[Access to health care throughout the country]. / Zugang zur Gesundheitsversorgung in der Fläche.

The legal basis for describing the regional care situation is based on the adjusted supply rate of the 'demand planning guideline'. However, it provides only limited information about the accessibility of medical care which is crucial for the reality of patients' lives. The aim of this review is to present geographic approaches that spatially measure access to dermatological care in its physical and digital dimension. Here, on the one hand, the classical geographic parameter 'accessibility' is addressed, and on the other hand, data from the Federal Ministry of Transport and Digital Infrastructure (BMVI) on broadband coverage are presented as access parameters of teledermatological applications. In addition to the methodological approach, limitations and potentials in the interpretation of the results, minimum standards are also considered. The access parameters presented here make it possible to investigate spatial disparities and to present them clearly via cartographic representations. While the example of accessibility with a car shows almost area-wide access to the nearest dermatology practice (≤ 30 min), investigations on public transport accessibility reveal rather heterogeneous accessibility. Particularly in the identification of 'dual care gaps', sub-areas with poor physical and digital accessibility, these approaches could support and advance the application of alternative care models. However, the approaches presented here focus on potential accessibility. Further dimensions on actual physician utilisation or availability-also with regard to minimum standards-should be the subject of future research.

[Methods for analysing spatial data : Using the example of skin cancer prevalence in Germany]. / Methoden zur Analyse räumlicher Daten : Beispiel der regionalen Hautkrebsprävalenz in Deutschland.

BACKGROUND: Studies show a spatial variation in skin cancer frequencies, but the causes have not been fully understood. When analysing spatial patterns and correlations, different approaches need to be considered, as the data have special features due to their spatial structure. AIM OF THE STUDY: Why the spatial consideration of skin cancer frequencies is important at all, and which methods of analysis are useful is considered in more detail in this article. The article provides an introduction and overview of statistical methods that are important for the spatial analysis of skin cancer frequencies. MATERIALS AND METHODS: At first it is shown which descriptive methods, such as statistical smoothing, can be applied. Next, spatial cluster and regression analyses will be discussed. Testing for spatial autocorrelation will be considered. RESULTS: In particular, the spatial dependence of the data on neighbouring regions, which if ignored can lead to biased estimates, is of particular importance in the analysis of spatial data and requires special spatial analysis methods. DISCUSSION: This article provides an introduction and overview of statistical methods relevant to the spatial analysis of skin cancers.

Regional variations in the use of statutory skin cancer screenings in Germany: population-based spatial multisource analysis.

BACKGROUND: Due to the increasing incidence of skin cancer, programmes for the prevention of skin cancer have been developed and implemented in Germany. However, utilization of skin cancer screenings shows marked regional differences. Reasons and predictors of such variations are unclear. OBJECTIVES: The objective of the study is to identify predictors for regional use of skin cancer screening variations in Germany. METHODS: Analysis of the population set of ambulatory claims data (2009-2015) of the statutory health insurances (SHI) in Germany (70.2 million people in 2015). Skin cancer screening utilization rate was determined on county level. Descriptive, cluster and multivariate analyses were performed to identify spatial patterns in skin cancer screening utilization. RESULTS: Overall, 6.5-7.9 million people participated in skin cancer screenings. Utilization rates of people ≥35 years of age were 9.74% (2009) and 10.96% (2015). Marked regional variations were identified between the counties. Dermatologists in Saxony and Westphalia-Lippe as well as general practitioners in Lower Saxony and North Rhine showed particularly high utilization rates. Multiple regression analyses demonstrated e.g. positive associations between the skin cancer screening utilization rates and employees with higher vocational qualifications and shorter travel time by car to the nearest major urban centre. CONCLUSION: Utilization rates of skin cancer screening vary largely in Germany with specific spatial patterns. Multivariate analyses demonstrate associations with socio-economic and geographical determinants. The results indicate the importance of health policy measures. These should be used in a more targeted manner in the regions in order to increase utilization of skin cancer screening.

Epidemiology of skin cancer in the German population: impact of socioeconomic and geographic factors.

