Miracle-dz/UniFAR-FTUs huggingface dataset:
Latent-state models for precision medicine

Observational longitudinal studies are a common means to study treatment efficacy and safety in chronic mental illness. In many such studies, treatment changes may be initiated by either the patient or by their clinician and can thus vary widely across patients in their timing, number, and type. Indeed, in the observational longitudinal pathway of the STEP-BD study of bipolar depression, one of the motivations for this work, no two patients have the same treatment history even after coarsening clinic visits to a weekly time-scale. Estimation of an optimal treatment regime using such data is challenging as one cannot naively pool together patients with the same treatment history, as is required by methods based on inverse probability weighting, nor is it possible to apply backwards induction over the decision points, as is done in Q-learning and its variants. Thus, additional structure is needed to effectively pool information across patients and within a patient over time. Current scientific theory for many chronic mental illnesses maintains that a patient's disease status can be conceptualized as transitioning among a small number of discrete states. We use this theory to inform the construction of a partially observable Markov decision process model of patient health trajectories wherein observed health outcomes are dictated by a patient's latent health state. Using this model, we derive and evaluate estimators of an optimal treatment regime under two common paradigms for quantifying long-term patient health. The finite sample performance of the proposed estimator is demonstrated through a series of simulation experiments and application to the observational pathway of the STEP-BD study. We find that the proposed method provides high-quality estimates of an optimal treatment strategy in settings where existing approaches cannot be applied without ad hoc modifications.
Muscarinic inhibition of M‐current and a potassium leak conductance in neurones of the rat basolateral amygdala.

1. Voltage‐clamp recordings using a single microelectrode were obtained from pyramidal neurones of the basolateral amygdala (BLA) in slices of the rat ventral forebrain. Slow inward current relaxations during hyperpolarizing voltage steps from a holding potential of ‐40 mV were identified as the muscarinic‐sensitive M‐current (IM), a time‐ and voltage‐dependent potassium current previously identified in other neuronal cell types. 2. Activation of IM was voltage dependent with a threshold of approximately ‐70 mV. At membrane potentials positive to this, the steady‐state current‐voltage (I‐V) relationship showed substantial outward rectification, reflecting the time‐ and voltage‐dependent opening of M‐channels. The underlying conductance (gM) also increased sharply with depolarization. 3. The reversal potential for IM was ‐84 mV in medium containing 3.5 mM K+. This was shifted positively by 27 mV when the external K+ concentration was raised to 15 mM. 4. The time courses of M‐current activation and deactivation were fitted by a single exponential. The time constant for IM decay, measured at 24 degrees C, was strongly dependent on membrane potential, ranging from 330 ms at ‐40 mV to 12 ms at ‐100 mV. 5. Bath application of carbachol (0.5‐40 microM) inhibited IM, as evidenced by the reduction or elimination of the slow inward M‐current relaxations evoked during hyperpolarizing steps from a holding potential of ‐40 mV. The outward rectification of the steady‐state I‐V relationship at membrane potentials positive to ‐70 mV was also largely eliminated. The inhibition of IM by carbachol was dose dependent and antagonized by atropine. 6. Carbachol produced an inward current shift at a holding potential of ‐40 mV that was only partially attributable to inhibition of IM. An inward current shift was also produced by carbachol at membrane potentials negative to ‐70 mV, where IM is inactive. These effects were dose dependent and antagonized by atropine. They were attributed to the muscarinic inhibition of a voltage‐insensitive potassium leak conductance (ILeak). 7. In most cells, carbachol reduced the slope of the instantaneous I‐V relationship obtained from a holding potential of ‐70 mV so that it crossed the control I‐V plot at the reversal potential for ILeak. This was found to be ‐108 mV in 3.5 mM K+ saline, shifting to ‐66 mV in 15 mM K+ saline. (ABSTRACT TRUNCATED AT 400 WORDS)
Pitfalls in looking for color transparency at intermediate energies.

