21 research outputs found
CreaciĂł dâun treball de sĂntesi i dâun portal web per a la gestiĂł i representaciĂł de les dades dâuna estaciĂł meteorolĂČgica
El treball de sĂntesi continua essent un element amb molta importĂ ncia dins del currĂculum dels tres primers cursos de lâeducaciĂł secundĂ ria obligatĂČria. Aquesta importĂ ncia ha fet que en el transcurs dels anys sâhagin desenvolupat un conjunt de programes dâactivitats per tal de donar resposta a aquest treball. En funciĂł dâaixĂČ, han nascut diverses ofertes, empreses i estades especialitzades en oferir mĂșltiples opcions per tal de desenvolupar-los.
Actualment, la recessiĂł econĂČmica Ă©s latent en gran part del territori catalĂ , i aixĂČ fa que sigui complicat que les famĂlies amb pocs recursos econĂČmics puguin costejar el preu que costa realitzar treballs de sĂntesi en aquest tipus de llocs.
Per aquest motiu, cada cop mĂ©s els centres desenvolupen ells mateixos diferents activitats per emmarcar-les dins dâun projecte de sĂntesi. Aquests treballs donen la llibertat de poder-se orientar en una temĂ tica concreta, fet que es pot aprofitar per treballar aspectes especĂfics del currĂculum o ampliar-los.
En base dâaquests motius es presenta el segĂŒent projecte de sĂntesi que consisteix en lâelaboraciĂł dâunes directrius i material per tal de dur a terme un projecte basat en la temĂ tica de la meteorologia en el curs de 1r dâESO, degut al gran nombre de continguts curriculars que guarden relaciĂł amb aquesta temĂ tica.
A mĂ©s a mĂ©s, tambĂ© es pretĂ©n donar continuĂŻtat al projecte âLa Xarxa MeteorolĂČgica Educativa de Catalunyaâ (Edumet) iniciat lâany 2004 pel Departament dâEducaciĂł. Aquest projecte actualment es troba bastant en desĂșs i gran part de les estacions meteorolĂČgiques que enviaven dades a la web han deixat de fer-ho. EndemĂ©s, molts dels enllaços que es troben a la web estan trencats, algunes de les estacions mai han enviat informaciĂł, i els que lâhan enviat daten del 2009
A pan-cancer clinical platform to predict immunotherapy outcomes and prioritize immuno-oncology combinations in early-phase trials
Immunooncology; Predictive biomarkers; Tumor microenvironmentInmunooncologĂa; Biomarcadores predictivos; Microambiente tumoralImmunooncologia; Biomarcadors predictius; Microambient tumoralBackground
Immunotherapy is effective, but current biomarkers for patient selection have proven modest sensitivity. Here, we developed VIGex, an optimized gene signature based on the expression level of 12 genes involved in immune response with RNA sequencing.
Methods
We implemented VIGex using the nCounter platform (Nanostring) on a large clinical cohort encompassing 909 tumor samples across 45 tumor types. VIGex was developed as a continuous variable, with cutoffs selected to detect three main categories (hot, intermediate-cold and cold) based on the different inflammatory status of the tumor microenvironment.
Findings
Hot tumors had the highest VIGex scores and exhibited an increased abundance of tumor-infiltrating lymphocytes as compared with the intermediate-cold and cold. VIGex scores varied depending on tumor origin and anatomic site of metastases, with liver metastases showing an immunosuppressive tumor microenvironment. The predictive power of VIGex-Hot was observed in a cohort of 98 refractory solid tumor from patients treated in early-phase immunotherapy trials and its clinical performance was confirmed through an extensive metanalysis across 13 clinically annotated gene expression datasets from 877 patients treated with immunotherapy agents. Last, we generated a pan-cancer biomarker platform that integrates VIGex categories with the expression levels of immunotherapy targets under development in early-phase clinical trials.
Conclusions
Our results support the clinical utility of VIGex as a tool to aid clinicians for patient selection and personalized immunotherapy interventions.A.H.C. would like to acknowledge fellowship funding from the Spanish Society of Medical Oncology (SEOM), CRIS Contra el Cancer and Hold'em For Life Oncology Fellowship. This research has been funded by the Comprehensive Program of Cancer Immunotherapy & Immunology II (CAIMI-II) supported by the BBVA Foundation (grant 53/2021) and the 2020â2021 Division of Medical Oncology and Hematology (DMOH) Fellowship award at Princess Margaret Cancer Centre. VHIO would like to acknowledge the Cellex Foundation for providing research facilities and equipment and the CERCA Programme from the Generalitat de Catalunya for their support of this research. Authors from VHIO acknowledge the State Agency for Research (Agencia Estatal de InvestigaciĂłn) for providing financial support as a Center of Excellence Severo Ochoa (CEX2020-001024-S/AEI/10.13039/501100011033). A.V. was the recipient of a project award from the FAECC (AVP/18/AECC/3219) and received funding from the Advanced Molecular Diagnostic (DIAMAV) program from the FERO Foundation. Graphical abstract was created with BioRender.com. Diagram in Figure 3B was created with SankeyMATIC (sankeymatic.com)
Impact of the COVID-19 pandemic in the early-onset colorectal cancer
COVID-19 pandemic; Early-onset colorectal cancerPandemia de COVID-19 Cåncer colorrectal precozPandÚmia de COVID-19; Cà ncer colorectal precoçThe COVID19 pandemic has affected the spectrum of cancer care worldwide. Early onset colorectal cancer (EOCRC) is defined as diagnosis below the age of 50. Patients with EOCRC faced multiple challenges during the COVID19 pandemic and in some institutions it jeopardized cancer diagnosis and care delivery. Our study aims to identify the clinicopathological features and outcomes of patients with EOCRC in our Centre during the first wave of the pandemic in comparison with the same period in 2019 and 2021.
