Subcellular Imaging of Voltage and Calcium Signals Reveals Neural Processing In Vivo.

A mechanistic understanding of neural computation requires determining how information is processed as it passes through neurons and across synapses. However, it has been challenging to measure membrane potential changes in axons and dendrites in vivo. We use in vivo, two-photon imaging of novel genetically encoded voltage indicators, as well as calcium imaging, to measure sensory stimulus-evoked signals in the Drosophila visual system with subcellular resolution. Across synapses, we find major transformations in the kinetics, amplitude, and sign of voltage responses to light. We also describe distinct relationships between voltage and calcium signals in different neuronal compartments, a substrate for local computation. Finally, we demonstrate that ON and OFF selectivity, a key feature of visual processing across species, emerges through the transformation of membrane potential into intracellular calcium concentration. By imaging voltage and calcium signals to map information flow with subcellular resolution, we illuminate where and how critical computations arise.

BlastAssist: a deep learning pipeline to measure interpretable features of human embryos.

STUDY QUESTION: Can the BlastAssist deep learning pipeline perform comparably to or outperform human experts and embryologists at measuring interpretable, clinically relevant features of human embryos in IVF? SUMMARY ANSWER: The BlastAssist pipeline can measure a comprehensive set of interpretable features of human embryos and either outperform or perform comparably to embryologists and human experts in measuring these features. WHAT IS KNOWN ALREADY: Some studies have applied deep learning and developed 'black-box' algorithms to predict embryo viability directly from microscope images and videos but these lack interpretability and generalizability. Other studies have developed deep learning networks to measure individual features of embryos but fail to conduct careful comparisons to embryologists' performance, which are fundamental to demonstrate the network's effectiveness. STUDY DESIGN, SIZE, DURATION: We applied the BlastAssist pipeline to 67 043 973 images (32 939 embryos) recorded in the IVF lab from 2012 to 2017 in Tel Aviv Sourasky Medical Center. We first compared the pipeline measurements of individual images/embryos to manual measurements by human experts for sets of features, including: (i) fertilization status (n = 207 embryos), (ii) cell symmetry (n = 109 embryos), (iii) degree of fragmentation (n = 6664 images), and (iv) developmental timing (n = 21 036 images). We then conducted detailed comparisons between pipeline outputs and annotations made by embryologists during routine treatments for features, including: (i) fertilization status (n = 18 922 embryos), (ii) pronuclei (PN) fade time (n = 13 781 embryos), (iii) degree of fragmentation on Day 2 (n = 11 582 embryos), and (iv) time of blastulation (n = 3266 embryos). In addition, we compared the pipeline outputs to the implantation results of 723 single embryo transfer (SET) cycles, and to the live birth results of 3421 embryos transferred in 1801 cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS: In addition to EmbryoScope™ image data, manual embryo grading and annotations, and electronic health record (EHR) data on treatment outcomes were also included. We integrated the deep learning networks we developed for individual features to construct the BlastAssist pipeline. Pearson's χ2 test was used to evaluate the statistical independence of individual features and implantation success. Bayesian statistics was used to evaluate the association of the probability of an embryo resulting in live birth to BlastAssist inputs. MAIN RESULTS AND THE ROLE OF CHANCE: The BlastAssist pipeline integrates five deep learning networks and measures comprehensive, interpretable, and quantitative features in clinical IVF. The pipeline performs similarly or better than manual measurements. For fertilization status, the network performs with very good parameters of specificity and sensitivity (area under the receiver operating characteristics (AUROC) 0.84-0.94). For symmetry score, the pipeline performs comparably to the human expert at both 2-cell (r = 0.71 ± 0.06) and 4-cell stages (r = 0.77 ± 0.07). For degree of fragmentation, the pipeline (acc = 69.4%) slightly under-performs compared to human experts (acc = 73.8%). For developmental timing, the pipeline (acc = 90.0%) performs similarly to human experts (acc = 91.4%). There is also strong agreement between pipeline outputs and annotations made by embryologists during routine treatments. For fertilization status, the pipeline and embryologists strongly agree (acc = 79.6%), and there is strong correlation between the two measurements (r = 0.683). For degree of fragmentation, the pipeline and embryologists mostly agree (acc = 55.4%), and there is also strong correlation between the two measurements (r = 0.648). For both PN fade time (r = 0.787) and time of blastulation (r = 0.887), there's strong correlation between the pipeline and embryologists. For SET cycles, 2-cell time (P < 0.01) and 2-cell symmetry (P < 0.03) are significantly correlated with implantation success rate, while other features showed correlations with implantation success without statistical significance. In addition, 2-cell time (P < 5 × 10-11), PN fade time (P < 5 × 10-10), degree of fragmentation on Day 3 (P < 5 × 10-4), and 2-cell symmetry (P < 5 × 10-3) showed statistically significant correlation with the probability of the transferred embryo resulting in live birth. LIMITATIONS, REASONS FOR CAUTION: We have not tested the BlastAssist pipeline on data from other clinics or other time-lapse microscopy (TLM) systems. The association study we conducted with live birth results do not take into account confounding variables, which will be necessary to construct an embryo selection algorithm. Randomized controlled trials (RCT) will be necessary to determine whether the pipeline can improve success rates in clinical IVF. WIDER IMPLICATIONS OF THE FINDINGS: BlastAssist provides a comprehensive and holistic means of evaluating human embryos. Instead of using a black-box algorithm, BlastAssist outputs meaningful measurements of embryos that can be interpreted and corroborated by embryologists, which is crucial in clinical decision making. Furthermore, the unprecedentedly large dataset generated by BlastAssist measurements can be used as a powerful resource for further research in human embryology and IVF. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by Harvard Quantitative Biology Initiative, the NSF-Simons Center for Mathematical and Statistical Analysis of Biology at Harvard (award number 1764269), the National Institute of Heath (award number R01HD104969), the Perelson Fund, and the Sagol fund for embryos and stem cells as part of the Sagol Network. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: Not applicable.

