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There is an increasing demand for real-world data pertaining to the usage of cancer treatments, especially in settings where no standard treatment is specifically recommended. This study presents the first real-world analysis of third-line treatment patterns in HER2-positive metastatic breast cancer (mBC) patients in Canada. The purpose was to assess evolution of clinical practice and identify unmet needs in post-second-line therapy. Retrospective data from medical records of 66 patients who received third-line treatment before 31st October 2018, and data from 56 patients who received third-line treatment after this date, extracted from the Personalize My Treatment (PMT) cancer patient registry, were analyzed. In the first cohort, the study revealed heterogeneity in the third-line setting, with trastuzumab, lapatinib, and T-DM1 being the main treatment options. Even though data were collected before the wide availability of tucatinib, neratinib and trastuzumab deruxtecan in Canada, the PMT cohort revealed the emergence of new therapeutic combinations and a shift from lapatinib usage to T-DM1 choice was observed. These findings underscore the evolving nature of third-line treatment strategies in Canada, a facet that is intrinsically tied to the availability of new drugs. The absence of a consensus on post-second-line treatment highlights the pressing need for more efficient therapeutic alternatives beyond the currently available options. This study not only offers valuable insights into the present landscape of third-line treatment in Canada but validates the significance and effectiveness of the PMT registry as a tool for generating pan-Canadian real-world evidence in oncology and its capacity to provide information on evolution of therapeutic practices.

The future of work and the ever-changing skills demand in the labour market has been a constant debate and pressing challenge for higher education institutions (HEI’s), governments and industry. In the current context, HEI’s must increase the transformational effect of education on people’s employability, on organizations’ competitiveness and on society’s progress. This paper presents the design and development of a mock-up career guidance tool to empower lifelong learners through digital reskilling and upskilling. We discuss the methods used for designing a skills alignment tool and a smart catalogue for identifying stackable training pathways in two specific disciplinary domains. The skills alignment methodology features a skill gap analysis (SGA) in the occupational domains of Data Science and Chemistry, linked to the evolution and demand of the European labour market through an ESCO compatible tool. The smart program catalog presents the necessary program information to facilitate the creation of stackable training pathways. Considerations are made for the importance of virtual career guidance tools for lifelong learners as we face the ever-changing demand of the labor market and as we continue to embrace online education, micro-credentialing and the digital transformation of higher education.

Abstract Background Acute kidney injury (AKI) requiring renal replacement therapy (RRT) is a serious complication in the ICU that results in increased mortality and risk of chronic kidney disease (CKD). Some studies suggest RRT modality may have an impact on long-term renal recovery after AKI. However, other predictive factors of severe long-term CKD in ICU patients with AKI requiring RRT are unknown. Methods We performed an ancillary study of the multicenter ELVIS trial in the population with AKI requiring RRT. Patients alive 3 months after RRT initiation were eligible. Serum creatinine levels available at 3, 6 and 12 months and 3 and 5 years were recorded. CKD stage was determined according to the glomerular filtration rate as estimated by the CKD-EPI formula. At each timepoint, two groups of patients were compared, a no/mild CKD group with normal or mildly to moderately decreased renal function (stages 1, 2 and 3 of the international classification) and a severe CKD group (stages 4 and 5). Our objective was to identify predictive factors of severe long-term CKD. Results Of the 287 eligible patients, 183 had follow-up at 3 months, 136 (74.3%) from the no/mild CKD group and 47 (25.7%) from the severe CKD group, and 122 patients at 5 years comprising 96 (78.7%) from the no/mild CKD group and 26 (21.3%) from the severe CKD group. Multivariate analysis showed that a long RRT period was associated with severe CKD up to 12 months (ORM12 = 1.03 95% CI [1.02–1.05] per day) and that a high SOFA score at the initiation of RRT was not associated with severe CKD up to 5 years (ORM60 = 0.85 95% CI [0.77–0.93] per point). Conclusion Severe long-term CKD was found in 21% of ICU survivors who underwent RRT for AKI. The duration of the RRT in AKI patients was identified as a new predictive factor for severe long-term CKD. This finding should be taken into consideration in future studies on the prognosis of ICU patients with AKI requiring RRT. Trial registration ELVIS trial was registered with ClinicalTrials.gov, number: NCT00875069 (June 16, 2014), and this ancillary study was registered with ClinicalTrials.gov, number: NCT03302624 (October 6, 2017).

