259594 research outputs found
Sort by
Genauigkeit der geschätzten Effektgröße in randomisierten kontrollierten kardiovaskulären Studien
No full textThema: Die geschätzte Effektgröße ist wichtig für die Berechnung der Stichprobengröße in randomisierten kontrollierten Studien (RCTs). Eine möglichst genaue Schätzung ist hierbei erstrebenswert. Fragestellung:Wie genau wird die Effektgröße in randomisierten kontrollierten kardiovaskulären Studien geschätzt und gibt es Faktoren, die mit der Genauigkeit korrelieren?Methodik:Es wurde eine systematische Literaturrecherche in der Medline-Datenbank durchgeführt. Es wurden randomisierte kontrollierte Studien zu kardiovaskulären Erkrankungen identifiziert, welche zwischen dem 01.01.2010 und dem 31.12.2019 im NEJM, The Lancet oder JAMA veröffentlicht wurden. Die Genauigkeit der Effektgröße wurde als Verhältnis zwischen der beobachteten und der geschätzten Effektgröße definiert. Mittels linearer Regression wurden die Korrelationen zu vorher festgelegten Eigenschaften der RCTs wie beispielsweise der Sponsorenschaft erfasst.Ergebnisse:Von den initial 875 erfassten Publikationen wurden 263 Überlegenheitsstudien in die Analyse eingeschlossen. 216 RCTs (82.1%) von diesen überschätzten die Effektgröße. Die mittlere Überschätzung betrug hierbei in der linearen Regression 23.1%. Studien mit einem zusammengesetzten Endpunkt, einer Verblindung oder fehlender spezifischer Begründung der Effektgrößenschätzung wiesen eine genauere Schätzung der Effektgröße auf.Zusammenfassung:Vier von fünf randomisierten kontrollierten kardiovaskulären Studien überschätzten die Effektgröße. Einzelne Eigenschaften der RCTs korrelierten mit einer genaueren Schätzung der Effektgröße
Syntax-aware differential fuzzing of black-box network protocol implementations
No full textProtocols for secure network communication are a cornerstone of our digitalized life, but implementing them is a complicated and error-prone task. Most such protocols are very complex, while their specifications tend to come as voluminous and sometimes ambiguous prose text. As a result, flaws in their implementations are hard to avoid, but easily cause interoperability issues or impair security. Identifying flaws in (i.e., testing) such implementations is of highest importance. One technique that has proven very successful for implementation testing is fuzzing. One of its key ideas is to generate test input in a randomized way. If the implementation under test runs into some exceptional execution state (e.g., crashes) while processing the input, a flaw in the tested implementation has been found. The outstanding advantage of fuzzing is that it allows full automation and features a very low barrier to deployment. On the other hand, its disadvantage is that relying on exceptional execution states typically implies the need for invasive forms of program monitoring and defeats the detectability of semantic flaws. Moreover is unspecific randomized input generation hardly suitable for testing implementations that expect complex and highly-structured input data. When it comes to testing implementations of complex network protocols like such for secure communication, however, both semantic flaws and complex message formats are a key concern. Therefore, in this thesis, we propose and study a novel concept called syntax-aware differential protocol fuzzing (SDPF). It addresses the aforementioned disadvantages of fuzzing in the following way. First, SDPF includes a novel protocol-independent, fuzzing-based, and response-guided input generation approach. It can be customized to become syntax-aware for binary-encoded messages with little manual effort. This allows to efficiently generate mostlyvalid protocol messages even for very complex message structures. Second, SDPF makes use of differential testing, i.e., it uses multiple implementations of the same protocol to gather evidence of implementation flaws from behavioural discrepancies. This can spare invasive program monitoring to some extent and enable sensitivity to semantic flaws without the need to explicitly distinguish correct from potentially incorrect implementation behaviour. Our work was the first to make differential testing applicable to the message processing and protocol logic routines of complex network protocols. Using the Transport Layer Security (TLS) protocol as a representative example, we experimentally show that our input generation approach finds more behavioural discrepancies and achieves better code coverage than other approaches. As is the case for differential testing in general, tracking down the root cause of a behavioural discrepancies remains as a manual task for a human tester. Unfortunately, the complexity of test messages often makes such manual investigation very timeconsuming. Besides, optional protocol features and liberal specifications can cause false positives and give rise to unprofitable investigation effort. To address this, we propose and study a novel concept called message feature-based differential testing. It probes and contrasts how different implementations react to the presence or absence of well-defined properties in