Blood Pressure Effect of Traffic-Related Air Pollution : A Crossover Trial of In-Vehicle Filtration.

BACKGROUND: Ambient air pollution, including traffic-related air pollution (TRAP), increases cardiovascular disease risk, possibly through vascular alterations. Limited information exists about in-vehicle TRAP exposure and vascular changes. OBJECTIVE: To determine via particle filtration the effect of on-roadway TRAP exposure on blood pressure and retinal vasculature. DESIGN: Randomized crossover trial. (ClinicalTrials.gov: NCT05454930). SETTING: In-vehicle scripted commutes driven through traffic in Seattle, Washington, during 2014 to 2016. PARTICIPANTS: Normotensive persons aged 22 to 45 years (n = 16). INTERVENTION: On 2 days, on-road air was entrained into the vehicle. On another day, the vehicle was equipped with high-efficiency particulate air (HEPA) filtration. Participants were blinded to the exposure and were randomly assigned to the sequence. MEASUREMENTS: Fourteen 3-minute periods of blood pressure were recorded before, during, and up to 24 hours after a drive. Image-based central retinal arteriolar equivalents (CRAEs) were measured before and after. Brachial artery diameter and gene expression were also measured and will be reported separately. RESULTS: Mean age was 29.7 years, predrive systolic blood pressure was 122.7 mm Hg, predrive diastolic blood pressure was 70.8 mm Hg, and drive duration was 122.3 minutes (IQR, 4 minutes). Filtration reduced particle count by 86%. Among persons with complete data (n = 13), at 1 hour, mean diastolic blood pressure, adjusted for predrive levels, order, and carryover, was 4.7 mm Hg higher (95% CI, 0.9 to 8.4 mm Hg) for unfiltered drives compared with filtered drives, and mean adjusted systolic blood pressure was 4.5 mm Hg higher (CI, -1.2 to 10.2 mm Hg). At 24 hours, adjusted mean diastolic blood pressure (unfiltered) was 3.8 mm Hg higher (CI, 0.02 to 7.5 mm Hg) and adjusted mean systolic blood pressure was 1.1 mm Hg higher (CI, -4.6 to 6.8 mm Hg). Adjusted mean CRAE (unfiltered) was 2.7 µm wider (CI, -1.5 to 6.8 µm). LIMITATIONS: Imprecise estimates due to small sample size; seasonal imbalance by exposure order. CONCLUSION: Filtration of TRAP may mitigate its adverse effects on blood pressure rapidly and at 24 hours. Validation is required in larger samples and different settings. PRIMARY FUNDING SOURCE: U.S. Environmental Protection Agency and National Institutes of Health.

Assessing the effectiveness of portable HEPA air cleaners for reducing particulate matter exposure in King County, Washington homeless shelters: Implications for community congregate settings.

Over four thousand portable air cleaners (PACs) with high-efficiency particulate air (HEPA) filters were distributed by Public Health - Seattle & King County to homeless shelters during the COVID-19 pandemic. This study aimed to evaluate the real-world effectiveness of these HEPA PACs in reducing indoor particles and understand the factors that affect their use in homeless shelters. Four rooms across three homeless shelters with varying geographic locations and operating conditions were enrolled in this study. At each shelter, multiple PACs were deployed based on the room volume and PAC's clean air delivery rate rating. The energy consumption of these PACs was measured using energy data loggers at 1-min intervals to allow tracking of their use and fan speed for three two-week sampling rounds, separated by single-week gaps, between February and April 2022. Total optical particle number concentration (OPNC) was measured at 2-min intervals at multiple indoor locations and an outdoor ambient location. The empirical indoor and outdoor total OPNC were compared for each site. Additionally, linear mixed-effects regression models (LMERs) were used to assess the relationship between PAC use time and indoor/outdoor total OPNC ratios (I/OOPNC). Based on the LMER models, a 10 % increase in the hourly, daily, and total time PACs were used significantly reduced I/OOPNC by 0.034 [95 % CI: 0.028, 0.040; p < 0.001], 0.051 [95 % CI: 0.020, 0.078; p < 0.001], and 0.252 [95 % CI: 0.150, 0.328; p < 0.001], respectively, indicating that keeping PACs on resulted in significantly lower I/OOPNC. The survey suggested that keeping PACs on and running was the main challenge when operating them in shelters. These findings suggested that HEPA PACs were an effective short-term strategy to reduce indoor particle levels in community congregate living settings during non-wildfire seasons and the need for formulating practical guidance for using them in such an environment.

