Comparison of Surface Elevation Changes of the Greenland and Antarctic Ice Sheets from Radar and Laser Altimetry

A primary purpose of satellite altimeter measurements is determination of the mass balances of the Greenland and Antarctic ice sheets and changes with time by measurement of changes in the surface elevations. Since the early 1990's, important measurements for this purpose have been made by radar altimeters on ERS-l and 2, Envisat, and CryoSat and a laser altimeter on ICESat. One principal factor limiting direct comparisons between radar and laser measurements is the variable penetration depth of the radar signal and the corresponding location of the effective depth of the radar-measured elevation beneath the surface, in contrast to the laser-measured surface elevation. Although the radar penetration depth varies significantly both spatially and temporally, empirical corrections have been developed to account for this effect. Another limiting factor in direct comparisons is caused by differences in the size of the laser and radar footprints and their respective horizontal locations on the surface. Nevertheless, derived changes in elevation, dHldt, and time-series of elevation, H(t), have been shown to be comparable. For comparisons at different times, corrections for elevation changes caused by variations in the rate offrrn compaction have also been developed. Comparisons between the H(t) and the average dH/dt at some specific locations, such as the Vostok region of East Antarctic, show good agreement among results from ERS-l and 2, Envisat, and ICESat. However, Greenland maps of dHidt from Envisat and ICESat for the same time periods (2003-2008) show some areas of significant differences as well as areas of good agreement. Possible causes of residual differences are investigated and described

An Aesthetic Factor Priority List of the Female Breast in Scandinavian Subjects

Background: There is little consensus about the relative determinative value of each individual factor in female breast aesthetics. When performing breast surgery with an aesthetic goal, certain factors will be more important than others. The purpose of this study was to make an aesthetic factor rank list to determine the relative contributions to overall breast aesthetics. Method: Volunteers were scanned using the 3-dimensional Vectra system. Ten Scandinavian plastic surgeons rated 37 subjects, using a validated scoring system with 49 scoring items. The correlation between specific aesthetic factors and overall breast aesthetic scores of the subjects were calculated using Pearson's r, Spearman's rho, and Kendall's tau. Results: A very strong correlation was found between overall breast aesthetic score and lower pole shape (0.876, P <0.0001). This was also true for upper pole shape (0.826, P <0.0001) and breast height (0.821, P <0.0001). A strong correlation was found between overall breast aesthetic score and nipple position (0.733, P <0.0001), breast size (0.644, P <0.0001), and breast width (0.632, P <0.0001). Factors that were only moderately correlated with aesthetic score were intermammary distance (0.496, P = 0.002), nipple size and projection (0.588, P <0.0001), areolar diameter (0.484, P <0.0001), and areolar shape (0.403, P <0.0001). Perceived symmetry was a weak factor (0.363, P = 0.027). Conclusions: Aesthetic factors of the female breast can be ranked in a priority list. Shape of the lower pole and upper pole and breast height are primary factors of female breast aesthetics. These should be prioritized in any aesthetic breast surgery. Vertical dimensional factors seem to be more determinative than horizontal factors.Peer reviewe

Roux-en-Y gastric bypass surgery of morbidly obese patients induces swift and persistent changes of the individual gut microbiota

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is an effective means to achieve sustained weight loss for morbidly obese individuals. Besides rapid weight reduction, patients achieve major improvements of insulin sensitivity and glucose homeostasis. Dysbiosis of gut microbiota has been associated with obesity and some of its co-morbidities, like type 2 diabetes, and major changes of gut microbial communities have been hypothesized to mediate part of the beneficial metabolic effects observed after RYGB. Here we describe changes in gut microbial taxonomic composition and functional potential following RYGB. METHODS: We recruited 13 morbidly obese patients who underwent RYGB, carefully phenotyped them, and had their gut microbiomes quantified before (n = 13) and 3 months (n = 12) and 12 months (n = 8) after RYGB. Following shotgun metagenomic sequencing of the fecal microbial DNA purified from stools, we characterized the gut microbial composition at species and gene levels followed by functional annotation. RESULTS: In parallel with the weight loss and metabolic improvements, gut microbial diversity increased within the first 3 months after RYGB and remained high 1 year later. RYGB led to altered relative abundances of 31 species (P < 0.05, q < 0.15) within the first 3 months, including those of Escherichia coli, Klebsiella pneumoniae, Veillonella spp., Streptococcus spp., Alistipes spp., and Akkermansia muciniphila. Sixteen of these species maintained their altered relative abundances during the following 9 months. Interestingly, Faecalibacterium prausnitzii was the only species that decreased in relative abundance. Fifty-three microbial functional modules increased their relative abundance between baseline and 3 months (P < 0.05, q < 0.17). These functional changes included increased potential (i) to assimilate multiple energy sources using transporters and phosphotransferase systems, (ii) to use aerobic respiration, (iii) to shift from protein degradation to putrefaction, and (iv) to use amino acids and fatty acids as energy sources. CONCLUSIONS: Within 3 months after morbidly obese individuals had undergone RYGB, their gut microbiota featured an increased diversity, an altered composition, an increased potential for oxygen tolerance, and an increased potential for microbial utilization of macro- and micro-nutrients. These changes were maintained for the first year post-RYGB. TRIAL REGISTRATION: Current controlled trials (ID NCT00810823, NCT01579981, and NCT01993511). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-016-0312-1) contains supplementary material, which is available to authorized users

