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Pathologic axillary lymph node (ALN) status is an important prognostic factor for staging breast cancer. Currently, status is determined by histopathology following surgical excision of sentinel lymph node(s), which is an invasive, time consuming, and costly procedure with potential morbidity to the patient. Here, we describe an imaging platform for noninvasive assessment of ALN status, eliminating the need for surgical examination of patients to rule out nodal involvement. A targeted imaging probe (MamAb-680) was developed by conjugation of a mammaglobin-A–specific monoclonal antibody to a near-infrared fluorescent dye. Using DNA and tissue microarray, mammaglobin-A was validated as a cell-surface target that is expressed in ALN-positive patient samples but is not expressed in normal lymph nodes. In vivo selectivity was determined by i.v. injection of MamAb-680 into mice with mammaglobin-A–positive and -negative mammary fat pad (MFP) tumors; and by peritumoral MFP injection of the targeted imaging probe in mice with spontaneous ALN metastases. Fluorescence imaging showed that probe was only retained in positive tumors and metastases. As few as 1,000 cells that endogenously express mammaglobin-A were detected in ALN, indicating high sensitivity of this method. Translation of this approach offers considerable potential as a noninvasive clinical strategy to stage breast cancer. Cancer Res; 71(3); 1050–9. ©2010 AACR.

Supplementary Figures 1-4 from A Mammaglobin-A Targeting Agent for Noninvasive Detection of Breast Cancer Metastasis in Lymph Nodes

Background Septic shock is a serious condition leading to increased mortality. Despite previous report of no benefit, thiamine has emerged as potential therapy to reduce mortality in septic shock patients. This study aimed to investigate the effect of thiamine in mortality rate in patients with septic shock. Methods Eight databases, including MEDLINE, EMBASE, Science Direct, Scopus, Cochrane, CINAHL, Open Grey, and Dart-Europe, were systematically searched from the inception of the database up to August 21, 2020. Studies evaluating the effectiveness of thiamine on mortality rate in septic shock patients compared between thiamine and placebo were included. We used random-effects model to analyze the mortality with risk ratio (RR) and 95% confidence interval (95% CI). The subgroup and sensitivity analysis were performed to examine the influence of variables. Publication bias was considered using funnel plot, Begg's test, and Egger's test. Results A total of 3,658 studies were retrieved and reviewed. Five studies were included for meta-analysis. In random-effects meta-analysis of the randomized controlled trials, although not statistically significant, there was a trend which suggested that thiamine may reduce mortality rate in septic shock patients (RR, 0.96; 95% CI: 0.72-1.28, P = 0.774). The result of sensitivity and subgroup analyses also supported the suggestion that thiamine may decrease mortality in septic shock patients. The Begg's test (P = 0.624) and Egger's test (P = 0.777) revealed no publication bias. Conclusions Although not statistically significant, thiamine may reduce mortality rate in septic shock patients. Further prospective studies with larger sample size are warranted.

Four new phosphonate MOFs were prepared with cationic dimethylbipiperdinium units: [La2(H2L)1.5(AcO)2Br·3.25H2O], α-PCMOF-21-Br; [La2(H2L)1.5(AcO)Cl2·5.25H2O], α-PCMOF-21-Cl; [La(H2L) (AcO)Br0.5·4....

Cationic frameworks are an emerging class of exceptional solid adsorbents capable of encapsulating highly toxic and persistent anionic pollutants. The controlled generation of cationic frameworks, however, lags behind the abundant design strategies devised to control the structures and topologies of neutral frameworks. In this regard, we report a rational approach that allows the conversion of the synthetic approach toward constructing a neutral framework into one allowing for the synthesis of a cationic one without incurring any changes to the overall topology or the selected metal ion. We demonstrate that the replacement of a functional group on an organic linker that promotes a similar coordination mode, but bearing one less negative charge, can yield the systematic generation of cationic frameworks. Moreover, we confirm the cationic nature of the metal-organic frameworks through preliminary anion-exchange experiments and propose a method to retain permanent porosity in cationic frameworks through the use of strongly binding anions. Altogether, these results show great promise for the construction of tunable nanoporous frameworks capable of carrying out anion-exchange processes.