Abstract The popular Discrete Fourier Transform (DFT) is known to be a sub‐optimal frequency estimation technique for a finite transform length. In order to approach the Cramer‐Rao Lower Bound (CRLB), many refinement techniques have been considered, but little considering both zero padding or tapering, also known as windowing or apodisation. In this paper, a frequency estimator with closed‐form combination of three DFT samples is generalized to zero padding and tapered data within the class of cosine windowing. Root Mean Squared Error (RMSE) is shown to approach the CRLB in the case of a single tone signal with additive white Gaussian noise. Compared to state‐of‐the‐art techniques, the proposed algorithm improves the frequency RMSE up to 1 dB when using significant zero‐padding lengths (K ≥ 2 N) and for small to moderate SNR, which is the most challenging case for practical radar applications.

Abstract Background Whether Intensive Care Unit (ICU) clinicians display unconscious bias towards cancer patients is unknown. The aim of this study was to compare the outcomes of critically ill patients with and without perceptions of excessive care (PECs) by ICU clinicians in patients with and without cancer. Methods This study is a sub-analysis of the large multicentre DISPROPRICUS study. Clinicians of 56 ICUs in Europe and the United States completed a daily questionnaire about the appropriateness of care during a 28-day period. We compared the cumulative incidence of patients with concordant PECs, treatment limitation decisions (TLDs) and death between patients with uncontrolled and controlled cancer, and patients without cancer. Results Of the 1641 patients, 117 (7.1%) had uncontrolled cancer and 270 (16.4%) had controlled cancer. The cumulative incidence of concordant PECs in patients with uncontrolled and controlled cancer versus patients without cancer was 20.5%, 8.1%, and 9.1% (p

Abstract Checkpoint protein inhibitor antibodies (CPI), including cytotoxic T-lymphocyte-associated antigen 4 inhibitors (ipilimumab, tremelimumab) and the programmed cell death protein 1 pathway/programmed cell death protein 1 ligand inhibitors (pembrolizumab, nivolumab, durvalumab, atezolizumab), have entered routine practice for the treatment of many cancers. They improve the outcome for many cancers, and more patients will be treated with CPI in the future. Although CPI can lead to adverse events (AE) less frequently than for chemotherapy, their use can require intensive care unit admission in case of severe immune-related adverse events (IrAE). Moreover, some of these events, particularly late events, are poorly documented, so a high level of suspicion should be maintained for patients receiving CPI. Intensivists should be aware in general of the known complications and appropriate management of these AE. Nevertheless, a multidisciplinary collaboration remains essential for their diagnosis and management. This review described the most severe complications related to CPI.

Abstract Background Although outcomes of critically ill patients with haematological malignancies (HMs) have been fully investigated in terms of organ failure and mortality, data are scarce on health-related quality of life (HRQOL) in this population. We aim to assess post-intensive care unit (ICU) burden and HRQOL of critically ill patients with HMs and to identify risk factors for quality-of-life (QOL) impairment. Results In total, 1011 patients with HMs who required ICU admission in 17 ICUs in France and Belgium were included in the study; 278 and 117 patients were evaluated for QOL at 3 months and 1 year, respectively, after ICU discharge. HRQOL was determined by applying the interview form of the Short Form 36 (SF-36) questionnaire. Psychological distress symptoms were evaluated using the Hospital Anxiety Depression Score (HADS) and the Impact of Event Scale (IES). In-hospital mortality rates at 3 months and 1 year were, respectively, 39.1, 50.7 and 57.2%, respectively. At 3 months, median [IQR] physical and mental component summary scores (PCS and MCS) (SF-36) were 37 [28–46] and 51 [45–58], respectively. PCS was lower in ICU patients with HMs when compared to general ICU septic patients (52 [5–13], p = 0.00001). The median combined HAD score was 8 [5–13], and the median IES score was 8 [3–16]. However, recovery during the first year after ICU discharge was not consistent in all dimensions of HRQOL. Three months after ICU discharge, the maximum daily Sequential Organ Failure Assessment score and status of the underlying malignancy at ICU admission were significantly associated with MCS impairment (− 0.54 points [95% CI − 0.99; − 0.1], p = 0.018 and − 4.83 points [95% CI − 8.44; − 1.22], p = 0.009, respectively). Conclusion HRQOL is strongly impaired in critically ill patients with HMs at 3 months and 1 year after ICU discharge. Organ failure and disease status are strongly associated with QOL. The kinetic evaluation of QOL at 3 months and 1 year offers the opportunity to focus on QOL aspects that may be improved by therapeutic interventions during the first year after ICU discharge.

