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Despite its importance in cardiovascular diseases and engineering applications, turbulence in pulsatile pipe flow remains little comprehended. Important advances have been made in the recent years in understanding the transition to turbulence in such flows, but the question remains of how turbulence behaves once triggered. In this paper, we explore the spatiotemporal intermittency of turbulence in pulsatile pipe flows at fixed Reynolds and Womersley numbers (Re=2400, Wo=8) and different pulsation amplitudes. Direct numerical simulations (DNS) were performed according to two strategies. First, we performed DNS starting from a statistically steady pipe flow. Second, we performed DNS starting from the laminar Sexl–Womersley flow and disturbed with the optimal helical perturbation according to a non-modal stability analysis. Our results show that the optimal perturbation is unable to sustain turbulence after the first pulsation period. Spatiotemporally intermittent turbulence only survives for multiple periods if puffs are triggered. We find that puffs in pulsatile pipe flow do not only take advantage of the self-sustaining lift-up mechanism, but also of the intermittent stability of the mean velocity profile.

Platinum-based chemotherapy remains a mainstay treatment for the management of advanced non-small cell lung cancer. A key cellular factor that contributes to sensitivity to platinums is the 5′-3′ structure-specific endonuclease excision repair cross-complementation group 1 (ERCC1)/ xeroderma pigmentosum group F (XPF). ERCC1/XPF is critical for the repair of platinum-induced DNA damage and has been the subject of intense research efforts to identify small molecule inhibitors of its nuclease activity for the purpose of enhancing patient response to platinum-based chemotherapy. As an alternative to small molecule inhibitors, small interfering RNA (siRNA) has often been described to be more efficient in interrupting protein–protein interactions. The goal of this study was therefore to determine whether biocompatible nanoparticles consisting of an amphiphilic triblock copolymer (polyethylenimine-polycaprolactone-polyethylene glycol (PEI-PCL-PEG)) and carrying siRNA targeted to ERCC1 and XPF made by microfluidic assembly are capable of efficient gene silencing and able to sensitize lung cancer cells to cisplatin. First, we show that our PEI-PCL-PEG micelleplexes carrying ERCC1 and XPF siRNA efficiently knocked down ERCC1/XPF protein expression to the same extent as the standard siRNA transfection reagent, Lipofectamine. Second, we show that our siRNA-carrying nanoparticles enhanced platinum sensitivity in a p53 wildtype model of non-small cell lung cancer in vitro. Our results suggest that nanoparticle-mediated targeting of ERCC1/XPF is feasible and could represent a novel therapeutic strategy for targeting ERCC1/XPF in vivo.

Resumo O artigo pretende trazer elementos relevantes para a apreensão do capitalismo contemporâneo, partindo da hipótese de que ele está sujeito a uma crise estrutural. Para tanto, o enfoque adotado atribui especial importância para a lógica de imposição do capital e seus dispositivos fetichistas que subordinam os diferentes países aos imperativos do processo de valorização capitalista. Tal enfoque é desenvolvido no bojo de um debate com as abordagens sistêmicas de Arrighi, Fiori e Wallerstein. Por articularem conjuntamente as esferas econômica, política e social do capitalismo, sugere-se que, tanto na exposição como também nas críticas cabíveis a tais abordagens, é possível trazer à tona questões importantes para o entendimento das transformações recentes. Abstract The article intends to bring relevant elements to the apprehension of contemporary capitalism, starting from the hypothesis that it is subject to a structural crisis. To this end, our approach attaches particular importance to the logic of imposition of capital and its fetishistic devices that subordinate the different countries to the imperatives of the capitalist valorization process. This approach is developed in the context of a debate on the systemic approaches of Arrighi, Fiori and Wallerstein. By articulating jointly the economic, political and social spheres of capitalism, it is suggested that, both in the exposition and in the criticisms applicable to such approaches, it is possible to raise important questions for the understanding of recent transformations.