T cell aging and Alzheimer's disease.

The brain has long been considered an immune-privileged organ due to the presence of the blood-brain barrier (BBB). However, recent discoveries have revealed the underestimated role of T cells in the brain through the meningeal lymphatic system. Age is the primary risk factor for Alzheimer's disease (AD), resulting in marked age-dependent changes in T cells. Manipulating peripheral T cell immune response has been shown to impact AD, but the relationship between T cell aging and AD remains poorly understood. Given the limited success of targeting amyloid beta (Aß) and the growing evidence of T cells' involvement in non-lymphoid organ aging, a deeper understanding of the relationship between T cells and AD in the context of aging is crucial for advancing therapeutic progress. In this review, we comprehensively examine existing studies on T cells and AD and offer an integrated perspective on their interconnections in the context of aging. This understanding can inform the development of new interventions to prevent or treat AD.

In vitro culture of bovine fibroblasts using select serum-free media supplemented with Chlorella vulgaris extract.

Standard cell culture practices require the addition of animal-derived serum to culture media to achieve adequate cell growth. Typically, 5-10% by volume of fetal bovine serum (FBS) is used, which accounts for a vast majority of the media cost while also imposing environmental and ethical concerns associated with the use of animal serum. Here we tested the efficacy of culturing cells by replacing serum in the media with algae extract and select additives. Using LC-MS, we compared molecular signatures of FBS to Chlorella algae extracts and identified NAD(H)/NADP(H) as common and relatively abundant features in their characteristic profiles. Bovine fibroblasts, cultured in serum-free media supplemented with C. vulgaris extract and just two growth factors plus insulin, showed significant growth with enhanced viability compared to control cells cultured without serum, albeit still lower than that of controls cultured with 10% FBS. Moreover, C. vulgaris extract enhanced cell viability beyond that of cells cultured with the two growth factors and insulin alone. These results suggest that key components in serum which are essential for cell growth may also be present in C. vulgaris extract, demonstrating that it may be used at least as a partial alternative to serum for cell culture applications.

Characterization of Annual Average Traffic-Related Air Pollution Concentrations in the Greater Seattle Area from a Year-Long Mobile Monitoring Campaign.

Growing evidence links traffic-related air pollution (TRAP) to adverse health effects. We designed an innovative and extensive mobile monitoring campaign to characterize TRAP exposure levels for the Adult Changes in Thought (ACT) study, a Seattle-based cohort. The campaign measured particle number concentration (PNC) to capture ultrafine particles (UFP), black carbon (BC), nitrogen dioxide (NO2), fine particulate matter (PM2.5), and carbon dioxide (CO2) at 309 roadside sites within a large, 1200 land km2 (463 mi2) area representative of the cohort. We collected about 29 two-minute measurements at each site during all seasons, days of the week, and most times of the day over a 1-year period. Validation showed good agreement between our BC, NO2, and PM2.5 measurements and monitoring agency sites (R2 = 0.68-0.73). Universal kriging-partial least squares models of annual average pollutant concentrations had cross-validated mean square error-based R2 (and root mean square error) values of 0.77 (1177 pt/cm3) for PNC, 0.60 (102 ng/m3) for BC, 0.77 (1.3 ppb) for NO2, 0.70 (0.3 µg/m3) for PM2.5, and 0.51 (4.2 ppm) for CO2. Overall, we found that the design of this extensive campaign captured the spatial pollutant variations well and these were explained by sensible land use features, including those related to traffic.

Source Apportionment of Environmental Combustion Sources using Excitation Emission Matrix Fluorescence Spectroscopy and Machine Learning.

