Understanding Water Level Changes in the Great Lakes by an ICA-Based Merging of Multi-Mission Altimetry Measurements

Accurately monitoring spatio-temporal changes in lake water levels is important for studying the impacts of climate change on freshwater resources, and for predicting natural hazards. In this study, we applied multi-mission radar satellite altimetry data from the Laurentian Great Lakes, North America to optimally reconstruct multi-decadal lake-wide spatio-temporal changes of water level. We used the results to study physical processes such as teleconnections of El Niño and southern oscillation (ENSO) episodes over approximately the past three-and-a-half decades (1985–2018). First, we assessed three reconstruction methods, namely the standard empirical orthogonal function (EOF), complex EOF (CEOF), and complex independent component analysis (CICA), to model the lake-wide changes of water level. The performance of these techniques was evaluated using in-situ gauge data, after correcting the Glacial Isostatic Adjustment (GIA) process using a contemporary GIA forward model. While altimeter-measured water level was much less affected by GIA, the averaged gauge-measured water level was found to have increased up to 14 cm over the three decades. Our results indicate that the CICA-reconstructed 35-year lake level was more accurate than the other two techniques. The correlation coefficients between the CICA reconstruction and the in situ water-level data were 0.96, 0.99, 0.97, 0.97, and 0.95, for Lake Superior, Lake Michigan, Lake Huron, Lake Erie, and Lake Ontario, respectively; ~7% higher than the original altimetry data. The root mean squares of errors (RMSE) were 6.07 cm, 4.89 cm, 9.27 cm, 7.71 cm, and 9.88 cm, respectively, for each of the lakes, and ~44% less than differencing with the original altimetry data. Furthermore, the CICA results indicated that the water-level changes in the Great Lakes were significantly correlated with ENSO, with correlation coefficients of 0.5–0.8. The lake levels were ~25 cm higher (~30 cm lower) than normal during EI Niño (La Niña) events

Pharmacokinetics and safety of ixazomib plus lenalidomide–dexamethasone in Asian patients with relapsed/refractory myeloma: a phase 1 study

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Propensity score analysis in the Genetic Analysis Workshop 17 simulated data set on independent individuals

Genetic Analysis Workshop 17 provided simulated phenotypes and exome sequence data for 697 independent individuals (209 case subjects and 488 control subjects). The disease liability in these data was influenced by multiple quantitative traits. We addressed the lack of statistical power in this small data set by limiting the genomic variants included in the study to those with potential disease-causing effect, thereby reducing the problem of multiple testing. After this adjustment, we could readily detect two common variants that were strongly associated with the quantitative trait Q1 (C13S523 and C13S522). However, we found no significant associations with the affected status or with any of the other quantitative traits, and the relationship between disease status and genomic variants remained obscure. To address the challenge of the multivariate phenotype, we used propensity scores to combine covariates with genetic risk factors into a single risk factor and created a new phenotype variable, the probability of being affected given the covariates. Using the propensity score as a quantitative trait in the case-control analysis, we again could identify the two common single-nucleotide polymorphisms (C13S523 and C13S522). In addition, this analysis captured the correlation between Q1 and the affected status and reduced the problem of multiple testing. Although the propensity score was useful for capturing and clarifying the genetic contributions of common variants to the disease phenotype and the mediating role of the quantitative trait Q1, the analysis did not increase power to detect rare variants

