Deep learning for robust and flexible tracking in behavioral studies for C. elegans.

Robust and accurate behavioral tracking is essential for ethological studies. Common methods for tracking and extracting behavior rely on user adjusted heuristics that can significantly vary across different individuals, environments, and experimental conditions. As a result, they are difficult to implement in large-scale behavioral studies with complex, heterogenous environmental conditions. Recently developed deep-learning methods for object recognition such as Faster R-CNN have advantages in their speed, accuracy, and robustness. Here, we show that Faster R-CNN can be employed for identification and detection of Caenorhabditis elegans in a variety of life stages in complex environments. We applied the algorithm to track animal speeds during development, fecundity rates and spatial distribution in reproductive adults, and behavioral decline in aging populations. By doing so, we demonstrate the flexibility, speed, and scalability of Faster R-CNN across a variety of experimental conditions, illustrating its generalized use for future large-scale behavioral studies.

Strengthening International Research in Long-Term Care: Recommended Common Data Elements to Support Clinical Staff Training.

The purpose of this study is to develop candidate common data element (CDE) items related to clinical staff training in long-term care (LTC) homes that can be used to enable international comparative research. This paper is part of the WE-THRIVE (Worldwide Elements to Harmonize Research in Long-Term Care Living Environments) group's initiative which aims to improve international academic collaboration. We followed best practices to develop CDEs by conducting a literature review of clinical staff (i.e., Regulated Nurses, Health Care Aides) training measures, and convening a subgroup of WE-THRIVE experts to review the literature review results to develop suitable CDEs. The international expert panel discussed and critically reflected on the current knowledge gaps from the literature review results. The panel proposed three candidate CDEs which focused on the presence of and the measurement of training. These three proposed CDEs seek to facilitate international research as well as assist in policy and decision-making regarding LTC homes worldwide. This study is a critical first step to develop candidate CDE items to measure staff training internationally. Further work is required to get feedback from other researchers about the proposed CDEs, and assess the feasibility of these CDEs in high and low resourced settings.

An automated platform to monitor long-term behavior and healthspan in Caenorhabditis elegans under precise environmental control.

Health and longevity in all organisms are strongly influenced by the environment. To fully understand how environmental factors interact with genetic and stochastic factors to modulate the aging process, it is crucial to precisely control environmental conditions for long-term studies. In the commonly used model organism Caenorhabditis elegans, existing assays for healthspan and lifespan have inherent limitations, making it difficult to perform large-scale longitudinal aging studies under precise environmental control. To address these constraints, we developed the Health and Lifespan Testing Hub (HeALTH), an automated, microfluidic-based system for robust longitudinal behavioral monitoring. Our system provides long-term (i.e. entire lifespan) spatiotemporal environmental control. We demonstrate healthspan and lifespan studies under a variety of genetic and environmental perturbations while observing how individuality plays a role in the aging process. This system is generalizable beyond aging research, particularly for short- or long-term behavioral assays, and could be adapted for other model systems.

Indications for Rituximab Use in an Integrated Health Care Delivery System.

