Miracle-dz/UniFAR-FTUs huggingface dataset:
Methods for proper handling of overrunning and underrunning in phase II designs for oncology trials

Phase II studies in oncology are frequently conducted as two‐stage single‐arm trials with a binary endpoint indicating tumor response. As a common feature of these designs, the sample sizes of the two stages and the decision rules for the interim and the final analysis have to be pre‐specified and adhered to strictly during the course of the trial in order to assure control of the type I error rate. In practice, however, the attained sample sizes often deviate from the planned ones leading to the situation of overrunning or underrunning. The currently available approaches to deal with this problem are either based on assumptions that are rarely met in practice or do not guarantee that the significance level is kept. However, strict control of the type I error rate plays an important role also for single‐arm cancer trials, as they are frequently a fundamental part of the registration information. We propose a general methodology that allows handling both unintentional and intentional overrunning and underrunning while strictly controlling the type I error rate. Application of the proposed procedure and some of its characteristics are illustrated with a real phase II oncology trial. Copyright © 2015 John Wiley & Sons, Ltd.
Rapid Changes of Body Weight after a Headstand: A Metrological Analysis

Despite recent rules from amateur wrestling sport-governing bodies intended to discourage extreme weight loss measures, wrestling culture still includes varied methods to make weight, including holding a headstand position immediately before stepping on the scale. The procedure, according to the notion, will reduce reported mass anywhere between 250 and 500g (weight between 2.45 and 4.89 N). The aim of this study was to compare any possible differences between the headstand procedure (HS) and a normal (CON) weight measure, using a metrological approach defined by the European Association of National Metrology Institutes. Seventeen adult men were weighed on a force plate before and after doing a headstand or standing normally for 30s. The order of treatment application was assigned randomly. Post-test weight was significantly larger than pre-test (mean±s.d.) (640.7±62.8 N and 640.3±62.7 N, respectively, p<0.0001) under both treatments. No treatment vs. time of test interaction was found. No significant difference was found between CON and HS weight (640.6±62.8 N and 640.9±62.9 N, respectively, p=0.3815). The metrological tests suggest that the statistical differences found are related to the force plate measuring errors in every pre-established time interval. The 45g (0.44 N) difference found between pretest and post-test lies within the uncertainty range identified for the equipment (±110 g or 1.08 N). In conclusion, a 30-second headstand has no significant effect on registered body weight. The small variations obtained were due to equipment-associated measuring errors. This experiment offers systematic empirical evidence to aid in the elimination of this unjustified practice among the wrestling community.
Room-temperature manipulation and decoherence of a single spin in diamond

Here, we report coherent control of the electron spin state of a single N-V center at room temperature. We demonstrate that we can coherently drive single-spin rotations Rabi nutations and undo low-frequency dephasing by application of a Hahn spin echo sequence. We use this capability to study the coherence of the N-V center as a function of applied magnetic field. By comparing the magnetic-field dependences of the decoherence rate and the photoluminescence, we find that the coherence of the N-V center spin is strongly affected by the resonant spin exchange with the surrounding nitrogen spins at specific magnetic fields. At other fields, we find evidence that the dephasing caused by spin flips of the nitrogen electrons is the main contribution to the observed decoherence. The N-V center consists of a substitutional nitrogen atom next to a vacancy in the diamond lattice. We study the negatively charged state of the N-V center N-V  , which has a
Vanishing Importance: Studying Immersive Effects of Game Audio Perception on Player Experiences in Virtual Reality

Sound and virtual reality (VR) are two important output modalities for creating an immersive player experience (PX). While prior research suggests that sounds might contribute to a more immersive experience in games played on screens and mobile displays, there is not yet evidence of these effects of sound on PX in VR. To address this, we conducted a within-subjects experiment using a commercial horror-adventure game to study the effects of a VR and monitor-display version of the same game on PX. Subsequently, we explored, in a between-subjects study, the effects of audio dimensionality on PX in VR. Results indicate that audio has a more implicit influence on PX in VR because of the impact of the overall sensory experience and that audio dimensionality in VR may not be a significant factor contributing to PX. Based on our findings and observations, we provide five design guidelines for VR games.
How Should We Lower Blood Pressure after Cerebral Hemorrhage? A Systematic Review and Meta-Analysis

