Comparing Group Means When Nonresponse Rates Differ

Missing data bias results if adjustments are not made accordingly. This thesis addresses this issue by exploring a scenario where data is missing at random depending on a covariate x. Four methods for comparing groups while adjusting for missingness are explored by conducting simulations: independent samples t-test with predicted mean stratification, independent samples t-test with response propensity stratification, independent samples t-test with response propensity weighting, and an analysis of covariance. Results show that independent samples t-test with response propensity weighting and analysis of covariance can appropriately adjust for bias. ANCOVA is the stronger method when the ANCOVA assumptions are met. When the ANCOVA assumptions are not met, a t-test with inverse response propensity score weighting is the superior method

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Early detection and tracking of bulbar changes in ALS via frequent and remote speech analysis

Abstract Bulbar deterioration in amyotrophic lateral sclerosis (ALS) is a devastating characteristic that impairs patients’ ability to communicate, and is linked to shorter survival. The existing clinical instruments for assessing bulbar function lack sensitivity to early changes. In this paper, using a cohort of N = 65 ALS patients who provided regular speech samples for 3–9 months, we demonstrated that it is possible to remotely detect early speech changes and track speech progression in ALS via automated algorithmic assessment of speech collected digitally

Language Analytics for Assessment of Mental Health Status and Functional Competency

Automated language analysis is becoming an increasingly popular tool in clinical research involving individuals with mental health disorders. Previous work has largely focused on using high-dimensional language features to develop diagnostic and prognostic models, but less work has been done to use linguistic output to assess downstream functional outcomes, which is critically important for clinical care. In this work, we study the relationship between automated language composites and clinical variables that characterize mental health status and functional competency using predictive modeling. Conversational transcripts were collected from a social skills assessment of individuals with schizophrenia (n = 141), bipolar disorder (n = 140), and healthy controls (n = 22). A set of composite language features based on a theoretical framework of speech production were extracted from each transcript and predictive models were trained. The prediction targets included clinical variables for assessment of mental health status and social and functional competency. All models were validated on a held-out test sample not accessible to the model designer. Our models predicted the neurocognitive composite with Pearson correlation PCC = 0.674; PANSS-positive with PCC = 0.509; PANSS-negative with PCC = 0.767; social skills composite with PCC = 0.785; functional competency composite with PCC = 0.616. Language features related to volition, affect, semantic coherence, appropriateness of response, and lexical diversity were useful for prediction of clinical variables. Language samples provide useful information for the prediction of a variety of clinical variables that characterize mental health status and functional competency

Language Analytics for Assessment of Mental Health Status and Functional Competency

Abstract Background and Hypothesis Automated language analysis is becoming an increasingly popular tool in clinical research involving individuals with mental health disorders. Previous work has largely focused on using high-dimensional language features to develop diagnostic and prognostic models, but less work has been done to use linguistic output to assess downstream functional outcomes, which is critically important for clinical care. In this work, we study the relationship between automated language composites and clinical variables that characterize mental health status and functional competency using predictive modeling. Study Design Conversational transcripts were collected from a social skills assessment of individuals with schizophrenia (n = 141), bipolar disorder (n = 140), and healthy controls (n = 22). A set of composite language features based on a theoretical framework of speech production were extracted from each transcript and predictive models were trained. The prediction targets included clinical variables for assessment of mental health status and social and functional competency. All models were validated on a held-out test sample not accessible to the model designer. Study Results Our models predicted the neurocognitive composite with Pearson correlation PCC = 0.674; PANSS-positive with PCC = 0.509; PANSS-negative with PCC = 0.767; social skills composite with PCC = 0.785; functional competency composite with PCC = 0.616. Language features related to volition, affect, semantic coherence, appropriateness of response, and lexical diversity were useful for prediction of clinical variables. Conclusions Language samples provide useful information for the prediction of a variety of clinical variables that characterize mental health status and functional competency

N4-hydroxycytidine, the active compound of Molnupiravir, promotes SARS-CoV-2 mutagenesis and escape from a neutralizing nanobody

Summary: N4-hydroxycytidine (NHC), the active compound of the drug Molnupiravir, is incorporated into SARS-CoV-2 RNA, causing false base pairing. The desired result is an “error catastrophe,” but this bears the risk of mutated virus progeny. To address this experimentally, we propagated the initial SARS-CoV-2 strain in the presence of NHC. Deep sequencing revealed numerous NHC-induced mutations and host-cell-adapted virus variants. The presence of the neutralizing nanobody Re5D06 selected for immune escape mutations, in particular p.E484K and p.F490S, which are key mutations of the Beta/Gamma and Omicron-XBB strains, respectively. With NHC treatment, nanobody resistance occurred two passages earlier than without. Thus, within the limitations of this purely in vitro study, we conclude that the combined action of Molnupiravir and a spike-neutralizing antagonist leads to the rapid emergence of escape mutants. We propose caution use and supervision when using Molnupiravir, especially when patients are still at risk of spreading virus