109 research outputs found
Breastfeeding in Bolivia – information and attitudes
BACKGROUND: The main objective of the present study was to investigate the relationship between the attitudes of the mother and her family towards breastfeeding and the actual feeding pattern in a Bolivian population. A second objective was to study the relationship between breastfeeding information, specified according to source and timing, and feeding pattern. METHODS: Cross-sectional interviews with 420–502 Bolivian mothers with an infant less than or equal to 1 year of age. Duration of exclusive breastfeeding, use of prelacteal food and/or colostrum were the main outcome measures. RESULTS: The attitudes of the mother, her partner (the infant's father) and the infant's grandmother towards breastfeeding did not influence the infant feeding pattern. Women who had received breastfeeding information from health care personnel before birth or on the maternity ward breastfed exclusively for a longer duration (adjusted p = 0.0233) and avoided prelacteal food to a greater extent (adjusted odds ratio (AOR) = 0.42; 95% confidence interval for adjusted odds ratio (95% CI AOR) = 0.23–0.72). Information from a doctor before birth or on the maternity ward was associated with less use of prelacteal food (AOR = 0.53; 95% CI AOR = 0.31–0.93), an increased use of colostrum (AOR = 3.30; 95% CI AOR = 1.16–9.37), but was not linked to the duration of exclusive breastfeeding (p = 0.1767). CONCLUSION: The current study indicates that breastfeeding information delivered by health care personnel in a non-trial setting may affect the infant feeding pattern including the use of prelacteal foods and colostrum. There was no evidence that the attitudes of the mother, or the infant's father or grandmother influenced actual feeding behavior. The lack of a "negative or neutral attitude" towards breastfeeding in the participants of the current study does, however, diminish the chances to link attitude to feeding behavior
Excess of serotonin affects neocortical pyramidal neuron migration
The serotonin transporter (SERT) is a key molecule involved in the homeostasis of extracellular levels of serotonin and is regulated developmentally. Genetic deletion of SERT in rodents increases extracellular levels of serotonin and affects cellular processes involved in neocortical circuit assembly such as barrel cortex wiring and cortical interneuron migration. Importantly, pharmacological blockade of SERT during brain development leads to phenotypes relevant to psychiatry in rodents and to an increased risk for autism spectrum disorders in humans. Furthermore, developmental adversity interacts with genetically-driven variations of serotonin function in humans and nonhuman primates to increase the risk for a variety of stress-related phenotypes. In this study, we investigate whether an excess of serotonin affects the migration of neocortical pyramidal neurons during development. Using in utero electroporation combined with time-lapse imaging to specifically monitor pyramidal neurons during late mouse embryogenesis, we show that an excess of serotonin reversibly affects the radial migration of pyramidal neurons. We further identify that the serotonin receptor 5-HT6 is expressed in pyramidal neuron progenitors and that 5-HT6 receptor activation replicates the effects of serotonin stimulation. Finally, we show that the positioning of superficial layer pyramidal neurons is altered in vivo in SERT knockout mice. Taken together, these results indicate that a developmental excess of serotonin decreases the migration speed of cortical pyramidal neurons, affecting a fundamental step in the assembly of neural circuits. These findings support the hypothesis that developmental dysregulation of serotonin homeostasis has detrimental effects on neocortical circuit formation and contributes to increased vulnerability to psychiatric disorders
Integrated Genomics Identifies Five Medulloblastoma Subtypes with Distinct Genetic Profiles, Pathway Signatures and Clinicopathological Features
BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children. Despite recent improvements in cure rates, prediction of disease outcome remains a major challenge and survivors suffer from serious therapy-related side-effects. Recent data showed that patients with WNT-activated tumors have a favorable prognosis, suggesting that these patients could be treated less intensively, thereby reducing the side-effects. This illustrates the potential benefits of a robust classification of medulloblastoma patients and a detailed knowledge of associated biological mechanisms. METHODS AND FINDINGS: To get a better insight into the molecular biology of medulloblastoma we established mRNA expression profiles of 62 medulloblastomas and analyzed 52 of them also by comparative genomic hybridization (CGH) arrays. Five molecular subtypes were identified, characterized by WNT signaling (A; 9 cases), SHH signaling (B; 15 cases), expression of neuronal differentiation genes (C and D; 16 and 11 cases, respectively) or photoreceptor genes (D and E; both 11 cases). Mutations in beta-catenin were identified in all 9 type A tumors, but not in any other tumor. PTCH1 mutations were exclusively identified in type B tumors. CGH analysis identified several