Introduction Google trends (GT) permet de connaitre la frequence a laquelle un terme a ete cherche dans Google. Son interet a ete demontre pour predire et detecter des foyers epidemiques. Cependant, aucune etude n’a evalue son interet pour detecter de nouveaux signes cutanes en integrant l’influence de facteurs externes i.e. confinement et couverture mediatique des nouveaux signes. L’objectif de ce travail est d’evaluer l’activite et l’influence de facteurs externes sur les recherches des signes cutanes lies a SARS-Cov-2 dans plusieurs pays. Materiel et methodes Deux recherches sur GT en incluant les termes 1/« orteil(s) » et « engelure(s) », et 2/« Coronavirus » ont ete realisees pour la periode 1er janvier - 16 mai 2020 dans 6 pays (France, Etats-Unis, Grande Bretagne (GB), Espagne, Italie et Allemagne). Pour chacun des pays, les facteurs externes i.e. date de confinement et annonce grand media des signes cutanes ont ete collectes. La sequence de recherche signes cutanes versus coronavirus a ete visualisee sur une figure commune en utilisant le ratio signes cutanes/coronavirus. Une regression lineaire par segments, en integrant les dates de confinement et d’annonce mediatique de chaque pays a ete realisee pour etudier l’impact des facteurs externes sur les recherches. Resultats Les volumes relatifs de recherche ou relative search volumes (RSVs) fournis par GT et lies aux engelures sont croissants sur la periode debutant mi-mars jusqu’aux annonces mediatiques (ou elle atteint un pic dans 3 pays). Le ratio RSVs engelures/RSVs Coronavirus, montre que l’interet relatif pour les engelures croit dans l’ensemble des pays. La regression lineaire par segments met en evidence : – apres le debut du confinement, un effet de seuil negatif (p – post annonces mediatiques, un effet de seuil positif et une pente decroissante (p – aucune variation en Allemagne. Le coefficient de determination R2 ajuste entre 0,305 et 0,351 pour la France, Espagne, Italie, et Etats-Unis montre une correlation moyenne entre le RSV et le temps. Discussion L’augmentation des RSVs signes cutanes avant les medias des la mi-mars temoigne d’un signal precoce present sur Google. Dans 4 pays, cet interet culmine au moment des annonces. Le ratio engelure/coronavirus montre cependant un seuil eleve de recherches apres les annonces en comparaison avec le coronavirus seul. Conclusion Un systeme d’alerte sur Google permettrait une detection precoce de symptomes cutanes associes a une maladie emergente. La prise en compte de facteurs, influencant les requetes, est necessaire pour garantir la fiabilite de tels systemes d’alerte.

Targeted therapy has held promise to be a successful anticancer treatment due to its specificity towards tumor cells that express the target receptors. However, not all targeting drugs used in the clinic are equally effective in tumor eradication. To examine which biochemical and biophysical properties of targeted agents are pivotal for their effective distribution inside the tumor and their efficient cellular uptake, we combine mathematical micro-pharmacological modeling with in vivo imaging of targeted human xenograft tumors in SCID mice. The mathematical model calibrated to experimental data was used to explore properties of the targeting ligand (diffusion and affinity) and ligand release schemes (rates and concentrations) with a goal to identify the properties of cells and ligands that enable high receptor saturation. By accounting for heterogeneities typical of in vivo tumors, our model was able to identify cell- and tissue-level barriers to efficient drug uptake. This work provides a base for utilizing experimentally measurable properties of a ligand-targeted agent and patient-specific attributes of the tumor tissue to support the development of novel targeted imaging agents and for improvement in their delivery to individual tumor cells.

Working with silica nanoparticle encapsulated BODIPY and xanthene photosensitizers, we have determined that singlet oxygen spends up to 78% of its lifetime inside the nanocarriers. Our systematic investigation indicates that hydrophobicity rules the photosensitizer distribution in nanoparticles, which in turn dictates the ability of these structures to release singlet oxygen.

Phosphonate monoesters (PMEs) as ligands for metal–organic frameworks can potentially direct topology, enhance water stability, and modify pore chemistry. Here, we show, experimentally and computationally, not only that is the ratio of phosphonate to phosphonate monoester significant, but also that gas sorption depends on the distribution of the monoesters in the structure. A phosphonate monoester ligand, 1,3,5-tri(4-phosphonato)benzene-tris(monoethylester), was coordinated to copper(II) to form two different frameworks based on the same copper–phosphonate chain building units, one dense (1) and the other with an experimental surface area over 1000 m2 g–1 (CALF-33-Et3). One of the three phosphonate monoesters in CALF-33-Et3 can be hydrolyzed to make an isostructural material, CALF-33-Et2H, with approximately the same surface areas but vastly superior CO2 sorption. Controlling the hydrolysis at this site allowed the partially hydrolyzed variants, CALF-33-Et3–xHx (where 0 < x < 1), to be prepared and their ...

