Search

The number of children requiring prolonged mechanical ventilation (PMV) has increased with the advancement of medical care. We aimed to estimate the prevalence of PMV worldwide, document demographic and clinical characteristics of children requiring PMV in paediatric intensive care units (PICUs), and to understand variation in clinical practice and health-care burden.

The hyperpolarization of biological samples using dissolution dynamic nuclear polarization (dDNP) has become an attractive method for the monitoring of fast chemical and enzymatic reactions using NMR by taking advantage of a large signal increase. This approach is actively developing but still needs key methodological breakthroughs to be used as an analytical method for the monitoring of complex networks of simultaneous metabolic pathways. In this article, we use the deceptively simple example of glucose-6-phosphate (G6P) oxidation reaction by the enzyme G6P dehydrogenase (G6PDH) to discuss some important methodological aspects of dDNP kinetic experiments, such as its robustness and its ability to provide repeatable results as well as the capacity of this time-resolved methodology to test kinetic models and hypotheses and to provide reliable parameter estimates. To illustrate the potential of our approach, we report the first direct and quantitative evidence of selectivity of G6PDH toward the β anomer of G6P.

Large electron backscatter diffraction area maps were used in the present work to characterize the microstructure and texture near the horizontal and vertical keyhole peripheries of the AA5182 alloy after friction stir spot welding. The findings demonstrate that the horizontal keyhole peripheric comprises a stirred zone (SZ) and a thermo-mechanically affected zone (TMAZ). The SZ started 300 µm away from the keyhole center and became thicker with increasing horizontal distance. The texture gradually changed from shear A1∗/A2∗components at the SZ to rolling cube, goss, and brass components at the TMAZ. The vertical keyhole peripheric is mainly composed of SZ with an onion ring grain structure and is dominated by the Cshear component.

Glucocorticoids probably improve outcomes in patients hospitalised for community acquired pneumonia (CAP). In this a priori planned exploratory subgroup analysis of the phase 3 randomised controlled Activated Protein C and Corticosteroids for Human Septic Shock (APROCCHSS) trial, we aimed to investigate responses to hydrocortisone plus fludrocortisone between CAP and non-CAP related septic shock.

Finding sensitive clinical outcome measures has become crucial in natural history studies and therapeutic trials of neuromuscular disorders. Here, we focus on 1‐year longitudinal data from quantitative magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy (31P MRS) in a placebo‐controlled study of sirolimus for inclusion body myositis (IBM), also examining their links to functional, strength, and clinical parameters in lower limb muscles. Quantitative MRI and 31P MRS data were collected at 3 T from a single site, involving 44 patients (22 on placebo, 22 on sirolimus) at baseline and year‐1, and 21 healthy controls. Assessments included fat fraction (FF), contractile cross‐sectional area (cCSA), and water T2in global leg and thigh segments, muscle groups, individual muscles, as well as 31P MRS indices in quadricepsor triceps surae. Analyses covered patient‐control comparisons, annual change assessments via standard t‐tests and linear mixed models, calculation of standardized response means (SRM), and exploration of correlations between MRI, 31P MRS, functional, strength, and clinical parameters. The quadricepsand gastrocnemius medialismuscles had the highest FF values, displaying notable heterogeneity and asymmetry, particularly in the quadriceps. In the placebo group, the median 1‐year FF increase in the quadriceps was 3.2% (P< 0.001), whereas in the sirolimus group, it was 0.7% (P= 0.033). Both groups experienced a significant decrease in cCSA in the quadricepsafter 1 year (P< 0.001), with median changes of 12.6% for the placebo group and 5.5% for the sirolimus group. Differences in FF and cCSA changes between the two groups were significant (P< 0.001). SRM values for FF and cCSA were 1.3 and 1.4 in the placebo group and 0.5 and 0.8 in the sirolimus group, respectively. Water T2values were highest in the quadricepsmuscles of both groups, significantly exceeding control values in both groups (P< 0.001) and were higher in the placebo group than in the sirolimus group. After treatment, water T2increased significantly only in the sirolimus group's quadriceps(P< 0.01). Multiple 31P MRS indices were abnormal in patients compared to controls and remained unchanged after treatment. Significant correlations were identified between baseline water T2and FF at baseline and the change in FF (P< 0.001). Additionally, significant correlations were observed between FF, cCSA, water T2, and functional and strength outcome measures. This study has demonstrated that quantitative MRI/31P MRS can discern measurable differences between placebo and sirolimus‐treated IBM patients, offering promise for future therapeutic trials in idiopathic inflammatory myopathies such as IBM.