Epigenetic activation of the FLT3 gene by ZNF384 fusion confers a therapeutic susceptibility in acute lymphoblastic leukemia.

FLT3 is an attractive therapeutic target in acute lymphoblastic leukemia (ALL) but the mechanism for its activation in this cancer is incompletely understood. Profiling global gene expression in large ALL cohorts, we identify over-expression of FLT3 in ZNF384-rearranged ALL, consistently across cases harboring different fusion partners with ZNF384. Mechanistically, we discover an intergenic enhancer element at the FLT3 locus that is exclusively activated in ZNF384-rearranged ALL, with the enhancer-promoter looping directly mediated by the fusion protein. There is also a global enrichment of active enhancers within ZNF384 binding sites across the genome in ZNF384-rearranged ALL cells. Downregulation of ZNF384 blunts FLT3 activation and decreases ALL cell sensitivity to FLT3 inhibitor gilteritinib in vitro. In patient-derived xenograft models of ZNF384-rearranged ALL, gilteritinib exhibits significant anti-leukemia efficacy as a monotherapy in vivo. Collectively, our results provide insights into FLT3 regulation in ALL and point to potential genomics-guided targeted therapy for this patient population

Ex vivo Drug Sensitivity Imaging-based Platform for Primary Acute Lymphoblastic Leukemia Cells

Resistance of acute lymphoblastic leukemia (ALL) cells to chemotherapy, whether present at diagnosis or acquired during treatment, is a major cause of treatment failure. Primary ALL cells are accessible for drug sensitivity testing at the time of new diagnosis or at relapse, but there are major limitations with current methods for determining drug sensitivity ex vivo. Here, we describe a functional precision medicine method using a fluorescence imaging platform to test drug sensitivity profiles of primary ALL cells. Leukemia cells are co-cultured with mesenchymal stromal cells and tested with a panel of 40 anti-leukemia drugs to determine individual patterns of drug resistance and sensitivity ("pharmacotype"). This imaging-based pharmacotyping assay addresses the limitations of prior ex vivo drug sensitivity methods by automating data analysis to produce high-throughput data while requiring fewer cells and significantly decreasing the labor-intensive time required to conduct the assay. The integration of drug sensitivity data with genomic profiling provides a basis for rational genomics-guided precision medicine. Key features Analysis of primary acute lymphoblastic leukemia (ALL) blasts obtained at diagnosis from bone marrow aspirate or peripheral blood. Experiments are performed ex vivo with mesenchymal stromal cell co-culture and require four days to complete. This fluorescence imaging-based protocol enhances previous ex vivo drug sensitivity assays and improves efficiency by requiring fewer primary cells while increasing the number of drugs tested to 40. It takes approximately 2-3 h for sample preparation and processing and a 1.5-hour imaging time. Graphical overview

