Time and Space Use of Adults with Intellectual Disabilities

Purpose: This study analyzed the time and space use of adults with intellectual disabilities (ID) in order to better understand the occupational patterns of this population. Methods: Time and space use data were collected through observation of 15 adults with ID during 4-hour periods on typical weekdays and weekend days. Data were coded into 12 time and 10 space use descriptive categories. Results: The participants used a greater variety of locations during weekdays that contributed to greater amounts of weekday time spent in a wider variety of activity categories. In contrast, the participants spent a majority of the observed weekend day time in the group home with less activity variety. Although the participants in this study lived in group homes and participated in day habilitation programs or supported employment, a majority of their midday time use occurred in passive activity categories in a minimum variety of locations. These results may be due to the types of activities offered by structured day habilitation programs and group homes. Conclusion: Occupational therapists may be key players to enhance the environments of people with ID by providing direct service and staff training to facilitate more diversity of active use of time and space for adults with ID

Saturation of a spin 1/2 particle by generalized Local control

We show how to apply a generalization of Local control design to the problem of saturation of a spin 1/2 particle by magnetic fields in Nuclear Magnetic Resonance. The generalization of local or Lyapunov control arises from the fact that the derivative of the Lyapunov function does not depend explicitly on the control field. The second derivative is used to determine the local control field. We compare the efficiency of this approach with respect to the time-optimal solution which has been recently derived using geometric methods.Comment: 12 pages, 4 figures, submitted to new journal of physics (2011

Advanced Multilevel Node Separator Algorithms

A node separator of a graph is a subset S of the nodes such that removing S and its incident edges divides the graph into two disconnected components of about equal size. In this work, we introduce novel algorithms to find small node separators in large graphs. With focus on solution quality, we introduce novel flow-based local search algorithms which are integrated in a multilevel framework. In addition, we transfer techniques successfully used in the graph partitioning field. This includes the usage of edge ratings tailored to our problem to guide the graph coarsening algorithm as well as highly localized local search and iterated multilevel cycles to improve solution quality even further. Experiments indicate that flow-based local search algorithms on its own in a multilevel framework are already highly competitive in terms of separator quality. Adding additional local search algorithms further improves solution quality. Our strongest configuration almost always outperforms competing systems while on average computing 10% and 62% smaller separators than Metis and Scotch, respectively

Hospital outbreak of carbapenem-resistant Enterobacterales associated with a bla OXA-48 plasmid carried mostly by Escherichia coli ST399

A hospital outbreak of carbapenem-resistant Enterobacterales was detected by routine surveillance. Whole genome sequencing and subsequent analysis revealed a conserved promiscuous blaOXA-48 carrying plasmid as the defining factor within this outbreak. Four different species of Enterobacterales were involved in the outbreak. Escherichia coli ST399 accounted for 35 of all the 55 isolates. Comparative genomics analysis using publicly available E. coli ST399 genomes showed that the outbreak E. coli ST399 isolates formed a unique clade. We developed a mathematical model of pOXA-48-like plasmid transmission between host lineages and used it to estimate its conjugation rate, giving a lower bound of 0.23 conjugation events per lineage per year. Our analysis suggests that co-evolution between the pOXA-48-like plasmid and E. coli ST399 could have played a role in the outbreak. This is the first study to report carbapenem-resistant E. coli ST399 carrying blaOXA-48 as the main cause of a plasmid-borne outbreak within a hospital setting. Our findings suggest complementary roles for both plasmid conjugation and clonal expansion in the emergence of this outbreak

Beef quality differentiation in the framework of the Serrana de Teruel endangered breed conservation programme