George S. Patton is a well-known American Army commander of the Second World War. The personal diary he kept from 1942 to 1945 is a must-read source to understand the history and the performance of the US Army in the war. However, the conflicting versions of this diary and the many after-the-fact additions can lead to significant misinterpretations of Patton's performance. This article examines the editorial evolutions of the diary, details what were the most significant modifications, and shows how they distorted what Patton thought of fellow officers as well as his role in the Normandy campaign and the Battle of the Bulge.

Pulsatile flow in a straight pipe is a model system for unsteady internal flows in industrial engineering and physiology. In some parameter regimes, the laminar flow is susceptible to helical perturbations, whose transient energy growth scales exponentially with the Reynolds number (Re). In this paper, we link the transient growth of these perturbations to the instantaneous linear instability of the laminar flow. We exploit this link to study the effect of the waveform on turbulence transition by performing linear stability and transient growth analyses of flows driven with different waveforms. We find a higher-energy growth in flows driven with longer low-velocity phases as well as with steeper deceleration and acceleration phases. Finally, we perform direct numerical simulations and show that cases with larger transient growth transition faster to turbulence and exhibit larger turbulence intensities. However, these same cases are also more prone to relaminarisation once turbulence has been established. This highlights that, in pulsatile flows, the linear mechanisms responsible for turbulence transition are distinctly different from the nonlinear mechanisms sustaining turbulence.

ObjectiveTo investigate the frequency of bone marrow oedema (BME) and fatty lesions (FL) suggestive of axial spondyloarthritis (axSpA) on MRI of the spine and sacroiliac joints (SIJ) in a general population sample.MethodsAs part of a community-based cohort project (Study of Health in Pomerania), volunteers underwent spinal (sagittal T1/T2) and SIJ (semicoronal short tau inversion recovery) MRI examinations. Two calibrated readers evaluated the images to detect BME in SIJ and vertebral corners (VC) and FL in VC suggestive of axSpA using Assessment of SpondyloArthritis international Society definitions.ResultsMRIs of 793 volunteers (49.4% males, mean age 37.3±6.3 years, 8.4% human leucocyte antigen-B27+) aged <45 years were evaluated. SIJ BME was seen in 136 (17.2%), VC BME in 218 (27.5%) and FL in 645 (81.4%) volunteers. SIJ BME in ≥1, ≥3 and ≥5 SIJ quadrants was seen in 136 (17.2%), 7 (0.9%) and 1 (0.1%) volunteers, respectively. In VC, BME≥1, ≥3 and ≥5 lesions were seen in 218 (27.5%), 38 (4.8%) and 6 (0.8%) volunteers, respectively, while FL≥1, ≥3 and ≥5 were seen in 645 (81.3%), 351 (44.3%) and 185 (23.3%) volunteers, respectively. Logistic regression analysis showed that BME and FL in VC were related to increasing age: OR 1.33, 95% CI 1.02 to 1.72, and OR 1.73, 95% CI 1.32 to 2.27, per decade increase, respectively.ConclusionsIn this large population-based study, a high frequency of inflammatory and fatty MRI lesions suggestive of axSpA was found, especially in the spine. This indicates a limited value of such MRI findings for diagnosis and classification of axSpA. The increasing frequency with age suggests that mechanical factors could play a role.

We present results from large-eddy simulations (LES) of turbulent pipe flow in a computational domain of 42 radii in length. Wide ranges of shear the Reynolds number and Smagorinsky model parameter are covered, 180 ≤ Reτ ≤ 1500 and 0.05 ≤ Cs ≤ 1.2, respectively. The aim is to asses the effect of Cs on the resolved flow field and turbulence statistics as well as to test whether very large scale motions (VLSM) in pipe flow can be isolated from the near-wall cycle by enhancing the dissipative character of the static Smagorinsky model with elevated Cs values. We found that the optimal Cs to achieve best agreement with reference data varies with Reτ and further depends on the wall normal location and the quantity of interest. Furthermore, for increasing Reτ, the optimal Cs for pipe flow LES seems to approach the theoretically optimal value for LES of isotropic turbulence. In agreement with previous studies, we found that for increasing Cs small-scale streaks in simple flow field visualisations are gradually quenched and replaced by much larger smooth streaks. Our analysis of low-order turbulence statistics suggests, that these structures originate from an effective reduction of the Reynolds number and thus represent modified low-Reynolds number near-wall streaks rather than VLSM. We argue that overdamped LES with the static Smagorinsky model cannot be used to unambiguously determine the origin and the dynamics of VLSM in pipe flow. The approach might be salvaged by e.g. using more sophisticated LES models accounting for energy flux towards large scales or explicit anisotropic filter kernels.