The link between particulate matter (PM) air pollution and negative health effects is well-established. Air pollution was estimated to cause 4.9 million deaths in 2017 and PM was responsible for 94% of these deaths. In order to inform effective mitigation strategies in the future, further study of PM and its health effects is important. Here, we present a method for identifying sources of combustion generated PM using excitation-emission matrix (EEM) fluorescence spectroscopy and machine learning (ML) algorithms. PM samples were collected during a health effects exposure assessment panel study in Seattle. We use archived field samples from the exposure study and the associated positive matrix factorization (PMF) source apportionment based on X-ray fluorescence and light absorbing carbon measurements to train convolutional neural network and principal component regression algorithms. We show EEM spectra from cyclohexane extracts of the archived filter samples can be used to accurately apportion mobile and vegetative burning sources but were unable to detect crustal dust, Cl-rich, secondary sulfate and fuel oil sources. The use of this EEM-ML approach may be used to conduct PM exposure studies that include source apportionment of combustion sources.

Activation of mTORC1 at late endosomes misdirects T cell fate decision in older individuals.

The nutrient-sensing mammalian target of rapamycin (mTOR) is integral to cell fate decisions after T cell activation. Sustained mTORC1 activity favors the generation of terminally differentiated effector T cells instead of follicular helper and memory T cells. This is particularly pertinent for T cell responses of older adults who have sustained mTORC1 activation despite dysfunctional lysosomes. Here, we show that lysosome-deficient T cells rely on late endosomes rather than lysosomes as an mTORC1 activation platform, where mTORC1 is activated by sensing cytosolic amino acids. T cells from older adults have an increased expression of the plasma membrane leucine transporter SLC7A5 to provide a cytosolic amino acid source. Hence, SLC7A5 and VPS39 deficiency (a member of the HOPS complex promoting early to late endosome conversion) substantially reduced mTORC1 activities in T cells from older but not young individuals. Late endosomal mTORC1 is independent of the negative-feedback loop involving mTORC1-induced inactivation of the transcription factor TFEB that controls expression of lysosomal genes. The resulting sustained mTORC1 activation impaired lysosome function and prevented lysosomal degradation of PD-1 in CD4+ T cells from older adults, thereby inhibiting their proliferative responses. VPS39 silencing of human T cells improved their expansion to pertussis and to SARS-CoV-2 peptides in vitro. Furthermore, adoptive transfer of CD4+ Vps39-deficient LCMV-specific SMARTA cells improved germinal center responses, CD8+ memory T cell generation, and recall responses to infection. Thus, curtailing late endosomal mTORC1 activity is a promising strategy to enhance T cell immunity.

Improving Air Pollution Predictions of Long-Term Exposure Using Short-Term Mobile and Stationary Monitoring in Two US Metropolitan Regions.

Mobile monitoring is increasingly employed to measure fine spatial-scale variation in air pollutant concentrations. However, mobile measurement campaigns are typically conducted over periods much shorter than the decadal periods used for modeling chronic exposure for use in air pollution epidemiology. Using the regions of Los Angeles and Baltimore and the time period from 2005 to 2014 as our modeling domain, we investigate whether including mobile or stationary passive sampling device (PSD) monitoring data collected over a single 2-week period in one or two seasons using a unified spatio-temporal air pollution model can improve model performance in predicting NO2 and NOx concentrations throughout the 9-year study period beyond what is possible using only routine monitoring data. In this initial study, we use data from mobile measurement campaigns conducted contemporaneously with deployments of stationary PSDs and only use mobile data collected within 300 m of a stationary PSD location for inclusion in the model. We find that including either mobile or PSD data substantially improves model performance for pollutants and locations where model performance was initially the worst (with the most-improved R2 changing from 0.40 to 0.82) but does not meaningfully change performance in cases where performance was already very good. Results indicate that in many cases, additional spatial information from mobile monitoring and personal sampling is potentially cost-efficient inexpensive way of improving exposure predictions at both 2-week and decadal averaging periods, especially for the predictions that are located closer to features such as roadways targeted by the mobile short-term monitoring campaign.

Field measurements of PM2.5 infiltration factor and portable air cleaner effectiveness during wildfire episodes in US residences.

