To demonstrate the capability of computer vision analysis to detect atypical orienting and attention behaviors in toddlers with autism spectrum disorder. One hundered and four toddlers of 16–31 ...months old (mean = 22) participated in this study. Twenty-two of the toddlers had autism spectrum disorder and 82 had typical development or developmental delay. Toddlers watched video stimuli on a tablet while the built-in camera recorded their head movement. Computer vision analysis measured participants’ attention and orienting in response to name calls. Reliability of the computer vision analysis algorithm was tested against a human rater. Differences in behavior were analyzed between the autism spectrum disorder group and the comparison group. Reliability between computer vision analysis and human coding for orienting to name was excellent (intra-class coefficient 0.84, 95% confidence interval 0.67–0.91). Only 8% of toddlers with autism spectrum disorder oriented to name calling on >1 trial, compared to 63% of toddlers in the comparison group (p = 0.002). Mean latency to orient was significantly longer for toddlers with autism spectrum disorder (2.02 vs 1.06 s, p = 0.04). Sensitivity for autism spectrum disorder of atypical orienting was 96% and specificity was 38%. Older toddlers with autism spectrum disorder showed less attention to the videos overall (p = 0.03). Automated coding offers a reliable, quantitative method for detecting atypical social orienting and reduced sustained attention in toddlers with autism spectrum disorder.
Carriers of germ-line mutations in BRCA1 and BRCA2 from families at high risk for cancer have been estimated to have an 85 percent risk of breast cancer. Since the combined frequency of BRCA1 and ...BRCA2 mutations exceeds 2 percent among Ashkenazi Jews, we were able to estimate the risk of cancer in a large group of Jewish men and women from the Washington, D.C., area.
We collected blood samples from 5318 Jewish subjects who had filled out epidemiologic questionnaires. Carriers of the 185delAG and 5382insC mutations in BRCA1 and the 6174delT mutation in BRCA2 were identified with assays based on the polymerase chain reaction. We estimated the risks of breast and other cancers by comparing the cancer histories of relatives of carriers of the mutations and noncarriers.
One hundred twenty carriers of a BRCA1 or BRCA2 mutation were identified. By the age of 70, the estimated risk of breast cancer among carriers was 56 percent (95 percent confidence interval, 40 to 73 percent); of ovarian cancer, 16 percent (95 percent confidence interval, 6 to 28 percent); and of prostate cancer, 16 percent (95 percent confidence interval, 4 to 30 percent). There were no significant differences in the risk of breast cancer between carriers of BRCA1 mutations and carriers of BRCA2 mutations, and the incidence of colon cancer among the relatives of carriers was not elevated.
Over 2 percent of Ashkenazi Jews carry mutations in BRCA1 or BRCA2 that confer increased risks of breast, ovarian, and prostate cancer. The risks of breast cancer may be overestimated, but they fall well below previous estimates based on subjects from high-risk families.
Observational behavior analysis plays a key role for the discovery and evaluation of risk markers for many neurodevelopmental disorders. Research on autism spectrum disorder (ASD) suggests that ...behavioral risk markers can be observed at 12 months of age or earlier, with diagnosis possible at 18 months. To date, these studies and evaluations involving observational analysis tend to rely heavily on clinical practitioners and specialists who have undergone intensive training to be able to reliably administer carefully designed behavioral-eliciting tasks, code the resulting behaviors, and interpret such behaviors. These methods are therefore extremely expensive, time-intensive, and are not easily scalable for large population or longitudinal observational analysis. We developed a self-contained, closed-loop, mobile application with movie stimuli designed to engage the child's attention and elicit specific behavioral and social responses, which are recorded with a mobile device camera and then analyzed via computer vision algorithms. Here, in addition to presenting this paradigm, we validate the system to measure engagement, name-call responses, and emotional responses of toddlers with and without ASD who were presented with the application. Additionally, we show examples of how the proposed framework can further risk marker research with fine-grained quantification of behaviors. The results suggest these objective and automatic methods can be considered to aid behavioral analysis, and can be suited for objective automatic analysis for future studies.