Blast disease caused by the fungus Magnaporthe oryzaeis one of the most devastating rice diseases. Disease resistance genes such as Pi-taor Pi-ta2are critical in protecting rice production from blast. Published work reports that Pi-tacodes for a nucleotide-binding and leucine-rich repeat domain protein (NLR) that recognizes the fungal protease-like effector AVR-Pita by direct binding. However, this model was challenged by the recent discovery that Pi-ta2 resistance, which also relies on AVR-Pita detection, is conferred by the unconventional resistance gene Ptr, which codes for a membrane protein with a cytoplasmic armadillo repeat domain. Here, using NLR Pi-taand PtrRNAi knockdown and CRISPR/Cas9 knockout mutant rice lines, we found that AVR-Pita recognition relies solely on Ptrand that the NLR Pi-tahas no role in it, indicating that it is not the Pi-taresistance gene. Different alleles of Ptrconfer different recognition specificities. The A allele of Ptr(PtrA) detects all natural sequence variants of the effector and confers Pi-ta2 resistance, while the B allele of Ptr(PtrB) recognizes a restricted set of AVR-Pitaalleles and, thereby, confers Pi-ta resistance. Analysis of the natural diversity in AVR-Pitaand of mutant and transgenic strains identified one specific polymorphism in the effector sequence that controls escape from PtrB-mediated resistance. Taken together, our work establishes that the M. oryzaeeffector AVR-Pita is detected in an allele-specific manner by the unconventional rice resistance protein Ptr and that the NLR Pi-ta has no function in Pi-ta resistance and the recognition of AVR-Pita.

In 2005, 10% of consultations in France ended without a prescription. In 2019, a review of the literature found 30 to 70% of prescription-free consultations in Northern Europe and 10 to 22% in Southern Europe and underlined the scarcity of quantitative data. Different factors contribute to this heterogeneity, such as product availability and status, modes of management, distribution channels, clinical practice recommendations, public policies targeting certain classes, etc. The main objective of our study was to quantify the rate of prescription-free consultations in general practice in France in 2021. The secondary objective was to characterize prescription-free consultations and analyze their determinants.

The FET protein family, comprising FUS, EWS, and TAF15, plays crucial roles in mRNA maturation, transcriptional regulation, and DNA damage response. Clinically, they are linked to Ewing family tumors and neurodegenerative diseases such as amyotrophic lateral sclerosis. The fusion protein

Purpose: Mitotane is the only approved treatment for metastatic adrenocortical carcinoma (ACC). Monitoring plasma levels is recommended, but its predictive value is insufficient. Methods: This prospective study of the French ENDOCAN-COMETE network aimed to investigate the prognostic role of plasma mitotane levels pharmacokinetics and free or bound to lipoprotein fraction measurements during six consecutive months. Lipoprotein fractions were isolated by ultracentrifugation, and mitotane level was determined by HPLC–UV. Total, free, and lipoprotein fraction bound plasma mitotane were monitored every two months for six months with morphological assessment. The primary endpoint was overall survival (OS). Results: 21 patients with metastatic ACC were included. Median overall survival was 23 months. The median free mitotane level per patient was 12% (± 7%), and the majority (88%) was bound to lipoprotein fractions. Several pharmacokinetics measures of total mitotane were related to OS: first level at one month (p= 0.026), mean level (p= 0.055), and area under the curve (AUC) (p= 0.048), with higher exposure associated to longer OS. Free mitotane (not bounded) and mitotane bounded to lipoprotein subfraction added no prognostic values. The relationship between the mitotane level and OS suggested a minimum “effective” threshold of 10–15 mg/L or an area under the curve above 100 mg/L/month with no individualized maximum value. Conclusion: This prospective study did not identify any added prognostic value of free mitotane level over the total level. Early total mitotane level measurements (before 3–6 months) were related to OS with a higher and faster exposure related to more prolonged survival.

