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Research waste occurs when randomised controlled trial (RCT) outcomes are heterogeneous or overlook domains that matter to patients (eg, relating to symptoms or functions). In this systematic review, we reviewed the outcome measures used in 450 RCTs of adult unipolar and bipolar depression registered between 2018 and 2022 and identified 388 different measures. 40% of the RCTs used the same measure (Hamilton Depression Rating Scale [HAMD]). Patients and clinicians matched each item within the 25 most frequently used measures with 80 previously identified domains of depression that matter to patients. Seven (9%) domains were not covered by the 25 most frequently used outcome measures (eg, mental pain and irritability). The HAMD covered a maximum of 47 (59%) of the 80 domains that matter to patients. An interim solution to facilitate evidence synthesis before a core outcome set is developed would be to use the most common measures and choose complementary scales to optimise domain coverage.

IMPORTANCE: The coexistence of underlying causes in patients with transient ischemic attack (TIA) or minor ischemic stroke as well as their associated 5-year risks are not well known. OBJECTIVE: To apply the ASCOD (atherosclerosis, small vessel disease, cardiac pathology, other cause, or dissection) grading system to assess coexistence of underlying causes of TIA and minor ischemic stroke and the 5-year risk for major vascular events. DESIGN, SETTING, AND PARTICIPANTS: This international registry cohort (TIAregistry.org) study enrolled 4789 patients from June 1, 2009, to December 31, 2011, with 1- to 5-year follow-up at 61 sites in 21 countries. Eligible patients had a TIA or minor stroke (with modified Rankin Scale score of 0 or 1) within the last 7 days. Among these, 3847 patients completed the 5-year follow-up by December 31, 2016. Data were analyzed from October 1, 2022, to June 15, 2023. EXPOSURE: Five-year follow-up. MAIN OUTCOMES AND MEASURES: Estimated 5-year risk of the composite outcome of stroke, acute coronary syndrome, or cardiovascular death. RESULTS: A total of 3847 patients (mean [SD] age, 66.4 [13.2] years; 2295 men [59.7%]) in 42 sites were enrolled and participated in the 5-year follow-up cohort (median percentage of 5-year follow-up per center was 92.3% [IQR, 83.4%-97.8%]). In 998 patients with probable or possible causal atherosclerotic disease, 489 (49.0%) had some form of small vessel disease (SVD), including 110 (11.0%) in whom a lacunar stroke was also probably or possibly causal, and 504 (50.5%) had no SVD; 275 (27.6%) had some cardiac findings, including 225 (22.6%) in whom cardiac pathology was also probably or possibly causal, and 702 (70.3%) had no cardiac findings. Compared with patients with none of the 5 ASCOD categories of disease (n = 484), the 5-year rate of major vascular events was almost 5 times higher (hazard ratio [HR], 4.86 [95% CI, 3.07-7.72]; P < .001) in patients with causal atherosclerosis, 2.5 times higher (HR, 2.57 [95% CI, 1.58-4.20]; P < .001) in patients with causal lacunar stroke or lacunar syndrome, and 4 times higher (HR, 4.01 [95% CI, 2.50-6.44]; P < .001) in patients with causal cardiac pathology. CONCLUSION AND RELEVANCE: The findings of this cohort study suggest that in patients with TIA and minor ischemic stroke, the coexistence of atherosclerosis, SVD, cardiac pathology, dissection, or other causes is substantial, and the 5-year risk of a major vascular event varies considerably across the 5 categories of underlying diseases. These findings further suggest the need for secondary prevention strategies based on pathophysiology rather than a one-size-fits-all approach.

Link adaptation algorithm that tailors the data transmission coding-rate to the dynamic channel state is an essential ingredient in any (modern) cellular network. Current link adaptation schemes are based on the usage of periodic pilots sent by the base station. The mobile terminal determines the optimal coding-rate to be employed based on processing the received pilots, and then reports its findings back to the base station. Herein, we show that these schemes perform far from optimal and do not come close to achieving the channel capacity. To address this shortcoming, we propose enhanced link adaptation scheme based on a rateless-like coding approach. According to the proposed scheme, the base station sends multiple re-transmissions, effectively combined at the receiver side, until decoding is successful. It is demonstrated that the proposed scheme can closely track the channel capacity, even for highly mobile terminals, hence achieving significant gains over current link adaptation schemes. From the practical side, we address several implementation-related issues thus paving the way for the adaptation of the proposed scheme to the use of 5G networks.

Previous studies have highlighted patients with chronic conditions seek for medical knowledge and therapeutics on their own. So far, no data exist on the health literacy of patients with gynecological conditions and especially those suffering from endometriosis, whose symptoms’ have a major impact on their daily lives.

