Smartphone as a Portable Detector, Analytical Device, or Instrument Interface

The Encyclopedia Britannia defines a smartphone as a mobile telephone with a display screen, at the same time serves as a pocket watch, calendar, addresses book and calculator and uses its own operating system (OS). A smartphone is considered as a mobile telephone integrated to a handheld computer. As the market matured, solid-state computer memory and integrated circuits became less expensive over the following decade, smartphone became more computer-like, and more more-advanced services, and became ubiquitous with the introduction of mobile phone networks. The communication takes place for sending and receiving photographs, music, video clips, e-mails and more. The growing capabilities of handheld devices and transmission protocols have enabled a growing number of applications. The integration of camera, access Wi-Fi, payments, augmented reality or the global position system (GPS) are features that have been used for science because the users of smartphone have risen all over the world. This chapter deals with the importance of one of the most common communication channels, the smartphone and how it impregnates in the science. The technological characteristics of this device make it a useful tool in social sciences, medicine, chemistry, detections of contaminants, pesticides, drugs or others, like so detection of signals or image

An Approach to an Inhibition Electronic Tongue to Detect On-Line Organophosphorus Insecticides Using a Computer Controlled Multi-Commuted Flow System

An approach to an inhibition bioelectronic tongue is presented. The work is focused on development of an automated flow system to carry out experimental assays, a custom potentiostat to measure the response from an enzymatic biosensor, and an inhibition protocol which allows on-line detections. A Multi-commuted Flow Analysis system (MCFA) was selected and developed to carry out assays with an improved inhibition method to detect the insecticides chlorpyrifos oxon (CPO), chlorfenvinfos (CFV) and azinphos methyl-oxon (AZMO). The system manifold comprised a peristaltic pump, a set of seven electronic valves controlled by a personal computer electronic interface and software based on LabView® to control the sample dilutions into the cell. The inhibition method consists in the injection of the insecticide when the enzyme activity has reached the plateau of the current; with this method the incubation time is avoided. A potentiostat was developed to measure the response from the enzymatic biosensor. Low limits of detection of 10 nM for CPO, CFV, and AZMO were achieved

Multi-parametric MR Imaging Biomarkers Associated to Clinical Outcomes in Gliomas: A Systematic Review

