Method for assessing correlation coefficients among multiple repeatedly measured biomarkers

Hypoglycemia and hyperglycemia in critically ill patients have been considered as being closely tied to mortality. However, clinical researchers and physicians have suspected that this relationship may be confounded by other time-updated biomarkers such as the acute physiology and the chronic health evaluation (APACHE) score which is a measurement of disease severity. To investigate the effect of dysglycemia on mortality while adjusting for time-dependent biomarkers, we first need to ensure that these time-updated biomarkers are associated with the main exposure variable, i.e., the time-dependent glucose levels. Several researchers have proposed methods to estimate the true correlation coefficient between two repeatedly measured continuous variables using the maximum likelihood method via the mixed effects modeling with an assumption that these two variables are measured at the same time points. In this study, we further extend the methods proposed by these researchers, and proposed a method that can be used to examine the correlation coefficients among multiple (two or more) variables measured repeatedly. The method we proposed can be applied to linked cases where repeated measurements are linked over time and to unlinked cases where measurements are not necessarily measured concurrently. The dataset we used for demonstration is the HighDensity ICU dataset, an electronic dataset from an eight-year observational cohort of more than 54,000 admissions recorded in twelve Intensive care units (ICUs) of a large tertiary care center. Several risk factors of mortality were recorded daily for the ICU admissions including glucose level, disease severity score, organ dysfunction scores, cumulative daily insulin doses, and caloric intake. Simulation studies were conducted to examine the empirical features of our proposed method under different underlying scenarios. In application, we compared our method with the methods proposed by previous researchers on correlation coefficients between any two risk factors. Public Health Significance: One of the objectives of the current on-going study is to find the relationship between the glucose level and the APACHE III score, both measured repeatedly, while controlling for other repeatedly measured biomarkers. Findings in this study not only can provide helpful information for physicians in the ICUs to optimize treatments in critically ill patients with septic shock, but also can provide biostatisticians a better statistical tool to estimate correlation between two longitudinally measured biomarkers that are adjusted for within-subject correlation while controlling for repeatedly measured confounding factors

An Inpatient Patient Safety Curriculum for Pediatric Residents.

Introduction: Patient safety is recognized as an important part of pediatric resident education. There is a lack of published safety curricula targeting pediatric residents. A local needs assessment showed that while residents felt safety was an important part of their current and future jobs, they did not feel prepared to apply safety principles to their future careers or participate in a root cause analysis (RCA). Methods: This curriculum was delivered to senior-level pediatric and multiple-board residents during five monthly, hour-long, multidisciplinary sessions. Sessions covered systems-based thinking, terminology, the second victim phenomenon, RCA, and medication errors, while providing feedback on recent event reports filed by residents. Resident knowledge, attitudes, and reporting behavior were evaluated prior to and following the curriculum. Results: Attendees showed statistically significant improved safety attitudes and preparedness to apply safety to their future endeavors; conversely, there were no significant changes in nonattendees. There were no significant changes in knowledge scores or event reporting. Answers to qualitative questions identified learning about the reporting process, RCAs, and follow-up on filed event reports as valuable parts of the curriculum. Residents desired more time to debrief about safety events. Discussion: The curriculum succeeded in engaging residents in patient safety and making them feel prepared for future practice. Residents showed a dissonance between their intentions to report and their actual reporting behaviors, the reasons for which require further exploration. Residents desired a forum to deal with the emotions involved in errors. This curriculum is easily transferable to other institutions with minor modifications

AuthCropper: Authenticated Image Cropper for Privacy Preserving Surveillance Systems

As surveillance systems are popular, the privacy of the recorded video becomes more important. On the other hand, the authenticity of video images should be guaranteed when used as evidence in court. It is challenging to satisfy both (personal) privacy and authenticity of a video simultaneously, since the privacy requires modifications (e.g., partial deletions) of an original video image while the authenticity does not allow any modifications of the original image. This paper proposes a novel method to convert an encryption scheme to support partial decryption with a constant number of keys and construct a privacy-aware authentication scheme by combining with a signature scheme. The security of our proposed scheme is implied by the security of the underlying encryption and signature schemes. Experimental results show that the proposed scheme can handle the UHD video stream with more than 17 fps on a real embedded system, which validates the practicality of the proposed scheme