fully or partly subtype-specific chromosomal aberrations. Monosomy of chromosome 6 occurred only in type A tumors, loss of 9q mostly occurred in type B tumors, whereas chromosome 17 aberrations, most common in medulloblastoma, were strongly associated with type C or D tumors. Loss of the inactivated X-chromosome was highly specific for female cases of type C, D and E tumors. Gene expression levels faithfully reflected the chromosomal copy number changes. Clinicopathological features significantly different between the 5 subtypes included metastatic disease and age at diagnosis and histology. Metastatic disease at diagnosis was significantly associated with subtypes C and D and most strongly with subtype E. Patients below 3 yrs of age had type B, D, or E tumors. Type B included most desmoplastic cases. We validated and confirmed the molecular subtypes and their associated clinicopathological features with expression data from a second independent series of 46 medulloblastomas. CONCLUSIONS: The new medulloblastoma classification presented in this study will greatly enhance the understanding of this heterogeneous disease. It will enable a better selection and evaluation of patients in clinical trials, and it will support the development of new molecular targeted therapies. Ultimately, our results may lead to more individualized therapies with improved cure rates and a better quality of life
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Evaluation of planar silicon pixel sensors with the RD53A readout chip for the Phase-2 Upgrade of the CMS Inner Tracker
Shared via Kudos: https://www.growkudos.com/publications/10.1088%25252F1748-0221%25252F18%25252F11%25252Fp11015The Large Hadron Collider at CERN will undergo an upgrade in order to increase its luminosity to 7.5 × 10^34 cm^-2s^-1. The increased luminosity during this High-Luminosity running phase, starting around 2029, means a higher rate of proton-proton interactions, hence a larger ionizing dose and particle fluence for the detectors. The current tracking system of the CMS experiment will be fully replaced in order to cope with the new operating conditions. Prototype planar pixel sensors for the CMS Inner Tracker with square 50 μm × 50 μm and rectangular 100 μm × 25 μm pixels read out by the RD53A chip were characterized in the lab and at the DESY-II testbeam facility in order to identify designs that meet the requirements of CMS during the High-Luminosity running phase. A spatial resolution of approximately 3.4 μm (2 μm) is obtained using the modules with 50 μm × 50 μm (100 μm × 25 μm) pixels at the optimal angle of incidence before irradiation. After irradiation to a 1 MeV neutron equivalent fluence of Φeq = 5.3 × 10^15 cm^-2, a resolution of 9.4 μm is achieved at a bias voltage of 800 V using a module with 50 μm × 50 μm pixel size. All modules retain a hit efficiency in excess of 99% after irradiation to fluences up to 2.1 × 10^16 cm^-2. Further studies of the electrical properties of the modules, especially crosstalk, are also presented in this paper.BMWFWandFWF(Austria);FNRSandFWO(Belgium);CERN;MSEandCSF(Croatia);Academy
of Finland, MEC, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF
(Germany); GSRT (Greece); NKFIA K124850, and Bolyai Fellowship of the Hungarian Academy of
Sciences (Hungary); DAE and DST (India); INFN (Italy); PAEC (Pakistan); SEIDI, CPAN, PCTI and
FEDER(Spain); Swiss Funding Agencies (Switzerland); MST (Taipei); STFC (United Kingdom);
DOEandNSF(U.S.A.). This project has received funding from the European Union’s Horizon 2020
research and innovation program under the Marie Skłodowska-Curie grant agreement No 884104
(PSI-FELLOW-III-3i) and project AIDA-2020, GA no. 654168. Individuals have received support
from HFRI (Greece)
In Silico Identification of Specialized Secretory-Organelle Proteins in Apicomplexan Parasites and In Vivo Validation in Toxoplasma gondii
Apicomplexan parasites, including the human pathogens Toxoplasma gondii and Plasmodium falciparum, employ specialized secretory organelles (micronemes, rhoptries, dense granules) to invade and survive within host cells. Because molecules secreted from these organelles function at the host/parasite interface, their identification is important for understanding invasion mechanisms, and central to the development of therapeutic strategies. Using a computational approach based on predicted functional domains, we have identified more than 600 candidate secretory organelle proteins in twelve apicomplexan parasites. Expression in transgenic T. gondii of eight proteins identified in silico confirms that all enter into the secretory pathway, and seven target to apical organelles associated with invasion. An in silico approach intended to identify possible host interacting proteins yields a dataset enriched in secretory/transmembrane proteins, including most of the antigens known to be engaged by apicomplexan parasites during infection. These domain pattern and projected interactome approaches significantly expand the repertoire of proteins that may be involved in host parasite interactions
The effects of Δ9-tetrahydrocannabinol on the dopamine system
