Cosmology with the Square Kilometre Array

We argue that the Square Kilometre Array has the potential to make both redshift (HI) surveys and radio continuum surveys that will revolutionize cosmological studies, provided that it has sufficient instantaneous field-of-view that these surveys can cover a hemisphere in a timescale ~1 yr. Adopting this assumption, we focus on two key experiments which will yield fundamental new measurements in cosmology, characterizing the properties of the mysterious dark energy which dominates the dynamics of today's Universe. Experiment I will map out ~10^9 HI galaxies to redshift z~1.5, providing the premier measurement of the clustering power spectrum of galaxies: accurately delineating the acoustic oscillations and the `turnover'. Experiment II will quantify the cosmic shear distortion of ~10^10 radio continuum sources, determining a precise power spectrum of the dark matter, and its growth as a function of cosmic epoch. We contrast the performance of the SKA in precision cosmology with that of other facilities which will, probably or possibly, be available on a similar timescale. We conclude that data from the SKA will yield transformational science as the direct result of four key features: (i) the immense cosmic volumes probed, exceeding future optical redshift surveys by more than an order of magnitude; (ii) well-controlled systematic effects such as the narrow `k-space window function' for Experiment I and the accurately-known `point-spread function' for Experiment II; (iii) the ability to measure with high precision large-scale modes in the clustering power spectra, for which nuisance effects such as non-linear structure growth, peculiar velocities and `galaxy bias' are minimised; and (iv) different degeneracies between key parameters to those which are inherent in the CMB.Comment: 20 pages, 8 figures. To appear in "Science with the Square Kilometer Array", eds. C.Carilli and S.Rawlings, New Astronomy Reviews (Elsevier: Amsterdam

Identification of the Regions in Factor V Mediating its Edocytosis by Megakaryocytes to Form the Unique Platelet-Derived Cofactor Molecule

Factor Va is a plasma protein that plays an important role in the regulation of blood coagulation by serving as the essential cofactor in thrombin generation via the prothrombinase complex. The procofactor, factor V, exists in two whole blood pools with 75-80% found in plasma, and 20-25% stored in the α-granules of platelets. As compared to the plasma procofactor, platelet-derived factor V is physically and functionally distinct, and displays a more procoagulant phenotype. Despite these profound differences, platelet-derived factor V originates via endocytosis of the plasma-derived procofactor by megakaryocytes. Endocytosis is mediated by two receptors: an unidentified, specific factor V receptor, and low density lipoprotein (LDL) receptor related protein-1 (LRP-1), a ubiquitous receptor that plays a role in endocytosis of proteins targeted for lysosomal degradation. These observations represent a novel role for LRP-1 in endocytosis of a protein that is functionally modified, and not targeted for lysosomal degradation. The goal of this study is to define the factor V regions involved in its interactions with the unidentified factor V receptor and LRP-1 expressed on megakaryocytes to begin to elucidate the molecular mechanisms regulating formation of the unique platelet-derived cofactor. Epitope mapping studies were performed using anti-factor V monoclonal antibodies, E9 and anti-factor V #2. Previous observations indicated that these factor Va light chain antibodies inhibited endocytosis of factor V by megakaryocytes. However, subsequent analyses demonstrated that only E9 inhibited both factor V binding and endocytosis. Thus, it was used for these studies. Western blotting of factor V and Va suggested that E9 recognizes a conformation-dependent epitope, which precluded the use of conventional epitope mapping approaches used for linear epitopes. E9 had no effect on factor Va cofactor activity in a plasma-based clotting assay suggesting that it does not perturb factor Va’s interactions with the membrane surface or factor Xa. Cleavage of lipid-bound factor Va by factor Xa at Arg1765 was also not affected by the presence of E9 suggesting that the epitope is not directed against this cleavage site. When E9 was used to immunoprecipitate the factor Xa-generated light chain cleavage products, both the 48/46 and 30 kDa light chain fragments were captured. These observations were confirmed using a solid phase competition assay where factor Xa-cleaved factor Va inhibited binding of 125I-factor V to E9 as well as intact factor V or Va. Limited proteolysis of the factor Va light chain with trypsin or Asp-N, generated products that were no longer detectable in this assay. These combined observations suggest that the anti-factor V light chain antibody, E9, has an epitope that is conformation-dependent and extremely labile. Future directions and alternative approaches are discussed

Vaginal carriage and antibiotic susceptibility profile of group B Streptococcus during late pregnancy in Ismailia, Egypt

