Monitoring of cerebral blood flow autoregulation: physiologic basis, measurement, and clinical implications.

Cerebral blood flow (CBF) autoregulation is the physiologic process whereby blood supply to the brain is kept constant over a range of cerebral perfusion pressures ensuring a constant supply of metabolic substrate. Clinical methods for monitoring CBF autoregulation were first developed for neurocritically ill patients and have been extended to surgical patients. These methods are based on measuring the relationship between cerebral perfusion pressure and surrogates of CBF or cerebral blood volume (CBV) at low frequencies (<0.05 Hz) of autoregulation using time or frequency domain analyses. Initially intracranial pressure monitoring or transcranial Doppler assessment of CBF velocity was utilised relative to changes in cerebral perfusion pressure or mean arterial pressure. A more clinically practical approach utilising filtered signals from near infrared spectroscopy monitors as an estimate of CBF has been validated. In contrast to the traditional teaching that 50 mm Hg is the autoregulation threshold, these investigations have found wide interindividual variability of the lower limit of autoregulation ranging from 40 to 90 mm Hg in adults and 20-55 mm Hg in children. Observational data have linked impaired CBF autoregulation metrics to adverse outcomes in patients with traumatic brain injury, ischaemic stroke, subarachnoid haemorrhage, intracerebral haemorrhage, and in surgical patients. CBF autoregulation monitoring has been described in both cardiac and noncardiac surgery. Data from a single-centre randomised study in adults found that targeting arterial pressure during cardiopulmonary bypass to above the lower limit of autoregulation led to a reduction of postoperative delirium and improved memory 1 month after surgery compared with usual care. Together, the growing body of evidence suggests that monitoring CBF autoregulation provides prognostic information on eventual patient outcomes and offers potential for therapeutic intervention. For surgical patients, personalised blood pressure management based on CBF autoregulation data holds promise as a strategy to improve patient neurocognitive outcomes.

Role of Cognitive Frailty in Older Adults With Cardiovascular Disease.

As the older adult population expands, an increasing number of patients affected by geriatric syndromes are seen by cardiovascular clinicians. One such syndrome that has been associated with poor outcomes is cognitive frailty: the simultaneous presence of cognitive impairment, without evidence of dementia, and physical frailty, which results in decreased cognitive reserve. Driven by common pathophysiologic underpinnings (eg, inflammation and neurohormonal dysregulation), cardiovascular disease, cognitive impairment, and frailty also share the following risk factors: hypertension, diabetes, obesity, sedentary behavior, and tobacco use. Cardiovascular disease has been associated with the onset and progression of cognitive frailty, which may be reversible in early stages, making it essential for clinicians to diagnose the condition in a timely manner and prescribe appropriate interventions. Additional research is required to elucidate the mechanisms underlying the development of cognitive frailty, establish preventive and therapeutic strategies to address the needs of older patients with cardiovascular disease at risk for cognitive frailty, and ultimately facilitate targeted intervention studies.

Poor olfaction prior to cardiac surgery: Association with cognition, plasma neurofilament light, and post-operative delirium.

OBJECTIVES: Post-operative delirium (POD) affects up to 50% of cardiac surgery patients, with higher incidence in older adults. There is increasing need for screening tools that identify individuals most vulnerable to POD. Here, we examined the relationship between pre-operative olfaction and both incident POD and POD severity in patients undergoing cardiac surgery. We also examined cross-sectional relationships between baseline olfaction, cognition, and plasma neurofilament light (NfL). METHODS: Individuals undergoing cardiac surgery (n = 189; mean age = 70 years; 75% men) were enrolled in a clinical trial of cerebral autoregulation monitoring. At baseline, odor identification performance (Brief Smell Identification Test), cognitive performance, and plasma concentrations of NfL levels (Simoa™ NF-Light Assay) were measured. Delirium was assessed with the Confusion Assessment Method (CAM) or CAM-ICU, and delirium severity was assessed using the Delirium Rating Scale-Revised-98. The association of baseline olfaction, delirium incidence, and delirium severity was examined in regression models adjusting for age, duration of cardiopulmonary bypass, logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE), and baseline cognition. RESULTS: Olfactory dysfunction was present in 30% of patients, and POD incidence was 44%. Pre-operative olfactory dysfunction was associated with both incident POD (OR = 3.17, p = 0.001) and greater severity of POD after cardiac surgery (OR = 3.94 p < 0.001) in models adjusted for age, duration of bypass, and a surgical risk score. The addition of baseline cognition attenuated the strength of the association, but it remained significant for incident POD (OR = 2.25, p = 0.04) and POD severity (OR 2.10, p = 0.04). Poor baseline olfaction was associated with greater baseline cognitive dysfunction (p < 0.001) and increased baseline plasma NfL concentrations (p = 0.04). Neither age, cognition, nor baseline NFL concentration modified the association of impaired olfaction and delirium outcomes. CONCLUSIONS: Olfactory assessment may be a useful pre-surgical screening tool for the identification of patients undergoing cardiac surgery at increased risk of POD. Identifying those at highest risk for severe delirium and poor cognitive outcomes following surgery would allow for earlier intervention and pre-operative rehabilitation strategies, which could ultimately impact the functional disability and morbidity associated with POD.

