Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamics of HIV-specific CD8+ T lymphocytes with changes in viral load.The RESTIM and COMET Study Groups.

The influence of HIV burden variations on the frequencies of Ag-specific CD8+ T cell responses was evaluated before and during highly active antiretroviral therapy by analyzing the number, diversity, and function of these cells. The frequencies of HLA-A2-restricted CD8+ PBL binding HLA-A2/HIV-epitope tetramers or producing IFN-gamma were below 1%. A panel of 16 CTL epitopes covering 15 HLA class I molecules in 14 patients allowed us to test 3.8 epitopes/patient and to detect 2.2 +/- 1.8 HIV epitope-specific CD8+ subsets per patient with a median frequency of 0.24% (0.11-4. 79%). During the first month of treatment, viral load rapidly decreased and frequencies of HIV-specific CD8 PBL tripled, eight new HIV specificities appeared of 11 undetectable at entry, while CMV-specific CD8+ PBL also appeared. With efficient HIV load control, all HIV specificities decayed involving a reduction of the CD8+CD27+CD11ahigh HIV-specific effector subset. Virus rebounds triggered by scheduled drug interruptions or transient therapeutic failures induced four patterns of epitope-specific CD8+ lymphocyte dynamics, i.e., peaks or disappearance of preexisting specificities, emergence of new specificities, or lack of changes. The HIV load rebounds mobilized both effector/memory HIV- and CMV-specific CD8+ lymphocytes. Therefore, frequencies of virus-specific CD8 T cells appear to be positively correlated to HIV production in most cases during highly active antiretroviral therapy, but an inverse correlation can also be observed with rapid virus changes that might involve redistribution, sequestration, or expansion of these Ag-specific CD8 T cells. Future strategies of therapeutic interruptions should take into account these various HIV-specific cell dynamics during HIV rebounds.
What can modern statistics offer imaging neuroscience?

This paper presents a mixed-effects model, region-of-interest analysis of a longitudinal functional magnetic resonance imaging (fMRI) study of drug effects on human memory function. A key region of interest is the human hippocampus, affected by brain disorders such as Alzheimer’s disease and schizophrenia. A brief section on human hippocampal cell microscopy complements the discussion of the macroscopic fMRI study. Statistical issues confronted in these two applications are then placed in a broader context for further discussion of the future roles of biostatisticians and our methods in the fertile intersection of applied mathematical abstraction and imaging neuroscience. Neuroscientific and fMRI background is provided for readers new to either area.
Modificación de los parámetros hemodinámicos y BIS durante la inducción con propofol versus propofol-ketamina en pacientes pediátricos

El manejo anestesico se engloba en tres fases: induccion, mantenimiento y emersion. Los farmacos intravenosos en la induccion tienen como objetivo mantener estabilidad y hemostasia en el paciente. Los farmacos mas empleados para este fi n no logran completamente este objetivo. La tendencia para contrarrestar estos efectos adversos consiste en combinar farmacos con mecanismo de accion diferente. Material y metodos: Estudio de ensayo clinico aleatorizado, ciego, que incluyo pacientes de 1-10 anos, ASA I-III, cirugia electiva, bajo anestesia general balanceada. Se formaron dos grupos: grupo propofol (grupo p) se administraron 3 mg/kg, grupo propofol-ketamina (grupo pk) se administro propofol 2.5 mg/kg y ketamina 0.5 mg/kg durante la induccion. Se registraron signos vitales basales, al minuto 1, 3 (intubacion endotraqueal), 5, 10 y a los 15 minutos. Resultados: Se incluyeron 29 pacientes, 15 para el grupo p y 14 para el grupo pk. Tanto la frecuencia cardiaca, tension arterial (sistolica, diastolica y media) y el indice biespectral disminuyeron en el grupo p, no asi en el grupo pk donde los signos vitales se mantuvieron estables. La saturacion no tuvo modifi caciones en ningun grupo. Sin diferencias estadisticamente signifi cativas. Conclusiones: La combinacion de propofol-ketamina comparado con el propofol como inductor unico clinicamente ofrece mayor estabilidad hemodinamica.
Production and Partial Purification of a Neutral Metalloprotease by Fungal Mixed Substrate Fermentation

