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Background: Health care accessibility is known to differ geographically. With this study we focused on analysing accessibility of general and specialized obstetric units in England and Germany with regard to urbanity, area deprivation and neonatal outcome using routine data.
Methods: We used a floating catchment area method to measure obstetric care accessibility, the degree of urbanization (DEGURBA) to measure urbanity and the index of multiple deprivation to measure area deprivation.
Results: Accessibility of general obstetric units was significantly higher in Germany compared to England (accessibility index of 16.2 vs. 11.6; p < 0.001), whereas accessibility of specialized obstetric units was higher in England (accessibility index for highest level of care of 0.235 vs. 0.002; p < 0.001). We further demonstrated higher obstetric accessibility for people living in less deprived areas in Germany (r = − 0.31; p < 0.001) whereas no correlation was present in England. There were also urban–rural disparities present, with higher accessibility in urban areas in both countries (r = 0.37–0.39; p < 0.001). The analysis did not show that accessibility affected neonatal outcomes. Finally, our computer generated model for obstetric care provider demand in terms of birth counts showed a very strong correlation with actual birth counts at obstetric units (r = 0.91–0.95; p < 0.001).
Conclusion: In Germany the focus of obstetric care seemed to be put on general obstetric units leading to higher accessibility compared to England. Regarding specialized obstetric care the focus in Germany was put on high level units whereas in England obstetric care seems to be more balanced between the different levels of care with larger units on average leading to higher accessibility.
Purpose: The coronavirus disease 2019 (COVID-19) poses major challenges to health-care systems worldwide. This pandemic demonstrates the importance of timely access to intensive care and, therefore, this study aims to explore the accessibility of intensive care beds in 14 European countries and its impact on the COVID-19 case fatality ratio (CFR).
Methods: We examined access to intensive care beds by deriving (1) a regional ratio of intensive care beds to 100,000 population capita (accessibility index, AI) and (2) the distance to the closest intensive care unit. The cross-sectional analysis was performed at a 5-by-5 km spatial resolution and results were summarized nationally for 14 European countries. The relationship between AI and CFR was analyzed at the regional level.
Results: We found national-level differences in the levels of access to intensive care beds. The AI was highest in Germany (AI = 35.3), followed by Estonia (AI = 33.5) and Austria (AI = 26.4), and lowest in Sweden (AI = 5) and Denmark (AI = 6.4). The average travel distance to the closest hospital was highest in Croatia (25.3 min by car) and lowest in Luxembourg (9.1 min). Subnational results illustrate that capacity was associated with population density and national-level inventories. The correlation analysis revealed a negative correlation of ICU accessibility and COVID-19 CFR (r = − 0.57; p < 0.001).
Conclusion: Geographical access to intensive care beds varies significantly across European countries and low ICU accessibility was associated with a higher proportion of COVID-19 deaths to cases (CFR). Important differences in access are due to the sizes of national resource inventories and the distribution of health-care facilities relative to the human population. Our findings provide a resource for officials planning public health responses beyond the current COVID-19 pandemic, such as identifying potential locations suitable for temporary facilities or establishing logistical plans for moving severely ill patients to facilities with available beds.
This article intends to give an overview about developments in European Regulatory and Health Technology Assessment (HTA) of new cancer drugs. As background information, it will refer to an overview article by Bergmann et al. [1], which pointed out the status and the limitations of the current system. The authors discussed possible steps to improve the interface between regulators and HTA bodies but stated that this alone will not be sufficient to overcome heterogeneous HTA assessments between HTA agencies. Major issues and challenges for the foreseeable future will be to overcome the heterogeneity of patient access decisions of pharmaceutical payers across Europe which is due to (i) considerably different scientific approaches and methodology to the more or less formal evaluation of cost-effectiveness; (ii) differing health priorities across the countries that reflect historically developed cultural differences and values or different unmet medical needs and (iii) different economic strengths among nations, regions and locales that necessarily drive health care budgetary decisions. The authors consider that this needs a science-based common position on methodology, greater commitments by politicians and health care decision makers to ensure equal access for patients across the EU to anti-tumour medicines. ...