To evaluate the safety and visual outcomes of intrastromal corneal ring segment (ICRS) implantation followed by transepithelial phototherapeutic keratectomy (te-PTK) and corneal cross-linking (CXL) in patients with mild keratoconus.

Dealing with electronic devices for high reliability applications in terrestrial environments, neutron-induced Single Event Effects must be investigated. In this paper, the experimental observation of an atmospheric-like neutron-induced Single Event Burnout (SEB) on a packaged commercial SiC power MOSFET is presented after irradiation at ISIS-ChipIr. The effects of the SEB in the electrical properties of the MOSFET are established, and the SiC damaged zone is observed by scanning electron microscopy. Based on this failure analysis at the die level, the distinct stages during the SEB mechanism can be defined. The sensitive volume where the secondary particle deposited enough energy to trigger the SEB mechanism is identified and located inside the SiC n-drift epitaxial layer near the epitaxial layer/substrate junction.

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BackgroundNon-serious adverse events (NSAEs) should be captured and reported because they can have a significant negative impact on patients and treatment adherence. However, the reporting of NSAEs in randomised controlled trials (RCTs) is limited.ObjectiveTo identify the most important NSAEs of antidepressants for patients and clinicians, to be evaluated in RCTs and meta-analyses.MethodsWe conducted online international surveys in English, German and French, including (1) adults prescribed an antidepressant for a depressive episode and (2) healthcare professionals (HCPs) prescribing antidepressants. Participants ranked the 30 most frequent NSAEs reported in the scientific literature. We fitted logit models for sets of ranked items and calculated for each AE the probability to be ranked higher than the least important AE. We also identified additional patient-important AEs not included in the ranking task via open-ended questions.FindingsWe included 1631 patients from 44 different countries (1290 (79.1%) women, mean age 39.4 (SD 13), 289 (37.1%) with severe depression (PHQ-9 score ≥20)) and 281 HCPs (224 (79.7%) psychiatrists). The most important NSAEs for patients were insomnia (95.9%, 95% CI 95.2% to 96.5%), anxiety (95.2%, 95% CI 94.3% to 95.9%) and fatigue (94.6%, 95% CI 93.6% to 95.4%). The most important NSAEs for HCPs were sexual dysfunction (99.2%, 95% CI 98.5% to 99.6%), weight gain (98.9%, 95% CI 97.7% to 99.4%) and erectile problems (98.8%, 95% CI 97.7% to 99.4%). Participants reported 66 additional NSAEs, including emotional numbing (8.6%), trouble with concentration (7.6%) and irritability (6%).ConclusionsThese most important NSAEs should be systematically reported in antidepressant trials.Clinical implicationsThe most important NSAEs should contribute to the core outcome set for harms in depression.

Background/objectives: To assess the ratio of scarred/active areas of fundus lesions in patients with presumed ocular toxoplasmosis. Subjects/methods: Retrospective monocentric study of patients with presumed ocular toxoplasmosis seen between May 2004 and February 2018. Patients with a positive anti-Toxoplasma serology presenting characteristic fundus lesions. Cases with images of both baseline active and scarred lesions of the fundus were included. The borders of each active or scarred lesion were delineated on colour photographs by two independent observers and the area of the lesions was calculated using Digimizer 4.2.2 (MedCalc Software, Ostend, Belgium). The interobserver variability of the measures was recorded and their means were used for further calculations. To study the ratio of the area of scarred retinochoroiditis over the area of the baseline active lesion (R). Results: A total of 171 cases (83 males, 88 females) with a mean age of 31.6 ± 13.8 years were included. The average areas of active and scarred retinochoroiditis were, respectively, 1.32 ± 1.59 and 1.79 ± 2.36 optic disc area. The average ratio between scarred and active areas of retinochoroiditis was 1.36 [range 0.54–2.18]. The administration of a systemic treatment [R= 1.25, p= 0.003], the absence of a pre-existing scar [R= 1.05, p< 0.001] and a peripapillary location of the lesion [R= 0.85, p< 0.001] were each significantly associated with smaller scarred/active area ratios. Conclusions: We assessed in a standardized manner the ratio of scarred/active areas of toxoplasmic lesions and showed that the area of scarred lesions was on average slightly larger than the area of active retinochoroiditis.