The problems and uncertainties in the search for color transparency at intermediate [ital Q][sup 2] are considered. We show that conventional (optical) model [distorted wave impulse approximation (DWIA)] predicts a substantial change of the transparency, T, with [ital Q][sup 2] in the kinematics of the Ne-18 ([ital e],[ital e][sup [prime]][ital p]) experiment, while the color transparency phenomenon may lead to nearly [ital Q][sup 2] independent T. In the case of [ital A]([ital p],2[ital p]) reaction we demonstrate that the conventional optical model describes well the 1 GeV [ital A]([ital p],2[ital p]) data but not the transparency observed at higher energies. We find also that DWIA (with or without color transparency) predicts strong dependence of T on the momentum of the struck nucleon which is consistent with the pattern of the Brookhaven National Laboratory [ital A]([ital p],2[ital p]) data at [ital p][sub [ital N]]=6 GeV/[ital c] and 10 GeV/[ital c].
Lung cancer and exposure to tobacco smoke in the household.

BACKGROUND The relation between passive smoking and lung cancer is of great public health importance. Some previous studies have suggested that exposure to environmental tobacco smoke in the household can cause lung cancer, but others have found no effect. Smoking by the spouse has been the most commonly used measure of this exposure. METHODS In order to determine whether lung cancer is associated with exposure to tobacco smoke within the household, we conducted a population-based case--control study of 191 patients with histologically confirmed primary lung cancer who had never smoked and an equal number of persons without lung cancer who had never smoked. Lifetime residential histories including information on exposure to environmental tobacco smoke were compiled and analyzed. Exposure was measured in terms of "smoker-years," determined by multiplying the number of years in each residence by the number of smokers in the household. RESULTS Household exposure to 25 or more smoker-years during childhood and adolescence doubled the risk of lung cancer (odds ratio, 2.07; 95 percent confidence interval, 1.16 to 3.68). Approximately 15 percent of the control subjects who had never smoked reported this level of exposure. Household exposure of less than 25 smoker-years during childhood and adolescence did not increase the risk of lung cancer. Exposure to a spouse's smoking, which constituted less than one third of total household exposure on average, was not associated with an increase in risk. CONCLUSIONS The possibility of recall bias and other methodologic problems may influence the results of case-control studies of environmental tobacco smoke. Nonetheless, our findings regarding exposure during early life suggest that approximately 17 percent of lung cancers among nonsmokers can be attributed to high levels of exposure to cigarette smoke during childhood and adolescence.
Physical-Layer Secret Key Generation With Colluding Untrusted Relays

In this paper, we propose a physical-layer secret key generation scheme for multiantenna legitimate nodes with the help of multiple untrusted relays, equipped with multiple antennas. The untrusted relays conform to the relaying transmission protocol of legitimate nodes, but they also eavesdrop the confidential information of an legitimate transmitter. The key generation scheme is designed with zero forcing (ZF) and minimum mean square error (MMSE) channel estimators for non-, partially, and fully colluding modes of untrusted relays. Furthermore, we propose a scheme adaptive to channel coherence time. Specifically, to achieve a higher secret key rate (SKR) within the channel coherence time, the number of relay and legitimate nodes' antennas are optimally determined and the most suitable antennas are selected for the key generation. Our results show that the proposed scheme achieves a higher SKR than a prior work, and non- and partially colluding modes provide a higher SKR than the fully colluding mode through the proposed scheme. We also verify that exploiting more antennas of untrusted relays does not always enhance the SKR by showing the existence of the optimal number of antennas of the relays participating in the scheme.
Superiority of 24-hour measurement of blood pressure over clinic values in determining prognosis in hypertension.

Long-term recordings of blood pressure in an individual could logically be expected to have greater prognostic power than values recorded in the clinic in view of the known inaccuracies and variability of the latter. This feature has been shown to be true in a large series investigated by Perloff and colleagues1. Specific components of the 24h profile may have greater prognostic power than others, ‘basal’ blood pressure (generally equated with night-time resting values) has been thought by some2 to have greater predictive value than that recorded during less standardised activity at other times of day. A further hypothesis is that high intrinsic blood pressure variability may play an independent role in determining cardiovascular pathology when measured either as a global index3 or as a specific component such as the slope of the early morning rise in pressure4.
Impact of continuous eye contact of a humanoid robot on user experience and interactions with professional user background