Wildfires have frequently occurred in the western United States (US) during the summer and fall seasons in recent years. This study measures the PM2.5 infiltration factor in seven residences recruited from five dense communities in Seattle, Washington, during a 2020 wildfire episode and evaluates the impacts of HEPA-based portable air cleaner (PAC) use on reducing indoor PM2.5 levels. All residences with windows closed went through an 18-to-24-h no filtration session, with five of seven following that period with an 18-to-24-h filtration session. Auto-mode PACs, which automatically adjust the fan speed based on the surrounding PM2.5 levels, were used for the filtration session. 10-s resolved indoor PM2.5 levels were measured in each residence's living room, while hourly outdoor levels were collected from the nearest governmental air quality monitoring station to each residence. Additionally, a time-activity diary in minute resolution was collected from each household. With the impacts of indoor sources excluded, indoor PM2.5 mass balance models were developed to estimate the PM2.5 indoor/outdoor (I/O) ratios, PAC effectiveness, and decay-related parameters. Among the seven residences, the mean infiltration factor ranged from 0.33 (standard deviation [SD]: 0.06) to 0.76 (SD: 0.05). The use of auto-mode PAC led to a 48%-78% decrease of indoor PM2.5 levels after adjusting for outdoor PM2.5 levels and indoor sources. The mean (SD) air exchange rates ranged from 0.30 (0.13) h-1 to 1.41 (3.18) h-1 while the PM2.5 deposition rate ranged from 0.10 (0.54) h-1 to 0.49 (0.47) h-1. These findings suggest that staying indoors, a common protective measure during wildfire episodes, is insufficient to prevent people's excess exposure to wildfire smoke, and provides quantitative evidence to support the utilization of auto-mode PACs during wildfire events in the US.

Distinct Ultrafine Particle Profiles Associated with Aircraft and Roadway Traffic.

The Mobile ObserVations of Ultrafine Particles study was a two-year project to analyze potential air quality impacts of ultrafine particles (UFPs) from aircraft traffic for communities near an international airport. The study assessed UFP concentrations within 10 miles of the airport in the directions of aircraft flight. Over the course of four seasons, this study conducted a mobile sampling scheme to collect time-resolved measures of UFP, CO2, and black carbon (BC) concentrations, as well as UFP size distributions. Primary findings were that UFPs were associated with both roadway traffic and aircraft sources, with the highest UFP counts found on the major roadway (I-5). Total concentrations of UFPs alone (10-1000 nm) did not distinguish roadway and aircraft features. However, key differences existed in the particle size distribution and the black carbon concentration for roadway and aircraft features. These differences can help distinguish between the spatial impact of roadway traffic and aircraft UFP emissions using a combination of mobile monitoring and standard statistical methods.

The GSK3ß-ß-catenin-TCF1 pathway improves naive T cell activation in old adults by upregulating miR-181a.

MicroRNAs play an important role in the regulation of T cell development, activation, and differentiation. One of the most abundant microRNAs in lymphocytes is miR-181a, which controls T cell receptor (TCR) activation thresholds in thymic selection as well as in peripheral T cell responses. We previously found that miR-181a levels decline in T cells in the elderly. In this study, we identified TCF1 as a transcriptional regulator of pri-miR-181a. A decline in TCF1 levels in old individuals accounted for the reduced miR-181a expression impairing TCR signaling. Inhibition of GSK3ß restored expression of miR-181a by inducing TCF1 in T cells from old adults. GSK3ß inhibition enhanced TCR signaling to increase downstream expression of activation markers and production of IL-2. The effect involved the upregulation of miR-181a and the inhibition of DUSP6 expression. Thus, inhibition of GSK3ß can restore responses of old T cells by inducing miR-181a expression through TCF1.

Impact of a computerized decision support tool deployed in two intensive care units on acute kidney injury progression and guideline compliance: a prospective observational study.

