Cosmology and Astrophysics with Dark Matter and Gaseous Halos

Multi-wavelength astronomical surveys promise to provide unprecedented data ondark matter halos from galactic to cluster scales in the coming decade. One of the new frontiers lies in studies of intracluster medium (ICM) and circumgalactic medium (CGM) for cosmology and galaxy formation. In this work, we will combine cosmological and idealized simulations to study the non-linear growth of structures and the effects of small scale astrophysics in the realistic cosmological settings. Specifically, we will investigate the connection between the dark matter halos and the cosmic web structures, focusing on the outer boundaries of dark matter and gaseous halos around cluster-size dark matter halos and the filamentary cold gas accretion feeding high redshift galaxies. We show that the edge of the phase space structure and accretion shock radii denote the outer boundaries of the halos and have the potential to advance cluster cosmology. We also investigate the roles of hydrodynamic and gravitational instabilities on the survival of cold gas streams feeding high-redshift galaxies. My research highlights the importance of understanding the growth of dark matter halos and their interactions with the cosmic web structures for advancing cosmology and astrophysics in the era of multi-wavelength astronomical surveys

Senti-Lexicon and Analysis for Restaurant Reviews of Myanmar Text

Social media has just become as an influential with the rapidly growing popularity of online customers reviews available in social sites by using informal languages and emoticons. These reviews are very helpful for new customers and for decision making process. Sentiment analysis is to state the feelings, opinions about people\u27s reviews together with sentiment. Most of researchers applied sentiment analysis for English Language. There is no research efforts have sought to provide sentiment analysis of Myanmar text. To tackle this problem, we propose the resource of Myanmar Language for mining food and restaurants\u27 reviews. This paper aims to build language resource to overcome the language specific problem and opinion word extraction for Myanmar text reviews of consumers. We address dictionary based approach of lexicon-based sentiment analysis for analysis of opinion word extraction in food and restaurants domain. This research assesses the challenges and problem faced in sentiment analysis of Myanmar Language area for future

Factors Affecting the Compliance of Myanmar Nurses in Performing Standard Precaution

Introduction: Exposure to pathogens is a serious issue for nurses. The literature explains that standard precaution have not consistently done in nursing. The purpose of this study was to analyze the factors affecting the compliance of nurses in Myanmar in performing standard precautions. Methods: This study used a cross-sectional design. Samples included 34 nurses in Waibagi Specialist Hospital (SHW), Myanmar. The independent variables were the characteristics of nurses, knowledge of standard precaution, and exposure to blood / body fluids and needle puncture wounds. The dependent variable was the performance of standard prevention. Data analyzed using descriptive analysis and logistic regression. Results: The result showed that almost respondents (91.18%) had a good knowledge about prevention standards and 73.5% of respondents had good adherence in performing standard precaution. However, in practice nurses have not been consistent in closing the needles that have been used correctly. The results showed that nurse characteristics did not significantly affect adherence to standard precaution with statistical test results as follows: age (p = 0.97), gender (p = 1.00), religion (p = 0.72), education (p = 0.85), work experience at SHW (p = 0, 84), education training program (p = 0.71), knowledge (p = 0.76), and needle stick injury (p = 0,17). But, there was a significant influence between adherence to standard precaution on the incidence of injury due to puncture needle with p value = 0.01. Discussion: The barriers to applying standard precautions by Myanmar nurses can be reduced by providing basic training, supervision and improvement of operational standard procedures

Germline PTPRD mutations in Ewing sarcoma: biologic and clinical implications.