Laser cladding of a Ni based powder on cast iron is performed by a 4kW continuous diode laser. For this, a robot programming method named “Wavering” is used. Indeed, this method allows to cover large surfaces (width higher than 5 mm and thickness higher than 4 mm). The cast iron substrate used during this work is employed for its thermal properties in glass mold Industry. However, it has drawbacks which are weak wear, corrosion, and abrasion resistance. Conventional techniques used to protect the molds, like Plasma Transferred Arc (PTA), affect the molds microstructure, but also the thermal and mechanical properties. The laser cladding of the Ni based alloy allows to protect the molds without affecting the cast iron thermal properties (low Heat Affected Zone). The purpose of this research is to produce a well bonded Ni based melted powder without pores or cracks on large and curvilinear surfaces. First, the coating, adapted to this substrate geometry, is optimized. Then, an investigation of the impact of the processing parameters (power, scanning speed and wavering frequency) on the microstructure is carried out. Besides, the mechanical behaviour is analysed by microhardness. In addition, the evolution of the Heat Affected Zone (HAZ) according to the processing parameters is observed. Two kinds of areas are inspected in terms of microstructure: a stable area obtained after a single pass and an interferenced area linked to superimposed passes. Those analyses led to a cladding parameter optimization to obtain perfect bonding, to avoid porosity propagation and to limit the HAZ emergence on curvilinear surfaces. Finally, in comparison with the PTA technique, it appears that laser cladding process with wavering method leads to a good coating of curvilinear surfaces.

Adjuvant treatment with mitotane is commonly used after resection of adrenocortical carcinoma; however, treatment remains controversial, particularly if risk of recurrence is not high. We aimed to assess the efficacy and safety of adjuvant mitotane compared with surveillance alone following complete tumour resection in patients with adrenocortical carcinoma considered to be at low to intermediate risk of recurrence.

Simulation of devices including thin electromagnetic shields is nowadays a significant challenge because of the fine mesh required and the associated computation time. Recently, the transmission line theory used to model field propagation through thin conductive layers has been revised to solve shielding problems leading to the development of the artificial material single layer (AMSL) method. Initially developed for single-layer materials, this method has been extended to multilayer configurations. This article presents an approach combining the homogenization of multilayer shields through energetic consideration and the second-order AMSL method to accurately model metal composite for magnetic shielding applications. A comparison between the proposed approach and that of AMSL method for multilayers is proposed in terms of accuracy and computational time. These two discretization methods are also compared to the Impedance Network Boundary Conditions (INBCs) approach. On the frequency range of validity of the proposed method, the maximum relative error compared to experimental results is lower than 8.5%.

Cold metal transfer (CMT) technology is considered in an application for wire arc additive manufacturing (WAAM) of refractory highly corrosion-resistant Inconel 625 alloy. Based on the fabricated wall, the suitability of CMT–WAAM for the sound formation of welds and homogeneous distribution of mechanical properties is shown. Microscopic analysis reveals that the microstructure of the deposited alloy along the height of the wall element is relatively uniform. Minor differences in the microstructure are observed in the bottom part, caused by welding specifically. It should be noted that there is a slight decrease in strength indicators from the bottom to the top of the welded product, but they do not exceed 5%, which is considered entirely satisfactory. This phenomenon is caused by structural transformations that take place under slightly different cooling conditions – namely, in the lower layers. The substrate on which the surfacing is carried out plays a more significant role in heat flow. This leads to more intensive cooling of the lower layers and, as a result, slightly higher values of strength.

ABSTRACTOccupational therapy, people, and assistive technology have a longstanding relationship. Occupational therapists have the broadest scope of allied health practice across the breadth of assistive products and advisory services. This commentary revisits key foundations of occupational therapy and assistive technology practice. It then examines the recent recommendations made within the inaugural WHO/UNICEF Global Report on Assistive Technology. Drawing on international exemplars of diverse practice and leadership linked to each of the report’s Recommendations, this article demonstrates core roles for occupational therapists as leaders and change agents in delivering on the imperatives identified for assistive technology and assistive technology users globally.

