Miracle-dz/UniFAR-FTUs huggingface dataset:
A stepwise approach to justify phase III randomized clinical trials and enhance the likelihood of a positive result

Multiple time-consuming, expensive, and negative phase III clinical trials involving many thousands of patients have been undertaken in critical care and continue to be funded. The vast majority of these clinical trials are negative. Furthermore, phase III studies frequently fail to achieve their planned recruitment target. Often such studies are based on small pilot studies with inadequate phase II trial data and limited mechanistic data to provide a sound scientific rationale. The body of research required to justify undertaking a phase III trial in the critically ill population has not been defined adequately. In particular, guidance on the design of phase II studies for evaluating treatments in the critically ill population is needed. Research to inform critical care practice will progress more efficiently and effectively if this can be achieved. The following article presents a template on the minimum evidence required to justify phase III clinical trials in the critically ill population.
Restitution des propriétés microphysiques et radiatives des nuages froids et mixtes à partir des données du système RALI (RAdar-LIdar)

Les nuages jouent un role important dans l'evolution de l'atmosphere meteorologique et dans le controle du climat. Or leur representation parametrique dans les modeles numeriques de prevision meteorologique et climatologique n'est toujours pas validee a ce jour. La preoccupation de la communaute scientifique internationale d'etre a meme de mieux controler a l'echelle globale l'effet radiatif des nuages a stimule plusieurs programmes spatiaux mettant en œuvre une combinaison radar-lidar (CLOUDSAT/CALIPSO et EarthCare). De telles experiences spatiales ont besoin de demonstrateurs aeroportes tels que RALI (systeme synergique RAdar nuage - LIdar), qu'il s'agisse de la mise au point des algorithmes de traitement de donnees, ou de la validation des produits de la mission spatiale. Ainsi, le projet RALI vise le developpement et l'exploitation d'une combinaison instrumentale radar-lidar aeroportee ou au sol, pour documenter les profils verticaux des proprietes microphysiques, dynamiques et radiatives des nuages glaces non precipitants. C'est dans ce cadre que s'inscrit cette these. Dans un premier temps, un modele inverse reliant les parametres de teledetection aux parametres nuageux a ete construit. Ce modele permet de s'affranchir de la forme de la distribution dimensionnelle des particules; il sert de base a l'application de l'algorithme synergique radar-lidar. Celui-ci, prenant en compte la variation verticale de la concentration des particules nuageuses, a egalement ete developpe. Des tests de simulation ont ete effectues afin de determiner sa robustesse, sa precision et les conditions optimales d'application. Les resultas obtenus sur des cas d'experimentations instrumentales (Clare'98, Carl'99 et Clare'2000), compares a des mesures in-situ microphysiques, ont montre sa capacite a restituer le rayon effectif des particules nuageuses, le contenu en glace et l'epaisseur optique des nuages sondes. L'algorithme est egalement capable de restituer le contenu en eau des couches de phase mixtes et sa capacite a ete testee sur un cas d'altocumulus de Clare'2000.
Tamm-Horsfall Protein Binds to Type 1 Fimbriated Escherichia coli and Prevents E. coli from Binding to Uroplakin Ia and Ib Receptors*

The adherence of uropathogenic Escherichia coli to the urothelial surface, a critical first step in the pathogenesis of urinary tract infection (UTI), is controlled by three key elements: E. coli adhesins, host receptors, and host defense mechanisms. Although much has been learned about E. coli adhesins and their urothelial receptors, little is known about the role of host defense in the adherence process. Here we show that Tamm-Horsfall protein (THP) is the principal urinary protein that binds specifically to type 1 fimbriated E. coli, the main cause of UTI. The binding was highly specific and saturable and could be inhibited by d-mannose and abolished by endoglycosidase H treatment of THP, suggesting that the binding is mediated by the high-mannose moieties of THP. It is species-conserved, occurring in both human and mouse THPs. In addition, the binding to THP was much greater with an E. coli strain bearing a phenotypic variant of the type 1 fimbrial FimH adhesin characteristic of those prevalent in UTI isolates compared with the one prevalent in isolates from the large intestine of healthy individuals. Finally, a physiological concentration of THP completely abolished the binding of type 1 fimbriated E. coli to uroplakins Ia and Ib, two putative urothelial receptors for type 1 fimbriae. These results establish, on a functional level, that THP contains conserved high-mannose moieties capable of specific interaction with type 1 fimbriae and strongly suggest that this major urinary glycoprotein is a key urinary anti-adherence factor serving to prevent type 1 fimbriated E. coli from binding to the urothelial receptors.
Expression of Cell Cycle Control Proteins in Primary Colorectal Tumors Does Not Always Predict Expression in Lymph Node Metastases 1

