Faculty Bibliography

Background: Our previous study showed that PH without a transplant (tx) had worse HRQoL compared to the US Standard Population and worsened with increased stone frequency. We now show the first longitudinal HRQoL profiles for PH patients with transplants.
Method(s): PH participants were enrolled from the Rare Kidney Stone Consortium registry. HRQoL was measured with a generic non-disease specific instrument (SF-36v2). Results were calculated as norm-based scores (NBS) based on US Standard Population (Mean domain score = 50). We created three groups based on the time of last stone event (<= 30 days, 31 - 365 days, >;366 days). The study compared HRQoL for participants with a kidney and/or liver transplant over 5 different time points.
Result(s): This sub-sample included 100 surveys of 32 PH participants (16 males and 16 females) with a tx. The mean age was 47 years for both males and females. This subsample includes 24 participants with liver/kidney tx (75%) and 8 with kidney tx only (25%). Participants with only a kidney tx reported significantly more stone events within a year (26% vs 13%, X2 =0.028). Two way ANOVA did not find a change in HRQoL profiles over time for PH participants with kidney or kidney/liver tx (figure). Most mean domain scores are 50 or above, except for the domain of General Health which was less. Participants with only a kidney tx scored significantly lower in role physical, bodily pain, general health, social function, and physical component score (data not shown) than participants with kidney/liver tx. There was no difference between male and female participants over time.
Conclusion(s): PH participants with kidney/liver tx achieve better HRQoL, measured with a non-disease specific generic instrument, than those with kidney alone; both are better when compared to the US Standard Population. The majority of PH participants with a tx are stone-free, with a direct beneficial impact on their HRQoL

How does neural activity generate perception? The spatial identities and temporal latencies of activated units correlate with external sensory features, but finding the subspace of activity that is consequential for perception, remains challenging. We trained mice to recognize synthetic odors: optogenetically-driven spatiotemporal patterns of glomerular activity in the olfactory bulb. We then performed precise spatial or temporal perturbations on trained patterns and measured how recognition changes. Changes in recognition reflect the perceptual relevance of the modified feature. We modeled recognition as the matching of glomerular activity to learned templates, and uncovered what forms a perceptually-meaningful pattern template: activation sequences ordered by latencies relative to each other, with surprisingly minimal effect of sniff. Within templates, spatially-identified glomeruli contribute additively, with larger contributions from earlier-activated glomeruli. Template matching with these perceptually-meaningful features can account for animals' responses, with the degree of mismatch predicting changes in recognition. The model accurately generalizes to novel spatio-temporal manipulations of patterns, and produces non-linear responses that resemble the non-linear responses in the data. This is the first report to our knowledge, that not only establishes a causal role for neural activity sequences in perception, but also uncovers the perceptually-relevant coding schemes governing these sequences. Our synthetic approach reveals the fundamental logic of the olfactory code, and provides a general framework for testing links between sensory activity and perception

The piriform cortex is the first area of integration for all peripheral odor information and it is believed to generate a unique and wholistic representation of behavioral relevance, sensory object. However, what properties of the cortical neural population activity define odor objects remains unknown. To address this question, we recorded cortical spiking responses to synthetic odors made of fully parameterized optogenetic activity patterns in the olfactory bulb, enabling independent and precise control of the incoming neural responses unattainable with natural odorants. Then, we measured changes in the neural response to a range of controlled spatial and temporal perturbations of the pattern for which we previously established their behavioral relevance. We developed an experimental approach to systematically probe cortical neural activity and found features of the population code which represent behaviorally relevant information

The Drosophila visual system integrates input from 800 ommatidia and extracts different features in stereotypically connected optic ganglia. The development of the Drosophila visual system is controlled by gene regulatory networks that control the number of precursor cells, generate neuronal diversity by integrating spatial and temporal information, coordinate the timing of retinal and optic lobe cell differentiation, and determine distinct synaptic targets of each cell type. In this chapter, we describe the known gene regulatory networks involved in the development of the different parts of the visual system and explore general components in these gene networks. Finally, we discuss the advantages of the fly visual system as a model for gene regulatory network discovery in the era of single-cell transcriptomics.

Background: The COVID-19 pandemic was associated with a greater incidence of AKI than expected. At the NY Harbor VA we faced an overwhelming number of AKI patients who were critically ill with multi-organ failure. We needed to invoke new mechanisms of providing kidney replacement therapy (KRT).
Method(s): We obtained 3 Tablo systems in late March, 2019. The machines have selfcontained reverse osmosis capabilities and so do not require other equipment to operate. They can make dialysate from concentrate and tap water and so do not require special plumbing adaptation. Their self-contained step-by-step procedures are relatively simple to follow and allow rapid training of previously unskilled personnel. Tablo generates 300 ml dialysate per minute, and blood flow was increased to up to 400 ml/min as tolerated.
Result(s): Training was completed by 2 nephrologists and 2 RNs without previous dialysis experience. We used the Tablo Hemodialysis System to provide KRT to critically ill patients. In the first week we demonstrated that water cultures and endotoxin testing were negative, and that AAMI water tests were acceptable. We used the machines to provide KRT for ICU patients with double-lumen dialysis catheters. In addition we used the machines on hospital wards where KRT had not been provided before because of a lack of the plumbing needs of conventional HD machines. We provided multiple treatments 3-6 times per week for 15 AKI patients, mean age 65 years. The mean of the best urea reduction ratio achieved in the first 1-4 treatments, if available, was 41% (often limited by hypotension and fulfillment of ultrafiltration, UF, needs). Most treatments were successful and were slowed for hypotension or tachycardia. Some were aborted because of water pressure alarms if sediment filters needed replacement, or lines clotted due to hypercoagulability associated with COVID-19. Personnel availability dictated that most treatments were 3-4 hours (and up to 8h), and generally achieved UF goals. Later HD nurses cannulated arteriovenous fistulas in ESKD patients and left treatment to non-HD nurses to complete.
Conclusion(s): By incorporating a user-friendly platform and an accelerated training program including nephrologists and RNs without previous dialysis experience, we were able to nearly double our capacity to deliver KRT during the surge