Colocalization of neurons in optical coherence microscopy and Nissl-stained histology in Brodmann’s area 32 and area 21

Published in final edited form as: Brain Struct Funct. 2019 January ; 224(1): 351–362. doi:10.1007/s00429-018-1777-z.Optical coherence tomography is an optical technique that uses backscattered light to highlight intrinsic structure, and when applied to brain tissue, it can resolve cortical layers and fiber bundles. Optical coherence microscopy (OCM) is higher resolution (i.e., 1.25 µm) and is capable of detecting neurons. In a previous report, we compared the correspondence of OCM acquired imaging of neurons with traditional Nissl stained histology in entorhinal cortex layer II. In the current method-oriented study, we aimed to determine the colocalization success rate between OCM and Nissl in other brain cortical areas with different laminar arrangements and cell packing density. We focused on two additional cortical areas: medial prefrontal, pre-genual Brodmann area (BA) 32 and lateral temporal BA 21. We present the data as colocalization matrices and as quantitative percentages. The overall average colocalization in OCM compared to Nissl was 67% for BA 32 (47% for Nissl colocalization) and 60% for BA 21 (52% for Nissl colocalization), but with a large variability across cases and layers. One source of variability and confounds could be ascribed to an obscuring effect from large and dense intracortical fiber bundles. Other technical challenges, including obstacles inherent to human brain tissue, are discussed. Despite limitations, OCM is a promising semi-high throughput tool for demonstrating detail at the neuronal level, and, with further development, has distinct potential for the automatic acquisition of large databases as are required for the human brain.Accepted manuscrip

Rerandomization and Regression Adjustment

Randomization is a basis for the statistical inference of treatment effects without strong assumptions on the outcome-generating process. Appropriately using covariates further yields more precise estimators in randomized experiments. R. A. Fisher suggested blocking on discrete covariates in the design stage or conducting analysis of covariance (ANCOVA) in the analysis stage. We can embed blocking into a wider class of experimental design called rerandomization, and extend the classical ANCOVA to more general regression adjustment. Rerandomization trumps complete randomization in the design stage, and regression adjustment trumps the simple difference-in-means estimator in the analysis stage. It is then intuitive to use both rerandomization and regression adjustment. Under the randomization-inference framework, we establish a unified theory allowing the designer and analyzer to have access to different sets of covariates. We find that asymptotically (a) for any given estimator with or without regression adjustment, rerandomization never hurts either the sampling precision or the estimated precision, and (b) for any given design with or without rerandomization, our regression-adjusted estimator never hurts the estimated precision. Therefore, combining rerandomization and regression adjustment yields better coverage properties and thus improves statistical inference. To theoretically quantify these statements, we discuss optimal regression-adjusted estimators in terms of the sampling precision and the estimated precision, and then measure the additional gains of the designer and the analyzer. We finally suggest using rerandomization in the design and regression adjustment in the analysis followed by the Huber--White robust standard error

Human cumulative culture: a comparative perspective

Many animals exhibit social learning and behavioural traditions, but human culture exhibits unparalleled complexity and diversity, and is unambiguously cumulative in character. These similarities and differences have spawned a debate over whether animal traditions and human culture are reliant on homologous or analogous psychological processes. Human cumulative culture combines high-fidelity transmission of cultural knowledge with beneficial modifications to generate a ‘ratcheting’ in technological complexity, leading to the development of traits far more complex than one individual could invent alone. Claims have been made for cumulative culture in several species of animals, including chimpanzees, orang-utans and New Caledonian crows, but these remain contentious. Whilst initial work on the topic of cumulative culture was largely theoretical, employing mathematical methods developed by population biologists, in recent years researchers from a wide range of disciplines, including psychology, biology, economics, biological anthropology, linguistics and archaeology, have turned their attention to the experimental investigation of cumulative culture. We review this literature, highlighting advances made in understanding the underlying process of cumulative culture and emphasizing areas of agreement and disagreement amongst investigators in separate fields

Aesthetic sense and social cognition: : a story from the Early Stone Age

Human aesthetic practices show a sensitivity to the ways that the appearance of an artefact manifests skills and other qualities of the maker. We investigate a possible origin for this kind of sensibility, locating it in the need for co-ordination of skill-transmission in the Acheulean stone tool culture. We argue that our narrative supports the idea that Acheulean agents were aesthetic agents. In line with this we offer what may seem an absurd comparison: between the Acheulean and the Quattrocento. In making it we display some hidden complexity in human aesthetic responses to an artefact. We conclude with a brief review of rival explanations—biological and/or cultural—of how this skills-based sensibility became a regular feature of human aesthetic practices