Objectives: Physical activity (PA) programs are recommended for breast cancer care. However, their modalities remain to be discussed. This study determined the best time to begin a personalized or adapted program based on cardiopulmonary exercise test function. This randomized controlled trial evaluated the effect of home-based adapted PA (APA) performed during or after treatment on cardiorespiratory fitness (CRF) at 12 months. Method: The primary endpoint was the peak oxygen consumption (VO 2peak ) at 12 months (group A vs C and B vs C). Secondary endpoints included the 6-minute walking test, assessment of muscle strength, fatigue, quality of life, anxiety, and depression, and a questionnaire on PA levels. All tests were evaluated at baseline and at 6 and 12 months. A total of 94 patients with breast cancer were randomized to 3 different groups: group A, performing 6 months of APA during adjuvant care; group B, 6 months of APA after adjuvant care; and group C, 12 months of APA during and after specific care. The program combined 1 resistance session and 2 aerobic sessions per week. Analysis of variance was used for repeated measures, Student’s t -test or the Mann–Whitney U -test for continuous variables, and χ 2 test for binary or categorical variables. Results: The study assessed 81 participants at 6 months and 73 at 12 months. The majority of patients completed more than 85% of the exercise sessions. The baseline for VO 2peak and secondary outcomes did not differ among the groups. VO 2peak increased during the exercise period and decreased during the chemotherapy period without APA, but at 12 months no significant difference was observed. The same variation was observed in the 6-minute walking test, with significance at 6 months between A+C versus B ( P = .04), but no difference among the groups at 12 months. In the 3 groups, no decreases in other studied parameters were noted, except at 6 months in group B without APA. Conclusion: Home-based APA in breast cancer patients has a positive effect on CRF and physical functions, with no differences based on the timing of this program based on specific cancer treatment. Trial Registration: ClinicalTrials.gouv.fr (NCT01795612). Registered 20 February 2013.

Abstract Objectives To assess outcomes at hospital discharge and day-120 after intensive care unit (ICU) discharge among patients with solid cancer admitted to ICU and to identify characteristics associated with in-hospital and day-120 after ICU discharge mortalities. Design International, multicenter, retrospective study. Setting Five ICUs in France and Brazil, two located in cancer centers, two in university affiliated and one in general hospitals. Patients Consecutive patients aged > 18 years, with underlying solid cancers (known before admission to the ICU or diagnosed during the stay in the ICU), admitted to the participating ICUs and discharged alive from the ICU from January 2006 to December 2011 were included in this study. Patients admitted after scheduled surgery or to secure procedure were excluded. Variables of interest were in-hospital and day-120 post-ICU mortality among patients discharged alive from the ICU. Interventions None. Measurements and results A total of 1053 patients aged 63 years (54–71) (median [IQR]) were included. Most of the patients were of the male gender (66.8%). The in-ICU, in-hospital, and four-month post-ICU discharge mortalities were, respectively, 41.3, 60.7, and 65.8%. Among patients discharged alive from the ICU, in multivariate analysis, factors associated with four months post-ICU discharge mortality were type of cancer (OR from 0.25 to 0.52 when compared to lung cancers), systemic extension of the disease (OR 2.54; 95% CI 1.87–3.45), need for invasive mechanical ventilation (OR 2.54; 95% CI 1.80–3.59), for vasopressors (OR 2.35; 95% CI 1.66–3.29), or renal replacement therapy (OR 1.54; 95% CI 0.99–2.38). A predictive score, “Oncoscore,” was built performing fairly in predicting 4 months post-ICU discharge outcome (AUC 0.74; 95% CI 0.71–0.77). Conclusion Despite the high day-120 mortality following the ICU discharge, our study reports a meaningful medium-term survival rate after the ICU discharge of solid cancer patients. Of utmost importance, the “Oncoscore” must be validated in prospective studies and cannot be used, in its form without external validation, for individual decision making. Prospective studies to answer questions not provided by this study are needed, including only patients with solid cancers admitted in the ICU for medical reasons or after emergency surgery.

Background: Adapted physical activity (APA) aids breast cancer patients. It is necessary to use an adapted target heart rate (HR) when prescribing exercise intensity. Methods: In total, 138 patients previously included in two published randomized clinical trials underwent the CPET and 6MWT before and after adjuvant therapy. Of these patients, 85 had performed APA, and 53 had received only the usual therapy. HRs were recorded during the two tests. Results: Before starting chemotherapy, good agreement (intraclass correlation (ICC) 0.69; confidence interval at 95% IC0.95 (0.591–0.769); p < 0.001) and a moderate correlation were evident between the 6MWT-HR and ventilatory threshold HR of the CPET (r = 0.70; p < 0.001). Good agreement and a high positive correlation were noted only in the group who engaged in APA (ICC 0.77; IC0.95 (0.659–0.848); p < 0.001; r = 0.8; p < 0.01); moderate agreement and a moderate positive correlation were apparent in the control group (ICC 0.57; IC0.95 (0.329–0.74); p < 0.001; r = 0.6; p < 0.01). The correlations were independent of age and body mass index. Conclusions: The 6MWT-HR can be used to prescribe exercise intensity for breast cancer patients both before and after specific treatment with concomitant APA.