BACKGROUND: Skin cancer being the most common cancer in Germany has shown increasing incidence in the past decade. Since mostly caused by excessive UV exposure, skin cancer is largely related to behaviour. So far, the impact of regional and sociodemographic factors on the development of skin cancer in Germany is unclear. OBJECTIVES: This study aimed to investigate the association of potential predictive factors with the prevalence of skin cancers in Germany. METHODS: Nationwide ambulatory care claims data from persons insured in statutory health insurances (SHI) with malignant melanoma (MM, ICD-10 C43) and non-melanocytic skin cancer (NMSC, ICD-10 C44) in the years 2009-2015 were analysed. In addition, sociodemographic population data and satellite-based UV and solar radiation data were associated. Descriptive and multivariate (spatial) statistical analyses (e.g. Bayes' smoothing) were conducted on county level. RESULTS: Data from 70.1 million insured persons were analysed. Age-standardized prevalences per 100 000 SHI insured persons for MM and NMSC were 284.7 and 1126.9 in 2009 and 378.5 and 1708.2 in 2015. Marked regional variations were observed with prevalences between 32.9% and 51.6%. Multivariate analysis shows among others statistically significant positive correlations between higher income and education, and MM/NMSC prevalence. CONCLUSION: Prevalence of MM and NMSC in Germany shows spatio-temporal dynamics. Our results demonstrate that regional UV radiation, sunshine hours and sociodemographic factors have significant impact on skin cancer prevalence in Germany. Individual behaviour obviously is a major determinant which should be subject to preventive interventions.

Probing the Interlayer Exciton Physics in a MoS2/MoSe2/MoS2 van der Waals Heterostructure.

Stacking atomic monolayers of semiconducting transition metal dichalcogenides (TMDs) has emerged as an effective way to engineer their properties. In principle, the staggered band alignment of TMD heterostructures should result in the formation of interlayer excitons with long lifetimes and robust valley polarization. However, these features have been observed simultaneously only in MoSe2/WSe2 heterostructures. Here we report on the observation of long-lived interlayer exciton emission in a MoS2/MoSe2/MoS2 trilayer van der Waals heterostructure. The interlayer nature of the observed transition is confirmed by photoluminescence spectroscopy, as well as by analyzing the temporal, excitation power, and temperature dependence of the interlayer emission peak. The observed complex photoluminescence dynamics suggests the presence of quasi-degenerate momentum-direct and momentum-indirect bandgaps. We show that circularly polarized optical pumping results in long-lived valley polarization of interlayer exciton. Intriguingly, the interlayer exciton photoluminescence has helicity opposite to the excitation. Our results show that through a careful choice of the TMDs forming the van der Waals heterostructure it is possible to control the circular polarization of the interlayer exciton emission.

Electrochemical Reaction in Single Layer MoS2: Nanopores Opened Atom by Atom.

Ultrathin nanopore membranes based on 2D materials have demonstrated ultimate resolution toward DNA sequencing. Among them, molybdenum disulfide (MoS2) shows long-term stability as well as superior sensitivity enabling high throughput performance. The traditional method of fabricating nanopores with nanometer precision is based on the use of focused electron beams in transmission electron microscope (TEM). This nanopore fabrication process is time-consuming, expensive, not scalable, and hard to control below 1 nm. Here, we exploited the electrochemical activity of MoS2 and developed a convenient and scalable method to controllably make nanopores in single-layer MoS2 with subnanometer precision using electrochemical reaction (ECR). The electrochemical reaction on the surface of single-layer MoS2 is initiated at the location of defects or single atom vacancy, followed by the successive removals of individual atoms or unit cells from single-layer MoS2 lattice and finally formation of a nanopore. Step-like features in the ionic current through the growing nanopore provide direct feedback on the nanopore size inferred from a widely used conductance vs pore size model. Furthermore, DNA translocations can be detected in situ when as-fabricated MoS2 nanopores are used. The atomic resolution and accessibility of this approach paves the way for mass production of nanopores in 2D membranes for potential solid-state nanopore sequencing.

Development and validation of a sleep questionnaire, SNoRE 3.0, to evaluate sleep in companion dogs.