INO80 function is required for mouse mammary gland development, but mutation alone may be insufficient for breast cancer

The aberrant function of ATP-dependent chromatin remodeler INO80 has been implicated in multiple types of cancers by altering chromatin architecture and gene expression; however, the underlying mechanism of the functional involvement of INO80 mutation in cancer etiology, especially in breast cancer, remains unclear. In the present study, we have performed a weighted gene co-expression network analysis (WCGNA) to investigate links between INO80 expression and breast cancer sub-classification and progression. Our analysis revealed that INO80 repression is associated with differential responsiveness of estrogen receptors (ERs) depending upon breast cancer subtype, ER networks, and increased risk of breast carcinogenesis. To determine whether INO80 loss induces breast tumors, a conditional INO80-knockout (INO80 cKO) mouse model was generated using the Cre-loxP system. Phenotypic characterization revealed that INO80 cKO led to reduced branching and length of the mammary ducts at all stages. However, the INO80 cKO mouse model had unaltered lumen morphology and failed to spontaneously induce tumorigenesis in mammary gland tissue. Therefore, our study suggests that the aberrant function of INO80 is potentially associated with breast cancer by modulating gene expression. INO80 mutation alone is insufficient for breast tumorigenesis

Incidence and risk factors of oral feeding intolerance in acute pancreatitis: Results from an international, multicenter, prospective cohort study

Background: Inability to advance to an oral diet, or oral feeding intolerance, is a common complication in patients with acute pancreatitis associated with worse clinical outcomes. The factors related to oral feeding intolerance are not well studied. Objective: We aimed to determine the incidence and risk factors of oral feeding intolerance in acute pancreatitis. Methods: Patients were prospectively enrolled in the Acute Pancreatitis Patient Registry to Examine Novel Therapies in Clinical Experience, an international acute pancreatitis registry, between 2015 and 2018. Oral feeding intolerance was defined as worsening abdominal pain and/or vomiting after resumption of oral diet. The timing of the initial feeding attempt was stratified based on the day of hospitalization. Multivariable logistic regression was performed to assess for independent risk factors/predictors of oral feeding intolerance. Results: Of 1233 acute pancreatitis patients included in the study, 160 (13%) experienced oral feeding intolerance. The incidence of oral feeding intolerance was similar irrespective of the timing of the initial feeding attempt relative to hospital admission day (p = 0.41). Patients with oral feeding intolerance were more likely to be younger (45 vs. 50 years of age), men (61% vs. 49%), and active alcohol users (44% vs. 36%). They also had higher blood urea nitrogen (20 vs. 15 mg/dl; p < 0.001) and hematocrit levels (41.7% vs. 40.5%; p = 0.017) on admission; were more likely to have a nonbiliary acute pancreatitis etiology (69% vs. 51%), systemic inflammatory response syndrome of 2 or greater on admission (49% vs. 35%) and at 48 h (50% vs. 26%), develop pancreatic necrosis (29% vs. 13%), moderate to severe acute pancreatitis (41% vs. 24%), and have a longer hospital stay (10 vs. 6 days; all p < 0.04). The adjusted analysis showed that systemic inflammatory response syndrome of 2 or greater at 48 h (odds ratio 3.10; 95% confidence interval 1.83-5.25) and a nonbiliary acute pancreatitis etiology (odds ratio 1.65; 95% confidence interval 1.01-2.69) were independent risk factors for oral feeding intolerance. Conclusion: Oral feeding intolerance occurs in 13% of acute pancreatitis patients and is independently associated with systemic inflammatory response syndrome at 48 h and a nonbiliary etiology

Changes in the Expression of Mitochondrial Morphology-Related Genes during the Differentiation of Murine Embryonic Stem Cells