Objectifs L’estimation du risque cardiovasculaire par des equations de type SCORE ou Framingham permet un ajustement personnalise des mesures de prevention primaire. Ces algorithmes peuvent etre sensibilises par la mise en evidence d’un atherome infra-clinique. Ainsi, le score calcique de l’aorte abdominale (SCAA), apparait comme un marqueur emergeant d’atherosclerose. Ce travail s’est propose d’etudier les correlations entre le SCAA et (1) le risque d’evenement cardiovasculaire a 10 ans, (2) les equations SCORE et ASCVD et (3) des indices de rigidite arterielle valides. Methodes Il s’agit d’une etude monocentrique, prospective, observationnelle. Des patients hypertendus, de plus de 45 ans, indemnes de maladie cardiovasculaire constituee, suivis dans un centre expert HTA ont ete inclus de maniere prospective entre juillet 2007 et novembre 2008 ( NCT00496717 ) et ont beneficie d’un scanner abdominal sans contraste iode. L’analyse a debute 1 cm au-dessus du depart des arteres renales se terminant au niveau de la bifurcation aorto-iliaque. Les calcifications ont ete definies par des plaques superieures ou egales a 2 pixels, d’une densite superieure ou egale a 130 unites Hounsfield. Le SCAA a ete calcule selon la methode d’Agatston validee pour les calcifications coronariennes. La pression arterielle (PA), la vitesse de l’onde pouls (VOP) et l’index de pression systolique (IPS) ont ete colliges. Resultats Une cohorte de 33 patients hypertendus (dont 5 femmes), âges de 64,2 ± 7,3 ans ont ete inclus. Ce groupe comprenait 7 diabetiques. L’IMC etait de 26,6 ± 3,4 kg/m2. L’estimation SCORE etait de 4,4 % (IQR 2,7-6,6) et ASCVD de 16,6 % (IQR 9,3-27,6). La PA systolique clinique etait de 138 (IQR 130-143) mmHg, la pression pulsee clinique de 55(IQR 48-62) mmHg et la VOP de 8,7 ± 2,4 m/s ; l’IPS etait de 1,10 (IQR 1-1,25). A 10 ans, 7 patients (21 %) ont presente un evenement cardiovasculaire et 3 (9 %) sont decedes (deces d’origine non-cardiovasculaire). Le SCAA etait correle au risque de presenter un evenement cardiovasculaire a 10 ans (p Conclusion Le SCAA relie l’atherosclerose a la rigidite arterielle et pourrait permettre une meilleure stratification du risque cardiovasculaire. Cette methode rapide, faiblement irradiante et precise pourrait representer une alternative a d’autres methodes operateur-dependantes.

A crystalline and permanently porous copper phosphonate monoester framework has been synthesized from a tetraaryl trigonal phosphonate monoester linker. This material has a surface area over 1000 m2 g−1, as measured by N2 sorption, the highest reported for a phosphonate-based metal–organic framework (MOF). The monoesters result in hydrophobic pore surfaces that give a low heat of adsorption for CO2 and low calculated selectivity for CO2 over N2 and CH4 in binary mixtures. By careful manipulation of synthetic conditions, it is possible to selectively remove some of the monoesters lining the pore to form a hydrogen phosphonate while giving an isomorphous structure. This increases the affinity of the framework for CO2 giving higher ambient uptake, higher heat of adsorption, and much higher calculated selectivity for CO2 over both N2 and CH4. Formation of the acid groups is noteworthy as complexation with the parent acid gives a different structure.

Warming is a major climate change concern, but the impact of high maximum temperatures depends upon the air’s moisture content. Trends in maximum summertime temperature, moisture, and heat index are tracked over three time periods: 1900–2011, 1950–2011, and 1979–2011; these trends differ notably from annual temperature trends. Trends are emphasized from two CRU datasets (CRUTS3.25 and CRUTS4.01) and two reanalyses (ERA-20C and 20CRv2). Maximum temperature trends tend towards warming that is stronger over the Great Lakes, the interior western and the northeastern contiguous United States. A warming hole in the Midwest generally decreases in size and magnitude when heat stress trends are calculated because the region has increasing moisture. CRU and nearly all reanalyses find cooling in the northern high plains that is not found in NOAA Climate Division trends. These NOAA trends are captured better by CRUTS401. Moistening in the northeast amplifies the heat stress there. Elsewhere the moisture trends are less clear. Drying over northern Texas (after 1996) in CRUTS401 translates into decreasing heat stress there (less so in CRUTS325). Though other reanalyses are not intended for long-term trends, MERRA-2 and ERA-Interim match observed trends better than other reanalyses.

Introduction Les therapies ciblees et les anticorps anti-PD1 ont bouleverse la prise en charge du melanome avance. L’association de ces approches s’avere prometteuse mais potentiellement toxique en phase II. Des essais cliniques de phase III sont en cours. Nous presentons les resultats de l’association d’un anti-PD1 a un anti-BRAF chez 9 patients atteints de melanome metastatique et traites en vie reelle. Patients et methodes Etude observationnelle retrospective monocentrique a partir d’une cohorte de patients suivis pour melanome metastatique mute BRAF. Resultats Neuf patients ont recu une association d’anti-PD1 (pembrolizumab n = 8, nivolumab n = 1) et de therapie ciblee (dabrafenib n = 9). Cette association etait instauree chez des patients ayant un melanome agressif (plus de 3 sites metastatiques et/ou metastases cerebrales), apres une ligne anterieure par therapies ciblees (TC), soit pour apparition de metastases cerebrales multiples (n = 6) avec bon controle extracranien sous TC, soit pour effets indesirables (EI) de grades 3–4 attribue a l’anti-MEK ou l’association (n = 5). Les LDH etaient elevees chez 3 patients. La duree mediane de traitement etait de 5 mois (2,5–28 mois), le traitement est en cours chez 4 patients. Le taux de reponse etait de 55 % (3 RC, 2 RP). Trois des 6 patients presentant une progression cerebrale a l’initiation de l’association anti-PD1 et anti-BRAF avaient une stabilisation ou une reponse partielle. Un seul patient presentait un EI de grade 3 (fievre grade 3) ayant motive une diminution de posologie du dabrafenib. Aucun des EI de grade 3/4 survenu sous bitherapie ciblee n’a recidive sous l’association anti-PD1 et anti-BRAF ( Tableau 1 ). Discussion Aucun des patients de l’etude n’avait recu un anti-PD1 seul au prealable. La decision d’associer d’emblee un anti-BRAF a un anti-PD1 reposait sur la progression cerebrale rapide ou d’un EI empechant la poursuite de l’association d’anti-BRAF et MEK, et la bonne reponse initiale a la therapie ciblee. L’objectif des nouvelles associations therapeutiques par immunotherapie et TC est d’obtenir une reponse tumorale rapide et prolongee. La frequence rapportee des EI de grade 3/4 sous anti-PD1 seuls est de 9 a 14 % pour le nivolumab et 10 a 14 % pour le pembrolizumab, et celle sous dabrafenib + trametinib (D + T) de 52 %. Les donnees preliminaires de l’etude Keynote-022 (pembrolizumab + D + T) rapportent des EI de grade 3/4 chez 73 % des patients, les EI immuno-medies etaient tous de grade Conclusion L’association d’un anti-BRAF a un anti-PD1 semble etre une ligne therapeutique efficace et bien toleree chez les patients ayant un melanome mute BRAF avec toxicite severe ou echappement sous bitherapie ciblee.

