91 research outputs found

    Joint attention revisited: Finding strengths among children with autism

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    Differences in joint attention (JA) are prominent for some children with autism and are often used as an indicator of the disorder. This study examined the JA competencies of young children with autism who demonstrated JA ability and compared them to children with developmental delays. Method: Forty children with autism and developmental delays were matched pairwise based on mental and chronological age. Videos of children engaging in play were coded for the frequency and forms (eye contact, gestures, affect, etc.) of JA. Additionally, concurrent language was compared among children with autism (N=32) by their JA ability. Results: Children with ASD entered into JA significantly less often than children with DD but once engaged, used the forms of JA similarly. For the matched pairs there were no differences in language but the children with autism who used JA had significantly better language than children with autism who did not (even after controlling for mental age). Conclusions: There is a group of young children with autism who can use JA but do so at lower frequencies than children with DD. Possible reasons include difficulty disengaging attention and limited intrinsic social motivation to share. Adult persistence is recommended to encourage JA

    Joint attention revisited: examining heterogeneity among children with autism

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    Joint attention has long been considered absent or deviant in children with autism. Although this deficit is seen, there is variability in joint attention within the population; some children with autism employ joint attention. Little is known about the profile of joint attention skills of these children or how joint attention use affects concurrent language. The present investigation examines the subgroup of children with autism who use joint attention and compares them both to children with autism who do not use joint attention and to pair-wise matched children with developmental disabilities. Two analyses were undertaken: Study 1 compared subgroups of children with autism (MA< 30 months). Thirty-two children with autism (16 with joint attention skills and 16 without) of similar age (M=43 months) and nonverbal MA scores were examined. The results of Study 1 indicated that children with joint attention skills had significantly higher concurrent language scores than those without. Study 2 compared 20 pairs of MA-matched children (20 children with autism and joint attention and 20 with developmental delays). Videos were coded for initiation and response to joint attention and many of its forms. The results from Study 2 showed that once engaged in joint attention bids, both groups used the forms in similar ways; no differences were found in point, show, other gestures, eye contact, affect, nor toward whom the bid was directed. Conversely, children with autism initiated significantly less frequently and adults offered them more bids in order to engage them in joint attention. Concurrent language scores of the matched groups were not significantly different. This investigation demonstrates that there is a subgroup of children with autism that uses joint attention. They use the forms in similar ways to children with developmental delays but engage in bids less frequently. Possible reasons for fewer bids are that children with autism are not intrinsically motivated to participate in social sharing and they have difficulty disengaging from a current focus of attention. Intervention recommendations include a goodness-of-fit model employing joint attention intervention for children from the lowest ability group and social/language interventions for others

    Prevalence and Risk Factors Associated With Long-term Opioid Use After Injury Among Previously Opioid-Free Workers

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    Importance Using opioids for acute pain can lead to long-term use and associated morbidity and mortality. Injury has been documented as a gateway to long-term opioid use in some populations, but data are limited for injured workers. Objective To evaluate the prevalence and risk factors of long-term opioid use after injury among workers in Tennessee who were opioid free at the time of injury. Design, Setting, and Participants This cohort study identified injured workers aged 15 to 99 years who reported only 1 injury to the Tennessee Bureau of Workers’ Compensation from March 2013 to December 2015 and had no opioid prescription in the 60 days before injury. Participants were matched to their prescription history in Tennessee’s prescription drug monitoring program. Analysis was conducted from November 2017 to March 2018. Logistic regression models were used to calculate adjusted odds ratios (ORs) and 95% CIs for associations of demographic, injury, and opioid use variables with long-term use. Main Outcomes and Measures The primary outcome was long-term opioid use, defined as having an opioid supplied for 45 or more days in the 90 days after injury. Results Among 58 278 injured workers who received opioids after injury (18 977 [32.5%] aged 15-34 years, 27 514 [47.2%] aged 35-54 years, and 11 787 [20.2%] aged 55-99 years; 32 607 [56.0%] men), 46 399 (79.6%) were opioid free at the time of injury. Among opioid-free injured workers, 1843 (4.0%) began long-term opioid use. After controlling for covariates, long-term use was associated with receiving 20 or more days’ supply in the initial opioid prescription compared with receiving less than 5 days’ supply (OR, 28.94; 95% CI, 23.44-35.72) and visiting 3 or more prescribers in the 90 days after injury compared with visiting 1 prescriber (OR, 14.91; 95% CI, 12.15-18.29). However, even just 5 days’ to 9 days’ supply was associated with an increase in the odds of long-term use compared with less than 5 days’ supply (OR, 1.83; 95% CI, 1.56-2.14). Conclusions and Relevance In this study of injured workers, injury was associated with long-term opioid use. The number of days’ supply of the initial opioid prescription was the strongest risk factor of developing long-term use, highlighting the importance of careful prescribing for initial opioid prescriptions

    Elimination of visceral leishmaniasis in the Indian subcontinent: a comparison of predictions from three transmission models.

