Modulated patterns in a reduced model of a transitional shear flow

We consider a close relative of plane Couette flow called Waleffe flow in which the fluid is confined between two free-slip walls and the flow driven by a sinusoidal force. We use a reduced model of such flows constructed elsewhere to compute stationary exact coherent structures of Waleffe flow in periodic domains with a large spanwise period. The computations reveal the emergence of stationary states exhibiting strong amplitude and wavelength modulation in the spanwise direction. These modulated states lie on branches exhibiting complex dependence on the Reynolds number but no homoclinic snaking

TGFβ inhibition stimulates collagen maturation to enhance bone repair and fracture resistance in a murine myeloma model

Multiple myeloma is a plasma cell malignancy that causes debilitating bone disease and fractures, in which TGFβ plays a central role. Current treatments do not repair existing damage and fractures remain a common occurrence. We developed a novel low tumour phase murine model mimicking the plateau phase in patients, as we hypothesized this would be an ideal time to treat with a bone anabolic. Using in vivo microCT we show substantial and rapid bone lesion repair (and prevention) driven by SD‐208 (TGFβ receptor I kinase inhibitor) and chemotherapy (bortezomib and lenalidomide) in mice with human U266‐GFP‐luc myeloma. We discovered that lesion repair occurred via an intramembranous fracture repair‐like mechanism and that SD‐208 enhanced collagen matrix maturation to significantly improve fracture resistance. Lesion healing was associated with VEGFA expression in woven bone, reduced osteocyte‐derived PTHrP, increased osteoblasts, decreased osteoclasts and lower serum TRACP‐5b. SD‐208 also completely prevented bone lesion development mice with aggressive JJN3 tumors, and was more effective than an anti‐TGFβ neutralizing antibody (1D11). We also discovered that SD‐208 promoted osteoblastic differentiation (and overcame the TGFβ‐induced block in osteoblastogenesis) in myeloma patient bone marrow stromal cells in vitro, comparable to normal donors. The improved bone quality and fracture‐resistance with SD‐208 provides incentive for clinical translation to improve myeloma patient quality of life by reducing fracture risk and fatality

Multi-wavelength observations of afterglow of GRB 080319B and the modeling constraints

We present observations of the afterglow of GRB 080319B at optical, mm and radio frequencies from a few hours to 67 days after the burst. Present observations along with other published multi-wavelength data have been used to study the light-curves and spectral energy distributions of the burst afterglow. The nature of this brightest cosmic explosion has been explored based on the observed properties and it's comparison with the afterglow models. Our results show that the observed features of the afterglow fits equally good with the Inter Stellar Matter and the Stellar Wind density profiles of the circum-burst medium. In case of both density profiles, location of the maximum synchrotron frequency $\nu_m$ is below optical and the value of cooling break frequency $\nu_c$ is below $X-$rays, $\sim 10^{4}$s after the burst. Also, the derived value of the Lorentz factor at the time of naked eye brightness is $\sim 300$ with the corresponding blast wave size of $\sim 10^{18}$ cm. The numerical fit to the multi-wavelength afterglow data constraints the values of physical parameters and the emission mechanism of the burst.Comment: 8 Pages, 3 Figures, Accepted for publication to Astronomy and Astrophysics on 02/04/200

The rise of fully turbulent flow

Over a century of research into the origin of turbulence in wallbounded shear flows has resulted in a puzzling picture in which turbulence appears in a variety of different states competing with laminar background flow. At slightly higher speeds the situation changes distinctly and the entire flow is turbulent. Neither the origin of the different states encountered during transition, nor their front dynamics, let alone the transformation to full turbulence could be explained to date. Combining experiments, theory and computer simulations here we uncover the bifurcation scenario organising the route to fully turbulent pipe flow and explain the front dynamics of the different states encountered in the process. Key to resolving this problem is the interpretation of the flow as a bistable system with nonlinear propagation (advection) of turbulent fronts. These findings bridge the gap between our understanding of the onset of turbulence and fully turbulent flows.Comment: 31 pages, 9 figure

On the evolution of environmental and mass properties of strong lens galaxies in COSMOS

