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Advances in whole-genome sequencing (WGS) promise to enable the accurate and comprehensive structural variant (SV) discovery. Dissecting SVs from WGS data presents a substantial number of challenges and a plethora of SV detection methods have been developed. Currently, evidence that investigators can use to select appropriate SV detection tools is lacking. In this article, we have evaluated the performance of SV detection tools on mouse and human WGS data using a comprehensive polymerase chain reaction-confirmed gold standard set of SVs and the genome-in-a-bottle variant set, respectively. In contrast to the previous benchmarking studies, our gold standard dataset included a complete set of SVs allowing us to report both precision and sensitivity rates of the SV detection methods. Our study investigates the ability of the methods to detect deletions, thus providing an optimistic estimate of SV detection performance as the SV detection methods that fail to detect deletions are likely to miss more complex SVs. We found that SV detection tools varied widely in their performance, with several methods providing a good balance between sensitivity and precision. Additionally, we have determined the SV callers best suited for low- and ultralow-pass sequencing data as well as for different deletion length categories.

Objective.Brain injury is the leading cause of long-term disability worldwide, often resulting in impaired hand function. Brain-machine interfaces (BMIs) offer a potential way to improve hand function. BMIs often target replacing lost function, but may also be employed in neurorehabilitation (nrBMI) by facilitating neural plasticity and functional recovery. Here, we report a novel nrBMI capable of acquiring high-γ(70-115 Hz) information through a unique post-traumatic brain injury (TBI) hemicraniectomy window model, and delivering sensory feedback that is synchronized with, and proportional to, intended grasp force.Approach. We developed the nrBMI to use electroencephalogram recorded over a hemicraniectomy (hEEG) in individuals with TBI. The nrBMI empowered users to exert continuous, proportional control of applied force, and provided continuous force feedback. We report the results of an initial testing group of three human participants with TBI, along with a control group of three skull- and motor-intact volunteers.Main results. All participants controlled the nrBMI successfully, with high initial success rates (2 of 6 participants) or performance that improved over time (4 of 6 participants). We observed high-γmodulation with force intent in hEEG but not skull-intact EEG. Most significantly, we found that high-γcontrol significantly improved the timing synchronization between neural modulation onset and nrBMI output/haptic feedback (compared to low-frequency nrBMI control).Significance. These proof-of-concept results show that high-γnrBMIs can be used by individuals with impaired ability to control force (without immediately resorting to invasive signals like electrocorticography). Of note, the nrBMI includes a parameter to change the fraction of control shared between decoded intent and volitional force, to adjust for recovery progress. The improved synchrony between neural modulations and force control for high-γsignals is potentially important for maximizing the ability of nrBMIs to induce plasticity in neural circuits. Inducing plasticity is critical to functional recovery after brain injury.

An 11-year-old U.S. fifth grader with a diagnosis of autism spectrum disorder (ASD) participated in a writing intervention using the self-regulated strategy development (SRSD) approach for story writing. The child summarized stories adapted from the Read Works® website using POW (Pick my idea, Organize my notes, and Write and say more) and WWW, What = 2, How = 2 (W = Who are the characters?, W = When does the story happen?, W = Where does the story happen?, What = 2, What happens first?, What happens next?, How = 2, How does the story end? and How do the characters feel?). Based on correct word sequence (CWS) calculations, the participant increased CWS from pre-test to post-test, and the total number of words she wrote also increased. This case study aims to provide speech-language pathologists with a guide for implementing the SRSD approach with their students with ASD and to inform future research.

This study examined preservice teacher coursework and experiences related to student trauma, classroom management, and self-care during a junior-year clinical placement (N = 25), as well as through follow-up interviews with a subgroup of participants one year later (N = 8). An inductive, thematic analysis led to the identification of four broad themes related to teacher-student relationships, field-based learning, adopting a philosophy of control versus flexibility, and the professional practice of self-care. All participants observed the impact of trauma in their classrooms, but only a few witnessed trauma-informed strategies that centered relationships and the humanistic side of teaching. Preservice teachers placed in trauma-informed classrooms felt the most prepared to implement trauma-informed strategies, while most preservice teachers questioned their ability to create a positive and responsive space for students who had experienced trauma. Data were used to create a conceptual model of findings to help guide future work with preservice teachers and clinical experiences.