Analysis of tumor markers focuses on expression in primary tumors with the assumption that this is representative of metastatic tumor, against which treatment is targeted. Few studies have compared the expression of such markers in primary and secondary tumors. In this study, several key genes involved in cell cycle regulation were investigated in colorectal tumors and corresponding lymph node metastases. The cell cycle regulators p53, cyclin D1, p21, p27, retinoblastoma protein (Rb), and proliferating cell nuclear antigen (PCNA) were examined in a series of 42 paired samples of primary colorectal and secondary lymph node tumors by immunohistochemistry. Expression of p53, p27, and Rb was similar in virtually all paired samples (p53, 38 of 42; p27, 39 of 42; Rb, 40 of 42), indicating that the pattern of these proteins in colorectal tumors may be used to predict that in lymph node tumors. It also suggests a lack of direct involvement in the metastatic process. A lower concordance for p21 and cyclin D1 staining was observed between primary and secondary tumors (p21, 19 of 42; cyclin D1, 22 of 42). p21 expression was more often observed in primary colorectal cancers, whereas cyclin D1 expression was more frequently seen in lymph node metastases, in keeping with the contrasting roles of these proteins as a cell cycle inhibitor (p21) and activator (cyclin D1). The PCNAlabeling index was found to vary considerably in a number of cases, thus limiting the ability to predict expression of this protein in lymph node metastases from the primary tumor. In addition, PCNA-labeling indices between paired samples were neither consistently higher nor lower, suggesting that the proliferative capacity of tumor cells is not directly related to their ability to metastasize.
Altered Expression of TAP-1 and Major Histocompatibility Complex Class I in Laryngeal Papillomatosis: Correlation of TAP-1 with Disease

ABSTRACT Recurrent respiratory papillomatosis (RRP) is an insidious disease caused by human papillomavirus (HPV) infection. It is characterized by a variable clinical course that can include frequent disease recurrence, significant morbidity, and occasional mortality. The mechanisms responsible for the variability in the clinical course and the persistence of latent HPV infection remain unknown. Effective T-cell-mediated clearance of HPV-infected cells may be defective in patients with RRP, leading to recurrent disease and failure to suppress latent HPV reactivation. This study describes the down-regulation of the transporter associated with antigen presentation (TAP-1) and the major histocompatibility complex (MHC) class I protein expression in laryngeal papilloma tissue biopsies and cell culture of primary explants. There was a statistically significant correlation between reduction of TAP-1 expression in biopsy tissues and rapid recurrence of disease. Patients with RRP had less frequent recurrence if their papillomas expressed TAP-1 at levels close to that of normal tissue, compared with those with very low expression of TAP-1, who had frequent recurrence (32 versus 5 weeks to the next surgical intervention). These findings suggest that HPV may evade immune recognition by down-regulating class I MHC cell surface expression via decreased TAP-1 levels. Expression of TAP-1 could be used for prognostic evaluation of disease severity. Gamma interferon was able to restore class I MHC expression at the surfaces of laryngeal papilloma cells in culture. This up-regulation of class I MHC antigen at the cell surface potentially allows the infected cell to become a target for the immune system again. This finding provides some promise for nonsurgical treatment of laryngeal papillomas.
Human Observer and Automatic Assessment of Movement Related Self-Efficacy in Chronic Pain: From Exercise to Functional Activity

