Abstract
Background
While prior studies of platelet transfusion in critical care have focused on transfusions given, proper analysis of clinical transfusion practice also requires consideration of ...the decision not to transfuse.
Study Design and Methods
We introduce a new method to assess transfusion practice based on decision time intervals (DTIs). Each patient's intensive care (ICU) stay was segmented into a series of DTIs defined by a time interval following results of a complete blood count (CBC). We studied the presence of 17 clinical factors during each DTI whether transfusion was given or not. We used a generalized linear mixed model to assess the most influential clinical triggers for platelet transfusion.
Results
Among 6125 ICU patients treated between October 2016 and October 2021, we analyzed 39,745 DTIs among patients (n = 2921) who had at least one DTI with thrombocytopenia (≤150,000/μL). We found no association between platelet count and two markers of bleeding: drop in hemoglobin and chest tube drainage. We found that the majority of DTIs were associated with no platelet transfusion regardless of the platelet count; that no specific platelet value triggered transfusion; but rather that multiple clinical factors in conjunction with the platelet count influenced the decision to transfuse.
Discussion
DTI analysis represents a new method to assess transfusion practice that considers both transfusions given and not given, and that analyzes clinical circumstances present when decisions regarding transfusion are made. The method is easily adapted to blood components other than platelet transfusions and is easily extended to other ICU and other hospital settings.
T lymphocyte activation by antigen conditions adaptive immune responses and immunopathologies, but we know little about its variation in humans and its genetic or environmental roots. We analyzed ...gene expression in CD4(+) T cells during unbiased activation or in T helper 17 (T(H)17) conditions from 348 healthy participants representing European, Asian, and African ancestries. We observed interindividual variability, most marked for cytokine transcripts, with clear biases on the basis of ancestry, and following patterns more complex than simple T(H)1/2/17 partitions. We identified 39 genetic loci specifically associated in cis with activated gene expression. We further fine-mapped and validated a single-base variant that modulates YY1 binding and the activity of an enhancer element controlling the autoimmune-associated IL2RA gene, affecting its activity in activated but not regulatory T cells. Thus, interindividual variability affects the fundamental immunologic process of T helper activation, with important connections to autoimmune disease.
To extend our understanding of the genetic basis of human immune function and dysfunction, we performed an expression quantitative trait locus (eQTL) study of purified CD4+ T cells and monocytes, ...representing adaptive and innate immunity, in a multi-ethnic cohort of 461 healthy individuals. Context-specific cis- and trans-eQTLs were identified, and cross-population mapping allowed, in some cases, putative functional assignment of candidate causal regulatory variants for disease-associated loci. We note an over-representation of T cell–specific eQTLs among susceptibility alleles for autoimmune diseases and of monocyte-specific eQTLs among Alzheimer's and Parkinson's disease variants. This polarization implicates specific immune cell types in these diseases and points to the need to identify the cell-autonomous effects of disease susceptibility variants.
Recently, cholangioscopy using narrow band imaging (NBI) has been used as a diagnostic modality for better visualization in hepatobiliary malignancies; however, there are few reports on it. Our aim ...is to evaluate the effectiveness of cholangioscopy using NBI in hepatobiliary malignancies.
Between January 2007 and December 2016, 152 cholangioscopies using percutaneous approach were conducted in total 123 patients. Among these, 36 patients were suspicious of hepatobiliary malignancies. Thirteen patients with an ambiguous margin on endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography (MRCP), for whom NBI tipped the balance in diagnosis of lesion and decision of lesion extent by adding NBI, were involved in our study.
Underlying diseases were all malignant in 13 patients (11 bile duct cancers, 1 liver cancer, 1 pancreas cancer with common bile duct invasion). In 7 cases with papillary type tumor, minute superficial spreading tumor was detected by NBI more easily, and NBI provided a better visualization of tumor vessel and margin evaluation in 4 cases with infiltrative tumor. In 2 cases with mucin-hypersecreting tumor, NBI showed better penetration through the mucin and gave us a much clearer image. Nine patients ultimately underwent surgical resection. The margins predicted by NBI cholangioscopy were consistent with the pathological margins on the resected specimens.
In conclusion, cholangioscopy using NBI is very useful for evaluation of suspected hepatobiliary malignancies with an ambiguous margin on ERCP or MRCP. It can give us an accurate pathologic mapping, and this information seems to be essential before deciding on a treatment strategy.
Abstract
Objectives
To investigate the benefits and challenges of introducing next generation chemistry and coagulation automation.
Methods
We replaced the Roche modular preanalytic system attached ...to Roche Cobas 6000 analyzers with the Roche 8100 preanalytical line attached to the Roche Cobas 8000 and Stago STA R Max analyzers. The system included 2 add-on buffers (AOBs) for automated specimen archival and retrieval and primary-tube specimen processing. We measured turnaround time (TAT) from specimen receipt to result for chemistry and coagulation tests before, during, and after system implementation. TAT for add-on tests was also measured.
Results
We completed the system implementation during a 17-month period using existing laboratory space. The TAT for chemistry, coagulation, and add-on tests decreased significantly (P <.005, P <.001, and P <.005, respectively). We encountered several challenges, including barcode-label errors, mechanical problems, and workflow issues due to lack of bidirectional track for coagulation testing.
Conclusions
Next generation laboratory automation yielded significantly shortened and less-variable TAT, particularly for add-on testing. Our approach could help other laboratories in the process of implementing and configuring automated systems.
