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Despite the availability of more than 20 antiseizure drugs (ASDs) for the treatment of epilepsy, up to 30% of patients continue to experience disabling seizures and are classified as having medically refractory epilepsy (MRE).1 Some patients with MRE are candidates for resective surgery or other palliative interventions, such as disconnection therapies (callosotomy or subpial transections).2 Unfortunately, the majority of refractory patients are not candidates for these surgical options due to having multifocal epileptogenic foci, foci localized to an eloquent brain area or because the focus cannot be adequately localized.3,4 For some of these patients, stimulation therapy (also known as neuromodulation) is an alternative palliative treatment option. This chapter will review the different neuromodulation modalities that are available as adjunctive treatment of MRE. The impact of neuromodulation on sudden unexplained death in epilepsy (SUDEP) will be explored in the final section.
Surgical site infections (SSIs) are common surgical complications that lead to increased costs. Depending on payer type, however, they do not necessarily translate into deficits for every hospital.
We investigated how surgical site infections (SSIs) influence the contribution margin in 2 reimbursement systems based on diagnosis-related groups (DRGs).
This preplanned observational health cost analysis was nested within a Swiss multicenter randomized controlled trial on the timing of preoperative antibiotic prophylaxis in general surgery between February 2013 and August 2015. A simulation of cost and income in the National Health Service (NHS) England reimbursement system was conducted.
Of 5,175 patients initially enrolled, 4,556 had complete cost and income data as well as SSI status available for analysis. SSI occurred in 228 of 4,556 of patients (5%). Patients with SSIs were older, more often male, had higher BMIs, compulsory insurance, longer operations, and more frequent ICU admissions. SSIs led to higher hospital cost and income. The median contribution margin was negative in cases of SSI. In SSI cases, median contribution margin was Swiss francs (CHF) −2045 (IQR, −12,800 to 4,848) versus CHF 895 (IQR, −2,190 to 4,158) in non-SSI cases. Higher ASA class and private insurance were associated with higher contribution margins in SSI cases, and ICU admission led to greater deficits. Private insurance had a strong increasing effect on contribution margin at the 10th, 50th (median), and 90th percentiles of its distribution, leading to overall positive contribution margins for SSIs in Switzerland. The NHS England simulation with 3,893 patients revealed similar but less pronounced effects of SSI on contribution margin.
Depending on payer type, reimbursement systems with DRGs offer only minor financial incentives to the prevention of SSI.
In interwar Germany, internationalism and nationalism coexisted in a public sphere that often transcended national borders. This seeming contradiction helps explain the mindset of an era, which simultaneously recognized interconnectedness while privileging national identity. Historians’ interest in internationalism has primarily focused on liberal and cooperative actors and on some selected examples demonstrating the dark sides of internationalism. Fewer historians, however, have analyzed the ambiguities and contradictions of liberal internationalism and the perseverance of the national as a frame of reference in internationalist discourses. Ernst Jäckh, best known as the founder of the Deutsche Hochschule für Politik, perhaps best represented this collision of values while simultaneously being one of the biggest proponents of such a view. Jäckh's internationalism permeated all his endeavors and served the goal of reintegrating Germany in the international community.
Environmental scientists and managers increasingly recognize that socio-cultural evaluations expand the understanding of human–nature relationships. Here, user groups’ perceptions of the benefits from and threats to nature were analysed in Tierra del Fuego National Park, Argentina. We hypothesized that the different relationships of users to this place would lead to significantly different valuations among local Ushuaia residents (n = 122), Argentine nationals (n = 147) and international tourists (n = 294). All users perceived a broad spectrum of benefits. The three groups assessed intrinsic and relational values more highly than instrumental benefits, and significant differences included a higher mean valuation of benefits by Argentine visitors. Overall, threats were less perceived than benefits, and significant differences included a higher mean threat assessment by Ushuaia residents. To explain these relationships, we found that mean valuations of benefits and threats were weakly related to increased biodiversity knowledge for residents and international tourists, but not for Argentine visitors. These findings can orient environmental management in Patagonia and elsewhere by identifying areas where information can improve user experiences and by contributing a more pluralistic understanding of nature from multiple stakeholders.
