Megatendenser – fremtidens kollektive transport i hovedstadsområdet

Artiklen er identisk med sammenfatningen i publikationen ”Megatendenser - fremtidens kollektive transport i hovedstadsområdet” som er udarbejdet af Metroselskabet og Hovedstadens Letbane i samarbejde med de to selskabers fælles ”Review Board”, der består af udvalgte danske forskere med særlig indsigt i transportområdet og byudvikling. Da publikationen også blev udarbejdet som led i et analysearbejde af Hovedstadens Letbane for Region Hovedstaden, har Region Hovedstaden ligeledes bidraget med input. Et centralt formål med analysen har været at give et overblik over, hvilke megatendenser og drivkræfter, der kan påvirke fremtidens transport i hovedstadsområdet, samt de kritiske usikkerheder der kan blive afgørende for, hvilken retning udviklingen kan gå. I analysen udpeges 1) Urbanisering 2) Hastig teknologisk udvikling og 3) Klimaforandringer som de tre mest betydningsfulde megatendenser for transportområdet i hovedstadsområdet. Derudover er der identificeret og beskrevet en række drivkræfter knyttet til de enkelte megatendenser samt de politiske, økonomiske, sociale og kulturelle drivkræfter, som også har betydning for den kollektive transport i hovedstadsområdet. Udover kortlægningen af megatendenser og drivkræfter har analysen givet anledning til en række konklusioner i kraft af de udfordringer og potentialer de beskrevne megatendenser og drivkræfter giver for den kollektive transport, herunder især betydningen af de førerløse biler. En central konklusion er, at hovedstadsområdet står over for en udfordring i forhold til at håndtere fremtidens mobilitet med forventet øget befolkningstilvækst og nye arbejdspladser. Førerløse biler som et individuelt tilbud kan ikke løse denne udfordring, selvom der er en forventning om, at de kan udnytte vejkapaciteten bedre på større veje. Der peges på, at det er usikkert om førerløse biler vil betyde en øget vejkapacitet i byområder, da biltrafikken allerede i dag kører tæt i byområder. Det konkluderes i rapporten, at der fortsat vil være behov for højklasset kollektiv transport i større byområder for at kunne tilbyde en effektiv mobilitet i fremtiden

Clinical presentation of calmodulin mutations: the International Calmodulinopathy Registry

Calmodulin; Cardiomyopathies; Neurological disordersCalmodulina; Miocardiopatías; Trastornos neurológicosCalmodulina; Miocardiopaties; Trastorns neurològicsAims: Calmodulinopathy due to mutations in any of the three CALM genes (CALM1-3) causes life-threatening arrhythmia syndromes, especially in young individuals. The International Calmodulinopathy Registry (ICalmR) aims to define and link the increasing complexity of the clinical presentation to the underlying molecular mechanisms. Methods and results: The ICalmR is an international, collaborative, observational study, assembling and analysing clinical and genetic data on CALM-positive patients. The ICalmR has enrolled 140 subjects (median age 10.8 years [interquartile range 5-19]), 97 index cases and 43 family members. CALM-LQTS and CALM-CPVT are the prevalent phenotypes. Primary neurological manifestations, unrelated to post-anoxic sequelae, manifested in 20 patients. Calmodulinopathy remains associated with a high arrhythmic event rate (symptomatic patients, n = 103, 74%). However, compared with the original 2019 cohort, there was a reduced frequency and severity of all cardiac events (61% vs. 85%; P = .001) and sudden death (9% vs. 27%; P = .008). Data on therapy do not allow definitive recommendations. Cardiac structural abnormalities, either cardiomyopathy or congenital heart defects, are present in 30% of patients, mainly CALM-LQTS, and lethal cases of heart failure have occurred. The number of familial cases and of families with strikingly different phenotypes is increasing. Conclusion: Calmodulinopathy has pleiotropic presentations, from channelopathy to syndromic forms. Clinical severity ranges from the early onset of life-threatening arrhythmias to the absence of symptoms, and the percentage of milder and familial forms is increasing. There are no hard data to guide therapy, and current management includes pharmacological and surgical antiadrenergic interventions with sodium channel blockers often accompanied by an implantable cardioverter-defibrillator.The ICalmR is one of the registries supported by ERN GUARD-Heart. This research was supported by the Italian Ministry of Health Ricerca Corrente ‘Registro internazionale delle calmodulinopatie’ to L.C., F.D., P.J.S., M.C.K., and C.S.; by the 2019-ATESP-0045 Fondo di Ateneo Quota Competitiva to L.C.; and partially by the Fondation Leducq grant 18CVD05 ‘Towards Precision Medicine with Human iPSCs for Cardiac Channelopathies’ to L.C., M.-C.K., L.S., and P.J.S. J.B., L.C., and P.J.S. were partially supported by the European Joint Programme on Rare Diseases: LQTS-NEXT grant. R.H. was supported by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, The Labatt Family Heart Centre, the Cartwright Family Fellowship, the Carter Heart Arrhythmia Trainee Fund and the Caitlin Elizabeth Morris fund. J.P.K. was supported by the Medical Research Council (MRC) Clinical Academic Research Partnership (CARP) Award (MR/T024062/1). G.R.W. was supported by an NIH K23HL130554 grant. A.A.M.W. was supported by the Netherlands Cardiovascular Research Initiative (CVON PREDICT-2). M.J.A. was supported in part by the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program. M.T.O. was supported in part by the Danish Independent Research Council (Grant no. 2032–00333B) and the Lundbeck Foundation (Grant no. R324-2019-1933). H.K.J. was supported by the Novo Nordisk Foundation (Grant NNF 18OC0031258)

