A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation.

The isocortex and hippocampal formation (HPF) in the mammalian brain play critical roles in perception, cognition, emotion, and learning. We profiled ∼1.3 million cells covering the entire adult mouse isocortex and HPF and derived a transcriptomic cell-type taxonomy revealing a comprehensive repertoire of glutamatergic and GABAergic neuron types. Contrary to the traditional view of HPF as having a simpler cellular organization, we discover a complete set of glutamatergic types in HPF homologous to all major subclasses found in the six-layered isocortex, suggesting that HPF and the isocortex share a common circuit organization. We also identify large-scale continuous and graded variations of cell types along isocortical depth, across the isocortical sheet, and in multiple dimensions in hippocampus and subiculum. Overall, our study establishes a molecular architecture of the mammalian isocortex and hippocampal formation and begins to shed light on its underlying relationship with the development, evolution, connectivity, and function of these two brain structures.

Digital Proxy of a Bio-Reactor (DIYBOT) combines sensor data and data analytics to improve greywater treatment and wastewater management systems.

Technologies to treat wastewater in decentralized systems are critical for sustainable development. Bioreactors are suitable for low-energy removal of inorganic and organic compounds, particularly for non-potable applications where a small footprint is required. One of the main problems associated with bioreactor use is sporadic spikes of chemical toxins, including nanoparticles. Here, we describe the development of DIYBOT (Digital Proxy of a Bio-Reactor), which enables remote monitoring of bioreactors and uses the data to inform decisions related to systems management. To test DIYBOT, a household-scale membrane aerated bioreactor with real-time water quality sensors was used to treat household greywater simulant. After reaching steady-state, silver nanoparticles (AgNP) representative of the mixture found in laundry wastewater were injected into the system to represent a chemical contamination. Measurements of carbon metabolism, effluent water quality, biofilm sloughing rate, and microbial diversity were characterized after nanoparticle exposure. Real-time sensor data were analyzed to reconstruct phase-space dynamics and extrapolate a phenomenological digital proxy to evaluate system performance. The management implication of the stable-focus dynamics, reconstructed from observed data, is that the bioreactor self-corrects in response to contamination spikes at AgNP levels below 2.0 mg/L. DIYBOT may help reduce the frequency of human-in-the-loop corrective management actions for wastewater processing.

The effect of Tegaderm™ versus EyeGard® on eyelid erythema during general anesthesia: a randomized-controlled trial.

PURPOSE: Application of adhesive tape to the eyelids during general anesthesia decreases the risk of corneal abrasion but may increase the risk of eyelid injury. The aim of this study was to determine if there is a difference in eyelid erythema when covering the eyelid with either Tegaderm™ or an EyeGard®. METHODS: We conducted a prospective, randomized, double-blind, split-face study of patients undergoing general anesthesia at an urban tertiary care academic medical centre. Each patient was randomized to having one eyelid covered with Tegaderm and the other with EyeGard. Photographs were taken prior to extubation and evaluated by three dermatologists. The primary outcome was the incidence of postoperative eyelid erythema. Secondary outcomes included the incidence of corneal abrasion and patient satisfaction. RESULTS: A total of 151 patients were included in our final analysis. Erythema was present on 117 (77%) eyelids covered with Tegaderm and 105 (70%) eyelids covered with EyeGard (% difference, 8; 95% confidence interval, 2 to 14; P = 0.03). No corneal abrasions were reported. The median [interquartile range] patient satisfaction score with eyelid condition was similar with Tegaderm vs EyeGard (5 [5-5] vs 5 [5-5], respectively; P = 0.84). CONCLUSION: We found a small increase in postoperative eyelid erythema when using Tegaderm compared with EyeGard. While EyeGard could decrease the risk of eyelid erythema, this should be balanced against other potential benefits of Tegaderm such as protection from fluids leaking onto the cornea. TRIAL REGISTRATION: www.ClinicalTrials.gov (NCT03549429); registered 8 June, 2018.

RéSUMé: OBJECTIF: L'application de ruban adhésif sur les paupières pendant l'anesthésie générale réduit le risque d'abrasion cornéenne mais pourrait augmenter le risque de lésion aux paupières. L'objectif de cette étude était de déterminer s'il existe une différence dans l'incidence d'érythème de la paupière lorsque l'on couvre la paupière à l'aide d'un Tegaderm™ ou d'un EyeGard®. MéTHODE: Nous avons réalisé une étude prospective, randomisée, à double insu et à visage divisé auprès de patients subissant une anesthésie générale dans un centre médical universitaire urbain de soins tertiaires. Chaque patient a été randomisé à avoir une paupière couverte de Tegaderm et l'autre d'un EyeGard. Des photos ont été prises avant l'extubation et évaluées par trois dermatologistes. Le critère d'évaluation principal était l'incidence d'érythème postopératoire de la paupière. Les critères secondaires comprenaient l'incidence d'abrasion cornéenne et la satisfaction des patients. RéSULTATS: Au total, 151 patients ont été inclus dans notre analyse finale. Il y avait présence d'érythème sur 117 (77 %) paupières couvertes de Tegaderm et 105 (70 %) paupières couvertes d'un EyeGard (% de différence, 8; intervalle de confiance 95 %, 2 à 14; P = 0,03). Aucune abrasion cornéenne n'a été rapportée. Le score médian [écart interquartile] de satisfaction des patients en ce qui touchait à l'état de leurs paupières était semblable pour le Tegaderm et le EyeGard (5 [5­5] vs 5 [5­5], respectivement; P = 0,84). CONCLUSION: Nous avons observé une légère augmentation du nombre d'érythèmes postopératoires de la paupière lors de l'utilisation du Tegaderm comparativement au EyeGard. Alors que le EyeGard pourrait réduire le risque d'érythème de la paupière, il convient de sous-peser ses avantages par rapport aux autres avantages potentiels du Tegaderm tels que la protection contre les liquides coulant sur la cornée. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT03549429); enregistrée le 8 juin 2018.