Severity of Inpatient Hospitalizations Among Undocumented Immigrants and Medi-Cal Patients in a Los Angeles, California, Hospital: 2019.

Objectives. To compare the severity of inpatient hospitalizations between undocumented immigrants and Medi-Cal patients in a large safety-net hospital in Los Angeles, California. Methods. We conducted a retrospective analysis of all 2019 inpatient stays at a Los Angeles hospital (n = 22 480), including patients of all races/ethnicities. We examined 3 measures by using insurance status to approximate immigration status: illness severity, length of hospital stay, and repeat hospitalizations. We calculated group differences between undocumented and Medi-Cal patients by using inverse probability weighted regression adjustment separately for patients aged 18 to 64 years and those aged 65 years and older. Results. Younger undocumented patients had less severe illness and shorter lengths of stay than their Medi-Cal counterparts. Older undocumented immigrants also had less severe illness, but had similar lengths of stay and were more likely to have repeated hospitalizations. Conclusions. While existing work suggests that undocumented immigrants could have more severe health care needs on account of their poorer access to medical care, we did not see clear health disadvantages among hospitalized undocumented immigrants, especially younger patients. There were fewer differences between undocumented and Medi-Cal patients who were older. (Am J Public Health. 2021;111(11):2019-2026. https://doi.org/10.2105/AJPH.2021.306485).