There has been a steep increase in empirical research in economics in the past 20–30 years. This chapter brings together several actors and stakeholders in these developments to discuss their drivers and implications. All types of data are considered: official data, data collected by researchers, lab experiments, randomized control trials, and proprietary data from private and public sources. When relevant, emphasis is placed on developments specific to Europe. The basic message of the chapter is that there is no single type of data that is superior to all others. We need to promote diversity of data sources for economic research and ensure that researchers are equipped to take advantage of them. All stakeholders – researchers, research institutions, funders, statistical agencies, central banks, journals, data firms, and policy-makers – have a role to play in this.
The past 20–30 years have witnessed a steady rise in empirical research in economics. In fact, a majority of articles published by leading journals these days are empirical, in stark contrast with the situation 40 or 50 years ago (Hamermesh, 2013). This change in the distribution of methodologies used in economic research was made possible by improved computing power but, more importantly, thanks to an increase in the quantity, quality and variety of data used in economics.
This chapter brings together several actors and stakeholders in these changes to discuss their drivers and implications. All types of data are considered. When relevant, emphasis is placed on developments specific to Europe. Sections 13.2 and 13.3 deal with official microdata. Section 13.2 focuses on the level of access to microdata in Europe and its determinants. Section 13.3 focuses on cross-country data harmonization. Section 13.4 then switches gears entirely and discusses the benefits and costs of large-scale data collection efforts led by researchers, instead of statistical offices. Section 13.5 discusses data produced by researchers, either in the context of lab experiments or in the context of randomized control trials. Both types of data have led to major advances; for the first one in our understanding of human behaviour and the robustness of economic institutions; for the second in our understanding of the impact of policies and themechanisms underlying them.
We agree with Lake and colleagues on their list of “key ingredients” for building human-like intelligence, including the idea that model-based reasoning is essential. However, we favor an approach that centers on one additional ingredient: autonomy. In particular, we aim toward agents that can both build and exploit their own internal models, with minimal human hand engineering. We believe an approach centered on autonomous learning has the greatest chance of success as we scale toward real-world complexity, tackling domains for which ready-made formal models are not available. Here, we survey several important examples of the progress that has been made toward building autonomous agents with human-like abilities, and highlight some outstanding challenges.
An efficient and robust method to measure vitamin D (25-hydroxy vitamin D3 (25(OH)D3) and 25-hydroxy vitamin D2 in dried blood spots (DBS) has been developed and applied in the pan-European multi-centre, internet-based, personalised nutrition intervention study Food4Me. The method includes calibration with blood containing endogenous 25(OH)D3, spotted as DBS and corrected for haematocrit content. The methodology was validated following international standards. The performance characteristics did not reach those of the current gold standard liquid chromatography-MS/MS in plasma for all parameters, but were found to be very suitable for status-level determination under field conditions. DBS sample quality was very high, and 3778 measurements of 25(OH)D3 were obtained from 1465 participants. The study centre and the season within the study centre were very good predictors of 25(OH)D3 levels (P<0·001 for each case). Seasonal effects were modelled by fitting a sine function with a minimum 25(OH)D3 level on 20 January and a maximum on 21 July. The seasonal amplitude varied from centre to centre. The largest difference between winter and summer levels was found in Germany and the smallest in Poland. The model was cross-validated to determine the consistency of the predictions and the performance of the DBS method. The Pearson’s correlation between the measured values and the predicted values was r 0·65, and the sd of their differences was 21·2 nmol/l. This includes the analytical variation and the biological variation within subjects. Overall, DBS obtained by unsupervised sampling of the participants at home was a viable methodology for obtaining vitamin D status information in a large nutritional study.
Vitamin E (α-tocopherol) is recognised as a key essential lipophilic antioxidant in humans protecting lipoproteins, PUFA, cellular and intra-cellular membranes from damage. The aim of this review was to evaluate the relevant published data about vitamin E requirements in relation to dietary PUFA intake. Evidence in animals and humans indicates a minimal basal requirement of 4–5 mg/d of RRR-α-tocopherol when the diet is very low in PUFA. The vitamin E requirement will increase with an increase in PUFA consumption and with the degree of unsaturation of the PUFA in the diet. The vitamin E requirement related to dietary linoleic acid, which is globally the major dietary PUFA in humans, was calculated to be 0·4–0·6 mg of RRR-α-tocopherol/g of linoleic acid. Animal studies show that for fatty acids with a higher degree of unsaturation, the vitamin E requirement increases almost linearly with the degree of unsaturation of the PUFA in the relative ratios of 0·3, 2, 3, 4, 5 and 6 for mono-, di-, tri-, tetra-, penta- and hexaenoic fatty acids, respectively. Assuming a typical intake of dietary PUFA, a vitamin E requirement ranging from 12 to 20 mg of RRR-α-tocopherol/d can be calculated. A number of guidelines recommend to increase PUFA intake as they have well-established health benefits. It will be prudent to assure an adequate vitamin E intake to match the increased PUFA intake, especially as vitamin E intake is already below recommendations in many populations worldwide.