During embryonic development, cells undergo changes in gene expression, signaling pathway activation/inactivation, metabolism, and intracellular organelle structures, which are mediated by mitochondria. Mitochondria continuously switch their morphology between elongated tubular and fragmented globular via mitochondrial fusion and fission. Mitochondrial fusion is mediated by proteins encoded by Mfn1, Mfn2, and Opa1, whereas mitochondrial fission is mediated by proteins encoded by Fis1 and Dnm1L. Here, we investigated the expression patterns of mitochondria-related genes during the differentiation of mouse embryonic stem cells (ESCs). Pluripotent ESCs maintain stemness in the presence of leukemia inhibitory factor (LIF) via the JAK-STAT3 pathway but lose pluripotency and differentiate in response to the withdrawal of LIF. We analyzed the expression levels of mitochondrial fusion- and fission-related genes during the differentiation of ESCs. We hypothesized that mitochondrial fusion genes would be overexpressed while the fission genes would be downregulated during the differentiation of ESCs. Though the mitochondria exhibited an elongated morphology in ESCs differentiating in response to LIF withdrawal, only the expression of Mfn2 was increased and that of Dnm1L was decreased as expected, the other exceptions being Mfn1, Opa1, and Fis1. Next, by comparing gene expression and mitochondrial morphology, we proposed an index that could precisely represent mitochondrial changes during the differentiation of pluripotent stem cells by analyzing the expression ratios of three fusion- and two fission-related genes. Surprisingly, increased Mfn2/Dnm1L ratio was correlated with elongation of mitochondria during the differentiation of ESCs. Moreover, application of this index to other specialized cell types revealed that neural stems cells (NSCs) and mouse embryonic fibroblasts (MEFs) showed increased Mfn2/Dnm1L ratio compared to ESCs. Thus, we suggest that the Mfn2/Dnm1L ratio could reflect changes in mitochondrial morphology according to the extent of differentiation

Racial Disparities in Human Papillomavirus Vaccination: Does Access Matter?

PurposeTo examine the association between race/ethnicity and human papillomavirus (HPV) vaccine initiation and to determine how access to health care influences this relationship.MethodsWe used nationally representative data from the National Survey of Family Growth to assess HPV vaccine initiation in 2,168 females aged 15-24&nbsp;years. A series of regression analyses were performed to determine the independent effect of race/ethnicity on HPV vaccine initiation after controlling for sociodemographic variables and health care access measures. Age-stratified regression analyses were also performed to assess whether the relationship between race/ethnicity and HPV vaccine initiation differed among females aged 15-18 and 19-24&nbsp;years.ResultsThere were significant racial/ethnic disparities in HPV vaccination; United States (US)-born Hispanics, foreign-born Hispanics, and African-Americans were less likely to have initiated vaccination than were whites (p &lt; .001). Adjusting for sociodemographic characteristics attenuated the disparity for both US-born and foreign-born Hispanics (adjusted odds ratio [AOR], .76; 95% confidence interval [CI], .50-1.16; and AOR, .67; 95% CI, .37-1.19) but not for African-Americans (AOR, .47, 95% CI, .33-.66). Adding health care access measures further attenuated the disparity for US-born and foreign-born Hispanics (AOR, .85, 95% CI, .54-1.34; and AOR, .84, 95% CI, .45-1.55). However, African-Americans remained less likely than whites to have initiated vaccination (AOR, .49, 95% CI, .36-.68). These racial/ethnic trends were similar for females aged 15-18 and 19-24&nbsp;years.ConclusionsLower rates of HPV vaccination among African-American females do not appear to be explained by differential access to health care. More research is necessary to elucidate factors contributing to HPV vaccination in this population

Efficient Generation of Neural Stem Cells from Embryonic Stem Cells Using a Three-Dimensional Differentiation System

Mouse embryonic stem cells (ESCs) are useful tools for studying early embryonic development and tissue formation in mammals. Since neural lineage differentiation is a major subject of organogenesis, the development of efficient techniques to induce neural stem cells (NSCs) from pluripotent stem cells must be preceded. However, the currently available NSC differentiation methods are complicated and time consuming. This study aimed to propose an efficient method for the derivation of NSCs from mouse ESCs; early neural lineage commitment was achieved using a three-dimensional (3D) culture system, followed by a two-dimensional (2D) NSC derivation. To select early neural lineage cell types during differentiation, Sox1-GFP transgenic ESCs were used. They were differentiated into early neural lineage, forming spherical aggregates, which were subsequently picked for the establishment of 2D NSCs. The latter showed a morphology similar to that of brain-derived NSCs and expressed NSC markers, Musashi, Nestin, N-cadherin, and Sox2. Moreover, the NSCs could differentiate into three subtypes of neural lineages, neurons, astrocytes, and oligodendrocytes. The results together suggested that ESCs could efficiently differentiate into tripotent NSCs through specification in 3D culture (for approximately 10 days) followed by 2D culture (for seven days)