Summary Five strains of fungi belonging to Aspergillus sp. were evaluated by casein agar plate assay and a wheat bran-based solid-state fermentation for selecting a neutral protease-producing culture. Based on the results, A. oryzae NRRL 2217 was selected for further studies. Sixteen different agro-industrial residues were evaluated for their potential to serve as a substrate for neutral protease production by this fungal strain. Results showed that a combination of coconut oil cake and wheat bran in the mass ratio of 1:3 was the best substrate for enzyme production. Various process parameters influencing protease production including fermentation time, initial moisture content, and fermentation temperature were optimised. The medium was supplemented with different nutrients in the form of organic and inorganic nitrogen and carbon sources. Supplementation of chitin increased the enzyme production significantly. Ammonium nitrate as inorganic nitrogen supplement slightly enhanced enzyme production. No organic nitrogen supplement was effective enhancer of enzyme production. Fermentation was performed under optimised conditions (initial moisture content V/m = 50 %, temperature 30 °C, 48 h). Partial purification of the enzyme resulted in a 3-fold increase in the specific activity of the enzyme. The partially purified enzyme was characterised by various features that govern the enzyme activity such as assay temperature, assay pH and substrate concentration. The effect of various metal ions and known protease inhibitors on the enzyme activity was also studied. The enzyme was found to be stable in pH range 7.0–7.5, and at temperature of 50 °C for 35 min. By the activating effect of divalent cations (Mg 2+ ,C a 2+ ,F e 2+ ) and inhibiting effect of certain chelating agents (EGTA, EDTA), the enzyme was found to be a metalloprotease.
A population-based case–control study of diet and melanoma risk in northern Italy

Abstract Objective We aimed at examining the association between dietary constituents and risk of cutaneous melanoma. Design In an area of northern Italy we recruited 59 newly diagnosed melanoma patients and 59 age- and sex-matched population controls, to whom we administered a validated semi-quantitative food-frequency questionnaire. Results We found an excess risk of melanoma in subjects with a higher energy-adjusted intake of total polyunsaturated fatty acids and, in particular, of linoleic acid (relative risk = 2.16 for intake in the highest tertile compared with the lowest tertile, P for linear trend = 0.061). Conversely, disease risk was inversely associated with the consumption of soluble carbohydrates (relative risk = 0.34 for intake in the upper vs. the lowest tertile adjusting for total energy intake, P for linear trend = 0.046). No other dietary factors, including alcohol, vitamins and trace elements, correlated with melanoma risk. The association of melanoma risk with linoleic acid and soluble carbohydrates intakes was further strengthened in multivariate analysis, and when analysis was limited to females. Conclusions Overall, these results indicate that an excess energy-adjusted intake of linoleic acid and a lower consumption of soluble carbohydrates may increase melanoma risk.
Modeling and optimal control of a three generation system

This paper interests to the modeling and the control of an energy production system. The studied system consists of a three-generator that exploit solar energy in addition to the fuel combustion source to produce energy in three different forms: electricity, cold for freezing and hot tap water. The studied system suffers from important energy loss and then a relatively poor efficiency. A state space representation is proposed for the modeling of this system. An optimal control law is then designed aiming to reduce energy loss and to improve the system efficiency. Simulation results are then exposed discussing the performance of the controlled system compared with its open loop behavior.
Review of computational approaches for predicting the physicochemical and biological properties of nanoparticles