Background: The optimal treatment of high blood pressure (BP) after acute intra-cerebral hemorrhage (ICH) is controversial. Summary: The aim of the study was to evaluate the safety and efficacy of early intensive vs. conservative BP lowering treatment in patients with ICH. Randomized controlled trials with active and control groups receiving intensive and conservative BP lowering treatments were identified. The following outcomes were assessed: 3-month mortality and combined death or major disability, 24-h hematoma growth, early neurological deterioration, occurrence of hypotension, severe hypotension, and serious treatment-emergent adverse events. Five trials were included involving 4,350 participants, 2,162 and 2,188 for intensive and conservative treatment groups, respectively. The pooled risk ratio of 3-month death or major disability was 0.96 (0.91-1.01) and the weighted mean difference in absolute hematoma growth was -1.53 (95% CI -2.94 to -0.12) mL in the intensive compared to conservative BP-lowering. There were no differences across the treatments in the incidence rates of 3-month mortality, early neurological deterioration, hypotension, and treatment-related adverse effects other than renal events. Key Messages: The early intensive anti-hypertensive treatment was overall safe and reduced the hematoma expansion in patients presenting with acute-onset spontaneous ICH and high BP levels.
Dose of exercise and health benefit.

Blair and Cooper's 1 informative editorial raises important issues regarding the dose of exercise and health benefits. We agree that sedentary men and women may benefit from becoming moderately active but disagree on the shape of the dose-response curve between physical activity and its health benefits. 2 We also interpret prospective epidemiological data, which show fewer deaths in men who improve their fitness over time, differently; Blair and Cooper believe the lower mortality is caused by increased physical activity, and I largely attribute the lower mortality to regression to the mean. The editorial claims that cardiorespiratory fitness (treadmill test duration) is more accurate and objective than reported physical activity. The reproducibility I have observed of self-reported weekly running distance (r=0.89) 3 is as strong as treadmill test duration from previous trials (r=0.89 in 30 sedentary men 4 and r=0.62 in 83 sedentary overweight men 5,6 ). I believe this amount of
Analysis of TV audience flow based on the lingered channel matrix

At present, the analysis of television ratings gives priority to ordinary sectional analysis which is represented by audience ratings, market share and other indices, and has little analysis of the audience flowing. Additionally, traditional research method of audience flowing has some problems such as high time cost, large storage space, weak reusability and no analysis about overall flow trend or audience clustering. This paper proposes a new scheme on the analysis of audience flowing. It is based on the established lingered channel matrix produced by raw viewing data. From the angle of channels (or programs) and users, this paper adopts the conventional mathematical statistics method and clustering algorithm to reflect audience flowing between different channels and their own viewing behavior in detail. The lingered channel matrix established by the scheme clearly shows the channel that audience linger at every moment, leaving the original viewing data away and avoiding the problem of high cost of time and storage space by repeatedly reading and processing raw data. Moreover, the matrix provides the data base for the subsequent extension research, in order to realize the analysis of TV audience flowing in a deeply vertical level.
Lack of red hair phenotype in a North‐African obese child homozygous for a novel POMC null mutation: nonsense‐mediated decay RNA evaluation and hair pigment chemical analysis

