Socio-cultural Perspectives of Latino Children with Autism and their Families.

Factors affecting disparities in early diagnosis and care for Latino children with autism spectrum disorders (ASD) are reviewed through a socio-cultural lens. Other models of disparities do not include the expansive factors that contribute to disparities among Latino children nor do they incorporate the family experience raising a child with autism. This dissertation provides a summary model that serves as a foundation for two studies. Study 1 applies the summary model to Latino families raising children with ASD. The findings suggest that Latina mothers reported lower levels of family burden and pessimism compared to White mothers and endorsed positively worded items on family well-being and functioning. Study 2 tests the feasibility of a novel intervention that blends evidence-based practices for autism with culturally informed practices to specifically meet the needs of Latino children and families. Spanish speaking Latina immigrant mothers of children with autism participated in two eight session modules about general autism knowledge and services, advocacy skills, and strategies to work with their children. Post-test data revealed mothers reported increased knowledge about autism, better understanding of how to advocate for their children and themselves, and increased efficacy in using intervention strategies compared to their pre-tests. Suggestions for future research in psychology, and social work practice to improve the development and implementation of policies for and practice with Latino children with ASD and their families are discussed.PHDSocial Work and PsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/100011/1/klopez_1.pd

Insulin gene polymorphisms in type I diabetes, Addison's disease and the polyglandular autoimmune syndrome type II

Background: Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from ß-cell autoimmunity. Methods: We investigated the role of the -2221Msp(C/T) and -23HphI(A/T) polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (T1D, n = 317), Addison´s disease (AD, n = 107) or Hashimoto´s thyroiditis (HT, n = 61)], those with a polyglandular autoimmune syndrome type II (combination of T1D and/or AD with HT or GD, n = 62) as well as in healthy controls (HC, n = 275). Results: T1D patients carried significantly more often the homozygous genotype "CC" -2221Msp(C/T) and "AA" -23HphI(A/T) polymorphisms than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 × 10-8, respectively). The distribution of insulin gene polymorphisms did not show significant differences between patients with AD, HT, or APS-II and HC. Conclusion: We demonstrate that the allele "C" of the -2221Msp(C/T) and "A" -23HphI(A/T) insulin gene polymorphisms confer susceptibility to T1D but not to isolated AD, HT or as a part of the APS-II

Design of a watershed-based nitrogen trading system or the Big and Little Wood Rivers Watershed

Thesis (M.Eng.)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering, 2003.Includes bibliographical references (leaves 68-71).A watershed-based nitrogen trading system was designed for the Big and Little Wood Rivers Watershed in south-central Idaho as a policy tool to help manage increasing nitrogen loads within the Watershed. The study was performed on behalf of the Blaine County Commissioners in response to concerns regarding increasing population growth and nitrogen loading in the Watershed. A trading framework was developed based on case studies and existing trading frameworks. The developed framework included selection of a trading arrangement, development of a trading cap, design of a credit distribution system, establishment of a trading ratio, and qualification of transaction costs. Potential problems with trading, including administration of the trading program, pre-quantification of transaction costs, uncertainty in data collection and source monitoring, spatial and temporal distribution of pollutants, and enforcement of the trading program, are discussed. A water balance was completed in order to understand the hydrologic conditions of the Watershed. Water inflow for the Watershed included 2.24 kg3/yr of precipitation. Water outflows for the Watershed included 1.87 kg3/yr of evapotranspiration and 0.33 kg3/yr of surface water outflow. A point source/non-point source trading arrangement was set for the Watershed based on the currently high proportion of nonpoint nitrogen sources (e.g. agricultural lands and rangeland) and the future potential for increases in the proportion of nitrogen from point sources (e.g. wastewater treatment plants). A yearly nitrogen cap in the range of 569,300 kg/yr and 720,500 kg/yr was suggested for the Watershed. This range was based on estimates for actual nitrogen stream flow concentration and loading within the Watershed and acceptable nitrogen concentration values from EPA Ecosystem classification data, trophic states, and published data. Trading credits would be distributed to point sources in proportion to their current acceptable discharge levels and to non-point sources in proportion to the amount of land used for agriculture or ranging. The trading ratio set between point and non-point sources varied continuously between 1:1 and 1:2.6 depending on the distance of the non-point source from the river.by Kristina Elizabeth Lopez-Bernal.M.Eng