Assessing the filtration efficiency and regulatory status of N95s and nontraditional filtering face-piece respirators available during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has severely disrupted supply chains for many types of Personal Protective Equipment (PPE), particularly surgical N95 filtering facepiece respirators (FFRs; "masks"). As a consequence, an Emergency Use Authorization (EUA) from the FDA has allowed use of industrial N95 respirators and importation of N95-type masks manufactured to international standards; these include KN95 masks from China and FFP2 masks from the European Union. METHODS: We conducted a survey of masks in the inventory of major academic medical centers in Boston, MA to determine provenance and manufacturer or supplier. We then assembled a testing apparatus at a university laboratory and performed a modified test of filtration performance using KCl and ambient particulate matter on masks from hospital inventories; an accompanying website shows how to build and use the testing apparatus. RESULTS: Over 100 different makes and models of traditional and nontraditional filtering facepiece respirators (N95-type masks) were in the inventory of surveyed U.S. teaching hospitals as opposed to 2-5 models under normal circumstances. A substantial number of unfamiliar masks are from unknown manufacturers. Many are not correctly labelled and do not perform to accepted standards and a subset are obviously dangerous; many of these masks are likely to be counterfeit. Due to the absence of publicly available information on mask suppliers and inconsistent labeling of KN95 masks, it is difficult to distinguish between legitimate and counterfeit products. CONCLUSIONS: Many FFRs available for procurement during the COVID-19 pandemic do not provide levels of fit and filtration similar to those of N95 masks and are not acceptable for use in healthcare settings. Based on these results, and in consultation with occupational health officers, we make six recommendations to assist end users in acquiring legitimate products. Institutions should always assess masks from non-traditional supply chains by checking their markings and manufacturer information against data provided by NIOSH and the latest FDA EUA Appendix A. In the absence of verifiable information on the legitimacy of mask source, institutions should consider measuring mask fit and filtration directly. We also make suggestions for regulatory agencies regarding labeling and public disclosure aimed at increasing pandemic resilience.

Does Cost Influence the Choice of Disposable Versus Reusable Instruments? Mailed Survey of Obstetrician/Gynaecologists.

OBJECTIVE: A "cost-awareness" campaign was undertaken at a tertiary hospital from 2015 to 2016 to raise awareness about costs of disposable versus reusable instruments in laparoscopic procedures. We undertook a before and after survey of obstetrician/gynecologists (Ob/Gyns) to find out if the campaign had affected their attitudes about choosing disposable versus less expensive reusable instruments. METHODS: In 2015 (before the cost-awareness campaign) and 2017 (after the cost-awareness campaign), all full-time university-associated Ob/Gyns were mailed a cover letter, questionnaire, and coffee card ($5) with a postage-paid return envelope. Responses (with unique identification) from Ob/Gyns who perform laparoscopic procedures were entered into a password-protected REDCap database on a secure server. All statistical analyses were performed using SAS software version 9.4 (SAS Institute Inc, Cary, NC) (Canadian Task Force Classification II-3). RESULTS: A total of 35 of 42 eligible Ob/Gyns (85%) with a median 10 years in practice completed questionnaires before and after the intervention. The majority had undertaken minimally invasive surgery training, mainly during residency (80%) and conferences (71%). Before the intervention, the three most important qualities influencing their decision to use a particular instrument were safety (66%), effectiveness (57%), and personal experience (49%). After the intervention, the three most important qualities were effectiveness (57%), safety (57%), and ease of use (46%). Device cost was ranked sixth (26%) before and seventh (17%) after the intervention. The majority (57%) of participants did not change their choice of disposable or reusable instruments, or they would make the choice according to the specific procedure. CONCLUSION: Given the current economy, operative costs are constantly under review. Knowledge about Ob/Gyns' attitudes provides information to design more effective awareness campaigns to encourage use of less costly instruments. To change practice, a campaign increasing Ob/Gyns' exposure to less expensive but safe and effective instruments may help to increase uptake and potentially lead to cost reduction. Cost awareness alone is unlikely to change practice.

Critical Contact Lens Oxygen Transmissibility and Tear Lens Oxygen Tension to Preclude Corneal Neovascularization.