cytokines from the nervous system itself. Proinflammatory cytokines, including IL-1b and tumour necrosis factor-a, are upregulated in response to trauma to the nerve and can act directly on receptors expressed by cells of the nervous system. It was shown in various experiments that exogenous IL-1b can directly induce hyperalgesia when injected into a peripheral nerve in mice, and mice with genetically impaired IL-1 signalling do not develop neuropathic pain behaviour. Experiments with IL-1RA also showed that mice treated with IL-1RA, compared with placebo, did not exhibit an allodynic response, and IL-1RA also reduced allodynia in mice with established allodynic response. There are no human studies of IL-1RA in patients with neuropathic pain to date. Our patient had recurrent urticarial rash, joint pain and fatigue with an IgM paraprotein compatible with Schnitzler’s syndrome. That the diagnosis was only made 2 years after the onset of her illness as a result of repeated serum electrophoresis and immunofixation highlights the importance of having a high clinical suspicion. Her intercostal neuralgia responded within 48 h to anakinra suggesting that IL-1 plays an important role in the development of neuropathic pain and Schnitzler’s syndrome. It is not clear whether this effect is due to the reduction of inflammation around the nerve or is a direct effect on IL-1 signalling in the neurons.
Intermittent Noise Induces Physiological Stress in a Coastal Marine Fish

Anthropogenic noise in the ocean has increased substantially in recent decades, and motorized vessels produce what is likely the most common form of underwater noise pollution. Noise has the potential to induce physiological stress in marine fishes, which may have negative ecological consequences. In this study, physiological effects of increased noise (playback of boat noise recorded in the field) on a coastal marine fish (the giant kelpfish, Heterostichus rostratus) were investigated by measuring the stress responses (cortisol concentration) of fish to increased noise of various temporal dynamics and noise levels. Giant kelpfish exhibited acute stress responses when exposed to intermittent noise, but not to continuous noise or control conditions (playback of recorded natural ambient sound). These results suggest that variability in the acoustic environment may be more important than the period of noise exposure for inducing stress in a marine fish, and provide information regarding noise levels at which physiological responses occur.
Physical-layer encryption on the public internet: a stochastic approach to the Kish-Sethuraman cipher

While information-theoretic security is often associated with the one-time pad and quantum key distribution, noisy transport media leave room for classical techniques and even covert operation. Transit times across the public internet exhibit a degree of randomness, and cannot be determined noiselessly by an eavesdropper. We demonstrate the use of these measurements for information-theoretically secure communication over the public internet.
Distinct cytokine and regulatory T cell profile at pleural sites of dual HIV/tuberculosis infection compared to that in the systemic circulation

Pleural tuberculosis (TB) remains a common presentation of Mycobacterium tuberculosis (MTB) infection in HIV/TB dually infected subjects, and both cellular and acellular components of the pleural milieu promote HIV‐1 replication; however, they remain uncharacterized. Using cytokine array of pleural fluid and real‐time reverse transcription–polymerase chain reaction (RT–PCR) and immunophenotype analysis, pleural fluid mononuclear cells (PFMC) were compared to systemic counterparts [i.e. plasma and peripheral blood mononuclear cells (PBMC)]. Significant increases in pleural fluid cytokines compared to plasma were limited to interleukin (IL)‐6, IL‐8, interferon (IFN)‐γ and transforming growth factor (TGF)‐β, and did not include other T helper type 1 (Th1) (IL‐2, IL‐15), Th2 or Th17 cytokines. Patterns and levels of cytokines were indistinguishable between pleural fluid from HIV/TB and TB patients. Forkhead box P3 (FoxP3) mRNA in PFMC was increased significantly and correlated highly with levels of IL‐6 and IL‐8, less with TGF‐β, and not with IFN‐γ. Among CD4 T cells, FoxP3‐reactive CD25hi were increased in HIV/TB dually infected subjects compared to their PBMC, and up to 15% of FoxP3+ CD25hi CD4 T cells were positive for IL‐8 by intracellular staining. These data implicate a dominant effect of MTB infection (compared to HIV‐1) at pleural sites of dual HIV/TB infection on the local infectious milieu, that include IL‐6, IL‐8, IFN‐γ and TGF‐β and regulatory T cells (Treg). A correlation in expansion of Treg with proinflammatory cytokines (IL‐6 and IL‐8) in pleural fluid was shown. Treg themselves may promote the inflammatory cytokine milieu through IL‐8.
Whispering Gallery Modes for Accurate Characterization of Optical Fibers’ Parameters