stimulation messages. One of the advantages of message feature-based differential testing over classical differential testing is that, for each discrepancy found, the respective message property naturally provides a very specific hint for a human tester where to start a manual investigation. Using TLS and its implementations as an example, we experimentally show how message featurebased differential testing can help to identify implementation flaws. As one of the key ingredients of SDPF and message feature-based differential testing, we propose and discuss a novel concept called Generic Message Trees (GMTs). A GMT is a versatile, tree-like data structure that enables a syntax-aware, user-friendly, unified, and efficient handling of binary-encoded network protocol messages. GMTs are one of the main drivers of the low-effort syntax awareness provided by our approaches. In the course of our experimental evaluations, we identified several previously-unknown implementation flaws in widespread open-source TLS implementations. Among them is a combination of two flaws in a single implementation, which in conjunction lead to a significant security vulnerability. Our work can be the basis for interesting further research in various directions. This includes, for example, the application to and evaluation on other protocols than TLS and the usability of our approach for remote implementation fingerprinting.Protokolle für sichere Netzwerkkommunikation stellen einen Grundpfeiler unseres digitalisierten Lebens dar; deren Implementierung ist jedoch eine schwierige und fehleranfällige Aufgabe. Entsprechende Protokolle sind meistens sehr komplex, während deren Spezifikationen dazu neigen, sehr umfangreich zu sein und auf teilweise uneindeutigem Prosatext zu basieren. Infolgedessen sind Implementierungsfehler kaum zu vermeiden, wobei diese jedoch leicht Interoperabilitätsprobleme verursachen oder die Sicherheit (Security) beeinträchtigen. Fehler in solchen Implementierungen zu identifizieren (d. h. diese zu testen) ist von größter Wichtigkeit. Eine Technik zum Testen von Implementierungen, die sich als sehr erfolgreich herausgestellt hat, ist Fuzzing. Eine wesentliche Idee dabei ist das zufallsbasierte Erzeugen von Testeingaben. Wenn die zu testende Implementierung beim Verarbeiten der Testeingabe in einen Ausnahmezustand gerät (z. B. abstürzt), wurde ein Fehler in dieser gefunden. Der besondere Vorteil von Fuzzing ist, dass es vollständig automatisiert ablaufen kann und sehr einfach einzusetzen ist. Der Nachteil hingegen ist, dass das Stützen auf Ausnahmezustände im Programmablauf der zu testenden Implementierung typischerweise die Notwendigkeit einer invasiven Form der Programmüberwachung mit sich bringt und die Erkennbarkeit von semantischen Fehlern ausschließt. Zudem ist eine unspezifische, zufallsgetriebene Eingabeerzeugung für ein Testen von Implementierungen, die komplexe und hochstrukturierte Eingabedaten erwarten, kaum geeignet. Beim Testen von Implementierungen komplexer Netzwerkprotokolle wie solcher für die sichere Kommunikation sind semantische Fehler und komplexe Nachrichtenformate jedoch zentrale Belange. Daher wird in der vorliegenden Arbeit ein neuartiges Konzept mit der Bezeichnung Syntax-aware differential protocol fuzzing (SDPF) vorgestellt und untersucht. Es adressiert die zuvor genannten Nachteile und Einschränkungen in folgender Weise. Erstens setzt SDPF ein neuartiges protokollunabhängiges, fuzzing-basiertes und reaktionsgeführtes Verfahren zur Generierung von Testeingaben ein. Dieses kann mit geringem Aufwand auf konkrete Nachrichtenformate mit Binärkodierung ausgelegt werden. Damit erlaubt es, selbst für sehr komplexe Nachrichtenformate weitestgehend gültige Nachrichten effizient zu erzeugen. Zweitens setzt SDPF auf differenzielles Testen; d. h. es nutzt mehrere Implementierungen des gleichen Protokolls, um aus Verhaltensdifferenzen Hinweise auf Fehlverhalten abzuleiten. Das macht invasive Programmüberwachung zu einem gewissen Grad entbehrlich und ermöglicht es, sensitiv auf semantische Fehler zu sein, ohne explizit korrektes von potenziell inkorrektem Implementierungsverhalten unterscheiden können zu müssen. Die vorliegende Arbeit hat erstmals die Anwendbarkeit von differenziellem Testen auf Routinen der Nachrichtenverarbeitung und Protokolllogik nachgewiesen. Am Beispiel des Transport Layer Security (TLS) Protokolls wird experimentell gezeigt, dass der verwendete Ansatz zur Generierung von Testeingaben mehr Verhaltensdifferenzen erzeugt und eine besser Code-Abdeckung erzielt als andere Ansätze. Wie allgemein beim Einsatz differenziellen Testens der Fall, bleibt das Aufspüren der Ursache von Verhaltensdifferenzen eine manuelle Aufgabe. Leider macht die Komplexität der Testnachrichten eine solche manuelle Analyse häufig sehr zeitaufwändig. Zudem können optionale Protokollfunktionalitäten und liberale Spezifikationen falsch-positive Ergebnisse hervorrufen, deren Untersuchung sich am Ende als wertlos herausstellt. Um dem zu begegnen, wird ein neuartiges Konzept mit der Bezeichnung Message feature-based differential testing vorgestellt und untersucht. Dabei werden die