La Serrana de Teruel es una raza bovina en peligro de extinción, criada tradicionalmente en áreas montañosas del Sur de Aragón (España). Con objeto de recuperar la raza, se realizó la caracterización morfológica, zootécnica y genética de la población existente. La raza presentó un grado medio-alto de armonía y homogeneidad, siendo la mayoría de individuos de perfil recto, eumétricos y sublongilíneos, aunque de menor tamaño al observado en otras razas filogenéticamente próximas. Los estudios de biodiversidad mostraron niveles altos de variabilidad genética y bajos de consanguinidad, a pesar del censo reducido (240 individuos en 2010), y proporcionaron las bases para llevar a cabo un programa sostenible de conservación. Para garantizar su mantenimiento a largo plazo, los bancos de germoplasma mantienen 6400 dosis de semen y 74 embriones. Paralelamente, se analizó la viabilidad comercial de la raza, a través del estudio de la calidad de canal y carne de las categorías comerciales de ternero, añojo y cebón (castrados con 9 meses), con edades a sacrificio de 12, 22 y 22 meses y pesos vivos de 470, 720 y 660 kg, respectivamente. Finalmente, se realizó un análisis prospectivo, según la opinión de expertos, de una nueva carne de vacuno con denominación de calidad, llamada ‘Serrana de Teruel’. Estos trabajos muestran la posibilidad de realizar una producción alternativa, tipo cebón, susceptible de acogerse a distintivos de calidad diferenciada, que podrían suponer un incentivo para la explotación de la Serrana de Teruel frente a otras razas, lo que favorecería su conservación a medio plazo.Serrana de Teruel is an endangered cattle breed raised traditionally in the mountainous areas of Southern Aragon (Spain). With the aim of recovering the breed, a characterization was carried out to determine the morphology, husbandry and genetic values of the Serrana de Teruel breed. Individuals showed a medium to high degree of homogeneity and harmony, most of the animals being of straight profile, and eumetrical and sublongilineal individuals, although smaller in size than other phylogenetically proximate breeds. Biodiversity studies showed good diversity values despite the breed’s low effective population size (240 individuals in 2010). These studies provided the basis for a sustainable programme of genetic conservation. In order to guarantee long-term maintenance, germplasm banks contain 6400 doses of semen and 74 embryos. Concurrently, the commercial viability of the breed was studied by means of an analysis of carcass and meat quality from three commercial categories – yearling, bull and steer (castrated at 9 months old) – with ages at slaughter of 12, 22 and 22 months and live weights of 470, 720 and 660 kg,, respectively. Good performances and high-quality products with no commercial constraints in the beef market were obtained. Finally, a prospective study for a new beef quality product labelled ‘Serrana de Teruel’ was performed, according to the opinions of experts. These studies provide the standard requirements for the alternative production of a labelled beef product that might create an incentive for the production of the Serrana de Teruel breed among other breeds, and thus favour the conservation of the breed in the medium termLa Serrana de Teruel est une race bovine rustique élevée dans les régions montagneuses du sud de l’Aragon (Espagne) qui est en danger d’extinction. Afin de récupérer cette race on a réalisé la caractérisation morphologique, génétique et zootechnique de la population existante. La race présente un degré moyen-élevé d’harmonie et d’uniformité, la plupart des animaux étant de profil droit, eumétrique et sublongiligne, bien que plus petit en taille que les autres races proches. Des études sur la biodiversité ont montré des niveaux élevés de diversité génétique et un faible niveau de consanguinité, malgré les effectifs limités d’animaux (240 individus en 2010), en fournissant les bases du programme de conservation. Afin de garantir le maintien à long terme, a été créée une banque de matériel génétique contenant 6400 doses de semence et 74 embryons. En parallèle, on a confirmé la viabilité commerciale de la race à travers l’étude de la qualité de la carcasse et de la viande pour les catégories commerciales de veau, taurillon et bouvillons (castrés à 9 mois), avec des âges à l’abattage de 12, 22 et 22 mois, et 470, 720 et 660 kg de poids vif, respectivement. Enfin, nous avons mené une analyse prospective, à dires d’experts, pour un nouveau label de qualité du boeuf appelé ‘Serrana de Teruel’. Ces travaux montrent la possibilité d’une production alternative, comme boeuf, susceptible de bénéficier d’une certification de qualité, ce qui pourrait créer une incitation pour l’exploitation de la Serrana de Teruel parmi les autres races, et ainsi favoriser sa préservation à long termePublishe

Class II MHC Self-Antigen Presentation in Human B and T Lymphocytes

Human CD4[superscript +] T cells process and present functional class II MHC-peptide complexes, but the endogenous peptide repertoire of these non-classical antigen presenting cells remains unknown. We eluted and sequenced HLA-DR-bound self-peptides presented by CD4[superscript +] T cells in order to compare the T cell-derived peptide repertoire to sequences derived from genetically identical B cells. We identified several novel epitopes derived from the T cell-specific proteome, including fragments of CD4 and IL-2. While these data confirm that T cells can present peptides derived from the T-cell specific proteome, the vast majority of peptides sequenced after elution from MHC were derived from the common proteome. From this pool, we identified several identical peptide epitopes in the T and B cell repertoire derived from common endogenous proteins as well as novel endogenous epitopes with promiscuous binding. These findings indicate that the endogenous HLA-DR-bound peptide repertoire, regardless of APC type and across MHC isotype, is largely derived from the same pool of self-protein.National Institutes of Health (U.S.) (grant P01AI039671)National Institutes of Health (U.S.) (P01AI045757