Strong electric field annihilation by particle–antiparticle pair creation, also known as the Schwinger effect, is a non-perturbative prediction of quantum electrodynamics. Its experimental demonstration remains elusive, as threshold electric fields are extremely strong and beyond current reach. Here, we propose a mesoscopic variant of the Schwinger effect in graphene, which hosts Dirac fermions with an approximate electron–hole symmetry. Using transport measurements, we report on universal one-dimensional Schwinger conductance at the pinchoff of ballistic graphene transistors. Strong pinchoff electric fields are concentrated within approximately 1 μm of the transistor’s drain and induce Schwinger electron–hole pair creation at saturation. This effect precedes a collective instability towards an ohmic Zener regime, which is rejected at twice the pinchoff voltage in long devices. These observations advance our understanding of current saturation limits in ballistic graphene and provide a direction for further quantum electrodynamic experiments in the laboratory.

L’unité sanitaire en milieu pénitentiaire de la maison d’arrêt d’Angoulême est rattachée au centre hospitalier d’Angoulême. Le but de cette étude était de réaliser une cartographie des risques de la prise en charge médicamenteuse au sein de la maison d’arrêt.

Purpose: Presence of venous vascular invasion is a criterion of intermediate risk of recurrence in papillary thyroid carcinoma (PTC). However, the presence and type of vascular invasion (lymphatic or venous) is often underreported and its impact on PTCs without other risk features remains unknown. The aim of this study was to evaluate the impact of both lymphatic and venous invasion on the risk of recurrence/persistence on otherwise low-risk PTCs. Methods: Retrospective study including patients with otherwise low-risk PTCs but with vascular invasion, diagnosed between 2013 and 2019. The persistence/recurrence during the follow-up was evaluated. Pathology was reviewed to confirm the presence of lymphovascular invasion and determine the type of invasion. Results: A total of 141 patients were included. Lymphovascular invasion was confirmed in 20.6%. After surgery, 48.9% (N= 69) of the patients received radioactive iodine (RAI). The median follow-up time was 4 [3–6] years. Overall, 6 (4.2%) patients experienced persistent/recurrent disease in the neck, including 3 with lymphovascular invasion, confirmed as “only lymphatic”. Overall, patients with tumors harboring lymphovascular invasion had sensibly more persistent/recurrence disease compared with those without lymphovascular invasion (10.3% vs 2.7%, p= 0.1), especially in the subgroup of patients not treated with RAI (20% vs 1.6%, p= 0.049) [OR 15.25, 95% CI 1.24-187.85, p= 0.033]. Conclusion: Lymphovascular invasion, including lymphatic invasion only, is associated with a sensibly higher risk of persistent/recurrent disease in otherwise low-risk PTCs, namely in patients not treated with RAI. Lymphatic invasion could have a role in risk-stratification systems for decision making.

Background/aimsThe COVID-19 crisis and the decisions made regarding population lockdown may have changed patient care. We aimed to investigate the incidence rate of rhegmatogenous retinal detachment (RRD) cases during the COVID-19 lockdown period.MethodsIn this nationwide database study, we identified hospital and clinic admissions of French residents for a first episode of RRD in France from 2017 to the lockdown period in 2020. The monthly hospital incidence rates of RRD procedures per 100 000 inhabitants before, during and after lockdown were computed for the whole country. Finally, we assessed the influence of viral incidence on the RRD incidence rate, comparing two regions with highly contrasting viral penetration.ResultsFrom January to July, the average monthly national hospital incidence rate of RRD decreased from a mean of 2.59/100 000 inhabitants during 2017–2019 to 1.57/100 000 inhabitants in 2020. Compared with 2019, during the 8-week lockdown period in 2020, a 41.6% decrease in the number of RRD procedures was observed (p<0.001) with the weekly incidence of RRD decreasing from 0.63/100 000 inhabitants in 2019 to 0.36/100 000 inhabitants. During the 4-month post-lockdown period, no increased activity related to postponed procedures was observed. No difference was found in the rate of RRD surgery when comparing two regions with highly contrasting viral incidence.ConclusionContainment may have been responsible for a decrease in the number of surgical procedures for RRD, without any compensating post-lockdown activity in France. These results might help increase awareness of the management of RRD emergencies.

