Miracle-dz/UniFAR-FTUs huggingface dataset:
Guidelines for pharmacokinetic and pharmacodynamic studies in early phase clinical trials

Introduction The Pharmacodynamic/ pharmacokinetic Technologies Advisory Committee (PTAC) of Cancer Research UK has the objective of increasing the extent of mechanistic and hypothesis testing in early phase clinical trials. PTAC reviews all applications submitted to the New Agents Committee (NAC) and with expertise in PET, MRI and MRS as well as many of the other currently emerging technologies, provides advice on the potential use of these techniques to add value to the development of new anticancer agents.
Action Design Research

Design research (DR) positions information technology artifacts at the core of the Information Systems discipline. However, dominant DR thinking takes a technological view of the IT artifact, paying scant attention to its shaping by the organizational context. Consequently, existing DR methods focus on building the artifact and relegate evaluation to a subsequent and separate phase. They value technological rigor at the cost of organizational relevance, and fail to recognize that the artifact emerges from interaction with the organizational context even when its initial design is guided by the researchers' intent. We propose action design research (ADR) as a new DR method to address this problem. ADR reflects the premise that IT artifacts are ensembles shaped by the organizational context during development and use. The method conceptualizes the research process as containing the inseparable and inherently interwoven activities of building the IT artifact, intervening in the organization, and evaluating it concurrently. The essay describes the stages of ADR and associated principles that encapsulate its underlying beliefs and values. We illustrate ADR through a case of competence management at Volvo IT.
Learning behaviour-performance maps with meta-evolution

The MAP-Elites quality-diversity algorithm has been successful in robotics because it can create a behaviorally diverse set of solutions that later can be used for adaptation, for instance to unanticipated damages. In MAP-Elites, the choice of the behaviour space is essential for adaptation, the recovery of performance in unseen environments, since it defines the diversity of the solutions. Current practice is to hand-code a set of behavioural features, however, given the large space of possible behaviour-performance maps, the designer does not know a priori which behavioural features maximise a map's adaptation potential. We introduce a new meta-evolution algorithm that discovers those behavioural features that maximise future adaptations. The proposed method applies Covariance Matrix Adaptation Evolution Strategy to evolve a population of behaviour-performance maps to maximise a meta-fitness function that rewards adaptation. The method stores solutions found by MAP-Elites in a database which allows to rapidly construct new behaviour-performance maps on-the-fly. To evaluate this system, we study the gait of the RHex robot as it adapts to a range of damages sustained on its legs. When compared to MAP-Elites with user-defined behaviour spaces, we demonstrate that the meta-evolution system learns high-performing gaits with or without damages injected to the robot.
Improving multi-view semi-supervised learning with agreement-based sampling

Semi-supervised learning algorithms are widely used to build strong learning models when there are not enough labeled instances. Some semi-supervised learning algorithms, including co-training and co-EM, use multiple views to build learning models. Past research has shown that multi-view learning usually shows advantages over learning with a single view. However, conditions such as independence of the views, which is often hard to achieve, makes successful application of such methods in real world problems difficult. We would like to know if the performance of a multi-view semi-supervised learning method can be improved even though the available views are not necessarily independent. In this paper, we propose a simple sampling method, agreement-based sampling, as one way of improving the classification performance of multi-view semi-supervised learning algorithms. We apply agreement-based sampling to three major multi-view semi-supervised learning algorithms: co-training, co-EM and multi-view semi-supervised ensemble. The experiments with real-world datasets show that our sampling method can indeed significantly improve the performance of these three algorithms. We also investigated the relation between the quality of the expanded labeled set generated by the semi-supervised learning algorithm and the classification error rate of the learned model.
Emerging drugs for acute bacterial meningitis

The management of acute bacterial meningitis is based on early antibiotic treatment to prevent unfavorable outcome (death and permanent sequelae). β-Lactam antibiotics, particularly third-generation cephalosporins, are effective against most agents of community-acquired acute bacterial meningitis. Resistance to β-lactams evolves, particularly in Streptococcus pneumoniae, that may lead to treatment failure. Evaluation of other antibiotics such as fourth-generation cephalosporin, new penems and quinolones is warranted. Adjunctive therapy aims to reduce tissue injuries provoked by the inflammatory response. The use of dexamethasone is still a matter of debate, but seems to be helpful under conditions of rapid etiological diagnosis and prompt management. Other drugs that neutralize bacterial factors or host mechanisms involved in induction of inflammatory response are under development.
THE KIDNEY IN THE CRITICALLY ILL