To discover microorganisms that naturally possess chemical weapons against the phytopathogen Fusarium oxysporum, the biological and chemical diversity of plant leaf endophytes was investigated. Endophytes were isolated from the palm tree Astrocaryum sciophyllumcollected in pristine forests of French Guiana. Several Xylariaceae inhibited the growth of F. oxysporumand were further explored. Antifungal specialized metabolites were isolated from the Xylariaceae BSNB-0294 strain in confrontation with the phytopathogen and led to the identification of undescribed compounds, i.e., two depsipeptides named xylariaceins, two metabolites containing a 3-imidazolinone moiety, and four new compounds including a nitro-phenylpropanamide and three phenylalanine analogues named xylariains A–D. In parallel, the chemical investigation of the phytopathogen during the coculture led to the identification of an unknown compound, which we named focicin. The production of focicin was exacerbated during the competition. Matrix-assisted laser desorption/ionization coupled to time-of-flight mass spectometry (MALDI-TOF MS) imaging of the competition between BSNB-0294 (endophytic strain) and F. oxysporumf.sp. ciceris(phytopathogen) highlighted time-dependent chemical interactions between the two microorganisms.

In a menopausal woman scheduled for curative surgery for pelvic organ prolapse (POP) by sacral colpopexy (SC), the question of concomitant hysterectomy is frequently considered by the surgeon. The risk of endometrial cancer (EC) exists in this population, and increases with age and body mass index. The French college of gynecologists and obstetricians (CNGOF) decided to issue good practice guidelines on subtotal hysterectomy (SH) for postmenopausal women scheduled for SC for POP.

Naive epiblast and embryonic stem cells (ESCs) give rise to all cells of adults. Such developmental plasticity is associated with genome hypomethylation. Here, we show that LIF–Stat3 signaling induces genomic hypomethylation via metabolic reconfiguration. Stat3-/-ESCs show decreased a-ketoglutarate production from glutamine, leading to increased Dnmt3aand Dnmt3bexpression and DNA methylation. Notably, genome methylation is dynamically controlled through modulation of a-ketoglutarate availability or Stat3 activation in mitochondria. Alpha-ketoglutarate links metabolism to the epigenome by reducing the expression of Otx2and its targets Dnmt3aand Dnmt3b. Genetic inactivation of Otx2or Dnmt3aand Dnmt3bresults in genomic hypomethylation even in the absence of active LIF–Stat3. Stat3-/-ESCs show increased methylation at imprinting control regions and altered expression of cognate transcripts. Single-cell analyses of Stat3-/-embryos confirmed the dysregulated expression of Otx2, Dnmt3aand Dnmt3bas well as imprinted genes. Several cancers display Stat3 overactivation and abnormal DNA methylation; therefore, the molecular module that we describe might be exploited under pathological conditions.

A unique collection of 292 extracts from 107 New Caledonian Euphorbiaceae species sensu latowas profiled by LC-MS2and the metabolite content organized by molecular networking. Based on the assumption that taxon-specific molecules are more likely to be structurally novel, taxonomic data were mapped on spectral networks to detect genus-specific clusters. Using this approach, a group of compounds unique to the genus Austrobuxuswas highlighted. The subsequent MS-guided purification of the fruit EtOAc extract of Austrobuxus carunculatusled to the isolation of 13 new monolactone and “norditerpene” picrotoxanes (2–14), along with the known tutin (1). The structures of the new compounds were elucidated by HRESIMS and NMR spectroscopic data analysis, and the absolute configurations of compounds 1, 3, 7, 11, 12, and 14were determined by single-crystal X-ray diffraction analysis. The relative and absolute configurations of compounds 4and 5were ascertained by chemical transformation of compound 3. The absolute configurations of other members of the series have been proposed on the basis of biogenetic considerations and specific rotation values of similar sign and magnitude. Compounds 1–14were evaluated for their antiproliferative activities against HCT116 colon, U87-MG glioblastoma, and A549 lung human cancer cell lines. Compounds bearing an acyl chain at C-2 (i.e., 2, 4, and 13) showed IC50values in the micromolar range for the three cell lines used.

Pulmonary arterial hypertension (PAH) is a rare and deadly disease affecting roughly 15–60 people per million in Europe with a poorly understood pathology. There are currently no diagnostic tools for early detection nor does a curative treatment exist. The lipid composition of arteries in lung tissue samples from human PAH and control patients were investigated using matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) combined with time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging. Using random forests as an IMS data analysis technique, it was possible to identify the ion at m/z885.6 as a marker of PAH in human lung tissue. The m/z885.6 ion intensity was shown to be significantly higher around diseased arteries and was confirmed to be a diacylglycerophosphoinositol PI(C18:0/C20:4) via MS/MS using a novel hybrid SIMS instrument. The discovery of a potential biomarker opens up new research avenues which may finally lead to a better understanding of the PAH pathology and highlights the vital role IMS can play in modern biomedical research.

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Many clinical trials have assessed treatments for depressive disorders and bipolar depression. However, whether, and which, assessed outcome domains really matter to patients, informal caregivers, and health-care professionals remains unclear.