Disruptions in epidermal growth factor receptor (EGFR) trafficking has been linked to tumor progression. Here the authors show that sortilin limits cell proliferation and tumor growth by promoting EGFR internalization.

Abstract Background Indications for red blood cell (RBC) transfusion in septic acute circulatory failure remain unclear. We addressed the practices and the prognostic impact of RBC transfusion in the early resuscitation of severe sepsis and septic shock in patients with hematological malignancies. Methods We performed a retrospective analysis of a prospectively collected database of patients with hematological malignancies who required intensive care unit (ICU) admission in 2010–2011. Patients with a main admission diagnosis of severe sepsis or septic shock were included in the present study. We assessed RBC transfusion during the first two days as part of initial resuscitation. Results Among the 1011 patients of the primary cohort, 631 (62.4%) were admitted to the ICU for severe sepsis (55%) or septic shock (45%). Among them, 210 (33.3%) patients received a median of 2 [interquartile 1–3] packed red cells during the first 48 h. Hemoglobin levels were lower in transfused patients at days 1 and 2 and became similar to those of non-transfused patients at day 3. Early RBC transfusion was more likely in patients with myeloid neoplasms and neutropenia. Transfused patients displayed more severe presentations as assessed by higher admission SOFA scores and blood lactate levels and the further requirements for organ failure supports. RBC transfusion within the first two days was associated with higher day 7 (20.5 vs. 13.3%, p = 0.02), in-ICU (39 vs. 25.2%, p

Au Québec, le programme ministériel prévoit un enseignement des savoirs grammaticaux au service des différentes compétences disciplinaires. Nous avons mené une recherche quasi-expérimentale cherchant vérifier et comparer les effets d'enseignements explicites inductif et déductif des complément du nom (CN) sur des rédactions d’élèves de 1re secondaire. Nous avons constaté une diminution significative du nombre d’erreurs et du nombre de répétitions. Aussi, à la phase de révision, les élèves ont corrigé davantage. Par ailleurs, peu de différences ont été observées entre les effets des deux approches, si ce n'est une diminution plus importante du nombre de répétitions pour l'approche inductive.

Since time-delay, Doppler effect and phase estimation are fundamental tasks in a plethora of engineering fields, tractable lower performance bounds for this problem are key tools of broad interest for a large variety of remote sensing applications. In the large sample regime and/or the high signal-to-noise ratio regime of the Gaussian conditional signal model, the Cramér–Rao bound (CRB) provides an accurate lower bound in the mean square error sense. In this contribution, we introduce firstly a new compact CRB expression for the joint time-delay and Doppler stretch estimation, considering a generic delayed and dilated band-limited signal. This generalizes known results for both wideband signals and the standard narrowband signal model where the Doppler effect on the band-limited baseband signal is not considered and amounts to a frequency shift. General compact closed-form CRB expressions for the amplitude and phase are also provided. These compact CRBs are expressed in terms of the baseband signal samples, making them especially easy to use whatever the baseband signal considered, therefore being valid for a variety of remote sensors. The new CRB expressions are validated in a positioning case study, both using synthetic and real data. These results show that the maximum likelihood estimator converges to the CRB at high signal-to-noise ratios, which confirms the exactness of the CRB. The CRB is further validated by comparing the ambiguity function and its 2nd order Taylor expansion where the perfect match also proves its exactness.

Global Navigation Satellite Systems (GNSS) are the main source of position, navigation, and timing (PNT) information and will be a key player in the next-generation intelligent transportation systems and safety-critical applications, but several limitations need to be overcome to meet the stringent performance requirements. One of the open issues is how to provide precise PNT solutions in harsh propagation environments. Under nominal conditions, the former is typically achieved by exploiting carrier phase information through precise positioning techniques, but these methods are very sensitive to the quality of phase observables. Another option that is gaining interest in the scientific community is the use of large bandwidth signals, which allow obtaining a better baseband resolution, and therefore more precise code-based observables. Two options may be considered: (i) high-order binary offset carrier (HO-BOC) modulations or (ii) the concept of GNSS meta-signals. In this contribution, we assess the time-delay and phase maximum likelihood (ML) estimation performance limits of such signals, together with the performance translation into the position domain, considering single point positioning (SPP) and RTK solutions, being an important missing point in the literature. A comprehensive discussion is provided on the estimators’ behavior, the corresponding ML threshold regions, the impact of good and bad satellite constellation geometries, and final conclusions on the best candidates, which may lead to precise solutions under harsh conditions. It is found that if the receiver is constrained by the receiver bandwidth, the best choices are the L1-M or E6-Public Regulated Service (PRS) signals. If the receiver is able to operate at 60 MHz, it is recommended to exploit the full-bandwidth Galileo E5 signal. In terms of robustness and performance, if the receiver can operate at 135 MHz, the best choice is to use the GNSS meta-signals E5 + E6 or B2 + B3, which provide the best overall performances regardless of the positioning method used, the satellite constellation geometry, or the propagation conditions.