In this article, we think-with nots, knots, and (k)nots in the interstices of theory, methodology, pedagogy, and art. We define the (k)not as a bringing together of nots--openings toward creativity, mapping, and disruption--and knots--openings toward connection, entanglement, and speculative futures. Playing (k)nots within our own relations, we-three-and-more are entangled in a complex (k)not of teachers "and" students, mentors "and" mentees, friends "and" collaborators, artists "and" scholars, who all share lived experiences in/with qualitative inquiry. Thinking with and creating the (k)not as a type of visual string figuring, we pass art back and forth with one another in this artful and pedagogical experiment. Inspired by Donna Haraway, we are pedagogical kin, string figurers who ask together, "what do these (k)nots produce in pedagogy as well as in methodology? What sort of living-thinking-being are we worlding together?"

This paper examines how histories of racism, slavery, and white supremacy continue to resonate in the present through the creation and curation of an audio compilation of student narratives. Grounded in posthuman theories, the sound compilation of layered student narratives offers a starting point for exploring the relational, embodied, and material web of affects that characterize the nomadic posthuman subject. This article takes up Braidotti's call to question who 'we' are in this together, what it means for 'us' to negotiate the convergence of the present together when we are not one and the same. Through compiling and overlapping student voices, this article works to attend to the patterns and differences in their tellings as ethical and relational starting positions. The tracing of stories and threads of student voices in the audio compilation 'puts to work' posthuman theory and offers possibilities for qualitative research methods grounded in posthuman theories.

This paper explores women's experiences in academia through collective biography from a feminist, transdisciplinary, intersectional frame. Crosscutting disciplines, classifications, and subject positions, we use dialogue to explore the nuances of what it is to be a woman in academia, and the experiences of building and developing community as women. We draw on data from a fall 2020 focus group where we each were part of a course in designing qualitative inquiry, as well as our reflections, memos, and conversations in dialogues that followed. These dialogues are accentuated with footnotes that function as a concurrent playlist of research, art, and music reflecting women's lives and experiences. We use poetic transcription and audio poetry to offer the texture of our experiences, offering both methodological and empirical implications for studying and researching women's experiences in academia.

This article reports on the development and initial feasibility of virtual assessment procedures for a sentence-writing probe for remote instructional purposes with intermediate-grade students. The study included a sample of 15 intermediate-grade children. The sentence-writing probe was administered through video conferencing software, an innovation of the times, across three sessions separated by 2 weeks. Scores derived from sentence probes included total number of words, a sentence accuracy score, and a word accuracy score, which were compared across time points. Results indicated no statistically significant differences across time points for the entire sample for all measures except the total number of words at Time 2. Measures obtained from the sentence-writing probe were significantly correlated with standardized measures of oral language. Findings from this study support the proof of concept that virtual assessment procedures can be used to assess sentence-level writing in intermediate-grade students. Future directions are provided regarding the utility of remote instruction for assessment purposes, the types of scores derived from measures, and future plans to scale up the assessment for use in research studies and as a curriculum-based evaluation tool.

Purpose: Literacy instruction is within the scope of practice of speechlanguage pathologists (SLPs) and is a documented service provided among school-based SLPs. The purpose of this investigation was to replicate Davis and Murza's (2019) study of Virginia school-based SLPs in another geographic location. This study gathered information regarding Midwestern SLPs' knowledge of "disciplinary literacy" and confidence providing services to school-aged children and adolescents with literacy goals and aligning their practice to educational standards. Method: Ninety-nine Midwestern school-based SLPs completed a 26-question online survey. The survey was replicated from Davis and Murza's (2019) investigation with a modification to include additional demographic information about participants. Results: The majority of school-based SLPs in this study were not familiar with the term disciplinary literacy but desired continuing education on the topic. A moderate relationship was found between SLPs' confidence in their ability to implement language therapy that impacts students' literacy achievement in both kindergarten through third grade and fourth through fifth grades, and the percentage of students on caseload with Individualized Education Program goals connected to literacy achievement. Conclusions: When compared to Davis and Murza's (2019) study, there are similarities noted, such as Midwestern SLPs are not completely comfortable or confident with implementing literacy intervention. The differences between these two studies exist in the relationship between experience and confidence in supporting literacy achievement. Additional information about the preprofessional coursework offerings, particularly those focused on adolescents, is of interest for future studies to understand the potential impacts on SLPs' confidence levels.