Emergence of Thelaziosis Caused by Thelazia callipaeda in Dogs and Cats, United States.

We report 2 autochthonous feline thelaziosis cases caused by the eyeworm Thelazia callipaeda and discuss the spread among dogs in the northeastern United States. Phylogenetic analysis suggests the parasite was introduced from Europe. Adopting a One Health approach is needed to limit further spread of T. callipaeda eyeworms in North America.

Continuous Monitoring of Cerebral Autoregulation in Adults Supported by Extracorporeal Membrane Oxygenation.

BACKGROUND: Impaired cerebral autoregulation (CA) is one of several proposed mechanisms of acute brain injury in patients supported by extracorporeal membrane oxygenation (ECMO). The primary aim of this study was to determine the feasibility of continuous CA monitoring in adult ECMO patients. Our secondary aims were to describe changes in cerebral oximetry index (COx) and other metrics of CA over time and in relation to functional neurologic outcomes. METHODS: This is a single-center prospective observational study. We measured COx, a surrogate measurement of cerebral blood flow measured by near-infrared spectroscopy, which is an index of CA derived from the moving correlation between mean arterial pressure (MAP) and slow waves of regional cerebral oxygen saturation. A COx value that approaches 1 indicates impaired CA. Using COx, we determined the optimal MAP (MAPOPT) and lower and upper limits of autoregulation for individual patients. These measurements were examined in relation to modified Rankin Scale (mRS) scores. RESULTS: Fifteen patients (median age 57 years [interquartile range 47-69]) with 150 autoregulation measurements were included for analysis. Eleven were on veno-arterial ECMO (VA-ECMO), and four were on veno-venous ECMO (VV-ECMO). Mean COx was higher on postcannulation day 1 than on day 2 (0.2 vs. 0.09, p < 0.01), indicating improved CA over time. COx was higher in VA-ECMO patients than in VV-ECMO patients (0.12 vs. 0.06, p = 0.04). Median MAPOPT for the entire cohort was highly variable, ranging from 55 to 110 mm Hg. Patients with mRS scores 0-3 (good outcome) at 3 and 6 months spent less time outside MAPOPT compared with patients with mRS scores 4-6 (poor outcome) (74% vs. 82%, p = 0.01). The percentage of time when observed MAP was outside the limits of autoregulation was higher on postcannulation day 1 than on day 2 (18.2% vs. 3.3%, p < 0.01). CONCLUSIONS: In ECMO patients, it is feasible to monitor CA continuously at the bedside. CA improved over time, most significantly between postcannulation days 1 and 2. CA was more impaired in VA-ECMO patients than in VV-ECMO patients. Spending less time outside MAPOPT may be associated with achieving a good neurologic outcome.

Human iPSC-Based Model of COPD to Investigate Disease Mechanisms, Predict SARS-COV-2 Outcome, and Test Preventive Immunotherapy.