[EN] Purpose: To systematically review evidence regarding the association of multi-parametric biomarkers with clinical outcomes and their capacity to explain relevant subcompartments of gliomas. Materials and Methods: Scopus database was searched for original journal papers from January 1st, 2007 to February 20th , 2017 according to PRISMA. Four hundred forty-nine abstracts of papers were reviewed and scored independently by two out of six authors. Based on those papers we analyzed associations between biomarkers, subcompartments within the tumor lesion, and clinical outcomes. From all the articles analyzed, the twenty-seven papers with the highest scores were highlighted to represent the evidence about MR imaging biomarkers associated with clinical outcomes. Similarly, eighteen studies defining subcompartments within the tumor region were also highlighted to represent the evidence of MR imaging biomarkers. Their reports were critically appraised according to the QUADAS-2 criteria. Results: It has been demonstrated that multi-parametric biomarkers are prepared for surrogating diagnosis, grading, segmentation, overall survival, progression-free survival, recurrence, molecular profiling and response to treatment in gliomas. Quantifications and radiomics features obtained from morphological exams (T1, T2, FLAIR, T1c), PWI (including DSC and DCE), diffusion (DWI, DTI) and chemical shift imaging (CSI) are the preferred MR biomarkers associated to clinical outcomes. Subcompartments relative to the peritumoral region, invasion, infiltration, proliferation, mass effect and pseudo flush, relapse compartments, gross tumor volumes, and high-risk regions have been defined to characterize the heterogeneity. For the majority of pairwise cooccurrences, we found no evidence to assert that observed co-occurrences were significantly different from their expected co-occurrences (Binomial test with False Discovery Rate correction, alpha=0.05). The co-occurrence among terms in the studied papers was found to be driven by their individual prevalence and trends in the literature. Conclusion: Combinations of MR imaging biomarkers from morphological, PWI, DWI and CSI exams have demonstrated their capability to predict clinical outcomes in different management moments of gliomas. Whereas morphologic-derived compartments have been mostly studied during the last ten years, new multi-parametric MRI approaches have also been proposed to discover specific subcompartments of the tumors. MR biomarkers from those subcompartments show the local behavior within the heterogeneous tumor and may quantify the prognosis and response to treatment of gliomas.This work was supported by the Spanish Ministry for Investigation, Development and Innovation project with identification number DPI2016-80054-R.Oltra-Sastre, M.; Fuster García, E.; Juan -Albarracín, J.; Sáez Silvestre, C.; Perez-Girbes, A.; Sanz-Requena, R.; Revert-Ventura, A.... (2019). 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Radiology 2016,280(3),880-889Yoo R-E.; Choi S.H.; Cho H.R.; Tumor blood flow from arterial spin labeling perfusion MRI: a key parameter in distinguishing high-grade gliomas from primary cerebral lymphomas, and in predicting genetic biomarkers in high-grade gliomas. J Magn Reson Imaging 2013,38(4),852-860Liberman G.; Louzoun Y.; Aizenstein O.; Automatic multi-modal MR tissue classification for the assessment of response to bevacizumab in patients with glioblastoma. Eur J Radiol 2013,82(2),e87-e94Ramadan S.; Andronesi O.C.; Stanwell P.; Lin A.P.; Sorensen A.G.; Mountford C.E.; Use of in vivo two-dimensional MR spectroscopy to compare the biochemistry of the human brain to that of glioblastoma. Radiology 2011,259(2),540-549Xintao H.; Wong K.K.; Young G.S.; Guo L.; Wong S.T.; Support vector machine multi-parametric MRI identification of pseudoprogression from tumor recurrence in patients with resected glioblastoma. 