Expression profiling of clonal lymphocyte cell cultures from Rett syndrome patients

BACKGROUND: More than 85% of Rett syndrome (RTT) patients have heterozygous mutations in the X-linked MECP2 gene which encodes methyl-CpG-binding protein 2, a transcriptional repressor that binds methylated CpG sites. Because MECP2 is subject to X chromosome inactivation (XCI), girls with RTT express either the wild type or mutant MECP2 in each of their cells. To test the hypothesis that MECP2 mutations result in genome-wide transcriptional deregulation and identify its target genes in a system that circumvents the functional mosaicism resulting from XCI, we performed gene expression profiling of pure populations of untransformed T-lymphocytes that express either a mutant or a wild-type allele. METHODS: Single T lymphocytes from a patient with a c.473C>T (p.T158M) mutation and one with a c.1308-1309delTC mutation were subcloned and subjected to short term culture. Gene expression profiles of wild-type and mutant clones were compared by oligonucleotide expression microarray analysis. RESULTS: Expression profiling yielded 44 upregulated genes and 77 downregulated genes. We compared this gene list with expression profiles of independent microarray experiments in cells and tissues of RTT patients and mouse models with Mecp2 mutations. These comparisons identified a candidate MeCP2 target gene, SPOCK1, downregulated in two independent microarray experiments, but its expression was not altered by quantitative RT-PCR analysis on brain tissues from a RTT mouse model. CONCLUSION: Initial expression profiling from T-cell clones of RTT patients identified a list of potential MeCP2 target genes. Further detailed analysis and comparison to independent microarray experiments did not confirm significantly altered expression of most candidate genes. These results are consistent with other reported data

Exaggerated CpH methylation in the autism-affected brain

BACKGROUND: The etiology of autism, a complex, heritable, neurodevelopmental disorder, remains largely unexplained. Given the unexplained risk and recent evidence supporting a role for epigenetic mechanisms in the development of autism, we explored the role of CpG and CpH (H = A, C, or T) methylation within the autism-affected cortical brain tissue. METHODS: Reduced representation bisulfite sequencing (RRBS) was completed, and analysis was carried out in 63 post-mortem cortical brain samples (Brodmann area 19) from 29 autism-affected and 34 control individuals. Analyses to identify single sites that were differentially methylated and to identify any global methylation alterations at either CpG or CpH sites throughout the genome were carried out. RESULTS: We report that while no individual site or region of methylation was significantly associated with autism after multi-test correction, methylated CpH dinucleotides were markedly enriched in autism-affected brains (~2-fold enrichment at p < 0.05 cutoff, p = 0.002). CONCLUSIONS: These results further implicate epigenetic alterations in pathobiological mechanisms that underlie autism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13229-017-0119-y) contains supplementary material, which is available to authorized users

A meta-analysis of pre-pregnancy maternal body mass index and placental DNA methylation identifies 27 CpG sites with implications for mother-child health

Higher maternal pre-pregnancy body mass index (ppBMI) is associated with increased neonatal morbidity, as well as with pregnancy complications and metabolic outcomes in offspring later in life. The placenta is a key organ in fetal development and has been proposed to act as a mediator between the mother and different health outcomes in children. The overall aim of the present work is to investigate the association of ppBMI with epigenome-wide placental DNA methylation (DNAm) in 10 studies from the PACE consortium, amounting to 2631 mother-child pairs. We identify 27 CpG sites at which we observe placental DNAm variations of up to 2.0% per 10 ppBMI-unit. The CpGs that are differentially methylated in placenta do not overlap with CpGs identified in previous studies in cord blood DNAm related to ppBMI. Many of the identified CpGs are located in open sea regions, are often close to obesity-related genes such as GPX1 and LGR4 and altogether, are enriched in cancer and oxidative stress pathways. Our findings suggest that placental DNAm could be one of the mechanisms by which maternal obesity is associated with metabolic health outcomes in newborns and children, although further studies will be needed in order to corroborate these findings.We would like to thank the Pregnancy and Childhood Epigenetics (PACE) consortium, as well as all the families that participated in these studies for their generous contribution. This work was partially funded by GVSAN2018111086 from the Basque Department of Health and PI18/01142 from ISCIII - Spanish Ministry of Science and Innovation - cofounded by the ERDF “A way to make Europe” to JRB and LSM, respectively; and by the Joint Programming Initiative – A Healthy Diet for a Healthy Life (JPI HDHL) (NutriPROGRAM). ACP was supported by grant GVSAN2019111085 from the Basque Department of Health to NFJ. Detailed acknowledgements and funding for each participating cohort are described in Supplementary Note 1