Introduction La survenue de sarcoidose a ete decrite sous immunotherapie ou therapie ciblee anti-BRAF seule, prescrites pour melanome metastatique. Tres peu de cas ont ete rapportes avec l’association dabrafenib et trametinib (D + T). Nous rapportons 6 cas de sarcoidose histologiquement confirmee induite par cette association. Materiel et methodes Il s’agit d’une etude observationnelle retrospective monocentrique realisee a partir d’une cohorte de patients traites par D + T pour un melanome avance mute BRAF. Ont ete inclus tous les cas de sarcoidose apparus sous traitement et histologiquement confirmes. Resultats Parmi 44 patients traites par D + T, 6 cas de sarcoidose (13,6 %) survenaient chez 4 femmes et 2 hommes d’âge median 59,2 ans. Quatre patients presentaient une sarcoidose cutanee isolee. Une atteinte viscerale associee, ganglionnaire mediastinale, salivaire et/ou hepatique existait chez 2 patients. Deux patients avaient deja developpe une sarcoidose (cutanee, articulaire, ophtalmique) sous vemurafenib seul, regressive sous corticoides locaux (et arret du vemurafenib chez la patiente 4). Le delai median d’apparition de la sarcoidose apres initiation de D + T etait de 7,3 mois (2 a 20 mois). Aucun patient ne necessitait de traitement systemique de la sarcoidose et l’association D + T etait poursuivie. Trois patients (50 %) etaient en reponse tumorale complete sans manifestation de la sarcoidose malgre la poursuite du D + T. Trois patients presentaient une reponse tumorale dissociee ou une progression et decedaient ( Fig. 1 et Tableau 1 ). Discussion La prevalence elevee de la sarcoidose dans notre cohorte est superieure a celle de la population generale (1–5/10 000) et a celle estimee sur une cohorte de patients atteints de melanome sans traitement systemique (0,58 %). Le role declenchant de la therapie ciblee, particulierement des anti-BRAF, dans la survenue de ces sarcoidoses est suggere par leur apparition peu apres le debut de la therapie ciblee chez des patients naifs de sarcoidose, et par la survenue de rechutes lors de la reintroduction d’anti-BRAF et d’anti-MEK. Il s’agit d’un effet secondaire possiblement sous-estime et qui peut etre confondu avec une progression tumorale. L’analyse anatomopathologique de lesions ganglionnaires ou viscerales apparaissant sous traitement doit donc toujours se discuter. La revue de la litterature montre que les sarcoidoses induites sous immunotherapie ou therapie ciblee semblent, le plus souvent, peu severes ne necessitant ni corticotherapie generale ni arret du traitement du melanome. Leur survenue ne semble pas alterer la survie globale. Conclusion Les inhibiteurs de BRAF et de MEK sont de potentiels facteurs declenchant de sarcoidose. Les mecanismes physiopathologiques de ces sarcoidoses induites ne sont que partiellement elucides.

This paper concerntrates on the analysis, design and control methodology in the machining servo system. The overall architecture of motion system is investigated to realize the drawbacks of traditional scheme. Then, this research proposes the suitable design of controller due to rapid calculation, high precision and friendly graphical user interface. The diagram of Fuzzy self-tuning PID and feedforward is constructed to drive the servo machine. The hardware platform of controller has been accomplised such as schematic, PCB artworks and soldering. Later, the middleware and firmware have been closed to promote the execution between controller and computer. The intelligent algorithm is embedded in board level by TMS320C6727 to overcome the problems, for example the existing nonlinear properties, external disturbances or servo lag phenomena. Based on the theoretical design, several simulation results are provided to verify the contributions. From the experimental performance, it can be seen clearly that this controller smoothly manipulate the servo motor, ensure real-time performance and high tracking position.

Most of quadcopter operate in the outdoor environment where is often complex and unpredicted. In order to control the quadcopter in unknown outdoor environment, it should be designed an excellent filter to estimate complete state vector which illustrates the movement of rigid body. In this paper, two filters such as Complementary and Kalman are investigated to compare the performance. Quadcopter collect only measurements from a low-cost inertial measurement unit, IMU-MPU6050. The raw data is put into filter to estimate the state vector in system. In the simulations, these filters are studied to implement in the model of quadrotor. Later, the hardware platform of quadcopter is built to denote experimental results in order to validate the effective design of Complementary filter and Kalman filter in quadcopter.