Patients with EOCRC visited for the first time at Vall d'Hebron University Hospital in Spain from the 1st March to 31st August of 2019, 2020 and 2021 were included in the analysis. 177 patients with EOCRC were visited for the first time between 2019 and 2021, of which 90 patients met the inclusion criteria (2019: 30 patients, 2020: 29 patients, 2021: 31 patients). Neither differences in frequency nor in stage at diagnosis or at first visit during the given periods were observed. Of note, indication of systemic therapy in the adjuvant or metastatic setting was not altered. Days to treatment initiation and enrollment in clinical trials in this subpopulation was not affected due to the COVID-19 outbreak.This work was supported by the Cancer Research UK (CRUK) grant OPTIMISTICC (C10674/A27140)
Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients
Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when = 50 years and symptomatic for <= 7days were included. The intervention consisted of 200-300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311); OR for hospitalization or death was 0.919 (CI 0.592-1.416). CP effect on hospital admission or death was largest in patients with <= 5 days of symptoms (OR 0.658, 95%CI 0.394-1.085). CP did not decrease the time to full symptom resolution
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Evaluation of CNA-IC50 correlations by known cancer driver mutations. Distributions of PCCs for cancer cell lines with mutated or wild-type proto-oncogenes or tumor suppressors as depicted in each figure. The rank position of negatively correlated drugs (pâ<â0.10) is shown. (EPS 975 kb
Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries
Abstract
Background
Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres.
Methods
This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and lowâmiddle-income countries.
Results
In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of âsingle-useâ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for lowâmiddle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia.
Conclusion
This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both highâ and lowâmiddleâincome countries
CreaciĂł dâun treball de sĂntesi i dâun portal web per a la gestiĂł i representaciĂł de les dades dâuna estaciĂł meteorolĂČgica
El treball de sĂntesi continua essent un element amb molta importĂ ncia dins del currĂculum dels tres primers cursos de lâeducaciĂł secundĂ ria obligatĂČria. Aquesta importĂ ncia ha fet que en el transcurs dels anys sâhagin desenvolupat un conjunt de programes dâactivitats per tal de donar resposta a aquest treball. En funciĂł dâaixĂČ, han nascut diverses ofertes, empreses i estades especialitzades en oferir mĂșltiples opcions per tal de desenvolupar-los.
Actualment, la recessiĂł econĂČmica Ă©s latent en gran part del territori catalĂ , i aixĂČ fa que sigui complicat que les famĂlies amb pocs recursos econĂČmics puguin costejar el preu que costa realitzar treballs de sĂntesi en aquest tipus de llocs.
Per aquest motiu, cada cop mĂ©s els centres desenvolupen ells mateixos diferents activitats per emmarcar-les dins dâun projecte de sĂntesi. Aquests treballs donen la llibertat de poder-se orientar en una temĂ tica concreta, fet que es pot aprofitar per treballar aspectes especĂfics del currĂculum o ampliar-los.
En base dâaquests motius es presenta el segĂŒent projecte de sĂntesi que consisteix en lâelaboraciĂł dâunes directrius i material per tal de dur a terme un projecte basat en la temĂ tica de la meteorologia en el curs de 1r dâESO, degut al gran nombre de continguts curriculars que guarden relaciĂł amb aquesta temĂ tica.
A mĂ©s a mĂ©s, tambĂ© es pretĂ©n donar continuĂŻtat al projecte âLa Xarxa MeteorolĂČgica Educativa de Catalunyaâ (Edumet) iniciat lâany 2004 pel Departament dâEducaciĂł. Aquest projecte actualment es troba bastant en desĂșs i gran part de les estacions meteorolĂČgiques que enviaven dades a la web han deixat de fer-ho. EndemĂ©s, molts dels enllaços que es troben a la web estan trencats, algunes de les estacions mai han enviat informaciĂł, i els que lâhan enviat daten del 2009
On the use of fractional calculus to improve the pulse arrival time (PAT) detection when using photoplethysmography (PPG) and electrocardiography (ECG) signals.