ObjectiveIdentify factors associated with presence and extension of spinal and sacroiliac joints (SIJ)–MRI lesions suggestive of axial spondyloarthritis (axSpA) in a population-based cohort (Study of Health in Pomerania) aged <45 years.MethodsSpinal (sagittal T1/T2) and SIJ (semicoronal STIR sequences) MRIs were evaluated by two trained blinded readers. The presence (yes/no) and extension (Berlin MRI Score) of bone marrow oedema (BME) were captured. Degenerative spinal lesions were excluded and discrepancies resolved by consensus. Cross-sectional associations between clinical factors and presence/extension of BME were analysed by logistic/negative binomial regression. Record linkage of claims data was applied to identify participants with axSpA.ResultsMRIs of 793 volunteers were evaluated. The presence of SIJ–BME (odds ratio) was strongly associated delivery during the last year (4.47, 1.49–13.41). For SIJ–BME extension, associations (incidence rate ratios, 95% CI) were found for delivery ((during last year) 4.52, 1.48–13.84), human leucocyte antigen (HLA)-B27+ (2.32, 1.30–4.14), body mass index (25–30 vs <25 kg/m²; 1.86 (1.19–2.89)) and back pain ((last 3 months) 1.55, 1.04–2.31), while for spinal BME, associations were found for age per decade (1.46, 1.13–1.90) and physically demanding work (1.46, 1.06–2.00). Record linkage was available for 694 (87.5%) participants and 9/694 (1.3%) had a record of axSpA (ICD M45.09).ConclusionThese population-based data support the hypothesis of mechanic strain contributing to BME in the general population aged <45 years and the role of HLA-B27+ as a severity rather than a susceptibility factor for SIJ–BME.

Background Coracoclavicular (CC) ligament reconstruction with semitendinosus tendon (ST) grafts has become more popular and has achieved relatively good results; however optimal reconstruction technique, single-tunnel or two-tunnel, still remains controversial. This paper is to compare the clinical and radiographic data of allogenous ST grafting with single- or two-tunnel reconstruction techniques of the AC joint. Methods The outcomes of 21 consecutive patients who underwent anatomical reduction and ST grafting for AC joint separation were reviewed retrospectively. Patients were divided into two groups: single-tunnel group (11) and two-tunnel group (10). All patients were evaluated clinically and radiographically using a modified UCLA rating scale. Results The majority of separations (18 of 21) were Rockwood type V, with one each in type III, IV and VI categories. The overall mean follow-up time was 16 months, and at the time of the latest follow-up, the overall mean UCLA rating score was 14.1 (range 8–20). The percentage of good-to-excellent outcomes was significantly higher for patients with the two-tunnel technique than for those with the one-tunnel technique (70% vs. 18%, respectively, p = 0.03). Within the single-tunnel group, there was no statistically significant difference in percentage of good-to-excellent outcomes between patients with vs. without tightrope augmentation (17% vs 20%, p > 0.99). Similarly, within the two-tunnel group, there was no significant difference in the percentage of good-to-excellent outcomes between the graft only and augment groups (67% vs. 75%, p > 0.99). Conclusion Anatomical reduction of the AC joint and reconstruction CC ligaments are crucial for optimal joint stability and function. Two-tunnel CC reconstruction with an allogenous ST graft provides superior significantly better radiographic and clinical results compared to the single-tunnel reconstruction technique.