Platelet transfusion as treatment for factor V deficiency in the parturient: a case report.

BACKGROUND: Congenital factor V deficiency, also called parahemophilia, is a rare hematological disorder that can be treated with platelet transfusion. CASE PRESENTATION: A 27-year-old G2P0100 with factor V deficiency was admitted for induction of labor and requested labor epidural analgesia. Throughout her hospital course, factor V levels were managed per recommendation from her hematologist, which included transfusing fresh frozen plasma (FFP) to maintain a factor V level of 50% before any neuraxial technique and 40% for postpartum hemostasis. The parturient required multiple transfusions of FFP to stay at this level, which eventually resulted in pulmonary edema. Given the request to maintain high levels of factor V, the parturient was transfused with platelets as an alternative source of factor V. The parturient eventually delivered a healthy neonate without signs of postpartum hemorrhage or epidural hematoma. CONCLUSION: A major learning point from this case is that platelet transfusion is an effective alternative in the management of factor V deficiency. Factor V released by platelets has enhanced procoagulant function, resulting in local factor V concentrations 100 times more than that of plasma, and has a significantly extended half-life. Platelet transfusion should be considered as a therapy in treating parturients with factor V deficiency.

Src deficient mice demonstrate behavioral and electrophysiological alterations relevant to psychiatric and developmental disease.

Much evidence suggests that hypofunction of the N-methyl-d-aspartate glutamate receptor (NMDAR) may contribute broadly towards a subset of molecular, cognitive and behavioral abnormalities common among psychiatric and developmental diseases. However, little is known about the specific molecular changes that lead to NMDAR dysfunction. As such, personalized approaches to remediating NMDAR dysfunction based on a specific etiology remains a challenge. Sarcoma tyrosine kinase (Src) serves as a hub for multiple signaling mechanisms affecting GluN2 phosphorylation and can be disrupted by convergent alterations of various signaling pathways. We recently showed reduced Src signaling in post mortem tissue from schizophrenia patients, despite increased MK-801 binding and NMDA receptor complex expression in the postsynaptic density (PSD). These data suggest that Src dysregulation may be an important underlying mechanism responsible for reduced glutamate signaling. Despite this evidence for a central role of Src in NMDAR signaling, little is known about how reductions in Src activity might regulate phenotypic changes in cognition and behavior. As such, the current study sought to characterize behavioral and electrophysiological phenotypes in mice heterozygous for the Src Acl gene (Src+/- mice). Src+/- mice demonstrated decreased sociability and working memory relative to Src+/+ (WT) mice while no significant differences were seen on locomotive activity and anxiety-related behavior. In relation to WT mice, Src+/- mice showed decreased mid-latency P20 auditory event related potential (aERP) amplitudes, decreased mismatch negativity (MMN) and decreased evoked gamma power, which was only present in males. These data indicate that Src+/- mice are a promising new model to help understand the pathophysiology of these electrophysiological, behavioral and cognitive changes. As such, we propose that Src+/- mice can be used in the future to evaluate potential therapeutic approaches by targeting increased Src activity as a common final pathway for multiple etiologies of SCZ and other diseases characterized by reduced glutamate function.

Racial Differences in Prostate Cancer Treatment: The Role of Socioeconomic Status.

OBJECTIVE: This study examines whether socioeconomic status (SES), measured at both the individual and neighborhood levels, is associated with receipt of definitive treatment for localized prostate cancer and whether these associations mediate racial differences in treatment between non-Hispanic White and non-Hispanic Black men. DESIGN: The Philadelphia Area Prostate Cancer Access Study (P2 Access) is a mailed, cross-sectional survey of men sampled from the Pennsylvania Cancer Registry, combined with neighborhood Census data. SETTING: Eight counties in southeastern Pennsylvania. PARTICIPANTS: 2,386 men with prostate adenocarcinoma. MAIN MEASURES: Receipt of definitive treatment, race, self-reported income, education, employment status, and neighborhood SES. RESULTS: Overall, Black and White men were equally likely to receive definitive treatment. Men living in neighborhoods with higher SES were more likely to receive definitive treatment (OR 1.57, 95%CI 1.01, 2.42). Among men who received definitive treatment, Black men were significantly less likely to receive radical prostatectomy compared with White men (OR .71, 95% CI .52, .98), as were men with some college education compared with those with a high school education or less (OR .66, 95% CI .47, .94). SES does not mediate racial differences in receipt of definitive treatment or the type of definitive treatment received, and associations with income or employment status were not significant. CONCLUSIONS: These results stress the importance of examining racial disparities within geographic areas and highlight the unique associations that different measures of SES, particularly neighborhood SES and education, may have with prostate cancer treatment.