Populations are locally adapted when they exhibit higher fitness than foreign populations in their native habitat. Maize landrace adaptations to highland and lowland conditions are of interest to researchers and breeders. To determine the prevalence and strength of local adaptation in maize landraces, we performed a reciprocal transplant experiment across an elevational gradient in Mexico. We grew 120 landraces, grouped into four populations (Mexican Highland, Mexican Lowland, South American Highland, South American Lowland), in Mexican highland and lowland common gardens and collected phenotypes relevant to fitness and known highland-adaptive traits such as anthocyanin pigmentation and macrohair density. 67k DArTseq markers were generated from field specimens to allow comparisons between phenotypic patterns and population genetic structure. We found phenotypic patterns consistent with local adaptation, though these patterns differ between the Mexican and South American populations. Quantitative trait differentiation (Q ST) was greater than neutral allele frequency differentiation (F ST) for many traits, signaling directional selection between pairs of populations. All populations exhibited higher fitness metric values when grown at their native elevation, and Mexican landraces had higher fitness than South American landraces when grown in these Mexican sites. As environmental distance between landraces' native collection sites and common garden sites increased, fitness values dropped, suggesting landraces are adapted to environmental conditions at their natal sites. Correlations between fitness and anthocyanin pigmentation and macrohair traits were stronger in the highland site than the lowland site, supporting their status as highland-adaptive. These results give substance to the long-held presumption of local adaptation of New World maize landraces to elevation and other environmental variables across North and South America.

Processed foods often include food additives such as xanthan gum, a complex polysaccharide with unique rheological properties, that has established widespread use as a stabilizer and thickening agent. Xanthan gums chemical structure is distinct from those of host and dietary polysaccharides that are more commonly expected to transit the gastrointestinal tract, and little is known about its direct interaction with the gut microbiota, which plays a central role in digestion of other dietary fibre polysaccharides. Here we show that the ability to digest xanthan gum is common in human gut microbiomes from industrialized countries and appears contingent on a single uncultured bacterium in the family Ruminococcaceae. Our data reveal that this primary degrader cleaves the xanthan gum backbone before processing the released oligosaccharides using additional enzymes. Some individuals harbour Bacteroides intestinalis that is incapable of consuming polymeric xanthan gum but grows on oligosaccharide products generated by the Ruminococcaceae. Feeding xanthan gum to germfree mice colonized with a human microbiota containing the uncultured Ruminococcaceae supports the idea that the additive xanthan gum can drive expansion of the primary degrader Ruminococcaceae, along with exogenously introduced B. intestinalis. Our work demonstrates the existence of a potential xanthan gum food chain involving at least two members of different phyla of gut bacteria and provides an initial framework for understanding how widespread consumption of a recently introduced food additive influences human microbiomes.

BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused global disruption of human health and activity. Being able to trace the early outbreak of SARS-CoV-2 within a locality can inform public health measures and provide insights to contain or prevent viral transmission. Investigation of the transmission history requires efficient sequencing methods and analytic strategies, which can be generally useful in the study of viral outbreaks.MethodsThe County of Los Angeles (hereafter, LA County) sustained a large outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To learn about the transmission history, we carried out surveillance viral genome sequencing to determine 142 viral genomes from unique patients seeking care at the University of California, Los Angeles (UCLA) Health System. 86 of these genomes were from samples collected before April 19, 2020.ResultsWe found that the early outbreak in LA County, as in other international air travel hubs, was seeded by multiple introductions of strains from Asia and Europe. We identified a USA-specific strain, B.1.43, which was found predominantly in California and Washington State. While samples from LA County carried the ancestral B.1.43 genome, viral genomes from neighboring counties in California and from counties in Washington State carried additional mutations, suggesting a potential origin of B.1.43 in Southern California. We quantified the transmission rate of SARS-CoV-2 over time, and found evidence that the public health measures put in place in LA County to control the virus were effective at preventing transmission, but might have been undermined by the many introductions of SARS-CoV-2 into the region.ConclusionOur work demonstrates that genome sequencing can be a powerful tool for investigating outbreaks and informing the public health response. Our results reinforce the critical need for the USA to have coordinated inter-state responses to the pandemic.