Reducing Down(stream)time: Pretraining Molecular GNNs using Heterogeneous AI Accelerators

The demonstrated success of transfer learning has popularized approaches that involve pretraining models from massive data sources and subsequent finetuning towards a specific task. While such approaches have become the norm in fields such as natural language processing, implementation and evaluation of transfer learning approaches for chemistry are in the early stages. In this work, we demonstrate finetuning for downstream tasks on a graph neural network (GNN) trained over a molecular database containing 2.7 million water clusters. The use of Graphcore IPUs as an AI accelerator for training molecular GNNs reduces training time from a reported 2.7 days on 0.5M clusters to 1.2 hours on 2.7M clusters. Finetuning the pretrained model for downstream tasks of molecular dynamics and transfer to a different potential energy surface took only 8.3 hours and 28 minutes, respectively, on a single GPU.Comment: Machine Learning and the Physical Sciences Workshop at the 36th conference on Neural Information Processing Systems (NeurIPS

Computational methods to analyze and predict the binding mode of inhibitors targeting both human and mushroom tyrosinase

Tyrosinase, a copper-containing enzyme critical in melanin biosynthesis, is a key drug target for hyperpigmentation and melanoma in humans. Testing the inhibitory effects of compounds using tyrosinase from Agaricus bisporus (AbTYR) has been a common practice to identify potential therapeutics from synthetic and natural sources. However, structural diversity among human tyrosinase (hTYR) and AbTYR presents a challenge in developing drugs that are therapeutically effective. In this study, we combined retrospective and computational analyses with experimental data to provide insights into the development of new inhibitors targeting both hTYR and AbTYR. We observed contrasting effects of Thiamidol™ and our 4-(4-hydroxyphenyl)piperazin-1-yl-derivative (6) on both enzymes; based on this finding, we aimed to investigate their binding modes in hTYR and AbTYR to identify residues that significantly improve affinity. All the information led to the discovery of compound [4-(4-hydroxyphenyl)piperazin-1-yl](2-methoxyphenyl)methanone (MehT-3, 7), which showed comparable activity on AbTYR (IC50 = 3.52 μM) and hTYR (IC50 = 5.4 μM). Based on these achievements we propose the exploitation of our computational results to provide relevant structural information for the development of newer dual-targeting molecules, which could be preliminarily tested on AbTYR as a rapid and inexpensive screening procedure before being tested on hTYR

Towards dating prehistoric rock art from central Iberia using luminescence from rock surfaces

Rock art is notoriously difficult to date numerically using established geochronological techniques. Recently, optically stimulated luminescence (OSL) rock surface dating has been used successfully to constrain the age of a Native American rock art in Utah, USA (Chapot et al., 2012). In this study, we follow a similar approach to constrain the age of two important rock art sites in the Iberian Peninsula: i) a Levantine Style rock art (Peña del Escrito, Villar del Humo, ~300 km SE of Madrid) characterised by naturalistic depictions and scenes of people and animals interacting, and ii) a Schematic rock art (Peña Escrita, Fuencaliente, ~400 km S of Madrid) of a more abstract style with human- and animal-like figures and more abstract elements as the main features. The time frame of the Levantine Style is controversial with dates proposed from before and after the Neolithic. In contrast, the Schematic Style is traditionally considered to be of Chalcolithic or Bronze Age. At both sites, rockfall has removed a part of the rock art and buried it on the toe of the cliff. For luminescence measurements, we collected three samples from the pigmented buried rock face at the sandstone Levantine Style site and a similar one from the quartzite Schematic Style site, together with corresponding dose rate samples from the underlying sediment/rock. Whole rock samples were cut in the usual manner and the luminescence signals measured as a function of depth. The sandstone samples have a weak fast-component OSL signal but are dominated by IRSL. In contrast, the quartzite sample is dominated by a strong fast component OSL signal with only weak IRSL. As expected, the observed OSL and IRSL profiles all show evidence of light exposure prior to burial. We present these profiles and relevant luminescence characteristics for the two styles of rock art

Addressing the Supportive Transportation Challenges of Community-Residing Older Adults

