Prospective Audit and Feedback for Antimicrobial Treatment of Patients Receiving Renal Replacement Therapy in Community-Based University Hospitals: A before-and-after Study.

In South Korea, because of manpower and budgetary limitations, antimicrobial stewardship programs have relied on preauthorization. This study analyzed the impact of a prospective audit and feedback (PAF) program targeting inpatients undergoing intermittent hemodialysis or continuous renal replacement therapy, which was implemented at two community-based university hospitals. During three years of PAF, 27,906 antimicrobial prescriptions were reviewed, with 622 (2.2%) interventions. The mean incidence density per 1000 patient days of multidrug-resistant organisms, except for carbapenem-resistant Acinetobacter baumannii, decreased in the study population, whereas it increased among inpatients. Multivariable Poisson regression analysis revealed that after PAF, the incidences of vancomycin-resistant Enterococcus and mortality decreased (incidence risk ratio, 95% confidence interval: 0.53, 0.31-0.93 and 0.70, 0.55-0.90, respectively). Notably, after PAF, incorrect antimicrobial dosing rates significantly decreased (tau -0.244; p = 0.02). However, the incidences of other multidrug-resistant organisms, Clostridioides difficile, length of stay, and readmission did not significantly change. This study shows that in patients undergoing intermittent hemodialysis or continuous renal replacement, targeted PAF can significantly reduce multidrug-resistant organism rates and all-cause hospital mortality, despite limited resources. Furthermore, it can improve antimicrobial dosage accuracy.

Institutional-specific smartphone application as a supplemental tool for an antimicrobial stewardship program in 2 large community-based hospitals: Acceptance of physicians and pharmacists.

PURPOSE: Antimicrobial stewardship programs (ASPs) have been a challenge in less resourceful health care settings. Medical smartphone applications (apps) can be accessible tools to support ASPs under such circumstances. A hospital-specific ASP app was prepared and the acceptance and usability of the study ASP app were evaluated by physicians and pharmacists in 2 community-based academic hospitals. METHODS: The exploratory survey was conducted 5 months following the implementation of the study ASP app. A questionnaire was developed, and the validity and reliability were analyzed using S-CVI/Ave (scale content validity index/Average) and Cronbach's alpha, respectively. The questionnaire consisted of demographics (3 items), acceptance (9 items), usability (10 items), and barriers (2 items). Descriptive analysis was conducted using a 5-point Likert scale, multiple selections, and free-text responses. RESULTS: Approximately 38.7% of 75 respondents (response rate, 23.5%) used the app. Most scored 4 or higher, indicating that the study ASP app was easy to install (89.7%), use (79.3%), and apply to clinical settings (69.0%). Frequently used contents were dosing (39.6%), the spectrum of activity (7.1%), and intravenous-to-oral conversion (7.1%). Barriers included limited time (38.2%) and insufficient content (20.6%). Users indicated that the study ASP app helped improve their knowledge on treatment guidelines (72.4%), antibiotic use (62.1%), and adverse reactions (69.0%). CONCLUSION: The study ASP app was well accepted by physicians and pharmacists and it can be useful to supplement ASPs activities in less resourceful hospitals with a large burden of patient care.

Hierarchical Structured Component Analysis for Microbiome Data Using Taxonomy Assignments.

The recent advent of high-throughput sequencing technology has enabled us to study the associations between human microbiome and diseases. The DNA sequences of microbiome samples are clustered as operational taxonomic units (OTUs) according to their similarity. The OTU table containing counts of OTUs present in each sample is used to measure correlations between OTUs and disease status and find key microbes for prediction of the disease status. Various statistical methods have been proposed for such microbiome data analysis. However, none of these methods reflects the hierarchy of taxonomy information. In this paper, we propose a hierarchical structural component model for microbiome data (HisCoM-microb) using taxonomy information as well as OTU table data. The proposed HisCoM-microb consists of two layers: one for OTUs and the other for taxa at the higher taxonomy level. Then we calculate simultaneously coefficient estimates of OTUs and taxa of the two layers inserted in the hierarchical model. Through this analysis, we can infer the association between taxa or OTUs and disease status, considering the impact of taxonomic structure on disease status. Both simulation study and real microbiome data analysis show that HisCoM-microb can successfully reveal the relations between each taxon and disease status and identify the key OTUs of the disease at the same time.