BACKGROUND: Acute kidney injury (AKI) affects a large proportion of the critically ill and is associated with worse patient outcomes. Early identification of AKI can lead to earlier initiation of supportive therapy and better management. In this study, we evaluate the impact of computerized AKI decision support tool integrated with the critical care clinical information system (CCIS) on patient outcomes. Specifically, we hypothesize that integration of AKI guidelines into CCIS will decrease the proportion of patients with Stage 1 AKI deteriorating into higher stages of AKI. METHODS: The study was conducted in two intensive care units (ICUs) at University Hospitals Bristol, UK, in a before (control) and after (intervention) format. The intervention consisted of the AKIN guidelines and AKI care bundle which included guidance for medication usage, AKI advisory and dashboard with AKI score. Clinical data and patient outcomes were collected from all patients admitted to the units. AKI stage was calculated using the Acute Kidney Injury Network (AKIN) guidelines. Maximum AKI stage per admission, change in AKI stage and other metrics were calculated for the cohort. Adherence to eGFR-based enoxaparin dosing guidelines was evaluated as a proxy for clinician awareness of AKI. RESULTS: Each phase of the study lasted a year, and a total of 5044 admissions were included for analysis with equal numbers of patients for the control and intervention stages. The proportion of patients worsening from Stage 1 AKI decreased from 42% (control) to 33.5% (intervention), p = 0.002. The proportion of incorrect enoxaparin doses decreased from 1.72% (control) to 0.6% (intervention), p < 0.001. The prevalence of any AKI decreased from 43.1% (control) to 37.5% (intervention), p < 0.05. CONCLUSIONS: This observational study demonstrated a significant reduction in AKI progression from Stage 1 and a reduction in overall development of AKI. In addition, a reduction in incorrect enoxaparin dosing was also observed, indicating increased clinical awareness. This study demonstrates that AKI guidelines coupled with a newly designed AKI care bundle integrated into CCIS can impact patient outcomes positively.

Impacts of the COVID-19 responses on traffic-related air pollution in a Northwestern US city.

This study evaluates the COVID-19 impacts on traffic-related air pollution, including ultrafine particles (UFPs), PM2.5, black carbon (BC), NO, NO2, NOx, and CO in a Northwestern US city. Hourly traffic, air pollutants, and meteorological data on/near a major freeway in the downtown of Seattle, Washington, were collected for five weeks before and ten weeks after the Washington Stay Home Order (SHO) was enacted, respectively (February 17-May 31, 2020). The pollutants between pre- and post-SHO periods were compared, and their differences were statistically tested. Besides, first-order multivariate autoregressive (MAR(1)) models were developed to reveal the impacts specific to the change of traffic due to the COVID-19 responses while controlling for meteorological conditions. Results indicate that compared with those in the post-SHO period, the median traffic volume and road occupancy decreased by 37% and 52%, respectively. As for pollutants, the median BC and PM2.5 levels significantly decreased by 25% and 33%, relatively, while NO, NO2, NOx, and CO decreased by 33%, 29%, 30%, and 17%, respectively. In contrast, neither size-resolved UFPs nor total UFPs showed significant changes between the two periods, although larger particles (≥115.5 nm) decreased by 4-29%. Additionally, significant differences were found in meteorological conditions between the two periods. Based on the MAR(1) models, controlling for meteorological conditions, the COVID-19 responses were associated with significant decreases in median levels of traffic-related pollutants including 11.5-154.0 nm particles (ranging from -3% [95% confidence interval (CI): -1%, -4%] to -12% [95% CI: -10%, -14%]), total UFPs (-7% [95% CI: -5%, -8%]), BC (-6% [95% CI: -5%, -7%]), PM2.5 (-2% [95% CI: -1%, -3%]), NO, NO2, NOx (ranging from -3% [95% CI: -2%, -4%] to -10% [95% CI: -18%, -12%]), and CO (-4% [95% CI, -3%, -5%]). These findings illustrate that the conclusion of the COVID-19 impacts on urban traffic-related air pollutant levels could be completely different in scenarios whether meteorology was adjusted for or not. Fully adjusting for meteorology, this study shows that the COVID-19 responses were associated with much more reductions in traffic-related UFPs than PM2.5 in the Seattle region, in contrast to the reverse trend from the direct empirical data comparison.

Developing a Low-Cost Passive Method for Long-Term Average Levels of Light-Absorbing Carbon Air Pollution in Polluted Indoor Environments.