Inter-Individual Variability and Conspecific Densities: Consequences for Population Regulation and Range Expansion

The presence of conspecifics can strongly modulate the quality of a breeding site. Both positive and negative effects of conspecifics can act on the same individuals, with the final balance between its costs and benefits depending on individual characteristics. A particular case of inter-individual variation found in many avian species is chromatic variability. Among birds, plumage coloration can co-vary with morphology, physiology and behavior as well as with age. These relationships suggest that cost-benefit balances of conspecific presence may be different for individuals with different colorations. We investigated whether inter-individual variability affects population regulation and expansion processes by analyzing potential differences in density-dependent productivity and settlement patterns in relation to plumage coloration in a population of a long-lived avian species recently undergoing a notable increase in numbers and distribution range. Our results show strong variation in the effect of density on productivity of breeding pairs depending on plumage coloration of their members. Productivity of dark birds decreased along the breeding density gradient while that of lighter breeders remained unchanged with conspecific density. In a similar way, our results showed an uneven occupation of localities by individuals with different plumage coloration in relation to local densities, with the breeding of lighter harriers more aggregated than that of dark-brown ones. At a population scale, darker birds had higher probability of colonization of the most isolated, empty sites. Explanations for species range expansion and population regulation usually make the inferred assumption that species traits are similar among individuals. However, in most species, there could be individual variation in niche requirements or dispersal propensities among individuals with different traits. Our results contribute to the growing appreciation that the individual traits, but not the average trait at the level of species, are important during population regulation and expansion processes

Promotoras as Mental Health Practitioners in Primary Care: A Multi-Method Study of an Intervention to Address Contextual Sources of Depression

We assessed the role of promotoras—briefly trained community health workers—in depression care at community health centers. The intervention focused on four contextual sources of depression in underserved, low-income communities: underemployment, inadequate housing, food insecurity, and violence. A multi-method design included quantitative and ethnographic techniques to study predictors of depression and the intervention’s impact. After a structured training program, primary care practitioners (PCPs) and promotoras collaboratively followed a clinical algorithm in which PCPs prescribed medications and/or arranged consultations by mental health professionals and promotoras addressed the contextual sources of depression. Based on an intake interview with 464 randomly recruited patients, 120 patients with depression were randomized to enhanced care plus the promotora contextual intervention, or to enhanced care alone. All four contextual problems emerged as strong predictors of depression (chi square, p < .05); logistic regression revealed housing and food insecurity as the most important predictors (odds ratios both 2.40, p < .05). Unexpected challenges arose in the intervention’s implementation, involving infrastructure at the health centers, boundaries of the promotoras’ roles, and “turf” issues with medical assistants. In the quantitative assessment, the intervention did not lead to statistically significant improvements in depression (odds ratio 4.33, confidence interval overlapping 1). Ethnographic research demonstrated a predominantly positive response to the intervention among stakeholders, including patients, promotoras, PCPs, non-professional staff workers, administrators, and community advisory board members. Due to continuing unmet mental health needs, we favor further assessment of innovative roles for community health workers

Primary care multidisciplinary teams in practice: a qualitative study.

BACKGROUND: Current recommendations for strengthening the US healthcare system consider restructuring primary care into multidisciplinary teams as vital to improving quality and efficiency. Yet, approaches to the selection of team designs remain unclear. This project describes current primary care team designs, primary care professionals' perceptions of ideal team designs, and perceived facilitating factors and barriers to implementing ideal team-based care. METHODS: Qualitative study of 44 health care professionals at 6 primary care practices in North Carolina using focus group discussions and surveys. Data was analyzed using framework content analysis. RESULTS: Practices used a variety of multidisciplinary team designs with the specific design being influenced by the social and policy context in which practices were embedded. Practices overwhelmingly located barriers to adopting ideal multidisciplinary teams as being outside of their individual practices and outside of their control. Participants viewed internal organizational contexts as the major facilitators of multidisciplinary primary care teams. The majority of practices described their ideal team design as including a social worker to meet the needs of socially complex patients. CONCLUSIONS: Primary care multidisciplinary team designs vary across practices, shaped in part by contextual factors perceived as barriers outside of the practices' control. Facilitating factors within practices provide a culture of support to team members, but they are insufficient to overcome the perceived barriers. The common desire to add social workers to care teams reflects practices' struggles to meet the complex demands of patients and external agencies. Government or organizational policies should avoid one-size-fits-all approaches to multidisciplinary care teams, and instead allow primary care practices to adapt to their specific contextual circumstances.American Academy of Family Physicians Foundation’s Joint Grant Award Program [#G1401JG