OBJECTIVE: The purpose of this study is to determine the peripheral oxygen transmissibility (pDk/t) and respective central oxygen transmissibility (cDk/t) in soft contact lenses (SCLs) which might preclude SCL-driven corneal neovascularization (NV) in healthy myopic SCL users. METHODS: Twenty subjectively successful SCL-wearing patients who presented with asymptomatic but active peripheral corneal NV (not ghost vessels) were recruited as study patients. Twenty-one patients who did not have NV were similarly recruited as controls. Demographic data were collected. Corneal NV was documented and photographed. Current habitual SCLs were collected and thicknesses measured to allow for the calculation of both pDk/t and cDk/t and estimation of local tear oxygen tensions. RESULTS: No statistical differences between study and control groups in patient age, refraction, or the numbers of years, days per week, or hours per day patients reported SCL wear were identified. Statistically significant differences were found between the two groups for both pDk/t (P=0.006) and cDk/t (P=0.004): mean (±SD) pDk/t was 38.0±23.5 and 19.2±17.7 Fatt units for control and study corneas, respectively. Mean cDk/t were 80.0±54.4 and 36.8±33.1 Fatt units for control and study corneas, respectively. Peripheral tear oxygen tension that "protected" corneas from vascular filling was over 84 mm Hg. CONCLUSION: Maintaining a pDk/t above 30 to 40 Fatt units with daily wear SCLs should protect most normal corneas from NV as a complication of SCL wear.

Genetically Encoded Voltage Indicators: Opportunities and Challenges.

UNLABELLED: A longstanding goal in neuroscience is to understand how spatiotemporal patterns of neuronal electrical activity underlie brain function, from sensory representations to decision making. An emerging technology for monitoring electrical dynamics, voltage imaging using genetically encoded voltage indicators (GEVIs), couples the power of genetics with the advantages of light. Here, we review the properties that determine indicator performance and applicability, discussing both recent progress and technical limitations. We then consider GEVI applications, highlighting studies that have already deployed GEVIs for biological discovery. We also examine which classes of biological questions GEVIs are primed to address and which ones are beyond their current capabilities. As GEVIs are further developed, we anticipate that they will become more broadly used by the neuroscience community to eavesdrop on brain activity with unprecedented spatiotemporal resolution. SIGNIFICANCE STATEMENT: Genetically encoded voltage indicators are engineered light-emitting protein sensors that typically report neuronal voltage dynamics as changes in brightness. In this review, we systematically discuss the current state of this emerging method, considering both its advantages and limitations for imaging neural activity. We also present recent applications of this technology and discuss what is feasible now and what we anticipate will become possible with future indicator development. This review will inform neuroscientists of recent progress in the field and help potential users critically evaluate the suitability of genetically encoded voltage indicator imaging to answer their specific biological questions.

The effect of childhood abuse on the risk of adult obesity.

BACKGROUND: The purpose of this study was to assess the association between childhood abuse and adult obesity. METHODS: We performed a comprehensive meta-analysis, which included studies that reported odds ratio (OR) estimates with 95% confidence intervals (CI). Summary estimates of association were obtained using a random-effects model. Heterogeneity among studies was evaluated using Cochran Q and I2 statistics. RESULTS: A total of 22 cohort studies (3 prospective, 19 retrospective) were included in this meta-analysis. The pooled OR was 1.23 (95% CI, 1.16-1.31). All 4 subcategories of abuse were associated with adult obesity: physical abuse (OR, 1.26; 95% CI, 1.10-1.42), psychological abuse (OR, 1.20; 95% CI, 1.07-1.33), sexual abuse (OR, 1.22; 95% CI, 1.05-1.38), and neglect (OR, 1.22; 95% CI, 1.12-1.32). Moreover, dose-response analysis showed that severe abuse (OR, 1.38; 95% CI, 1.14-1.1.62) was significantly associated with adult obesity compared with light/moderate abuse (OR, 1.01; 95% CI, 0.84-1.18). Although slight publication bias was observed (Egger test P = .05), effect sizes remained statistically significant in sensitivity analyses. CONCLUSIONS: This research demonstrated a remarkably consistent association between childhood abuse and adult obesity. Medical practitioners need to be aware of the important role of childhood abuse in the development of obesity.

CD151 restricts the α6 integrin diffusion mode.