Whispering gallery modes (WGMs) are surface modes that propagate azimuthally around resonators with rotational symmetry (toroidal, spherical, or, as in our case, cylindrical shaped, since the optical fiber itself plays the role of the microresonator). These modes are resonant in optical wavelength, and the spectral position of the resonances depends on the radius and the refractive index of the microresonator material. Due to the high-quality factor of the resonances (as high as 10 7 in cylindrical microresonators), they allow measuring different parameters with high sensitivities and very low detection limits. Here, we report the use of WGMs to characterize the properties of the material that forms the microresonator. In particular, we highlight the use of this technique to measure temperature profiles along conventional and special fibers (such as photosensitive or doped fibers), elasto-optic coefficients, and UV-induced absorption loss coefficients of different photosensitive fibers. These parameters of the fibers set the optical response of fiber-based components and may change when the device is in use in an optical system; thus, this technique allows an accurate characterization of the devices and leads to proper designs of components with specific optical responses.
Information Contents of a Signal at Repeated Positioning Measurements of the Coordinate Measuring Machine (CMM) by Laser Interferometer

Abstract The input of this paper lies in displaying possibilities how to determine the condition of a coordinate measuring machine (CMM) based on a large number of repeated measurements. The number of repeated measurements exceeds common requirements for determining positioning accuracy. The total offset in the accuracy of spatial positioning consists of partial inaccuracies of individual axes. 6 basic errors may be defined at each axis. In a triaxial set, that translates into 18 errors, to which an offset from the perpendicularity between the axial pairs must be added. Therefore, the combined number of errors in a single position is 21. These errors are systemic and stem from the machine’s geometry. In addition, there are accidental errors to account for as well. Accidental errors can be attributed to vibrations, mass inertness, passive resistance, and in part to fluctuations in temperature. A peculiar set of systemic errors are time-varying errors. The nature of those errors may be reversible, for instance if they result from influence of temperature or elastic deformation. They can be also irreversible, for example as a result of wear and tear or line clogging, due to loosened connection or permanent deformation of a part post collision. A demonstration of thermal equalizing of the machine’s parts may also be observed in case of failure to adhere to a sufficient time interval from the moment the air-conditioning is turned on. Repeated measurements done on a selected axis with linear interferometer can provide complex information on the CMM condition and also on the machine’s interaction with the given technical environment.
Genomics of human longevity

In animal models, single-gene mutations in genes involved in insulin/IGF and target of rapamycin signalling pathways extend lifespan to a considerable extent. The genetic, genomic and epigenetic influences on human longevity are expected to be much more complex. Strikingly however, beneficial metabolic and cellular features of long-lived families resemble those in animals for whom the lifespan is extended by applying genetic manipulation and, especially, dietary restriction. Candidate gene studies in humans support the notion that human orthologues from longevity genes identified in lower species do contribute to longevity but that the influence of the genetic variants involved is small. Here we discuss how an integration of novel study designs, labour-intensive biobanking, deep phenotyping and genomic research may provide insights into the mechanisms that drive human longevity and healthy ageing, beyond the associations usually provided by molecular and genetic epidemiology. Although prospective studies of humans from the cradle to the grave have never been performed, it is feasible to extract life histories from different cohorts jointly covering the molecular changes that occur with age from early development all the way up to the age at death. By the integration of research in different study cohorts, and with research in animal models, biological research into human longevity is thus making considerable progress.
Overcoming partial shading issue of PV modules by using a resonant switched capacitor converter

Partial shading effect is one of the most serious challenges in photovoltaic (PV) structures. In this paper a new switched-capacitor convertor has been proposed to reduce the partial shading problems. The proposed converter is a combination of dual-phase and half bridge converters that reduce the partial shading effect base on Differential Power Processing (DPP) technique, the proposed converter can increase the output voltage, as well. Also, soft switching is realized by the converter which leads to high efficiency value. The resonant power converter principle operation mode has been analyzed, mathematically. To verify the given analyses two 60 W prototype converters have been implemented.
Remediating a Design Tool: Implications of Digitizing Sticky Notes