Disturbances in the sleep-wake cycle are a debilitating, yet rather common condition not only in humans, but also in family dogs. While there is an emerging need for easy-to-use tools to document sleep alterations (in order to ultimately treat and/or prevent them), the veterinary tools which yield objective data (e.g. polysomnography, activity monitors) are both labor intensive and expensive. In this study, we developed a modified version of a previously used sleep questionnaire (SNoRE) and determined criterion validity in companion dogs against polysomnography and physical activity monitors (PAMs). Since a negative correlation between sleep time and cognitive performance in senior dogs has been demonstrated, we evaluated the correlation between the SNoRE scores and the Canine Dementia Scale (CADES, which includes a factor concerning sleep). There was a significant correlation between SNoRE 3.0 questionnaire scores and polysomnography data (latency to NREM sleep, ρ = 0.507, p < 0.001) as well as PAMs' data (activity between 1:00 and 3:00 AM, p < 0.05). There was a moderate positive correlation between the SNoRE 3.0 scores and the CADES scores (ρ = 0.625, p < 0.001). Additionally, the questionnaire structure was validated by a confirmatory factor analysis, and it also showed an adequate test-retest reliability. In conclusion the present paper describes a valid and reliable questionnaire tool, that can be used as a cost-effective way to monitor dog sleep in clinical settings.

Visibility of dichalcogenide nanolayers.

Dichalcogenides with the common formula MX(2) are layered materials with electrical properties that range from semiconducting to superconducting. Here, we describe optimal imaging conditions for the optical detection of ultrathin, two-dimensional dichalcogenide nanocrystals containing single, double and triple layers of MoS(2), WSe(2) and NbSe(2). A simple optical model is used to calculate the contrast for nanolayers deposited on wafers with varying thicknesses of SiO(2). The model is extended for imaging using the green channel of a video camera. Using AFM and optical imaging we confirm that single layers of MoS(2) and WSe(2) can be detected on 90 and 270 nm SiO(2) using optical means. By measuring contrast under broadband green illumination we are also able to distinguish between nanostructures containing single, double and triple layers of MoS(2) and WSe(2.) We observe and discuss discrepancies in the case of NbSe(2).

[Parameters for measuring the regional healthcare situation : A comparison of different healthcare parameters by the example of ophthalmologic care in the metropolitan region Hamburg]. / Parameter zur Messung der regionalen Versorgungssituation : Ein Vergleich verschiedener Versorgungsparameter am Beispiel der augenärztlichen Versorgung in der Metropolregion Hamburg.

BACKGROUND: Regional ophthalmologic care in Germany is ensured through the guidelines of the Federal Joint Committee's requirement planning and the adjusted supply rate defined therein. Although the adjusted supply rate is an official instrument for assessing the actual healthcare situation in Germany, earlier studies revealed limitations. Factors such as public transport accessibility or the existence of other healthcare professions are not considered to a sufficient extent, although they have a profound impact on the healthcare situation. The latter in particular have a strong supportive function in regional healthcare. OBJECTIVE: This study aimed to critically compare different parameters to evaluate the regional healthcare situation using the example of ophthalmologic care. MATERIAL AND METHODS: For this purpose a score was calculated for the districts of the Hamburg metropolitan region based on the exemplary parameters "density of ophthalmologists with orthoptic focus on a district level (offer/100,000 inhabitants)", "percentage of population with public transport accessibility to next ophthalmologist <30 min on a district level", "percentage of population with public transport accessibility to next ophthalmologist with orthoptic focus <30 min on a district level" and compared with the results of the adjusted supply rate. RESULTS: While the adjusted supply rate could not identify any case of undersupply in any of the districts, the other included parameters sometimes revealed clear differences in supply. CONCLUSION: The healthcare situation is heterogeneous by consideration of different parameters. This needs to be taken into account when assessing the regional healthcare situation for requirement planning.

LCT 13910 C/T polymorphism, serum calcium, and bone mineral density in postmenopausal women.