Racial Differences in Geographic Access to Medical Care as Measured by Patient Report and Geographic Information Systems.

BACKGROUND: Geographic access-the travel burden required to reach medical care-is an important aspect of care. Studies, which typically rely on geographic information system (GIS) calculated travel times, have found some evidence of racial disparities in spatial access to care. However, the validity of these studies depends on the accuracy of travel times by patient race. OBJECTIVES: To determine if there are racial differences when comparing patient-reported and GIS-calculated travel times. RESEARCH DESIGN: Data came from the Philadelphia Area Prostate Cancer Access Study (P Access), a cohort study of men diagnosed with localized prostate cancer. We conducted cross-sectional analysis of 2136 men using multivariable linear mixed-effects models to examine the effect of race on differences in patient-reported and GIS-calculated travel times to urology and radiation oncology cancer providers. RESULTS: Patient-reported travel times were, on an average, longer than GIS-calculated times. For urology practices, median patient-reported travel times were 12.7 minutes longer than GIS-calculated travel times for blacks versus 7.2 minutes longer for whites. After adjusting for potential confounders, including socioeconomic status and car access, the difference was significantly greater for black patients than white patients (2.0 min; 95% confidence interval, 0.58-3.44). CONCLUSIONS: GIS-calculated travel time may underestimate access to care, especially for black patients. Future studies that use GIS-calculated travel times to examine racial disparities in spatial access to care might consider including patient-reported travel times and controlling for factors that might affect the accuracy of GIS-calculated travel times.

A multidimensional view of racial differences in access to prostate cancer care.

BACKGROUND: Racial disparities in prostate cancer treatment and outcomes are widespread and poorly understood. In the current study, the authors sought to determine whether access to care, measured across multiple dimensions, contributed to racial differences in prostate cancer. METHODS: The Philadelphia Area Prostate Cancer Access Study (P2 Access) included 2374 men diagnosed with localized prostate cancer between 2012 and 2014. Men were surveyed to assess their experiences accessing care (response rate of 51.1%). The authors determined appointment availability at 151 urology practices using simulated patient telephone calls and calculated travel distances using geospatial techniques. Multivariable logistic regression models were used to determine the association between 5 different domains of access (availability, accessibility, accommodation, affordability, and acceptability) and receipt of treatment, perceived quality of care, and physician-patient communication. RESULTS: There were 1907 non-Hispanic white and 394 black men in the study cohort. Overall, approximately 85% of the men received definitive treatment with no differences noted by race. Black men were less likely to report a high quality of care (69% vs 81%; P<.001) and good physician-patient communication (60% vs 71%; P<.001) compared with white men. In adjusted models, none of the 5 domains of access were found to be associated with definitive treatment overall or with radical prostatectomy. All access domains were associated with perceived quality of care and communication, although these domains did not mediate racial disparities. CONCLUSIONS: To the authors' knowledge, the current study presents the first comprehensive assessment of prostate cancer care access, treatment, and patient experience, demonstrating that although access was related to overall perceived quality of care and better physician-patient communication, it did not appear to explain observed racial differences. Cancer 2017;123:4449-57. © 2017 American Cancer Society.

EEG biomarkers of target engagement, therapeutic effect, and disease process.

Studies suggest that abnormalities in glutamate and GABA signaling contribute to deficits in schizophrenia and related conditions and that these neurochemical abnormalities produce changes in electroencephalographic (EEG) indices, including event-related potentials and event-related power within specific frequency ranges. Furthermore, clinical studies suggest that a subset of EEG biomarkers is associated with symptoms. This review addresses the relationship between EEG and behavior in preclinical models of N-methyl-d-aspartate (NMDA)-receptor hypofunction, as well as how these models can be used to screen therapies. Data from schizophrenia patients are juxtaposed with data from animal models, and EEG and behavioral data from mice with disruption of NMDA receptors in excitatory and/or inhibitory neurons are then compared to the pattern observed in schizophrenia. Also discussed are results following exposure to potential therapeutic agents, including GABAB agonists. Furthermore, evidence demonstrates that elevated resting gamma power is associated with deficits in social interactions. Consistent with elevated baseline noise, excitatory neurons from transgenic mice show increased intrinsic excitability in in vitro-slice patch-clamp studies across model systems. GABAB receptor agonists reduce this excitability, improve gamma-band responses, and reverse behavioral deficits in mice. Data suggest that baseline gamma power is associated with social function and GABAB agonists may be useful for schizophrenia. Translational EEG biomarkers reflect target engagement and can contribute to the design of more efficient drug trials, likely accelerating the development of new therapeutics for central nervous system disorders.