Laminin-binding integrins (α3ß1, α6ß1, α6ß4, α7ß1) are almost always expressed together with tetraspanin CD151. In every coexpressing cell analyzed to date, CD151 makes a fundamental contribution to integrin-dependent motility, invasion, morphology, adhesion and/or signaling. However, there has been minimal mechanistic insight into how CD151 affects integrin functions. In MDA-MB-231 mammary cells, tetraspanin CD151 knockdown impairs α6 integrin clustering and functions without decreasing α6 integrin expression or activation. Furthermore, CD151 knockdown minimally affects the magnitude of α6 integrin diffusion, as measured using single particle tracking. Instead, CD151 knockdown has a novel and unexpected dysregulating effect on the mode of α6 integrin diffusion. In control cells α6 integrin shows mostly random-confined diffusion (RCD) and some directed motion (DMO). In sharp contrast, in CD151-knockdown cells α6 integrin shows mostly DMO. In control cells α6 diffusion mode is sensitive to actin disruption, talin knockdown and phorbol ester stimulation. By contrast, CD151 knockdown cell α6 integrin is sensitive to actin disruption but desensitized to talin knockdown or phorbol ester stimulation, indicating dysregulation. Both phorbol ester and EGF stimulate cell spreading and promote α6 RCD in control cells. By contrast, CD151-ablated cells retain EGF effects but lose phorbol-ester-stimulated spreading and α6 RCD. For α6 integrins, physical association with CD151 promotes α6 RCD, in support of α6-mediated cable formation and adhesion. By comparison, for integrins not associated with CD151 (e.g. αv integrins), CD151 affects neither diffusion mode nor αv function. Hence, CD151 support of α6 RCD is specific and functionally relevant, and probably underlies diverse CD151 functions in skin, kidney and cancer cells.

Breast reconstruction satisfaction rates at a large county hospital.

BACKGROUND: It has been previously reported that the indigent patient population is less likely to seek breast reconstruction. It has also been reported that lower income women who do chose to undergo reconstruction are less satisfied with the results. This study assesses the level of breast reconstruction satisfaction in women treated at Los Angeles County Medical Center (LAC). For those women with lower satisfaction, we seek to identify the root source of this dissatisfaction. METHODS: Patients who underwent breast reconstruction at LAC from 2007 to 2012 were identified by Current Procedural Terminology codes. Eligible participants were administered the BREAST-Q postreconstruction module. Demographic data were obtained from the patient and/or their medical records. RESULTS: A total of 65 patients completed the surveys. The satisfaction scores for the appearance of the breast were 61 (24) and satisfaction with overall outcome was 80 (26). The occurrence of major complications was associated with lower satisfaction scores with respect to the appearance of the breast (P<0.0001) and overall outcome (P=0.02). In addition, patients with delayed reconstruction were also noted to be more satisfied with respect to appearance of the breast (P=0.03). CONCLUSIONS: Despite suggestions that the indigent and the underserved patient population are less satisfied with the results of their breast reconstruction procedures, patients at LAC demonstrated comparable satisfaction levels to other published reports. The occurrence of major complications and immediate reconstruction were significantly associated with lower levels of satisfaction.

A recurrent neural circuit in Drosophila deblurs visual inputs.

A critical goal of vision is to detect changes in light intensity, even when these changes are blurred by the spatial resolution of the eye and the motion of the animal. Here we describe a recurrent neural circuit in Drosophila that compensates for blur and thereby selectively enhances the perceived contrast of moving edges. Using in vivo, two-photon voltage imaging, we measured the temporal response properties of L1 and L2, two cell types that receive direct synaptic input from photoreceptors. These neurons have biphasic responses to brief flashes of light, a hallmark of cells that encode changes in stimulus intensity. However, the second phase was often much larger than the first, creating an unusual temporal filter. Genetic dissection revealed that recurrent neural circuitry strongly shapes the second phase of the response, informing the structure of a dynamical model. By applying this model to moving natural images, we demonstrate that rather than veridically representing stimulus changes, this temporal processing strategy systematically enhances them, amplifying and sharpening responses. Comparing the measured responses of L2 to model predictions across both artificial and natural stimuli revealed that L2 tunes its properties as the model predicts in order to deblur images. Since this strategy is tunable to behavioral context, generalizable to any time-varying sensory input, and implementable with a common circuit motif, we propose that it could be broadly used to selectively enhance sharp and salient changes.