DUST EMISSION AND STAR FORMATION IN STEPHAN\u27S QUINTET

We analyze a comprehensive set of MIR/FIR observations of Stephan\u27s Quintet (SQ), taken with the Spitzer Space Telescope. Our study reveals the presence of a luminous (L IR 4.6 × 1043 erg s-1) and extended component of infrared dust emission, not connected with the main bodies of the galaxies, but roughly coincident with the X-ray halo of the group. We fitted the inferred dust emission spectral energy distribution of this extended source and the other main infrared emission components of SQ, including the intergalactic shock, to elucidate the mechanisms powering the dust and polycyclic aromatic hydrocarbon emission, taking into account collisional heating by the plasma and heating through UV and optical photons. Combining the inferred direct and dust-processed UV emission to estimate the star formation rate (SFR) for each source we obtain a total SFR for SQ of 7.5 M yr-1, similar to that expected for non-interacting galaxies with stellar mass comparable to the SQ galaxies. Although star formation in SQ is mainly occurring at, or external to the periphery of the galaxies, the relation of SFR per unit physical area to gas column density for the brightest sources is similar to that seen for star formation regions in galactic disks. We also show that available sources of dust in the group halo can provide enough dust to produce up to L IR 1042 erg s-1 powered by collisional heating. Though a minority of the total infrared emission (which we infer to trace distributed star-formation), this is several times higher than the X-ray luminosity of the halo, so could indicate an important cooling mechanism for the hot intergalactic medium (IGM) and account for the overall correspondence between FIR and X-ray emission. We investigate two potential modes of star formation in SQ consistent with the data, fueled either by gas from a virialized hot IGM continuously accreting onto the group, whose cooling is enhanced by grains injected from an in situ population of intermediate mass stars, or by interstellar gas stripped from the galaxies. The former mode offers a natural explanation for the observed baryon deficiency in the IGM of SQ as well as for the steep L X-T X relation of groups such as SQ with lower velocity dispersions

HLA-matched sibling transplantation with G-CSF mobilized PBSCs and BM decreases GVHD in adult patients with severe aplastic anemia

<p>Abstract</p> <p>Background</p> <p>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for severe aplastic anemia (SAA). However, graft failure and graft-versus-host disease (GVHD) are major causes of the early morbidity in Allo-HSCT.</p> <p>Methods</p> <p>To reduce graft failure and GVHD, we treated fifteen patients with SAA using high- dose of HSCT with both G-CSF mobilized PB and BMSCs from HLA-identical siblings to treat patients with SAA.</p> <p>Results</p> <p>All patients had successful bone marrow engraftment. Only one patient had late rejection. Median time to ANC greater than 0.5 × 10⁹/L and platelet counts greater than 20 × 10⁹/L was 12 and 16.5 days, respectively. No acute GVHD was observed. The incidence of chronic GVHD was 6.67%. The total three-year probability of disease-free survival was 79.8%.</p> <p>Conclusion</p> <p>HSCT with both G-CSF mobilized PB and BMSCs is a promising approach for heavily transfused and/or allo-immunized patients with SAA.</p

Selection of diagnostic features on breast MRI to differentiate between malignant and benign lesions using computer-aided diagnosis: differences in lesions presenting as mass and non-mass-like enhancement

Purpose: To investigate methods developed for the characterisation of the morphology and enhancement kinetic features of both mass and non-mass lesions, and to determine their diagnostic performance to differentiate between malignant and benign lesions that present as mass versus non-mass types. Methods: Quantitative analysis of morphological features and enhancement kinetic parameters of breast lesions were used to differentiate among four groups of lesions: 88 malignant (43 mass, 45 non-mass) and 28 benign (19 mass, 9 non-mass). The enhancement kinetics was measured and analysed to obtain transfer constant (Ktrans) and rate constant (kep). For each mass eight shape/margin parameters and 10 enhancement texture features were obtained. For the lesions presenting as nonmass-like enhancement, only the texture parameters were obtained. An artificial neural network (ANN) was used to build the diagnostic model. Results: For lesions presenting as mass, the four selected morphological features could reach an area under the ROC curve (AUC) of 0.87 in differentiating between malignant and benign lesions. The kinetic parameter (kep) analysed from the hot spot of the tumour reached a comparable AUC of 0.88. The combined morphological and kinetic features improved the AUC to 0.93, with a sensitivity of 0.97 and a specificity of 0.80. For lesions presenting as non-mass-like enhancement, four texture features were selected by the ANN and achieved an AUC of 0.76. The kinetic parameter kepfrom the hot spot only achieved an AUC of 0.59, with a low added diagnostic value. Conclusion: The results suggest that the quantitative diagnostic features can be used for developing automated breast CAD (computer-aided diagnosis) for mass lesions to achieve a high diagnostic performance, but more advanced algorithms are needed for diagnosis of lesions presenting as non-mass-like enhancement. © The Author(s) 2009