Chronic inflammation and dysregulated repair mechanisms after epithelial damage have been implicated in chronic obstructive pulmonary disease (COPD). However, the lack of ex vivo-models that accurately reflect multicellular lung tissue hinders our understanding of epithelial-mesenchymal interactions in COPD. Through a combination of transcriptomic and proteomic approaches applied to a sophisticated in vitro iPSC-alveolosphere with fibroblasts model, epithelial-mesenchymal crosstalk was explored in COPD and following SARS-CoV-2 infection. These experiments profiled dynamic changes at single-cell level of the SARS-CoV-2-infected alveolar niche that unveiled the complexity of aberrant inflammatory responses, mitochondrial dysfunction, and cell death in COPD, which provides deeper insights into the accentuated tissue damage/inflammation/remodeling observed in patients with SARS-CoV-2 infection. Importantly, this 3D system allowed for the evaluation of ACE2-neutralizing antibodies and confirmed the potency of this therapy to prevent SARS-CoV-2 infection in the alveolar niche. Thus, iPSC-alveolosphere cultured with fibroblasts provides a promising model to investigate disease-specific mechanisms and to develop novel therapeutics.

Sleep fragmentation disrupts Lyme arthritis resolution in mice.

STUDY OBJECTIVES: Lyme arthritis is a common late-stage complication of infection by Borrelia burgdorferi, the agent of Lyme disease. Patients with Lyme arthritis report increased levels of sleep disturbance associated with pain. Using a mouse model of experimental Lyme arthritis, we investigated the effect of disrupted sleep on the development and resolution of joint inflammation. METHODS: Lyme arthritis-susceptible C3H/HeJ mice (n = 10/group) were infected with B. burgdorferi and were left either alone (control) or subjected to sleep fragmentation (SF). Arthritis development or resolution were monitored. The impact of SF on immune and inflammatory parameters such as arthritis severity scores, anti-borrelia antibody production, and bacterial clearance was measured. We also determined the effect of SF on arthritis resolution in C3H mice deficient in leukotriene (LT) B4 signaling (BLT1/2-/-) who display delayed Lyme arthritis resolution. RESULTS: SF had no significant impact on Lyme arthritis development or inflammatory parameters regardless of whether SF treatment began 1 week prior to or congruent with infection. However, initiation of SF at the peak of arthritis resulted in a significant delay in arthritis resolution as measured by joint edema, arthritis severity scores, and decreased bacterial clearance from the joint. This was accompanied by significant changes in joint cytokine transcription levels (e.g., increased TNFα and decreased IL-4). SF has no significant impact on Lyme arthritis resolution in the BLT1/2-/- mice. CONCLUSIONS: Poor sleep, especially near the peak of arthritis inflammation, may delay initiation of resolution programs possibly through altering cytokine production and host immune responses, leading to defects in spirochete clearance and prolonged disease.

Association of perioperative plasma concentration of neurofilament light with delirium after cardiac surgery: a nested observational study.

BACKGROUND: Neurofilament light is a blood-based biomarker of neuroaxonal injury that can provide insight into perioperative brain vulnerability and injury. Prior studies have suggested that increased baseline and postoperative concentrations of neurofilament light are associated with delirium after noncardiac surgery, but results are inconsistent. Results have not been reported in cardiac surgery patients, who are among those at highest risk for delirium. We hypothesised that perioperative blood concentrations of neurofilament light (both baseline and change from baseline to postoperative day 1) are associated with delirium after cardiac surgery. METHODS: This study was nested in a trial of arterial blood pressure targeting during cardiopulmonary bypass using cerebral autoregulation metrics. Blood concentrations of neurofilament light were measured at baseline and on postoperative day 1. The primary outcome was postoperative delirium. Regression models were used to examine the associations between neurofilament light concentration and delirium and delirium severity, adjusting for age, sex, race, logistic European System for Cardiac Operative Risk Evaluation, bypass duration, and cognition. RESULTS: Delirium occurred in 44.6% of 175 patients. Baseline neurofilament light concentration was higher in delirious than in non-delirious patients (median 20.7 pg ml-1 [IQR 16.1-33.2] vs median 15.5 pg ml-1 [IQR 12.1-24.2], P<0.001). In adjusted models, greater baseline neurofilament light concentration was associated with delirium (odds ratio, 1.027; 95% confidence interval, 1.003-1.053; P=0.029) and delirium severity. From baseline to postoperative day 1, neurofilament light concentration increased by 42%, but there was no association with delirium. CONCLUSIONS: Baseline neurofilament light concentration, but not change from baseline to postoperative day 1, was associated with delirium after cardiac surgery.