Reaktionen mehrerer Implementierungen des gleichen Protokolls auf das Vorhanden- oder Nichtvorhandensein wohldefinierter Eigenschaften in Eingabenachrichten sondiert und gegenübergestellt. Ein Vorteil dieses Ansatzes gegenüber klassischem differenziellem Testen ist, dass sich für jede identifizierte Verhaltens- bzw. Reaktionsdifferenz aus der betrachteten Nachrichteneigenschaft auf natürliche Weise ein deutlicher Hinweis zur Unterstützung der manuellen Ursachensuche ergibt. Es wird experimentell am Beispiel von TLS gezeigt, wie der Ansatz das Aufspüren von Implementierungsfehlern unterstützen kann. Als einen Grundpfeiler der beiden vorgenannten Ansätze (Syntax-aware differential protocol fuzzing und Message feature-based differential testing) wird ein neuartiges Konzept mit der Bezeichnung Generic Message Trees (GMTs) vorgeschlagen und diskutiert. Ein GMT ist eine vielseitige, baumartige Datenstruktur, die bei Unabhängigkeit vom Nachrichtenformat trotzdem einen nutzerfreundlichen, einheitlichen, und effizienten Umgang mit binärkodierten Netzwerkprotokollnachrichten erlaubt. GMTs sind einer der Träger der Möglichkeit der aufwandsarmen Berücksichtigung des jeweiligen Nachrichtenformats in den vorgenannten Ansätzen. Im Zuge der experimentellen Untersuchung wurden mehrere zuvor unbekannte Implementierungsfehler in verbreiteten open-source TLS-Implementierungen entdeckt. Darunter ist auch eine Kombination zweier Fehler in einer einzelnen Implementierung, welche in Zusammenwirkung zu einer bedeutsamen Schwachstelle führen. Die vorliegende Arbeit kann als Basis weiterer, interessanter Untersuchungen in verschiedensten Richtungen dienen. Hierzu zählt z. B. die Anwendung und Untersuchung des Ansatzes auf andere Protokolle als TLS sowie die Nutzung zum Fingerprinting von Implementierungen über das Netzwerk
Fault-melt interaction and its implications for Venusian Tectonic regimes in Aphrodite Terra, Venus
No full textVenus is believed to be deformed in a stagnant-lid, episodic-lid, or a plutonic-squishy-lid regime with mantle convection occurring beneath a unified lithosphere [1-3]. Its surface age, estimated at 240–800 Ma from impact crater records [4], suggests either a catastrophic resurfacing event involving rapid lithospheric recycling [5] or continuous, regionally tectonic and volcanic processes [6]. Here we raise a key question how strain localization occurs on Venus: do Venusian faults show evidence of multi-stage activation capable of leading to large-scale lithospheric deformation, and is it possible to use this to unravel the tectonic history of Venus?To address this, we focused our investigation on the equatorial chasmata system in Eastern Aphrodite Terra, Venus, whose origin continues to be a subject of scientific debate. This study documents that the troughs consistently exhibit asymmetric cross-sectional profiles, with steeper slopes intersected by large-scale faults trending subparallel to the trough axis. These shear zones dip at low angles and occasionally form terraces along the slope profile, exposing sections of the shear planes. The shear planes are radar-smooth and exhibit radar emissivities distinct from the adjacent hanging wall and footwall. We propose that these fault planes be coated with melt films, which in some cases display flow features along downslope trajectories.The formation of these melt films is explored in the context of frictional melting during co-seismic faulting. Frictional melting may be enhanced on Venus due to its elevated ambient temperatures and the likely water-free, mafic composition of its rocks. However, multi-incremental friction-induced melting is unlikely to result in significant strain localization, and the volume of melt generated even under Venusian conditions is insufficient to be resolved in the available SAR imagery. Instead, we hypothesize that the fault planes act as conduits for transporting magma from shallow subsurface reservoirs to the surface. Volcanic centers and edifices near the steep chasmata slopes and within corona interiors are potential sources for shallow subsurface melt reservoirs. Melt veneers along the fault planes may reduce friction coefficients, facilitating normal faulting at shallow dip angles.The overall morphology of the troughs suggests that the faults were initially formed as thrust faults and later reactivated. Evidence of their youthfulness is provided by fresh hummocky landslide deposits originating from the steep hanging wall scarps, which partially obscure the exposed fault planes. They were likely triggered by fault-induced seismicity, suggesting that faulting on Venus is seismogenic. Seismic moments for the studied shear zones have been calculated to support fault activation
Hubs and interaction: the brain’s meta-loop
