Myocardial expression of a constitutively active alpha 1B-adrenergic receptor in transgenic mice induces cardiac hypertrophy.

Transgenic mice were generated by using the alpha-myosin heavy chain promoter coupled to the coding sequence of a constitutively active mutant alpha 1B-adrenergic receptor (AR). These transgenic animals demonstrated cardiac-specific expression of this alpha 1-AR with resultant activation of phospholipase C as shown by increased myocardial diacylglycerol content. A phenotype consistent with cardiac hypertrophy developed in adult transgenic mice with increased heart/body weight ratios, myocyte cross-sectional areas, and ventricular atrial natriuretic factor mRNA levels relative to nontransgenic controls. These transgenic animals may provide insight into the biochemical triggers that induce hypertrophy in cardiac disease and serve as a convenient experimental model for studies of this condition

Evaluation of critical congenital heart defects screening using pulse oximetry in the neonatal intensive care unit.

ObjectiveTo evaluate the implementation of early screening for critical congenital heart defects (CCHDs) in the neonatal intensive care unit (NICU) and potential exclusion of sub-populations from universal screening.Study designProspective evaluation of CCHD screening at multiple time intervals was conducted in 21 NICUs across five states (n=4556 infants).ResultsOf the 4120 infants with complete screens, 92% did not have prenatal CHD diagnosis or echocardiography before screening, 72% were not receiving oxygen at 24 to 48 h and 56% were born ⩾2500 g. Thirty-seven infants failed screening (0.9%); none with an unsuspected CCHD. False positive rates were low for infants not receiving oxygen (0.5%) and those screened after weaning (0.6%), yet higher among infants born at <28 weeks (3.8%). Unnecessary echocardiograms were minimal (0.2%).ConclusionGiven the majority of NICU infants were ⩾2500 g, not on oxygen and not preidentified for CCHD, systematic screening at 24 to 48 h may be of benefit for early detection of CCHD with minimal burden

The Evolution of X-ray Clusters of Galaxies

Considerable progress has been made over the last decade in the study of the evolutionary trends of the population of galaxy clusters in the Universe. In this review we focus on observations in the X-ray band. X-ray surveys with the ROSAT satellite, supplemented by follow-up studies with ASCA and Beppo-SAX, have allowed an assessment of the evolution of the space density of clusters out to z~1, and the evolution of the physical properties of the intra-cluster medium out to z~0.5. With the advent of Chandra and Newton-XMM, and their unprecedented sensitivity and angular resolution, these studies have been extended beyond redshift unity and have revealed the complexity of the thermodynamical structure of clusters. The properties of the intra-cluster gas are significantly affected by non-gravitational processes including star formation and Active Galactic Nucleus (AGN) activity. Convincing evidence has emerged for modest evolution of both the bulk of the X-ray cluster population and their thermodynamical properties since redshift unity. Such an observational scenario is consistent with hierarchical models of structure formation in a flat low density universe with Omega_m=0.3 and sigma_8=0.7-0.8 for the normalization of the power spectrum. Basic methodologies for construction of X-ray-selected cluster samples are reviewed and implications of cluster evolution for cosmological models are discussed.Comment: 40 pages, 15 figures. Full resolution figures can be downloaded from http://www.eso.org/~prosati/ARAA

Macroscopic effects of the spectral structure in turbulent flows

Two aspects of turbulent flows have been the subject of extensive, split research efforts: macroscopic properties, such as the frictional drag experienced by a flow past a wall, and the turbulent spectrum. The turbulent spectrum may be said to represent the fabric of a turbulent state; in practice it is a power law of exponent \alpha (the "spectral exponent") that gives the revolving velocity of a turbulent fluctuation (or "eddy") of size s as a function of s. The link, if any, between macroscopic properties and the turbulent spectrum remains missing. Might it be found by contrasting the frictional drag in flows with differing types of spectra? Here we perform unprecedented measurements of the frictional drag in soap-film flows, where the spectral exponent \alpha = 3 and compare the results with the frictional drag in pipe flows, where the spectral exponent \alpha = 5/3. For moderate values of the Reynolds number Re (a measure of the strength of the turbulence), we find that in soap-film flows the frictional drag scales as Re^{-1/2}, whereas in pipe flows the frictional drag scales as Re^{-1/4} . Each of these scalings may be predicted from the attendant value of \alpha by using a new theory, in which the frictional drag is explicitly linked to the turbulent spectrum. Our work indicates that in turbulence, as in continuous phase transitions, macroscopic properties are governed by the spectral structure of the fluctuations.Comment: 6 pages, 3 figure

Inhibiting ERK Activation with CI-1040 Leads to Compensatory Upregulation of Alternate MAPKs and Plasminogen Activator Inhibitor-1 following Subtotal Nephrectomy with No Impact on Kidney Fibrosis

Extracellular-signal regulated kinase (ERK) activation by MEK plays a key role in many of the cellular processes that underlie progressive kidney fibrosis including cell proliferation, apoptosis and transforming growth factor β1-mediated epithelial to mesenchymal transition. We therefore assessed the therapeutic impact of ERK1/2 inhibition using a MEK inhibitor in the rat 5/6 subtotal nephrectomy (SNx) model of kidney fibrosis. There was a twentyfold upregulation in phospho-ERK1/2 expression in the kidney after SNx in Male Wistar rats. Rats undergoing SNx became hypertensive, proteinuric and developed progressive kidney failure with reduced creatinine clearance. Treatment with the MEK inhibitor, CI-1040 abolished phospho- ERK1/2 expression in kidney tissue and prevented phospho-ERK1/2 expression in peripheral lymphocytes during the entire course of therapy. CI-1040 had no impact on creatinine clearance, proteinuria, glomerular and tubular fibrosis, and α-smooth muscle actin expression. However, inhibition of ERK1/2 activation led to significant compensatory upregulation of the MAP kinases, p38 and JNK in kidney tissue. CI-1040 also increased the expression of plasminogen activator inhibitor-1 (PAI-1), a key inhibitor of plasmin-dependent matrix metalloproteinases. Thus inhibition of ERK1/2 activation has no therapeutic effect on kidney fibrosis in SNx possibly due to increased compensatory activation of the p38 and JNK signalling pathways with subsequent upregulation of PAI-1

