Summary The detrimental effects of stress on human health are being increasingly recognized. There is a critical need for the establishment of a biomarker that accurately measures its intensity and ...course over time. Such a biomarker would allow monitoring of stress, increase understanding of its pathophysiology and may help identify appropriate and successful management strategies. Whereas saliva and urine cortisol capture real-time levels, hair cortisol analysis presents a complementary means of monitoring stress, capturing systemic cortisol exposure over longer periods of time. This novel approach for cortisol quantification is being increasingly used to identify the effects of stress in a variety of pathological situations, from chronic pain to acute myocardial infarctions. Because of its ability to provide a long-term, month-by-month measure of systemic cortisol exposure, hair cortisol analysis is becoming a useful tool, capable of answering clinical questions that could previously not be answered by other tests. In this paper we review the development, current status, limitations and outstanding questions regarding the use of hair cortisol as a biomarker of chronic stress.
Neonatal pain-related stress is associated with elevated salivary cortisol levels to age 18 months in children born very preterm, compared to full-term, suggesting early programming effects. ...Importantly, interactions between immune/inflammatory and neuroendocrine systems may underlie programming effects. We examined whether cortisol changes persist to school age, and if common genetic variants in the promoter region of the NFKBIA gene involved in regulation of immune and inflammatory responses, modify the association between early experience and later life stress as indexed by hair cortisol levels, which provide an integrated index of endogenous HPA axis activity. Cortisol was assayed in hair samples from 128 children (83 born preterm ≤ 32 weeks gestation and 45 born full-term) without major sensory, motor or cognitive impairments at age 7 years. We found that hair cortisol levels were lower in preterm compared to term-born children. Downregulation of the HPA axis in preterm children without major impairment, seen years after neonatal stress terminated, suggests persistent alteration of stress system programming. Importantly, the etiology was gender-specific such that in preterm boys but not girls, specifically those with the minor allele for NFKBIA rs2233409, lower hair cortisol was associated with greater neonatal pain (number of skin-breaking procedures from birth to term), independent of medical confounders. Moreover, the minor allele (CT or TT) of NFKBIA rs2233409 was associated with higher secretion of inflammatory cytokines, supporting the hypothesis that neonatal pain-related stress may act as a proinflammatory stimulus that induces long-term immune cell activation. These findings are the first evidence that a long-term association between early pain-related stress and cortisol may be mediated by a genetic variants that regulate the activity of NF-κB, suggesting possible involvement of stress/inflammatory mechanisms in HPA programming in boys born very preterm.
The generation, detection, and quantification of high-energy proton spectra that are produced from laser-target interaction methodologies is a field of increasingly growing popularity over the last ...20 years. Generation methods such as target normal sheath acceleration or similar allow for collimated laminar ion beams to be produced in a compact environment through the use of short-burst terawatt lasers and are a growing field of investment. This project details the development and refinement of a python-based code to analyze time-of-flight ion spectroscopy data, with the intent to pinpoint the maximum proton energy within the incident beam to as reliable and accurate a value as possible within a feasible processing time. TOF data for 2.2 × 1016 W/cm2 intensity laser shots incident on a 2 mm Cu target that were gathered from the PERLA 1 kHz laser at the HiLASE center were used as training and testing data with the implementation of basic machine learning techniques to train these methods to the data being used. These datasets were used to ensure more widely applicable functionality, and accurate calculation to within 1% accuracy of an assumed correct value was seen to be consistently achievable for these datasets. This wider functionality indicates a high level of accuracy for previously unseen TOF datasets, regardless of signal/noise levels or dataset size, allowing for free use of the code in the wider field.
Principal component analysis (PCA) is the most commonly used dimensionality reduction technique for detecting and diagnosing faults in chemical processes. Although PCA contains certain optimality ...properties in terms of fault detection, and has been widely applied for fault diagnosis, it is not best suited for fault diagnosis. Discriminant partial least squares (DPLS) has been shown to improve fault diagnosis for small-scale classification problems as compared with PCA. Fisher's discriminant analysis (FDA) has advantages from a theoretical point of view. In this paper, we develop an information criterion that automatically determines the order of the dimensionality reduction for FDA and DPLS, and show that FDA and DPLS are more proficient than PCA for diagnosing faults, both theoretically and by applying these techniques to simulated data collected from the Tennessee Eastman chemical plant simulator.