We introduce an automated, real-time geohazard assessment system designed specifically for underground mining. The system, which we call Geoscience INTEGRATOR, is based on the quantitative 4D geohazard computational strategy that we previously developed and reported on at the Seventh International Conference on Deep and High Stress Mining in Sudbury, Canada, in September 2014. The computational strategy relies on modelling multiple, independent hazard criteria related to geology, structure, rock mass condition, stress, seismicity, mine geometry, and support on the rock interface where the hazards occur, and building a statistical model that relates past hazard occurrence to the state of those criteria at the time of the hazard (McGaughey 2014). Further research and development has been carried out since then with the objective of developing an operational computational infrastructure that enables practical geohazard assessment using this approach. We have developed a system for automatically assembling and managing the required inputs, managing the geohazard assessment computational processes, and providing meaningful reports to mine operators. This has been accomplished within three recent Canadian research programs managed by the Centre for Excellence in Mining Innovation (CEMI): ‘Smart Underground Monitoring and Integrated Technologies’ (SUMIT), ‘Mining Observatory Data Control Centre’ (MODCC), and ‘Ultra-Deep Mining Network’ (UDMN). The initial system design objective under the SUMIT program was a capability to “provide researchers with user-friendly access to mine datasets and their contextual information to facilitate and optimise research efforts.” The system was further developed in the ensuing projects to provide a powerful 3D visualisation interface and to support, track, and automatically report on 4D dynamic mine models and associated geohazards in a deep operating mine context. It is now being deployed to manage multi-institution, multi-site data from both SUMIT and other major research projects in addition to implementations at operating mine sites to improve rockburst and other types of geotechnical hazard assessment. Keywords: geohazard, rockburst, seismicity, machine learning, data management

Objective The aim of this study was to compare the proteome composition of gingival crevicular fluid obtained from healthy periodontium, gingivitis and chronic periodontitis affected sites. Background Owing to its site-specific nature, gingival crevicular fluid is ideal for studying biological processes that occur during periodontal health and disease progression. However, few studies have been conducted into the gingival crevicular fluid proteome due to the small volumes obtained. Methods Fifteen males were chosen for each of three different groups, healthy periodontium, gingivitis and chronic periodontitis. They were categorized based on clinical measurements including probing depth, bleeding on probing, plaque index, radiographic bone level, modified gingival index and smoking status. Gingival crevicular fluid was collected from each patient, pooled into healthy, gingivitis and chronic periodontitis groups and their proteome analyzed by gel electrophoresis and liquid chromatography electrospray ionization ion trap tandem mass spectrometry. Results One hundred and twenty-one proteins in total were identified, and two-thirds of these were identified in all three conditions. Forty-two proteins were considered to have changed in abundance. Of note, cystatin B and cystatin S decreased in abundance from health to gingivitis and further in chronic periodontitis. Complement proteins demonstrated an increase from health to gingivitis followed by a decrease in chronic periodontitis. Immunoglobulins, keratin proteins, fibronectin, lactotransferrin precursor, 14-3-3 protein zeta/delta, neutrophil defensin 3 and alpha-actinin exhibited fluctuations in levels. Conclusion The gingival crevicular fluid proteome in each clinical condition was different and its analysis may assist us in understanding periodontal pathogenesis.

La moitié des décès évitables suite à une blessure au combat serait secondaire à un phénomène hémorragique. Afin de réduire cette mortalité, de nombreux moyens existent pour lutter contre ces hémorragies, dont le garrot dit tourniquet contre les hémorragies de membres, largement diffusé actuellement auprès de nos troupes. Après une présentation générale des garrots et en particulier des modèles les plus utilisés, les études ayant évalué l’utilisation en situations théorique et pratique du garrot sont analysées. Les garrots les plus efficaces d’un point de vue théorique sont les garrots dédiés et notamment le CATTM, le SOFTTTM et l’EMTTM. D’un point de vue pratique, il est démontré que les garrots tourniquets sont largement utilisés sur le terrain et permettent de sauver des vies. À la lumière de cette revue de la littérature, des consignes d’utilisation du garrot sont proposées.

Les complications après chirurgie d’exérèse pulmonaire sont fréquentes et potentiellement graves. Parmi elles, l’hémothorax est une complication pariétale dont la survenue peut être précoce. Un état de choc hémorragique débutant et la quantité de sang recueilli dans les drains suffisent à la diagnostiquer. En l’absence de ces signes classiques, le diagnostic d’hémothorax n’est pas toujours évident, notamment en cas de caillotage ou de drain bouché. Traire les drains est un acte indispensable faisant partie intégrante de la surveillance post-opératoire des drains. Le scanner thoracique permet le plus souvent d’évoquer voire de confirmer le diagnostic d’hémothorax compte tenu du contexte chirurgical, d’en identifier l’origine en cas de saignement actif à haut débit mis en évidence par l’injection de produit de contraste et d’orienter la prise en charge thérapeutique vers la chirurgie ou l’embolisation.