Generations of farmer selection in the central Mexican highlands have produced unique maize varieties adapted to the challenges of the local environment. In addition to possessing great agronomic and cultural value, Mexican highland maize represents a good system for the study of local adaptation and acquisition of adaptive phenotypes under cultivation. In this study, we characterize a recombinant inbred line population derived from the B73 reference line and the Mexican highland maize variety Palomero Toluqueño. B73 and Palomero Toluqueño showed classic rank-changing differences in performance between lowland and highland field sites, indicative of local adaptation. Quantitative trait mapping identified genomic regions linked to effects on yield components that were conditionally expressed depending on the environment. For the principal genomic regions associated with ear weight and total kernel number, the Palomero Toluqueño allele conferred an advantage specifically in the highland site, consistent with local adaptation. We identified Palomero Toluqueño alleles associated with expression of characteristic highland traits, including reduced tassel branching, increased sheath pigmentation and the presence of sheath macrohairs. The oligogenic architecture of these three morphological traits supports their role in adaptation, suggesting they have arisen from consistent directional selection acting at distinct points across the genome. We discuss these results in the context of the origin of phenotypic novelty during selection, commenting on the role of de novo mutation and the acquisition of adaptive variation by gene flow from endemic wild relatives.

Abstract Background Apnoea of prematurity (AOP) is one of the most common diagnoses among preterm infants. AOP often leads to hypoxemia and bradycardia which are associated with an increased risk of death or disability. In addition to caffeine therapy and non-invasive respiratory support, doxapram might be used to reduce hypoxemic episodes and the need for invasive mechanical ventilation in preterm infants, thereby possibly improving their long-term outcome. However, high-quality trials on doxapram are lacking. The DOXA-trial therefore aims to investigate the safety and efficacy of doxapram compared to placebo in reducing the composite outcome of death or severe disability at 18 to 24 months corrected age. Methods The DOXA-trial is a double blinded, multicentre, randomized, placebo-controlled trial conducted in the Netherlands, Belgium and Canada. A total of 396 preterm infants with a gestational age below 29 weeks, suffering from AOP unresponsive to non-invasive respiratory support and caffeine will be randomized to receive doxapram therapy or placebo. The primary outcome is death or severe disability, defined as cognitive delay, cerebral palsy, severe hearing loss, or bilateral blindness, at 18–24 months corrected age. Secondary outcomes are short-term neonatal morbidity, including duration of mechanical ventilation, bronchopulmonary dysplasia and necrotising enterocolitis, hospital mortality, adverse effects, pharmacokinetics and cost-effectiveness. Analysis will be on an intention-to-treat principle. Discussion Doxapram has the potential to improve neonatal outcomes by improving respiration, but the safety concerns need to be weighed against the potential risks of invasive mechanical ventilation. It is unknown if the use of doxapram improves the long-term outcome. This forms the clinical equipoise of the current trial. This international, multicentre trial will provide the needed high-quality evidence on the efficacy and safety of doxapram in the treatment of AOP in preterm infants. Trial registration ClinicalTrials.gov NCT04430790 and EUDRACT 2019-003666-41. Prospectively registered on respectively June and January 2020.

