Bias-Variation Dilemma Challenges Clinical Trials: Inherent Limitations of Randomized Controlled Trials and Meta-Analyses Comparing Hernia Therapies

Purpose: Evaluation of hernia therapies according to the current rules of Evidence Based Medicine is widely reduced to results of RCTs or meta-analyses. RCTs have been accepted as a most important tool to confirm a superior effect of an intervention. Unfortunately, in hernia surgery, comparisons of RCTs and correspondingly their use in meta-analyses, are not, surprisingly often, able to confirm any significant impact of a specific procedure due to intrinsic restrictions in a multi-causal\ud setting with its web of influences. Methods: Based on our own experiences of clinical studies in surgery, the present article outlines several situations, with their respective reasons, which argue the severe limitations of RCTs and meta-analysis to define an optimum treatment. Results: Metaanalyses accumulate the variations of each trial, which then may cover any clear causal relationship. RCTs usually are dealing with subgroups of standard patients thus excluding the majority of our patients. Low statistical power of current cohort sizes restricts the analysis of subgroups or of effects with low incidences. Simple comparisons of means frequently are hampered by nonlinear relationships to outcome. The relevance of a specific variable is difficult to separate from other influences. The limited surveillance period of studies ignores a delayed change in outcome. Randomization cannot guarantee a standardized patient’s condition. All the arguments have to be considered as a crucial and fundamental consequence of the bias-variance dilemma or principle of uncertainty in medicine, and underline the many limitations of RCTs to evaluate any specific impact of hernia therapies on e.g. infection, pain or recurrence. Conclusions: Many surgical issues\ud cannot be and should not be investigated by RCTs, in particular, if a marked patients’ heterogeneity\ud has to be considered or the low incidences of the outcome readout cannot be addressed with sufficient statistical power without getting lost in the variation mire. Registries with their non-restricted data-acquisition should be regarded as reliable alternatives for postoperative outcome quality surveillance studies

Demand during peak hours versus peak-driving demand: Revisiting one size fits all dynamic grid tariffs

Electricity grid tariffs should reflect network costs in order to provide efficient incentives for timing electricity use and investment in new technologies. We compare tariff designs that deal with existing and expected future grid congestion. Although common volumetric tariff designs such as Time-Of-Use are partly cost-reflective, their designs have fundamental drawbacks in terms of the principles of cost allocations and potentially may lead to social disparities. In a case study of 1.56 million Danish households divided into 90 socio-techno-economic categories, we compare three alternative grid tariffs and investigate their impact on annual electricity bills. This study shows that penalizing consumption above a certain threshold leads to higher costs for owners of electric vehicles regardless of the timing of their consumption. In contrast, penalizing consumption during system peaks mainly affects the electricity bills of heat pump owners. The results of our design simultaneously applying a time-dependent threshold and a system peak tariff show (a) a range of different allocations that distribute the burden of additional grid costs across both technologies and (b) strong positive outcomes, including reduced expenses for lower-income groups and smaller households. Our study offers policymakers a menu that assigns grid costs to demand technologies, thereby giving them valuable input.Comment: 30 pages, 18 figures, journal articl

Variability in electricity consumption by category of consumer: the impact on electricity load profiles

Residential electrification of transport and heat is changing consumption and its characteristics significantly. Previous studies have demonstrated the impact of socio-techno-economic determinants on residential consumption. However, they fail to capture the distributional characteristics of such consumer groups, which impact network planning and flexibility assessment. Using actual residential electricity consumption profile data for 720,000 households in Denmark, we demonstrate that heat pumps are more likely to influence aggregated peak consumption than electric vehicles. At the same time, other socio-economic factors, such as occupancy, dwelling area and income, show little impact. Comparing the extrapolation of a comprehensive rollout of heat pumps or electric vehicles indicates that the most common consumer category deploying heat pumps has 14% more maximum consumption during peak load hours, 46% more average consumption and twice the higher median compared to households owning an electric vehicle. Electric vehicle show already flexibility with coincidence factors that ranges between 5-15% with a maximum of 17% whereas heat pumps are mostly baseload. The detailed and holistic outcomes of this study support flexibility assessment and grid planning in future studies but also the operation of flexible technologies.Comment: 37 pages, 18 figures, journal articl

