Characterizing injury patterns and outcomes in hospitalized trauma patients with non-English Language Preferences.

INTRODUCTION: Patients with Non-English Language Preferences (NELP) experience challenges navigating the US healthcare system which can lead to disparate outcomes. This study sought to investigate injury patterns and outcomes in hospitalized trauma patients with NELP. METHODS: A retrospective review was performed at a trauma center from January 2019-December 2020. An institutional database of all emergency department video consultations for interpreter services was cross-referenced with the trauma registry and comparisons were made between NELP and English-preferred (EP) speaking patients. RESULTS: During the study, 257 NELP patients were hospitalized after traumatic injury. Twenty-two percent had work related injuries compared to only 3.0% in the EP cohort (p < 0.001). When propensity score matched, there were no significant differences in ICU and hospital length of stay or mortality between NELP and EP patients. DISCUSSION: Trauma patients are linguistically diverse and understanding their injury patterns and outcomes is crucial for guiding culturally and linguistically appropriate injury prevention.

Relationship between body mass index and the incidence of inguinal hernia repairs: a population-based study in Olmsted County, MN.

PURPOSE: The relationship between body mass index (BMI) and the risk of inguinal hernia development is unclear. To explore the relationship, we determined whether the incidence of inguinal hernia repairs (IHR) varied across patients with different BMI categories. STUDY DESIGN: A population-based incidence study was undertaken. We reviewed all IHR performed on adult residents of Olmsted County, MN from 2004 to 2008. Cases were ascertained through the Rochester Epidemiology Project, a records-linkage system with more than 97% population coverage. RESULTS: During the study period, a total of 1,168 IHR were performed on 879 men and 107 women. The median BMI of the cohort was 26.7 kg/m2 (range 14.9-58.1, interquartile range 23.9-28.9). Incidence rates varied significantly as a function of BMI (p<0.001). Rates were highest among men who were either normal weight or overweight (419.8 and 421.1 per 100,000 person-years for BMI<25 and BMI 25-29.9, respectively), and lowest for obese and morbidly obese men (273.5 and 99.4 per 100,000 person-years for BMI 30-34.9 and BMI C 35, respectively). Findings were similar across all age categories and in patients who had an IHR that was initial or recurrent, direct or indirect, and unilateral or bilateral. CONCLUSIONS: The incidence of IHR decreased as BMI increased. Obese and morbidly obese patients had a lower incidence of IHR than those who were normal weight or overweight. The causal mechanisms leading to such a relationship are unclear and warrant further study.

Trends in emergent inguinal hernia surgery in Olmsted County, MN: a population-based study.

BACKGROUND: Evidence suggests that watchful waiting of inguinal hernias (IH) is safe because the risk of acute strangulation requiring an emergent repair is low. However, population-based incidence rates are lacking, and it is unknown whether the incidence of emergent inguinal hernia repairs (IHR) has changed over time. STUDY DESIGN: A retrospective review of all IHR performed on adult residents of Olmsted County, Minnesota from 1989 to 2008 was performed using the Rochester epidemiology project, a record-linkage system that covers more than 97 % of the population (2010 US Census = 146,466). Incidence rates/100,000 person-years were calculated, and trends over time were evaluated using Poisson regression. RESULTS: A total of 4,026 IHR were performed on 3,599 patients; 136 repairs (3.8 %) were emergent. Of these, 19 patients (14 %) had bowel resection and three (2 %) died within 30 days of the repair. Rates/100,000 person-years yielded an overall incidence of 7.6 for emergent IHR and 200.0 for elective IHR. Emergent IHR rates increased with age. Overall emergent IHR rates declined from 18.2 to 12.4 in men and from 6.4 to 2.4 in women from 1989 to 2008 (p > 0.05). Older age, obesity, a high ASA risk score, a femoral and/or a recurrent hernia were more likely to be associated with an emergent IHR (all p ≤ 0.05). CONCLUSION: The incidence of emergent IHR is low. This risk has decreased over the past 20 years. However, patients who are either ≥70 years old, obese, with a high ASA score, or with a femoral or recurrent hernias are more likely to require an emergent IHR and could benefit from elective operative intervention if deemed adequate surgical candidates.

NID2 and HOXA9 promoter hypermethylation as biomarkers for prevention and early detection in oral cavity squamous cell carcinoma tissues and saliva.