HPV18 L1 and long control region sequences variation and E6/E7 differential expression in nasopharyngeal and cervical cancers: a comparative study.

BACKGROUND: The role of high-risk human papillomaviruses (hr-HPVs) in cervical cancer (CC) pathogenesis has long been established. Knowledge about the involvement of hr-HPVs in the etiology of nasopharyngeal cancers (NPC) was not well appreciated until the early 2000s when a clear link began to emerge. However, it is not clear whether HPV oncogenesis in the different epithelial cancers is associated with L1 gene and long-control region (LCR) sequences variation. This study aimed to investigate the HPV18 L1 gene and LCR sequences variation in cervical and nasopharyngeal biopsies, and assessed E6 and E7 genes expression level in both cancers. METHOD: Four-hundred and three (403) formalin-fixed paraffin-embedded tissues originating from nasopharyngeal (NPC) (279) and cervical (CC) (124) sites were collected from a pathology laboratory, Pathologist Without Borders, Accra, Ghana. Haematoxylin and eosin staining was carried out to confirm the presence of cancer on prepared biopsy sections. DNA was extracted from the confirmed cancer biopsies, followed by PCR using MY09/GP5+ /6+ primers to detect the presence of HPV and specific primers for the amplification of L1 gene and LCR. Sanger sequencing was carried out to determine HPV genotypes, and L1 and LCR sequences variant of HPV18s in CC and NPC biopsies. The HPV18 E6/E7 mRNA expression pattern in both cancers was determined using RT-qPCR. RESULTS: Most of the NPC (45%) and CC (55%) biopsies were HPV18 positive. Comparison of HPV18 L1 sequences obtained from cervical and nasopharyngeal cancer tissues, the L1 sequences from the NPC were highly dissimilar with a 59-100% variation among themselves, and in relation to the reference strains. However, the L1 sequences from the CC were more similar with a 91.0-100% variation among the amplified sequences. Also, the LCR sequences from CC were quite different relative to that of NPC. Results for the differential expression of E6/E7 in the two cancers showed a higher fold change in E6 expression in the CC tissues than the NPC tissues while a reverse expression pattern was found for E7 gene. CONCLUSION: The current study reports for the first-time variations in HPV18 L1 and LCR sequences, and differential expression of E6/E7 genes in NPC compared to CC, suggesting a possible adaptation mechanism of the virus at different cancer sites.

Diel activity structures the occurrence of a mammal community in a human-dominated landscape.

Anthropogenic developments alter the environment and resources available to wildlife communities. In response to these real or perceived threats from this development, species may adjust their spatial occurrence. Additionally, wildlife species may adjust when in diel time (24-h light-dark cycle) they occupy sites on the landscape to adapt to changing conditions. However, many wildlife studies only focus on where a species does and does not occur, ignoring how species may shift their diel activity at sites to mitigate threats. We used a multi-state diel occupancy modeling framework to investigate how a community of mammals (mesocarnivores, urban-adapted omnivores, and herbivore/small mammals) respond to differing levels of anthropogenic development and forest cover across two climatic seasons. We collected camera trap data at 240 survey locations across the summer and winter of 2021-2022. We modeled multi-state diel occupancy for 14 mammal species with extent of development/forest and season hypothesized to influence diel occupancy and season hypothesized to influence the probability of detection. We found that all species displayed heterogeneity in both diel occupancy and detection either by extent of development/forest and or season. Within the mesocarnivore species group, coyote and red fox were less sensitive to development and had higher occupancy probability at these sites in general but used them more during the night, while more sensitive mesocarnivores including fisher and bobcat occupied the day state only when there was increasing forest cover. Our results highlight the importance of incorporating diel activity in habitat modeling to better understand the relationship between a species and its landscape, particularly in a region that is vulnerable to increased anthropogenic pressure.

Prediction of lactate concentrations after cardiac surgery using machine learning and deep learning approaches.