Le nourrisson et l’enfant présentent des spécificités physiologiques qui les exposent aux risques de complications respiratoires. Le nourrisson met notamment en jeu des phénomènes actifs, pour prévenir la survenue de troubles ventilatoires, qui sont abolis lors de l’anesthésie. L’anesthésiste doit donc être particulièrement vigilant à maintenir des paramètres ventilatoires optimaux du début de l’induction jusqu’à la période postopératoire. Ainsi, on recommandera d’appliquer une pression positive de fin d’expiration (PEEP) ≥ 5 cmH2O du début à la fin, une FiO2 relativement basse, un volume courant<10mL/kg (et idéalement entre 6 et 8mL/kg), tout en limitant l’espace mort instrumental. Les manœuvres de recrutement seront à envisager au cas par cas, mais ne doivent jamais être réalisées manuellement sans contrôle des volumes et des pressions. Enfin, il conviendra d’éviter la ventilation manuelle, notamment pour les transferts vers la salle de surveillance post-interventionnelle chez les enfants à risque. En effet, cela génère des volumes supraphysiologiques en l’absence de PEEP ou avec une FiO2 élevée et fera donc perdre tout le bénéfice de la ventilation protectrice réalisée en peropératoire.

Purpose: Prostate cancer is the most common cancer in the Caribbean. We present world-standardized incidence (WSI) and mortality (WSM) rates for urological cancers for French overseas territories. Materials and Methods: Standardized incidence ratio (SIR) and standardized mortality ratio (SMR) were calculated for 2008–2014, 2007–2014 and 2010–2014 in Guadeloupe, Martinique and French Guiana. Results: For prostate cancer, in Guadeloupe and Martinique, the WSI rates are among the highest in the world (173.0 and 164.5 per 100,000 person-years) and 94.4 in French Guiana. Mortality remains more than twice that observed in mainland France, at 23.0 in Guadeloupe and Martinique, and 16.9 in French Guiana. Conclusions: Identifying the profile of patients with urological cancers is key to understanding the needs of patients in these regions.

Purpose: Adrenocortical carcinoma (ACC) is a very rare and aggressive malignant disease. Therefore, overall survival (OS) has long been considered as the best endpoint. Yet, a unique endpoint is not optimal to take into account the heterogeneity in tumor profile and the diversification of therapeutic option. The purpose of this mini review was to describe endpoints used in the past, present and future in the field of ACC. Methods: Pubmed and Clinicaltrial.gov were used to identify relevant studies. Results: Before year 2000 only three endpoints were regularly used: OS, recurrence-free survival (RFS) and response rate. These endpoints were used because ACC was seen as a homogeneous diseases with a high recurrence rate and low rate of long-term survival. Since 2000; along with the apparition of new class of drug, progression-free survival (PFS) has been more and more used. Other endpoints as “time to chemotherapy” or “Progression-free survival 2” were used to evaluate multimodal therapies or treatment with a delayed action. Finally, there is a hope that in the near future, quality of life along with other patient-reported outcomes may be used more frequently. Conclusion: While OS and PFS are currently the most used endpoints in ACC, new endpoints are needed to better take into account the challenges offered by different situations and treatment strategies.

Des anémies inflammatoires paranéoplasiques chez des patients suivis pour phéochromocytomes ou paragangliomes métastatiques (PPGLm) sont occasionnellement décrites, cependant aucune étude n’a rapporté leurs fréquences et décrit leurs caractéristiques.

La qualité de vie et le bien-être psychologique des patients traités pour un cancer de la thyroïde sont essentiels compte tenu de leur survie très prolongée. Le traitement fait appel à une chirurgie souvent complétée par une thérapie par iode radioactif (RAI). Cette étude vise à examiner les effets potentiels de la thérapie par RAI sur la qualité de vie liée à la santé (Qdv), les symptômes d’anxiété et de dépression, et l’état nutritionnel six mois après traitement.