SummaryGroup B Streptococcus (GBS) infection has long been recognized as a frequent cause of morbidity and mortality in newborn infants. The purpose of this study was to determine the colonization rate with GBS and the antibiotic susceptibility profile in pregnant women attending Gynecological clinics in Egypt. One-hundred and fifty vaginal swabs were collected from pregnant women at 35–40 weeks of gestation. In comparison to culture, direct latex agglutination testing revealed 100% sensitivity and 93.75% specificity. Thirty-eight specimens (25.3%) were found to be positive for GBS. Each isolate was tested for susceptibility to penicillin G, ampicillin, cefotaxime, erythromycin, clindamycin and vancomycin. Erythromycin-resistant isolates were further classified by double-disk method. All isolates were susceptible to penicillin G, ampicillin and vancomycin. Resistance to cefotaxime was detected in three isolates (7.89%). Five isolates (13.15%) were resistant to erythromycin and nine isolates (23.68%) were resistant to clindamycin. Four (80%) isolates had constitutive macrolide–lincosamide–StreptograminB resistance (cMLSBB) resistance and one (20%) isolate had inducible resistance (iMLSB) resistance. GBS colonization was found to be high in our region. Latex agglutination testing and Islam medium are reliable methods to detect GBS in late pregnancy; however, latex agglutination test is rapid and simpler. Penicillin G remains the first choice antibiotic for treatment of GBS infections

Prognostic impact of Additional Chromosomal Abnormalities in Egyptian Chronic Myeloid Leukemia Patients

BACKGROUND: Emergence of additional chromosomal abnormalities (ACAs) in chronic myeloid leukemia (CML) is associated with disease progression to advanced phases and reflects the genetic instability of CML. AIM: Is to evaluate the frequency of ACAs in chronic phase (CP) and advanced disease (AP) CML patients and study their impact on patient’s outcome, overall survival (OS) and event-free survival (EFS). RESULTS: The studied group (n = 73) included 31 males (43%) and 42 females (57%). Median age of patients at diagnosis was 37 years (17–76). Median TLC was 208×109/L (2.1–784.2), median Hb was 9.4 g/dL (5.7–13), and median platelets count was 290.5×109/L (13–1271). We identified 32 patients (44%) with ACAs. ACAs emergence was significantly associated with advanced phases of CML (13/21, 62%) compared to CP (19/52, 36%) (p = 0.048). ACAs were associated with lower median OS and EFS in CP compared to AP (38 vs. 120 ms) and (58.3 vs. 77 ms) (p = 0.026 and p = 0.065, respectively). Early molecular responders (6/17, 35%) at 3 months, and 6 months (10/26, 38%) developed ACAs less than nonoptimal responders. Disease phase, hepatomegaly and bone marrow eosinophilia were significant predictors of OS (p < 0.001, p = 0.02, p = 0.04, respectively). CONCLUSION: Early identification of ACAs in Ph+ metaphases at diagnosis and during therapy predicts CML outcome. ACAs emergence occurred at a higher frequency and at a younger age in our CML patients and are related to inferior EFS and OS

Madurella mycetomatis Is Highly Susceptible to Ravuconazole

The current treatment of eumycetoma utilizing ketoconazole is unsatisfactory because of high recurrence rates, which often leads to complications and unnecessary amputations, and its comparatively high cost in endemic areas. Hence, an effective and affordable drug is required to improve therapeutic outcome. E1224 is a potent orally available, broad-spectrum triazole currently being developed for the treatment of Chagas disease. E1224 is a prodrug that is rapidly converted to ravuconazole. Plasma levels of E1224 are low and transient, and its therapeutically active moiety, ravuconazole is therapeutically active. In the present study, the in vitro activity of ravuconazole against Madurella mycetomatis, the most common etiologic agent of eumycetoma, was evaluated and compared to that of ketoconazole and itraconazole. Ravuconazole showed excellent activity with MICs ranging between ≤0.002 and 0.031 μg/ml, which were significantly lower than the MICs reported for ketoconazole and itraconazole. On the basis of our findings, E1224 with its resultant active moiety, ravuconazole, could be an effective and affordable therapeutic option for the treatment of eumycetoma

Dark energy constraints from cosmic shear power spectra: impact of intrinsic alignments on photometric redshift requirements