This contribution analyzes the fundamental performance limits of traditional two-step Global Navigation Satellite System (GNSS) receiver architectures, which are directly linked to the achievable time-delay estimation performance. In turn, this is related to the GNSS baseband signal resolution, i.e., bandwidth, modulation, autocorrelation function, and the receiver sampling rate. To provide a comprehensive analysis of standard point positioning techniques, we consider the different GPS and Galileo signals available, as well as the signal combinations arising in the so-called GNSS meta-signal paradigm. The goal is to determine: (i) the ultimate achievable performance of GNSS code-based positioning systems; and (ii) whether we can obtain a GNSS code-only precise positioning solution and under which conditions. In this article, we provide clear answers to such fundamental questions, leveraging on the analysis of the Cramér–Rao bound (CRB) and the corresponding Maximum Likelihood Estimator (MLE). To determine such performance limits, we assume no external ionospheric, tropospheric, orbital, clock, or multipath-induced errors. The time-delay CRB and the corresponding MLE are obtained for the GPS L1 C/A, L1C, and L5 signals; the Galileo E1 OS, E6B, E5b-I, and E5 signals; and the Galileo E5b-E6 and E5a-E6 meta-signals. The results show that AltBOC-type signals (Galileo E5 and meta-signals) can be used for code-based precise positioning, being a promising real-time alternative to carrier phase-based techniques.

Epidemiological studies of neurological complications in patients with hematological malignancies are scant. The objective of the study was to identify determinants of survival in patients with hematological malignancy and neurological failure.Post hoc analysis of a prospective study of adults with hematological malignancies admitted for any reason to one of 17 university or university-affiliated participating ICUs in France and Belgium (2010-2012). The primary outcome was vital status at hospital discharge.Of the 1011 patients enrolled initially, 226 (22.4%) had neurological failure. Presenting manifestations were dominated by drowsiness or stupor (65%), coma (32%), weakness (26%), and seizures (19%). Neuroimaging, lumbar puncture, and electroencephalography were performed in 113 (50%), 73 (32%), and 63 (28%) patients, respectively. A neurosurgical biopsy was done in 1 patient. Hospital mortality was 50%. By multivariate analysis, factors independently associated with higher hospital mortality were poor performance status (odds ratio [OR], 3.99; 95%CI, 1.82-9.39; P = 0.0009), non-Hodgkin's lymphoma (OR, 2.60; 95%CI, 1.35-5.15; P = 0.005), shock (OR, 1.95; 95%CI, 1.04-3.72; P = 0.04), and respiratory failure (OR, 2.18; 95%CI, 1.14-4.25; P = 0.02); and factors independently associated with lower hospital mortality were GCS score on day 1 (OR, 0.88/point; 95%CI, 0.81-0.95; P = 0.0009) and autologous stem cell transplantation (OR, 0.25; 95%CI, 0.07-0.75; P = 0.02).In ICU patients with hematological malignancies, neurological failure is common and often fatal. Independent predictors of higher hospital mortality were type of underlying hematological malignancy, poor performance status, hemodynamic and respiratory failures, and severity of consciousness impairment. Knowledge of these risk factors might help to optimize management strategies.

Avec l’avènement du Web, les étudiants universitaires d’aujourd’hui ont développé des compétences et des stratégies qui relèvent de la littératie numérique afin de produire leurs travaux. Un questionnaire a été élaboré afin d’établir les stratégies qu’ils mobilisent dans la mise en oeuvre de compétences informationnelles, rédactionnelles et de référencement documentaire, et une partie du questionnaire portait sur les connaissances des étudiants universitaires sur le plagiat. Les résultats préliminaires obtenus ont permis de valider le questionnaire et de constater que les étudiants souhaitent être davantage formés aux diverses stratégies et compétences en plus d’en apprendre davantage sur le plagiat.