Abstract Background Dominance and other non-additive genetic effects arise from the interaction between alleles, and historically these phenomena play a major role in quantitative genetics. However, most genome-wide association studies (GWAS) assume alleles act additively. Results We systematically investigate both dominance—here representing any non-additive within-locus interaction—and additivity across 574 physiological and gene expression traits in three mammalian stocks: F2 intercross pigs, rat heterogeneous stock, and mice heterogeneous stock. Dominance accounts for about one quarter of heritable variance across all physiological traits in all species. Hematological and immunological traits exhibit the highest dominance variance, possibly reflecting balancing selection in response to pathogens. Although most quantitative trait loci (QTLs) are detectable as additive QTLs, we identify 154, 64, and 62 novel dominance QTLs in pigs, rats, and mice respectively that are undetectable as additive QTLs. Similarly, even though most cis-acting expression QTLs are additive, gene expression exhibits a large fraction of dominance variance, and trans-acting eQTLs are enriched for dominance. Genes causal for dominance physiological QTLs are less likely to be physically linked to their QTLs but instead act via trans-acting dominance eQTLs. In addition, thousands of eQTLs are associated with alternatively spliced isoforms with complex additive and dominant architectures in heterogeneous stock rats, suggesting a possible mechanism for dominance. Conclusions Although heritability is predominantly additive, many mammalian genetic effects are dominant and likely arise through distinct mechanisms. It is therefore advantageous to consider both additive and dominance effects in GWAS to improve power and uncover causality.

Abstract Objectives This release note describes the Maize GxE project datasets within the Genomes to Fields (G2F) Initiative. The Maize GxE project aims to understand genotype by environment (GxE) interactions and use the information collected to improve resource allocation efficiency and increase genotype predictability and stability, particularly in scenarios of variable environmental patterns. Hybrids and inbreds are evaluated across multiple environments and phenotypic, genotypic, environmental, and metadata information are made publicly available. Data description The datasets include phenotypic data of the hybrids and inbreds evaluated in 30 locations across the US and one location in Germany in 2020 and 2021, soil and climatic measurements and metadata information for all environments (combination of year and location), ReadMe, and description files for each data type. A set of common hybrids is present in each environment to connect with previous evaluations. Each environment had a collaborator responsible for collecting and submitting the data, the GxE coordination team combined all the collected information and removed obvious erroneous data. Collaborators received the combined data to use, verify and declare that the data generated in their own environments was accurate. Combined data is released to the public with minimal filtering to maintain fidelity to the original data.

Abstract Background Cardiovascular events, driven by endothelial dysfunction, are a recognised complication of COVID-19. SARS-CoV-2 infections remain a persistent concern globally, and an understanding of the mechanisms causing endothelial dysfunction, particularly the role of inflammation, nitric oxide, and whether sex differences exist in this response, is lacking. We have previously demonstrated important sex differences in the inflammatory response and its impact on endothelial function and separately that the ingestion of inorganic nitrate can protect the endothelium against this dysfunction. In this study, we will investigate whether sex or a dietary inorganic nitrate intervention modulates endothelial function and inflammatory responses after the COVID-19 vaccine. Methods DiNOVasc-COVID-19 is a double-blind, randomised, single-centre, placebo-controlled clinical trial. A total of 98 healthy volunteers (49 males and 49 females) will be recruited. Participants will be randomised into 1 of 2 sub-studies: part A or part B. Part A will investigate the effects of sex on vascular and inflammatory responses to the COVID-19 vaccine. Part B will investigate the effects of sex and dietary inorganic nitrate on vascular and inflammatory responses to the COVID-19 vaccine. In part B, participants will be randomised to receive 3 days of either nitrate-containing beetroot juice (intervention) or nitrate-deplete beetroot juice (placebo). The primary outcome for both sub-studies is a comparison of the change in flow-mediated dilatation (FMD) from baseline after COVID-19 vaccination. The study has a power of > 80% to assess the primary endpoint. Secondary endpoints include change from baseline in inflammatory and leukocyte counts and in pulse wave analysis (PWA) and pulse wave velocity (PWV) following the COVID-19 vaccination. Discussion This study aims to evaluate whether sex or dietary influences endothelial function and inflammatory responses in healthy volunteers after receiving the COVID-19 vaccine. Trial registration ClinicalTrials.gov NCT04889274. Registered on 5 May 2023. The study was approved by the South Central – Oxford C Research Ethics Committee (21/SC/0154).