Les corticosurrénalomes métastatiques (CSM) sont des cancers agressifs avec peu de ressources thérapeutiques. La détermination de l’expression des protéines du système MMR (MLH1, MSH2, MSH6, PMS2) en immunohistochimie (IHC) est maintenant recommandée. L’objectif de ce travail est de décrire la présentation phénotypique des ACC métastatiques avec mutation des gènes MMR.

Le pronostic des corticosurrénalomes est hétérogène. La classification transcriptomique sépare les adénomes (cluster « C2 ») des corticosurrénalomes et en identifie deux clusters, « C1A » et « C1B » de pronostic différent. Le RNA-seq3′ permet de déterminer le transcriptome sur tissus fixés et inclus en paraffine, même sur des ARN très dégradés, mais au prix de données manquantes sur 10 à 50 % des transcrits. Notre objectif est de tester un algorithme de réseau de neurones pour prédire la classe moléculaire en routine.

Les phéochromocytomes et paragangliomes métastatiques (PPGLm) sont des cancers très rares avec un pronostic hétérogène. La meilleure séquence thérapeutique systémique reste à définir.

Les tumeurs neuroendocrines bronchiques (TNE) sont associées à un syndrome carcinoïde dans 10 à 40 % des cas. Du fait de leur rareté, les recommandations reposent principalement sur des données de patients avec TNE intestinales et aucune étude ne s’intéresse spécifiquement au syndrome carcinoïde des TNE bronchiques et à son impact pronostique.

Au stade métastatique, il est recommandé de proposer une étude moléculaire aux patients porteurs de corticosurrénalome afin d’identifier une potentielle cible thérapeutique. L’impact de la médecine de précision sur la prise en charge de ces patients n’est pas connu.

Les corticosurrénalomes (CS) et les phéochromocytomes et paragangliomes malins (PPMs) présentent des trajectoires thérapeutiques opposées. Le CS, moins rare et plus homogène que les PPMs, permet des essais thérapeutiques de phase III et une standardisation au diagnostic plus simple. Malgré des progrès liés aux facteurs pronostiques (mENSAT – GRAS) et à l’immunothérapie, la médiane de survie des CS métastatiques reste inférieure à 2ans en 2024. La phase III GALACCTICC ciblant IGF2 dans les CS a échoué, et les altérations moléculaires comme p53 ou la voie Wnt-B caténine ne sont pas encore traitables. En revanche, les PPMs, tumeurs ultra-rares à pronostic hétérogène, ont récemment bénéficié d’innovations. L’étude FIRSTMAPPP, publiée en 2024, a démontré la supériorité du Sunitinib pour ces tumeurs. La recherche translationnelle a permis de cibler la mutation SDHB, ouvrant la voie à une approche thérapeutique personnalisée. En 2024, la médecine personnalisée pour les CS est limitée au Mitotane, ciblant la mitochondrie surrénalienne, et aux rares cas avec une mutation du système MMR sensible à l’immunothérapie.

Since conventional cooling systems with channels are not adequate to achieve a high aspect quality with a short cycle time, a better concept has to be used to control the fast variation of temperature in the mold, close to the injected part. Recently, with advanced manufacturing technologies like 3D-printing, rapid heat cycle molding are developing, using for example lattice structures as heat exchanger inside the mold. Our work proposes an experimental study to analyze the influence of four lattice structures that were specifically designed for this industrial application. An instrumented bench was developed at the laboratory scale, to test the thermal efficiency of the lattice. The material and geometry of the lattice structures were selected based on their thermomechanical properties and their efficiency as a heat-exchanger. The instrumentation of the bench consists in measuring the flow rate and the pressures in the fluid, and also the temperatures at various locations. This allows us to determine the performances of the lattice structure. The results show that the denser the lattice structure, the better, whether considering the mechanical resistance or the thermohydraulic performances. The key element to understand this phenomenon is the average velocity of the fluid flowing inside the lattice structure, accelerating when the porosity decreases and thus bringing a more intense heat exchange.

