Hidden in Plain Sight: Subgroup Shifts Escape OOD Detection

The safe application of machine learning systems in healthcare relies on valid performance claims. Such claims are typically established in a clinical validation setting designed to be as close as possible to the intended use, but inadvertent domain or population shifts remain a fundamental problem. In particular, subgroups may be differently represented in the data distribution in the validation compared to the application setting. For example, algorithms trained on population cohort data spanning all age groups may be predominantly applied in elderly people. While these data are not “out-of distribution”, changes in the prevalence of different subgroups may have considerable impact on algorithm performance or will at least render original performance claims invalid. Both are serious problems for safely deploying machine learning systems. In this paper, we demonstrate the fundamental limitations of individual example out-of-distribution detection for such scenarios, and show that subgroup shifts can be detected on a population-level instead. We formulate population-level shift detection in the framework of statistical hypothesis testing and show that recent state-of-the-art statistical tests can be effectively applied to subgroup shift detection in a synthetic scenario as well as real histopathology images

Epidemiological associations between brachycephaly and upper respiratory tract disorders in dogs attending veterinary practices in England

Background: Brachycephalic dog breeds are increasingly common. Canine brachycephaly has been associated with upper respiratory tract (URT) disorders but reliable prevalence data remain lacking. Using primary-care veterinary clinical data, this study aimed to report the prevalence and breed-type risk factors for URT disorders in dogs. Results: The sampling frame included 170,812 dogs attending 96 primary-care veterinary clinics participating within the VetCompass Programme. Two hundred dogs were randomly selected from each of three extreme brachycephalic breed types (Bulldog, French Bulldog and Pug) and three common small-to medium sized breed types (moderate brachycephalic: Yorkshire Terrier and non-brachycephalic: Border Terrier and West Highland White Terrier). Information on all URT disorders recorded was extracted from individual patient records. Disorder prevalence was compared between groups using the chi-squared test or Fisher’s test, as appropriate. Risk factor analysis used multivariable logistic regression modelling. During the study, 83 (6.9 %) study dogs died. Extreme brachycephalic dogs (median longevity: 8.6 years, IQR: 2.4-10.8) were significantly younger at death than the moderate and non-brachycephalic group of dogs (median 12.7 years, IQR 11.1-15.0) (P \u3c 0.001). A higher proportion of deaths in extreme brachycephalic breed types were associated with URT disorders (4/24 deaths, 16.7 %) compared with the moderate and non-brachycephalic group (0/59 deaths, 0.0 %) (P = 0.001). The prevalence of having at least one URT disorder in the extreme brachycephalic group was higher (22.0 %, 95 % confidence interval (CI): 18.0-26.0) than in the moderate and non-brachycephalic group (9.7 %, 95 % CI: 7.1-12.3, P \u3c 0.001). The prevalence of URT disorders varied significantly by breed type: Bulldogs 19.5 %, French Bulldogs 20.0 %, Pugs 26.5 %, Border Terriers 9.0 %, West Highland White Terriers 7.0 % and Yorkshire Terriers 13.0 % (P \u3c 0.001). After accounting for the effects of age, bodyweight, sex, neutering and insurance, extreme brachycephalic dogs had 3.5 times (95 % CI: 2.4-5.0, P \u3c 0.001) the odds of at least one URT disorder compared with the moderate and non-brachycephalic group. Conclusions: In summary, this study reports that URT disorders are commonly diagnosed in Bulldog, French Bulldog, Pug, Border Terrier, WHWT and Yorkshire Terrier dogs attending primary-care veterinary practices in England. The three extreme brachycephalic breed types (Bulldog, French Bulldog and Pug) were relatively short-lived and predisposed to URT disorders compared with three other small-to-medium size breed types that are commonly owned (moderate brachycephalic Yorkshire Terrier and non-brachycephalic: Border Terrier and WHWT). Conclusions: In summary, this study reports that URT disorders are commonly diagnosed in Bulldog, French Bulldog, Pug, Border Terrier, WHWT and Yorkshire Terrier dogs attending primary-care veterinary practices in England. The three extreme brachycephalic breed types (Bulldog, French Bulldog and Pug) were relatively short-lived and predisposed to URT disorders compared with three other small-to-medium size breed types that are commonly owned (moderate brachycephalic Yorkshire Terrier and non-brachycephalic: Border Terrier and WHWT)