Le cancer de la prostate (CaP) est le plus fréquent des cancers masculins en 2018 en Europe. La question du dépistage du CaP en population générale a été débattue après la publication d’études internationales européenne (ERSPC) et nord-américaine (PLCO). Il n’existe pas aujourd’hui de dépistage organisé du CaP. L’objectif de cette analyse était d’évaluer la pratique du dépistage du CaP dans la population française sans antécédent de cancer entre 2005 et 2016.

The segmental organization of the vertebral column is established early in embryogenesis, when pairs of somites are rhythmically produced by the presomitic mesoderm (PSM). The tempo of somite formation is controlled by a molecular oscillator known as the segmentation clock1,2. Although this oscillator has been well-characterized in model organisms1,2, whether a similar oscillator exists in humans remains unknown. Genetic analyses of patients with severe spine segmentation defects have implicated several human orthologues of cyclic genes that are associated with the mouse segmentation clock, suggesting that this oscillator might be conserved in humans3. Here we show that human PSM cells derived in vitro—as well as those of the mouse4—recapitulate the oscillations of the segmentation clock. Human PSM cells oscillate with a period two times longer than that of mouse cells (5 h versus 2.5 h), but are similarly regulated by FGF, WNT, Notch and YAP signalling5. Single-cell RNA sequencing reveals that mouse and human PSM cells in vitro follow a developmental trajectory similar to that of mouse PSM in vivo. Furthermore, we demonstrate that FGF signalling controls the phase and period of oscillations, expanding the role of this pathway beyond its classical interpretation in ‘clock and wavefront’ models1. Our work identifying the human segmentation clock represents an important milestone in understanding human developmental biology.

Cataract surgery is one of the most common operations in health care. Femtosecond laser-assisted cataract surgery (FLACS) enables more precise ocular incisions and lens fragmentation than does phacoemulsification cataract surgery (PCS). We hypothesised that FLACS might improve outcomes in cataract surgery compared with PCS despite having higher costs.

Antivirals are infrequently prescribed in European primary care for influenza-like illness, mostly because of perceived ineffectiveness in real world primary care and because individuals who will especially benefit have not been identified in independent trials. We aimed to determine whether adding antiviral treatment to usual primary care for patients with influenza-like illness reduces time to recovery overall and in key subgroups.

The objective of our study was to study the impact of discoid excision for deep endometriosis (DE) with colorectal involvement on fertility outcomes.

The aims of this study were to describe survival outcomes in patients with ovarian cancer aged ≥80 years and to explore predictors of poor prognosis.

La prise en charge du cancer du sein connaît une transformation significative depuis plusieurs décennies, marquée par une tendance à la désescalade thérapeutique. Cette évolution est soutenue par le vieillissement de la population, l’augmentation de l’espérance de vie et les progrès dans les méthodes de détection par imagerie sénologique, renforcées récemment par l’intégration des algorithmes d’intelligence artificielle. Les données définitives de l’essai ICE3, présentées lors du 25econgrès annuel de l’American Society of Breast Surgery (ASBrS), en conjonction avec les publications récentes des essais intitulés LUMINA et SOUND, inaugurent une nouvelle phase dans la gestion des cancers du sein à faible risque dans une population ciblée, offrant une alternative à la chirurgie conventionnelle. Cet article explore les fondements de la cryoablation mammaire, en passant en revue les indications cliniques établies, les techniques de réalisation, ainsi que les principes de la cryo-immunologie.

Purpose This clinical investigation compared the performance and safety of Eyestil Plus® (SIFI) and Vismed Multi® (TRB Chemedica) for reducing keratitis lesions in moderate-to-severe dry eye disease (DED) patients.Materials and methods This was a randomised, double-blind, multicentre investigation. 96 adults (>18 years of age) with moderate-to-severe DED received Eyestil Plus® (N= 48) or Vismed Multi® (n= 48) 6 times daily for 3 months. The primary objective clinical performance after 1 month as global corneal and conjunctival staining scores. The secondary objectives were clinical performance after 3 months, tear film stability (tear break up time (TBUT), tear production (Schirmer test), patient-reported outcomes (PROs), investigator satisfaction, and safety.Results 96 participants were randomised to receive the clinical investigations’ treatments, 82.3% of them were female and their mean age was 65.8 years. The non-inferiority of Eyestil Plus® for moderate-to-severe DED was demonstrated at 1 month. No statistical difference was found for any of the study's objectives: change at 1 and 3 months of the global corneal and conjunctival staining score (p-value = 0.506 and 0.661, respectively), change at 1 and 3 months (p-value = 0.538 and 0.302) for TBUT test; change at 3 months for Schirmer test (p-value = 0.540). There were no changes for PROs either. Investigator satisfaction was high for both products. 16.6% of the participants experienced adverse events.Conclusion This clinical investigation showed the non-inferiority of Eyestil Plus® compared to Vismed Multi® regarding performance and safety in a moderate-to-severe DED population.