Combining samples for genetic association is standard practice in human genetic analysis of complex traits, but is rarely undertaken in rodent genetics. Here, using 23 phenotypes and genotypes from two independent laboratories, we obtained a sample size of 3076 commercially available outbred mice and identified 70 loci, more than double the number of loci identified in the component studies. Fine-mapping in the combined sample reduced the number of likely causal variants, with a median reduction in set size of 51%, and indicated novel gene associations, including Pnpo, Ttll6, and GM11545 with bone mineral density, and Psmb9 with weight. However, replication at a nominal threshold of 0.05 between the two component studies was low, with less than one-third of loci identified in one study replicated in the second. In addition to overestimates in the effect size in the discovery sample (Winner's Curse), we also found that heterogeneity between studies explained the poor replication, but the contribution of these two factors varied among traits. Leveraging these observations, we integrated information about replication rates, study-specific heterogeneity, and Winner's Curse corrected estimates of power to assign variants to one of four confidence levels. Our approach addresses concerns about reproducibility and demonstrates how to obtain robust results from mapping complex traits in any genome-wide association study.

BackgroundIndividuals with Tourette Syndrome and Persistent Tic Disorders (collectively TS) often experience premonitory urges-aversive physical sensations that precede tics and are temporarily relieved by tic expression. The relationship between tics and premonitory urges plays a key role in the neurobehavioral treatment model of TS, which underlies first-line treatments such as the Comprehensive Behavioral Intervention for Tics (CBIT). Despite the efficacy of CBIT and related behavioral therapies, less than 40% of adults with TS respond to these treatments. Further examination of the relationship between premonitory urges, tic severity, and tic impairment can provide new insights into therapeutic targets to optimize behavioral treatment outcomes. This study examined whether urge intolerance-difficulty tolerating premonitory urges-predicted tic severity and tic-related impairment among adults with TS.MethodsParticipants were 80 adults with TS. Assessments characterized premonitory urge, distress tolerance, tic severity, and tic impairment. We used structural equation modeling (SEM) to examine the construct of urge intolerance-comprised of premonitory urge ratings and distress tolerance ratings. We first evaluated a measurement model of urge intolerance through bifactor modeling, including tests of the incremental value of subfactors that reflect premonitory urge severity and distress tolerance within the model. We then evaluated a structural model where we predicted clinician-rated tic severity and tic impairment by the latent variable of urge intolerance established in our measurement model.ResultsAnalyses supported a bifactor measurement model of urge intolerance among adults with TS. Consistent with theoretical models, higher levels of urge intolerance predicted greater levels of clinician-rated tic severity and tic impairment.ConclusionThis investigation supports the construct of urge intolerance among adults with TS and distinguishes it from subcomponents of urge severity and distress tolerance. Given its predictive relationship with tic severity and tic impairment, urge intolerance represents a promising treatment target to improve therapeutic outcomes in adults with TS.