Polyherbal formula SC-E3 inhibits rheumatoid arthritis activity in a mouse model of type-II collagen-induced arthritis.

OBJECTIVE: SC-E3 is a polyherbal formula that contains five medicinal herbs used frequently in traditional herbal medicine. In our previous study, we demonstrated the antioxidant and anti-inflammatory effects of SC-E3. The present study examined the effects of SC-E3 in a mouse model of type-II collagen-induced arthritis (CIA). METHODS: In vivo, male DBA/1J mice were immunized by intradermal injection of bovine type-II collagen and complete or incomplete Freund's adjuvant, to induce arthritis. SC-E3 was orally administered daily for 23 days. In vitro, bone marrow-derived macrophages (BMMs) were treated with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) in the absence or presence of SC-E3. RESULTS: Administrations of SC-E3 were found to have anti-arthritic effects in the joints of CIA mice, as evidenced by reduced paw swelling, bone erosion and deformation, inflammatory cell infiltration, and inflammation in synovial membrane. SC-E3 also reduced serum levels of tumor necrosis factor-α, interleukin-1ß, aspartate aminotransferase and alanine aminotransferase. Furthermore, tartrate-resistant acid phosphatase-positive osteoclast numbers in the joints were significantly lower in SC-E3-treated CIA mice than in CIA mice. In addition, the differentiations of BMMs to multinucleated osteoclasts induced by M-CSF and RANKL stimulation were dose-dependently reduced by SC-E3. CONCLUSION: These results suggest that SC-E3 possesses substantial anti-arthritic activity because it inhibits pro-inflammatory cytokines and osteoclastogenesis, and that SC-E3 has potential therapeutic use for the treatment of rheumatoid arthritis.

Changes in serum fibronectin levels predict tumor recurrence in patients with early hepatocellular carcinoma after curative treatment.

Fibronectin, a matrix glycoprotein aberrantly expressed in various tumor cells, is a known candidate biomarker for the early diagnosis of hepatocellular carcinoma (HCC). In this study, we investigated whether serum fibronectin levels could predict tumor recurrence in patients with early-stage HCC after curative treatment. A total of 83 patients who showed complete response after initial curative treatment were included. The levels of serum fibronectin at baseline and 4-6 weeks after initial treatment were analyzed with regard to their associations with recurrence. Multivariate logistic regression analyses were performed to construct a prognostic nomogram. Baseline fibronectin levels were not significantly correlated with tumor size, number, stage, and serum α-fetoprotein levels. However, decrease in serum fibronectin levels after treatment was significantly associated with reduced HCC recurrence in multivariate logistic regression (odds ratio, 0.009; p < 0.001). Furthermore, a nomogram consisting of gender and changes in serum fibronectin showed a good discriminatory capability for the prediction of HCC recurrence with an area under the receiver-operating curve of 0.87. In conclusion, changes in serum fibronectin levels may be a surrogate indicator for assessment of treatment response in patients with early HCC after curative treatment.

MS1-Level Proteome Quantification Platform Allowing Maximally Increased Multiplexity for SILAC and In Vitro Chemical Labeling.

Quantitative proteomic platforms based on precursor intensity in mass spectrometry (MS1-level) uniquely support in vivo metabolic labeling with superior quantification accuracy but suffer from limited multiplexity (≤3-plex) and frequent missing quantities. Here we present a new MS1-level quantification platform that allows maximal multiplexing with high quantification accuracy and precision for the given labeling scheme. The platform currently comprises 6-plex in vivo SILAC or in vitro diethylation labeling with a dedicated algorithm and is also expandable to higher multiplexity (e.g., nine-plex for SILAC). For complex samples with broad dynamic ranges such as total cell lysates, our platform performs highly accurately and free of missing quantities. Furthermore, we successfully applied our method to measure protein synthesis rate under heat shock response in human cells by 6-plex pulsed SILAC experiments, demonstrating the unique biological merits of our in vivo platform to disclose translational regulations for cellular response to stress.