La endometriosis urinaria es una localización rara que afecta a menos del 1% de las pacientes. La afectación vesical es su forma más frecuente. Los síntomas son inespecíficos y el diagnóstico se basa en las pruebas de imagen. En lo que respecta a la afectación ureteral compresiva o invasiva, es más rara y a menudo se inscribe en un cuadro de endometriosis pélvica profunda extensa. La afectación ureteral suele ser asintomática y puede dar lugar a la destrucción oligosintomática del riñón afectado. Como con cualquier forma de endometriosis, no existe un tratamiento médico curativo. El tratamiento quirúrgico consiste en una cistectomía parcial para las afectaciones vesicales, una ureterólisis y, si es preciso, una ureterectomía segmentaria para las afectaciones ureterales.

Depuis le LASIK (laser in situ keratomileusis), première opération de chirurgie de l’œil réalisée à l’aide d’un laser femtoseconde, les applications rendues possibles grâce à ce type de laser n’ont cessé de se développer. La sophistication des systèmes utilisés lors de ces opérations nécessite une collaboration étroite entre les praticiens et les constructeurs, notamment pour répondre aux inconforts et aux effets secondaires ressentis par certains patients.

A coupled-mode model is developed for the wave–current–seabed interaction problem with application to wave propagation and scattering by non-homogeneous currents of general vertical structure in variable bathymetry regions. The formulation is based on a velocity representation defined by a series of local vertical modes containing the propagating and evanescent modes, able to analytically treat the continuity condition and the bottom boundary condition on sloping parts of the seabed. Using the above representation in Euler equations, a coupled system of differential equations on the horizontal plane is derived with respect to the unknown horizontal velocity modal amplitudes. Under the assumption of small-amplitude waves, the system is linearized, and the dispersion characteristics of the model are studied for arbitrary vertical distribution of the mean flow indicating very fast convergence of the modal series over the whole frequency band of interest. Furthermore, interesting cases of wave–seabed–current interactions are studied and numerical results are compared against available experimental data indicating a very good performance.

Molecular networking (MN) allows one to organize tandem mass spectrometry (MS/MS) data by spectral similarities. Cosine-score used as a metric to calculate the distance between two spectra is based on peak lists containing fragments and neutral losses from MS/MS spectra. Until now, the workflow excluded the generation of the molecular network from electron ionization (EI) MS data as no selection of the putative parent ion is achieved when performing classical gas chromatography (GC)-EI-MS analysis. In order to fill this gap, new functionalities on MetGem 1.2.2 software (https://github.com/metgem/metgem/releases) have been implemented, and results from a large EI-MS database and GC-EI-MS analysis will be exemplified.

Background In patients with non-cardio-embolic stroke, atorvastatin 80 mg/day reduced the relative risk of recurrent stroke by 16%, and a post hoc analysis showed that achieving an LDL-c of less than 70 mg/dL reduced the relative risk by 28% as compared to an on-treatment LDL of 100 mg/dL or more. Current guidelines from the French drug agency recommend treating with a statin after an ischaemic stroke to a target of less than 100 mg/dL, but no study directly tested LDL-c targets. The Treat Stroke to Target (TST) trial will compare the efficacy of achieving an LDL-c of less than 70 mg/dL versus an achieved LDL-c of 100 ± 10 mg/dL for secondary prevention in patients with recent ischaemic stroke of atherosclerotic origin. Main hypothesis: An achieved on-treatment LDL-c of less than 70 mg/dL will reduce by 25% the risk of recurrent ischaemic stroke, myocardial infarction, urgent coronary or carotid revascularisation following new symptoms requiring hospitalisation, and vascular death compared with on-treatment LDL-c of 100 ± 10 mg/dL.Design Patients are randomised to either LDL-c levels, and the investigator who is not blinded can use the lipid-lowering agent of his/her choice available on the market (including statins and ezetimibe), in order to achieve the assigned LDL-c level. To be eligible for enrolment, patients have a recent ischaemic stroke or TIA of atherosclerotic origin with at least one arterial stenosis of a cerebral artery, enrolled between acute phase of the qualifying stroke (once the neurological deficit is stabilised) and three months. The initial planned sample size of 3760 participants followed three years was amended to allow follow-up of all enrolled patients until 385 primary efficacy outcome events have occurred, and no later than 31 December 2019. Patients will be recruited in 76 sites in two countries (France and South Korea) between March 2010 and December 2018 (last included patient followed up to one year). Safety outcomes will include haemorrhagic strokes and new onset diabetes. All primary endpoints will be adjudicated by an endpoint committee, blinded to the assigned LDL-c level. Two sub-studies assess (1) the relative effect of assigned LDL-c levels on occurrence of new atherosclerotic plaque as detected by carotid ultrasound during follow-up, using M’ATH software for repositioning and (2) the genetic and biomarker drivers of recurrent primary endpoints according to assigned LDL-c lowering arm, in atherosclerotic strokes.Summary The TST trial is evaluating the benefits of achieving an LDL-c less than 70 mg/dL for secondary stroke prevention in ischaemic stroke patients of atherosclerotic origin. Main results are anticipated in 2020 or earlier (ClinicalTrials.gov NCT01252875).