The United States is currently experiencing an opioid crisis, with more than 47,000 deaths in 2017 due to opioid overdoses. Current approaches for opioid identification and quantification in body fluids include immunoassays and chromatographic methods (e.g., LC-MS, GC-MS), which require expensive instrumentation and extensive sample preparation. Our aim was to develop a portable point-of-care device that can be used for the instant detection of opioids in body fluids. Here, we reported the development of a morphine-sensitive fluorescence-based sensor chip to sensitively detect morphine in the blood using a homogeneous immunoassay without any washing steps. Morphine-sensitive illuminating peptides were identified using a high throughput one-bead one-compound (OBOC) combinatorial peptide library approach. The OBOC libraries contain a large number of random peptides with a molecular rotor dye, malachite green (MG), that are coupled to the amino group on the side chain of lysine at different positions of the peptides. The OBOC libraries were then screened for fluorescent activation under a confocal microscope, using an anti-morphine monoclonal antibody as the screening probe, in the presence and absence of free morphine. Using this novel three-step fluorescent screening assay, we were able to identify the peptide-beads that fluoresce in the presence of an anti-morphine antibody, but lost fluorescence when the free morphine was present. After the positive beads were decoded using automatic Edman microsequencing, the morphine-sensitive illuminating peptides were then synthesized in soluble form, functionalized with an azido group, and immobilized onto microfabricated PEG-array spots on a glass slide. The sensor chip was then evaluated for the detection of morphine in plasma. We demonstrated that this proof-of-concept platform can be used to develop fluorescence-based sensors against morphine. More importantly, this technology can also be applied to the discovery of other novel illuminating peptidic sensors for the detection of illicit drugs and cancer biomarkers in body fluids.

Resume L’osteonecrose du genou postoperatoire apres meniscectomie realisee par voie arthroscopique (OGPM) a ete recensee en 1991. Cette complication rare est lourde de consequences pour une intervention de routine. Sa physiopathologie demeure mal comprise, son diagnostic difficile et sa prise en charge mal codifiee. Sa distinction floue avec l’osteonecrose du genou spontanee (OGS) peut entrainer des confusions diagnostiques. Notre travail realise une mise au point sur l’epidemiologie, la physiopathologie, le diagnostic, le pronostic et traitement de l’OGPM a partir d’une revue de litterature et de deux cas survenus dans le service de chirurgie de l’hopital d’instruction des armees de Brest. En conclusion, l’hypothese de la fracture de contrainte sur insuffisance osseuse apres meniscectomie se dessine, ce qui rend le terme « osteonecrose » moins adapte, bien qu’on ne puisse encore totalement l’eliminer. Le diagnostic differentiel essentiel est l’OGS preoperatoire non diagnostiquee que l’on peut eviter par une IRM realisee apres sa fenetre diagnostique. Le chirurgien doit connaitre l’eventualite de l’OGPM si la douleur du patient persiste malgre une meniscectomie correcte. La rechercher par une IRM permet de debuter un traitement medical precoce, meme si ce dernier doit souvent laisser place a une chirurgie. Les mesures preventives sont essentielles et equivalentes aux mesures d’economie meniscale actuellement recommandees.

Interesterification was previously found to impact stearic acid absorption in a randomized cross-over study, when human volunteers consumed a 70:30 wt% high-oleic sunflower and canola stearin blend (NIE) compared to the same blend which had undergone either chemical (CIE) or enzymatic (EIE) interesterification. In this research, in vitro lipid digestion, bioaccessibility, and changes in undigested lipid composition and melting behavior of these same test fats were investigated using the dynamic, multi-compartmental TIM-1 digestion model and compared with the previous human study. Overall, TIM-1 bioaccessibility was higher with interesterification (p < 0.05). Oleic acid bioaccessibility was higher than stearic acid bioaccessibility for NIE, and vice versa for the interesterified blends (p < 0.05). Stearic acid was more concentrated in the undigested triacylglycerols (TAG) from NIE, corresponding to a relatively higher melting temperature of the undigested lipids. The results confirm the impact of TAG composition, fatty acid position and/or physical properties on lipid digestion. TIM-1 bioaccessibility was linearly correlated (R2 = 0.8640) with postprandial serum TAG concentration in the human study. Therefore, the in vitro digestion model offered predictive insights related to the impacts of lipid interesterificaton on absorption.

Pathologic axillary lymph node (ALN) status is an important prognostic factor for staging breast cancer. Currently, status is determined by histopathology following surgical excision of sentinel lymph node(s), which is an invasive, time consuming, and costly procedure with potential morbidity to the patient. Here, we describe an imaging platform for noninvasive assessment of ALN status, eliminating the need for surgical examination of patients to rule out nodal involvement. A targeted imaging probe (MamAb-680) was developed by conjugation of a mammaglobin-A–specific monoclonal antibody to a near-infrared fluorescent dye. Using DNA and tissue microarray, mammaglobin-A was validated as a cell-surface target that is expressed in ALN-positive patient samples but is not expressed in normal lymph nodes. In vivo selectivity was determined by i.v. injection of MamAb-680 into mice with mammaglobin-A–positive and -negative mammary fat pad (MFP) tumors; and by peritumoral MFP injection of the targeted imaging probe in mice with spontaneous ALN metastases. Fluorescence imaging showed that probe was only retained in positive tumors and metastases. As few as 1,000 cells that endogenously express mammaglobin-A were detected in ALN, indicating high sensitivity of this method. Translation of this approach offers considerable potential as a noninvasive clinical strategy to stage breast cancer. Cancer Res; 71(3); 1050–9. ©2010 AACR.