Efficacy and safety of nanoparticle-albumin-bound paclitaxel compared with solvent-based taxanes for metastatic breast cancer: A meta-analysis.

The curative effects of nanoparticle albumin-bound (nab)-paclitaxel in the first-line treatment of metastatic breast cancer (MBC) are still controversial, with even more after the removal of marketing approval of indication of bevacizumab. Five electronic databases and the related resources were searched for eligible randomized clinical trials (RCTs) without year and language restrictions to perform a meta-analysis. The studies were comparing the efficacy and safety between nab-paclitaxel chemotherapy versus solvent-based (sb)-taxanes chemotherapy such as sb-paclitaxel and docetaxel. The primary end points were overall response rate (ORR) and disease control rate (DCR). Secondary end points were progression-free survival (PFS), overall survival (OS), adverse events (AEs), and dose discontinuation rate (DDR). Five RCTs (1,554 patients) were finally identified from 1,902 studies. When compared to sb-paclitaxel, nab-paclitaxel showed significant beneficial effects in terms of ORR (OR 2.39, 95% CI 1.69-3.37, p < 0.001), DCR (OR 1.89, 95% CI 1.07-3.35, p = 0.03), and PFS (HR 0.75, 95% CI 0.62-0.90, p = 0.002). Nab-paclitaxel also showed significantly longer OS (HR 0.73, 95% CI 0.54-0.99, p = 0.04) than docetaxel. AEs and DDR were comparable between the two arms. Using nab-paclitaxel could significantly improve efficacy with comparable toxicities in the treatment of MBC.

Antimicrobial Stewardship Programs in Community Health Systems Perceived by Physicians and Pharmacists: A Qualitative Study with Gap Analysis.

Antimicrobial stewardship program (ASP) is one of the most important strategies for managing infectious disease treatment and preventing antimicrobial resistance. The successful implementation of ASP in the community health system (CHS) has been challenging. We evaluated perceptions of current ASP, potential setbacks of ASP implementation, and future demands on ASP services among physicians and pharmacists in the CHS. The qualitative research was conducted through in-depth individual interviews and focus group discussions with 11 physicians and 11 pharmacists. In addition, a quantitative gap analysis was conducted to assess the different awareness and demands on services of ASP and preferred antimicrobial-related problems (ARP). In overall, perceptions of ASP varied by profession. The identified setbacks were unorganized institutional leadership, the undefined roles of healthcare professionals, a lack of reimbursement, the hierarchical structure of the health system, and the labor-intensive working environment of pharmacy services. Although demands for ASP improvement were similar among professionals, they had different preferences in prioritizing each service item of ASP/ARP development and the profession responsible for each service. Continuous administrative and financial investments, understanding ASP contents, ASP-specific information technology, and interdisciplinary collaboration with good communication among healthcare professions are needed to continue the progression of ASP.

Circulating Microbiota-Based Metagenomic Signature for Detection of Hepatocellular Carcinoma.

Circulating microbial dysbiosis is associated with chronic liver disease including nonalcoholic steatohepatitis and alcoholic liver disease. In this study, we evaluated whether disease-specific alterations of circulating microbiome are present in patients with cirrhosis and hepatocellular carcinoma (HCC), and their potential as diagnostic biomarkers for HCC. We performed cross-sectional metagenomic analyses of serum samples from 79 patients with HCC, 83 with cirrhosis, and 201 matching healthy controls, and validated the results in the same number of subjects. Serum bacterial DNA was analyzed using high-throughput pyrosequencing after amplification of the V3-V4 hypervariable regions of 16S rDNA. Blood microbial diversity was significantly reduced in HCC, compared with cirrhosis and control. There were significant differences in the relative abundances of several bacterial taxa that correlate with the presence of HCC, thus defining a specific blood microbiome-derived metagenomic signature of HCC. We identified 5 microbial gene markers-based model which distinguished HCC from controls with an area under the receiver-operating curve (AUC) of 0.879 and a balanced accuracy of 81.6%. In the validation, this model accurately distinguished HCC with an AUC of 0.875 and an accuracy of 79.8%. In conclusion, circulating microbiome-based signatures may be potential biomarkers for the detection HCC.

gpart: human genome partitioning and visualization of high-density SNP data by identifying haplotype blocks.