Precise definitions of recurrences and optimal treatment strategy are yet to be clearly defined among patients with cervical cancer (CC). The purpose of this study was to develop a reproducible classification of CC recurrence.

The species Euphorbia pithyusaand Euphorbia cupaniiare two closely related Mediterranean spurges for which their taxonomic relationships are still being debated. Herein, the diterpene ester content of E. cupaniiwas investigated using liquid chromatography coupled to tandem mass spectrometry. The use of molecular networking coupled to unsupervised substructure annotation (MS2LDA) indicated the presence of new premyrsinane/myrsinane diterpene esters in the E. cupaniifractions. A structure-guided isolation procedure yielded 16 myrsinane (11a–h, 12, and 13) and premyrsinane esters (14a–cand 15a–c), along with four 4β-phorbol esters (16a–cand 17) that showed inhibitory activity against chikungunya virus replication. The structures of the 16 new compounds (11a–c, 11h, 12, 13, 14a–c, 15a–c, 16a–c, and 17) were characterized by NMR spectroscopy and X-ray crystallography. To further uncover the diterpene ester content of these two species, the concept of combinatorial network annotation propagation (C-NAP) was developed. By leveraging the fact that the diterpene esters of Euphorbiaspecies are made up of limited building blocks, a combinatorial database of theoretical structures was created and used for C-NAP that made possible the annotation of 123 premyrsinane or myrsinane esters, from which 74% are not found in any compound database.

An MRI is recommended for an ovarian mass that is indeterminate on ultrasound. The ROMA score (combining CA125 and HE4) can also be calculated (grade A). In presumed early-stage ovarian or tubal cancers, the following procedures should be performed: an omentectomy (at a minimum, infracolic), an appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (grade B) for all histologic types, except the expansile mucinous subtypes, for which lymphadenectomies can be omitted (grade C). Minimally invasive surgery is recommended for early-stage ovarian cancer, when there is no risk of tumor rupture (grade B). For FIGO stages III or IV ovarian, tubal, and primary peritoneal cancers, a contrast-enhanced computed tomography (CT) scan of the thorax/abdomen/pelvis is recommended (grade B), as well as laparoscopic exploration to take multiple biopsies (grade A) and a carcinomatosis score (Fagotti score at a minimum) (grade C) to assess the possibility of complete surgery (i.e., leaving no macroscopic tumor residue). Complete surgery by a midline laparotomy is recommended for advanced ovarian, tubal, or primary peritoneal cancer (grade B). For advanced cancers, para-aortic and pelvic lymphadenectomies are recommended when metastatic adenopathy is clinically or radiologically suspected (grade B). When adenopathy is not suspected and when complete peritoneal surgery is performed as the initial surgery for advanced cancer, the lymphadenectomies can be omitted because they do not modify either the medical treatment or overall survival (grade B). Primary surgery (before other treatment) is recommended whenever it appears possible to leave no tumor residue (grade B).

Adjuvant chemotherapy by carboplatin and paclitaxel is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). After primary surgery is complete, 6 cycles of intravenous chemotherapy (grade A) are recommended, or a discussion with the patient about intraperitoneal chemotherapy, according to her risk-benefit ratio. After complete interval surgery for FIGO stage III, hyperthermic intraperitoneal chemotherapy (HIPEC) can be proposed, in accordance with the modalities of the OV-HIPEC trial (grade B). In cases of postoperative tumor residue or in FIGO stage IV tumors, chemotherapy associated with bevacizumab is recommended (grade A).

Using a modified atmospheric pressure photoionization (APPI) source coupled to a tunable vacuum ultraviolet source at the SOLEIL synchrotron radiation facility, we determined the appearance energy of protonated methanol monomer and dimers at different source temperatures. The experimental data indicated that protonated monomers can be formed through the direct photoionization of neutral methanol by the second emission band of a krypton discharge UV lamp at 116.49 nm (10.64 eV) explaining why methanol can be considered as a weak dopant under APPI conditions. This point is in contradiction with the previously proposed mechanism where photoionization of methanol dimer was followed by the dissociation of the protonated methanol dimer into protonated methanol monomer.