Among the 100 strong lens candidates found in the COSMOS field, 20 with redshifts in the range [0.34,1.13], feature multiple images of background sources. Using the multi-wavelength coverage of the field and its spectroscopic follow-up, we characterize the evolution with redshift of the environment and of the dark-matter (DM) fraction of the lens galaxies. We present new redshift of the strong lens candidates. The lens environment is characterized by the projected 10 closest galaxies around each lens and by the number of galaxies with a projected distance less than 1Mpc at the lens galaxy redshift. In both cases, we perform similar measurements on a control sample of twin non-lens early type galaxies (ETGs). In addition, we identify group members and field galaxies in the X-ray and optical catalogs of galaxy groups. From those catalogs, we measure the external shear contribution at the lens galaxy positions. The systems are then modeled using a SIE plus the external shear due to the groups. We observe that the average stellar mass of lens galaxies increases with z and that the environment of lens galaxies is compatible with that of the twins. During the lens modeling, we notice that, when let free, the external shear points in a direction which is the mean direction of the external shear due to groups and of the closest galaxy to the lens. We notice that the DM fraction of the lens galaxies within the Einstein radius decreases as the redshift increases. Given these, we conclude that, while the environment of lens galaxies is compatible with that of non-lens ETGS, their mass properties evolves significantly with redshift: it is still not clear whether this advocates in favor of a stronger lensing bias toward massive objects at high redshift or is simply representative of the high proportion of massive and high stellar density galaxies at high redshift.Comment: Accepted for publication in A&A. Significant modifications in the paper but similar conclusion

Order-of-magnitude speedup for steady states and traveling waves via Stokes preconditioning in Channelflow and Openpipeflow

Steady states and traveling waves play a fundamental role in understanding hydrodynamic problems. Even when unstable, these states provide the bifurcation-theoretic explanation for the origin of the observed states. In turbulent wall-bounded shear flows, these states have been hypothesized to be saddle points organizing the trajectories within a chaotic attractor. These states must be computed with Newton's method or one of its generalizations, since time-integration cannot converge to unstable equilibria. The bottleneck is the solution of linear systems involving the Jacobian of the Navier-Stokes or Boussinesq equations. Originally such computations were carried out by constructing and directly inverting the Jacobian, but this is unfeasible for the matrices arising from three-dimensional hydrodynamic configurations in large domains. A popular method is to seek states that are invariant under numerical time integration. Surprisingly, equilibria may also be found by seeking flows that are invariant under a single very large Backwards-Euler Forwards-Euler timestep. We show that this method, called Stokes preconditioning, is 10 to 50 times faster at computing steady states in plane Couette flow and traveling waves in pipe flow. Moreover, it can be carried out using Channelflow (by Gibson) and Openpipeflow (by Willis) without any changes to these popular spectral codes. We explain the convergence rate as a function of the integration period and Reynolds number by computing the full spectra of the operators corresponding to the Jacobians of both methods.Comment: in Computational Modelling of Bifurcations and Instabilities in Fluid Dynamics, ed. Alexander Gelfgat (Springer, 2018

Feasibility and safety of setting up a donor breastmilk bank in a neonatal prem unit in a resource limited setting: An observational, longitudinal cohort study

<p>Abstract</p> <p>Background</p> <p>The beneficial effects of human milk on decreasing rates of paediatric infections such as necrotizing enterocolitis (NEC) and sepsis have been clearly demonstrated. Donor breastmilk has been encouraged as the milk of choice when a mother's own breastmilk is not available. The objectives of this study were to assess feasibility of providing donor breastmilk to infants in a resource limited Neonatal Prem Unit (NPU). In addition we sought to determine whether donor breastmilk could be safely pasteurized and administered to infants without any adverse events.</p> <p>Methods</p> <p>Low birth weight infants < 1800 g and under 32 weeks gestational age were followed up in the NPU over a 3 week period; feeding data and morbidity data was collected in order to determine if there were any adverse events associated with donor breastmilk. Samples of pasteurized breastmilk were cultured to check for any bacterial contamination.</p> <p>Results</p> <p>191 infants met the inclusion criteria of whom 96 received their mother's own breastmilk. Of the 95 infants who were potentially eligible to receive donor milk, only 40 did in fact receive donor milk. There was no evidence of bacterial contamination in the samples analyzed, and no evidence of adverse events from feeding with donor breastmilk.</p> <p>Conclusion</p> <p>It is feasible to supply donor breastmilk to infants in an NPU in a resource limited setting, however staff needs to be sensitized to the importance of donor breastmilk to improve uptake rates. Secondly we showed that it is possible to supply donor breastmilk according to established guidelines with no adverse events therefore making it possible to prevent NEC and other side effects often associated with formula feeding of premature infants.</p