Vortrag im Rahmen des Symposiums der Universitätsbibliothek Frankfurt am Main in Kooperation mit der Frankfurter Buchmesse 2011 "Economy and Acceptance of Open Access Strategies", am 14.10.2011.
From the late middle ages to early modern times (ca. 1200-1600) the Lübeck City Council was the most important courthouse in the Baltic. About 100 cities and towns on its shores lived according to the law of Lübeck. The paper deals with the old theory that Imperial law, i.e. mainly the learned Ius commune, was generally rejected by the council on the grounds of its foreign nature. The paper rejects this view with the help of 8 case studies. There exist rather spectacular statements against Imperial Law, but a closer look reveals that they have to be seen in the light of a specific practical context. They must not be confounded with general statements in which the council had no interest. Its attitude towards Learned Law was flexible and purely pragmatic.
Acceleration of Biomedical Image Processing and Reconstruction with FPGAs
Increasing chip sizes and better programming tools have made it possible to increase the boundaries of application acceleration with reconfigurable computer chips. In this thesis the potential of acceleration with Field Programmable Gate Arrays (FPGAs) is examined for applications that perform biomedical image processing and reconstruction. The dataflow paradigm was used to port the analysis of image data for localization microscopy and for 3D electron tomography from an imperative description towards the FPGA for the first time.
After the primitives of image processing on FPGAs are presented, a general workflow is given for analyzing imperative source code and converting it to a hardware pipeline where every node processes image data in parallel. The theoretical foundation is then used to accelerate both example applications. For localization microscopy, an acceleration of 185 compared to an Intel i5 450 CPU was achieved, and electron tomography could be sped up by a factor of 5 over an Nvidia Tesla C1060 graphics card while maintaining full accuracy in both cases.
In this article, the author shows that progress of info-communications is a key factor of society changes, as it radically changes the key aspects of human life. Studying the time of progress and comparing it with the most important anthropic characteristic - length of human life, he comes to the conclusion that our generation has witnessed the tipping point in the rate of development of human civilization. This showing up in the fact that the present stage of the scientific and technological advance lead to the transformation, perhaps on the same scale, what were the appearance of written language and publishing, but these multiple fundamental changes in the life of society occur within the life of a single generation. In these circumstances, the task of forecasting, in its traditional setting, is becoming increasingly inaccurate. According to the author, the only possibility is to venture outside the framework of formal logic and technocratic approaches and try to find answers to these questions by generating new meanings of the realities surrounding us and in this context philosophy has a special role.
We report the first measurements of 1,1,1,2,3,3,3-heptafluoropropane (HFC-227ea), a substitute for ozone depleting compounds, in air samples originating from remote regions of the atmosphere and present evidence for its accelerating growth. Observed mixing ratios ranged from below 0.01 ppt in deep firn air to 0.59 ppt in the current northern mid-latitudinal upper troposphere. Firn air samples collected in Greenland were used to reconstruct a history of atmospheric abundance. Year-on-year increases were deduced, with acceleration in the growth rate from 0.029 ppt per year in 2000 to 0.056 ppt per year in 2007. Upper tropospheric air samples provide evidence for a continuing growth until late 2009. Furthermore we calculated a stratospheric lifetime of 370 years from measurements of air samples collected on board high altitude aircraft and balloons. Emission estimates were determined from the reconstructed atmospheric trend and suggest that current "bottom-up" estimates of global emissions for 2005 are too high by a factor of three.