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Magn Reson Imaging 2014,32(7),854-859Van Cauter S.; De Keyzer F.; Sima D.M.; Integrating diffusion kurtosis imaging, dynamic susceptibility-weighted contrast-enhanced MRI, and short echo time chemical shift imaging for grading gliomas. Neuro-oncol 2014,16(7),1010-1021Seeger A.; Braun C.; Skardelly M.; Comparison of three different MR perfusion techniques and MR spectroscopy for multiparametric assessment in distinguishing recurrent high-grade gliomas from stable disease. Acad Radiol 2013,20(12),1557-1565Chawalparit O.; Sangruchi T.; Witthiwej T.; Diagnostic performance of advanced mri in differentiating high-grade from low-grade gliomas in a setting of routine service. J Med Assoc Thai 2013,96(10),1365-1373Li Y.; Lupo J.M.; Parvataneni R.; Survival analysis in patients with newly diagnosed glioblastoma using pre- and postradiotherapy MR spectroscopic imaging. Neuro-oncol 2013,15(5),607-617Shankar J.J.S.; Woulfe J.; Silva V.D.; Nguyen T.B.; Evaluation of perfusion CT in grading and prognostication of high-grade gliomas at diagnosis: a pilot study. AJR Am J Roentgenol 2013,200(5)Zinn P.O.; Mahajan B.; Sathyan P.; Radiogenomic mapping of edema/cellular invasion MRI-phenotypes in glioblastoma multiforme. PLoS One 2011,6(10)Matsusue E.; Fink J.R.; Rockhill J.K.; Ogawa T.; Maravilla K.R.; Distinction between glioma progression and post-radiation change by combined physiologic MR imaging. Neuroradiology 2010,52(4),297-306Juan-Albarracín J.; Fuster-Garcia E.; Manjón J.V.; Automated glioblastoma segmentation based on a multiparametric structured unsupervised classification. PLoS One 2015,10(5)Itakura H.; Achrol A.S.; Mitchell L.A.; Magnetic resonance image features identify glioblastoma phenotypic subtypes with distinct molecular pathway activities. Sci Transl Med 2015,7(303)Ion-Margineanu A.; Van Cauter S.; Sima D.M.; Tumour relapse prediction using multiparametric MR data recorded during follow-up of GBM patients. BioMed Res Int 2015,2015Durst C.R.; Raghavan P.; Shaffrey M.E.; Multimodal MR imaging model to predict tumor infiltration in patients with gliomas. Neuroradiology 2014,56(2),107-115Yoon J.H.; Kim J.H.; Kang W.J.; Grading of cerebral glioma with multi-parametric MR Imaging and 18F-FDG-PET: concordance and accuracy. European Radiol 2014,24(2),380-389Demerath T.; Simon-Gabriel C.P.; Kellner E.; Mesoscopic imaging of glioblastomas: are diffusion, perfusion and spectroscopic measures influenced by the radiogenetic phenotype? Neuroradiol J 2017,30(1),36-47Qin L.; Li X.; Stroiney A.; Advanced MRI assessment to predict benefit of anti-programmed cell death 1 protein immunotherapy response in patients with recurrent glioblastoma. Neuroradiology 2017,59(2),135-145Boult J.K.R.; Borri M.; Jury A.; Investigating intracranial tumour growth patterns with multiparametric MRI incorporating Gd-DTPA and USPIO-enhanced imaging. NMR Biomed 2016,29(11),1608-1617Server A.; Kulle B.; Gadmar Ø.B.; Josefsen R.; Kumar T.; Nakstad P.H.; Measurements of diagnostic examination performance using quantitative apparent diffusion coefficient and proton MR spectroscopic imaging in the preoperative evaluation of tumor grade in cerebral gliomas. Eur J Radiol 2011,80(2),462-470Chang P.D.; Chow D.S.; Yang P.H.; Filippi C.G.; Lignelli A.; Predicting glioblastoma recurrence by early changes in the apparent diffusion coefficient value and signal intensity on FLAIR images. AJR Am J Roentgenol 2017,208(1),57-65Yi C.; Shangjie R.; Volume of high-risk intratumoralsubregions at multi-parametric MR imaging predicts overall survival and complements molecular analysis of glioblastoma. 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Exome-wide Rare Variant Analysis Identifies TUBA4A Mutations Associated with Familial ALS