In the growing field of nanotechnology there is a need to determine the physicochemical and potential toxicological properties of nanomaterials since many industrial, medical and consumer applications are based on an understanding of these properties and on a controlled exposure to the materials. This document provides a literature review on the current status of computational studies aimed at predicting the physicochemical properties and biological effects (including toxicity) of nanomaterials, with an emphasis on medical applications. Although a number of models have been published for physicochemical property prediction, very few models have been published for predicting biological effects, toxicity or the underlying mechanisms of action. This is due to two main reasons: a) nanomaterials form a colloidal phase when in contact with biological systems making the definition and calculation of properties (descriptors) suitable for the prediction of toxicity a new and challenging task, and b) nanomaterials form a very heterogeneous class of materials, not only in terms of their chemical composition, but also in terms of size, shape, agglomeration state, and surface reactivity. There is thus an urgent need to extend the traditional structure-activity paradigm to develop methods for predicting the toxicity of nanomaterials, and to make the resulting models readily available. This document concludes by proposing some lines of research to fill the gap in knowledge and predictive methodology. LIST OF ABBREVIATIONS CAS Chemical Abstract Service CDNP Combustion-Derived Nanoparticle CNN Computational Neural Networks CNT Carbon Nanotube CPMD Car-Parrinello Molecular Dynamics DFT Density Functional Theory EINECS European INventory of Existing commercial Chemical Substances EU European Union JRC Joint Research Centre LSER Linear Solvation Energy Relationship LSSVM Least-Squares Support Vector Machine MC Monte Carlo MCDM Multi-Criteria Decision Making MD Molecular Dynamics MI-QSAR Membrane-Interaction Quantitative Structure-Activity Relationship MOT Mobile Order Theory MLR Multilinear Regression MNP Manufactured Nanoparticle NM Nanomaterial NP Nanoparticle OECD Organisation for Economic Co-operation and Development PAH Polycyclic Aromatic Hydrocarbon PE Polyethylene PM Particulate Matter QD Quantum Dot QSAR Quantitative Structure-Activity Relationship REACH Registration, Evaluation, Authorisation and Restriction of Chemicals ROS Reactive Oxygen Species SAR Structure-Activity Relationship SMILES Simplified Molecular Input Line Entry System SVF Synthetic Vitreous Fibres SWNT Single Wall Nanotube
Bayesian, and Non-Bayesian, Cause-Specific Competing-Risk Analysis for Parametric and Nonparametric Survival Functions: The R Package CFC

The R package CFC performs cause-specific, competing-risk survival analysis by computing cumulative incidence functions from unadjusted, cause-specific survival functions. A high-level API in CFC enables end-to-end survival and competing-risk analysis, using a single-line function call, based on the parametric survival regression models in the survival package. A low-level API allows users to achieve more flexibility by supplying their custom survival functions, perhaps in a Bayesian setting. Utility methods for summarizing and plotting the output allow population-average cumulative incidence functions to be calculated, visualized and compared to unadjusted survival curves. Numerical and computational optimization strategies are employed for efficient and reliable computation of the coupled integrals involved. To address potential integrable singularities caused by infinite cause-specific hazards, particularly near time-from-index of zero, integrals are transformed to remove their dependency on hazard functions, making them solely functions of causespecific, unadjusted survival functions. This implicit variable transformation also provides for easier extensibility of CFC to handle custom survival models since it only requires the users to implement a maximum of one function per cause. The transformed integrals are numerically calculated using a generalization of Simpson's rule to handle the implicit change of variable from time to survival, while a generalized trapezoidal rule is used as reference for error calculation. An OpenMP-parallelized, efficient C++ implementation - using packages Rcpp and RcppArmadillo - makes the application of CFC in Bayesian settings practical, where a potentially large number of samples represent the posterior distribution of cause-specific survival functions.
Analgesic action of metoclopramide in prosthetic hip surgery

Prosthetic hip surgery was performed under subarachnoidal anaesthesia with bupivacaine 16–20 mg and morphine 0.2 mg. Preoperatively, metoclopramide 1 mg · kg‐1 was given i.v. , followed by an infusion of 1.5 mg · kg‐1 over 9 h (n= 17). Control patients received corresponding volumes of solvent (n = 23). The design of the study was double blind. The characteristics of the spinal block (level of analgesia to pinprick and muscular block) and postoperative VAS pain scores were similar in both groups. During the 24 h following the start of the infusion, four patients receiving metoclopramide required i.v. opioids, compared to 15 in the control group (P<0.05). The pain‐free period was longer (P<0.05) in the metoclopramide group. Arterial PcO2‐levels were increased, reaching a maximum within 6 h of infusion, with no significant difference between the groups. The study suggests an analgesic action of metoclopramide.
Shadows of the Mind