Clinicians tailor intervention in chronic pain rehabilitation to movement related self-efficacy (MRSE). This motivates us to investigate automatic MRSE estimation in this context towards the development of technology that is able to provide appropriate support in the absence of a clinician. We first explored clinical observer estimation, which showed that body movement behaviours, rather than facial expressions or engagement behaviours, were more pertinent to MRSE estimation during physical activity instances. Based on our findings, we built a system that estimates MRSE from bodily expressions and bodily muscle activity captured using wearable sensors. Our results (F1 scores of 0.95 and 0.78 in two physical exercise types) provide evidence of the feasibility of automatic MRSE estimation to support chronic pain physical rehabilitation. We further explored automatic estimation of MRSE with a reduced set of low-cost sensors to investigate the possibility of embedding such capabilities in ubiquitous wearable devices to support functional activity. Our evaluation for both exercise and functional activity resulted in F1 score of 0.79. This result suggests the possibility of (and calls for more studies on) MRSE estimation during everyday functioning in ubiquitous settings. We provide a discussion of the implication of our findings for relevant areas.
A novel slow (< 1 Hz) oscillation of neocortical neurons in vivo: depolarizing and hyperpolarizing components

We describe a novel slow oscillation in intracellular recordings from cortical association areas 5 and 7, motor areas 4 and 6, and visual areas 17 and 18 of cats under various anesthetics. The recorded neurons (n = 254) were antidromically and orthodromically identified as corticothalamic or callosal elements receiving projections from appropriate thalamic nuclei as well as from homotopic foci in the contralateral cortex. Two major types of cells were recorded: regular- spiking (mainly slow-adapting, but also fast-adapting) neurons and intrinsically bursting cells. A group of slowly oscillating neurons (n = 21) were intracellularly stained and found to be pyramidal-shaped cells in layers III-VI, with luxuriant basal dendritic arbors. The slow rhythm appeared in 88% of recorded neurons. It consisted of slow depolarizing envelopes (lasting for 0.8–1.5 sec) with superimposed full action potentials or presumed dendritic spikes, followed by long- lasting hyperpolarizations. Such sequences recurred rhythmically at less than 1 Hz, with a prevailing oscillation between 0.3 and 0.4 Hz in 67% of urethane-anesthetized animals. While in most neurons (approximately 70%) the repetitive spikes superimposed on the slow depolarization were completely blocked by slight DC hyperpolarization, 30% of cells were found to display relatively small (3–12 mV), rapid, all-or-none potentials after obliteration of full action potentials. These fast spikes were suppressed in an all-or-none fashion at Vm more negative than -90 mV. The depolarizing envelope of the slow rhythm was reduced or suppressed at a Vm of -90 to -100 mV and its duration was greatly reduced by administration of the NMDA blocker ketamine. In keeping with this action, most (56%) neurons recorded in animals under ketamine and nitrous oxide or ketamine and xylazine anesthesia displayed the slow oscillation at higher frequencies (0.6–1 Hz) than under urethane anesthesia (0.3–0.4 Hz). In 18% of the oscillating cells, the slow rhythm mainly consisted of repetitive (15–30 Hz), relatively short-lasting (15–25 msec) IPSPs that could be revealed by bringing the Vm at more positive values than -70 mV. The long-lasting (approximately 1 sec) hyperpolarizing phase of the slow oscillation was best observed at the resting Vm and was reduced at about -100 mV. Simultaneous recording of another cell across the membrane demonstrated synchronous inhibitory periods in both neurons. Intracellular diffusion of Cl- or Cs+ reduced the amplitude and/or duration of cyclic long- lasting hyperpolaryzations. (ABSTRACT TRUNCATED AT 400 WORDS)
Up to 10-year follow-up of the Symax stem in THA: a Danish single-centre study