Spread of Mutant Middle East Respiratory Syndrome Coronavirus with Reduced Affinity to Human CD26 during the South Korean Outbreak

The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe respiratory infection with a high mortality rate (similar to 35%). MERS-CoV has been a global threat due to continuous outbreaks in the Arabian peninsula and international spread by infected travelers since 2012. From May to July 2015, a large outbreak initiated by an infected traveler from the Arabian peninsula swept South Korea and resulted in 186 confirmed cases with 38 deaths (case fatality rate, 20.4%). Here, we show the rapid emergence and spread of a mutant MERS-CoV with reduced affinity to the human CD26 receptor during the South Korean outbreak. We isolated 13 new viral genomes from 14 infected patients treated at a hospital and found that 12 of these genomes possess a point mutation in the receptor-binding domain (RBD) of viral spike (S) protein. Specifically, 11 of these genomes have an I529T mutation in RBD, and 1 has a D510G mutation. Strikingly, both mutations result in reduced affinity of RBD to human CD26 compared to wild-type RBD, as measured by surface plasmon resonance analysis and cellular binding assay. Additionally, pseudotyped virus bearing an I529T mutation in S protein showed reduced entry into host cells compared to virus with wild-type S protein. These unexpected findings suggest that MERS-CoV adaptation during human-to-human spread may be driven by host immunological pressure such as neutralizing antibodies, resulting in reduced affinity to host receptor, and thereby impairs viral fitness and virulence, rather than positive selection for a better affinity to CD26. IMPORTANCE Recently, a large outbreak initiated by an MERS-CoV-infected traveler from the Middle East swept South Korea and resulted in 186 confirmed cases with 38 deaths. This is the largest outbreak outside the Middle East, and it raised strong concerns about the possible emergence of MERS-CoV mutations. Here, we isolated 13 new viral genomes and found that 12 of them possess a point mutation in the receptor-binding domain of viral spike protein, resulting in reduced affinity to the human cognate receptor, CD26, compared to the wild-type virus. These unexpected findings suggest that MERS-CoV adaptation in humans may be driven by host immunological pressure.111819Ysciescopu

Daratumumab plus bortezomib, cyclophosphamide, and dexamethasone in Asian patients with newly diagnosed AL amyloidosis: subgroup analysis of ANDROMEDA

Subcutaneous daratumumab plus bortezomib/cyclophosphamide/dexamethasone (VCd; D-VCd) improved outcomes versus VCd for patients with newly diagnosed immunoglobulin light-chain (AL) amyloidosis in the phase 3 ANDROMEDA study. We report a subgroup analysis of Asian patients (Japan; Korea; China) from ANDROMEDA. Among 388 randomized patients, 60 were Asian (D-VCd, n = 29; VCd, n = 31). At a median follow-up of 11.4 months, the overall hematologic complete response rate was higher for D-VCd versus VCd (58.6% vs. 9.7%; odds ratio, 13.2; 95% confidence interval [CI], 3.3–53.7; P < 0.0001). Six-month cardiac and renal response rates were higher with D-VCd versus VCd (cardiac, 46.7% vs. 4.8%; P = 0.0036; renal, 57.1% vs. 37.5%; P = 0.4684). Major organ deterioration progression-free survival (MOD-PFS) and major organ deterioration event-free survival (MOD-EFS) were improved with D-VCd versus VCd (MOD-PFS: hazard ratio [HR], 0.21; 95% CI, 0.06–0.75; P = 0.0079; MOD-EFS: HR, 0.16; 95% CI, 0.05–0.54; P = 0.0007). Twelve deaths occurred (D-VCd, n = 3; VCd, n = 9). Twenty-two patients had baseline serologies indicating prior hepatitis B virus (HBV) exposure; no patient experienced HBV reactivation. Although grade 3/4 cytopenia rates were higher than in the global safety population, the safety profile of D-VCd in Asian patients was generally consistent with the global study population, regardless of body weight. These results support D-VCd use in Asian patients with newly diagnosed AL amyloidosis. ClinicalTrials.gov Identifier: NCT03201965

