141 research outputs found
Institutional conditions for integrated mobility services (IMS): Towards a framework for analysis
The present text is a theoretical framework that has been developed with the aim to generate knowledge of and policy recommendations for the promotion of integrated mobility services (IMS), with specific regard to institutional dimensions. Integrated mobility services are services where the passenger’s transport needs are met by a service that not only integrates a range of mobility services, both public and private, but also provides one-stop access to all services through a common interface. These types of services are currently being developed in several cities globally, and the purpose of the project is to understand and explain how institutions can enable, but also impede, their realization. Institutions are defined as a relatively stable collection of rules and practices, embedded in structures that enable action. In the project a broad theoretical approach, developed by an interdisciplinary research team, will be applied. As such, the framework includes factors at the macro, meso and micro levels, thus including extensive societal trends as well as individual\u27s needs and behaviour. The macro level includes broader social and political factors, including both formal rules and more informal social norms and perceptions. The division between formal and informal variables recur on the meso and micro levels respectively. The meso level – which includes both public and private actors at regional and local levels – consists of both formal institutional factors such as taxation and regulations, and informal factors such as organizational culture and inherited networks between regional actors. Each actor enters the collaborative processes that signify IMS with their own ideals, interests and expectations, and it is in these processes of negotiation that the framework takes it point of departure. It is also in this context that business models will be developed, another central aspect of the realisation of IMS. Finally, the framework also includes the micro level, where an individual perspective is placed at centre stage. Individuals are affected by various formal incentives and push factors, as well as more informal aspects such as self-image and social status. Through the application of the framework in a number of case studies, empirical findings will help illuminate which institutional factors enable or constrain the development of IMS. The findings will provide the empirical and analytical foundation for suggestions on how formal and informal rules and practices can be modified to enable new IMS to contribute to sustainable mobility
Dead or alive: sediment DNA archives as tools for tracking aquatic evolution and adaptation
DNA can be preserved in marine and freshwater sediments both in bulk sediment and in intact, viable resting stages. Here, we assess the potential for combined use of ancient, environmental, DNA and timeseries of resurrected long-term dormant organisms, to reconstruct trophic interactions and evolutionary adaptation to changing environments. These new methods, coupled with independent evidence of biotic and abiotic forcing factors, can provide a holistic view of past ecosystems beyond that offered by standard palaeoecology, help us assess implications of ecological and molecular change for contemporary ecosystem functioning and services, and improve our ability to predict adaptation to environmental stress
Recommended from our members
ARHGEF9 disease: Phenotype clarification and genotype-phenotype correlation.
