Free-Circulating Methylated DNA in Blood for Diagnosis, Staging, Prognosis, and Monitoring of Head and Neck Squamous Cell Carcinoma Patients: An Observational Prospective Cohort Study

Abstract BACKGROUND Circulating cell-free DNA methylation testing in blood has recently received regulatory approval for screening of colorectal cancer. Its application in other clinical settings, including staging, prognosis, prediction, and recurrence monitoring is highly promising, and of particular interest in head and neck squamous cell carcinomas (HNSCCs) that represent a heterogeneous group of cancers with unsatisfactory treatment guidelines. METHODS Short stature homeobox 2 (SHOX2) and septin 9 (SEPT9) DNA methylation in plasma from 649 prospectively enrolled patients (training study: 284 HNSCC/122 control patients; testing study: 141 HNSCC/102 control patients) was quantified before treatment and longitudinally during surveillance. RESULTS In the training study, 59% of HNSCC patients were methylation-positive at 96% specificity. Methylation levels correlated with tumor and nodal category (P &amp;lt; 0.001). Initially increased methylation levels were associated with a higher risk of death [SEPT9: hazard ratio (HR) = 5.27, P = 0.001; SHOX2: HR = 2.32, P = 0.024]. Disease recurrence/metastases were detected in 47% of patients up to 377 days earlier compared to current clinical practice. The onset of second cancers was detected up to 343 days earlier. In the testing study, sensitivity (52%), specificity (95%), prediction of overall survival (SEPT9: HR = 2.78, P = 0.022; SHOX2: HR = 2.50, P = 0.026), and correlation with tumor and nodal category (P &amp;lt;0.001) were successfully validated. CONCLUSIONS Methylation testing in plasma is a powerful diagnostic tool for molecular disease staging, risk stratification, and disease monitoring. Patients with initially high biomarker levels might benefit from intensified treatment and posttherapeutic surveillance. The early detection of a recurrent/metastatic disease or a second malignancy could lead to an earlier consecutive treatment, thereby improving patients' outcomes. </jats:sec

Comparative Analysis of Pyrosequencing and a Phylogenetic Microarray for Exploring Microbial Community Structures in the Human Distal Intestine

Background Variations in the composition of the human intestinal microbiota are linked to diverse health conditions. High-throughput molecular technologies have recently elucidated microbial community structure at much higher resolution than was previously possible. Here we compare two such methods, pyrosequencing and a phylogenetic array, and evaluate classifications based on two variable 16S rRNA gene regions. Methods and Findings Over 1.75 million amplicon sequences were generated from the V4 and V6 regions of 16S rRNA genes in bacterial DNA extracted from four fecal samples of elderly individuals. The phylotype richness, for individual samples, was 1,400–1,800 for V4 reads and 12,500 for V6 reads, and 5,200 unique phylotypes when combining V4 reads from all samples. The RDP-classifier was more efficient for the V4 than for the far less conserved and shorter V6 region, but differences in community structure also affected efficiency. Even when analyzing only 20% of the reads, the majority of the microbial diversity was captured in two samples tested. DNA from the four samples was hybridized against the Human Intestinal Tract (HIT) Chip, a phylogenetic microarray for community profiling. Comparison of clustering of genus counts from pyrosequencing and HITChip data revealed highly similar profiles. Furthermore, correlations of sequence abundance and hybridization signal intensities were very high for lower-order ranks, but lower at family-level, which was probably due to ambiguous taxonomic groupings. Conclusions The RDP-classifier consistently assigned most V4 sequences from human intestinal samples down to genus-level with good accuracy and speed. This is the deepest sequencing of single gastrointestinal samples reported to date, but microbial richness levels have still not leveled out. A majority of these diversities can also be captured with five times lower sampling-depth. HITChip hybridizations and resulting community profiles correlate well with pyrosequencing-based compositions, especially for lower-order ranks, indicating high robustness of both approaches. However, incompatible grouping schemes make exact comparison difficult