Plasma proteome analysis of patients with type 1 diabetes with diabetic nephropathy

<p>Abstract</p> <p>Background</p> <p>As part of a clinical proteomics program focused on diabetes and its complications we are looking for new and better protein biomarkers for diabetic nephropathy. The search for new and better biomarkers for diabetic nephropathy has, with a few exceptions, previously focused on either hypothesis-driven studies or urinary based investigations. To date only two studies have investigated the proteome of blood in search for new biomarkers, and these studies were conducted in sera from patients with type 2 diabetes. This is the first reported in depth proteomic study where plasma from type 1 diabetic patients was investigated with the goal of finding improved candidate biomarkers to predict diabetic nephropathy. In order to reach lower concentration proteins in plasma a pre-fractionation step, either hexapeptide bead-based libraries or anion exchange chromatography, was performed prior to surface enhanced laser desorption/ionization time-of-flight mass spectrometry analysis.</p> <p>Results</p> <p>Proteomic analysis of plasma from a cross-sectional cohort of 123 type 1 diabetic patients previously diagnosed as normoalbuminuric, microalbuminuric or macroalbuminuric, gave rise to 290 peaks clusters of which 16 were selected as the most promising biomarker candidates based on statistical performance, including independent component analysis. Four of the peaks that were discovered have been identified as transthyretin, apolipoprotein A1, apolipoprotein C1 and cystatin C. Several yet unidentified proteins discovered by this novel approach appear to have more potential as biomarkers for diabetic nephropathy.</p> <p>Conclusion</p> <p>These results demonstrate the capacity of proteomic analysis of plasma, by confirming the presence of known biomarkers as well as revealing new biomarkers for diabetic nephropathy in plasma in type 1 diabetic patients.</p

A Lactobacilli diet that confers MRSA resistance causes amino acid depletion and increased antioxidant levels in the C. elegans host

Probiotic bacteria are increasingly popular as dietary supplements and have the potential as alternatives to traditional antibiotics. We have recently shown that pretreatment with Lactobacillus spp. Lb21 increases the life span of C. elegans and results in resistance toward pathogenic methicillin-resistant Staphylococcus aureus (MRSA). The Lb21-mediated MRSA resistance is dependent on the DBL-1 ligand of the TGF-β signaling pathway. However, the underlying changes at the metabolite level are not understood which limits the application of probiotic bacteria as timely alternatives to traditional antibiotics. In this study, we have performed untargeted nuclear magnetic resonance-based metabolic profiling. We report the metabolomes of Lactobacillus spp. Lb21 and control E. coli OP50 bacteria as well as the nematode-host metabolomes after feeding with these diets. We identify 48 metabolites in the bacteria samples and 51 metabolites in the nematode samples and 63 across all samples. Compared to the control diet, the Lactobacilli pretreatment significantly alters the metabolic profile of the worms. Through sparse Partial Least Squares discriminant analyses, we identify the 20 most important metabolites distinguishing probiotics from the regular OP50 food and worms fed the two different bacterial diets, respectively. Among the changed metabolites, we find lower levels of essential amino acids as well as increased levels of the antioxidants, ascorbate, and glutathione. Since the probiotic diet offers significant protection against MRSA, these metabolites could provide novel ways of combatting MRSA infections