Abstract Acute kidney injury (AKI) is a common and serious complication in the intensive care setting. It seldom occurs in isolation, but is mostly part of a multiple organ dysfunction syndrome (1-3). The pathogenesis is frequently multifactorial, with sepsis contributing to 50% of the cases (1,4,5). The development of AKI in critically-ill patients is “bad news”: patients with AKI have a high morbidity and mortality (6,7). In addition, AKI, even in its mildest from, is not only a marker of illness severity but appears to be independently associated with mortality (8-12). Prevention of AKI is therefore a major goal to improve outcome of critically-ill patients. Treatment of established AKI is largely supportive. The optimal modality for renal replacement therapy in critically-ill patients still remains a matter of debate (13,14). The majority of survivors recover renal function (15-18).
Modeling and analysis of a microfabricatec piezoelectric cantilever for energy harvesting

A piezoelectric micro-cantilever energy harvester was designed for a standard industry process and its expected power generation capability was simulated using two different analytical models: a simplified one-dimensional model and a circuit equivalent model. The estimated power obtained was compared with the results of similar structures published by other authors, adopting a novel performance parameter for a fairer comparison. Based on the results and on the current scenario of ultra low power electronic systems an applicability assessment was made, evaluating the possible use of the proposed structure to power a wireless sensor network node.
Design of Low complexity Fault Tolerant Parallel FFTs Using Partial Summation

The increasing demand of low complexity and error tolerant design in signal processing systems is a reliability issue at ground level. Complex circuit is consistently affected by soft errors in modern electronic circuits. Fast Fourier transforms (FFTs) plays a key role in many communication and signal processing systems. Different algorithms have been used in earlier techniques for achieving fault tolerant coverage design. In real time application systems, numbers of blocks operating in parallel are frequently used. The proposed work exploits a technique to implement fault tolerance parallel FFT with reduced low complexity of circuit area and power. In Partial summation along with error detection and correction hamming code is used for designing soft error tolerant parallel FFT shelter. This new method achieves lower complexity proportional to that of FFT design size. Based on these two schemes, two modified preserve techniques that combine the use of error correction codes and Partial summation are proposed and evaluated. First method, the Parity-Partial Summation and ECC uses one FFT with minimum Partial Sum blocks for reducing hardware area. Secondly, Parallel Partial Summation ECC used for correcting errors in multiple FFTs protective methods. The result for 4-paralle1 and 6paralle1 FFTs shows that the proposed technique effectively reduces area and power of fault tolerant design along with improved fault coverage.
Neuronal mechanisms underlying control of a brain–computer interface

Brain–computer interfaces (BCIs) enable humans or animals to communicate or control external devices without muscle activity using electric brain signals. The BCI used here is based on self‐regulation of slow cortical potentials (SCPs), a skill that most people and paralyzed patients can acquire with training periods of several hours up to months. The neurophysiological mechanisms and anatomical sources of SCPs and other event‐related brain potentials have been described but the neural mechanisms underlying the self‐regulation skill for the use of a BCI are unknown. To uncover the relevant areas of brain activation during regulation of SCPs, the BCI was combined with functional magnetic resonance imaging. The electroencephalogram was recorded inside the magnetic resonance imaging scanner in 12 healthy participants who learned to regulate their SCP with feedback and reinforcement. The results demonstrate activation of specific brain areas during execution of the brain regulation skill allowing a person to activate an external device; a successful positive SCP shift compared with a negative shift was closely related to an increase of the blood oxygen level‐dependent response in the basal ganglia. Successful negativity was related to an increased blood oxygen level‐dependent response in the thalamus compared with successful positivity. These results may indicate learned regulation of a cortico‐striatal‐thalamic loop modulating local excitation thresholds of cortical assemblies. The data support the assumption that human subjects learn the regulation of cortical excitation thresholds of large neuronal assemblies as a prerequisite for direct brain communication using an SCP‐driven BCI. This skill depends critically on an intact and flexible interaction between the cortico‐basal ganglia‐thalamic circuits.
Managing Cultures into the Past

And on top of the box sits this white man and he knows where the key is because he’s the one that put the people in the box and hid the key. Every now and then the white man changes masks. Sometimes it’s benevolent and sometimes it’s indignant. But always the persons underneath remain the same no matter how many times he changes his masks. (Excerpt from Hyllus Maris, ‘The Concrete Box’ in Paperbark [1990: 124])
Adrenergic responses of rat colonic muscularis mucosae