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    We present three transmission models of visceral leishmaniasis (VL) in the Indian subcontinent (ISC) with structural differences regarding the disease stage that provides the main contribution to transmission, including models with a prominent role of asymptomatic infection, and fit them to recent case data from 8 endemic districts in Bihar, India. Following a geographical cross-validation of the models, we compare their predictions for achieving the WHO VL elimination targets with ongoing treatment and vector control strategies. All the transmission models suggest that the WHO elimination target (<1 new VL case per 10,000 capita per year at sub-district level) is likely to be met in Bihar, India, before or close to 2020 in sub-districts with a pre-control incidence of 10 VL cases per 10,000 people per year or less, when current intervention levels (60% coverage of indoor residual spraying (IRS) of insecticide and a delay of 40days from onset of symptoms to treatment (OT)) are maintained, given the accuracy and generalizability of the existing data regarding incidence and IRS coverage. In settings with a pre-control endemicity level of 5/10,000, increasing the effective IRS coverage from 60 to 80% is predicted to lead to elimination of VL 1-3 years earlier (depending on the particular model), and decreasing OT from 40 to 20days to bring elimination forward by approximately 1year. However, in all instances the models suggest that L. donovani transmission will continue after 2020 and thus that surveillance and control measures need to remain in place until the longer-term aim of breaking transmission is achieved

    Mechanism of Disruption of the Amt-GlnK Complex by PII-Mediated Sensing of 2-Oxoglutarate

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    GlnK proteins regulate the active uptake of ammonium by Amt transport proteins by inserting their regulatory T-loops into the transport channels of the Amt trimer and physically blocking substrate passage. They sense the cellular nitrogen status through 2-oxoglutarate, and the energy level of the cell by binding both ATP and ADP with different affinities. The hyperthermophilic euryarchaeon Archaeoglobus fulgidus possesses three Amt proteins, each encoded in an operon with a GlnK ortholog. One of these proteins, GlnK2 was recently found to be incapable of binding 2-OG, and in order to understand the implications of this finding we conducted a detailed structural and functional analysis of a second GlnK protein from A. fulgidus, GlnK3. Contrary to Af-GlnK2 this protein was able to bind both ATP/2-OG and ADP to yield inactive and functional states, respectively. Due to the thermostable nature of the protein we could observe the exact positioning of the notoriously flexible T-loops and explain the binding behavior of GlnK proteins to their interaction partner, the Amt proteins. A thermodynamic analysis of these binding events using microcalorimetry evaluated by microstate modeling revealed significant differences in binding cooperativity compared to other characterized PII proteins, underlining the diversity and adaptability of this class of regulatory signaling proteins

    Viral to metazoan marine plankton nucleotide sequences from the Tara Oceans expedition

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    A unique collection of oceanic samples was gathered by the Tara Oceans expeditions (2009–2013), targeting plankton organisms ranging from viruses to metazoans, and providing rich environmental context measurements. Thanks to recent advances in the field of genomics, extensive sequencing has been performed for a deep genomic analysis of this huge collection of samples. A strategy based on different approaches, such as metabarcoding, metagenomics, single-cell genomics and metatranscriptomics, has been chosen for analysis of size-fractionated plankton communities. Here, we provide detailed procedures applied for genomic data generation, from nucleic acids extraction to sequence production, and we describe registries of genomics datasets available at the European Nucleotide Archive (ENA, www.ebi.ac.uk/ena). The association of these metadata to the experimental procedures applied for their generation will help the scientific community to access these data and facilitate their analysis. This paper complements other efforts to provide a full description of experiments and open science resources generated from the Tara Oceans project, further extending their value for the study of the world’s planktonic ecosystems

    The Monarch Initiative in 2024: an analytic platform integrating phenotypes, genes and diseases across species.

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    Bridging the gap between genetic variations, environmental determinants, and phenotypic outcomes is critical for supporting clinical diagnosis and understanding mechanisms of diseases. It requires integrating open data at a global scale. The Monarch Initiative advances these goals by developing open ontologies, semantic data models, and knowledge graphs for translational research. The Monarch App is an integrated platform combining data about genes, phenotypes, and diseases across species. Monarch\u27s APIs enable access to carefully curated datasets and advanced analysis tools that support the understanding and diagnosis of disease for diverse applications such as variant prioritization, deep phenotyping, and patient profile-matching. We have migrated our system into a scalable, cloud-based infrastructure; simplified Monarch\u27s data ingestion and knowledge graph integration systems; enhanced data mapping and integration standards; and developed a new user interface with novel search and graph navigation features. Furthermore, we advanced Monarch\u27s analytic tools by developing a customized plugin for OpenAI\u27s ChatGPT to increase the reliability of its responses about phenotypic data, allowing us to interrogate the knowledge in the Monarch graph using state-of-the-art Large Language Models. The resources of the Monarch Initiative can be found at monarchinitiative.org and its corresponding code repository at github.com/monarch-initiative/monarch-app
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