We analyze the implications of the governance structure in academic faculties for their recruitment decisions when competing for new researchers. The value to individual members through social interaction within the faculty depends on the average status of their fellow members. In recruitment decisions, incumbent members trade off the effect of entry on average faculty status against alternative uses of the recruitment budget if no entry takes place. We show that the best candidates join the best faculties but that they receive lower wages than some lesser ranking candidates. We also study the allocation of surplus created by the entry of a new faculty member and show that faculties with symmetric status distributions maximize their joint surplus under majority voting.
Nano-granular metals are materials that fall into the general class of granular electronic systems in which the interplay of electronic correlations, disorder and finite size effects can be studied. The charge transport in nano-granular metals is dominated by thermally-assisted, sequential and correlated tunneling over a temperature-dependent number of metallic grains. Here we study the frequency-dependent conductivity (AC conductivity) of nano-granular Platinum with Pt nano-grains embedded into amorphous carbon (C). We focus on the transport regime on the insulating side of the insulator metal transition reflected by a set of samples covering a range of tunnel-coupling strengths. In this transport regime polarization contributions to the AC conductivity are small and correlation effects in the transport of free charges are expected to be particularly pronounced. We find a universal behavior in the frequency dependence that can be traced back to the temperature-dependent zero-frequency conductivity (DC conductivity) of Pt/C within a simple lumped-circuit analysis. Our results are in contradistinction to previous work on nano-granular Pd/ZrO2ZrO2 in the very weak coupling regime where polarization contributions to the AC conductivity dominated. We describe possible future applications of nano-granular metals in proximity impedance spectroscopy of dielectric materials.
Solenogastres (Aplacophora) is a small clade of marine, shell-less worm-molluscs with close to 300 valid species. Their distribution ranges across all oceans, and whereas the vast majority of species has been collected and described from the continental shelf and slope, only few species are known from depths below 4,000 m. Following traditional taxonomy, identification of specimens to species level is complex and time-consuming and requires detailed investigations of morphology and anatomy—often resulting in the exclusion of the clade in biodiversity or biogeographic studies. During the KuramBio expedition (Kuril-Kamchatka Biodiversity Studies) to the abyssal plain of the Northwest Pacific and the Kuril-Kamchatka Trench, 33 solenogaster specimens were sampled from 4,830 m to 5,397 m. Within this study we present an efficient workflow to address solenogaster diversity, even when confronted with a high degree of singletons and minute body sizes, hampering the use of single individuals for multiple morphological and molecular approaches. We combine analyses of external characters and scleritome with molecular barcoding based on a self-designed solenogaster specific set of mitochondrial primers. Overall we were able to delineate at least 19 solenogaster lineages and identify 15 species to family level and beyond. Based on our approach we identified three key lineages from the two regionally most species-rich families (Acanthomeniidae and Pruvotinidae) for deeper taxonomic investigations and describe the novel abyssal species Amboherpia abyssokurilensis sp. nov. (Cavibelonia, Acanthomeniidae) using microanatomical 3D-reconstructions. Our study more than doubles the previous records of solenogaster species from the Northwest Pacific and its marginal seas. Almost all lineages are reported for the first time from the region of the (Northwest) Pacific, vastly expanding distribution ranges of the respective clades. Moreover it doubles the number of Solenogastres collected from abyssal depths on a global scale and underlines the lack of exploratory α-diversity work in the abyssal zone for reliable species estimates in marine biodiversity.
Purpose: The diagnosis of abusive head trauma (AHT) is complex and neuroimaging plays a crucial role. Our goal was to determine whether non-neuroradiologists with standard neuroradiology knowledge perform as well as neuroradiologists with experience in pediatric neuroimaging in interpreting MRI in cases of presumptive AHT (pAHT).
Methods: Twenty children were retrospectively evaluated. Patients had been diagnosed with pAHT (6 patients), non-abusive head trauma-NAHT (5 patients), metabolic diseases (3 patients), and benign enlargement of the subarachnoid spaces (BESS) (6 patients). The MRI was assessed blindly, i.e., no clinical history was given to the 3 non-neuroradiologists and 3 neuroradiologists from 2 different institutions.