Two compact H-band (220–325 GHz) low-noise millimeter-wave monolithic integrated circuit (MMIC) amplifiers have been developed, based on a grounded coplanar waveguide (GCPW) technology utilizing 50 and 35 nm metamorphic high electron mobility transistors (mHEMTs). For low-loss packaging of the circuits, a set of waveguide-to-microstrip transitions has been realized on 50-μm-thick GaAs substrates demonstrating an insertion loss of <0.5 dB at 243 GHz. By applying the 50 nm gate-length process, a four-stage cascode amplifier module achieved a small-signal gain of 30.6 dB at 243 GHz and more than 28 dB in the bandwidth from 218 to 280 GHz. A second amplifier module, based on the 35-nm mHEMT technology, demonstrated a considerably improved gain of 34.6 dB at 243 GHz and more than 32 dB between 210 and 280 GHz. At the operating frequency, the two broadband low-noise amplifier modules achieved a room temperature noise figure of 5.6 dB (50 nm) and 5.0 dB (35 nm), respectively.
The hindguts of lower termites harbor highly diverse, endemic communities of symbiotic protists, bacteria, and archaea essential to the termite's ability to digest wood. Despite over a century of experimental studies, ecological roles of many of these microbes are unknown, partly because almost none can be cultivated. Many of the protists associate with bacterial symbionts, but hypotheses for their respective roles in nutrient exchange are based on genomes of only two such bacteria. To show how the ecological roles of protists and nutrient transfer with symbiotic bacteria can be elucidated by direct imaging, we combined stable isotope labeling (13C-cellulose) of live termites with analysis of fixed hindgut microbes using correlated scanning electron microscopy, focused ion beam-scanning electron microscopy (FIB-SEM), transmission electron microscopy, and high resolution imaging mass spectrometry (NanoSIMS). We developed methods to prepare whole labeled cells on solid substrates, whole labeled cells milled with a FIB-SEM instrument to reveal cell interiors, and ultramicrotome sections of labeled cells for NanoSIMS imaging of 13C enrichment in protists and associated bacteria. Our results show these methods have the potential to provide direct evidence for nutrient flow and suggest the oxymonad protist Oxymonas dimorpha phagocytoses and enzymatically degrades ingested wood fragments, and may transfer carbon derived from this to its surface bacterial symbionts.
Vitamin D deficiency is associated with osteoporosis and is thought to increase the risk of cancer and CVD. Despite these numerous potential health effects, data on vitamin D status at the population level and within key subgroups are limited. The aims of the present study were to examine patterns of 25-hydroxyvitamin D (25(OH)D) levels worldwide and to assess differences by age, sex and region. In a systematic literature review using the Medline and EMBASE databases, we identified 195 studies conducted in forty-four countries involving more than 168 000 participants. Mean population-level 25(OH)D values varied considerably across the studies (range 4·9–136·2 nmol/l), with 37·3 % of the studies reporting mean values below 50 nmol/l. The highest 25(OH)D values were observed in North America. Although age-related differences were observed in the Asia/Pacific and Middle East/Africa regions, they were not observed elsewhere and sex-related differences were not observed in any region. Substantial heterogeneity between the studies precluded drawing conclusions on overall vitamin D status at the population level. Exploratory analyses, however, suggested that newborns and institutionalised elderly from several regions worldwide appeared to be at a generally higher risk of exhibiting lower 25(OH)D values. Substantial details on worldwide patterns of vitamin D status at the population level and within key subgroups are needed to inform public health policy development to reduce risk for potential health consequences of an inadequate vitamin D status.