Δ(9)-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, is a pressing concern to global mental health. Patterns of use are changing drastically due to legalisation, availability of synthetic analogues (‘spice’), cannavaping and aggrandizements in the purported therapeutic effects of cannabis. Many of THC’s reinforcing effects are mediated by the dopamine system. Due to complex cannabinoid-dopamine interactions there is conflicting evidence from human and animal research fields. Acute THC causes increased dopamine release and neuron activity, whilst long-term use is associated with blunting of the dopamine system. Future research must examine the long-term and developmental dopaminergic effects of the drug
Trapping in irradiated p-on-n silicon sensors at fluences anticipated at the HL-LHC outer tracker
The degradation of signal in silicon sensors is studied under conditions expected at the CERN High-Luminosity LHC. 200 m thick n-type silicon sensors are irradiated with protons of different energies to fluences of up to neq/cm. Pulsed red laser light with a wavelength of 672 nm is used to generate electron-hole pairs in the sensors. The induced signals are used to determine the charge collection efficiencies separately for electrons and holes drifting through the sensor. The effective trapping rates are extracted by comparing the results to simulation. The electric field is simulated using Synopsys device simulation assuming two effective defects. The generation and drift of charge carriers are simulated in an independent simulation based on PixelAV. The effective trapping rates are determined from the measured charge collection efficiencies and the simulated and measured time-resolved current pulses are compared. The effective trapping rates determined for both electrons and holes are about 50% smaller than those obtained using standard extrapolations of studies at low fluences and suggests an improved tracker performance over initial expectations
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Evaluation of HPK +- planar pixel sensors for the CMS Phase-2 upgrade
Data availability:
Data will be made available on request.The article archived on this institutional repository is a preprint made available on arXiv, arXiv:2212.04793v1 [physics.ins-det] (license: CC BY-NC-ND 4.0 - https://creativecommons.org/licenses/by-nc-nd/4.0/). It has not been certified by peer review. You are advised to consult the final version published by Elsevier at: https://doi.org/10.1016/j.nima.2023.168326 (the pubished version is copyright © 2023 Elsevier B.V. All rights reserved).To cope with the challenging environment of the planned high luminosity upgrade of the Large Hadron Collider (HL-LHC), scheduled to start operation in 2029, CMS will replace its entire tracking system. The requirements for the tracker are largely determined by the long operation time of 10 years with an instantaneous peak luminosity of up to 7.5 × 10^34 cm^−2^s−1 in the ultimate performance scenario. Depending on the radial distance from the interaction point, the silicon sensors will receive a particle fluence corresponding to a non-ionizing energy loss of up to Φeq = 3.5 × 10^16 cm^−2. This paper focuses on planar pixel sensor design and qualification up to a fluence of Φeq = 1.4 × 10^16 cm^−2. For the development of appropriate planar pixel sensors an R&D program was initiated, which includes n+-p sensors on 150 mm (6'') wafers with an active thickness of 150 μm with pixel sizes of 100 × 25 μm^2 and 50 × 50 μm^2 manufactured by Hamamatsu Photonics K.K. (HPK). Single chip modules with ROC4Sens and RD53A readout chips were made. Irradiation with protons and neutrons, as well was an extensive test beam campaign at DESY were carried out. This paper presents the investigation of various assemblies mainly with ROC4Sens readout chips. It demonstrates that multiple designs fulfill the requirements in terms of breakdown voltage, leakage current and efficiency. The single point resolution for 50 × 50 μm^2 pixels is measured as 4.0 μm for non-irradiated samples, and 6.3 μm after irradiation to Φeq = 7.2 × 10^15 cm^−2.This work was supported by the German Federal Ministry of Education and Research (BMBF) in the framework of the “FIS-Projekt - Fortführung des CMS-Experiments zum Einsatz am HL-LHC: Verbesserung des Spurdetektors für das Phase-2 Upgrade des CMS-Experiments” and supported by the H2020 project AIDA-2020, GA no. 654168. The measurements leading to these results have been performed at the Test Beam Facility at DESY Hamburg (Germany), a member of the Helmholtz Association (HGF).
The tracker groups gratefully acknowledge financial support from the following funding agencies: BMWFW and FWF (Austria); FNRS, Belgium and FWO (Belgium); CERN, Switzerland; MSE and CSF (Croatia); Academy of Finland, Finland, MEC, Canada, and HIP (Finland); CEA, United States and CNRS/IN2P3 (France); BMBF, DFG, United States, and HGF (Germany); GSRT (Greece); NKFIA K124850, and Bolyai Fellowship of the Hungarian Academy of Sciences (Hungary); DAE, India and DST (India); INFN (Italy); PAEC (Pakistan); SEIDI, Spain, CPAN, PCTI and FEDER (Spain); Swiss Funding Agencies (Switzerland); MST (Taipei); STFC (United Kingdom); DOE and NSF (U.S.A.). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 884104 (PSI-FELLOW-III-3i). Individuals have received support from HFRI (Greece)
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