Results: Blindly, neuroradiologists demonstrated higher levels of sensitivity and positive predictive value in the diagnosis of pAHT (89%) than non-neuroradiologists (50%). Neuroradiologists chose correctly pAHT as the most probable diagnosis 16 out of 18 times; in contrast, non-neuroradiologists only chose 9 out of 18 times. In our series, the foremost important misdiagnosis for pAHT was NAHT (neuroradiologists twice and non-neuroradiologists 5 times). Only victims of motor vehicle accidents were blindly misdiagnosed as pAHT. No usual household NAHT was not misdiagnosed as pAHT. Neuroradiologists correctly ruled out pAHT in all cases of metabolic diseases and BESS.
Conclusion: MRI in cases of suspected AHT should be evaluated by neuroradiologists with experience in pediatric neuroimaging. Neuroradiologists looked beyond the subdural hemorrhage (SDH) and were more precise in the assessment of pAHT and its differential diagnosis than non-neuroradiologists were. It seems that non-neuroradiologists mainly assess whether or not a pAHT is present depending on the presence or absence of SDH.
Peracarid data were collected in the Southern Ocean and South Atlantic Ocean. Sampling was performed during nine different expeditions on board of RRS James Clark Ross and RV Polarstern, using epibenthic sledges (EBS) at depth ranging between 160–6348 m at 109 locations. The correlation between environmental variables and peracarid abundance was investigated. Abundance data comprise a total of 128570 peracarids (52366 were amphipods, 28516 were cumaceans, 36142 isopods, 5676 mysidaceans and 5870 were tanaidaceans). The presented data are useful to investigate the composition and abundance patterns of peracarid orders at a wide depth range and spatial scale in the Southern Ocean. They can also be reused to compare their abundance with that of other taxa in broader ecological surveys.
Climate change is influencing some environmental variables in the Southern Ocean (SO) and this will have an effect on the marine biodiversity. Peracarid crustaceans are one of the dominant and most species-rich groups of the SO benthos. To date, our knowledge on the influence of environmental variables in shaping abundance and species composition in the SO’s peracarid assemblages is limited, and with regard to ice coverage it is unknown. The aim of our study was to assess the influence of sea ice coverage, chlorophyll-a, and phytoplankton concentrations on abundance, distribution and assemblage structure of peracarids. In addition, the influence of other physical parameters on peracarid abundance was assessed, including depth, temperature, salinity, sediment type, current velocity, oxygen, iron, nitrate, silicate and phosphate. Peracarids were sampled with an epibenthic sledge (EBS) in different areas of the Atlantic sector of the SO and in the Weddell Sea. Sampling areas were characterized by different regimes of ice coverage (the ice free South Orkney Islands, the seasonally ice-covered Filchner Trough and the Eastern Antarctic Peninsula including the Prince Gustav Channel which was formerly covered by a perennial ice shelf). In total 64766 individuals of peracarids were collected and identified to order level including five orders: Amphipoda, Cumacea, Isopoda, Mysidacea, and Tanaidacea. Amphipoda was the most abundant taxon, representing 32% of the overall abundances, followed by Cumacea (31%), Isopoda (29%), Mysidacea (4%), and Tanaidacea (4%). The Filchner Trough had the highest abundance of peracarids, while the South Orkney Islands showed the lowest abundance compared to other areas. Ice coverage was the main environmental driver shaping the abundance pattern and assemblage structure of peracarids and the latter were positively correlated with ice coverage and chlorophyll-a concentration. We propose that the positive correlation between sea ice and peracarid abundances is likely due to phytoplankton blooms triggered by seasonal sea ice melting, which might increase the food availability for benthos. Variations in ice coverage extent and seasonality due to climate change would strongly influence the abundance and assemblage structure of benthic peracarids.