SUMMARY: For the analysis of high-throughput genomic data produced by next-generation sequencing (NGS) technologies, researchers need to identify linkage disequilibrium (LD) structure in the genome. In this work, we developed an R package gpart which provides clustering algorithms to define LD blocks or analysis units consisting of SNPs. The visualization tool in gpart can display the LD structure and gene positions for up to 20 000 SNPs in one image. The gpart functions facilitate construction of LD blocks and SNP partitions for vast amounts of genome sequencing data within reasonable time and memory limits in personal computing environments. AVAILABILITY AND IMPLEMENTATION: The R package is available at https://bioconductor.org/packages/gpart. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Deuterium-Free, Three-Plexed Peptide Diethylation for Highly Accurate Quantitative Proteomics.

The deuterium, a frequently used stable isotope in isotopic labeling for quantitative proteomics, could deteriorate the accuracy and precision of proteome quantification owing to the retention time shift of deuterated peptides from the hydrogenated counterpart. We introduce a novel three-plexed peptide "diethylation" using only 13C isotopologues of acetaldehyde and demonstrate that the accuracy and precision of our method in proteome quantification are significantly superior to the conventional deuterium-based dimethylation labeling in both a single-shot and multidimensional LC-MS/MS analysis of the HeLa proteome. Furthermore, in time-resolved profiling of Xenopus laevis early embryogenesis, our 3-plexed diethylation outperformed isobaric labeling approaches in terms of the quantification accuracy or the number of protein identifications, generating more than two times more differentially expressed proteins. Our cost-effective and highly accurate 3-plexed diethylation method could contribute to various types of quantitative proteomics applications in which three of multiplexity would be sufficient.

Factors influencing disordered eating behavior based on the theory of triadic influence.

PURPOSE: The objective of this study was to identify factors influencing disordered eating behaviors in female college students based on the theory of triadic influence. DESIGN AND METHOD: The participants in this study were 307 college females in Korea. Data were analyzed using t-tests, correlation coefficients, and multiple regression analyses. FINDINGS: Multiple regression analysis revealed that objectified body consciousness, social physique anxiety, and sociocultural attitudes toward appearance influenced disordered eating behavior (R2  = 0.33, F = 51.32, P < 0.001). PRACTICE IMPLICATIONS: This study suggests the development of a nursing program for college females that considers the factors influencing personal, social, and cultural streams will be effective.

HO-1 Induction by Selaginella tamariscina Extract Inhibits Inflammatory Response in Lipopolysaccharide-Stimulated RAW 264.7 Macrophages.

Selaginella Herba is the dried, aerial part of Selaginella tamariscina (P.Beauv.) Spring and has been used to treat amenorrhea, abdominal pain, headaches, and hematuria in Korea. However, scientific evidence regarding the anti-inflammatory activity and action mechanism of Selaginella tamariscina is lacking. Thus, the present study was performed to investigate the anti-inflammatory and antioxidant activities of Selaginella tamariscina ethanol extract (STE) against lipopolysaccharide (LPS)-induced inflammatory responses and identify the molecular mechanism responsible. STE was prepared by heating in 70% ethanol and its quality was confirmed by HPLC. STE dose-dependently inhibited the productions of inflammatory mediators (NO and PGE2) and proinflammatory cytokines (IL-1ß and IL-6) in LPS-stimulated RAW 264.7 cells. STE markedly suppressed the phosphorylations of MAPKs, IκB-α, and NF-κB and the nuclear translocation of NF-κB induced by LPS stimulation. In addition, STE exhibited good free radical scavenging activity and prevented ROS generation by LPS. STE also upregulated the expression of Nrf2 and HO-1 and promoted the nuclear translocation of Nrf2. Taken together, STE was found to have anti-inflammatory and antioxidant effects on RAW 264.7 macrophages and the mechanism appeared to involve the MAPK, NF-κB, and Nrf2/HO-1 signaling pathways. These results suggest that STE might be useful for preventing or treating inflammatory diseases and provide scientific evidence that supports the developments of herbal prescriptions or novel natural products.