Genome-wide analyses demonstrate novel loci that predispose to drusen formation

PURPOSE. To test whether genes for drusen formation are independent of age-related macular degeneration (AMD) pathogenesis. METHODS. A genome-wide model-free linkage analysis was performed, using two semiquantitative drusen traits, size and type, on two sets of data: (1) 325 individuals (225 sib pairs) from the Beaver Dam Eye Study (BDES), and (2) 297 individuals (346 sib pairs) from the Family Age Related Maculopathy Study (FARMS). Apolipoprotein E (APOE) genotypes were used as a covariate in a multipoint sibpair analysis. RESULTS. The authors found evidence of linkage on 19q13.31 (D19S245), with size of drusen in both the BDES (P ϭ 0.0287) and the FARMS (P ϭ 0.0013; P ϭ 0.0005, combined). In the BDES, type showed linkage evidence on 3p24.3 (D3S1768; P ϭ 0.0189) and 3q25.1 (D3S2404; P ϭ 0.0141); the linkage on 3p24.3 was also found with size (D3S1768; P ϭ 0.0264). In the FARMS, size showed evidence of linkage at 5q33.3 (D5S820; P ϭ 0.0021), 14q32.33 (D14S1007; P ϭ 0.0013), and 16p13.13 (D16S2616; P ϭ 0.0015) and type at 21q21.2 (D21S2052; P ϭ 0.0070). For size in the FARMS, there was a small increase in P-value at marker D19S245 from 0.0044 to 0.0111, and from 0.0044 to 0.0064, when the 4-carrier and the 3-carrier genotype were the covariates, respectively. CONCLUSIONS. The results show that APOE effects may be mediated early in the progression of ARM to AMD and thus may not be detected by standard genome scans for more severe disease. (Invest Ophthalmol Vis Sci. 2005;46:3081-3088

Injection of Human Bone Marrow and Mononuclear Cell Extract into Infarcted Mouse Hearts Results in Functional Improvement

Background: We have previously shown that mouse whole bone marrow cell (BMC) extract results in improvement of cardiac function and decreases scar size in a mouse model of myocardial infarction (MI), in the absence of intact cells. It is not clear if thes

10.ペースメーカー移植術の経験(第609回千葉医学会例会・第1外科教室談話会)

Five supporting tables. A table caption of each is given within the file. (XLSX 84 kb

Prognostic utility of the breast cancer index and comparison to Adjuvant! Online in a clinical case series of early breast cancer

Introduction\ud Breast Cancer Index (BCI) combines two independent biomarkers, HOXB13:IL17BR (H:I) and the 5-gene molecular grade index (MGI), that assess estrogen-mediated signalling and tumor grade, respectively. BCI stratifies early-stage estrogen-receptor positive (ER+), lymph-node negative (LN-) breast cancer patients into three risk groups and provides a continuous assessment of individual risk of distant recurrence. Objectives of the current study were to validate BCI in a clinical case series and to compare the prognostic utility of BCI and Adjuvant!Online (AO).\ud \ud Methods\ud Tumor samples from 265 ER+LN- tamoxifen-treated patients were identified from a single academic institution's cancer research registry. The BCI assay was performed and scores were assigned based on a pre-determined risk model. Risk was assessed by BCI and AO and correlated to clinical outcomes in the patient cohort.\ud \ud Results\ud BCI was a significant predictor of outcome in a cohort of 265 ER+LN- patients (median age: 56-y; median follow-up: 10.3-y), treated with adjuvant tamoxifen alone or tamoxifen with chemotherapy (32%). BCI categorized 55%, 21%, and 24% of patients as low, intermediate and high-risk, respectively. The 10-year rates of distant recurrence were 6.6%, 12.1% and 31.9% and of breast cancer-specific mortality were 3.8%, 3.6% and 22.1% in low, intermediate, and high-risk groups, respectively. In a multivariate analysis including clinicopathological factors, BCI was a significant predictor of distant recurrence (HR for 5-unit increase = 5.32 [CI 2.18-13.01; P = 0.0002]) and breast cancer-specific mortality (HR for a 5-unit increase = 9.60 [CI 3.20-28.80; P < 0.0001]). AO was significantly associated with risk of recurrence. In a separate multivariate analysis, both BCI and AO were significantly predictive of outcome. In a time-dependent (10-y) ROC curve accuracy analysis of recurrence risk, the addition of BCI+AO increased predictive accuracy in all patients from 66% (AO only) to 76% (AO+BCI) and in tamoxifen-only treated patients from 65% to 81%.\ud \ud Conclusions\ud This study validates the prognostic performance of BCI in ER+LN- patients. In this characteristically low-risk cohort, BCI classified high versus low-risk groups with ~5-fold difference in 10-year risk of distant recurrence and breast cancer-specific death. BCI and AO are independent predictors with BCI having additive utility beyond standard of care parameters that are encompassed in AO