To search for novel strategies to enhance the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis pathways in glioblastoma, we used the B-cell lymphoma 2/Bcl2-like 2-inhibitor ABT-737. Here we report that ABT-737 and TRAIL cooperate to induce apoptosis in several glioblastoma cell lines in a highly synergistic manner (combination index <0.1). Interestingly, the concerted action of ABT-737 and TRAIL to trigger the accumulation of truncated Bid (tBid) at mitochondrial membranes is identified as a key underlying mechanism. ABT-737 and TRAIL cooperate to cleave BH3-interacting domain death agonist (Bid) into its active fragment tBid, leading to increased accumulation of tBid at mitochondrial membranes. Coinciding with tBid accumulation, the activation of Bcl2-associated X protein (Bax), loss of mitochondrial membrane potential, release of cytochrome-c and second mitochondria-derived activator of caspase (Smac) into the cytosol and caspase activation are strongly increased in cotreated cells. Of note, knockdown of Bid significantly decreases ABT-737- and TRAIL-mediated Bax activation and apoptosis. Also, caspase-3 silencing reduces ABT-737- and TRAIL-induced Bid cleavage and apoptosis, indicating that a caspase-3-driven, mitochondrial feedback loop contributes to Bid processing. Importantly, ABT-737 profoundly enhances TRAIL-triggered apoptosis in primary cultured glioblastoma cells derived from tumor material, underlining the clinical relevance. Also, ABT-737 acts in concert with TRAIL to suppress tumor growth in an in vivo glioblastoma model. In conclusion, the rational combination of ABT-737 and TRAIL cooperates to trigger tBid mitochondrial accumulation and apoptosis. This approach presents a promising strategy for targeting the apoptosis pathways in glioblastoma, which warrants further investigation.
Background: Intracerebral haemorrhage growth is associated with poor clinical outcome and is a therapeutic target for improving outcome. We aimed to determine the absolute risk and predictors of intracerebral haemorrhage growth, develop and validate prediction models, and evaluate the added value of CT angiography.
Methods: In a systematic review of OVID MEDLINE—with additional hand-searching of relevant studies' bibliographies— from Jan 1, 1970, to Dec 31, 2015, we identified observational cohorts and randomised trials with repeat scanning protocols that included at least ten patients with acute intracerebral haemorrhage. We sought individual patient-level data from corresponding authors for patients aged 18 years or older with data available from brain imaging initially done 0·5–24 h and repeated fewer than 6 days after symptom onset, who had baseline intracerebral haemorrhage volume of less than 150 mL, and did not undergo acute treatment that might reduce intracerebral haemorrhage volume. We estimated the absolute risk and predictors of the primary outcome of intracerebral haemorrhage growth (defined as >6 mL increase in intracerebral haemorrhage volume on repeat imaging) using multivariable logistic regression models in development and validation cohorts in four subgroups of patients, using a hierarchical approach: patients not taking anticoagulant therapy at intracerebral haemorrhage onset (who constituted the largest subgroup), patients taking anticoagulant therapy at intracerebral haemorrhage onset, patients from cohorts that included at least some patients taking anticoagulant therapy at intracerebral haemorrhage onset, and patients for whom both information about anticoagulant therapy at intracerebral haemorrhage onset and spot sign on acute CT angiography were known.
Findings: Of 4191 studies identified, 77 were eligible for inclusion. Overall, 36 (47%) cohorts provided data on 5435 eligible patients. 5076 of these patients were not taking anticoagulant therapy at symptom onset (median age 67 years, IQR 56–76), of whom 1009 (20%) had intracerebral haemorrhage growth. Multivariable models of patients with data on antiplatelet therapy use, data on anticoagulant therapy use, and assessment of CT angiography spot sign at symptom onset showed that time from symptom onset to baseline imaging (odds ratio 0·50, 95% CI 0·36–0·70; p<0·0001), intracerebral haemorrhage volume on baseline imaging (7·18, 4·46–11·60; p<0·0001), antiplatelet use (1·68, 1·06–2·66; p=0·026), and anticoagulant use (3·48, 1·96–6·16; p<0·0001) were independent predictors of intracerebral haemorrhage growth (C-index 0·78, 95% CI 0·75–0·82). Addition of CT angiography spot sign (odds ratio 4·46, 95% CI 2·95–6·75; p<0·0001) to the model increased the C-index by 0·05 (95% CI 0·03–0·07).