Cosmic shear constrains cosmology by exploiting the apparent alignments of pairs of galaxies due to gravitational lensing by intervening mass clumps. However galaxies may become (intrinsically) aligned with each other, and with nearby mass clumps, during their formation. This effect needs to be disentangled from the cosmic shear signal to place constraints on cosmology. We use the linear intrinsic alignment model as a base and compare it to an alternative model and data. If intrinsic alignments are ignored then the dark energy equation of state is biased by ~50 per cent. We examine how the number of tomographic redshift bins affects uncertainties on cosmological parameters and find that when intrinsic alignments are included two or more times as many bins are required to obtain 80 per cent of the available information. We investigate how the degradation in the dark energy figure of merit depends on the photometric redshift scatter. Previous studies have shown that lensing does not place stringent requirements on the photometric redshift uncertainty, so long as the uncertainty is well known. However, if intrinsic alignments are included the requirements become a factor of three tighter. These results are quite insensitive to the fraction of catastrophic outliers, assuming that this fraction is well known. We show the effect of uncertainties in photometric redshift bias and scatter. Finally we quantify how priors on the intrinsic alignment model would improve dark energy constraints.Comment: 14 pages and 9 figures. Replaced with final version accepted in "Gravitational Lensing" Focus Issue of the New Journal of Physics at http://www.iop.org/EJ/abstract/1367-2630/9/12/E0

The WiggleZ Dark Energy Survey: Direct constraints on blue galaxy intrinsic alignments at intermediate redshifts

Correlations between the intrinsic shapes of galaxy pairs, and between the intrinsic shapes of galaxies and the large-scale density field, may be induced by tidal fields. These correlations, which have been detected at low redshifts (z<0.35) for bright red galaxies in the Sloan Digital Sky Survey (SDSS), and for which upper limits exist for blue galaxies at z~0.1, provide a window into galaxy formation and evolution, and are also an important contaminant for current and future weak lensing surveys. Measurements of these alignments at intermediate redshifts (z~0.6) that are more relevant for cosmic shear observations are very important for understanding the origin and redshift evolution of these alignments, and for minimising their impact on weak lensing measurements. We present the first such intermediate-redshift measurement for blue galaxies, using galaxy shape measurements from SDSS and spectroscopic redshifts from the WiggleZ Dark Energy Survey. Our null detection allows us to place upper limits on the contamination of weak lensing measurements by blue galaxy intrinsic alignments that, for the first time, do not require significant model-dependent extrapolation from the z~0.1 SDSS observations. Also, combining the SDSS and WiggleZ constraints gives us a long redshift baseline with which to constrain intrinsic alignment models and contamination of the cosmic shear power spectrum. Assuming that the alignments can be explained by linear alignment with the smoothed local density field, we find that a measurement of \sigma_8 in a blue-galaxy dominated, CFHTLS-like survey would be contaminated by at most +/-0.02 (95% confidence level, SDSS and WiggleZ) or +/-0.03 (WiggleZ alone) due to intrinsic alignments. [Abridged]Comment: 18 pages, 12 figures, accepted to MNRAS; v2 has correction to one author's name, NO other changes; v3 has minor changes in explanation and calculations, no significant difference in results or conclusions; v4 has an additional footnote about model interpretation, no changes to data/calculations/result

Mixed Endometrial Epithelial Carcinoma: Epidemiology, Treatment and Survival Rates-A 10-Year Retrospective Cohort Study from a Single Institution

Mixed endometrial carcinoma (MEEC) refers to rare endometrial tumours that are composed of two or more distinct histotypes, at least one of which is serous or clear cell. The aim of this study was to evaluate the epidemiology, treatment outcomes and survival rates of patients with mixed endometrial carcinoma. The medical records of 34 patients diagnosed with MEEC between March 2010 and January 2020 were reviewed retrospectively. Clinicopathological variables and treatment strategies were assessed, and overall survival and disease-free survival rates were evaluated. The histology of endometrioid and serous component was found in 26 (76.5%) patients, followed by serous and clear-cell components (5/34, 14.5%) and mixed endometrioid serous and clear-cell components (3/34, 8.8%). The median age at diagnosis was 70 years (range 52-84), and the median follow-up time was 55 months. The 5-year disease-free survival and the 5-year overall survival were 50.4% and 52.4%, respectively. Advanced disease stage was identified as an independent predictor of inferior disease-free (&lt;0.003) and overall survival (p &lt; 0.001). Except for stage, none of the traditional prognostic factors was associated with disease recurrence or death from disease. MEECs represent rare high-risk endometrial carcinomas with significant diagnostic and treatment challenges. Undoubtedly, the implementation of a molecular analysis can offer further diagnostic and management insights