Devant une masse ovarienne indéterminée à l’échographie, une IRM est recommandée et le score ROMA (associant CA125 et HE4) peut être proposé (grade A). En cas de cancer de l’ovaire ou de la trompe, de stade présumé précoce, il est recommandé une omentectomie (au minimum infracolique), une appendicectomie, des biopsies péritonéales multiples, une cytologie péritonéale (grade C) et une lymphadénectomie pelvienne et lomboaortique (grade B) pour tous les types histologiques, excepté le sous-type mucineux expansif où la lymphadénectomie peut être omise (grade C). La chirurgie mini-invasive est recommandée pour un cancer de l’ovaire de stade précoce, en l’absence de risque de rupture de la tumeur (grade B). La chimiothérapie adjuvante par carboplatine et paclitaxel est recommandée pour tous les cancers de l’ovaire ou de la trompe de haut grade, de stade FIGO I-IIA (grade A). Devant un cancer de l’ovaire, de la trompe ou du péritoine primitif de stade FIGO III ou IV, il est recommandé de réaliser un scanner thoraco-abdomino-pelvien avec injection (grade B) et une exploration cœlioscopique pour réaliser des biopsies multiples (grade A) et évaluer par un score de carcinose (à minima le score de Fagotti) (grade C) la possibilité d’une chirurgie complète (i.e. résidu tumoral nul macroscopique). Il est recommandé une chirurgie complète par laparotomie médiane pour les cancers avancés de l’ovaire, de la trompe ou du péritoine primitif (grade B). Il est recommandé dans les cancers avancés de réaliser des lymphadénectomies lomboaortiques et pelviennes en cas de suspicion clinique ou radiologique d’adénopathie métastatique (grade B). En l’absence d’adénopathie suspecte clinique ou radiologique et en cas de chirurgie péritonéale complète lors d’une chirurgie initiale pour cancer avancé, il est possible de ne pas réaliser de lymphadénectomie car elle ne modifie pas le traitement médical, ni la survie globale (grade B). Une chirurgie première est recommandée chaque fois qu’un résidu tumoral nul est possible (grade B). Après une chirurgie première complète, il est recommandé de réaliser 6 cycles de chimiothérapie intraveineuse (grade A) ou de proposer une chimiothérapie intrapéritonéale (grade B), à discuter avec la patiente en fonction du rapport bénéfice/risque. Après une chirurgie intervallaire complète pour un stade FIGO III, la chimiothérapie hyperthermique intra-péritonéale (CHIP) peut être proposée selon les modalités de l’essai OV-HIPEC (grade B). En cas de résidu tumoral post-chirurgie ou de stade FIGO IV, une chimiothérapie associée à du bévacizumab est recommandée (grade A).

From a set of 292 Euphorbiaceae extracts, the use of a molecular networking (MN)-based prioritization approach highlighted three clusters (MN1–3) depicting ions from the bark extract of Codiaeum peltatum. Based on their putative antiviral potential and structural novelty, the MS-guided purification of compounds present in MN1 and MN2 afforded two new daphnane-type diterpenoid orthoesters (DDO), codiapeltines A (1) and B (2), the new actephilols B (3) and C (4), and four known 1,4-dioxane-fused phenanthrene dimers (5–8). The structures of the new compounds were elucidated by NMR spectroscopic data analysis, and the absolute configurations of compounds 1and 2were deduced by comparison of experimental and calculated ECD spectra. Codiapeltine B (2) is the first daphnane bearing a 9,11,13-orthoester moiety, establishing a new major structural class of DDO. Compounds 1–8and four recently reported monoterpenyl quinolones (9–12) detected in MN3 were investigated for their selective activities against chikungunya virus replication and their antipolymerase activities against the NS5 proteins of dengue and zika viruses. Compounds 3–8exhibited strong inhibitory activities on both dengue and zika NS5 in primary assays, but extensive biological analyses indicated that only actephilol B (3) displayed a specific interaction with the NS5 targets.

We studied a post operative classification of surgical complexity in endometriosis.

Molecular networking (MN) is becoming a standard bioinformatics tool in the metabolomic community. Its paradigm is based on the observation that compounds with a high degree of chemical similarity share comparable MS2fragmentation pathways. To afford a clear separation between MS2spectral clusters, only the most relevant similarity scores are selected using dedicated filtering steps requiring time-consuming parameter optimization. Depending on the filtering values selected, some scores are arbitrarily deleted and a part of the information is ignored. The problem of creating a reliable representation of MS2spectra data sets can be solved using algorithms developed for dimensionality reduction and pattern recognition purposes, such as t-distributed stochastic neighbor embedding (t-SNE). This multivariate embedding method pays particular attention to local details by using nonlinear outputs to represent the entire data space. To overcome the limitations inherent to the GNPS workflow and the networking architecture, we developed MetGem. Our software allows the parallel investigation of two complementary representations of the raw data set, one based on a classic GNPS-style MN and another based on the t-SNE algorithm. The t-SNE graph preserves the interactions between related groups of spectra, while the MN output allows an unambiguous separation of clusters. Additionally, almost all parameters can be tuned in real time, and new networks can be generated within a few seconds for small data sets. With the development of this unified interface (https://metgem.github.io), we fulfilled the need for a dedicated, user-friendly, local software for MS2comparison and spectral network generation.