We propose a low-cost passive method for monitoring long-term average levels of light-absorbing carbon air pollution in polluted indoor environments. Building on prior work, the method here estimates the change in reflectance of a passively exposed surface through analysis of digital images. To determine reproducibility and limits of detection, we tested low-cost passive samplers with exposure to kerosene smoke in the laboratory and to environmental pollution in 20 indoor locations. Preliminary results suggest robust reproducibility (r = 0.99) and limits of detection appropriate for longer-term (~1-3 months) monitoring in households that use solid fuels. The results here suggest high precision; further testing involving "gold standard" measurements is needed to investigate accuracy.

Ecto-NTPDase CD39 is a negative checkpoint that inhibits follicular helper cell generation.

Vaccination is a mainstay in preventive medicine, reducing morbidity and mortality from infection, largely by generating pathogen-specific neutralizing antibodies. However, standard immunization strategies are insufficient with increasing age due to immunological impediments, including defects in T follicular helper (Tfh) cells. Here, we found that Tfh generation is inversely linked to the expression of the ecto-NTPDase CD39 that modifies purinergic signaling. The lineage-determining transcription factor BCL6 inhibited CD39 expression, while increased Tfh frequencies were found in individuals with a germline polymorphism preventing transcription of ENTPD1, encoding CD39. In in vitro human and in vivo mouse studies, Tfh generation and germinal center responses were enhanced by reducing CD39 expression through the inhibition of the cAMP/PKA/p-CREB pathway, or by blocking adenosine signaling downstream of CD39 using the selective adenosine A2a receptor antagonist istradefylline. Thus, purinergic signaling in differentiating T cells can be targeted to improve vaccine responses, in particular in older individuals who have increased CD39 expression.

Critical care transfer in an English critical care network: Analysis of 1124 transfers delivered by an ad-hoc system.

BACKGROUND: Critical care transfers between hospitals are time critical high-risk episodes for unstable patients who often require urgent lifesaving intervention. This study aimed to establish the scale, nature and safety of current transfer practice in the South West Critical Care Network (SWCCN) in England. METHODS: The SWCCN database contains prospectively collected data in accordance with national guidelines. It was interrogated for all adult (>15 years of age) patients from January 2012 to November 2017. RESULTS: A total of 1124 inter-hospital transfers were recorded, with the majority (935, 83.2%) made for specialist treatment. The transferring team included a doctor in 998 (88.8%) and nurse in 935 (93.7%) transfers. In 204 (18.1%) transfers, delays occurred, with the commonest cause being availability of transport. Critical incidents occurred in 77 (6.9%). CONCLUSIONS: This is the first published data on the transfer activity of a UK adult critical care network. It demonstrates that current ad-hoc provision is not meeting the longstanding expectations of national guidelines in terms of training, clinical experience and timeliness. The authors hope that this study may inform national conversation regarding the development of National Health Service commissioned inter-hospital transfer services for adult patients in England.

Using Vehicles' Rendezvous for In Situ Calibration of Instruments in Fleet Vehicle-Based Air Pollution Mobile Monitoring.

This study examines the feasibility of the in situ calibration of instruments for fleet vehicle-based mobile monitoring of ultrafine particles (UFPs) and black carbon (BC) by comparing rendezvous vehicle measurements. Two vehicles with identical makes and models of UFP and BC monitors as well as GPS receivers were sampled within 140 m of each other for 2 h in total during winter in Seattle, Washington. To identify an optimal intervehicle distance for rendezvous calibration, 6 different buffers within 0-140 m for UFP monitors and 5 different buffers within 0-90 m for BC monitors were chosen, and the results of calibration were compared against a reference scenario, which consisted of mobile colocation measurements with both sets of the UFP and BC monitors deployed in one of the vehicles. Results indicate that the optimal distances for rendezvous calibration are 10-80 m for UFP monitors and 0-30 m for BC monitors. In comparison with the mobile colocation calibration, the rendezvous calibration shows a normalized root mean squared deviation of 6-14% and a normalized mean absolute deviation of 4-8% for these monitors. Criteria for applying a rendezvous calibration approach are presented, and an extension of this approach to an instrumented fleet of mobile monitoring vehicles is discussed.

uMBD: A Materials-Ready Dispersion Correction That Uniformly Treats Metallic, Ionic, and van der Waals Bonding.