Galectin-1 (Gal-1) is a multifunctional carbohydrate-binding protein and plays a key role in cancer cell proliferation, apoptosis, cell cycle, tumor angiogenesis and evasion of immune responses. It is also directly involved in the process of angiogenesis and tumor immune escape. An elevated level of Gal-1 has been found in many cancers, including prostate cancer. We show by immunohistochemistry in human prostate tissue that Gal-1 expression level was very low in all non-tumor samples and highly expressed in prostate cancer tissues. In addition, Gal-1 was progressively upregulated from low- , intermediate- to high-grade prostate cancer. Taken together, Gal-1 is an excellent therapeutic target against cancer. Yet, no inhibitors against Gal-1 have been approved by the FDA for cancer treatment due to lack of potent, specific and in vivo effective molecules. We recently discovered a novel small-molecule inhibitor of Gal-1, named LLS2, through a high-throughput one-bead two-compound combinatorial library approach. LLS2 exhibits cytotoxic activity against prostate cancer and ovarian cancer cells. We synthesized a series of LLS2 analogs and performed structure-activity relationship studies, leading to a more potent inhibitor LLS30 that induced apoptosis in castration-resistant prostate cancer cells expressing high levels of Gal-1. Molecular modeling study showed LLS30 bound to the sugar-binding groove of Gal-1. In enzalutamide (ENZ)-resistant 22Rv1 prostate cancer cells expressing high levels of Gal-1 and androgen receptor (AR) splice variants, LLS30 could inhibit expression of AR splice variants and sensitize the cells to ENZ in a dose-dependent manner. Downregulation of Gal-1 by siRNA prevented the expression of alternatively spliced AR variants. More importantly, LLS30 showed potent in vivo antitumor efficacy and synergistic activities with docetaxel and ENZ against PC-3 and 22Rv1 prostate cancer models, respectively. Blood chemistry test from the treated animal showed minimum effect of LLS30 on the liver and kidney functions, implying low toxicity. LLS30 is an excellent drug candidate for preclinical development as a novel prostate cancer therapeutic. Citation Format: Ruiwu Liu, Tsung-Chieh Shih, Sophie Kiss, Xiaocen Li, Ting Wang, Jonathan S. Huynh, Chun-Te Wu, Yong Duan, Paramita M. Ghosh, Kit S. Lam. A novel class of small-molecule inhibitors of galectin-1 for prostate cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4860.

Introduction La maladie de Still est responsable classiquement d’une eruption urticarienne fugace vesperale. D’autres manifestations dermatologiques moins typiques sont decrites : pseudo-urticaire fixe et eruption pseudo-dermatomyosite. Nous rapportons un cas d’inflammation periorbitaire symptomatique chez une patiente de 45 ans suivie pour une maladie de Still depuis l’âge de 12 ans, en interruption therapeutique. Observations Apres 32 annees d’evolution d’une maladie de Still, ou arthrite juvenile idiopathique systemique, la patiente etait en remission durable sous perfusions mensuelles de tocilizumab (Roactemra®) et 9 mg/j de prednisone. Apres une pause therapeutique de 3 mois pour une chirurgie digestive compliquee de surinfection locale et 6 semaines apres la reprise du tocilizumab, la malade a presente un œdeme douloureux palpebral periorbital gauche fixe et d’aggravation progressive en 8 semaines. Il n’y avait ni baisse d’acuite visuelle ni trouble oculomoteur ou autre signe neurologique. D’autres symptomes apparaissaient rapidement : une odynophagie, une eruption cutanee maculeuse erythemateuse des avant-bras et des cuisses, une fievre a 38,4 °C, des arthralgies d’horaire inflammatoire des genoux, poignets, coude droit et inter- et metacarpophalangiennes. Biologiquement, la C-reactive proteine etait elevee a 20 mg/L (N Fig. 1 et 2 ). Conclusion La dacryoadenite est une localisation peu frequente de la maladie de Still. Il faut savoir evoquer ce diagnostic devant un oedeme periorbitaire. La particularite de cette atteinte reside dans son caractere fixe, contrastant avec l’eruption cutanee pseudo-urticarienne evanescente accompagnant la fievre vesperale habituellement decrite. Nous rapportons ici le premier cas de dacryoadenite efficacement traite par anakinra.

Resume Introduction La myocardite aigue est l’une des manifestations extradigestives des maladies inflammatoires chroniques de l’intestin (MICI) les moins frequentes. Elle peut apparaitre de facon concomitante ou non a la MICI elle-meme. Observations Nous rapportons deux observations de myocardite aigue, l’une apparue au cours de l’evolution d’une recto-colite hemorragique et l’autre la revelant. Dans ces deux observations la presentation etait aspecifique avec une douleur thoracique aigue et le diagnostic etait obtenu par l’IRM cardiaque. L’evolution etait favorable dans les deux cas. Conclusion Les etiologies des myocardites sont multiples et le diagnostic de manifestations extradigestives liees a une MICI est un diagnostic d’elimination. Les examens doivent etre effectues rapidement devant toute suspicion de myocardite et l’IRM cardiaque a une place importante. Le traitement habituellement prescrit est celui recommande dans les myocardites d’autre etiopathogenie : colchicine, acide acetylsalicylique.