COVID-19-Related Emergency Department Visits Among Undocumented Patients in Los Angeles County.

Undocumented immigrants may be vulnerable to poor COVID-19 outcomes, but also may be less likely to seek medical care. To our knowledge, there have not been any investigations of potential COVID-19 disparities by immigration status. We analyzed emergency department (ED) visit data from March 20, 2020 to September 30, 2020 among patients in a safety-net hospital in Los Angeles County (n=30,023). We compared the probability of COVID-19-related ED visits between undocumented immigrants and Medi-Cal patients. We also examined differences in these comparisons over time. Undocumented patients had higher odds of COVID-19-related ED visits than Medi-Cal patients (OR: 1.41, 95% CI: 1.24-1.60) for all months in the study period except September. Even in the earliest days of the pandemic, undocumented patients were more likely than Medi-Cal patients to have a COVID-19-related ED visit. Additional analyses suggest this was likely because of higher COVID-19 exposure rather than differences in ED utilization.

Psychiatric Admissions Among Undocumented Immigrants at an Urban County Hospital.

Little is known about the inpatient mental health needs of undocumented immigrants in the United States. Based on existing literature, we hypothesized that undocumented patients would have fewer psychiatric admissions than documented patients. We reviewed 2019 inpatient admission data for Hispanic/Latino patients at an urban hospital. Patients were coded as undocumented or documented using insurance proxies. Multivariable logistic regression was used to report odds ratio of admission diagnoses of interest by documentation status. There were no significant differences in psychiatric admissions between undocumented patients (2.1%) and documented patients (2.8%) (p=.77). Compared with documented counterparts, undocumented patients were more likely to be admitted for alcohol-related disorders (AOR=1.59, 95%CI=1.31-1.93) but had lower proportions of admission for substance-related disorders, mood disorders, anxiety disorders, and suicide and intentional self-inflicted injury among others. Future studies should examine factors contributing to alcohol use disorder and barriers to accessing and using mental health care.

Comparison between qPCR, VIDAS immunoassays, and agar streaking for the detection of Listeria monocytogenes from food and environmental surfaces containing and not containing Listeria innocua.

Comparisons among a qPCR assay, VIDAS® assays and a conventional agar streaking method following the same enrichment for the detection of Listeria monocytogenes were performed under two challenging conditions. In the first comparison, L. innocua and L. monocytogenes were coinoculated into sausages at ratios (L. innocua-to-L. monocytogenes) of 10, 100, 1000, and 10 000. qPCR provided the most sensitive detection at all ratios after both 24-h and 48-h enrichments. A modified VIDAS® LMO2 assay (i.e., replacement of the kit-specified enrichment scheme with the enrichment scheme used in this study) and agar streaking yielded equivalent results when the ratio was 10 and 100; agar streaking was more sensitive when the ratio was 1000; neither method could detect L. monocytogenes at the ratio of 10 000. Enrichment duration of 48 h was needed for modified VIDAS® to detect L. monocytogenes when the ratio was 1000. Agar streaking after 24-h enrichment isolated L. monocytogenes better than after 48-h enrichment when the ratio was 100 and 1000. In the second comparison, we followed the validation guidelines of AOAC International and inoculated L. monocytogenes, without any L. innocua, onto lettuce and stainless-steel surfaces at low levels. The numbers of positive samples detected by qPCR, VIDAS® LIS assay, modified VIDAS® LMO2 assay, and agar streaking after 48-h enrichment were not statistically different. Our data showed that qPCR was the most sensitive method, while agar streaking and VIDAS® performed reasonably well. Streaking after 24-h enrichment was needed when background flora could overgrow L. monocytogenes during prolonged enrichment, and this is critical for confirming rapid screening assays. Appropriate selection of enrichment duration and rapid assays will enhance the testing of L. monocytogenes in food and environmental samples.