SUMMARY: LCT 13910 CC genotype is associated with lactose intolerance, a condition often resulting in reduced milk intake. Women with the CC genotype were found to have decreased serum calcium and reduced bone mineral density. INTRODUCTION: The CC genotype of the 13910 C/T polymorphism of the LCT gene is linked to lactose intolerance and low calcium intake. METHODS: We studied 595 postmenopausal women, including 267 osteoporotic, 200 osteopenic, and 128 healthy subjects. Genotyping, osteodensitometry, and laboratory measurements were carried out. RESULTS: Frequency of aversion to milk consumption was 20% for CC genotype and 10% for TT + TC genotypes (p = 0.03). The albumin-adjusted serum calcium was 2.325 +/- 0.09 mmol/L for CC genotype and 2.360 +/- 0.16 mmol/L for TT + TC genotypes (p = 0.031). Bone mineral density (BMD; Z score) was lower in the CC than TT + TC genotypes, respectively, at the radius (0.105 +/- 1.42 vs 0.406 +/- 1.32; p = 0.038), at the total hip (-0.471 +/- 1.08 vs -0.170 +/- 1.09; p = 0.041), and at the Ward's triangle (-0.334 +/- 0.87 vs -0.123 +/- 0.82; p = 0.044). CONCLUSION: LCT 13910 C/T polymorphism is associated with decreased serum calcium level and lower BMD in postmenopausal women.

Progressive increase of human papillomavirus carriage rates in potentially malignant and malignant oral disorders with increasing malignant potential.

INTRODUCTION: We investigated the potential role of human papillomaviruses (HPVs) in potentially malignant oral disorders, oral leukoplakia (OL) and oral lichen planus (OLP), and in oral squamous cell cancer (OSCC) in an Eastern Hungarian population with a high incidence of OSCC. METHODS: Excised tumor samples (65 OSCC patients) and exfoliated cells from potentially malignant lesions (from 44 and 119 patients with OL and OLP, respectively) as well as from healthy controls (72 individuals) were analysed. OLPs were classified based on clinical appearance, 61 patients had erosive-atrophic lesions (associated with higher malignancy risk, EA-OLP) and 58 had non-erosive non-atrophic lesions (with lower risk of becoming malignant, non-EA-OLP), respectively. Exfoliated cells collected from apparently healthy mucosa accompanied each lesion sample. HPV was detected by MY/GP polymerase chain reaction (PCR) and genotyped by restriction analysis of amplimers. Copy numbers in lesions were determined using real-time PCR. Prevalence rates, copy number distributions, and association with risk factors and diseases were analysed using chi-square test, t-test, and logistic regression, respectively. RESULTS: We detected HPVs significantly more frequently in lesions than in controls (P < or = 0.001 in all comparisons). HPV prevalence increased gradually with increasing severity of lesions (32.8, 40.9, and 47.7% in OLP, OL, and OSCC, respectively). Copy number distribution patterns roughly corresponded to prevalence rates, but OLP and OL were comparable. HPV prevalence differed significantly between EA-OLP and non-EA-OLP groups (42.6 vs. 22.4%); EA-OLP group showed a prevalence similar to that found in OL. CONCLUSION: HPVs may be involved in the development or progression of not only OSCC but also of potentially malignant oral lesions.

Could vectors' fear of predators reduce the spread of plant diseases?

Predators influence the behaviour of prey and by doing so they potentially reduce pathogen transmission by a vector. Arthropod predators have been shown to reduce the consumption of plant biomass by pest herbivores, but their cascading non-consumptive effect on vector insects' feeding behaviour and subsequent pathogen transmission has not been investigated experimentally before. Here we experimentally examined predator-mediated pathogen transmission mechanisms using the plant pathogen Wheat Dwarf Virus that is transmitted by the leafhopper, Psammotettix alienus. We applied in situ hybridization to localize which leaf tissues were infected with transmitted virus DNA in barley host plants, proving that virus occurrence is restricted to phloem tissues. In the presence of the spider predator, Tibellus oblongus, we recorded the within leaf feeding behaviour of the herbivore using electrical penetration graph. The leafhopper altered its feeding behaviour in response to predation risk. Phloem ingestion, the feeding phase when virus acquisition occurs, was delayed and was less frequent. The phase when pathogen inoculation takes place, via the secretion of virus infected vector saliva, was shorter when predator was present. Our study thus provides experimental evidence that predators can potentially limit the spread of plant pathogens solely through influencing the feeding behaviour of vector organisms.