Interpretation: In this large patient-level meta-analysis, models using four or five predictors had acceptable to good discrimination. These models could inform the location and frequency of observations on patients in clinical practice, explain treatment effects in prior randomised trials, and guide the design of future trials.
Funding: UK Medical Research Council and British Heart Foundation.
By analyzing 𝑒+𝑒− annihilation data with an integrated luminosity of 2.93 fb−1 collected at the center-of-mass energy √𝑠=3.773 GeV with the BESIII detector, we present the first absolute measurements of the branching fractions of twenty Cabibbo-suppressed hadronic 𝐷0(+) decays involving multiple pions. The highest four branching fractions obtained are ℬ(𝐷0→𝜋+𝜋−𝜋0) = (1.343±0.013stat±0.016syst)%, ℬ(𝐷0→𝜋+𝜋−2𝜋0) = (1.002±0.019stat±0.024syst)%, ℬ(𝐷+→2𝜋+𝜋−𝜋0) = (1.165±0.021stat±0.021syst)%, and ℬ(𝐷+→2𝜋+𝜋−2𝜋0) = (1.074±0.040stat±0.030syst)%. The 𝐶𝑃 asymmetries for the six decays with highest signal yields are also determined and found to be compatible with zero.
By analyzing e+e− annihilation data with an integrated luminosity of 2.93 fb−1 collected at the center-of-mass energy s√= 3.773 GeV with the BESIII detector, we present the first absolute measurements of the branching fractions of twenty Cabibbo-suppressed hadronic D0(+) decays involving multiple pions. The largest four branching fractions obtained are B(D0→π+π−π0) = >(1.343±0.013stat±0.016syst)%, B(D0→π+π−2π0) = (0.998±0.019stat±0.024syst)%, B(D+→2π+π−π0)
(1.174±0.021stat±0.021syst)%, and B(D+→2π+π−2π0) = (1.074±0.040stat±0.030syst)%. The CP asymmetries for the six decays with highest event yields are also determined.
We show the absence of an instability of homogeneous (chiral) condensates against spatially inhomogeneous perturbations for various 2+1-dimensional four-fermion and Yukawa models. All models are studied at non-zero baryon chemical potential, while some of them are also subjected to chiral and isospin chemical potential. The considered theories contain up to 16 Lorentz-(pseudo)scalar fermionic interaction channels. We prove the stability of homogeneous condensates by analyzing the bosonic two-point function, which can be expressed in a purely analytical form at zero temperature. Our analysis is presented in a general manner for all of the different discussed models. We argue that the absence of an inhomogeneous chiral phase (where the chiral condensate is spatially non-uniform) follows from this lack of instability. Furthermore, the existence of a moat regime, where the bosonic wave function renormalization is negative, in these models is ruled out.
We show the absence of an instability of homogeneous (chiral) condensates against spatially inhomogeneous perturbations for various 2+1-dimensional four-fermion and Yukawa models. All models are studied at non-zero baryon chemical potential, while some of them are also subjected to chiral and isospin chemical potential. The considered theories contain up to 16 Lorentz-(pseudo)scalar fermionic interaction channels. We prove the stability of homogeneous condensates by analyzing the bosonic two-point function, which can be expressed in a purely analytical form at zero temperature. Our analysis is presented in a general manner for all of the different discussed models. We argue that the absence of an inhomogeneous chiral phase (where the chiral condensate is spatially non-uniform) follows from this lack of instability. Furthermore, the existence of a moat regime, where the bosonic wave function renormalization is negative, in these models is ruled out.