Differentially methylated oral squamous cell carcinoma (OSCC) biomarkers, identified in vitro and validated in well-characterized surgical specimens, have shown poor clinical correlation in cohorts with different risk profiles. To overcome this lack of relevance, we used the HumanMethylation27 BeadChip, publicly available methylation and expression array data, and quantitative methylation specific PCR to uncover differential methylation in OSCC clinical samples with heterogeneous risk profiles. A two stage design consisting of discovery and prevalence screens was used to identify differential promoter methylation and deregulated pathways in patients diagnosed with OSCC and head and neck squamous cell carcinoma. Promoter methylation of KIF1A (κ = 0.64), HOXA9 (κ = 0.60), NID2 (κ = 0.60), and EDNRB (κ = 0.60) had a moderate to substantial agreement with clinical diagnosis in the discovery screen. HOXA9 had 68% sensitivity, 100% specificity, and a 0.81 Area Under the Curve (AUC). NID2 had 71% sensitivity, 100% specificity, and a 0.79 AUC. In the prevalence screen, HOXA9 (κ = 0.82) and NID2 (κ = 0.80) had an almost perfect agreement with histologic diagnosis. HOXA9 had 85% sensitivity, 97% specificity, and a 0.95 AUC. NID2 had 87% sensitivity, 95% specificity, and a 0.91 AUC. A HOXA9 and NID2 gene panel had 94% sensitivity, 97% specificity, and a 0.97 AUC. In saliva, from OSCC cases and controls, HOXA9 had 75% sensitivity, 53% specificity, and a 0.75 AUC. NID2 had 87% sensitivity, 21% specificity, and a 0.73 AUC. This phase I Biomarker Development Trial identified a panel of differentially methylated genes in normal and OSCC clinical samples from patients with heterogeneous risk profiles. This panel may be useful for early detection and cancer prevention studies.

Epigenetic memory in induced pluripotent stem cells.

Somatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. Through different mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an 'epigenetic memory' of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSCs with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer is more effective at establishing the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment.

Estimation and assessment of raw copy numbers at the single locus level.

MOTIVATION: Although copy-number aberrations are known to contribute to the diversity of the human DNA and cause various diseases, many aberrations and their phenotypes are still to be explored. The recent development of single-nucleotide polymorphism (SNP) arrays provides researchers with tools for calling genotypes and identifying chromosomal aberrations at an order-of-magnitude greater resolution than possible a few years ago. The fundamental problem in array-based copy-number (CN) analysis is to obtain CN estimates at a single-locus resolution with high accuracy and precision such that downstream segmentation methods are more likely to succeed. RESULTS: We propose a preprocessing method for estimating raw CNs from Affymetrix SNP arrays. Its core utilizes a multichip probe-level model analogous to that for high-density oligonucleotide expression arrays. We extend this model by adding an adjustment for sequence-specific allelic imbalances such as cross-hybridization between allele A and allele B probes. We focus on total CN estimates, which allows us to further constrain the probe-level model to increase the signal-to-noise ratio of CN estimates. Further improvement is obtained by controlling for PCR effects. Each part of the model is fitted robustly. The performance is assessed by quantifying how well raw CNs alone differentiate between one and two copies on Chromosome X (ChrX) at a single-locus resolution (27kb) up to a 200kb resolution. The evaluation is done with publicly available HapMap data. AVAILABILITY: The proposed method is available as part of an open-source R package named aroma.affymetrix. Because it is a bounded-memory algorithm, any number of arrays can be analyzed.

On the utility of pooling biological samples in microarray experiments.

Over 15% of the data sets catalogued in the Gene Expression Omnibus Database involve RNA samples that have been pooled before hybridization. Pooling affects data quality and inference, but the exact effects are not yet known because pooling has not been systematically studied in the context of microarray experiments. Here we report on the results of an experiment designed to evaluate the utility of pooling and the impact on identifying differentially expressed genes. We find that inference for most genes is not adversely affected by pooling, and we recommend that pooling be done when fewer than three arrays are used in each condition. For larger designs, pooling does not significantly improve inferences if few subjects are pooled. The realized benefits in this case do not outweigh the price paid for loss of individual specific information. Pooling is beneficial when many subjects are pooled, provided that independent samples contribute to multiple pools.