Relación entre el estado nutricional y el ausentismo escolar en estudiantes de escuelas rurales

Objetivo Determinar el estado nutricional, las prevalencias de desnutrición y sobrepeso de estudiantes en escuelas rurales y su relación con tasas de ausentismo escolar. Métodos Estudio descriptivo en 34 escuelas rurales de Anapoima y La Mesa en 2013. Una muestra de 785 (82,4 %) estudiantes fueron seleccionados por muestreo por conveniencia. Criterios de inclusión: estudiante matriculado en 2013 de los grados 0-5 (edades 5-16) con consentimiento de  padres o acudientes y asentimiento del estudiante. Se tomaron medidas de peso y talla. Se registraron tasas de ausencia (general y por enfermedad). Resultados 422 estudiantes fueron varones (53,8 %) y 524 (66,8 %) tenían entre 5-9 años. La prevalencia de talla baja para la edad fue 10,1 % (n=79). La delgadez fue 1,75 % (n=13), el sobrepeso 14,3 % (n=112) y la obesidad 4,5 % (n=45).Las tasas de episodios de ausentismo general y por enfermedad por niño al año fueron 5,7 y 1,4 respectivamente. Los estudiantes con baja talla para la edad y sobrepeso tuvieron un número significativamente mayor de días de ausencias en comparación con los estudiantes con adecuado estado nutricional (p0,01). Los estudiantes con talla baja para la edad tuvieron las tasas más altas de ausentismo.Conclusiones Coexistencia de  desnutrición y obesidad en el área de estudio. Relación significativa entre el mayor número de días de ausentismo general y por enfermedad con el retardo en el crecimiento y el sobrepeso en los escolares

Tumor volume and cancer stem cell expression as prognostic markers for high-dose loco-regional failure in head and neck squamous cell carcinoma - A DAHANCA 19 study

BACKGROUND AND PURPOSE: Reliable and accessible biomarkers for patients with Head and Neck Squamous Cell Carcinoma (HNSCC) are warranted for biologically driven radiotherapy (RT). This study aimed to investigate the prognostic value of putative cancer stem cell (CSC) markers, hypoxia, and tumor volume using loco-regional high-dose failure (HDF) as endpoint.MATERIALS AND METHODS: Tumor tissue was retrieved from patients treated with primary chemo-(C-)RT and nimorazole for HNSCC in the Danish Head and Neck Cancer Study Group (DAHANCA) 19 study. Tumor volume, hypoxic classification, and expression of CSC markers CD44, SLC3A2, and MET were analyzed. For patients with eligible data on all parameters (n = 340), the risk of HDF following primary chemo-(C-)RT were analyzed by these biomarkers as a whole and stratified for p16-positive oropharynx (p16 + OPSCC) vs p16-negative (p16-) tumors (oral cavity, p16- oropharynx, hypopharynx and larynx).RESULTS: Higher risk of HDF was seen for patients with larger primary and nodal volume (&gt;25 cm3, Hazard Ratio (HR): 3.00 [95 % CI: 1.73-5.18]), high SLC3A2 (HR: 2.99 [1.28-6.99]), CD44 (&gt;30 % positive, HR: 2.29 [1.05-5.00]), and p16- tumors (HR: 2.53 [1.05-6.11]). p16- tumors had a higher CSC marker expression than p16 + OPSCC. The factors associated with the highest risk of HDF were larger volume (HR: 3.29 [1.79-6.04]) for p16- tumors (n = 178) and high SLC3A2 (HR: 6.19 [1.58-24.23]) for p16 + OPSCC (n = 162).CONCLUSION: Tumor volume, p16, and CSC markers are potential biomarkers for HDF for patients with HNSCC treated with (C-)RT. Lower expression of CSC in p16 + OPSCC may contribute to better tumor control.</p