A micro air vehicle with a bird-mimetic up-down and twisting wing drive system was developed in this study. The Flap- ping-wing Micro Air Vehicle （FMAV）, with a 50 cm wingspan and a double-crank ...drive system, performed successful flights of up to 23 min. The performance and capabilities of the FMAV were enhanced by adapting a number of unique features, such as a bird-mimetic wing shape with a span-wise camber and an up-down and twisting wing drive mechanism with double-crank linkages, This lift-enhancing design by mimicking the flapping mechanism of a bird＇s wing enabled the 210 g FMAV to fly autonomously in an outdoor field under wind speeds of less than 5 m.s-1. Autonomous flight was enabled by installing a flight control computer with a micro-electro-mechanical gyroscope and accelerometers, along with a micro video camera and an ultralight wireless communication system inside the fuselage. A comprehensive wind tunnel test shows that the FMAV with a high-camber wing and double-crank mechanism generates more lift and less net thrust than the FMAV with a flat wing and single-crank mechanism, which confirms the improved performance of the developed FMAV, as well as the superior slow flying or hovering capabilities of the FMAV with a high-camber wing and double-crank wing drive system.
Motivation: In the human genome, ‘CpG islands’, CG-rich regions located in or near gene promoters, are normally unmethylated. However, in cancer cells, CpG islands frequently gain methylation, ...resulting in silencing of growth-limiting tumor suppressor genes. To our knowledge, the potential relationship between CpG island hypermethylation, transcription factor (TF) binding in local promoter regions and transcriptional control has not been previously explored in a genome-wide context. Results: In this study, we utilized bioinformatics tools and TF binding site(TFBs) databases to globally analyze sequences methylated in a laboratory model for the development of drug-resistant cancer. Our results demonstrated that four TFBS were enriched in hypermethylated sequences. More interestingly, overrepresentation of these TFBS was observed in hyper-/hypo-methylated sequences where significant changes in methylation levels were observed in drug-resistant cancer cells. In summary, we believe that these findings offer a means to further explore the relationship between DNA methylation and gene expression in drug resistance and tumorigenesis. Contact: sunkim2@indiana.edu; knephew@indiana.edu
To present a new method for displaying blood utilization data based on analysis of decision time intervals (DTIs).
Retrospective study of patients treated in a medical intensive care unit (ICU), ...surgical ICU, or postcardiac surgery ICU at an academic hospital between January 2018 and June 2023. Each patient's episode of care was divided into a series of DTIs. Transfusions during each time interval were recorded.
In total, 16,562 patients received 6980 units of plasma and 21,034 units of red blood cells during 111,557 time intervals of care. Patients had international normalized ratio (INR) values ranging from less than 1.0 to more than 4.0. Data on plasma transfusion at different INR values were displayed as the number of transfusion episodes, number of units given, or the proportion of DTIs with transfusion. Clinicians transfused plasma on 1.5% of occasions when the INR was 1.5 or less and on 2.2% of occasions when the INR was less than 2.0. Plasma was transfused without red blood cells in only 0.75% of DTIs. Transfusion practice was statistically different among the 3 ICUs.
Compared with traditional methods of displaying the results of blood audits, DTI analysis displays information regarding the decision both to transfuse and to not transfuse. Utilization reviews that display data based on decision time analysis reveal clinical practice patterns very different from those suggested by traditional displays of plasma audit data.
Epigenetics is the study of chromatin modifications that affect gene expression without altering DNA nucleotide sequences. This review highlights a prominent role for epigenetic therapies, ...particularly those that reverse aberrant DNA methylation and histone acetylation, in the potential treatment of cancer. Administration of such therapies to reverse epigenetic "silencing" of tumor suppressors, including genes involved in chemotherapy responses, could prove useful in the management of cancer patients. In this review, we summarize recent advances in the use of methyltransferase and histone deacetylase inhibitors and possible synergistic combinations of these to achieve maximal tumor suppressor gene re-expression. Moreover, when used in combination with conventional chemotherapeutic agents, epigenetic-based therapies may provide a means to resensitize drug-resistant tumors to established treatments. As specific, aberrant epigenetic modifications are frequently associated with distinct cancer types, and likely occur early in tumorigenesis, these have potential utility as biomarkers. Finally, future directions are addressed, including alternative epigenetic targets, gene-specific modifications, and the use of bioinformatics.
Purpose - The purpose of this paper is to present the procedure and results from instrumented flight test performed on the flapping MAVs being developed by the authors. A test is performed using a ...test measurement system to obtain the real characteristics of the flapping vehicles during their flight.Design methodology approach - The test is performed in an indoor flight test facility, equipped with a motion capture system and tracking cameras. Spatial position data are obtained from the vehicles with retro-reflective tracking markers attached. A quantitative analysis is carried out through the investigation and interpretation of the test data for the flight performance assessment of the vehicles.Findings - The finding of the analysis addresses that the test enabled the numerical measurement of vehicles' flying performance and shows the present vehicles have combined characteristics of both birds and insects.Practical implications - The test metrics attempted in the present study are applicable to the test and evaluation of general flapping micro air vehicles. Thus, this testing method will be useful for the development of future micro air vehicle system.Originality value - Full-scale instrumented flight test and measurement of performance parameters of flapping micro air vehicles other than visual observation are unprecedented and expected to present the guideline of systematic test and evaluation of flapping micro air vehicles.
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