Nutrition and Clinical Outcomes of Nutrition Support in Multidisciplinary Team for Critically Ill Patients.

BACKGROUND: To examine the outcomes of the implementation of a multidisciplinary nutrition support team (NST) that included a pharmacist for critically ill patients in the intensive care unit (ICU). METHODS: Data were retrospectively collected from electronic medical records and compared between the pre-NST group (n = 73) and post-NST group (n = 75). Patients were included if they received enteral or parenteral nutrition support for at least 72 hours in the ICU of an approximately 900-bed, top-tier university medical center. The percentage of goal kcal, the percentage of goal protein, serum albumin level, total lymphocyte count, C-reactive protein, duration of mechanical ventilation use, hospital length of stay (LOS), ICU LOS, and mortality were evaluated. RESULTS: There were significant differences in the percentage of goal kcal (66.9% ± 25.9% vs 86.2% ± 27.5%; P < 0.001) and the percentage of goal protein (67.0% ± 29.9% vs 81.7% ± 30.7%; P < 0.05) between the pre-NST and post-NST groups. A higher percentage of goal kcal was associated with a significant decrease in the ICU LOS (P < 0.05) and hospital LOS (P < 0.05). The percentage of goal kcal was associated with mortality rate (odd ratio, 0.977; 95% confidential interval, 0.959-0.996; P = 0.016). CONCLUSION: Implementation of a multidisciplinary NST service for critically ill patients was associated with higher percentages of goal kcal and goal protein, as well as a shortened duration of mechanical ventilation use. Higher energy supply was associated with a reduced mortality rate.

A new haplotype block detection method for dense genome sequencing data based on interval graph modeling of clusters of highly correlated SNPs.

Motivation: Linkage disequilibrium (LD) block construction is required for research in population genetics and genetic epidemiology, including specification of sets of single nucleotide polymorphisms (SNPs) for analysis of multi-SNP based association and identification of haplotype blocks in high density sequencing data. Existing methods based on a narrow sense definition do not allow intermediate regions of low LD between strongly associated SNP pairs and tend to split high density SNP data into small blocks having high between-block correlation. Results: We present Big-LD, a block partition method based on interval graph modeling of LD bins which are clusters of strong pairwise LD SNPs, not necessarily physically consecutive. Big-LD uses an agglomerative approach that starts by identifying small communities of SNPs, i.e. the SNPs in each LD bin region, and proceeds by merging these communities. We determine the number of blocks using a method to find maximum-weight independent set. Big-LD produces larger LD blocks compared to existing methods such as MATILDE, Haploview, MIG ++, or S-MIG ++ and the LD blocks better agree with recombination hotspot locations determined by sperm-typing experiments. The observed average runtime of Big-LD for 13 288 240 non-monomorphic SNPs from 1000 Genomes Project autosome data (286 East Asians) is about 5.83 h, which is a significant improvement over the existing methods. Availability and implementation: Source code and documentation are available for download at http://github.com/sunnyeesl/BigLD. Contact: yyoo@snu.ac.kr. Supplementary information: Supplementary data are available at Bioinformatics online.

Resilience Mediates Impact of Some Childhood Maltreatment on Post-Traumatic Stress Symptoms in Conscripted Marines in the Republic of Korea.

