Seamless nowcasting system development at the Finnish Meteorological Institute

Presentación realizada en la 3rd European Nowcasting Conference, celebrada en la sede central de AEMET en Madrid del 24 al 26 de abril de 2019

Colonic Involvement in a Patient with Chronic Lymphocytic Leukaemia

Various gastrointestinal infiltrations have been described in patients with chronic lymphocytic leukaemia (CLL). Here, we report a 69-year-old man with CLL and anaemia in whom the macroscopic finding of colonoscopy was normal, but the histological specimens revealed lymphocytic leukemia in ileum and in colon. If a CLL patient has any symptoms suggesting a possible GI manifestation of the haematologic disease or anaemia not explained by bone marrow infiltration or hemolysis, the diagnostic evaluation should include endoscopies with adequate biopsies

Dissociable neural systems for unconditioned acute and sustained fear

Fear protects organisms by increasing vigilance and preparedness, and by coordinating survival responses during life-threatening encounters. The fear circuit must thus operate on multiple timescales ranging from preparatory sustained alertness to acute fight-or-flight responses. Here we studied the brain basis of sustained and acute fear using naturalistic functional magnetic resonance imaging (fMRI) enabling analysis of different time-scales of fear responses. Subjects (N ​= ​37) watched feature-length horror movies while their hemodynamic brain activity was measured with fMRI. Time-variable intersubject correlation (ISC) was used to quantify the reliability of brain activity across participants, and seed-based phase synchronization was used for characterizing dynamic connectivity. Subjective ratings of fear were used to assess how synchronization and functional connectivity varied with emotional intensity. These data suggest that acute and sustained fear are supported by distinct neural pathways, with sustained fear amplifying mainly sensory responses, and acute fear increasing activity in brainstem, thalamus, amygdala and cingulate cortices. Sustained fear increased ISC in regions associated with acute fear, and also amplified functional connectivity within this network. The results were replicated in an independent experiment with a different subject sample and stimulus movie. The functional interplay between cortical networks involved in sustained anticipation of, and acute response to, threat involves a complex and dynamic interaction that depends on the proximity of threat, and the need to employ threat appraisals and vigilance for decision making and response selection

Dissociable neural systems for unconditioned acute and sustained fear

Fear protects organisms by increasing vigilance and preparedness, and by coordinating survival responses during life-threatening encounters. The fear circuit must thus operate on multiple timescales ranging from preparatory sustained alertness to acute fight-or-flight responses. Here we studied the brain basis of sustained and acute fear using naturalistic functional magnetic resonance imaging (fMRI) enabling analysis of different time-scales of fear responses. Subjects (N ​= ​37) watched feature-length horror movies while their hemodynamic brain activity was measured with fMRI. Time-variable intersubject correlation (ISC) was used to quantify the reliability of brain activity across participants, and seed-based phase synchronization was used for characterizing dynamic connectivity. Subjective ratings of fear were used to assess how synchronization and functional connectivity varied with emotional intensity. These data suggest that acute and sustained fear are supported by distinct neural pathways, with sustained fear amplifying mainly sensory responses, and acute fear increasing activity in brainstem, thalamus, amygdala and cingulate cortices. Sustained fear increased ISC in regions associated with acute fear, and also amplified functional connectivity within this network. The results were replicated in an independent experiment with a different subject sample and stimulus movie. The functional interplay between cortical networks involved in sustained anticipation of, and acute response to, threat involves a complex and dynamic interaction that depends on the proximity of threat, and the need to employ threat appraisals and vigilance for decision making and response selection.</p

Dissociable Roles of Cerebral mu-Opioid and Type 2 Dopamine Receptors in Vicarious Pain: A Combined PET-fMRI Study

Neuroimaging studies have shown that seeing others in pain activates brain regions that are involved in first-hand pain, suggesting that shared neuromolecular pathways support processing of first-hand and vicarious pain. We tested whether the dopamine and opioid neurotransmitter systems involved in nociceptive processing also contribute to vicarious pain experience. We used in vivo positron emission tomography to quantify type 2 dopamine and mu-opioid receptor (D2R and MOR, respectively) availabilities in brains of 35 subjects. During functional magnetic resonance imaging, the subjects watched short movie clips depicting persons in painful and painless situations. Painful scenes activated pain-responsive brain regions including anterior insulae, thalamus and secondary somatosensory cortices, as well as posterior superior temporal sulci. MOR availability correlated negatively with the haemodynamic responses during painful scenes in anterior and posterior insulae, thalamus, secondary and primary somatosensory cortices, primary motor cortex, and superior temporal sulci. MOR availability correlated positively with orbitofrontal haemodynamic responses during painful scenes. D2R availability was not correlated with the haemodynamic responses in any brain region. These results suggest that the opioid system contributes to neural processing of vicarious pain, and that interindividual differences in opioidergic system could explain why some individuals react more strongly than others to seeing pain

Going carless in different urban fabrics: socio-demographics of household car ownership

Diverse physical features of urban areas alongside socio-demographic characteristics affect car ownership, and hence the daily mobility choices. As a case of sustainable mobility, we explore how various urban environments and socio-demographics associate with the spatial and social distribution of household car ownership and carlessness in the Helsinki Metropolitan Area, Finland. Three urban fabrics characterizing the study area are established based on the transportation mode (walking, public transportation, or automobile) the physical urban environment primarily supports. The national level Monitoring System of Spatial Structure and Urban Form database, and the National Travel Survey (2016) are utilized to further include spatial and socio-demographic variables into our analysis across these fabrics. Our results show that households with and without cars differ in terms of residential distance to the city center, neighborhood density, house type, and socio-demographic profiles. Single pensioners and students are most likely to be carless, whereas families represent the opposite. Within the carless households the differences are also evident between different groups. For the more affluent households residing in dense and well-connected areas, and mostly possessing driver's licenses, carlessness is presumably a choice. Contrarily, many other carless households represent the less affluent often located in the more distant, low-density, and less accessible areas, while also possessing less driver's licenses, making carlessness more of a constraint, as the local urban fabric does not support such lifestyle. Consequently, carless households should be increasingly recognized as a focus group in sustainable urban planning in terms of identifiable best practices and potential vulnerability

Therapeutic targeting of membrane-associated GRP78 in leukemia and lymphoma : preclinical efficacy in vitro and formal toxicity study of BMTP-78 in rodents and primates

Translation of drug candidates into clinical settings requires demonstration of preclinical efficacy and formal toxicology analysis for filling an Investigational New Drug (IND) application with the US Food and Drug Administration (FDA). Here, we investigate the membrane-associated glucose response protein 78 (GRP78) as a therapeutic target in leukemia and lymphoma. We evaluated the efficacy of the GRP78-targeted proapoptotic drug bone metastasis targeting peptidomimetic 78 (BMTP-78), a member of the D (KLAKLAK)2-containing class of agents. BMTP-78 was validated in cells from patients with acute myeloid leukemia and in a panel of human leukemia and lymphoma cell lines, where it induced dose-dependent cytotoxicity in all samples tested. Based on the in vitro efficacy of BMTP-78, we performed formal good laboratory practice toxicology studies in both rodents (mice and rats) and nonhuman primates (cynomolgus and rhesus monkeys). These analyses represent required steps towards an IND application of BMTP-78 for theranostic first-in-human clinical trials.Peer reviewe