BACKGROUND: Rituximab is a top-selling biologic that was first approved by the FDA in 1997 for a non-Hodgkin lymphoma orphan indication. It has since been approved for additional orphan indications, with rheumatoid arthritis as the only FDA-approved, nonorphan indication. Evidence suggests that rituximab is frequently used off-label, but information on its use over time and indications for use in the United States is limited. OBJECTIVE: To assess incident rituximab use over time in an integrated health care delivery system. METHODS: This was a cross-sectional, retrospective study. Data were collected from administrative databases and manual chart reviews. Patients who received their first rituximab infusion between October 1, 2009, and December 31, 2017, and who were not a part of a clinical trial were included. Indication for use (FDA-approved orphan/nonorphan, off-label) was determined. Proportions of use were assessed over time. Multivariable logistic regression modeling was performed to assess factors associated with receiving rituximab for an FDA-approved indication. RESULTS: A total of 1,674 patients were included. The majority (66.4%) of patients had an FDA-approved indication, with lymphoma being the most common approved indication (66.4%). The most common indication for off-label use was neurologic conditions (72.7%), predominantly demyelinating diseases. Off-label indication use increased from 1.2% in 2009 to 55.6% in 2017. Factors associated with rituximab use for an FDA-approved indication included increased age (adjusted odds ratio [AOR] = 1.05, 95% CI = 1.04-1.07) and increased burden of chronic disease (chronic disease score: AOR = 1.07, 95% CI = 1.02-1.12; Charlson Comorbidity Index score: AOR = 3.52, 95% CI = 3.03-4.10). CONCLUSIONS: Off-label use of rituximab grew dramatically over the course of the study. With the recent FDA approval of the rituximab biosimilar and its expected lower price, off-label use will likely continue to rise. Opportunities for cost savings and to ensure appropriate use of these medications should be evaluated. DISCLOSURES: This study was funded by Kaiser Permanente. All authors except Hansen are employed by Kaiser Permanente. Hansen has nothing to disclose. Preliminary results were presented at the Mountain States Conference for Residents and Preceptors in May 2019 in Salt Lake City, UT, and at an encore presentation October 2019 at the American College of Clinical Pharmacy Annual Meeting in New York, NY.

A portable, low-cost device for precise control of specimen temperature under stereomicroscopes.

To facilitate precise and convenient control of biological sample temperature, we developed a low-cost device that can be used independently or with any stereomicroscope. The purpose of the device is to control the thermal environment during experimental intervals in which a specimen must be manipulated outside of an incubator, e.g. for dissection or slide-mounting in preparation for imaging. Sample temperatures can be both cooled to below and heated to above room temperatures, and stably maintained at a precision of +/- 0.1˚C. To demonstrate the utility of this device, we report improved characterization of the penetrance of a short-acting temperature-sensitive allele in C. elegans embryos, and identification of the upper temperature threshold for embryonic viability for six Caenorhabditis species. By controlling the temperature environment even as a specimen is manipulated, this device offers consistency and flexibility, reduces environmental noise, and enables precision timing in experiments requiring temperature shifts.

Spatial variation in mandibular bone elastic modulus and its effect on structural bending stiffness: A test case using the Taï Forest monkeys.

OBJECTIVES: We investigated how heterogeneity in material stiffness affects structural stiffness in the cercopithecid mandibular cortical bone. We assessed (1) whether this effect changes the interpretation of interspecific structural stiffness variation across four primate species, (2) whether the heterogeneity is random, and (3) whether heterogeneity mitigates bending stress in the jaw associated with food processing. MATERIALS AND METHODS: The sample consisted of Taï Forest, Cote d'Ivoire, monkeys: Cercocebus atys, Piliocolobus badius, Colobus polykomos, and Cercopithecus diana. Vickers indentation hardness samples estimated elastic moduli throughout the cortical bone area of each coronal section of postcanine corpus. For each section, we calculated maximum area moment of inertia, Imax (structural mechanical property), under three models of material heterogeneity, as well as spatial autocorrelation statistics (Moran's I, IMORAN ). RESULTS: When the model considered material stiffness variation and spatial patterning, Imax decreased and individual ranks based on structural stiffness changed. Rank changes were not significant across models. All specimens showed positive (nonrandom) spatial autocorrelation. Differences in IMORAN were not significant among species, and there were no discernable patterns of autocorrelation within species. Across species, significant local IMORAN was often attributed to proximity of low moduli in the alveolar process and high moduli in the basal process. DISCUSSION: While our sample did not demonstrate species differences in the degree of spatial autocorrelation of elastic moduli, there may be mechanical effects of heterogeneity (relative strength and rigidity) that do distinguish at the species or subfamilial level (i.e., colobines vs. cercopithecines). The potential connections of heterogeneity to diet and/or taxonomy remain to be discovered.