The role of frailty in modifying physical function and quality of life over time in older men with metastatic castration-resistant prostate cancer.

INTRODUCTION: As treatment options for metastatic castration-resistant prostate cancer (mCRPC) expand and its patient population ages, consideration of frailty is increasingly relevant. Using a novel frailty index (FI) and two common frailty screening tools, we examined quality of life (QoL) and physical function (PF) in frail versus non-frail men receiving treatment for mCRPC. MATERIALS AND METHODS: Men aged 65+ starting docetaxel chemotherapy, abiraterone, or enzalutamide for mCRPC were enrolled in a multicenter prospective cohort study. QoL, fatigue, pain, and mood were measured with the Functional Assessment of Cancer Therapy-General scale, the Edmonton Symptom Assessment System tiredness and pain subscales, and the Patient Health Questionnaire-9. PF was evaluated with grip strength, four-meter gait speed, five times Sit-to-Stand Test, and instrumental activities of daily living. Frailty was determined using the Vulnerable Elders Survey (VES-13), the Geriatric 8 (G8), and an FI constructed from 36 variables spanning laboratory abnormalities, geriatric syndromes, functional status, social support, as well as emotional, cognitive, and physical deficits. We categorized patients as non-frail (FI ≤ 0.2, VES < 3, G8 > 14), pre-frail (FI > 0.20, ≤0.35), or frail (FI > 0.35, VES ≥ 3, G8 ≤ 14); assessed correlation between the three tools; and performed linear mixed-effects regression analyses to examine longitudinal differences in outcomes (0, 3, 6 months) by frailty status. A sensitivity analysis with worst-case imputation was conducted to explore attrition. RESULTS: We enrolled 175 men (mean age 74.9 years) starting docetaxel (n = 71), abiraterone (n = 37), or enzalutamide (n = 67). Our FI demonstrated moderate correlation with the VES-13 (r = 0.607, p < 0.001) and the G8 (r = -0.520, p < 0.001). Baseline FI score was associated with worse QoL (p < 0.001), fatigue (p < 0.001), pain (p < 0.001), mood (p < 0.001), PF (p < 0.001), and higher attrition (p < 0.01). Over time, most outcomes remained stable, although pain improved, on average, regardless of frailty status (p = 0.007), while fatigue (p = 0.045) and mood (p = 0.015) improved in frail patients alone. DISCUSSION: Among older men receiving care for mCRPC, frailty may be associated with worse baseline QoL and PF, but over time, frail patients may experience largely similar trends in QoL and PF as their non-frail counterparts. Further study with larger sample size and longer follow-up may help elucidate how best to incorporate frailty into treatment decision-making for mCRPC.

Impact of treatment on elder-relevant physical function and quality of life outcomes in older adults with metastatic castration-resistant prostate cancer.

INTRODUCTION: Understanding physical function (PF) and quality of life (QoL) treatment effects are important in treatment decision-making for older adults with cancer. However, data are limited for older men with metastatic castration-resistant prostate cancer (mCRPC). We evaluated the effects of treatment on PF and QoL in older men with mCRPC. MATERIALS AND METHODS: Men aged 65+ with mCRPC were enrolled in this multicenter prospective observational study. PF measures included instrumental activities of daily living, grip strength, chair stands, and gait speed. QoL measures included fatigue, pain, mood, and Functional Assessment of Cancer Therapy (FACT)-General total and sub-scale scores. Outcomes were collected at baseline, three, and six months. Linear mixed effects regression models were used to examine PF and QoL differences over time across various treatment cohorts. RESULTS: We enrolled 198 men starting chemotherapy (n = 71), abiraterone (n = 37), enzalutamide (n = 67), or radium-223 (n = 23). At baseline, men starting chemotherapy had worse measures of PF, QoL, pain, and mood than the other groups. Over time, all PF measures remained stable, pain improved, but functional wellbeing (FWB) and mood worsened significantly for all cohorts. However, change over time in all outcomes was not appreciably different between treatment cohorts. Worst-case sensitivity analyses identified attrition (ranging from 22 to 42% by six months) as a major limitation of our study, particularly for the radium-223 cohort. DISCUSSION: FWB and mood were most prone to deterioration over time, whereas pain improved with treatment. Although patients initiating chemotherapy had worse baseline PF and QoL, chemotherapy was not associated with significantly greater worsening over time compared to other common therapies for mCRPC. These findings may assist in treatment discussions with patients. However, given the modest sample size, attrition, and timeframe of follow-up, the impact of treatment on PF and QoL outcomes in this setting requires further study, particularly for radium-223.