To analyze the prevalence and risk factors for retinopathy of prematurity (ROP) and severe (treatment-requiring) ROP.

PURPOSE:To compare posterior corneal features and their discriminating power for differentiating normal corneas from subclinical keratoconus using the Placido dual-Scheimpflug analyzer.METHODS:Patients were retrospectively included in the study. The preoperative normal right eyes of 79 patients imaged with a Placido dual-Scheimpflug system and with a stable postoperative LASIK follow-up of a minimum of 36 months were included in the normal group and were compared to 39 contralateral topographically normal eyes with clinically evident keratoconus in the fellow eye. The posterior surface variables measured were categorized according to the feature of the corneal shape they were characterizing (curvature, elevation, asymmetry, and eccentricity) and compared between the two groups using the Student's two-sample Patients were retrospectively included in the study. The preoperative normal right eyes of 79 patients imaged with a Placido dual-Scheimpflug system and with a stable postoperative LASIK follow-up of a minimum of 36 months were included in the normal group and were compared to 39 contralateral topographically normal eyes with clinically evident keratoconus in the fellow eye. The posterior surface variables measured were categorized according to the feature of the corneal shape they were characterizing (curvature, elevation, asymmetry, and eccentricity) and compared between the two groups using the Student's two-sample ttest. The discriminating ability of the posterior surface variables was compared by receiver operator characteristics curves.RESULTS:Variables that related to asymmetry and elevation of the posterior surface were statistically significantly different between groups (Variables that related to asymmetry and elevation of the posterior surface were statistically significantly different between groups (P< .05), whereas eccentricity and curvature–related parameters were not. Receiver operator characteristics curves analysis showed that the maximum posterior elevation over the best-fit toric and aspheric surface reference shape had the highest discriminating ability for distinguishing normal corneas from subclinical keratoconus, with an area under the curve of 0.877, followed by the asphericity asymmetry index, with an area under the curve of 0.871, and posterior inferior-superior value, with an area under the curve of 0.851.CONCLUSIONS:Posterior cornea measured with a dual-Scheimpflug analyzer provides useful parameters for differentiating normal corneas from subclinical keratoconus. Of the posterior surface parameters, asymmetry and elevation seem to be the most sensitive shape modifications for differentiating both populations.[[J Refract Surg.2018;34(10):664–670.]

AbstractWe continue the analysis of large deviations for randomly connected neural networks used as models of the brain. The originality of the model relies on the fact that the directed impact of one particle onto another depends on the state of both particles, and they have random Gaussian amplitude with mean and variance scaling as the inverse of the network size. Similarly to the spatially extended case (see Cabana and Touboul (2018)), we show that under sufficient regularity assumptions, the empirical measure satisfies a large deviations principle with a good rate function achieving its minimum at a unique probability measure, implying, in particular, its convergence in both averaged and quenched cases, as well as a propagation of a chaos property (in the averaged case only). The class of model we consider notably includes a stochastic version of the Kuramoto model with random connections.

AbstractIn a series of two papers, we investigate the large deviations and asymptotic behavior of stochastic models of brain neural networks with random interaction coefficients. In this first paper, we take into account the spatial structure of the brain and consider first the presence of interaction delays that depend on the distance between cells and then the Gaussian random interaction amplitude with a mean and variance that depend on the position of the neurons and scale as the inverse of the network size. We show that the empirical measure satisfies a large deviations principle with a good rate function reaching its minimum at a unique spatially extended probability measure. This result implies an averaged convergence of the empirical measure and a propagation of chaos. The limit is characterized through a complex non-Markovian implicit equation in which the network interaction term is replaced by a nonlocal Gaussian process with a mean and covariance that depend on the statistics of the solution over the whole neural field.

Le traitement par chimiothérapie intrapéritonéale hyperthermique (CHIP) améliore la survie globale du cancer de l’ovaire avec carcinose péritonéale. Cependant, les complications associées et la toxicité limitent son utilisation. Pour améliorer la technique chirurgicale, des modèles animaux permettant de travailler sur de grands groupes sans logistique lourde sont nécessaires. Nous avons entrepris de développer et d’évaluer la morbidité d’une procédure de CHIP chez la souris.

Comparer la précision du positionnement des implants toriques et les résultats réfractifs entre un système peropératoire de marquage digital et un marquage manuel.