This work investigates the impact of simply keeping eye-contact on users' perceptions of the humanoid robot NAO during the carry and handover phases of a fetch- and-handover scenario. Two conditions of NAO looking either towards its planned path or towards the human test subject's face are implemented in a within-subjects design. Evaluations of user experience and acceptance are conducted based on evaluated measures of human-robot interaction. The results of the user study reveal a significant increase of anthropomorphism, animacy, and social presence in the eye-contact condition even without an intelligent gaze control implementation. Additionally, significant interactions with the professional background of the test participants are found.
Intercalation of a Zn(II) complex containing ciprofloxacin drug between DNA base pairs

ABSTRACT In this study, an attempt has been made to study the interaction of a Zn(II) complex containing an antibiotic drug, ciprofloxacin, with calf thymus DNA using spectroscopic methods. It was found that Zn(II) complex could bind with DNA via intercalation mode as evidenced by: hyperchromism in UV–Vis spectrum; these spectral characteristics suggest that the Zn(II) complex interacts with DNA most likely through a mode that involves a stacking interaction between the aromatic chromophore and the base pairs of DNA. DNA binding constant (Kb = 1.4 × 104 M−1) from spectrophotometric studies of the interaction of Zn(II) complex with DNA is comparable to those of some DNA intercalative polypyridyl Ru(II) complexes 1.0 −4.8 × 104 M−1. CD study showed stabilization of the right-handed B form of DNA in the presence of Zn(II) complex as observed for the classical intercalator methylene blue. Thermodynamic parameters (ΔH < 0 and ΔS < 0) indicated that hydrogen bond and Van der Waals play main roles in this binding prose. Competitive fluorimetric studies with methylene blue (MB) dye have shown that Zn(II) complex exhibits the ability of this complex to displace with DNA-MB, indicating that it binds to DNA in strong competition with MB for the intercalation.
Autonomous car driving by a humanoid robot

Enabling a humanoid robot to drive a car requires the development of a set of basic primitive actions. These include walking to the vehicle, manually controlling its commands (e.g., ignition, gas pedal, and steering) and moving with the whole body to ingress/egress the car. We present a sensor‐based reactive framework for realizing the central part of the complete task, consisting of driving the car along unknown roads. The proposed framework provides three driving strategies by which a human supervisor can teleoperate the car or give the robot full or partial control of the car. A visual servoing scheme uses features of the road image to provide the reference angle for the steering wheel to drive the car at the center of the road. Simultaneously, a Kalman filter merges optical flow and accelerometer measurements to estimate the car linear velocity and correspondingly compute the gas pedal command for driving at a desired speed. The steering wheel and gas pedal reference are sent to the robot control to achieve the driving task with the humanoid. We present results from a driving experience with a real car and the humanoid robot HRP‐2Kai. Part of the framework has been used to perform the driving task at the DARPA Robotics Challenge.
Tissue cages in calves for studies on pharmacokinetic/pharmacodynamic relationships of antimicrobials

Knowledge on pharmacokinetic/pharmacodynamic (PK/PD) relationships of antimicrobials may assist in defining a dose that maximises effect while minimising side effects such as selection of resistance. The aim of this thesis was to develop a model for studies of PK/PD relationships of antimicrobials in presence of the host defences. To this end, the usefulness of subcutaneously implanted tissue cages was explored. Tissue cages implanted in calves were infected with Escherichia coli and the calves were treated iv with different doses of trimethoprim + sulfadoxine. Irrespective of dose, no effect was noted in cages infected before treatment. In vitro studies and analysis of thymidine indicate that the effect of trimethoprim was antagonised by thymidine in tissue cage fluid. When the antimicrobial is administered systemically as above, the pharmacokinetics of the drug in tissue cage fluid is typically sluggish. It was shown that if tissue cages with a constant diffusion area but different volumes are used, and drug is injected directly into the cages, the volume of the cage will determine the elimination rate of the drug. Thereby, by varying the dose and cage-type, a range of concentration-time profiles can be simulated. To explore the utility of this concept, the effects of penicillin and danofloxacin against infections with Mannheimia haemolytica in tissue cages in calves were studied. For penicillin, the area under the curve to minimum inhibitory concentration (MIC) and time above MIC were equally predictive for effect. For danofloxacin, the area under the curve to MIC predicted the effect, and the magnitude needed for near maximum effect was 240-244 h. These results are in line with information for other fluoroquinolone-bacterial combinations. The advantage of the described model is that different concentration-time profiles can be simulated, and concentrations of drug at the site of infection and bacterial counts can be monitored over time in presence of the host defences. Its validity needs to be challenged by direct comparisons with other models, and by clinical studies. The results suggest it can be a useful intermediary step between in vitro studies and clinical trials aiming at drug dosage optimisation.
Economic evaluation of wind generation projects in electricity markets