This book attempts to take a firm grip on a corner of the slippery issue of consciousness. It is directly related to Roger Penrose's earlier, hugely successful work, The Emperor's New Mind. Although much space is devoted to painstaking replies to the criticisms made of the earlier book, this is not simply a sequel. It contains a number of new ideas, some of which are still being actively debated seven years after the book was first published.
Outcome of tracheobronchial injuries: a long-term perspective.

BACKGROUND Tracheobronchial injuries are relatively uncommon, and few data are available on the long-term effects of their treatment. METHODS All injuries involving the larynx and trachea, trachea alone, and mainstem bronchus (MSB) treated by one surgeon were followed if they survived 48 hours. RESULTS Sixty patients were treated from 1976 to 2001 for blunt and penetrating injuries: 6 laryngotracheal injuries, 27 tracheal wounds, and 27 injuries to the mainstem bronchus. Follow-up ranged from 1 to 26 years. One of six laryngotracheal wounds had a good result. One required tracheal resection and one required permanent tracheostomy. Patients who survived tracheal resection and end-to-end anastomosis had good outcomes; two had granulomata caused by permanent suture use. One patient treated by primary repair developed stenosis requiring resection. Fourteen patients with MSB injury were treated by pneumonectomy, eight of whom survived. Three developed stump leak/empyema and three had cor pulmonale on long-term follow-up. Ten patients had repair of blunt MSB injuries; two developed bronchial stenosis requiring pneumonectomy. CONCLUSION Laryngotracheal and MSB injuries often had less than optimal outcomes on long-term observation. Tracheal injuries treated by resection and end-to-end repairs had excellent outcomes. The data should be useful in counseling patients/families and planning follow-up strategies for patients with tracheobronchial injuries.
Impact of the ‘2 week wait’ directive for suspected cancer on service provision in a symptomatic breast clinic

The ‘2 week wait’ directive (Health Service Circular (HSC) 1998/242) guaranteeing that ‘everyone with suspected breast cancer will be able to see a specialist within two weeks of their general practitioner (GP) deciding they need to be seen urgently’ is a unique audited approach to access for the British National Health Service, the effects of which have been assessed in a non‐academic symptomatic breast clinic.
SniffDroid: Detection of Inter-App Privacy Leaks in Android

Android has deprecated the use of readable/writeable mode for shared preferences from API level 17. Hence, the researchers are not paying much attention towards the privacy leak via shared preferences. However, Android app developers are still using these modes in practice. This may have serious ramifications such as privacy leakage, privilege escalation, etc, and may pose a severe threat to an user’s privacy. In this paper, we present an automaton based static analysis technique named SniffDroid to detect the inter-app privacy leaks via shared preferences in Android. To evaluate the performance of SniffDroid in real-time, we tested it on our developed dataset of 21 apps and 240 Google playstore apps. These apps are chosen from various categories such as banking, wallet, location, shopping, etc. SniffDroid conducts analysis at the component level. The empirical results of the proposed method indicate that SniffDroid operates in linear time w.r. t. the number of components. It works efficiently on apps of all sizes and is scalable.
A Flexible AGC Algorithm for the Hellenic Interconnected System