Introduction: The design of the cementless Symax-HA femoral stem is based on geometrical analysis of human femoral anatomy to optimise the fit within the femur. The stem combines an anatomical proximal section enabling a metaphyseal anchorage with a straight distal section. This results in an improved proximal load transfer. We aimed to determine the overall survival of total hip arthroplasty (THA) in patients operated at our institution with the Symax stem. Secondly, we investigated the cause of revision for patients having THA including the Symax stem. Methods: The study is a registry study with results from a single centre, Vejle Hospital. From the Danish Hip -Arthroplasty Registry, we identified all THAs operated with the Symax stem. The primary outcome was revision. The secondary outcomes were aseptic loosening, periprosthetic fracture, and all other causes for revision. Results: In total, 1,055 THAs were performed in 875 patients. The median 6.5-year survival rate was 97.5% (95% confidence interval [CI]: 96.6%-98.3%). 29 THAs had undergone revision due to the following causes: periprosthetic fracture (n = 11); aseptic loosening of the cup (n = 1); infection (n = 5); dislocation (n = 10); and component failure (n = 2). There was no revision due to aseptic loosening of the stem. Conclusions: From the Danish Hip Arthroplasty Registry, we identified the overall 6.5-year survival rate to be 95% for cementless THAs. In the present study, the Symax stem has a median 6.5-year survival rate at 97.5% (96.6%-98.3%). No revisions were due to aseptic loosening but the stem had a relative high prevalence of periprosthetic fractures.
Prolonged Prophylaxis in Orthopedic Surgery: Insights from the United States

The U.S. Hip and Knee Registry is a voluntary national registry of outcome data for hip and knee surgery. In total, 469 orthopedic surgeons from 325 hospitals reported data on 7677 patients who underwent total hip arthroplasty (THA) and 11,461 patients who underwent total knee arthroplasty (TKA). Data on patients enrolled between 1996 and 2000 indicate that 40% of THA patients and 42% of TKA patients received prophylaxis for a period of 8 to 21 days, including the in-hospital period. Prolonged prophylaxis for more than 21 days was used in 49% of THA patients and 44% of TKA patients. Moreover, year on year, data indicate that the percentage of patients who receive prophylaxis for longer than 21 days is gradually increasing. In 2000, 53% of THA patients and 47% of TKA patients received prophylaxis for longer than 21 days.
Allocation of periodic task modules with precedence and deadline constraints in distributed real-time systems

The authors address the problem of allocating (assigning and scheduling) periodic task modules to processing nodes (PNs) in distributed real-time systems subject to task precedence and timing constraints. Using the branch-and-bound technique, a module allocation algorithm (MAA) is proposed to find an optimal allocation that maximizes the probability of meeting task deadlines. To incorporate both timing and logical correctness into module allocation, the probability of meeting task deadlines is used as the objective function. The MAA is then applied to find an optimal allocation of task modules in a distributed system. The timing aspects embedded in the objective function drive the MAA not only to assign task modules to PNs, but also to use a module scheduling algorithm for scheduling all modules assigned to each PN so that all tasks may be completed in time. Several numerical examples are presented to demonstrate the effectiveness and practicality of the proposed algorithms. <<ETX>>
Stage of cancer at diagnosis for Medicare HMO and fee-for-service enrollees.

OBJECTIVES Health maintenance organizations (HMOs) with Medicare contracts often provide cancer screening and preventive services not covered under fee-for-service. This study compared cancer patients in HMOs and fee-for-service on stage at diagnosis. METHODS The study examined stage at diagnosis for aged Medicare enrollees in HMOs and fee-for-service, using information from the Surveillance, Epidemiology, and End Results program, linked with Medicare enrollment files. Twelve cancer sites were investigated, and demographics, area of residence, year of diagnosis (1985 to 1989), and education at the census tract level were controlled. RESULTS HMO enrollees were diagnosed at earlier stages for cancers of the female breast, cervix, colon, and melanomas and at later stages for stomach cancer. There were no differences for cancers of the prostate, rectum, buccal cavity and pharynx, bladder, uterus, kidney, and ovary. HMO effects were strongest in areas with large, mature HMOs. CONCLUSIONS Compared with fee-for-service enrollees, HMO enrollees were diagnosed at earlier stages for cancer sites for which effective screening services are available. The earlier detection of certain cancers among HMO enrollees may result from coverage of screening services and, perhaps, promotion by HMOs of such services.
Thymic stromal lymphopoietin is a critical mediator of IL‐13‐driven allergic inflammation