Ewing sarcoma occurs in children, adolescents and young adults. High STAT3 levels have been reported in approximately 50% of patients with Ewing sarcoma, and may be important in tumorigenesis. Protein tyrosine phosphatase delta (PTPRD) is a tumor suppressor that inhibits STAT3 activation. To date, while somatic mutations in PTPRD have been reported in diverse tumors, germline mutations of PTPRD have not been investigated in Ewing sarcoma or other cancers. We identified a novel germline mutation in the PTPRD gene in three of eight patients (37.5%) with metastatic Ewing sarcoma. Although the functional impact in two of the patients is unclear, in one of them the aberration was annotated as a W775stop germline mutation, and would be expected to lead to gene truncation and, hence, loss of the STAT3 dephosphorylation function of PTPRD. Since STAT3 is phosphorylated after being recruited to the insulin growth factor receptor (IGF-1R), suppression of IGF-1R could attenuate the enhanced STAT3 activation expected in the presence of PTPRD mutations. Of interest, two of three patients with germline PTPRD mutations achieved durable complete responses following treatment with IGF-1R monoclonal antibody-based therapies. Our pilot data suggest that PTPRD germline mutations may play a role in the development of Ewing sarcoma, a disease of young people, and their presence may have implications for therapy

Novel secondary somatic mutations in Ewing's sarcoma and desmoplastic small round cell tumors.

BackgroundEwing's sarcoma (ES) and desmoplastic small round cell tumors (DSRCT) are small round blue cell tumors driven by an N-terminal containing EWS translocation. Very few somatic mutations have been reported in ES, and none have been identified in DSRCT. The aim of this study is to explore potential actionable mutations in ES and DSRCT.MethodologyTwenty eight patients with ES or DSRCT had tumor tissue available that could be analyzed by one of the following methods: 1) Next-generation exome sequencing platform; 2) Multiplex PCR/Mass Spectroscopy; 3) Polymerase chain reaction (PCR)-based single- gene mutation screening; 4) Sanger sequencing; 5) Morphoproteomics.Principal findingsNovel somatic mutations were identified in four out of 18 patients with advanced ES and two of 10 patients with advanced DSRCT (six out of 28 (21.4%));KRAS (n = 1), PTPRD (n = 1), GRB10 (n = 2), MET (n = 2) and PIK3CA (n = 1). One patient with both PTPRD and GRB10 mutations and one with a GRB10 mutation achieved a complete remission (CR) on an Insulin like growth factor 1 receptor (IGF1R) inhibitor based treatment. One patient, who achieved a partial remission (PR) with IGF1R inhibitor treatment, but later developed resistance, demonstrated a KRAS mutation in the post-treatment resistant tumor, but not in the pre-treatment tumor suggesting that the RAF/RAS/MEK pathway was activated with progression.ConclusionsWe have reported several different mutations in advanced ES and DSRCT that have direct implications for molecularly-directed targeted therapy. Our technology agnostic approach provides an initial mutational roadmap used in the path towards individualized combination therapy

Advanced gynecologic malignancies treated with a combination of the VEGF inhibitor bevacizumab and the mTOR inhibitor temsirolimus.

BackgroundBevacizumab and temsirolimus are active agents in gynecologic tumors. Temsirolimus attenuates upregulation of HIF-1α levels, a resistance mechanism for antiangiogenics, and targets the PI3-kinase/AKT/mTOR axis, commonly aberrant in these tumors.Patients and methodsWe analyzed safety and responses in 41 patients with gynecologic cancers treated as part of a Phase I study of bevacizumab and temsirolimus.ResultsMedian age of the 41 women was 60 years (range, 33-80 years); median number of prior systemic therapies was 4 (1-11). Grade 3 or 4 treatment-related toxicities included: thrombocytopenia (10%), mucositis (2%), hypertension (2%), hypercholesterolemia (2%), fatigue (7%), elevated aspartate aminotransferase (2%), and neutropenia (2%). Twenty-nine patients (71%) experienced no treatment-related toxicity greater than grade 2. Full FDA-approved doses of both drugs (bevacizumab 15mg/kg IV Q3weeks and temsirolimus 25mg IV weekly) were administered without dose-limiting toxicity. Eight patients (20%) achieved stable disease (SD) > 6 months and 7 patients (17%), a partial response (PR) [total = 15/41 patients (37%)]. Eight of 13 patients (62%) with high-grade serous histology (ovarian or primary peritoneal) achieved SD > 6 months/PR.ConclusionBevacizumab and temsirolimus was well tolerated. Thirty-seven percent of heavily-pretreated patients achieved SD > 6 months/PR, suggesting that this combination warrants further study