Investments in new generation, specially in renewables, grew up in several countries contributing to change the generation mix. Among these new technologies, wind power became an important source in the sense that the share in installed capacity is large in countries as Germany, Denmark, Spain and Portugal namely considering the prices paid to the generated power. These subsidizing schemes are in several cases responsible for a large amount of the final end user costs meaning that in the future new ways of integrating this power in the grid have to be adopted. This means that for investors it is important to evaluate from a economic point of view the interest of new wind power projects admitting changes in current tariff schemes. For regulatory agencies it is also important to investigate the impact of changes in current schemes. This paper details an approach to characterize this type of investments in terms of the Net Present Value, NPV, and the Internal Return Rate, IRR, so that more sounded investment and policy decisions are adopted.
Purification and Characterization of Monolysocardiolipin Acyltransferase from Pig Liver Mitochondria*

In mammalian tissues cardiolipin is rapidly remodeled by monolysocardiolipin acyltransferase subsequent to its de novo biosynthesis (Ma, B. J., Taylor, W. A, Dolinsky, V. W., and Hatch, G. M. (1999) J. Lipid Res. 40, 1837–1845). We report here the purification and characterization of a monolysocardiolipin acyltransferase activity from pig liver mitochondria. Monolysocardiolipin acyltransferase activity was purified over 1000-fold by butanol extraction, hydroxyapatite chromatography, and preparative SDS-PAGE. The purified 74-kDa protein catalyzed acylation of monolysocardiolipin to cardiolipin with [14C]linoleoyl coenzyme A. Photoaffinity labeling of the protein with 12-[(4-[125I]azidosalicyl)amino]dodecanoyl coenzyme A indicated coenzyme A was bound at its active site and photoaffinity cross-linking of 12-[(4-azidosalicyl)amino]dodecanoyl coenzyme A to the enzyme inhibited enzyme activity. Enzyme activity was optimum at pH 7.0, and the enzyme did not utilize other lysophospholipids as substrate. The purified enzyme was heat-labile and exhibited an isoelectric point of pH 5.4. To determine the enzymes kinetic mechanism the effect of varying concentrations of linoleoyl coenzyme A and monolysocardiolipin on initial velocity were determined. Double-reciprocal plots revealed parallel lines consistent with a ping pong kinetic mechanism. When the enzyme was incubated in the absence of monolysocardiolipin, coenzyme A was produced from linoleoyl coenzyme A at a rate consistent with the formation of an enzyme-linoleate intermediate. The true K m value for linoleoyl coenzyme A and true K m value for monolysocardiolipin were 100 and 44 μm, respectively. The calculated V max was 6802 pmol/min·mg of protein. A polyclonal antibody, raised in rabbits to the purified protein, cross-reacted with the protein in crude pig liver mitochondrial fractions. In liver mitochondria prepared from thyroxine-treated rats, the level of the protein was elevated compared with euthyroid controls indicating that expression of monolysocardiolipin acyltransferase is regulated by thyroid hormone. The study represents the first purification and characterization of a monolysocardiolipin acyltransferase activity from any organism.
Un outil de visualisation de classifications et d'intégration de données phénotypiques et génétiques pour faciliter le codage des maladies rares