Background: Although conventional prediction models for surgical patients often ignore intraoperative time-series data, deep learning approaches are well-suited to incorporate time-varying and non-linear data with complex interactions. Blood lactate concentration is one important clinical marker that can reflect the adequacy of systemic perfusion during cardiac surgery. During cardiac surgery and cardiopulmonary bypass, minute-level data is available on key parameters that affect perfusion. The goal of this study was to use machine learning and deep learning approaches to predict maximum blood lactate concentrations after cardiac surgery. We hypothesized that models using minute-level intraoperative data as inputs would have the best predictive performance. Methods: Adults who underwent cardiac surgery with cardiopulmonary bypass were eligible. The primary outcome was maximum lactate concentration within 24 h postoperatively. We considered three classes of predictive models, using the performance metric of mean absolute error across testing folds: (1) static models using baseline preoperative variables, (2) augmentation of the static models with intraoperative statistics, and (3) a dynamic approach that integrates preoperative variables with intraoperative time series data. Results: 2,187 patients were included. For three models that only used baseline characteristics (linear regression, random forest, artificial neural network) to predict maximum postoperative lactate concentration, the prediction error ranged from a median of 2.52 mmol/L (IQR 2.46, 2.56) to 2.58 mmol/L (IQR 2.54, 2.60). The inclusion of intraoperative summary statistics (including intraoperative lactate concentration) improved model performance, with the prediction error ranging from a median of 2.09 mmol/L (IQR 2.04, 2.14) to 2.12 mmol/L (IQR 2.06, 2.16). For two modelling approaches (recurrent neural network, transformer) that can utilize intraoperative time-series data, the lowest prediction error was obtained with a range of median 1.96 mmol/L (IQR 1.87, 2.05) to 1.97 mmol/L (IQR 1.92, 2.05). Intraoperative lactate concentration was the most important predictive feature based on Shapley additive values. Anemia and weight were also important predictors, but there was heterogeneity in the importance of other features. Conclusion: Postoperative lactate concentrations can be predicted using baseline and intraoperative data with moderate accuracy. These results reflect the value of intraoperative data in the prediction of clinically relevant outcomes to guide perioperative management.

Continuous Monitoring of Cerebral Autoregulation in Adults Supported by Extracorporeal Membrane Oxygenation.

Background: Impaired cerebral autoregulation (CA) is one of several proposed mechanisms of acute brain injury in patients supported by extracorporeal membrane oxygenation (ECMO). The primary aim of this study was to determine the feasibility of continuous CA monitoring in adult ECMO patients. Our secondary aims were to describe changes in cerebral oximetry index (COx) and other metrics of CA over time and in relation to functional neurologic outcomes. Methods: This is a single-center prospective observational study. We measured Cox, a surrogate measurement of cerebral blood flow, measured by near-infrared spectroscopy, which is an index of CA derived from the moving correlation between mean arterial pressure and slow waves of regional cerebral oxygen saturation. A COx value that approaches 1 indicates impaired CA. Using COx, we determined the optimal MAP (MAPOPT), lower and upper limits of autoregulation for individual patients. These measurements were examined in relation to modified Rankin Scale (mRS) scores. Results: Fifteen patients (median age=57 years [IQR=47-69]) with 150 autoregulation measurements were included for analysis. Eleven were on veno-arterial ECMO and 4 on veno-venous. Mean COx was higher on post-cannulation day 1 than on day 2 (0.2 vs 0.09, p<0.01), indicating improved CA over time. COx was higher in VA-ECMO patients than in VV-ECMO (0.12 vs 0.06, p=0.04). Median MAPOPT for entire cohort was highly variable, ranging 55-110 mmHg. Patients with mRS 0-3 (good outcome) at 3 and 6 months spent less time outside of MAPOPT compared to patients with mRS 4-6 (poor outcome) (74% vs 82%, p=0.01). The percentage of time when observed MAP was outside the limits of autoregulation was higher on post-cannulation day 1 than on day 2 (18.2% vs 3.3%, p<0.01). Conclusions: In ECMO patients, it is feasible to monitor CA continuously at the bedside. CA improved over time, most significantly between post-cannulation days 1 and 2. CA was more impaired in VA-ECMO than VV-ECMO. Spending less time outside of MAPOPT may be associated with achieving a good neurologic outcome.

Knowledge, attitudes and practices regarding malaria prevention and control in communities in the Eastern Region, Ghana, 2020.