The ability to get to where you want to go, when you want to go there is a key factor for aging-in-place in our communities. It is often taken for granted until that ability is compromised. The informal network of family and friends, if it exists, is not likely to be a sustainable transportation alternative for persons with cognitive impairment or for older adults with limitations that may not fit eligibility criteria for senior transportation services, where they exist. The purpose of this study was to investigate the potential of communities to address the specialized supportive mobility needs of community-residing older adults. A major conclusion to emerge from the research is the connection of mobility to healthcare

Beyond On-Hold Messages: Conversational Time-Buying in Task-Oriented Dialogue

Lopez Gambino MS, Zarrieß S, Schlangen D. Beyond On-Hold Messages: Conversational Time-Buying in Task-Oriented Dialogue. In: Jokinen K, Stede M, DeVault D, Louis A, eds. 18th Annual Meeting of the Special Interest Group on Discourse and Dialogue. Proceedings of the conference. 2017: 241-246

Generation of Leukaemia-Derived Dendritic Cells (DCleu) to improve anti-leukaemic activity in AML: selection of the most efficient response modifier combinations

Dendritic cells (DC) and leukaemia derived DC (DC(leu)) are potent stimulators of anti-leukaemic activity in acute myeloid leukaemia (AML) and can be generated from mononuclear cells in vitro following standard DC/DC(leu)-generating protocols. With respect to future clinical applications though, DC/DC(leu)-generating protocols specifically designed for application in a whole-blood-(WB)-environment must be established. Therefore, we developed ten new DC/DC(leu)-generating protocols (kits; Kit-A/-C/-D/-E/-F/-G/-H/-I/-K/-M) for the generation of DC/DC(leu) from leukaemic WB, containing calcium-ionophore, granulocyte-macrophage-colony-stimulating-factor (GM-CSF), tumour-necrosis-factor-alpha, prostaglandin-E(1) (PGE(1)), prostaglandin-E(2) (PGE(2)) and/or picibanil (OK-432). All protocols were evaluated regarding their performance in generating DC/DC(leu) using refined classification and/or ranking systems; DC/DC(leu) were evaluated regarding their performance in stimulating anti-leukaemic activity using a cytotoxicity fluorolysis assay. Overall, we found the new kits capable to generate (mature) DC/DC(leu) from leukaemic WB. Through refined classification and ranking systems, we were able to select Kit-I (GM-CSF + OK-432), -K (GM-CSF + PGE(2)) and -M (GM-CSF + PGE(1)) as the most efficient kits in generating (mature) DC/DC(leu), which are further competent to stimulate immunoreactive cells to show an improved anti-leukaemic cytotoxicity as well. This great performance of Kit-I, -K and -M in mediating DC/DC(leu)-based anti-leukaemic immunity in a WB-environment in vitro constitutes an important and directive step for translating DC/DC(leu)-based immunotherapy of AML into clinical application

Polybrominated Diphenyl Ethers (PBDEs) and Bioaccumulative Hydroxylated PBDE Metabolites in Young Humans from Managua, Nicaragua

OBJECTIVE: Our aim was to investigate exposure to polybrominated diphenyl ethers (PBDEs) in a young urban population in a developing country, with focus on potentially highly exposed children working informally as scrap scavengers at a large municipal waste disposal site. We also set out to investigate whether hydroxylated metabolites, which not hitherto have been found retained in humans, could be detected. METHODS: We assessed PBDEs in pooled serum samples obtained in 2002 from children 11-15 years of age, working and sometimes also living at the municipal waste disposal site in Managua, and in nonworking urban children. The influence of fish consumption was evaluated in the children and in groups of women 15-44 years of age who differed markedly in their fish consumption. Hydroxylated PBDEs were assessed as their methoxylated derivates. The chemical analyses were performed by gas chromatography/mass spectrometry, using authentic reference substances. RESULTS: The children living and working at the waste disposal site showed very high levels of medium brominated diphenyl ethers. The levels observed in the referent children were comparable to contemporary observations in the United States. The exposure pattern was consistent with dust being the dominating source. The children with the highest PBDE levels also had the highest levels of hydroxylated metabolites. CONCLUSIONS: Unexpectedly, very high levels of PBDEs were found in children from an urban area in a developing country. Also, for the first time, hydroxylated PBDE metabolites were found to bioaccumulate in human serum