No full textWe must reconcile the needs of the internal world and the demands of the external world to make decisions relevant to homeostasis, well-being, and flexible behavior. Engagement with the internal (eg interoceptive) world is linked to medial brain systems, whereas the extrapersonal space (eg exteroceptive) is associated with lateral brain systems. Using Human Connectome Project data, we found three association tracts connecting the action-related frontal lobe with perception-related posterior lobes. A lateral dorsal tract and a medial dorsal tract interact independently with a ventral tract at frontal and posterior hubs. The two frontal and the two posterior hubs are interconnected, forming a meta-loop that integrates lateral and medial brain systems. The four anatomical hubs correspond to the common nodes of the intrinsic cognitive brain networks such as the default mode network. These functional networks depend on the integration of both realms. Thus, the positioning of functional cognitive networks can be understood as the intersection of long anatomical association tracts. The strength of structural connectivity within lateral and medial brain systems correlates with performance on behavioral tests assessing theory of mind. The meta-loop provides an anatomical framework to associate neurological and psychiatric symptoms with functional and structural changes
Special diets and nutrient intakes in morbidly obese US adults in comparison to the 2020-2025 Dietary Guidelines for Americans
No full textBackgroundMorbid Obesity (MO), defined by a Body Mass Index (BMI) > 40 kg/m2, is the most severe form of obesity. The risk of suffering from any chronic medical condition is almost twice as high in MO as compared to overweight. Despite obesity being one of the most serious contemporary public health concerns, there is a paucity of nutrient intake data in adults with MO. Nutritional assessments in morbidly obese adults are often based on individuals seeking weight loss surgery rather than focusing on the general community.MethodsUsing National Health and Nutrition Examination Surveys data (NHANES, 2007–2016), we estimated nutrient intakes in the general US population with MO, thereby focusing on a comparative assessment to the Dietary Guidelines for Americans (DGA, 2020–2025). Nutrient intakes were assessed in morbidly obese US adults with a BMI > 40 kg/m2, regardless of their intention to seek weight loss treatment and regardless of reporting special diets. Sex- and age-specific nutrient intake assessments were performed, with the aim to identify population subgroups that may warrant particular attention from a public health perspective.ResultsThe study sample comprised 1,708 participants with MO. This may be extrapolated to represent 14,047,276 US Americans. MO was more prevalent in females as compared to males (65.60% vs 34.40%) and the sample’s average age was 46.25 years, with a tendency towards a lower mean age in higher BMI groups. The alignment with the DGA was poor across both sexes, and particularly with regard to the nutrients of public health concern (fiber, calcium), saturated fatty acid intake and the intakes of several fat-soluble vitamins. Fiber intake was found to be particularly low in females with MO. Total energy intake was not associated with BMI in participants with MO. Morbidly obese individuals frequently reported special diets, with up to 28% of the examined population disclosing at least one special diet.ConclusionsUsing a descriptive epidemiological approach, we identified numerous sociodemographic and nutritional factors associated with MO. The poor alignment with US national dietary guidelines warrants special considerations and dedicated public health nutrition efforts to combat the increasing obesity-related burden
Glaciations and landscape change in the Lower Aare Valley (Northern Switzerland) through the Middle Pleistocene
No full textThroughout the Pleistocene, valley glaciers repeatedly advanced into the forelands of the European Alps. However, the corresponding geological record is highly fragmentary and the regional glaciation history, especially prior to the last glacial maximum, is still poorly documented. We explored the archives of the Lower Aare Valley in the confluence area of the Aare river with Reuss and Limmat, focusing on the overdeepened Gebenstorf-Stilli Trough. In four scientific boreholes, ∼350 m of drill cores were recovered, and complemented with investigations of outcrops and reflection seismics in the nearby glaciofluvial Habsburg-Rinikerfeld Palaeochannel. The integrative interpretation of these data provides new insights into the local landscape evolution: We identified two generations of glacial basin infill in the Gebenstorf-Stilli Trough that are overlain by glaciofluvial gravels, and two distinct glaciofluvial gravel bodies in the neighboring paleochannel. In this specific local setting, gravel petrographic compositions and their statistical analysis prove to be powerful tools to identify inputs from the confluent catchments, to aid in lithostratigraphic classification, and to interpret the depositional and landscape histories. We suggest that it is mainly the penultimate glaciation, characterized by three separate ice advances, that shaped the present-day study area, and whose deposits are preserved in the Middle Pleistocene archives
Direct measurement of necking strain using optical contour analysis on isotropic ductile stainless steel
