ORFs 1a and 1b), membrane-associated proteins (ORFs 2 to 6) and the nucleocapsid protein (ORF7) have been identified. Sequence comparisons have indicated that LV is distantly related to the coronaviruses and toroviruses and closely related to lactate dehydrogenase-elevating virus (LDV) and equine arteritis virus (EAV). A 3' nested set of six subgenomic RNAs is produced in LV-infected alveolar lung macrophages. These subgenomic RNAs contain a leader sequence, which is derived from the 5' end of the viral genome. Altogether, these data show that LV is closely related evolutionarily to LDV and EAV, both members of a recently proposed family of positive-stranded RNA viruses, the Arteriviridae.

Epitope mapping of envelope glycoprotein E1 of hog cholera virus strain Brescia.

Four antigenic domains (A, B, C and D) on envelope glycoprotein E1 (gp51-54) of hog cholera virus strain Brescia have been specified by using 13 monoclonal antibodies (MAbs) that recognize non-conserved and conserved epitopes. It was shown that the non-conserved epitopes map to the N-terminal half of E1 by analysis of chimeric E1 proteins of strains Brescia and C. Conserved epitopes, however, could not be mapped using this approach. Here we describe mapping of both conserved and non-conserved epitopes on E1 by the use of an extensive set of single and double deletion mutants of E1 of strain Brescia. Deletion mutants were transiently expressed in COS1 cells and analysed by immunostaining with the 13 MAbs directed against strain Brescia and four MAbs directed against strain C. All MAbs bound to the N-terminal half of E1, i.e. amino acids 690 to 866 encoded by the sequence of strain Brescia. Domain B and one epitope in domain C are located between residues 690 and 773. Other epitopes in domain C are located on an extended region, i.e. between residues 690 and 800. Conserved epitopes of domain A are mapped between residues 766 and 866, whereas the only non-conserved epitope in this domain is located between residues 766 and 813. Domain D, represented by one MAb, is located in the same region as this non-conserved epitope of domain A, i.e. between residues 766 and 800. The results suggest the presence of two distinct antigenic units on E1, one consisting of domains B and C and the other consisting of domain A.

Subgenomic RNAs of Lelystad virus contain a conserved leader-body junction sequence.

During the replication of Lelystad virus in alveolar lung macrophages, a 3'-coterminal nested set of six subgenomic RNAs (RNA2 to RNA7) is formed. These contain a common leader sequence derived from the 5' non-coding region of the genomic RNA. In this study, the sequence of the junction sites, i.e. the sites where the leader sequence joins to the body of the subgenomic RNA, was determined for all six subgenomic RNAs. For each subgenomic RNA, six to nine cDNA clones were isolated by means of reverse transcription and PCR. The nucleotide sequence at the junction site was identical for all eight cDNA clones derived from subgenomic RNA4. However, heterogeneity was observed in the nucleotide sequence surrounding the junction sites of the cDNA clones derived from subgenomic RNAs 2, 3, 5, 6 and 7. This heterogeneity suggests that the fusion of the leader to the body of the subgenomic RNA may be imprecise. The junction sites of the six subgenomic RNAs had a conserved sequence motif of six nucleotides (UCAACC or a highly similar sequence). The distance between the junction site and the translation initiation codon of the downstream open reading frame varied from nine to 83 nucleotides.

Lelystad virus, the causative agent of porcine epidemic abortion and respiratory syndrome (PEARS), is related to LDV and EAV.

The genome of Lelystad virus (LV), the causative agent of porcine epidemic abortion and respiratory syndrome (previously known as mystery swine disease), was shown to be a polyadenylated RNA molecule. The nucleotide sequence of the LV genome was determined from a set of overlapping cDNA clones. A consecutive sequence of 15,088 nucleotides was obtained. Eight open reading frames (ORFs) that might encode virus-specific proteins were identified. ORF1a and ORF1b are predicted to encode the viral RNA polymerase because the amino acid sequence contains sequence elements that are conserved in RNA polymerases of the torovirus Berne virus (BEV), equine arteritis virus (EAV), lactate dehydrogenase-elevating virus (LDV), the coronaviruses, and other positive-strand RNA viruses. A heptanucleotide slippery sequence (UUUAAAC) and a putative pseudoknot structure, which are both required for efficient ribosomal frameshifting during translation of the RNA polymerase ORF1b of BEV, EAV, and the coronaviruses, were identified in the overlapping region of ORF1a and ORF1b of LV. ORFs 2 to 6 probably encode viral membrane-associated proteins, whereas ORF7 is predicted to encode the nucleocapsid protein. Comparison of the amino acid sequences of the ORFs identified in the genome of LV, LDV, and EAV indicated that LV and LDV are more closely related than LV and EAV. A 3' nested set of six subgenomic RNAs was detected in LV-infected cells. These subgenomic RNAs contain a common leader sequence that is derived from the 5' end of the genomic RNA and that is joined to the 3' terminal body sequence. Our results indicate that LV is closely related evolutionarily to LDV and EAV, both members of a recently proposed family of positive-strand RNA viruses, the Arteriviridae.

A preliminary map of epitopes on envelope glycoprotein E1 of HCV strain Brescia.

Monoclonal antibodies (MAbs) directed against envelope glycoprotein E1 (gp51-54) of hog cholera virus (HCV) strain Brescia have been shown to recognize four different antigenic domains A, B, C and D. Epitopes of within domain A have mainly been found conserved among HCV strains, whereas epitopes within domains B, C and D are not conserved. We used transiently expressed hybrid E1 genes of HCV strains Brescia and "C" to map the non-conserved epitopes on E1. Epitopes in domains B and C are located within the ultimate N-terminal 104 amino acids. The non-conserved subdomain A3 is most probably located between domains B/C and a hydrophobic region, which is highly conserved between HCV strains Brescia and "C". The conserved subdomains A1 and A2 are probably located in the vicinity and C-terminally of this conserved, hydrophobic region, which is near the centre of the E1 amino acid sequence.