Fine-grained descending control of steering in walking Drosophila.

Locomotion involves rhythmic limb movement patterns that originate in circuits outside the brain. Purposeful locomotion requires descending commands from the brain, but we do not understand how these commands are structured. Here we investigate this issue, focusing on the control of steering in walking Drosophila. First, we describe different limb "gestures" associated with different steering maneuvers. Next, we identify a set of descending neurons whose activity predicts steering. Focusing on two descending cell types downstream from distinct brain networks, we show that they evoke specific limb gestures: one lengthens strides on the outside of a turn, while the other attenuates strides on the inside of a turn. Notably, a single descending neuron can have opposite effects during different locomotor rhythm phases, and we identify networks positioned to implement this phase-specific gating. Together, our results show how purposeful locomotion emerges from brain cells that drive specific, coordinated modulations of low-level patterns.

Care provided by older adults in active cancer treatment to a spouse: A scoping review.

OBJECTIVES: Older adults with cancer may be spousal caregivers for partners with one or more chronic conditions, and there has not been an overview of the needs of this population. Therefore, we conducted a scoping review to assess what is known about the type and amount of spousal care provided by older adults (≥65 years) with any type of cancer, in the active treatment phase. MATERIALS AND METHODS: A search strategy was designed with a Health Sciences Librarian and performed using the following electronic databases from inception to January 2021: Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (Embase), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PsycInfo. Two independent reviewers screened all abstracts and full-text studies for inclusion. RESULTS: Searches were run February 26, 2020, and re-run January 8, 2021. A total of 8887 titles and abstracts were screened and 32 selected for full text review, but only two case reports were included in this review. The two case reports discussed the experience of an older adult with cancer, in active treatment, as the caregiver to a spouse. However, the type and amount of care provided by the caregiver to the spouse was not specified in either report. In both reports, caregivers declined cancer therapy to focus on the needs of the care recipients. CONCLUSION: Only two case reports were identified that examined the experiences of older adults with cancer acting as caregivers to a spouse. It is important for future studies to address this gap to better understand the needs of this population and develop future supportive interventions.

Usability Evaluation of Augmented Reality: A Neuro-Information-Systems Study.

This study introduces an experimental paradigm for a usability test of emerging technologies in a management information system (MIS). The usability test included both subjective and objective evaluations. For the subjective evaluation, a usability questionnaire and a NASA-TLX scale were adopted. For the objective evaluation, methods of Neuro-Information-Systems (NeuroIS) were used. From a NeuroIS perspective, this study used mobile fNIRS and eye tracking glasses for multimodal measurements, which solved the problem of ecological validity of cognitive neuroscience tools used in real-world behavior experiments. This study used Augmented Reality (AR) integrated into the Internet of Things (IoT) as an experimental object. Comparing the differences in the neuroimaging data, the physiological data, the usability questionnaire, and the NASA-TLX scale data between the two information-search modes (AR versus a website), information search with AR had a higher efficiency and a lower cognitive load compared with information search with a website during the process of consumption decision-making. The usability experiment results demonstrate that AR, as an emerging technology in retail, can effectively enhance consumer experiences and increase their purchase intention. The experimental paradigm, combining both subjective and objective evaluations in this study, could be applied to a usability test for emerging technologies, such as augmented reality, virtual reality, artificial intelligence, wearable technology, robotics, and big data. It provides a practical experimental solution for the user experience in human-computer-interactions with the adoption of emerging technologies.