BACKGROUND: In sub-Saharan Africa countries including Ghana, the malaria burden remains unacceptably high and still a serious health challenge. Evaluating a community's level of knowledge, attitude, and practice (KAP) regarding malaria is essential to enabling appropriate preventive and control measures. This study aimed to evaluate knowledge of malaria, attitudes toward the disease, and adoption of control and prevention practices in some communities across the Eastern Region of Ghana. METHODS: A cross­sectional based study was carried out in 13 communities across 8 districts from January -June, 2020. Complete data on socio-demographic characteristics and KAP were obtained from 316 randomly selected household respondents by a structured pre-tested questionnaire. Associations between KAP scores and socio-demographic profiles were tested by Chi-square and binary logistic regression. Data analysis was done with SPSS version 26.0. RESULTS: Most respondents (85.4%) had good knowledge score about malaria. Preferred choice of treatment seeking place (50.6%) was the health center/clinic. All respondents indicated they would seek treatment within 24 hours. Mosquito coils were the preferred choice (58.9%) against mosquito bites. Majority of households (58.5%) had no bed nets and bed net usage was poor (10.1%). Nearly half of the respondents (49.4%) had a positive attitude toward malaria and 40.5% showed good practices. Chi-square analysis showed significant associations for gender and attitude scores (p = 0.033), and educational status and practice scores (p = 0.023). Binary logistic regression analysis showed that 51-60 year-olds were less likely to have good knowledge (OR = 0.20, p = 0.04) than 15-20 year-olds. Respondents with complete basic schooling were less likely to have good knowledge (OR = 0.33, p = 0.04) than those with no formal schooling. A positive attitude was less likely in men (OR = 0.61, p = 0.04). Good malaria prevention practice was lower (OR = 0.30, p = 0.01) in participants with incomplete basic school education compared to those with no formal schooling. CONCLUSION: Overall scores for respondents' knowledge, though good, was not reflected in attitudes and levels of practice regarding malaria control and prevention. Behavioral change communication, preferably on radio, should be aimed at attitudes and practice toward the disease.

Impact of Sources of Strength on adolescent suicide deaths across three randomized trials.

Universal interventions are key to reducing youth suicide rates, yet no universal intervention has demonstrated reduction in suicide mortality through an RCT. This study pooled three cluster-RCTs of Sources of Strength (n=78 high schools), a universal social network-informed intervention. In each trial, matched pairs of schools were assigned to immediate intervention or wait-list. Six schools were assigned without a pair due to logistical constraints. During the study period, no suicides occurred in intervention schools vs four in control schools, that is, suicide rates of 0 vs. 20.86/100,000, respectively. Results varied across statistical tests of impact. A state-level exact test pooling all available schools showed fewer suicides in intervention vs. control schools (p=0.047); whereas a stricter test involving only schools with a randomised pair found no difference (p=0.150). Results suggest that identifying mortality-reducing interventions will require commitment to new public-health designs optimised for population-level interventions, including adaptive roll-out trials.

12/15-lipoxygenase activity promotes efficient inflammation resolution in a murine model of Lyme arthritis.

Infection of C3H/HeJ (C3H) mice with Borrelia burgdorferi results in the development of a robust inflammatory arthritis that peaks around 3-4 weeks post-infection and then spontaneously resolves over the next few weeks. Mice lacking cyclooxygenase (COX)-2 or 5-lipoxygenase (5-LO) activity develop arthritis similar to wild-type mice but display delayed or prolonged joint resolution. Since 12/15-lipoxygenase (12/15-LO) activity is generally down-stream of both COX-2 and 5-LO activity and results in the production of pro-resolution lipids such as lipoxins and resolvins among others, we investigated the impact of 12/15-LO deficiency on the resolution of Lyme arthritis in mice on a C3H background. We found the expression of Alox15 (12/15-LO gene) peaked around 4-weeks post-infection in C3H mice suggesting a role for 12/15-LO in mediating arthritis resolution. A deficiency in 12/15-LO resulted in exacerbated ankle swelling and arthritis severity during the resolution phase without compromising anti-Borrelia antibody production and spirochete clearance. However, clearance of inflammatory cells was impeded. Therapeutic treatment of B. burgdorferi-infected C3H mice with lipoxin A4 (LXA4) near the peak of disease resulted in significantly decreased ankle swelling and a switch of joint macrophages to a resolving phenotype but did not directly impact arthritis severity. These results demonstrate that 12/15-LO lipid metabolites are important components of inflammatory arthritis resolution in murine Lyme arthritis and may be a therapeutic target for treatment of joint edema and pain for Lyme arthritis patients without compromising spirochete clearance.