Alexander disease (AxD) is a rare and fatal neurodegenerative disorder caused by mutations in the gene encoding glial fibrillary acidic protein (GFAP). In this report, a mouse model of AxD (GFAPTg;Gfap+/R236H) was analyzed that contains a heterozygous R236H point mutation in murine Gfap as well as a transgene with a GFAP promoter to overexpress human GFAP. Using label-free quantitative proteomic comparisons of brain tissue from GFAPTg;Gfap+/R236H versus wild-type mice confirmed upregulation of the glutathione metabolism pathway and indicated proteins were elevated in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which had not been reported previously in AxD. Relative protein-level differences were confirmed by a targeted proteomics assay, including proteins related to astrocytes and oligodendrocytes. Of particular interest was the decreased level of the oligodendrocyte protein, 2-hydroxyacylsphingosine 1-beta-galactosyltransferase (Ugt8), since Ugt8-deficient mice exhibit a phenotype similar to GFAPTg;Gfap+/R236H mice (e.g., tremors, ataxia, hind-limb paralysis). In addition, decreased levels of myelin-associated proteins were found in the GFAPTg;Gfap+/R236H mice, consistent with the role of Ugt8 in myelin synthesis. Fabp7 upregulation in GFAPTg;Gfap+/R236H mice was also selected for further investigation due to its uncharacterized association to AxD, critical function in astrocyte proliferation, and functional ability to inhibit the anti-inflammatory PPAR signaling pathway in models of amyotrophic lateral sclerosis (ALS). Within Gfap+ astrocytes, Fabp7 was markedly increased in the hippocampus, a brain region subjected to extensive pathology and chronic reactive gliosis in GFAPTg;Gfap+/R236H mice. Last, to determine whether the findings in GFAPTg;Gfap+/R236H mice are present in the human condition, AxD patient and control samples were analyzed by Western blot, which indicated that Type I AxD patients have a significant fourfold upregulation of FABP7. However, immunohistochemistry analysis showed that UGT8 accumulates in AxD patient subpial brain regions where abundant amounts of Rosenthal fibers are located, which was not observed in the GFAPTg;Gfap+/R236H mice.

BackgroundAfter a diagnosis of Alzheimer's disease and related disorders, people living with dementia (PWD) and caregivers wonder what disease trajectory to expect and how to plan for functional and cognitive decline. This qualitative study aimed to identify patient and caregiver experiences receiving anticipatory guidance about dementia from a specialty dementia clinic.ObjectiveTo examine PWD and caregiver perspectives on receiving anticipatory guidance from a specialty dementia clinic.MethodsWe conducted semi-structured interviews with PWD, and active and bereaved family caregivers, recruited from a specialty dementia clinic. Interviews were recorded, transcribed, and systematically summarized. Thematic analysis identified anticipatory guidance received from clinical or non-clinical sources and areas where respondents wanted additional guidance.ResultsOf 40 participants, 9 were PWD, 16 were active caregivers, and 15 were bereaved caregivers. PWD had a mean age of 75 and were primarily male (n = 6/9); caregivers had a mean age of 67 and were primarily female (n = 21/31). Participants felt they received incomplete or "hesitant" guidance on prognosis and expected disease course via their clinicians and filled the gap with information they found via the internet, books, and support groups. They appreciated guidance on behavioral, safety, and communication issues from clinicians, but found more timely and advance guidance from other non-clinical sources. Guidance on legal and financial planning was primarily identified through non-clinical sources.ConclusionPWD and caregivers want more information about expected disease course, prognosis, and help planning after diagnosis. Clinicians have an opportunity to improve anticipatory guidance communication and subsequent care provision.

Structural hippocampal abnormalities are common in many neurological and psychiatric disorders, and variation in hippocampal measures is related to cognitive performance and other complex phenotypes such as stress sensitivity. Hippocampal subregions are increasingly studied, as automated algorithms have become available for mapping and volume quantification. In the context of the Enhancing Neuro Imaging Genetics through Meta Analysis Consortium, several Disease Working Groups are using the FreeSurfer software to analyze hippocampal subregion (subfield) volumes in patients with neurological and psychiatric conditions along with data from matched controls. In this overview, we explain the algorithm's principles, summarize measurement reliability studies, and demonstrate two additional aspects (subfield autocorrelation and volume/reliability correlation) with illustrative data. We then explain the rationale for a standardized hippocampal subfield segmentation quality control (QC) procedure for improved pipeline harmonization. To guide researchers to make optimal use of the algorithm, we discuss how global size and age effects can be modeled, how QC steps can be incorporated and how subfields may be aggregated into composite volumes. This discussion is based on a synopsis of 162 published neuroimaging studies (01/2013-12/2019) that applied the FreeSurfer hippocampal subfield segmentation in a broad range of domains including cognition and healthy aging, brain development and neurodegeneration, affective disorders, psychosis, stress regulation, neurotoxicity, epilepsy, inflammatory disease, childhood adversity and posttraumatic stress disorder, and candidate and whole genome (epi-)genetics. Finally, we highlight points where FreeSurfer-based hippocampal subfield studies may be optimized.

The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes.