Renal Tumor Invasion Depth and Diameter are the Two Most Accurate Anatomical Features Regarding the Choice of Radical Versus Partial Nephrectomy

Background and Aims: To evaluate simple tumor characteristics (renal tumor diameter and parenchymal invasion depth) compared with more complex classifications, that is, Renal Tumor Invasion Index (RTII) and Preoperative Aspects and Dimensions Used for an Anatomical classification, in predicting the type of nephrectomy (radical vs partial) performed. Material and Methods: A total of 915 patients who had undergone either partial nephrectomy (n=388, 42%) or radical nephrectomy (n=527, 58%) were identified from the Helsinki University Hospital kidney tumor database between 1 January 2006 and 31 December 2014. Tumor maximum diameter and depth of invasion into the parenchyma were estimated from computed tomography or magnetic resonance imaging images and compared with Preoperative Aspects and Dimensions Used for an Anatomical and Renal Tumor Invasion Index. Logistic regression and receiver operating curves were used to compare the parameters at predicting the type of nephrectomy. Results and conclusion: All the anatomical variables of receiver operating curve/area under the curve analyses were significant predictors for the type of nephrectomy. Parenchymal invasion (area under the curve 0.91; 95% confidence interval, 0.89-0.93), RTII (area under the curve 0.91; 95% confidence interval, 0.89-0.93), and diameter (area under the curve 0.91; 95% confidence interval, 0.89-0.93) performed significantly better than Preoperative Aspects and Dimensions Used for an Anatomical classification (area under the curve 0.88; 95% confidence interval, 0.85-0.89). In multivariable analysis, invasion depth was the best predictor of nephrectomy type (percentage correct, 85.6%). Addition of one anatomic parameter into the model of non-anatomical cofactors improved the accuracy of the model significantly, but the addition of more parameters did not. Parenchymal invasion depth and tumor diameter are the most accurate anatomical features for predicting the nephrectomy type. All potential anatomical classification systems should be tested against these two simple characteristics.Peer reviewe

Impact of menstrual function on hormonal response to repeated bouts of intense exercise

Background: Strenous exercise stimulates the hypothalamic-pituitary (HP) axis in order to ensure homeostasis and promote anabolism. Furthermore, exercise stimulates a transient increase in the neurotrophin brain-derived neurotrophic factor (BDNF) suggested to mediate the anxiolytic effects of exercise. Athletes with secondary functional hypothalamic amenorrhea (FHA) have been reported to have lower BDNF, and a blunted HP axis response to exercise as athletes with overtraining syndrome. Aim: The aim of the study was to investigate the hormonal and BDNF responses to a two-bout maximal exercise protocol with four hours of recovery in between in FHA and eumenorrheic (EUM) athletes. Methods: Eumenorrheic (n = 16) and FHA (n = 14) endurance athletes were recruited from national teams and competitive clubs. Protocols included gynecological examination; body composition (DXA); 7-day assessment of energy availability; blood sampling pre and post the two exercises tests. Results: There were no differences between groups in hormonal responses to the first exercise bout. After the second exercise bout IGFBP-3 increased more in FHA compared with EUM athletes (2.1 ± 0.5 vs. 0.6 ± 0.6 μg/L, p = 0.048). There were non-significant trends toward higher increase in IGF-1 (39.3 ± 4.3 vs. 28.0 ± 4.6 μg/L, p = 0.074), BDNF (96.5 ± 22.9 vs. 34.4 ± 23.5 μg/L, p = 0.058), GH to cortisol ratio (0.329 ± 0.010 vs. 0.058 ± 0.010, p = 0.082), and decrease in IGF-1 to IGFBP-3 ratio (−2.04 ± 1.2 vs. 0.92 ± 1.22, p = 0.081) in athletes with FHA compared with EUM athletes. Furthermore, there was a non-significant trend toward a higher increase in prolactin to cortisol ratio in EUM athletes compared with athletes with FHA (0.60 ± 0.15 vs. 0.23 ± 0.15, p = 0.071). No differences in the hormonal or BDNF responses between the two exercise bouts as a result of menstrual function were found. Conclusion: No major differences in the hormonal or BDNF responses between the two exercise bouts as a result of menstrual function could be detected

Quantum feedback control of a superconducting qubit: Persistent Rabi oscillations

The act of measurement bridges the quantum and classical worlds by projecting a superposition of possible states into a single, albeit probabilistic, outcome. The time-scale of this "instantaneous" process can be stretched using weak measurements so that it takes the form of a gradual random walk towards a final state. Remarkably, the interim measurement record is sufficient to continuously track and steer the quantum state using feedback. We monitor the dynamics of a resonantly driven quantum two-level system -- a superconducting quantum bit --using a near-noiseless parametric amplifier. The high-fidelity measurement output is used to actively stabilize the phase of Rabi oscillations, enabling them to persist indefinitely. This new functionality shows promise for fighting decoherence and defines a path for continuous quantum error correction.Comment: Manuscript: 5 Pages and 3 figures ; Supplementary Information: 9 pages and 3 figure

Stabilizing entanglement autonomously between two superconducting qubits

Quantum error-correction codes would protect an arbitrary state of a multi-qubit register against decoherence-induced errors, but their implementation is an outstanding challenge for the development of large-scale quantum computers. A first step is to stabilize a non-equilibrium state of a simple quantum system such as a qubit or a cavity mode in the presence of decoherence. Several groups have recently accomplished this goal using measurement-based feedback schemes. A next step is to prepare and stabilize a state of a composite system. Here we demonstrate the stabilization of an entangled Bell state of a quantum register of two superconducting qubits for an arbitrary time. Our result is achieved by an autonomous feedback scheme which combines continuous drives along with a specifically engineered coupling between the two-qubit register and a dissipative reservoir. Similar autonomous feedback techniques have recently been used for qubit reset and the stabilization of a single qubit state, as well as for creating and stabilizing states of multipartite quantum systems. Unlike conventional, measurement-based schemes, an autonomous approach counter-intuitively uses engineered dissipation to fight decoherence, obviating the need for a complicated external feedback loop to correct errors, simplifying implementation. Instead the feedback loop is built into the Hamiltonian such that the steady state of the system in the presence of drives and dissipation is a Bell state, an essential building-block state for quantum information processing. Such autonomous schemes, broadly applicable to a variety of physical systems as demonstrated by a concurrent publication with trapped ion qubits, will be an essential tool for the implementation of quantum-error correction.Comment: 39 pages, 7 figure

Adaptive Mesh Refinement for Characteristic Grids

I consider techniques for Berger-Oliger adaptive mesh refinement (AMR) when numerically solving partial differential equations with wave-like solutions, using characteristic (double-null) grids. Such AMR algorithms are naturally recursive, and the best-known past Berger-Oliger characteristic AMR algorithm, that of Pretorius & Lehner (J. Comp. Phys. 198 (2004), 10), recurses on individual "diamond" characteristic grid cells. This leads to the use of fine-grained memory management, with individual grid cells kept in 2-dimensional linked lists at each refinement level. This complicates the implementation and adds overhead in both space and time. Here I describe a Berger-Oliger characteristic AMR algorithm which instead recurses on null \emph{slices}. This algorithm is very similar to the usual Cauchy Berger-Oliger algorithm, and uses relatively coarse-grained memory management, allowing entire null slices to be stored in contiguous arrays in memory. The algorithm is very efficient in both space and time. I describe discretizations yielding both 2nd and 4th order global accuracy. My code implementing the algorithm described here is included in the electronic supplementary materials accompanying this paper, and is freely available to other researchers under the terms of the GNU general public license.Comment: 37 pages, 15 figures (40 eps figure files, 8 of them color; all are viewable ok in black-and-white), 1 mpeg movie, uses Springer-Verlag svjour3 document class, includes C++ source code. Changes from v1: revised in response to referee comments: many references added, new figure added to better explain the algorithm, other small changes, C++ code updated to latest versio

Probing the quantum vacuum with an artificial atom in front of a mirror

Quantum fluctuations of the vacuum are both a surprising and fundamental phenomenon of nature. Understood as virtual photons flitting in and out of existence, they still have a very real impact, \emph{e.g.}, in the Casimir effects and the lifetimes of atoms. Engineering vacuum fluctuations is therefore becoming increasingly important to emerging technologies. Here, we shape vacuum fluctuations using a "mirror", creating regions in space where they are suppressed. As we then effectively move an artificial atom in and out of these regions, measuring the atomic lifetime tells us the strength of the fluctuations. The weakest fluctuation strength we observe is 0.02 quanta, a factor of 50 below what would be expected without the mirror, demonstrating that we can hide the atom from the vacuum

Discrete cilia modelling with singularity distributions

We discuss in detail techniques for modelling flows due to finite and infinite arrays of beating cilia. An efficient technique, based on concepts from previous ‘singularity models’ is described, that is accurate in both near and far-fields. Cilia are modelled as curved slender ellipsoidal bodies by distributing Stokeslet and potential source dipole singularities along their centrelines, leading to an integral equation that can be solved using a simple and efficient discretisation. The computed velocity on the cilium surface is found to compare favourably with the boundary condition. We then present results for two topics of current interest in biology. 1) We present the first theoretical results showing the mechanism by which rotating embryonic nodal cilia produce a leftward flow by a ‘posterior tilt,’ and track particle motion in an array of three simulated nodal cilia. We find that, contrary to recent suggestions, there is no continuous layer of negative fluid transport close to the ciliated boundary. The mean leftward particle transport is found to be just over 1 μm/s, within experimentally measured ranges. We also discuss the accuracy of models that represent the action of cilia by steady rotlet arrays, in particular, confirming the importance of image systems in the boundary in establishing the far-field fluid transport. Future modelling may lead to understanding of the mechanisms by which morphogen gradients or mechanosensing cilia convert a directional flow to asymmetric gene expression. 2) We develop a more complex and detailed model of flow patterns in the periciliary layer of the airway surface liquid. Our results confirm that shear flow of the mucous layer drives a significant volume of periciliary liquid in the direction of mucus transport even during the recovery stroke of the cilia. Finally, we discuss the advantages and disadvantages of the singularity technique and outline future theoretical and experimental developments required to apply this technique to various other biological problems, particularly in the reproductive system

Sex-biased parental care and sexual size dimorphism in a provisioning arthropod

The diverse selection pressures driving the evolution of sexual size dimorphism (SSD) have long been debated. While the balance between fecundity selection and sexual selection has received much attention, explanations based on sex-specific ecology have proven harder to test. In ectotherms, females are typically larger than males, and this is frequently thought to be because size constrains female fecundity more than it constrains male mating success. However, SSD could additionally reflect maternal care strategies. Under this hypothesis, females are relatively larger where reproduction requires greater maximum maternal effort – for example where mothers transport heavy provisions to nests. To test this hypothesis we focussed on digger wasps (Hymenoptera: Ammophilini), a relatively homogeneous group in which only females provision offspring. In some species, a single large prey item, up to 10 times the mother’s weight, must be carried to each burrow on foot; other species provide many small prey, each flown individually to the nest. We found more pronounced female-biased SSD in species where females carry single, heavy prey. More generally, SSD was negatively correlated with numbers of prey provided per offspring. Females provisioning multiple small items had longer wings and thoraxes, probably because smaller prey are carried in flight. Despite much theorising, few empirical studies have tested how sex-biased parental care can affect SSD. Our study reveals that such costs can be associated with the evolution of dimorphism, and this should be investigated in other clades where parental care costs differ between sexes and species

Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures

The potassium-chloride co-transporter KCC2, encoded by SLC12A5, plays a fundamental role in fast synaptic inhibition by maintaining a hyperpolarizing gradient for chloride ions. KCC2 dysfunction has been implicated in human epilepsy, but to date, no monogenic KCC2-related epilepsy disorders have been described. Here we show recessive loss-of-function SLC12A5 mutations in patients with a severe infantile-onset pharmacoresistant epilepsy syndrome, epilepsy of infancy with migrating focal seizures (EIMFS). Decreased KCC2 surface expression, reduced protein glycosylation and impaired chloride extrusion contribute to loss of KCC2 activity, thereby impairing normal synaptic inhibition and promoting neuronal excitability in this early-onset epileptic encephalopathy