ObjectiveWe aimed to generate a review and description of the phenotypic and genotypic spectra of ARHGEF9 mutations.MethodsPatients with mutations or chromosomal disruptions affecting ARHGEF9 were identified through our clinics and review of the literature. Detailed medical history and examination findings were obtained via a standardized questionnaire, or if this was not possible by reviewing the published phenotypic features.ResultsA total of 18 patients (including 5 females) were identified. Six had de novo, 5 had maternally inherited mutations, and 7 had chromosomal disruptions. All females had strongly skewed X-inactivation in favor of the abnormal X-chromosome. Symptoms presented in early childhood with delayed motor development alone or in combination with seizures. Intellectual disability was severe in most and moderate in patients with milder mutations. Males with severe intellectual disability had severe, often intractable, epilepsy and exhibited a particular facial dysmorphism. Patients with mutations in exon 9 affecting the protein's PH domain did not develop epilepsy.ConclusionsARHGEF9 encodes a crucial neuronal synaptic protein; loss of function of which results in severe intellectual disability, epilepsy, and a particular facial dysmorphism. Loss of only the protein's PH domain function is associated with the absence of epilepsy
Tiltak for bedre nitrogenforvaltning i norsk jordbruk
Rapporten er en del av et forprosjekt som skal gi grunnlag for utarbeidelse av en handlingsplan for god nitrogenutnyttelse i jordbruket. Det er beskrevet en rekke tiltak med potensiale for bedre utnyttelse av nitrogenressursene som forvaltes i norsk jordbruk. For mer detaljer henvises til teksten i rapporten og oversikten i tabell 1. Se side 5 for utfyllende sammendrag.Tiltak for bedre nitrogenforvaltning i norsk jordbrukpublishedVersio
Muligheter for en mer effektiv utnytelse av planterestene - Agronomi som sikrer god jordhelse, avling og plantehelse i korn
Tap av organisk materiale, jordpakking og erosjon truer jordhelsa på kornareal. Problemer med dette vil antagelig øke i et våtere klima og medføre store kostnader for både gårdbrukere og samfunn. Fremover må vi passe på å stabilisere erosjonsutsatt jordoverflate og sikre en god infiltrasjon av nedbør. På kornareal er lav årlig tilførsel av karbon en begrensende faktor for aggregering og stabilisering, men dette kan forbedres ved å beholde halmen på jordet eller bruke en tilpasset fangvekststrategi. En bør trolig skjevfordele tilført organisk materiale mer mot jordas overflate og dermed stimulere mikrobiell aktivitet i jordas toppsjikt. Da må en minimere jordarbeidingsintensiteten. Slik redusert jordarbeiding fører også til utvikling av et kontinuerlig poresystem nedover i profilet som kan øke infiltrasjonen etter kraftige nedbørsepisoder og dermed bidra til å dempe flomtopper. Store mengder plantemateriale ved jordoverflaten gir imidlertid også noen utfordringer. Det trengs økt kunnskap om ugrasbekjempelse, spesielt i et scenario der glyfosat blir forbudt. Minimal jordarbeiding med planterester på jordoverflaten kan også øke angrep av sopp. Integrerte plantevernstrategier bør identifisere arter og sorter av matplanter og fangvekster som kan bidra til å begrense forekomst av patogener i jord og halmrester. Bedre jordhelse på kornareal er en tverrfaglig utfordring og krever en varig endring av dagens dyrkingspraksis.Muligheter for en mer effektiv utnytelse av planterestene - Agronomi som sikrer god jordhelse, avling og plantehelse i kornpublishedVersio
A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity
The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLC?2 pathway as drug-target
A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity
The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer’s disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLCγ2 pathway as drug-target.Fil: van der Lee, Sven J.. Vrije Universiteit Amsterdam; Países BajosFil: Conway, Olivia J.. Mayo Clinic Cancer Center; Estados UnidosFil: Jansen, Iris. Vrije Universiteit Amsterdam; Países BajosFil: Carrasquillo, Minerva M.. Mayo Clinic Cancer Center; Estados UnidosFil: Kleineidam, Luca. Universitat Bonn; Alemania. German Center for Neurodegenerative Diseases; Alemania. University Hospital Cologne; AlemaniaFil: van den Akker, Erik. Leiden University. Leiden University Medical Center; Países Bajos. Delft University of Technology; Países BajosFil: Hernández, Isabel. Universitat Internacional de Catalunya; España. Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas ; EspañaFil: van Eijk, Kristel R.. University of Utrecht; Países BajosFil: Stringa, Najada. Vrije Universiteit Amsterdam; Países BajosFil: Chen, Jason A.. University of California at Los Angeles; Estados UnidosFil: Zettergren, Anna. University of Gothenburg; SueciaFil: Andlauer, Till F. M.. Max Planck Institute of Psychiatry; Alemania. Universitat Technical Zu Munich; Alemania. German Competence Network Multiple Sclerosis; AlemaniaFil: Diez Fairen, Monica. University Hospital Mutua de Terrassa; España. Fundacio per la Recerca Biomedica I Social Mutua Terrassa; EspañaFil: Simon Sanchez, Javier. Deutsches Zentrum für Neurodegenerative Erkrankungen; Alemania. Eberhard Karls Universität Tübingen; AlemaniaFil: Lleó, Alberto. Universitat Autònoma de Barcelona; España. Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas ; EspañaFil: Zetterberg, Henrik. Sahlgrenska University Hospital; Suecia. University of Gothenburg; Suecia. University College London; Estados UnidosFil: Nygaard, Marianne. University of Southern Denmark; DinamarcaFil: Blauwendraat, Cornelis. National Institute of Neurological Disorders and Stroke; Estados UnidosFil: Savage, Jeanne E.. Vrije Universiteit Amsterdam; Países BajosFil: Mengel From, Jonas. University of Southern Denmark; DinamarcaFil: Moreno Grau, Sonia. Universitat Internacional de Catalunya; EspañaFil: Wagner, Michael. Universitat Bonn; Alemania. Deutsches Zentrum für Neurodegenerative Erkrankungen; AlemaniaFil: Fortea, Juan. Universitat Autònoma de Barcelona; España. Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas ; EspañaFil: Keogh, Michael J.. University of Newcastle; Reino Unido. University of Cambridge; Reino UnidoFil: Blennow, Kaj. Sahlgrenska University Hospital; Suecia. University of Gothenburg; SueciaFil: Skoog, Ingmar. University of Gothenburg; SueciaFil: Friese, Manuel A.. German Competence Network Multiple Sclerosis; Alemania. Universitätsklinikum Hamburg‐Eppendorf; AlemaniaFil: Pletnikova, Olga. University Johns Hopkins; Estados UnidosFil: Zulaica, Miren. Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas ; España. Instituto Biodonostia; EspañaFil: Dalmasso, Maria Carolina. University Hospital Cologne; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin
Finger creases lend a hand in Kabuki syndrome.
International audienceKabuki syndrome (KS) is a rare syndrome associating malformations with intellectual deficiency and numerous visceral, orthopedic, endocrinological, immune and autoimmune complications. The early establishment of a diagnostic of KS leads to better care of the patients and therefore prevents complications such as perception deafness, severe complications of auto-immune diseases or obesity. However, the diagnosis of KS remains difficult because based on the appreciation of facial features combined with other highly variable features. We describe a novel sign, namely the attenuation and/or congenital absence of the IPD crease of the third and fourth fingers associated with limitation of flexion of the corresponding joints, which seems to be specific of KS and could help the clinician to diagnose KS
Infants and newborns with Atypical Teratoid Rhabdoid Tumors (ATRT) and Extracranial Malignant Rhabdoid Tumors (eMRT) in the EU-RHAB registry: a unique and challenging population
SIMPLE SUMMARY: Malignant rhabdoid tumors (MRT) are deadly tumors that predominantly affect infants and young children. Even when considering the generally young age of these patients, the treatment of infants below the age of six months represents a particular challenge due to the vulnerability of this patient population. The aim of our retrospective study was to assess the available information on prognostic factors, genetics, toxicity of treatment and long-term outcomes of MRT. We confirmed that, in a cohort of homogenously treated infants with MRT, significant predictors of outcome were female sex, localized stage, absence of a GLM and maintenance therapy, and these significantly favorably influence prognosis. Stratification-based biomarker-driven tailored trials may be a key option to improve survival rates. ABSTRACT: Introduction: Malignant rhabdoid tumors (MRT) predominantly affect infants and young children. Patients below six months of age represent a particularly therapeutically challenging