Coupling Superconducting Qubits via a Cavity Bus

Superconducting circuits are promising candidates for constructing quantum bits (qubits) in a quantum computer; single-qubit operations are now routine, and several examples of two qubit interactions and gates having been demonstrated. These experiments show that two nearby qubits can be readily coupled with local interactions. Performing gates between an arbitrary pair of distant qubits is highly desirable for any quantum computer architecture, but has not yet been demonstrated. An efficient way to achieve this goal is to couple the qubits to a quantum bus, which distributes quantum information among the qubits. Here we show the implementation of such a quantum bus, using microwave photons confined in a transmission line cavity, to couple two superconducting qubits on opposite sides of a chip. The interaction is mediated by the exchange of virtual rather than real photons, avoiding cavity induced loss. Using fast control of the qubits to switch the coupling effectively on and off, we demonstrate coherent transfer of quantum states between the qubits. The cavity is also used to perform multiplexed control and measurement of the qubit states. This approach can be expanded to more than two qubits, and is an attractive architecture for quantum information processing on a chip.Comment: 6 pages, 4 figures, to be published in Natur

A reduced integer programming model for the ferry scheduling problem

We present an integer programming model for the ferry scheduling problem, improving existing models in various ways. In particular, our model has reduced size in terms of the number of variables and constraints compared to existing models by a factor of approximately O(n), where n being the number of ports. The model also handles efficiently load/unload time constraints, crew scheduling and passenger transfers. Experiments using real world data produced high quality solutions in 12 hours using CPLEX 12.4 with a performance guarantee of within 15% of optimality, on average. This establishes that using a general purpose integer programming solver is a viable alternative in solving the ferry scheduling problem of moderate size.Comment: To appear in Public Transpor

The role of ongoing dendritic oscillations in single-neuron dynamics

The dendritic tree contributes significantly to the elementary computations a neuron performs while converting its synaptic inputs into action potential output. Traditionally, these computations have been characterized as temporally local, near-instantaneous mappings from the current input of the cell to its current output, brought about by somatic summation of dendritic contributions that are generated in spatially localized functional compartments. However, recent evidence about the presence of oscillations in dendrites suggests a qualitatively different mode of operation: the instantaneous phase of such oscillations can depend on a long history of inputs, and under appropriate conditions, even dendritic oscillators that are remote may interact through synchronization. Here, we develop a mathematical framework to analyze the interactions of local dendritic oscillations, and the way these interactions influence single cell computations. Combining weakly coupled oscillator methods with cable theoretic arguments, we derive phase-locking states for multiple oscillating dendritic compartments. We characterize how the phase-locking properties depend on key parameters of the oscillating dendrite: the electrotonic properties of the (active) dendritic segment, and the intrinsic properties of the dendritic oscillators. As a direct consequence, we show how input to the dendrites can modulate phase-locking behavior and hence global dendritic coherence. In turn, dendritic coherence is able to gate the integration and propagation of synaptic signals to the soma, ultimately leading to an effective control of somatic spike generation. Our results suggest that dendritic oscillations enable the dendritic tree to operate on more global temporal and spatial scales than previously thought

Somatic VHL gene alterations in MEN2-associated medullary thyroid carcinoma

BACKGROUND: Germline mutations in RET are responsible for multiple endocrine neoplasia type 2 (MEN2), an autosomal dominantly inherited cancer syndrome that is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia/adenoma. Recent studies suggest a "second hit" mechanism resulting in amplification of mutant RET. Somatic VHL gene alterations are implicated in the pathogenesis of MEN2 pheochromocytomas. We hypothesized that somatic VHL gene alterations are also important in the pathogenesis of MEN2-associated MTC. METHODS: We analyzed 6 MTCs and 1 C-cell hyperplasia (CCH) specimen from 7 patients with MEN2A and RET germline mutations in codons 609, 618, 620, or 634, using microdissection, microsatellite analysis, phosphorimage densitometry, and VHL mutation analysis. RESULTS: First, we searched for allelic imbalance between mutant and wild-type RET by using the polymorphic markers D10S677, D10S1239, and RET on thyroid tissue from these patients. Evidence for RET amplification by this technique could be demonstrated in 3 of 6 MTCs. We then performed LOH analysis using D3S1038 and D3S1110 which map to the VHL gene locus at 3p25/26. VHL gene deletion was present in 3 MTCs. These 3 MTCs also had an allelic imbalance between mutant and wild-type RET. Mutation analysis of the VHL gene showed a somatic frameshift mutation in 1 MTC that also demonstrated LOH at 3p25/26. In the 2 other MTCs with allelic imbalance of RET and somatic VHL gene deletion, no somatic VHL mutation could be detected. The CCH specimen did neither reveal RET imbalance nor somatic VHL gene alterations. CONCLUSION: These data suggest that a RET germline mutation is necessary for development of CCH, that allelic imbalance between mutant and wild-type RET may set off tumorigenesis, and that somatic VHL gene alterations may not play a major role in tumorigenesis of MEN2A-associated MTC