Establishing the diagnosis and coding for a rare disease (RD) needs to characterize multiple information including patient's phenotype and genotype. A major barrier to coding is a lack of consolidation of such information, scattered in several resources such as Orphanet, OMIM or HPO. We developed a web portal, Linking Open data for RD (LORD), offering an integrated view of 8,336 RDs linked to more than 12,500 signs and 3,000 genes. It allows navigating through the relationships between diseases, signs and genes, and provides Application Programming Interfaces for its integration in information systems (IS). LORD is dedicated to the 131 French RD reference centers and 501 competence centers, for coding RD diagnoses in the health IS. Articles courts des 15es Journées francophones d’informatique médicale, JFIM 2014, pages 198–203 Fès, Maroc, 12–13 juin 2014 Mots-clés : Ontologies des maladies rares ; Big Data ; Codage diagnostique ; Web sémantique ; Informatique médicale ; Services web
Shell Composition Has No Net Impact on Large-Scale Evolutionary Patterns in Mollusks

A major suspected bias in the fossil record of skeletonized groups is variation in preservability owing to differences in shell composition. However, despite extensive changes in shell composition over the 500-million-year history of marine bivalves, genus duration and shell composition show few significant relationships, and of those, virtually all are contrary to bias from preferential loss of highly reactive shell types. Distortion of large-scale temporal patterns in marine bivalves owing to preservability is thus apparently weak or randomly distributed, which increases the likelihood that observed patterns in this and other shelled groups carry a strong biological signal.
[Intestinal parasites in dogs and cats with gastrointestinal symptoms in Santiago, Chile].

BACKGROUND There is an increasing importance of pet-transmitted infections, some of those are considered emerging infections. AIM To determine the species and frequency of intestinal parasites in pets with diarrhea (hemorrhagic gastroenteritis excluded). MATERIAL AND METHODS A descriptive retrospective study. Fecal samples from 972 dogs and 230 cats consulting in two veterinary practices in Santiago, between 1996 and 2003, were studied using Burrows' technique. RESULTS Protozoa were found in 64.8% of dogs and in 66.5% of cats; helminthes in 24% of dogs and 45.2% of cats. The species found in dogs were Blastocystis sp. in 36%, Ameba sp. in 31%, Giardia intestinalis in 22%, Toxocara canis in 11%, Chilomastix sp. in 10%, Isospora sp. in 9%, Trichuris vulpis in 9%, Trichomonas sp. in 5%, Sarcocystis sp. in 4%, Dipylidium caninum in 2%, Ancylostomideos in 2%, Toxascaris leonina in 1%, Physaloptera sp. in 1%, Taenia sp. in 0.4%. Species found in cats were Blastocystis sp. in 37%, Ameba sp. in 30%, G intestinalis in 19%, Chilomastix sp. in 12%, Isospora sp. in 12%, Toxocara cati in 10%, D caninum in 7%, Sarcocystis sp. in 5%, Trichomona sp. in 5%, Toxoplasma gondii in 4%, Taenia sp. in 2% and Physaloptera sp. in 1%. Forty eight percent of parasites found in dogs and 49% found in cats have zoonotic potential. In dogs younger than six months Blastocystis sp. , Ameba sp. , G intestinalis, Chilomastix sp. , Isospora sp. and T canis were significantly more common; the same was observed for Isospora in young cats. Approximately 60% of infected animals bore more than one parasite. CONCLUSIONS A high rate of intestinal parasitism in pets with diarrhea was found; an important proportion of them have zoonotic potential.
Intra-ocular pressure, glaucoma, and glaucoma suspects in a defined population.

TOTAL population studies are the only certain way of gaining reliable information on the prevalence of insidious conditions like chronic simple glaucoma. The sine qua non of a total population study is exact knowledge of the composition of the population. In the Rhondda valley the Medical Research Council has laboriously carried out a census so that the exact number of persons and their age and sex are known for this area. Over the past 15 years the M.R. C. has earned the co-operation of this population by its efforts in detecting miners' pneumoconiosis, pulmonary tuberculosis, and other diseases. Such a situation was admirably suited for a total population study of the prevalence of glaucoma, and in the summer of 1963 the authors carried out such a study. To our knowledge the only previous similar study is that done by Str6mberg (1962) at Skovde in Sweden.