Distribution of HLA-A, -B and -DRB1 Genes and Haplotypes in the Tujia Population Living in the Wufeng Region of Hubei Province, China

BACKGROUND: The distribution of HLA alleles and haplotypes varies widely between different ethnic populations and geographic areas. Before any genetic marker can be used in a disease-associated study it is therefore essential to investigate allelic frequencies and establish a genetic database. METHODOLOGY/PRINCIPAL FINDINGS: This is the first report of HLA typing in the Tujia group using the Luminex HLA-SSO method HLA-A, -B and -DRB1 allelic distributions were determined in 124 unrelated healthy Tujia individuals, and haplotypic frequencies and linkage disequilibrium parameters were estimated using the maximum-likelihood method. In total 10 alleles were detected at the HLA-A locus, 21 alleles at the HLA-B locus and 14 alleles at the HLA-DRB1 locus. The most frequently observed alleles in the HLA-I group were HLA-A*02 (35.48%), A*11 (28.23%), A*24 (15.73%); HLA-B*40 (25.00%), B*46 (16.13%), and B*15 (15.73%). Among HLA-DRB1 alleles, high frequencies of HLA-DRB1*09 (25.81%) were observed, followed by HLA-DRB1*15 (12.9%), and DRB1*12 (10.89%). The two-locus haplotypes at the highest frequency were A*02-B*46A (8.47%), followed by A*11-B*40 (7.66%), A*02-B*40 (8.87%), A*11-B*15 (6.45%), A*02-B*15 (6.05%), B*40-DRB1*09 (9.27%) and B*46-DRB1*09 (6.45%). The most common three-locus haplotypes found in the Tujia population were A*02-B*46-DRB1*09 (4.84%) and A*02-B*40-DRB1*09 (4.03%). Fourteen two-loci haplotypes had significant linkage disequilibrium. Construction of a neighbor-joining phylogenetic tree and principal component analysis using the allelic frequencies at HLA-A was performed to compare the Tujia group and twelve other previously reported populations. The Tujia population in the Wufeng of Hubei Province had the closest genetic relationship with the central Han population, and then to the Shui, the Miao, the southern Han and the northern Han ethnic groups. CONCLUSIONS/SIGNIFICANCE: These results will become a valuable source of data for tracing population migration, planning clinical organ transplantation, carrying out HLA-linked disease-associated studies and forensic identification

Theory of mind impairment and its clinical correlates in patients with schizophrenia, major depressive disorder and bipolar disorder.

BACKGROUND: Although Theory of Mind (ToM) impairment has been observed in patients with a wide range of mental disorders, the similarity and uniqueness of these deficits across diagnostic groups has not been thoroughly investigated. METHODS: We recruited 35 participants with schizophrenia (SCZ), 35 with bipolar disorder (BD), 35 with major depressive disorder (MDD), and 35 healthy controls in this study. All participants were matched in age, gender proportion and IQ estimates. The Yoni task, capturing both the cognitive and affective components of ToM at the first- and second-order level was administered. Repeated-measure ANOVA and MANOVA were conducted to compare the group differences in ToM performance. A network was then constructed with ToM performances, psychotic and depressive symptoms, and executive function as nodes exploring the clinical correlates of ToM. RESULTS: Overall, ToM impairments were observed in all patient groups compared with healthy controls, with patients with SCZ performing worse than those with BD. In second-order conditions, patients with SCZ and MDD showed deficits in both cognitive and affective conditions, while patients with BD performed significantly poorer in cognitive conditions. Network analysis showed that second-order affective ToM performance was associated with psychotic and depressive symptoms as well as executive dysfunction, while second-order affective ToM performance and negative symptoms showed relatively high centrality in the network. CONCLUSIONS: Patients with SCZ, MDD and BD exhibited different types and severity of impairments in ToM sub-components. Impairment in higher-order affective ToM appears to be closely related to clinical symptoms in both psychotic and affective disorders