group. Toxicity to developing organ sites limits intensity of treatment. Information on prognostic factors, genetics, toxicity of treatment and long-term outcomes is sparse. Methods: Clinical, genetic, and treatment data of 100 patients (aged below 6 months at diagnosis) from 13 European countries were analyzed (2005–2020). Tumors and matching blood samples were examined for SMARCB1 mutations using FISH, MLPA and Sanger sequencing. DNA methylation subgroups (ATRT-TYR, ATRT-SHH, and ATRT-MYC) were determined using 450 k / 850 k-profiling. Results: A total of 45 patients presented with ATRT, 29 with extracranial, extrarenal (eMRT) and 9 with renal rhabdoid tumors (RTK). Seventeen patients demonstrated synchronous tumors (SYN). Metastases (M+) were present in 27% (26/97) at diagnosis. A germline mutation (GLM) was detected in 55% (47/86). DNA methylation subgrouping was available in 50% (31 / 62) with ATRT or SYN; for eMRT, methylation-based subgrouping was not performed. The 5-year overall (OS) and event free survival (EFS) rates were 23.5 ± 4.6% and 19 ± 4.1%, respectively. Male sex (11 ± 5% vs. 35.8 ± 7.4%), M+ stage (6.1 ± 5.4% vs. 36.2 ± 7.4%), presence of SYN (7.1 ± 6.9% vs. 26.6 ± 5.3%) and GLM (7.7 ± 4.2% vs. 45.7 ± 8.6%) were significant prognostic factors for 5-year OS. Molecular subgrouping and survival analyses confirm a previously described survival advantage for ATRT-TYR. In an adjusted multivariate model, clinical factors that favorably influence the prognosis were female sex, localized stage, absence of a GLM and maintenance therapy. Conclusions: In this cohort of homogenously treated infants with MRT, significant predictors of outcome were sex, M-stage, GLM and maintenance therapy. We confirm the need to stratify which patient groups benefit from multimodal treatment, and which need novel therapeutic strategies. Biomarker-driven tailored trials may be a key option
Infants and Newborns with Atypical Teratoid Rhabdoid Tumors (ATRT) and Extracranial Malignant Rhabdoid Tumors (eMRT) in the EU-RHAB Registry: A Unique and Challenging Population
Malignant rhabdoid tumors (MRT) predominantly affect infants and young
children. Patients below six months of age represent a particularly therapeutically challenging group.
Toxicity to developing organ sites limits intensity of treatment. Information on prognostic factors,
genetics, toxicity of treatment and long-term outcomes is sparse. Methods: Clinical, genetic, and
treatment data of 100 patients (aged below 6 months at diagnosis) from 13 European countries were
analyzed (2005–2020). Tumors and matching blood samples were examined for SMARCB1 mutations
using FISH, MLPA and Sanger sequencing. DNA methylation subgroups (ATRT-TYR, ATRT-SHH,
and ATRT-MYC) were determined using 450 k / 850 k-profiling. Results: A total of 45 patients
presented with ATRT, 29 with extracranial, extrarenal (eMRT) and 9 with renal rhabdoid tumors (RTK).
Seventeen patients demonstrated synchronous tumors (SYN). Metastases (M+) were present in 27%
(26/97) at diagnosis. A germline mutation (GLM) was detected in 55% (47/86). DNA methylation
subgrouping was available in 50% (31 / 62) with ATRT or SYN; for eMRT, methylation-based
subgrouping was not performed. The 5-year overall (OS) and event free survival (EFS) rates were
23.5 ± 4.6% and 19 ± 4.1%, respectively. Male sex (11 ± 5% vs. 35.8 ± 7.4%), M+ stage (6.1 ± 5.4%
vs. 36.2 ± 7.4%), presence of SYN (7.1 ± 6.9% vs. 26.6 ± 5.3%) and GLM (7.7 ± 4.2% vs. 45.7 ± 8.6%)
were significant prognostic factors for 5-year OS. Molecular subgrouping and survival analyses
confirm a previously described survival advantage for ATRT-TYR. In an adjusted multivariate model,
clinical factors that favorably influence the prognosis were female sex, localized stage, absence of
a GLM and maintenance therapy. Conclusions: In this cohort of homogenously treated infants
with MRT, significant predictors of outcome were sex, M-stage, GLM and maintenance therapy. We confirm the need to stratify which patient groups benefit from multimodal treatment, and which
need novel therapeutic strategies. Biomarker-driven tailored trials may be a key option
- …