A comparison of normalization methods for high density oligonucleotide array data based on variance and bias.

MOTIVATION: When running experiments that involve multiple high density oligonucleotide arrays, it is important to remove sources of variation between arrays of non-biological origin. Normalization is a process for reducing this variation. It is common to see non-linear relations between arrays and the standard normalization provided by Affymetrix does not perform well in these situations. RESULTS: We present three methods of performing normalization at the probe intensity level. These methods are called complete data methods because they make use of data from all arrays in an experiment to form the normalizing relation. These algorithms are compared to two methods that make use of a baseline array: a one number scaling based algorithm and a method that uses a non-linear normalizing relation by comparing the variability and bias of an expression measure. Two publicly available datasets are used to carry out the comparisons. The simplest and quickest complete data method is found to perform favorably. AVAILABILITY: Software implementing all three of the complete data normalization methods is available as part of the R package Affy, which is a part of the Bioconductor project http://www.bioconductor.org. SUPPLEMENTARY INFORMATION: Additional figures may be found at http://www.stat.berkeley.edu/~bolstad/normalize/index.html

Electrocorticographic gamma activity during word production in spoken and sign language.

OBJECTIVE: To investigate the functional-neuroanatomic substrates of word production using signed versus spoken language. METHODS: The authors studied single-word processing with varying input and output modalities in a 38-year-old woman with normal hearing and speech who had become proficient in sign language 8 years before developing intractable epilepsy. Subdural electrocorticography (ECoG) was performed during picture naming and word reading (visual inputs) and word repetition (auditory inputs); these tasks were repeated with speech and with sign language responses. Cortical activation was indexed by event-related power augmentation in the 80- to 100-Hz gamma band, and was compared with general principles of functional anatomy and with subject-specific maps of the same or similar tasks using electrical cortical stimulation (ECS). RESULTS: Speech outputs activated tongue regions of the sensorimotor cortex, and sign outputs activated hand regions. In addition, signed word production activated parietal regions that were not activated by spoken word production. Posterior superior temporal gyrus was activated earliest and to the greatest extent during auditory word repetition, and the basal temporal-occipital cortex was activated similarly during naming and reading, reflecting the different modalities of input processing. With few exceptions, topographic patterns of ECoG gamma were consistent with ECS maps of the same or similar language tasks. CONCLUSIONS: Spoken and signed word production activated many of the same cortical regions, particularly those processing auditory and visual inputs; however, they activated different regions of sensorimotor cortex, and signing activated parietal cortex more than did speech. This study illustrates the utility of electrocorticographic gamma for studying the neuroanatomy and processing dynamics of human language.

Cross-correlation of fetal cardiac and somatic activity as an indicator of antenatal neural development.

OBJECTIVE: In this study, we wanted to model the emergence of coupling between fetal cardiac and somatic activity in normal and at-risk fetuses. STUDY DESIGN: One hundred six fetuses of uncomplicated pregnancies were longitudinally monitored at 20, 24, 28, 32, 36, and 38 weeks of gestation by using a fetal actocardiograph and computerized data collection. Twenty-six fetuses of complicated pregnancies were also included. Statistical time series analysis techniques were used to examine the relation between fetal movement and fetal heart rate. RESULTS: A linear increase was found in the magnitude of the cross-correlation function between fetal movement and fetal heart rate as gestation advanced, with coalescence around a peak lag of 5 seconds by 32 weeks. Fetuses that delivered before term evidenced accelerated fetal movement and fetal heart rate coupling, whereas fetuses affected by deleterious conditions showed a decline in developmental trajectory. CONCLUSIONS: The cross-correlation between fetal cardiac and somatic activity is an indicator of neuroregulation in human fetuses.

Assessing homeostasis through circadian patterns.

An organism is thought to be in a dynamic state of homeostasis when each physiological and behavioral system reaches a delicate balance within the framework of other regulatory processes. Many biological systems target specific set-point variables and generate circadian patterns. In this article, we focus on specific measurements representative of two systems, namely deep-body temperature and activity counts. We examine data collected every 30 minutes in mice, assume there are underlying circadian patterns, and extend the approach presented in Brumback and Rice (1998, Journal of the American Statistical Association 93, 961-976) in order to obtain estimates in the presence of correlated data. We then assess homeostasis using these estimates and their statistical properties.