Michelson Interferometer for Global High-Resolution Thermospheric Imaging (MIGHTI) On-Orbit Wind Observations: Data Analysis and Instrument Performance.

The design, principles of operation, calibration, and data analysis approaches of the Michelson Interferometer for Global High-resolution Thermospheric Imaging (MIGHTI) on the NASA Ionospheric Connection (ICON) satellite have been documented prior to the ICON launch. Here we update and expand on the MIGHTI wind data analysis and discuss the on-orbit instrument performance. In particular, we show typical raw data and we describe key processing steps, including the correction of a "signal-intensity dependent phase shift," which is necessitated by unexpected detector behavior. We describe a new zero-wind calibration approach that is preferred over the originally planned approach due to its higher precision. Similar to the original approach, the new approach is independent of any a priori data. A detailed update on the wind uncertainties is provided and compared to the mission requirements, showing that MIGHTI has met the ICON mission requirements. While MIGHTI observations are not required to produce absolute airglow brightness profiles, we describe a relative brightness profile product, which is included in the published data. We briefly review the spatial resolution of the MIGHTI wind data in addition to the data coverage and data gaps that occurred during the nominal mission. Finally, we include comparisons of the MIGHTI wind data with ground-based Fabry-Perot interferometer observations and meteor radar observations, updating previous studies with more recent data, again showing good agreement. The data processing steps covered in this work and all the derived wind data correspond to the MIGHTI data release Version 5 (v05).

Molecular epidemiology of Cryptosporidium species in Kpong and its environs, Ghana.

BACKGROUND: Cryptosporidium is a ubiquitous enteric protozoan pathogen infecting humans, domestic animals, and wildlife worldwide. It is a waterborne pathogen with recognized zoonotic potential and a definite cause of diarrhea and nutritional disorders in institutional and community settings. One challenge facing the world's supply of clean drinking water is contamination from feces and soil. It has been established that small quantities of oocysts, the infective stage, can cause human disease. Also, their resistance to chlorination and other water treatment procedures has been demonstrated. Kpong, a community in the Lower Manya Krobo Municipality of the Eastern Region of Ghana, is one of the primary sources of water supply to Accra, the capital city of Ghana. Being able to determine the effectiveness of water treatment processes and identifying sources of contamination of this pathogen in our water bodies is thus of public health importance. The study aimed to conduct molecular epidemiology of Cryptosporidium spp. in the Lower Manya Krobo Municipality. METHODOLOGY/PRINCIPAL FINDINGS: A total of 230 samples, 180 fecal samples from cattle and 50 water samples (tap water and well water) were collected from the following communities: Kpong, Akwernor, Ablotsi, Nuaso, and Atua, all in the Lower Manya Krobo Municipality. Samples were screened for Cryptosporidium by microscopy and PCR. The 18S rRNA gene was amplified by nested polymerase chain reaction (PCR), and the final product was sequenced. The prevalence of Cryptosporidium from the fecal samples was estimated as 10% (18/180) by microscopy, while all 50 water samples were negative. However, PCR gave the prevalence of Cryptosporidium as 47.8% (86/180) for fecal samples and 20% (10/50) for water samples. Based on the 18S rRNA gene, three sequenced samples showed high homology to C. parvum species. The phylogenetic analysis confirmed this as these sequences clustered with C. parvum sequences from other countries. CONCLUSION/SIGNIFICANCE: Cryptosporidium parvum was identified as the persistent species in the study communities. This outcome supports the evidence that domesticated animals serve as potential reservoirs of zoonotic transmission of cryptosporidiosis. The persistence of cryptosporidiosis in cattle indicates its presence in the human population. In addition, the presence of Cryptosporidium parvum in the wells makes it alarming and necessary to consider a holistic approach such as One Health Strategies to identify and control cases in humans.

Investigation on the driver-victim pairs in pedestrian and bicyclist crashes by latent class clustering and random forest algorithm.