Although it is known that post-traumatic stress symptoms (PTSS) can result from military service, the variance in PTSS unexplained by military service warrants further investigation, and no researchers have investigated South Korean Marines' vulnerability during their 2-year conscripted service as the first line of national defense against threats from North Korea. This study was designed to examine whether resilience mediated the relationship between childhood maltreatment and PTSS in 169 Korean conscripts into the Marine Corps. In a cross-sectional study design, the Childhood Trauma Questionnaire-Short Form was used to measure childhood maltreatment, including abuse and neglect. The Impact of Event Scale-Revised and the Connor-Davidson Resilience Scale were used to measure PTSS and resilience. Structural equation modeling was used for data analysis. Half the conscripts reported at least one type of childhood maltreatment, and 22.3% had high PTSS, even in a short period of service. Childhood abuse was significantly associated with PTSS during military service, a relationship that was not mediated by resilience. However, resilience mediated the relationship between childhood neglect and PTSS during military service. Assessment of childhood maltreatment and resilience prior to military service is crucial for identifying conscripts at increased risk for PTSS during even brief military service. In addition to direct interventions for abuse effects among all Marines, interventions enhancing resilience may benefit conscripts who experienced childhood neglect. © 2016 Wiley Periodicals, Inc.

Akt activation by Evodiae Fructus extract protects ovary against 4-vinylcyclohexene diepoxide-induced ovotoxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Evodiae Fructus (EF) is the dried, unripe fruit of Evodia rutaecarpa Benth., and one of the main components of traditional herbal prescriptions issued for the treatment of sterility caused by irregular menstruation in Korea. However, scientific evidence regarding the efficacy and action mechanism of EF is lacking. AIM OF THE STUDY: In this study, the authors established an in vitro screening tool to identify promising new drug candidates in herbal medicines for the prevention and treatment of premature ovarian failure. The protective effects of EF extracts against 4-vinylcyclohexene diepoxide (VCD)-induced ovotoxicity were investigated and the molecular mechanism responsible was sought. MATERIAL AND METHODS: EF extract was prepared by boiling EF in water and its quality was confirmed by high performance liquid chromatography. CHO-K1 (Chinese hamster ovary cells) and COV434 (human ovarian granulosa cells) cells were plated, pretreated with EF extract for 2h and then treated with 1.5mM or 0.5mM VCD for 24h, respectively. Cell viabilities were measured using an MTT assay, and protein levels were determined by western blotting. RESULTS: VCD significantly suppressed the viability of both CHO-K1 and COV434 cells in a dose-dependent manner and induced the apoptosis of CHO-K1 cells at 1.5mM. EF extract dose-dependently blocked the ovotoxicity induced by treatment with VCD. Furthermore, EF extract significantly activated Akt and downstream effectors such as mTOR and GSK-3ß in CHO-K1 cells. The ability of EF extract to prevent cytotoxicity by VCD was antagonized by pretreatment of LY294002, a PI3K/Akt inhibitor. CONCLUSION: EF has the ability to protect ovary cells against VCD-induced ovotoxicity, probably via Akt activation. These results suggest that the beneficial effects of EF might be useful for preventing premature ovarian failure or unexplained infertility caused by environmental factors.

Off-site evaluation of three-dimensional ultrasound for the diagnosis of thyroid nodules: comparison with two-dimensional ultrasound.

OBJECTIVES: We compared the diagnostic performance of off-site evaluation between prospectively obtained 3D and 2D ultrasound for thyroid nodules. METHODS: 3D and 2D ultrasonographies were preoperatively obtained from 85 consecutive patients (mean age, 51 years; age range, 28-83 years) who were referred for a total thyroidectomy. Three radiologists independently evaluated 3D and 2D images of 91 pathologically confirmed thyroid nodules (30 benign and 61 malignant nodules) for nodule characterization. Diagnostic performance, interobserver agreement and time for scanning were compared between 3D and 2D. RESULTS: 3D had significantly higher sensitivities than 2D for predicting malignancy (78.7 % vs. 61.2 %, P < 0.01) and extrathyroidal extension (66.7 % vs. 46.4 %, P = 0.03) in malignancy. In terms of specificities, there were no statistically significant differences between 2D and 3D for predicting malignancy (78.4 % vs. 74.8 %, P = 1.00) and extrathyroidal extension (63.6 % vs. 57.6 %, P = 0.46). With respect to interobserver agreement, 3D showed moderate agreement (κ = 0.53) for predicting extrathyroidal extension in malignancy compared with 2D ultrasound, which showed fair agreement (κ = 0.37). 3D saved time (30 ± 56.52 s) for scanning compared with 2D. CONCLUSION: For off-site evaluation, 3D US is more useful for diagnosis of thyroid nodules than 2D US. KEY POINTS: • 3D had higher sensitivity than 2D for predicting malignancy and extrathyroidal extension. • 3D showed better agreement for predicting extrathyroidal extension in malignancy than 2D. • 3D thyroid ultrasound saved time for scanning compared with 2D. • For off-site evaluation of thyroid nodules, 3D is more useful than 2D.