Mental health burden for NHS healthcare staff during the COVID-19 pandemic: first results of a longitudinal survey

Background The current investigation aimed to assess the mental health burden on healthcare workers during the early stages of the COVID-19 pandemic. Methods A link to an online survey was sent to an estimate of 18,100 employees of Sheffield Teaching Hospitals NHS Foundation Trust (STH) who had access to email. The survey was completed between 2nd and June 12, 2020.1390 healthcare workers (medical, nursing, administrative and other professions) participated in the first survey. Data from a general population sample (n = 2025) was used for comparison. Severity of somatic symptoms was measured by the PHQ-15. Severity and probable diagnosis of depression, anxiety, and PTSD were measured by the PHQ-9, GAD-7, and ITQ. Linear and logistic regressions were performed to determine if population group predicted the severity of mental health outcomes, and probable diagnosis of depression, anxiety, and PTSD. Additionally, ANCOVAs were performed to compare mental health outcomes between occupational roles in HCWs. Analysis was performed using SPSS. Findings Healthcare workers are more likely to experience greater severity of somatic symptoms, as well as severity and probable diagnosis of depression and anxiety, compared to the general population, but not increased traumatic stress symptoms. Scientific and technical, nursing and admin staff were more likely to experience worse mental health outcomes, compared to medical staff. Interpretation The COVID-19 pandemic has led to increased mental health burden in some, but not all healthcare workers during the first acute phase of the pandemic. The findings from the current investigation provide valuable insights into which healthcare workers are particularly vulnerable to developing adverse mental health outcomes during and after a pandemic

Tasquinimod suppresses tumor cell growth and bone resorption by targeting immunosuppressive myeloid cells and inhibiting c-MYC expression in multiple myeloma

Background: Immunotherapy emerged as a promising treatment option for multiple myeloma (MM) patients. However, therapeutic efficacy can be hampered by the presence of an immunosuppressive bone marrow microenvironment including myeloid cells. S100A9 was previously identified as a key regulator of myeloid cell accumulation and suppressive activity. Tasquinimod, a small molecule inhibitor of S100A9, is currently in a phase Ib/IIa clinical trial in MM patients (NCT04405167). We aimed to gain more insights into its mechanisms of action both on the myeloma cells and the immune microenvironment. Methods: We analyzed the effects of tasquinimod on MM cell viability, cell proliferation and downstream signaling pathways in vitro using RNA sequencing, real-time PCR, western blot analysis and multiparameter flow cytometry. Myeloid cells and T cells were cocultured at different ratios to assess tasquinimod-mediated immunomodulatory effects. The in vivo impact on immune cells (myeloid cell subsets, macrophages, dendritic cells), tumor load, survival and bone disease were elucidated using immunocompetent 5TMM models. Results: Tasquinimod treatment significantly decreased myeloma cell proliferation and colony formation in vitro, associated with an inhibition of c-MYC and increased p27 expression. Tasquinimod-mediated targeting of the myeloid cell population resulted in increased T cell proliferation and functionality in vitro. Notably, short-term tasquinimod therapy of 5TMM mice significantly increased the total CD11b+ cells and shifted this population toward a more immunostimulatory state, which resulted in less myeloid-mediated immunosuppression and increased T cell activation ex vivo. Tasquinimod significantly reduced the tumor load and increased the trabecular bone volume, which resulted in prolonged overall survival of MM-bearing mice in vivo. Conclusion: Our study provides novel insights in the dual therapeutic effects of the immunomodulator tasquinimod and fosters its evaluation in combination therapy trials for MM patients