ABSTRACTIntroductionThe most frequent radioactive (RAI) refractory thyroid cancers are papillary thyroid carcinoma, followed by poorly differentiated thyroid carcinoma. They are rare and lethal. In recent years, significant therapeutic progress has been achieved.Areas coveredThis paper offers insights on refractoriness to RAI treatment and the optimization of treatment initiation and treatment choice. Clinical trials performed with anti-angiogenic kinase inhibitors and with targeted inhibitors in patients with BRAF, RAS mutation or RET, TRK or ALK fusion are discussed.Expert opinionThese treatments provide high response rates. Anti-angiogenic kinase inhibitors improve median progression-free-survival; however, their benefit in terms of overall survival has been shown in only few subsets of patients. Treatment sequencing is challenging; in the absence of targetable abnormality, lenvatinib should be used as first-line treatment. Options for second-line treatment include lenvatinib (if not given at first line), cabozantinib or the addition of an anti-checkpoint antibody. In patients with a targetable abnormality, specific inhibitors, might be used as first-line treatment and lenvatinib as second line or vice-versa. Further studies are needed, based on documented genomic and immunologic characteristics of the tumor to assess the potential role of combination and redifferentiation therapy.

To describe the causes of postoperative acute endophthalmitis at the national level longitudinally.

Strategies that individualize the care of cancer patients receiving oral anticancer agents offer opportunities to improve treatment adherence and patient care. However, the impact of digital remote monitoring systems in this setting has not been evaluated. Here, we report the results of a phase 3 trial (CAPRI, NCT02828462) to assess the impact of a nurse navigator-led program on treatment delivery for patients with metastatic cancer. Patients receiving approved oral anticancer agents were randomized (1:1) to an intervention combining a nurse navigator-led follow-up system and a web portal–smartphone application on top of usual care, or to usual symptom monitoring at the discretion of the treating oncologist, for a duration of 6 months. The primary objective included optimization of the treatment dose. Secondary objectives were grade ≥3 toxicities, patient experience, rates and duration of hospitalization, response and survival, and quality of life. In 559 evaluable patients the relative dose intensity was higher in the experimental arm (93.4% versus 89.4%, P= 0.04). The intervention improved the patient experience (Patient Assessment of Chronic Illness Care score, 2.94 versus 2.67, P= 0.01), reduced the days of hospitalization (2.82 versus 4.44 days, P= 0.02), and decreased treatment-related grade ≥3 toxicities (27.6% versus 36.9%, P= 0.02). These findings show that patient-centered care through remote monitoring of symptoms and treatment may improve patient outcomes and experience.

A 1000 m-thick sequence of Upper Cretaceous sediments outcropping in the Isabena Valley (Tremp-Graus Basin, Spain) has been studied to explore the evolution of environmental conditions that prevailed in this basin. A biostratigraphic study based on calcareous nannofossils was carried out to better constraint the age of the deposits, supplemented by carbon isotope stratigraphy on bulk carbonates. Clay mineral assemblages were identified by X-Ray diffraction combined with organic matter (OM) characterisation by Rock–Eval pyrolysis. The Late Campanian Event and Campanian Maastrichtian Boundary Event are clearly identified from the new δ13Ccarbdataset. The clay assemblage is composed of a complex mixture of chlorite, illite, kaolinite and mixed-layers including illite–smectite and chlorite–smectite. A progressive illitisation of smectite is recorded from the top to the base of the section due to the increasing burial depth. This evolution is consistent with increasing Tmaxvalues of OM evolving from 425 (immature OM) to 449 °C (mature OM) from the top to the base of the section. Thus, detrital minerals are preserved only in the upper part of the section. The clay sedimentation is dominated by smectites likely originating from the Ebro massif, while increasing proportions of kaolinite are recorded from the uppermost Campanian and during the Maastrichtian. This evolution of the clay mineral assemblage is interpreted as a result from a change of source from south to northeast, with contributions from kaolinite-rich weathering profiles (including bauxites) to the northeast of the study area, reflecting a more hydrolysing climate.