A flexible automatic generation control (AGC) algorithm is described that has been developed for the Hellenic interconnected system. The algorithm includes the three well-known load frequency control (LFC) types (flat frequency, flat tie-line, and tie-line bias) and introduces four operating modes that depend on the magnitude of the measured area control error (ACE). These modes are the steady-state operating mode, the normal operating mode, and two distinct emergency modes. The LFC stability margins are calculated for the case of slow-acting, flat frequency control. The effects of integral feedback are also considered and analyzed. An approximate economic dispatch algorithm is presented that makes use of a predetermined table of the economic loading of units. Simulation results are reported that demonstrate satisfactory operation of the AGC system. Detailed transient stability program simulations demonstrate that a number of ACE measurements per measuring period are necessary to avoid dangerous false emergencies. >
Spinal Surgery and Ophthalmic Complications: A French Survey With Review of 17 Cases

Objectives Ocular complications after spine surgery are incompletely understood and are not as rare as implied by recent publications. In 13 out of 15 published case reports, ocular complications are attributed mainly to compression. But in 66 cases reported in 4 series in the literature, compression seems to play a role in less than 10 cases. However, 3 out of the 4 series lack sufficient detail to support this mechanism clearly. Our objectives were to identify the mechanisms and specific risk factors associated with this devastating complication, to help in prevention. Methods A 2-page survey was sent to all French orthopedic centers specializing in spine surgery (28 centers) requesting information regarding any patients who had experienced visual deficits after spine surgery. Respondents were asked to identify presence of commonly cited preoperative risk factors, including ophthalmologic diagnosis and local signs (eyelid or conjunctival edema, periorbital numbness, or paresthesia) and intraoperative risks, such as positioning of the head, to clarify the possible mechanisms. Seventeen patients were thus included. Results Two main mechanisms were identified. First, ocular compression (9 cases) characterized by a unilateral definitive blindness with local signs due to a central retinal artery occlusion. Second, internal carotid thromboembolism (4 cases) associated with head rotation toward the ipsilateral side, causing an ischemic optic neuropathy with a unilateral partial and potentially regressive visual loss. Conclusions The authors propose 2 preventive measures: modification of horseshoe-shaped headrest and precautions with lateral rotation of the head in patients with carotid atheroma.
The relationship between anti-vascular endothelial growth factor and fibrosis in proliferative retinopathy: clinical and laboratory evidence

Purpose To investigate the progression of epiretinal membranes after intravitreal bevacizumab (IVB) injection therapy in patients with proliferative membranes and evaluate the changes in fibrosis-related cytokines in retinal pigment epithelial cells and glial cells after treatment with bevacizumab. Methods Retrospective study of the proliferative membranes in patients with and without IVB therapy. In vitro, the human adult retinal pigment epithelial (ARPE-19) cells and BV2 microglial cell lines were incubated in different bevacizumab concentrations under hypoxic conditions. Cell culture supernatants and cell lysates were harvested after incubation for 24, 48 or 72 hours for ELISA and western blot. Results Bevacizumab accelerated fibrosis in patients with proliferative membranes. Immunofluorescence analysis revealed more intense transforming growth factor β2 (TGFβ2) and connective tissue growth factor (CTGF) staining in IVB-treated proliferative diabetic retinopathy (PDR) membranes compared with membranes of patients not receiving IVB therapy. This result was consistent with real-time PCR results. Bevacizumab incubation significantly upregulated TGFβ2 and CTGF in ARPE-19 cells and BV2 microglial cells, but ciliary neurotrophic factor (CNTF) expression was upregulated only in BV2 microglial cells. Conclusions Anti-vascular endothelial growth factor treatment likely accelerates fibrosis in PDR patients via upregulation of TGFβ2, CTGF and CNTF, suggesting the importance of adjunctive therapy for retinal fibrosis.
Fluctuating trade-offs favour precocial maturity in male Soay sheep

Although trade-offs between reproductive effort and survival are commonly proposed, empirical studies that quantify the true costs and benefits of breeding activity are rare. This information is crucial, however, for examining the adaptive value of important life history traits such as age at maturity. Here we estimate both the survival cost, and genetic benefits, of precocial male maturity in a highly polygynous naturally limited population of Soay sheep. While we demonstrate that early reproduction does indeed carry a survival cost, we find that young males also achieve unexpectedly high reproductive success and that precocial mating is favoured due to the fluctuating demographic structure of the population.