Vacuum ultraviolet excitation luminescence spectroscopy of few-layered MoS2.

We report on vacuum ultraviolet (VUV) excited photoluminescence (PL) spectra emitted from a chemical vapor deposited MoS2 few-layered film. The excitation spectrum was recorded by monitoring intensities of PL spectra at ~1.9 eV. A strong wide excitation band peaking at 7 eV was found in the excitation. The PL excitation band is most intensive at liquid helium temperature and completely quenched at 100 K. Through first-principles calculations of photoabsorption in MoS2, the excitation was explicated and attributed to transitions of electrons from p- and d- type states in the valence band to the d- and p-type states in the conduction band. The obtained photon-in/photon-out results clarify the excitation and emission behavior of the low dimensional MoS2 when interacting with the VUV light sources.

Structure, microstructure, and magnetism in ferrimagnetic bioceramics.

The structural and magnetic properties of ferrimagnetic bioglass ceramics in the system [0.45(CaO,P2O5)(0.52 - x)SiO2 xFe2O3 0.03Na2O], x = 0.05, 0.10, 0.15, 0.20 and heat-treated at the temperature range 600-1100 degrees C are assessed. The structure and microstructure of the samples are characterized with X-ray diffraction, scanning electron microscopy, and energy dispersive X-ray spectroscopy. Calcium phosphate and magnetite develop as the two major crystalline phases. For x = 0.10 and 0.20, calcium phosphate undergoes a gradual transition from the monoclinic to the rhombohedral crystal system (SG P21/a-->R3c) as the heat-treatment temperature increases from 800 to 1100 degrees C. Dendrites of iron oxide with crystallites of various sizes are observed to form within a glassy matrix enriched in calcium, phosphorous, and silicon. Saturation magnetization, remanence, and coercivity are found from dc magnetic measurements. They vary with the specific processing parameters of the composites, and these are correlated with the observed structure and microstructure of the materials.

Distribution of Q188R and N314D mutations in the Hungarian galactosemic population.

The most common causes of galactosemia are mutations of the gene coding galactose-1-phosphate uridyltransferase. Since genotype may correlate with the outcome of the disease, and probably not all of the naturally occurring disease associated mutations are described, characterization of the genotypes in different galactosemic populations are in progress. So far the most extensively examined mutations are the Q188R and the N314D. The first one is associated with the classical galactosemia producing a severe clinical picture with an early onset in homozygous patients. The N314D mutation is associated with the Duarte phenotype, which means a milder form of the disease with a later onset of the symptoms. We studied these mutations in the whole Hungarian galactosemic population by PCR and restriction analysis. We have found the frequency of the Q188R mutation at 33.3%, and the N314D mutation at 11.1%. These results differ from other published data in any other populations. Since the incidence of the disease is the same in Hungary as in other European countries, our study suggests that it is worth to investigate for other mutations in the Hungarian population, of which frequency should be consequently higher.

Pacing-induced delayed protection against arrhythmias is attenuated by aminoguanidine, an inhibitor of nitric oxide synthase.

1. Cardiac pacing, in anaesthetized dogs, protects against ischaemia and reperfusion-induced ventricular arrhythmias when this is initiated 24 h after the pacing stimulus. Now we have examined whether this delayed cardioprotection afforded by cardiac pacing is mediated through nitric oxide. 2. Twenty-two dogs were paced (4 x 5 min periods at 220 beats min(-1)) by way of the right ventricle, 24 h prior to a 25 min period of coronary artery occlusion. Nine of these dogs were given the inhibitor of induced nitric oxide synthase, aminoguanidine (50 mg kg(-1) i.v.), 0.5 h prior to coronary artery occlusion. Sham-operated non-paced dogs with and without aminoguanidine treatment served as controls. 3. Pacing markedly (P<0. 05) reduced arrhythmia severity (ventricular fibrillation, VF, during occlusion 15%; survival from the combined ischaemia-reperfusion insult 62%) compared to control, sham-operated, unpaced dogs (VF during occlusion 58%; survival 17%). This protection was attenuated by the administration of aminoguanidine prior to coronary artery occlusion (survival from the combined ischaemia-reperfusion insult 11%, which was significantly (P<0.05) less than in the paced dogs not given aminoguanidine and similar to the controls). Aminoguanidine had no significant effects on coronary artery occlusion when given to dogs that had not been paced. In the dose used aminoguanadine transiently elevated systemic arterial pressure by a mean of 20 mmHg and reduced heart rate by a mean of 22 beats min(-1). 4. These results suggest that nitric oxide, probably derived from induced nitric oxide synthase, contributes significantly to the delayed cardioprotection afforded by cardiac pacing.