Left ventricular trabeculations in cardiac MRI: reference ranges and association with cardiovascular risk factors in UK Biobank

Background The extent of left ventricular (LV) trabeculation and its relationship with cardiovascular (CV) risk factors is unclear. Purpose To apply automated segmentation to UK Biobank cardiac MRI scans to (a) assess the association between individual characteristics and CV risk factors and trabeculated LV mass (LVM) and (b) establish normal reference ranges in a selected group of healthy UK Biobank participants. Materials and Methods In this cross-sectional secondary analysis, prospectively collected data from the UK Biobank (2006 to 2010) were retrospectively analyzed. Automated segmentation of trabeculations was performed using a deep learning algorithm. After excluding individuals with known CV diseases, White adults without CV risk factors (reference group) and those with preexisting CV risk factors (hypertension, hyperlipidemia, diabetes mellitus, or smoking) (exposed group) were compared. Multivariable regression models, adjusted for potential confounders (age, sex, and height), were fitted to evaluate the associations between individual characteristics and CV risk factors and trabeculated LVM. Results Of 43 038 participants (mean age, 64 years ± 8 [SD]; 22 360 women), 28 672 individuals (mean age, 66 years ± 7; 14 918 men) were included in the exposed group, and 7384 individuals (mean age, 60 years ± 7; 4729 women) were included in the reference group. Higher body mass index (BMI) (β = 0.66 [95% CI: 0.63, 0.68]; P < .001), hypertension (β = 0.42 [95% CI: 0.36, 0.48]; P < .001), and higher physical activity level (β = 0.15 [95% CI: 0.12, 0.17]; P < .001) were associated with higher trabeculated LVM. In the reference group, the median trabeculated LVM was 6.3 g (IQR, 4.7–8.5 g) for men and 4.6 g (IQR, 3.4–6.0 g) for women. Median trabeculated LVM decreased with age for men from 6.5 g (IQR, 4.8–8.7 g) at age 45–50 years to 5.9 g (IQR, 4.3–7.8 g) at age 71–80 years (P = .03). Conclusion Higher trabeculated LVM was observed with hypertension, higher BMI, and higher physical activity level. Age- and sex-specific reference ranges of trabeculated LVM in a healthy middle-aged White population were established

Dual EGFR inhibition in combination with anti-VEGF treatment in colorectal cancer.

Preclinical studies demonstrate that epidermal growth factor receptor (EGFR) signals through both kinase-dependent and independent pathways and that combining a small-molecule EGFR inhibitor, EGFR antibody, and/or anti-angiogenic agent is synergistic. We conducted a dose-escalation, phase I study combining erlotinib, cetuximab, and bevacizumab. The subset of patients with metastatic colorectal cancer was analyzed for safety and antitumor activity. Forty-one patients with heavily pretreated metastatic colorectal cancer received treatment on a range of dose levels. The most common treatment-related grade ≥2 adverse events were rash (68%), hypomagnesemia (37%), and fatigue (15%). Thirty of 34 patients (88%) treated at the full FDA-approved doses of all three drugs tolerated treatment without drug-related dose-limiting effects. Eleven patients (27%) achieved stable disease (SD) ≥6 months and three (7%) achieved a partial response (PR) (total SD&gt;6 months/PR= 14 (34%)). Of the 14 patients with SD≥6 months/PR, eight (57%) had received prior sequential bevacizumab and cetuximab, two (5%) had received bevacizumab and cetuximab concurrently, and four (29%) had received prior bevacizumab but not cetuximab or erlotinib (though three had received prior panitumumab). The combination of bevacizumab, cetuximab, and erlotinib was well tolerated and demonstrated antitumor activity in heavily pretreated patients with metastatic colorectal cancer