In spite of recent advances in the genetics and neuroscience of early childhood mental health, behavioral observation is still the gold standard in screening, diagnosis, and outcome assessment. ...Unfortunately, clinical observation is often subjective, needs significant rater training, does not capture data from participants in their natural environment, and is not scalable for use in large populations or for longitudinal monitoring. To address these challenges, we developed and tested a self-contained app designed to measure toddlers' social communication behaviors in a primary care, school, or home setting. Twenty 16-30 month old children with and without autism participated in this study. Toddlers watched the developmentally-appropriate visual stimuli on an iPad in a pediatric clinic and in our lab while the iPad camera simultaneously recorded video of the child's behaviors. Automated computer vision algorithms coded emotions and social referencing to quantify autism risk behaviors. We validated our automatic computer coding by comparing the computer-generated analysis of facial expression and social referencing to human coding of these behaviors. We report our method and propose the development and testing of measures of young children's behaviors as the first step toward development of a novel, fully integrated, low-cost, scalable screening tool for autism and other neurodevelopmental disorders of early childhood.
NASA’s Global Ecosystem Dynamics Investigation (GEDI) is collecting spaceborne full waveform lidar data with a primary science goal of producing accurate estimates of forest aboveground biomass ...density (AGBD). This paper presents the development of the models used to create GEDI’s footprint-level (~25 m) AGBD (GEDI04_A) product, including a description of the datasets used and the procedure for final model selection. The data used to fit our models are from a compilation of globally distributed spatially and temporally coincident field and airborne lidar datasets, whereby we simulated GEDI-like waveforms from airborne lidar to build a calibration database. We used this database to expand the geographic extent of past waveform lidar studies, and divided the globe into four broad strata by Plant Functional Type (PFT) and six geographic regions. GEDI’s waveform-to-biomass models take the form of parametric Ordinary Least Squares (OLS) models with simulated Relative Height (RH) metrics as predictor variables. From an exhaustive set of candidate models, we selected the best input predictor variables, and data transformations for each geographic stratum in the GEDI domain to produce a set of comprehensive predictive footprint-level models. We found that model selection frequently favored combinations of RH metrics at the 98th, 90th, 50th, and 10th height above ground-level percentiles (RH98, RH90, RH50, and RH10, respectively), but that inclusion of lower RH metrics (e.g. RH10) did not markedly improve model performance. Second, forced inclusion of RH98 in all models was important and did not degrade model performance, and the best performing models were parsimonious, typically having only 1-3 predictors. Third, stratification by geographic domain (PFT, geographic region) improved model performance in comparison to global models without stratification. Fourth, for the vast majority of strata, the best performing models were fit using square root transformation of field AGBD and/or height metrics. There was considerable variability in model performance across geographic strata, and areas with sparse training data and/or high AGBD values had the poorest performance. These models are used to produce global predictions of AGBD, but will be improved in the future as more and better training data become available.
•NASA’s GEDI collects spaceborne lidar data used for mapping aboveground biomass.•A global database of field and airborne lidar was compiled.•Models stratified by Plant Functional Type and geographic region outperform a global model.•GEDI04_A models are OLS models predicting biomass as a function of RH metrics.•Maximum forest height is an important predictor of biomass across geographic domains.
Drought is the most important environmental stress limiting crop yields. The C4 cereal sorghum Sorghum bicolor (L.) Moench is a critical food, forage, and emerging bioenergy crop that is notably ...drought-tolerant. We conducted a large-scale field experiment, imposing preflowering and postflowering drought stress on 2 genotypes of sorghum across a tightly resolved time series, from plant emergence to postanthesis, resulting in a dataset of nearly 400 transcriptomes. We observed a fast and global transcriptomic response in leaf and root tissues with clear temporal patterns, including modulation of well-known drought pathways. We also identified genotypic differences in core photosynthesis and reactive oxygen species scavenging pathways, highlighting possible mechanisms of drought tolerance and of the delayed senescence, characteristic of the stay-green phenotype. Finally, we discovered a large-scale depletion in the expression of genes critical to arbuscular mycorrhizal (AM) symbiosis, with a corresponding drop in AM fungal mass in the plants’ roots.
The microenvironment of lymphoid organs can aid healthy immune function through provision of both structural and molecular support. In mice, fibroblastic reticular cells (FRCs) create an essential ...T-cell support structure within lymph nodes, while human FRCs are largely unstudied. Here, we show that FRCs create a regulatory checkpoint in human peripheral T-cell activation through 4 mechanisms simultaneously utilised. Human tonsil and lymph node-derived FRCs constrained the proliferation of both naïve and pre-activated T cells, skewing their differentiation away from a central memory T-cell phenotype. FRCs acted unilaterally without requiring T-cell feedback, imposing suppression via indoleamine-2,3-dioxygenase, adenosine 2A Receptor, prostaglandin E2, and transforming growth factor beta receptor (TGFβR). Each mechanistic pathway was druggable, and a cocktail of inhibitors, targeting all 4 mechanisms, entirely reversed the suppressive effect of FRCs. T cells were not permanently anergised by FRCs, and studies using chimeric antigen receptor (CAR) T cells showed that immunotherapeutic T cells retained effector functions in the presence of FRCs. Since mice were not suitable as a proof-of-concept model, we instead developed a novel human tissue-based in situ assay. Human T cells stimulated using standard methods within fresh tonsil slices did not proliferate except in the presence of inhibitors described above. Collectively, we define a 4-part molecular mechanism by which FRCs regulate the T-cell response to strongly activating events in secondary lymphoid organs while permitting activated and CAR T cells to utilise effector functions. Our results define 4 feasible strategies, used alone or in combinations, to boost primary T-cell responses to infection or cancer by pharmacologically targeting FRCs.