Tension of knotted surgical sutures shows tissue specific rapid loss in a rodent model

<p>Abstract</p> <p>Background</p> <p>Every surgical suture compresses the enclosed tissue with a tension that depends from the knotting force and the resistance of the tissue. The aim of this study was to identify the dynamic change of applied suture tension with regard to the tissue specific cutting reaction.</p> <p>Methods</p> <p>In rabbits we placed single polypropylene sutures (3/0) in skin, muscle, liver, stomach and small intestine. Six measurements for each single organ were determined by tension sensors for 60 minutes. We collected tissue specimens to analyse the connective tissue stability by measuring the collagen/protein content.</p> <p>Results</p> <p>We identified three phases in the process of suture loosening. The initial rapid loss of the first phase lasts only one minute. It can be regarded as cutting through damage of the tissue. The percentage of lost tension is closely related to the collagen content of the tissue (r = -0.424; p = 0.016). The second phase is characterized by a slower decrease of suture tension, reflecting a tissue specific plastic deformation. Phase 3 is characterized by a plateau representing the remaining structural stability of the tissue. The ratio of remaining tension to initial tension of phase 1 is closely related to the collagen content of the tissue (r = 0.392; p = 0.026).</p> <p>Conclusions</p> <p>Knotted non-elastic monofilament sutures rapidly loose tension. The initial phase of high tension may be narrowed by reduction of the surgeons' initial force of the sutures' elasticity to those of the tissue. Further studies have to confirm, whether reduced tissue compression and less local damage permits improved wound healing.</p

Повышение конкурентоспособности предприятия как фактор экономического роста промышленности России на примере нефтяного комплекса

Объектом исследования является: конкурентоспособность АО "Сибирская Сервисная Компания". Предметом исследования являются: факторы и условия конкурентоспособности предприятия, влияющие на экономический рост промышленности. Цель работы – разработка мероприятий по повышению конкурентоспособности АО "Сибирская Сервисная Компания". В результате исследования: разработаны мероприятия по повышению конкурентоспособности АО "Сибирская Сервисная Компания". Практическое значение: на основе оценки эндогенных и экзогенных факторов разработаны сводные мероприятия, дана оценка эффективности от внедрения организационных и технико–технологических мероприятий по повышению конкурентоспособности предприятия.The object of study is: the competitiveness of JSC "Siberian Service Company". The subject of the study are: factors and conditions of enterprise competitiveness, affecting the economic growth of industry. The purpose of the work is the development of measures to increase the competitiveness of Siberian Service Company JSC. As a result of the study: measures were developed to increase the competitiveness of Siberian Service Company JSC. Practical value: based on the assessment of endogenous and exogenous factors, summary measures have been developed, an assessment of the effectiveness of the introduction of organizational, technical and technological measures to increase the competitiveness of the enterprise has been given

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Peri-implant diseases

When celebrating 100 yr of dental research in the Nordic dental research commu- nity (i.e. Nordisk Odontologisk Fo€rening (NOF)), it is relevant to include dental implant treatment. In essence, the successful progress of implant treatment has added both to the quality of life for patients and also to many aspects of profes- sional development and job satisfaction for dentists. When appreciating the success story it also seems relevant to highlight some of the problems related to this treat- ment. Both technical and biological complications have often been ignored when reporting long-term results following implant treatment. Different opinions have been expressed in relation to the etiology of peri-implant diseases. Some even choose to ignore this condition as a clinical problem. This article presents a short overview of peri-implant diseases (i.e. peri-implant mucositis and peri-implantitis). The lack of internationally agreed disease definitions for peri-implant diseases, as with periodontitis, results in wide variation of estimates for the occurrence of peri- implant diseases when epidemiological data are reported. The profession still strives to find and define the best way to deal with peri-implant diseases once they are accurately diagnosed. Awareness of the tissue conditions in the peri-implant area, and relevant action when indicated, seems to be critical for the continued long-term successful outcome of dental implant treatment

Spatio-Temporal Dynamics of Algae and Macrophyte Cover in Urban Lakes: A Remote Sensing Analysis of Bellandur and Varthur Wetlands in Bengaluru, India

Gefördert durch den Publikationsfonds der Universität Kasse