Sticky notes are ubiquitous in design processes because of their tangibility and ease of use. Yet, they have well-known limitations in professional design processes, as documentation and distribution are cumbersome at best. This paper compares the use of sticky notes in ideation with a remediated digital sticky notes setup. The paper contributes with a nuanced understanding of what happens when remediating a physical design tool into digital space, by emphasizing focus shifts and breakdowns caused by the technology, but also benefits and promises inherent in the digital media. Despite users' preference for creating physical notes, handling digital notes on boards was easier and the potential of proper documentation make the digital setup a possible alternative. While the analogy in our remediation supported a transfer of learned handling, the users' experiences across technological setups impact their use and understanding, yielding new concerns regarding cross-device transfer and collaboration.
Brain Reward Circuits in Morphine Addiction

Morphine is the most potent analgesic for chronic pain, but its clinical use has been limited by the opiate’s innate tendency to produce tolerance, severe withdrawal symptoms and rewarding properties with a high risk of relapse. To understand the addictive properties of morphine, past studies have focused on relevant molecular and cellular changes in the brain, highlighting the functional roles of reward-related brain regions. Given the accumulated findings, a recent, emerging trend in morphine research is that of examining the dynamics of neuronal interactions in brain reward circuits under the influence of morphine action. In this review, we highlight recent findings on the roles of several reward circuits involved in morphine addiction based on pharmacological, molecular and physiological evidences.
An Experiment to Prove the Effect of Low-Level Magnetic Fields Resulting from Ionospheric Changes on Humans

Abstract The investigation presented in the paper was performed in the laboratories of the Department of Theoretical and Experimental Electrical Engineering, Faculty of Electrical Engineering and Communication, Brno University of Technology, between April 22 and June 26, 2014. We examined a homogeneous sample of male and female participants comprising a total of 49 persons aged 19 to 26. The time required for the measurement of psychophysiological parameters corresponded to 19 minutes, encompassing five stages: Basic (5 mins.), Color (2 mins.), Rest (5 mins.), Math (2 mins.), and Rest (5 mins.). All the measuring cycles were carried out using a BioGraph Infiniti device (Thought Technology, Ltd.). Generally, the impact of the environment upon living organisms constitutes a crucial problem examined by today’s science. In this context, the present article describes the results of an investigation focused on ionosphere parameter variation and its role in the basic function of the nervous system. The discussed research concentrates on the measurement and detection of changes in the region of very low electromagnetic field frequencies; the authors introduce and verify related theoretical and experimental procedures to define the effects that influence brain activity and the cardiovascular system.
PARTIAL REPRODUCTIVE ISOLATION OF A RECENTLY DERIVED RESIDENT‐FRESHWATER POPULATION OF THREESPINE STICKLEBACK (GASTEROSTEUS ACULEATUS) FROM ITS PUTATIVE ANADROMOUS ANCESTOR

We used no‐choice mating trials to test for assortative mating between a newly derived resident‐freshwater population (8–22 generations since founding) of threespine stickleback (Gasterosteus aculeatus) in Loberg Lake, Alaska and its putative anadromous ancestor as well as a morphologically convergent but distantly related resident‐freshwater population. Partial reproductive isolation has evolved between the Loberg Lake population and its ancestor within a remarkably short time period. However, Loberg stickleback readily mate with morphologically similar, but distantly related resident‐freshwater stickleback. Partial premating isolation is asymmetrical; anadromous females and smaller resident‐freshwater males from Loberg Lake readily mate, but the anadromous males and smaller Loberg females do not. Our results indicate that premating isolation can begin to evolve in allopatry within a few generations after isolation as a correlated effect of evolution of reduced body size.