Both thymic stromal lymphopoietin (TSLP) and IL‐13 are essential cytokines for the development of allergic inflammation. However, a causal link between TSLP and IL‐13 has not yet been fully elucidated. This study aimed to investigate whether IL‐13 induces TSLP expression and whether the induction contributes to the development of allergic inflammation. We found that IL‐13 induced TSLP expression in mouse nasal tissue specimens in a Stat6‐dependent manner. In addition, intranasal challenge of mice with IL‐13 induced TSLP expression in the nasal epithelium. Importantly, intranasal IL‐13 challenge induced eosinophilia and goblet cell hyperplasia in the nasal mucosa in mice, which was inhibited by the blockade of TSLP activity with anti‐TSLP Ab. These findings suggest that TSLP is an important mediator of IL‐13‐driven allergic inflammation in the nasal mucosa. Taken together with the recent findings that IL‐13 is a critical downstream element for TSLP‐driven allergic inflammation, TSLP may function both upstream and downstream of IL‐13, thus providing an additional rationale as to why TSLP plays such a central role in the development of allergic inflammation.
Multipolar expansion sensors for near field characterization

This paper introduces a new generation of magnetic field sensors, based on the spherical harmonics decomposition concept. The measurement principle is similar to a spatial filtering: according to the coil shape, the sensors are just sensitive to a specific component of the multipolar expansion. Five coil shapes are determined, in order to account for the first two orders of the harmonic decomposition. The way of determining the coil shape is first explained, and a validation is proposed using a finite element software.
CXCR2: a target for pancreatic cancer treatment?

Introduction: Pancreatic cancer, a leading cause of cancer deaths worldwide, is very aggressive and has minimally effective treatment options. For those who have no surgical options, medical treatments are limited. The chemokine receptor CXCR2 has become the subject of much interest recently because of multiple studies indicating its involvement in cancer and inflammatory conditions. Research now indicates that CXCR2 and its ligands are intimately involved in tumor regulation and growth and that inhibition of its function shows promising results in multiple cancer types, including pancreatic cancer. Areas covered: In this study, the authors review basic molecular and structural details of CXCR2, as well as the known functions of CXCR2 and several of its ligands in inflammation and cancer biology with specific attention to pancreatic cancer. Then the future possibilities and questions remaining for pharmacological intervention against CXCR2 in pancreatic cancer are explored. Expert opinion: Many current inhibitory strategies already exist for targeting CXCR2 in vitro as well as in vivo. Clinically speaking, CXCR2 is an exciting potential target for pancreatic cancer; however, CXCR2 is functionally important for multiple processes and therapeutic options would benefit from further work toward understanding of these roles as well as structural and target specificity.
Assessing Organizational Citizenship Behavior in the French Context: Evidence for the Four-Dimensional Model

Although researchers have extensively studied organizational citizenship behavior (OCB) in the U.S. context, OCB measurement has received relatively limited attention in other contexts, specifically in the French-language context. Using 2 samples (for Study 1, N = 292; for Study 2, N = 355), the author investigated OCB in a French-language context. Using an exploratory factorial analysis in Study 1, the author found a 4-factor model (altruism, civic virtue, sportsmanship, helping others). Using a confirmatory factor analysis in Study 2, the author confirmed a 4-factor model. Data provided results that show some differences and similarities between U.S. and French contexts.
Oxygen, the lung and the diver: friends and foes?

Worldwide, the number of professional and sports divers is increasing. Most of them breathe diving gases with a raised partial pressure of oxygen (PO2). However, if the PO2 is between 50 and 300 kPa (375–2250 mmHg) (hyperoxia), pathological pulmonary changes can develop, known as pulmonary oxygen toxicity (POT). Although in its acute phase, POT is reversible, it can ultimately lead to non-reversible pathological changes. Therefore, it is important to monitor these divers to prevent them from sustaining irreversible lesions. This review summarises the pulmonary pathophysiological effects when breathing oxygen with a PO2 of 50–300 kPa (375–2250 mmHg). We describe the role and the limitations of lung function testing in monitoring the onset and development of POT, and discuss new techniques in respiratory medicine as potential markers in the early development of POT in divers. To prevent the early development of pulmonary oxygen toxicity divers must be properly monitored http://ow.ly/RVJL301fySb
Does medical school cause health anxiety and worry in medical students?

Objectives The aim of this study was to investigate the self‐reported experience of health anxiety and worry in medical students compared with control subjects. It was hypothesised that medical students would experience more health anxiety as a consequence of being exposed to medical education, compared to students who are not routinely exposed to such knowledge.