Exome sequencing is an effective strategy for identifying human disease genes. However, this methodology is difficult in late-onset diseases where limited availability of DNA from informative family members prohibits comprehensive segregation analysis. To overcome this limitation, we performed an exome-wide rare variant burden analysis of 363 index cases with familial ALS (FALS). The results revealed an excess of patient variants within TUBA4A, the gene encoding the Tubulin, Alpha 4A protein. Analysis of a further 272 FALS cases and 5,510 internal controls confirmed the overrepresentation as statistically significant and replicable. Functional analyses revealed that TUBA4A mutants destabilize the microtubule network, diminishing its repolymerization capability. These results further emphasize the role of cytoskeletal defects in ALS and demonstrate the power of gene-based rare variant analyses in situations where causal genes cannot be identified through traditional segregation analysis

First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus: Latin American Group for the Study of Lupus (GLADEL, Grupo Latino Americano de Estudio del Lupus)-Pan-American League of Associations of Rheumatology (PANLAR)

Systemic lupus erythematosus (SLE), a complex and heterogeneous autoimmune disease, represents a significant challenge for both diagnosis and treatment. Patients with SLE in Latin America face special problems that should be considered when therapeutic guidelines are developed. The objective of the study is to develop clinical practice guidelines for Latin American patients with lupus. Two independent teams (rheumatologists with experience in lupus management and methodologists) had an initial meeting in Panama City, Panama, in April 2016. They selected a list of questions for the clinical problems most commonly seen in Latin American patients with SLE. These were addressed with the best available evidence and summarised in a standardised format following the Grading of Recommendations Assessment, Development and Evaluation approach. All preliminary findings were discussed in a second face-to-face meeting in Washington, DC, in November 2016. As a result, nine organ/system sections are presented with the main findings; an 'overarching' treatment approach was added. Special emphasis was made on regional implementation issues. Best pharmacologic options were examined for musculoskeletal, mucocutaneous, kidney, cardiac, pulmonary, neuropsychiatric, haematological manifestations and the antiphospholipid syndrome. The roles of main therapeutic options (ie, glucocorticoids, antimalarials, immunosuppressant agents, therapeutic plasma exchange, belimumab, rituximab, abatacept, low-dose aspirin and anticoagulants) were summarised in each section. In all cases, benefits and harms, certainty of the evidence, values and preferences, feasibility, acceptability and equity issues were considered to produce a recommendation with special focus on ethnic and socioeconomic aspects. Guidelines for Latin American patients with lupus have been developed and could be used in similar settings.Fil: Pons Estel, Bernardo A.. Centro Regional de Enfermedades Autoinmunes y Reumáticas; ArgentinaFil: Bonfa, Eloisa. Universidade de Sao Paulo; BrasilFil: Soriano, Enrique R.. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Cardiel, Mario H.. Centro de Investigación Clínica de Morelia; MéxicoFil: Izcovich, Ariel. Hospital Alemán; ArgentinaFil: Popoff, Federico. Hospital Aleman; ArgentinaFil: Criniti, Juan M.. Hospital Alemán; ArgentinaFil: Vásquez, Gloria. Universidad de Antioquia; ColombiaFil: Massardo, Loreto. Universidad San Sebastián; ChileFil: Duarte, Margarita. Hospital de Clínicas; ParaguayFil: Barile Fabris, Leonor A.. Hospital Angeles del Pedregal; MéxicoFil: García, Mercedes A.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Amigo, Mary Carmen. Centro Médico Abc; MéxicoFil: Espada, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Catoggio, Luis J.. Hospital Italiano. Instituto Universitario. Escuela de Medicina; ArgentinaFil: Sato, Emilia Inoue. Universidade Federal de Sao Paulo; BrasilFil: Levy, Roger A.. Universidade do Estado de Rio do Janeiro; BrasilFil: Acevedo Vásquez, Eduardo M.. Universidad Nacional Mayor de San Marcos; PerúFil: Chacón Díaz, Rosa. Policlínica Méndez Gimón; VenezuelaFil: Galarza Maldonado, Claudio M.. Corporación Médica Monte Sinaí; EcuadorFil: Iglesias Gamarra, Antonio J.. Universidad Nacional de Colombia; ColombiaFil: Molina, José Fernando. Centro Integral de Reumatología; ColombiaFil: Neira, Oscar. Universidad de Chile; ChileFil: Silva, Clóvis A.. Universidade de Sao Paulo; BrasilFil: Vargas Peña, Andrea. Hospital Pasteur Montevideo; UruguayFil: Gómez Puerta, José A.. Hospital Clinic Barcelona; EspañaFil: Scolnik, Marina. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Pons Estel, Guillermo J.. Centro Regional de Enfermedades Autoinmunes y Reumáticas; Argentina. Hospital Provincial de Rosario; ArgentinaFil: Ugolini Lopes, Michelle R.. Universidade de Sao Paulo; BrasilFil: Savio, Verónica. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Drenkard, Cristina. University of Emory; Estados UnidosFil: Alvarellos, Alejandro J.. Hospital Privado Universitario de Córdoba; ArgentinaFil: Ugarte Gil, Manuel F.. Universidad Cientifica del Sur; Perú. Hospital Nacional Guillermo Almenara Irigoyen; PerúFil: Babini, Alejandra. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Cavalcanti, André. Universidade Federal de Pernambuco; BrasilFil: Cardoso Linhares, Fernanda Athayde. Hospital Pasteur Montevideo; UruguayFil: Haye Salinas, Maria Jezabel. Hospital Privado Universitario de Córdoba; ArgentinaFil: Fuentes Silva, Yurilis J.. Universidad de Oriente - Núcleo Bolívar; VenezuelaFil: Montandon De Oliveira E Silva, Ana Carolina. Universidade Federal de Goiás; BrasilFil: Eraso Garnica, Ruth M.. Universidad de Antioquia; ColombiaFil: Herrera Uribe, Sebastián. Hospital General de Medellin Luz Castro de Gutiérrez; ColombiaFil: Gómez Martín, DIana. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Robaina Sevrini, Ricardo. Universidad de la República; UruguayFil: Quintana, Rosana M.. Hospital Provincial de Rosario; Argentina. Centro Regional de Enfermedades Autoinmunes y Reumáticas; ArgentinaFil: Gordon, Sergio. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; ArgentinaFil: Fragoso Loyo, Hilda. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Rosario, Violeta. Hospital Docente Padre Billini; República DominicanaFil: Saurit, Verónica. Hospital Privado Universitario de Córdoba; ArgentinaFil: Appenzeller, Simone. Universidade Estadual de Campinas; BrasilFil: Dos Reis Neto, Edgard Torres. Universidade Federal de Sao Paulo; BrasilFil: Cieza, Jorge. Hospital Nacional Edgardo Rebagliati Martins; PerúFil: González Naranjo, Luis A.. Universidad de Antioquia; ColombiaFil: González Bello, Yelitza C.. Ceibac; MéxicoFil: Collado, María Victoria. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Sarano, Judith. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Retamozo, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Sattler, María E.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Gamboa Cárdenas, Rocio V.. Hospital Nacional Guillermo Almenara Irigoyen; PerúFil: Cairoli, Ernesto. Universidad de la República; UruguayFil: Conti, Silvana M.. Hospital Provincial de Rosario; ArgentinaFil: Amezcua Guerra, Luis M.. Instituto Nacional de Cardiologia Ignacio Chavez; MéxicoFil: Silveira, Luis H.. Instituto Nacional de Cardiologia Ignacio Chavez; MéxicoFil: Borba, Eduardo F.. Universidade de Sao Paulo; BrasilFil: Pera, Mariana A.. Hospital Interzonal General de Agudos General San Martín; ArgentinaFil: Alba Moreyra, Paula B.. Universidad Nacional de Córdoba. Facultad de Medicina; ArgentinaFil: Arturi, Valeria. Hospital Interzonal General de Agudos General San Martín; ArgentinaFil: Berbotto, Guillermo A.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Gerling, Cristian. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; ArgentinaFil: Gobbi, Carla Andrea. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gervasoni, Viviana L.. Hospital Provincial de Rosario; ArgentinaFil: Scherbarth, Hugo R.. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; ArgentinaFil: Brenol, João C. Tavares. Hospital de Clinicas de Porto Alegre; BrasilFil: Cavalcanti, Fernando. Universidade Federal de Pernambuco; BrasilFil: Costallat, Lilian T. Lavras. Universidade Estadual de Campinas; BrasilFil: Da Silva, Nilzio A.. Universidade Federal de Goiás; BrasilFil: Monticielo, Odirlei A.. Hospital de Clinicas de Porto Alegre; BrasilFil: Seguro, Luciana Parente Costa. Universidade de Sao Paulo; BrasilFil: Xavier, Ricardo M.. Hospital de Clinicas de Porto Alegre; BrasilFil: Llanos, Carolina. Universidad Católica de Chile; ChileFil: Montúfar Guardado, Rubén A.. Instituto Salvadoreño de la Seguridad Social; El SalvadorFil: Garcia De La Torre, Ignacio. Hospital General de Occidente; MéxicoFil: Pineda, Carlos. Instituto Nacional de Rehabilitación; MéxicoFil: Portela Hernández, Margarita. Umae Hospital de Especialidades Centro Medico Nacional Siglo Xxi; MéxicoFil: Danza, Alvaro. Hospital Pasteur Montevideo; UruguayFil: Guibert Toledano, Marlene. Medical-surgical Research Center; CubaFil: Reyes, Gil Llerena. Medical-surgical Research Center; CubaFil: Acosta Colman, Maria Isabel. Hospital de Clínicas; ParaguayFil: Aquino, Alicia M.. Hospital de Clínicas; ParaguayFil: Mora Trujillo, Claudia S.. Hospital Nacional Edgardo Rebagliati Martins; PerúFil: Muñoz Louis, Roberto. Hospital Docente Padre Billini; República DominicanaFil: García Valladares, Ignacio. Centro de Estudios de Investigación Básica y Clínica; MéxicoFil: Orozco, María Celeste. Instituto de Rehabilitación Psicofísica; ArgentinaFil: Burgos, Paula I.. Pontificia Universidad Católica de Chile; ChileFil: Betancur, Graciela V.. Instituto de Rehabilitación Psicofísica; ArgentinaFil: Alarcón, Graciela S.. Universidad Peruana Cayetano Heredia; Perú. University of Alabama at Birmingahm; Estados Unido

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

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 low–middle-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 ‘single-use’ 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 low–middle-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 high– and low–middle–income countries