High Energy Bounds on Soft N=4 SYM Amplitudes from AdS/CFT

Using the AdS/CFT correspondence, we study the high-energy behavior of colorless dipole elastic scattering amplitudes in N=4 SYM gauge theory through the Wilson loop correlator formalism and Euclidean to Minkowskian analytic continuation. The purely elastic behavior obtained at large impact-parameter L, through duality from disconnected AdS_5 minimal surfaces beyond the Gross-Ooguri transition point, is combined with unitarity and analyticity constraints in the central region. In this way we obtain an absolute bound on the high-energy behavior of the forward scattering amplitude due to the graviton interaction between minimal surfaces in the bulk. The dominant "Pomeron" intercept is bounded by alpha less than or equal to 11/7 using the AdS/CFT constraint of a weak gravitational field in the bulk. Assuming the elastic eikonal approximation in a larger impact-parameter range gives alpha between 4/3 and 11/7. The actual intercept becomes 4/3 if one assumes the elastic eikonal approximation within its maximally allowed range L larger than exp{Y/3}, where Y is the total rapidity. Subleading AdS/CFT contributions at large impact-parameter due to the other d=10 supergravity fields are obtained. A divergence in the real part of the tachyonic KK scalar is cured by analyticity but signals the need for a theoretical completion of the AdS/CFT scheme.Comment: 25 pages, 3 eps figure

Toward Understanding Massive Star Formation

Although fundamental for astrophysics, the processes that produce massive stars are not well understood. Large distances, high extinction, and short timescales of critical evolutionary phases make observations of these processes challenging. Lacking good observational guidance, theoretical models have remained controversial. This review offers a basic description of the collapse of a massive molecular core and a critical discussion of the three competing concepts of massive star formation: - monolithic collapse in isolated cores - competitive accretion in a protocluster environment - stellar collisions and mergers in very dense systems We also review the observed outflows, multiplicity, and clustering properties of massive stars, the upper initial mass function and the upper mass limit. We conclude that high-mass star formation is not merely a scaled-up version of low-mass star formation with higher accretion rates, but partly a mechanism of its own, primarily owing to the role of stellar mass and radiation pressure in controlling the dynamics.Comment: 139 pages, 18 figures, 5 tables, glossar

Pimecrolimus 1% cream for anogenital lichen sclerosus in childhood

BACKGROUND: Lichen sclerosus is a chronic inflammatory disease with a predilection of the anogenital region. Because of the potential side effects of repeated local application of potent glucocorticosteroids, equally-effective, safer therapeutic options are required, especially in the treatment of children. CASE PRESENTATIONS: We report on the efficacy of twice-daily application of pimecrolimus 1% cream in four prepubertal girls (range of age: 4 to 9 years) who suffered from anogenital lichen sclerosus. After three to four-month treatment, all patients had almost complete clinical remission including relief from itch, pain and inflammation. Only minor improvement was observed for the white sclerotic lesions. No significant side effects have been observed. CONCLUSIONS: Topical pimecrolimus appears to be an effective and safe treatment for children with anogenital lichen sclerosus. The clinical benefits observed in the four patient presented particularly include relief of pruritus, pain and inflammation. Vehicle-controlled studies on a larger number of patients are now warranted to substantiate our promising findings, and to investigate long-term efficacy and safety of topical pimecrolimus in anogenital lichen sclerosus

At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data

Background: Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR) are pivotal to detecting current coronavirus disease (COVID-19) and duration of detectable virus indicating potential for infectivity. / Methods: We conducted an individual participant data (IPD) systematic review of longitudinal studies of RT-PCR test results in symptomatic SARS-CoV-2. We searched PubMed, LitCOVID, medRxiv, and COVID-19 Living Evidence databases. We assessed risk of bias using a QUADAS-2 adaptation. Outcomes were the percentage of positive test results by time and the duration of detectable virus, by anatomical sampling sites. / Results: Of 5078 studies screened, we included 32 studies with 1023 SARS-CoV-2 infected participants and 1619 test results, from − 6 to 66 days post-symptom onset and hospitalisation. The highest percentage virus detection was from nasopharyngeal sampling between 0 and 4 days post-symptom onset at 89% (95% confidence interval (CI) 83 to 93) dropping to 54% (95% CI 47 to 61) after 10 to 14 days. On average, duration of detectable virus was longer with lower respiratory tract (LRT) sampling than upper respiratory tract (URT). Duration of faecal and respiratory tract virus detection varied greatly within individual participants. In some participants, virus was still detectable at 46 days post-symptom onset. / Conclusions: RT-PCR misses detection of people with SARS-CoV-2 infection; early sampling minimises false negative diagnoses. Beyond 10 days post-symptom onset, lower RT or faecal testing may be preferred sampling sites. The included studies are open to substantial risk of bias, so the positivity rates are probably overestimated