Designing Health Professions Curricula for the Future

Purpose. This study investigated how health professions’ curriculum incorporates the five core competencies identified by the National Academies Institute of Medicine (IOM) in preparing students for integrated and innovative interdisciplinary clinical practice. These core competencies include patient-centered care, interdisciplinary teams, evidence-based practice, quality improvement, and informatics. Methods. Data collection included a self-designed, cross-sectional, selfadministered questionnaire mailed to 500 U.S. programs in medicine, nursing, pharmacy and physical therapy combined with semi-structured follow-up phone interviews. Microsoft Excel and SPSS 14.0 were used to develop descriptive and inferential statistics with results reported using standard frequency analysis. Responses to open-ended questions were analyzed for common themes. Results. 100 programs responded via curriculum committee chairs and program chairs. Across disciplines, 80% of respondents recognized IOM competencies; physical therapy (PT) reporting the lowest awareness. The main barriers to implementing core competencies were adding more curriculum hours (64%) and administrative challenges (36%). Curricular integration is achieved primarily through joint experiential educational and clinical experiences and through student interaction with other healthcare profession practitioners. Conclusions. Awareness of IOM core competencies is lacking across disciplines. All programs should increase familiarity with the IOM core competencies as well as curricula application of these concepts to foster student development as members of integrated, multidisciplinary healthcare teams. Health professions programs should examine how they can better incorporate the IOM core competencies to promote efficient and collaborative delivery of quality care for the 21st century

Comparing the T scores from bone sonometer measurements in Hispanic and non-Hispanic white womenoptimally controlled on dual oral diabetes medications.

Ethnicity is an important risk factor for the development of osteoporosis. Non-Hispanic white or Asian women are commonly considered at higher risk than other ethnicities. Hispanics in the U.S. are of Mexican, Caribbean, Central American, or South American descent. Conclusive data on the relative risk of osteoporosis in Hispanic women based upon heritage within the Hispanic population are not available. Objective: To investigate whether Hispanic white women are at a significantly lower risk than non-Hispanic whites for the development of osteoporosis. Methods: Cross-sectional study. Setting: Community health screenings. Participants: Hispanic and non-Hispanic white women. Intervention: Bone density measurements of the non-dominant heel. Descriptive statistics and inferential statistics including regression analyses were performed using SPSS 14.0. Main Outcomes Measure: T scores. Results: Overall, measurements were obtained from 352 women (209 Hispanic & 143 non-Hispanic white) ranging in age from 55-97 years old. The mean T score obtained for Hispanic women was -1.194 and -1.280 for non-Hispanic white women. The correlation between the obtained T score and age was negative (r = -0.36, p<0.01), reflecting bone loss with increasing age. Regression analysis using age and ethnicity showed that ethnicity was a non-significant contributor to the best-fit regression line (t=0.60, p=0.55). Conclusion: This study indicates that Hispanic white women may be at comparable risk of developing osteoporosis as non-Hispanic white women

Comparing the T scores from bone sonometer measurements in Hispanic and non-Hispanic white womenoptimally controlled on dual oral diabetes medications.

Ethnicity is an important risk factor for the development of osteoporosis. Non-Hispanic white or Asian women are commonly considered at higher risk than other ethnicities. Hispanics in the U.S. are of Mexican, Caribbean, Central American, or South American descent. Conclusive data on the relative risk of osteoporosis in Hispanic women based upon heritage within the Hispanic population are not available. Objective: To investigate whether Hispanic white women are at a significantly lower risk than non-Hispanic whites for the development of osteoporosis. Methods: Cross-sectional study. Setting: Community health screenings. Participants: Hispanic and non-Hispanic white women. Intervention: Bone density measurements of the non-dominant heel. Descriptive statistics and inferential statistics including regression analyses were performed using SPSS 14.0. Main Outcomes Measure: T scores. Results: Overall, measurements were obtained from 352 women (209 Hispanic & 143 non-Hispanic white) ranging in age from 55-97 years old. The mean T score obtained for Hispanic women was -1.194 and -1.280 for non-Hispanic white women. The correlation between the obtained T score and age was negative (r = -0.36, p<0.01), reflecting bone loss with increasing age. Regression analysis using age and ethnicity showed that ethnicity was a non-significant contributor to the best-fit regression line (t=0.60, p=0.55). Conclusion: This study indicates that Hispanic white women may be at comparable risk of developing osteoporosis as non-Hispanic white women