Addition of Digital Breast Tomosynthesis to Full-Field Digital Mammography in the Diagnostic Setting: Additional Value and Cancer Detectability.

PURPOSE: The purpose of this study was to assess the value of adding digital breast tomosynthesis (DBT) to full-field digital mammography (FFDM) in the diagnostic workup of breast cancer and to determine which lesion variables affect cancer detectability in the combined modality. METHODS: Between March and May 2012, paired FFDM and DBT images were obtained from 203 women as part of a diagnostic workup for breast cancer. Images from FFDM alone, DBT alone, and DBT combined with FFDM were reviewed in separate sessions by six blinded readers. Jackknife alternative free-response receiver operating characteristic (JAFROC) figure of merit (FOM), sensitivity, and specificity were compared between the modalities. Lesion characteristics affecting the cancer detection rate when using the combined modality were also analyzed. RESULTS: Among the 203 women, 126 women had a total of 129 malignancies and 77 women had total of 77 benign lesions. The overall JAFROC FOM of the combined modality was higher than that of FFDM alone (0.827 vs. 0.775, p<0.001) and that of DBT alone was higher than that of FFDM alone (0.807 vs. 0.775, p=0.027). The overall sensitivity of the combined modality was higher than that of FFDM alone (80.0% vs. 73.2%, p<0.001) and that of DBT alone was higher than that of FFDM alone (78.3% vs. 73.2%, p=0.007). Compared to FFDM alone, the combined modality detected an additional 48 cancers. Using the combined modality, the presence of masses or microcalcifications was significantly associated with the cancer detection rate (p<0.001). CONCLUSION: The combination of DBT with FFDM results in a higher diagnostic yield than FFDM alone. Additionally, DBT alone performs better than FFDM alone. However, even when DBT is combined with FFDM, breast cancers with no discernible masses and those lacking calcifications are difficult to detect.

Effects of Single Nucleotide Polymorphism Marker Density on Haplotype Block Partition.

Many researchers have found that one of the most important characteristics of the structure of linkage disequilibrium is that the human genome can be divided into non-overlapping block partitions in which only a small number of haplotypes are observed. The location and distribution of haplotype blocks can be seen as a population property influenced by population genetic events such as selection, mutation, recombination and population structure. In this study, we investigate the effects of the density of markers relative to the full set of all polymorphisms in the region on the results of haplotype partitioning for five popular haplotype block partition methods: three methods in Haploview (confidence interval, four gamete test, and solid spine), MIG++ implemented in PLINK 1.9 and S-MIG++. We used several experimental datasets obtained by sampling subsets of single nucleotide polymorphism (SNP) markers of chromosome 22 region in the 1000 Genomes Project data and also the HapMap phase 3 data to compare the results of haplotype block partitions by five methods. With decreasing sampling ratio down to 20% of the original SNP markers, the total number of haplotype blocks decreases and the length of haplotype blocks increases for all algorithms. When we examined the marker-independence of the haplotype block locations constructed from the datasets of different density, the results using below 50% of the entire SNP markers were very different from the results using the entire SNP markers. We conclude that the haplotype block construction results should be used and interpreted carefully depending on the selection of markers and the purpose of the study.