A new multifrequency test generation technique for detecting catastrophic and parametric failures in this class of circuits is presented. Testability transfer factors for circuit elements are introduced and we use them to construct an efficient dynamic test set. Fault detectability and fault coverage are also defined. We also describe the signature analysis methodology used to evaluate the generated test set. Circuits from the suite of analog and mixed-signal benchmark circuits are used to validate our approach. The approach presented may be used to construct input signals for the selection of an external stimulus applied through an arbitrary waveform generator.

The purpose of this study was to obtain preliminary data on pathological gambling rates within a metropolitan Chinese community to determine if more costly extensive epidemiological surveys were justified. Two thousand survey questionnaires were distributed to parents through children attending a local Chinese speaking school. A response rate of 27.4% was obtained. Over a quarter of respondents were born overseas in either Mainland China or Hong Kong. Results indicated that gambling was not a popular activity with 60.0% of respondents stating that they never gambled. Of those who gambled, a third of respondents identified lotto as the preferred form. Using a Chinese translation version of the SOGS and a cut-off score of 10, a prevalence estimate of 2.9% for pathological gambling was found with males showing a higher rate (4.3%) as compared to females (1.6%). Respondents reporting a prior history of gambling in their country of origin were more likely to be classified as probable pathological gamblers. Despite the use of a sample of convenience, changes to the wording of two items in the Chinese translation of the SOGS and the possibility of false positive cases in the present study, it is concluded that further research into problem gambling in this community should be undertaken.

ReRAM has been considered as one of the potential technologies for the next-generation nonvolatile memory, given its fast access speed, high reliability, and multi-level capability. Multiple-layered architectures have been used for several megabit test-chips and memory macros [1-3]. This paper presents a MeOx-based 32Gb ReRAM test chip developed in 24nm technology.

Acute myocarditis is one of the less common extra-intestinal manifestations of inflammatory bowel diseases (IBD). It may reveal IBD or occur during the follow-up.We report two patients who presented an acute myocarditis associated with ulcerative colitis that reveal the disease in one of them. Clinical features at presentation were non specific and both patients presented with chest pain. Diagnosis was obtained with cardiac MRI. Outcome was favourable in the two patients.Etiologies of myocarditis are various and the diagnosis of extra-intestinal manifestations related to IBD remains a diagnosis of exclusion. Cardiac MRI is an important diagnostic tool. Colchicine and acétylsalicylic acid are commonly prescribed in a first therapeutic approach.

The study objectives were to check whether recommended vancomycin doses were related to pharmacological objectives for intensive care patients: steady-state plasma concentration (SSc) and ratio SSc/MIC (Minimal Inhibiting Concentration). The authors tried to identify variability factors for vancomycin plasmatic concentrations at peak.This monocentric, observational, and retrospective survey was performed on 66 intensive care patients treated by antibiotics including vancomycin, alone or in combination, as a curative treatment for a severe infection with Gram-positive bacteria. Vancomycin was dosed at 15mg/kg during the first hour, then 40 to 60mg/kg per 24hour. Vancomycin SSc and bacteria MIC were recorded. The SSc/MIC ratio was determined and was considered efficient when superior to 8.Forty-two percent of vancomycin SSc were within the effectiveness rate. Twenty-three percent of SSc/MIC ratios were superior to 8. The rate of clinical recovery was 71 %. The length of antibiotherapy was identified as positively interacting with biological effectiveness, unlike severe sepsis, a factor of negative interaction on vancomycin SSc in this study.Less than half of the SSc and less than a quarter of the SSc/MIC ratios were at effective rates in our study. Therefore, adequacy between dosage, administration, and monitoring should be reviewed.

1. 1. The biosynthesis of polyunsaturated fatty acids (PUFA) of the n-6 and n-3 series was investigated in cultured Sertoli cells. 18:2n-6, 18:3n-6, 20:2n-6, 18:3n-3 and 20:3n-3 were added individually at a concentration of 20 μmol to culture media. 2. 2. Maximum incorporation of 20- and 22-carbon PUFA into membrane lipids was observed after 72 hr of incubation with all the exogenous substrates used. 3. 3. As reported in other cell systems, the Δ6 desaturation was the first rate-limiting step; the major factor regulating this activity was the concentration of linoleic acid or α-linolenic acid in the medium. 4. 4. Our data show that the Δ5-desaturation represents a second regulatory step in PUFA biosynthesis. 5. 5. The sum of n-6 and n-3 PUFA of the 22 carbon chain length constantly represented between 11 and 12% of total fatty acids, regardless of the exogenous substrate used. 6. 6. Our kinetic studies of the incorporation of PUFA of the n-6 and n-3 series did not permit detection 7. of a Δ8 desaturase activity.