Pedestrians and bicyclists from marginalized and underserved populations experienced disproportionate fatalities and injury rates due to traffic crashes in the US. This disparity among road users of different races and the increasing trend of traffic risk for underserved racial groups called for an urgent agenda for transportation policy making and research to ensure equity in roadway safety. Pedestrian and bicyclist crashes involved drivers and pedestrians/bicyclists; the latter were usually victims. Traditional safety studies did not account for the interaction between the two parties and assumed that they were independent from each other. In this study we paired the driver and pedestrian/bicyclist involved in the same crash to understand the socioeconomic and demographic make-up of the two parties involved in crashes and assessed the geographic distribution of these crashes and crash-contributing factors. For this purpose, we applied thelatent class clustering analysis (LCA) to classify different crash types and analyze the patterns of the crashes based on the income and ethnicity of both drivers and victims involved in pedestrian and bicyclist crashes. We then used random forest algorithms and partial dependence plots (PDPs) to model and interpreted the contributing factors of the clusters in both pedestrian and bicyclist models. The clustering results showed a pattern of social segregation in pedestrian and bicyclist crashes that drivers and victims with similar socioeconomic characteristics tend to be involved in one crash. Pedestrian/bicyclist exposure, driver's age, victim's age, year of the car in use, annual average daily traffic (AADT), speed limit, roadbed width, and lane width were the most influential factors contributing to this pattern. Crashes that involved drivers and victims with lower income and non-white ethnicity tended to happen in the location with higher pedestrian/bicyclist exposure, higher speed limit, and wider road. The findings of this research can help to inform the decision-making process for improving safety to ensure equitable and sustainable safety for all road users and communities.

Incidence of Dementia Following Hospitalization With Infection Among Adults in the Atherosclerosis Risk in Communities (ARIC) Study Cohort.

Importance: Factors associated with the risk of dementia remain to be fully understood. Systemic infections are hypothesized to be such factors and may be targets for prevention and screening. Objective: To investigate the association between hospitalization with infection and incident dementia. Design, Setting, and Participants: Data from the community-based Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study, were used. Enrollment occurred at 4 research centers in the US, initiated in 1987 to 1989. The present study includes data up to 2019, for 32 years of follow-up. Data analysis was performed from April 2021 to June 2022. Exposures: Hospitalizations with infections were identified via medical record review for selected International Classification of Diseases, Ninth Revision (ICD-9) and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes, from baseline until administrative censoring or dementia diagnosis. Participants were considered unexposed until first hospitalization with infection and exposed thereafter. Selected infection subtypes were also considered. Main Outcomes and Measures: Incident dementia and time-to-event data were identified through surveillance of ICD-9 and ICD-10 hospitalization and death certificate codes, in-person assessments, and telephone interviews. A sensitivity analysis was conducted excluding cases occurring within 3 years or beyond 20 years from exposure. Data were collected before study hypothesis formulation. Results: Of the 15 792 ARIC study participants, an analytical cohort of 15 688 participants who were dementia free at baseline and of Black or White race were selected (8658 female [55.2%]; 4210 Black [26.8%]; mean [SD] baseline age, 54.7 [5.8] years). Hospitalization with infection occurred among 5999 participants (38.2%). Dementia was ascertained in 2975 participants (19.0%), at a median (IQR) of 25.1 (22.2-29.1) years after baseline. Dementia rates were 23.6 events per 1000 person-years (95% CI, 22.3-25.0 events per 1000 person-years) among the exposed and 5.7 events per 1000 person-years (95% CI, 5.4-6.0 events per 1000 person-years) among the unexposed. Patients hospitalized with infection were 2.02 (95% CI, 1.88-2.18; P < .001) and 1.70 (95% CI, 1.55-1.86; P < .001) times more likely to experience incident dementia according to unadjusted and fully adjusted Cox proportional hazards models compared with individuals who were unexposed. When excluding individuals who developed dementia less than 3 years or more than 20 years from baseline or the infection event, the adjusted hazard ratio was 5.77 (95% CI, 4.92-6.76; P < .001). Rates of dementia were significantly higher among those hospitalized with respiratory, urinary tract, skin, blood and circulatory system, or hospital acquired infections. Multiplicative and additive interactions were observed by age and APOE-ε genotype. Conclusions and Relevance: Higher rates of dementia were observed among participants who experienced hospitalization with infection. These findings support the hypothesis that infections are factors associated with higher risk of dementias.