We have investigated adrenoceptor‐mediated responses of muscularis mucosae from the proximal, mid and distal regions of the rat colon. Noradrenaline‐induced relaxations of the muscularis mucosae in each region were unaffected by atenolol, butoxamine or propranolol, but they were attenuated by the selective β3‐adrenoceptor antagonist cyanopindolol. The β3‐adrenoceptor agonist CL216343 elicited concentration‐dependent relaxation of the muscularis mucosae in all regions of the colon. Isoprenaline, a non‐selective β‐adrenoceptor agonist, evoked concentration‐dependent relaxations of the muscularis mucosae in all regions, but only in the proximal colon were these significantly larger than the maximum noradrenaline‐induced relaxation. The α1‐adrenoceptor agonist methoxamine caused large contractions of the proximal colonic muscularis mucosae. When proximal tissue was pretreated with phentolamine, an α1‐adrenoceptor antagonist, maximal noradrenaline‐ and isoprenaline‐induced relaxations did not differ significantly. Although the mid colonic muscularis mucosae was also found to possess excitatory α1‐adrenoceptors, these were associated with small contractions and did not modify the muscle's inhibitory responses to noradrenaline. Distal colonic muscularis mucosae lacked excitatory adrenoceptors and only responded to noradrenaline with β3‐adrenoceptor‐mediated relaxations. No evidence was obtained for functional α2‐adrenoceptors on the muscularis mucosae in any region of the rat colon. These data demonstrated that noradrenaline‐induced relaxation of the rat colonic muscularis mucosae was mediated via β3‐adrenoceptors throughout, but in the proximal region this was modified by concurrent excitatory α1‐adrenoceptor activation. Based upon these observations it appeared unlikely that noradrenaline‐induced relaxation of rat colonic muscularis mucosae would be functionally linked to the secretory responses of the corresponding mucosa during periods of increased sympathetic activity.
Osteopathic Manipulative Treatment in the Management of Notalgia Paresthetica

Abstract Notalgia paresthetica is a chronic sensory neuropathy characterized by pruritus of the upper to middle back, typically below the left shoulder blade. Symptoms may include pain, hyperesthesia, paresthesia, and hyperpigmentation of the affected area. Although the etiologic process of this condition is poorly understood, recent correlations with degenerative spinal changes suggest that spinal nerve impingement may play a role. The authors report the case of a 59-year-old woman with notalgia paresthetica who received one 20-minute session of osteopathic manipulative treatment that focused primarily on thoracic spine and rib somatic dysfunctions. After treatment, the patient reported immediate improvement of symptoms. A discussion of this condition based on previously published literature is also provided.
Some interfaces of dendritic cell biology

The field of dendritic cell (DC) biology is robust, with several new approaches to analyze their role in vivo and many newly recognized functions in the control of immunity and tolerance. There also is no shortage of mysteries and challenges. To introduce this volume, I would like to summarize four interfaces of DC research with other lines of investigation and highlight some current issues. One interface is with hematopoiesis. DCs constitute a distinct lineage of white blood cell development with some unique features, such as their origin from both lymphoid and myeloid progenitors, the existence of several distinct subsets, and an important final stage of differentiation termed “maturation,” which occurs in response to inflammation and infection, and is pivotal for determining the subsequent immune response. A second interface is with lymphocyte biology. DCs are now known to influence many different classes of lymphocytes (B, NK, NKT) and many types of T cell responses (Th1/Th2, regulatory T cells, peripheral T cell deletion), not just the initial priming or induction of T cell‐mediated immunity, which was the first function to be uncovered. DCs are sentinels, controlling many of the afferent or inductive limbs of immune function, alerting the immune system and controlling its early decisions. A third interface is with cell biology. This is a critical discipline to understand at the subcellular and molecular levels the distinct capacities of DCs to handle antigens, to move about the body in a directed way, to bind and activate lymphocytes, and to exert many quality controls on the type of responses, for both tolerance and immunity. A fourth interface is with medicine. Here DCs are providing new approaches to disease pathogenesis and therapy. This interface is perhaps the most demanding, because it requires research with humans. Human research currently is being slowed by the need to deal with many challenges in the design of such studies, and the need to excite, attract and support the young scientists who are essential to move human investigation forward. Nonetheless, DCs are providing new opportunities to study patients and the many clinical conditions that involve the immune system.
Multi-cue road boundary detection using stereo vision

In this paper, we propose a multi-cue fusion approach to detect the road boundary using stereo vision, which fits road boundary with a few edge points. Firstly boundary areas are determined in accordance with the normal vector information. Based on the cues of normal vector, height and color in the boundary area, three Bayes models are established respectively. Then the Naive Bayes framework could provide the confidence level of each point in the boundary area, which fuses three kinds of cues. In each boundary area, the point with the highest confidence level would be output. Finally, the support vector regression (SVR) method fits curb curves according to the correct edge points. Extensive experiments tested on KITTIRoad benchmark demonstrate that our method reaches the state-of-the-art.
Concomitant HIV infection in newly diagnosed multiple myeloma patients is hard to recognise and should be tested for routinely in areas of high endemicity.