Materials design increasingly relies on first-principles calculations for screening important candidates and for understanding quantum mechanisms. Density functional theory (DFT) is by far the most popular first-principles approach due to its efficiency and accuracy. However, to accurately predict structures and thermodynamics, DFT must be paired with a van der Waals (vdW) dispersion correction. Therefore, such corrections have been the subject of intense scrutiny in recent years. Despite significant successes in organic molecules, no existing model can adequately cover the full range of common materials, from metals to ionic solids, hampering the applications of DFT for modern problems such as battery design. Here, we introduce a universally optimized vdW-corrected DFT method that demonstrates an unbiased reliability for predicting molecular, layered, ionic, metallic, and hybrid materials without incurring a large computational overhead. We use our method to accurately predict the intercalation potentials of layered electrode materials of a Li-ion battery system, a problem for which the existing state-of-the-art methods fail. Thus, we envisage broad use of our method in the design of chemo-physical processes of new materials.

Determinants governing T cell receptor α/ß-chain pairing in repertoire formation of identical twins.

The T cell repertoire in each individual includes T cell receptors (TCRs) of enormous sequence diversity through the pairing of diverse TCR α- and ß-chains, each generated by somatic recombination of paralogous gene segments. Whether the TCR repertoire contributes to susceptibility to infectious or autoimmune diseases in concert with disease-associated major histocompatibility complex (MHC) polymorphisms is unknown. Due to a lack in high-throughput technologies to sequence TCR α-ß pairs, current studies on whether the TCR repertoire is shaped by host genetics have so far relied only on single-chain analysis. Using a high-throughput single T cell sequencing technology, we obtained the largest paired TCRαß dataset so far, comprising 965,523 clonotypes from 15 healthy individuals including 6 monozygotic twin pairs. Public TCR α- and, to a lesser extent, TCR ß-chain sequences were common in all individuals. In contrast, sharing of entirely identical TCRαß amino acid sequences was very infrequent in unrelated individuals, but highly increased in twins, in particular in CD4 memory T cells. Based on nucleotide sequence identity, a subset of these shared clonotypes appeared to be the progeny of T cells that had been generated during fetal development and had persisted for more than 50 y. Additional shared TCRαß in twins were encoded by different nucleotide sequences, implying that genetic determinants impose structural constraints on thymic selection that favor the selection of TCR α-ß pairs with entire sequence identities.

Descriptive study of differences in acute kidney injury progression patterns in General and Cardiac Intensive Care Units.

BACKGROUND: Acute kidney injury is common in critically ill patients with detrimental effects on mortality, length of stay and post-discharge outcomes. The Acute Kidney Injury Network developed guidelines based on urine output and serum creatinine to classify patients into stages of acute kidney injury. METHODS: In this analysis we utilize the Acute Kidney Injury Network guidelines to evaluate the acute kidney injury stage in patients admitted to general and cardiac intensive care units over a period of 18 months. Acute kidney injury stage was calculated in real time hourly based on the guidelines and using these temporal stage scores calculated for the population; the prevalence and progression of acute kidney injury stage was compared between the two units. We hypothesized that the prevalence and progression of acute kidney injury stage between the two units may be different. RESULTS: More cardiac intensive care unit patients had no acute kidney injury (stage <1) during their intensive care unit stay but more cardiac intensive care unit patients developed acute kidney injury (stage >1), compared to the General Intensive Care Unit. Both at intensive care unit admission and discharge, more General Intensive Care Unit patients had acute kidney injury; however, the number of cardiac intensive care unit patients with acute kidney injury was three times higher at discharge than admission. Acute kidney injury developed in a different pattern in the two intensive care units over five days of intensive care unit stay. In the General Intensive Care Unit, acute kidney injury was most prevalent on second day of intensive care unit stay and in cardiac intensive care unit acute kidney injury was most prevalent on the third day of intensive care unit stay. We observed the biggest increase in new acute kidney injury in the first day of General Intensive Care Unit and second day of the cardiac intensive care unit stay. CONCLUSIONS: The study demonstrates the different trends of acute kidney injury pattern in general and cardiac intensive care unit patient populations highlighting the earlier development of acute kidney injury on General Intensive Care Unit and more prevalence of acute kidney injury on discharge from cardiac intensive care unit.