Traumatic hemorrhage and chain of survival Latif, Rana K; Clifford, Sean P; Baker, Jeffery A ...
Scandinavian journal of trauma, resuscitation and emergency medicine,
05/2023, Letnik:
31, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Trauma is the number one cause of death among Americans between the ages of 1 and 46 years, costing more than $670 billion a year. Following death related to central nervous system injury, hemorrhage ...accounts for the majority of remaining traumatic fatalities. Among those with severe trauma that reach the hospital alive, many may survive if the hemorrhage and traumatic injuries are diagnosed and adequately treated in a timely fashion. This article aims to review the recent advances in pathophysiology management following a traumatic hemorrhage as well as the role of diagnostic imaging in identifying the source of hemorrhage. The principles of damage control resuscitation and damage control surgery are also discussed. The chain of survival for severe hemorrhage begins with primary prevention; however, once trauma has occurred, prehospital interventions and hospital care with early injury recognition, resuscitation, definitive hemostasis, and achieving endpoints of resuscitation become paramount. An algorithm is proposed for achieving these goals in a timely fashion as the median time from onset of hemorrhagic shock and death is 2 h.
Recent studies on pediatric acute myeloid leukemia (pAML) have revealed pediatric-specific driver alterations, many of which are underrepresented in the current classification schemas. To ...comprehensively define the genomic landscape of pAML, we systematically categorized 887 pAML into 23 mutually distinct molecular categories, including new major entities such as UBTF or BCL11B, covering 91.4% of the cohort. These molecular categories were associated with unique expression profiles and mutational patterns. For instance, molecular categories characterized by specific HOXA or HOXB expression signatures showed distinct mutation patterns of RAS pathway genes, FLT3 or WT1, suggesting shared biological mechanisms. We show that molecular categories were strongly associated with clinical outcomes using two independent cohorts, leading to the establishment of a new prognostic framework for pAML based on these updated molecular categories and minimal residual disease. Together, this comprehensive diagnostic and prognostic framework forms the basis for future classification of pAML and treatment strategies.
Structurally intact tropical forests sequestered about half of the global terrestrial carbon uptake over the 1990s and early 2000s, removing about 15 per cent of anthropogenic carbon dioxide ...emissions
. Climate-driven vegetation models typically predict that this tropical forest 'carbon sink' will continue for decades
. Here we assess trends in the carbon sink using 244 structurally intact African tropical forests spanning 11 countries, compare them with 321 published plots from Amazonia and investigate the underlying drivers of the trends. The carbon sink in live aboveground biomass in intact African tropical forests has been stable for the three decades to 2015, at 0.66 tonnes of carbon per hectare per year (95 per cent confidence interval 0.53-0.79), in contrast to the long-term decline in Amazonian forests
. Therefore the carbon sink responses of Earth's two largest expanses of tropical forest have diverged. The difference is largely driven by carbon losses from tree mortality, with no detectable multi-decadal trend in Africa and a long-term increase in Amazonia. Both continents show increasing tree growth, consistent with the expected net effect of rising atmospheric carbon dioxide and air temperature
. Despite the past stability of the African carbon sink, our most intensively monitored plots suggest a post-2010 increase in carbon losses, delayed compared to Amazonia, indicating asynchronous carbon sink saturation on the two continents. A statistical model including carbon dioxide, temperature, drought and forest dynamics accounts for the observed trends and indicates a long-term future decline in the African sink, whereas the Amazonian sink continues to weaken rapidly. Overall, the uptake of carbon into Earth's intact tropical forests peaked in the 1990s. Given that the global terrestrial carbon sink is increasing in size, independent observations indicating greater recent carbon uptake into the Northern Hemisphere landmass
reinforce our conclusion that the intact tropical forest carbon sink has already peaked. This saturation and ongoing decline of the tropical forest carbon sink has consequences for policies intended to stabilize Earth's climate.
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