Interest Groups, NGOs or Civil Society Organisations? The Framing of Non-State Actors in the EU

Scholars have used varying terminology for describing non-state entities seeking to influence public policy or work with the EU’s institutions. This paper argues that the use of this terminology is not and should not be random, as different ‘frames’ come with different normative visions about the role(s) of these entities in EU democracy. A novel bibliometric analysis of 780 academic publications between 1992 and 2020 reveals that three frames stand out: The interest group frame, the NGO frame, as well as the civil society organisation frame; a number of publications also use multiple frames. This article reveals the specific democratic visions contained in these frames, including a pluralist view for interest groups; a governance view for NGOs as ‘third sector’ organisations, and participatory and deliberative democracy contributions for civil society organisations. The use of these frames has dynamically changed over time, with ‘interest groups’ on the rise. The results demonstrate the shifting focus of studies on non-state actors in the EU and consolidation within the sub-field; the original visions of European policy-makers emerging from the 2001 White Paper on governance may only partially come true

Synthesis of Glass Nanofibers Using Femtosecond Laser Radiation Under Ambient Condition

We report the unique growth of nanofibers in silica and borosilicate glass using femtosecond laser radiation at 8 MHz repetition rate and a pulse width of 214 fs in air at atmospheric pressure. The nanofibers are grown perpendicular to the substrate surface from the molten material in laser-drilled microvias where they intertwine and bundle up above the surface. The fibers are few tens of nanometers in thickness and up to several millimeters in length. Further, it is found that at some places nanoparticles are attached to the fiber surface along its length. Nanofiber growth is explained by the process of nanojets formed in the molten liquid due to pressure gradient induced from the laser pulses and subsequently drawn into fibers by the intense plasma pressure. The attachment of nanoparticles is due to the condensation of vapor in the plasma

Franck-Condon blockade in suspended carbon nanotube quantum dots

Understanding the influence of vibrational motion of the atoms on electronic transitions in molecules constitutes a cornerstone of quantum physics, as epitomized by the Franck-Condon principle of spectroscopy. Recent advances in building molecular-electronics devices and nanoelectromechanical systems open a new arena for studying the interaction between mechanical and electronic degrees of freedom in transport at the single-molecule level. The tunneling of electrons through molecules or suspended quantum dots has been shown to excite vibrational modes, or vibrons. Beyond this effect, theory predicts that strong electron-vibron coupling dramatically suppresses the current flow at low biases, a collective behaviour known as Franck-Condon blockade. Here we show measurements on quantum dots formed in suspended single-wall carbon nanotubes revealing a remarkably large electron-vibron coupling and, due to the high quality and unprecedented tunability of our samples, admit a quantitative analysis of vibron-mediated electronic transport in the regime of strong electron-vibron coupling. This allows us to unambiguously demonstrate the Franck-Condon blockade in a suspended nanostructure. The large observed electron-vibron coupling could ultimately be a key ingredient for the detection of quantized mechanical motion. It also emphasizes the unique potential for nanoelectromechanical device applications based on suspended graphene sheets and carbon nanotubes.Comment: 7 pages, 3 figure

Task-Dependent Interaction between Parietal and Contralateral Primary Motor Cortex during Explicit versus Implicit Motor Imagery

Both mental rotation (MR) and motor imagery (MI) involve an internalization of movement within motor and parietal cortex. Transcranial magnetic stimulation (TMS) techniques allow for a task-dependent investigation of the interhemispheric interaction between these areas. We used image-guided dual-coil TMS to investigate interactions between right inferior parietal lobe (rIPL) and left primary motor cortex (M1) in 11 healthy participants. They performed MI (right index-thumb pinching in time with a 1 Hz metronome) or hand MR tasks, while motor evoked potentials (MEPs) were recorded from right first dorsal interosseous. At rest, rIPL conditioning 6 ms prior to M1 stimulation facilitated MEPs in all participants, whereas this facilitation was abolished during MR. While rIPL conditioning 12 ms prior to M1 stimulation had no effect on MEPs at rest, it suppressed corticomotor excitability during MI. These results support the idea that rIPL forms part of a distinct inhibitory network that may prevent unwanted movement during imagery tasks