The pulse arrival time (PAT) has been considered a surrogate measure for pulse wave velocity (PWV), although some studies have noted that this parameter is not accurate enough. Moreover, the inter-beat interval (IBI) time series obtained from successive pulse wave arrivals can be employed as a surrogate measure of the RR time series avoiding the use of electrocardiogram (ECG) signals. Pulse arrival detection is a procedure needed for both PAT and IBI measurements and depends on the proper fiducial points chosen. In this paper, a new set of fiducial points that can be tailored using several optimization criteria is proposed to improve the detection of successive pulse arrivals. This set is based on the location of local maxima and minima in the systolic rise of the pulse wave after fractional differintegration of the signal. Several optimization criteria have been proposed and applied to high-quality recordings of a database with subjects who were breathing at different rates while sitting or standing. When a proper fractional differintegration order is selected by using the RR time series as a reference, the agreement between the obtained IBI and RR is better than that for other state-of-the-art fiducial points. This work tested seven different traditional fiducial points. For the agreement analysis, the median standard deviation of the difference between the IBI and RR time series is 5.72 ms for the proposed fiducial point versus 6.20 ms for the best-performing traditional fiducial point, although it can reach as high as 9.93 ms for another traditional fiducial point. Other optimization criteria aim to reduce the standard deviation of the PAT (7.21 ms using the proposed fiducial point versus 8.22 ms to 15.4 ms for the best- and worst-performing traditional fiducial points) or to minimize the standard deviation of the PAT attributable to breathing (3.44 ms using the proposed fiducial point versus 4.40 ms to 5.12 ms for best- and worst-performing traditional fiducial points). The use of these fiducial points may help to better quantify the beat-to-beat PAT variability and IBI time series
Developmental outcome of electroencephalographic findings in SYNGAP1 encephalopathy
SYNGAP1 haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. Standardized questionnaires were employed to collect clinical, electroencephalographic and genetic data. We investigated electroencephalographic findings, focusing on the cortical distribution of interictal abnormalities and their changes with age. Among the 36 SYNGAP1-DEE cases 18 presented variants in the SYNGAP1 gene that had never been previously reported. The mean age of diagnosis was 8 years and 8 months, ranging from 2 to 17 years, with 55.9% being male. All subjects had global neurodevelopmental/language delay and behavioral abnormalities; 83.3% had moderate to profound intellectual disability (ID), 91.7% displayed autistic traits, 73% experienced sleep disorders and 86.1% suffered from epileptic seizures, mainly eyelid myoclonia with absences (55.3%). A total of 63 VEEGs were revised, observing a worsening of certain EEG findings with increasing age. A disorganized background was observed in all age ranges, yet this was more common among older cases. The main IEDs were bilateral synchronous and asynchronous posterior discharges, accounting for â„50% in all age ranges. Generalized alterations with maximum amplitude in the anterior region showed as the second most frequent IED (â„15% in all age ranges) and were also more common with increasing age. Finally, diffuse fast activity was much more prevalent in cases with 6 years or older. To the best of our knowledge, this is the first study to analyze EEG features across different age groups, revealing an increase in interictal abnormalities over infancy and adolescence. Our findings suggest that SYNGAP1 haploinsufficiency has complex effects in human brain development, some of which might unravel at different developmental stages. Furthermore, they highlight the potential of baseline EEG to identify candidate biomarkers and the importance of natural history studies to develop specialized therapies and clinical trials
Cancer network activity associated with therapeutic response and synergism
Cancer patients often show no or only modest benefit from a given therapy. This major problem in oncology is generally attributed to the lack of specific predictive biomarkers, yet a global measure of cancer cell activity may support a comprehensive mechanistic understanding of therapy efficacy. We reasoned that network analysis of omic data could help to achieve this goal. A measure of "cancer network activity" (CNA) was implemented based on a previously defined network feature of communicability. The network nodes and edges corresponded to human proteins and experimentally identified interactions, respectively. The edges were weighted proportionally to the expression of the genes encoding for the corresponding proteins and relative to the number of direct interactors. The gene expression data corresponded to the basal conditions of 595 human cancer cell lines. Therapeutic responses corresponded to the impairment of cell viability measured by the half maximal inhibitory concentration (IC) of 130 drugs approved or under clinical development. Gene ontology, signaling pathway, and transcription factor-binding annotations were taken from public repositories. Predicted synergies were assessed by determining the viability of four breast cancer cell lines and by applying two different analytical methods. The effects of drug classes were associated with CNAs formed by different cell lines. CNAs also differentiate target families and effector pathways. Proteins that occupy a central position in the network largely contribute to CNA. Known key cancer-associated biological processes, signaling pathways, and master regulators also contribute to CNA. Moreover, the major cancer drivers frequently mediate CNA and therapeutic differences. Cell-based assays centered on these differences and using uncorrelated drug effects reveals novel synergistic combinations for the treatment of breast cancer dependent on PI3K-mTOR signaling. Cancer therapeutic responses can be predicted on the basis of a systems-level analysis of molecular interactions and gene expression. Fundamental cancer processes, pathways, and drivers contribute to this feature, which can also be exploited to predict precise synergistic drug combinations. The online version of this article (doi:10.1186/s13073-016-0340-x) contains supplementary material, which is available to authorized users