No full textTo accurately determine yield stress curves for ductile metals, it is essential to account for the triaxial stress state that develops during necking, which complicates the extraction of the equivalent uniaxial stress state. This study introduces a simple yet effective approach to address this challenge. Using a single-camera setup with backlight illumination, silhouette images of the specimen during tensile testing are captured. From these images, the specimen contours are extracted digitally, enabling strain computation based on changes in contour geometry. Simultaneously, a novel curvature-fitting algorithm is employed to calculate stress triaxiality. The accuracy of this method is validated through comparison with finite element simulations, and its applicability spans from the onset of necking to the point of fracture. This approach is demonstrated on 303 stainless steel, showcasing the accurate recovery of equivalent uniaxial true stress–true strain relationships under varying triaxiality conditions. Furthermore, as these stress and strain measures are energy-conjugate, the mechanical work within the neck can be calculated, enabling a direct determination of the Taylor-Quinney coefficient using infrared thermography. The method offers a robust framework for experimental analysis and provides a straightforward route for mechanical and thermal coupling studies. To facilitate broader adoption, an open-source implementation of the program is made available
Twist-drill craniostomy with pressure-controlled fibrinolytic irrigation therapy for the evacuation of bilateral acute traumatic subdural hematoma: illustrative case
No full textBACKGROUNDBilateral acute subdural hematomas (aSDHs) present a significant challenge for neurosurgeons, particularly due to the risk of contralateral hematoma enlargement following unilateral evacuation and subsequent volume shifts. This complexity is further compounded in elderly patients with preexisting health conditions.OBSERVATIONSThis case report presents a novel minimally invasive approach for managing bilateral aSDHs in a 76-year-old female. The patient developed bilateral aSDHs following head trauma and was considered high risk for general anesthesia and bilateral craniotomies. A minimally invasive technique was utilized, involving twist-drill craniostomy under local anesthesia combined with pressure-controlled fibrinolytic therapy using the IRRAflow and LiquoGuard 7 systems. The patient was treated with continuous pressure–controlled irrigation therapy using an electrolyte solution containing 200,000 IU/l of urokinase infused at a rate of 100 ml/hr. The patient showed significant improvement, with complete resolution of the hematomas and no residual neurological deficits.LESSONSThis case demonstrates the effectiveness of minimally invasive techniques that avoid the risks associated with general anesthesia and craniotomies. While these findings are promising, they should be interpreted with caution and require prospective confirmation in a larger cohort of patients. Nonetheless, they align with the recent literature that supports minimally invasive approaches for aSDHs
Burrowing facilitated the survival of mammals in harsh and fluctuating climates
No full textSpecies’ ability to cope with climatic instability varies greatly, influenced by factors such as dispersal, physiological adaptations, and phylogenetic conservatism. Here, we investigate how burrowing behavior, a key component of species’ endurance strategies and ecosystem functioning, shaped the contemporary patterns of species richness and range size as well as the diversification of mammalian lineages. Analyzing 4,407 terrestrial mammal species, excluding bats, combined with novel trait data on 3,096 species, we reveal contrasting responses to climatic factors between burrowing and non-burrowing species. Burrowing lineages are disproportionately species-rich at lower temperatures and productivity. Both range size and species richness steeply increase with climate seasonality in burrowing species as opposed to non-burrowing species. The proportion of burrowing species increases with latitude, with regions above 20°, especially those exhibiting greater Pleistocene temperature changes, being almost exclusively composed of burrowing species. Trait conservatism, higher net diversification rates, and Eocene peak diversification provide the evolutionary context for these contemporary patterns, underscoring the role of burrowing for mammalian radiations into temperate climates. Moreover, the lower extinction rate of burrowing species and peak diversification at the Cretaceous-Paleogene (K-Pg) boundary support the longstanding hypothesis that burrowing behavior promoted survival during the “impact winter” that marks the replacement of non-avian dinosaurs by mammals. Our study highlights the potential of readily available trait information for understanding the ecological and evolutionary processes that shape species distributions through space and time. The careful integration of divergent environmental constraints bears vast improvements for forecasts of species' responses to climatic changes and global models of biodiversity patterns