[Determination of thermostable and thermolabile enterotoxins in Escherichia coli strains by genetic, biological, and immunoserological methods]. / Opredelenie termostabil'nogo i termolabil'nogo énterotoksinov v shtammakh Escherichia coli geneticheskimi, biologicheskimi i immunoserologicheskimi metodami.

The Escherichia coli strains (75) isolated from patients suffering from diarrhea were screened for ability to produce the temperature-labile or stable toxins (ST or LT) by the different techniques (the hybridization with DNA probes, biological, enzyme immunoassay). The majority of tested strains was shown to harbor the tox-genes controlling the synthesis of ST, LT or both enterotoxins. However, the phenotypic expression of the genes was registered in only some of the strains. The hybridization with the DNA probes is noted to be most perspective in the mass screening of toxigenic strains. The DNA probe used contained the fused estA-eltB genes that makes one able to detect the genes for both enterotoxins.

[Androgen receptor gene (CAG)n of spinal and bulbar muscular atrophy found in the normal child population in Hungary]. / A spinalis és bulbaris muscularis atrophia androgénreceptor génjében található (CAG)n ismétlödések polimorfizmusa normális hazai gyermekpopulációban.

A simple and accurate molecular biology method was developed for the diagnosis of the spinal and bulbar muscular atrophy. With this method DNA isolated from peripheral blood of 40 unaffected, apparently healthy children was assayed for the CAG repeat polymorphism responsible for the disease. The results were compared with population genetic studies of international references, and the data showed no differences between the Hungarian repeat length and findings of others. Our experience shows, that this method can be used for the differential diagnosis of muscular atrophies and praenatal diagnostics in affected families.

[Incidence of factor V G1681A (Leiden) mutation in samplings from the Hungarian population]. / A faktor V G1691A (Leiden) mutáció gyakorisága magyar népességmintákban.

Thromboembolic disorders affect 0.1% of the adult population. Two main groups of the underlying predisposition factors can be identified: environmental factors (e.g. dietary habits, physical activity, surgical interventions, pregnancy etc.) and several genetic predispositions (e.g. inherited anticoagulant defects). After the discovery of the genetic mutation of factor V, called Leiden mutation, it turned out, that this mutation is responsible for the development of resistance to activated protein C in majority of the cases. The importance of the Leiden mutation is further emphasised by population based investigations, which makes it the most frequent thrombosis risk factor known today. In our study we have identified 43 heterozygotes and 3 homozygotes with Leiden mutation in total of 665 samples. The 6.47% heterozigocy is in the range of earlier reports from Europe. The homozygote/heterozygote distribution deviated from the value predicted by the Hardy-Weinberg law.

[Mutation analysis in the CTG-base multiplication in a family with myotonic dystrophy in three generations]. / Mutációanalízis a CTG-bázishármas megsokszorozódásának vizsgálatával egy háromgenerációs myotoniás dystrophiás családban.

A PCR-based method with a novel silver staining detection was developed for the determination of CTG repeat number in the 3' untranslated region of the MD-PK gene responsible for myotonic dystrophy. Through the investigation of a family with affected members in three generations the application of the method is presented. According to the results, healthy individuals were verified easily, and the repeat number in patients with mild features or with premutation could be determined accurately. In severe clinical forms, e.g. congenital myopathy, the expansion can be deduced only from the lack of amplification, however, this is also helpful if the segregation of familial alleles is known.