BACKGROUND Over the past three decades much has changed in the treatment and outcomes of patients suffering concurrently from both multiple myeloma (MM) and HIV. While the prevalence of MM appears to be higher in HIV-positive individuals than in those who are uninfected, early recognition of patients suffering from both diseases is difficult and little information is available on their demographics and clinical presentation. OBJECTIVE To compare the presenting features of HIV-positive patients diagnosed with MM with those of HIV-negative patients. METHODS A single-centre, retrospective cohort study included 16 HIV-positive and 73 HIV-negative patients diagnosed with MM, in order to compare variables related to the clinical presentation of both conditions. RESULTS HIV-positive patients presented with MM at a significantly younger age, and had fewer osteolytic lesions, less renal impairment and lower neutrophil counts. Disease stage, gender, pathological fractures, bone marrow plasmacytosis, plasmacytomas and lymphocyte counts were comparable, emphasising the difficulty of identifying these patients. The HIV-positive patients had relatively high CD4 counts and a low prevalence of abnormal Freelite kappa/lambda ratios. All HIV-positive patients presented with paraproteins of the immunoglobulin G (IgG) type, implying a possible relationship between MM and an IgG response to HIV antigens. CONCLUSIONS On the basis of our findings and literature on the treatment of both diseases, we suggest that HIV be tested for routinely in younger MM patients, especially in areas with a high prevalence of HIV. The integration of our results into the sparse knowledge on the role of HIV infection-related MM provides possible new insights into the interaction between these diseases.
Intracellular Retention of Caveolin 1 in Presenilin-deficient Cells*

Mutations in genes encoding presenilins (PS1 and PS2) are responsible for the majority of early onset familial Alzheimer's disease. PS, a critical component of γ-secretase, is responsible for the intramembranous cleavage of amyloid precursor protein and Notch. Other physiological functions have been assigned to PS without any clear identification of the mechanisms underlying these multiple biological roles. The early embryonic lethality of PS1 and PS2 double knock-out (PS1/2 null) mice prevents the evaluation of physiological roles of PS. To investigate new functions for presenilins, we performed a proteomic approach by using cells derived from PS1/2 null blastocysts and wild type controls. We identified a presenilin-dependent cell-surface binding of albumin. Binding of albumin depends on intact caveolae on the cellular surface. Abnormal caveolin 1 localization in PS1/2 null cells was associated with a loss of caveolae and an absence of caveolin 1 expression within lipid rafts. Expressing PS1 or PS2 but not the intracellular form of Notch1 in PS1/2 null cells restored normal caveolin 1 localization, demonstrating that presenilins are required for the subcellular trafficking of caveolin 1 independently from Notch activity. Despite an expression of both caveolin 1 and PS1 within lipid raft-enriched fractions after sucrose density centrifugation in wild type cells, no direct interaction between these two proteins was detected, implying that presenilins affect caveolin 1 trafficking in an indirect manner. We conclude that presenilins are required for caveolae formation by controlling transport of intracellular caveolin 1 to the plasma membrane.
Optimal Wireless Power Transfer to Systems in an Enclosed Resonant Cavity

This letter describes the development and implementation of an impedance-matching (IM) method for achieving optimal power transfer efficiencies (PTE's) in cavity resonator wireless power transfer (WPT) systems. Specifically, we develop a bandpass filter (BPF) circuit model and utilize network analysis to predict and realize maximum achievable PTE to miniature systems enclosed within a hollow metallic cylindrical cavity excited in TM010 resonant mode. Measured PTE results are demonstrated matching closely with the developed theory and circuit simulations. We achieve a peak PTE of 33% to a 5-mm-diameter receive coil that occupies a volume that is 5.23 ×106 times smaller than the volume of the cylindrical cavity. Our achieved PTE is 4 times larger than the PTE achieved to a system with no optimal IM network but only a single resonant capacitor connected in series with the receive coil. The model and results presented illustrate our optimal design methodology for realizing maximum achievable PTE in cavity resonator WPT systems.
Mirror, Mirror on the Wall: Attracting Passers-by to Public Touch Displays With User Representations

In this paper, we investigate how effectively users' representations convey interactivity and foster interaction on large information touch displays. This research is motivated by the fact that user representations have been shown to be very efficient in playful applications that support mid-air interaction. At the same time, little is known about the effects of applying this approach to settings with a different primary mode of interaction, e.g. touch. It is also unclear how the playfulness of user representations influences the interest of users in the displayed information. To close this gap, we combine a touch display with screens showing life-sized video representations of passers-by. In a deployment, we compare different spatial arrangements to understand how passers-by are attracted and enticed to interact, how they explore the application, and how they socially behave. Findings reveal that (a) opposing displays foster interaction, but (b) may also reduce interaction at the main display; (c) a large intersection between focus and nimbus helps to notice interactivity; (d) using playful elements at information displays is not counterproductive; (e) mixed interaction modalities are hard to understand.