Introduction: Some patients with end-stage disease who may neither want nor benefit from aggressive resuscitation receive such treatment if they cannot communicate in an emergency. Timely access to ...patients’ current resuscitation wishes, or “code status,” should be a key metric of electronic health records (EHR). We sought to determine what percentage of a cohort of patients with end-stage disease who present to the emergency department (ED) have accessible, code status documents, and for those who do, how quickly can this documentation be retrieved. Methods: In this cross-sectional study of ED patients with end-stage disease (eg, palliative care, metastatic malignancy, home oxygen, dialysis) conducted during purposefully sampled random accrual times we performed a standardized, timed review of available health records, including accompanying transfer documents. We also interviewed consenting patients and substitute decision makers to compare available code status documents to their current wishes. Results: Code status documentation was unavailable within 15 minutes of ED arrival in most cases (54/85, or 63%). Retrieval time was under five minutes in the rest, especially when “one click deep” in the EHR. When interviewed, 20/32 (63%) expressed “do not resuscitate” wishes, 10 of whom had no supporting documentation. Patients from assisted-living (odds ratio OR 6.7; 95% confidence interval CI, 1.7-26) and long-term care facilities (OR 13; 95% CI, 2.5-65) were more likely to have a documented code status available compared to those living in the community. Conclusion: The majority of patients with end-stage disease, including half of those who would not wish resuscitation from cardiorespiratory arrest, did not have code status documents readily available upon arrival to our tertiary care ED. Patients living in the community with advanced disease may be at higher risk for unwanted resuscitative efforts should they present to hospital in extremis. While easily retrievable code status documentation within the EHR shows promise, its accuracy and validity remain important considerations.
Recently, hair cortisol has become a topic of global interest as a biomarker of chronic stress. Different research groups have been using different methods for extraction and analysis, making it ...difficult to compare results across studies. A critical examination of the reported analytical methods is important to facilitate standardization and allow for a uniform interpretation.
This study qualitatively compared four published procedures from laboratories in Germany, the Netherlands, USA and Canada. Multiple aspects of their procedures were compared.
A major difference among the laboratories was the ELISA kit used: the Canadian laboratory used the kit from ALPCO Diagnostics (Salem, MA, USA), the American laboratory used the kit from DRG International (Springfield, NJ, USA), the German laboratory used the kit from DRG Instruments GmbH (Marburg, Germany), or IBL (Hamburg, Germany), and the Dutch used the kit from Salimetrics (Suffolk, UK). In addition, there are noted differences in hair mass used as well as washing and extraction procedures. The range of hair cortisol levels determined in healthy volunteers by the four groups was within 2.3-fold: Koren, 46.1 pg/mg; Van Rossum, 29.72 pg/mg; Kirschbaum, 20 pg/mg and Laudenslager ~ 27 pg/mg.
The relative similarities in hair cortisol values in volunteers among the four laboratories should facilitate a quality assurance exchange program, as a necessary step toward clinical use of this novel test.
Recently, hair cortisol has become a topic of global interest as a biomarker of chronic stress. Different research groups have been using different methods for extraction and analysis, making it ...difficult to compare results across studies. A critical examination of the reported analytical methods is important to facilitate standardization and allow for a uniform interpretation. This study qualitatively compared four published procedures from laboratories in Germany, the Netherlands, USA and Canada. Multiple aspects of their procedures were compared. A major difference among the laboratories was the ELISA kit used: the Canadian laboratory used the kit from ALPCO Diagnostics (Salem, MA, USA), the American laboratory used the kit from DRG International (Springfield, NJ, USA), the German laboratory used the kit from DRG Instruments GmbH (Marburg, Germany), or IBL (Hamburg, Germany), and the Dutch used the kit from Salimetrics (Suffolk, UK). In addition, there are noted differences in hair mass used as well as washing and extraction procedures. The range of hair cortisol levels determined in healthy volunteers by the four groups was within 2.3-fold: Koren, 46.1 pg/mg; Van Rossum, 29.72 pg/mg; Kirschbaum, 20 pg/mg and Laudenslager ~ 27 pg/mg. The relative similarities in hair cortisol values in volunteers among the four laboratories should facilitate a quality assurance exchange program, as a necessary step toward clinical use of this novel test.
Principal component analysis (PCA) is a well-known data dimensionality technique that has been used to detect faults during the operation of industrial processes. Dynamic principal component analysis ...(DPCA) and canonical variate analysis (CVA) are data dimensionality techniques which take into account serial correlations, but their effectiveness in detecting faults in industrial processes has not been extensively tested. In this paper, score/state and residual space PCA, DPCA, and CVA are applied to the Tennessee Eastman process simulator, which was designed to simulate a wide variety of faults occurring in a chemical plant based on a facility at Eastman Chemical. This appears to be the first application of residual space CVA statistics for detecting faults in a large-scale process.
Statistics quantifying variations in the residual space were usually more sensitive but less robust to the faults than the statistics quantifying the variations in the score or state space. The statistics exhibiting a small missed detection rate tended to exhibit small detection delays and vice versa. A residual-based CVA statistic proposed in this paper gave the best overall sensitivity and promptness, but the initially proposed threshold for the statistic lacked robustness. This motivated increasing the threshold to achieve a specified missed detection rate.
Visiting patients at home allows us insight into their family and community support structures, and improves our understanding of functional limitations, such as safe stairwells and fire hazards. In ...the aftermath of the Baltimore protests, The Johns Hopkins Bloomberg School of Public Health unveiled a plan to "Engage Baltimore," by informing students of issues in the community, encouraging participation in service opportunities, and fostering a vital dialogue between students and their neighboring community.
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