Dynamical models for sand ripples beneath surface waves

We introduce order parameter models for describing the dynamics of sand ripple patterns under oscillatory flow. A crucial ingredient of these models is the mass transport between adjacent ripples, which we obtain from detailed numerical simulations for a range of ripple sizes. Using this mass transport function, our models predict the existence of a stable band of wavenumbers limited by secondary instabilities. Small ripples coarsen in our models and this process leads to a sharply selected final wavenumber, in agreement with experimental observations.Comment: 9 pages. Shortened version of previous submissio

A particle model of rolling grain ripples under waves

A simple model is presented for the formation of rolling grain ripples on a flat sand bed by the oscillatory flow generated by a surface wave. An equation of motion is derived for the individual ripples, seen as "particles", on the otherwise flat bed. The model account for the initial apperance of the ripples, the subsequent coarsening of the ripples and the final equilibrium state. The model is related to physical parameters of the problem, and an analytical approximation for the equilibrium spacing of the ripples is developed. It is found that the spacing between the ripples scale with the square-root of the non-dimensional shear stress (the Shields parameter) on a flat bed. The results of the model are compared with measurements, and reasonable agreement between the model and the measurements is demonstrated.Comment: 9 pages incl. figures. Revised versio

Safety of fertility preservation techniques before and after anticancer treatments in young women with breast cancer: a systematic review and meta-analysis

Study question: Is it safe to perform controlled ovarian stimulation (COS) for fertility preservation before starting anticancer therapies or ART after treatments in young breast cancer patients? Summary answer: Performing COS before, or ART following anticancer treatment in young women with breast cancer does not seem to be associated with detrimental prognostic effect in terms of breast cancer recurrence, mortality or event-free survival (EFS). What is known already: COS for oocyte/embryo cryopreservation before starting chemotherapy is standard of care for young women with breast cancer wishing to preserve fertility. However, some oncologists remain concerned on the safety of COS, particularly in patients with hormone-sensitive tumors, even when associated with aromatase inhibitors. Moreover, limited evidence exists on the safety of ART in breast cancer survivors for achieving pregnancy after the completion of anticancer treatments. Study design, size, duration: The present systematic review and meta-analysis was carried out by three blinded investigators using the keywords 'breast cancer' and 'fertility preservation'; keywords were combined with Boolean operators. Eligible studies were identified by a systematic literature search of Medline, Web of Science, Embase and Cochrane library with no language or date restriction up to 30 June 2021. Participants/materials, setting, methods: To be included in this meta-analysis, eligible studies had to be case-control or cohort studies comparing survival outcomes of women who underwent COS or ART before or after breast cancer treatments compared to breast cancer patients not exposed to these strategies. Survival outcomes of interest were cancer recurrence rate, relapse rate, overall survival and number of deaths. Adjusted relative risk (RR) and hazard ratio (HR) with 95% CI were extracted. When the number of events for each group were available but the above measures were not reported, HRs were estimated using the Watkins and Bennett method. We excluded case reports or case series with <10 patients and studies without a control group of breast cancer patients who did not pursue COS or ART. Quality of data and risk of bias were assessed using the Newcastle-Ottawa Assessment Scale. Main results and the role of chance: A total of 1835 records were retrieved. After excluding ineligible publications, 15 studies were finally included in the present meta-analysis (n = 4643). Among them, 11 reported the outcomes of breast cancer patients who underwent COS for fertility preservation before starting chemotherapy, and 4 the safety of ART following anticancer treatment completion. Compared to women who did not receive fertility preservation at diagnosis (n = 2386), those who underwent COS (n = 1594) had reduced risk of recurrence (RR 0.58, 95% CI 0.46-0.73) and mortality (RR 0.54, 95% CI 0.38-0.76). No detrimental effect of COS on EFS was observed (HR 0.76, 95% CI 0.55-1.06). A similar trend of better outcomes in terms of EFS was observed in women with hormone-receptor-positive disease who underwent COS (HR 0.36, 95% CI 0.20-0.65). A reduced risk of recurrence was also observed in patients undergoing COS before neoadjuvant chemotherapy (RR 0.22, 95% CI 0.06-0.80). Compared to women not exposed to ART following completion of anticancer treatments (n = 540), those exposed to ART (n = 123) showed a tendency for better outcomes in terms of recurrence ratio (RR 0.34, 95% CI 0.17-0.70) and EFS (HR 0.43, 95% CI 0.17-1.11). Limitations, reasons for caution: This meta-analysis is based on abstracted data and most of the studies included are retrospective cohort studies. Not all studies had matching criteria between the study population and the controls, and these criteria often differed between the studies. Moreover, rate of recurrence is reported as a punctual event and it is not possible to establish when recurrences occurred and whether follow-up, which was shorter than 5 years in some of the included studies, is adequate to capture late recurrences. Wider implications of the findings: Our results demonstrate that performing COS at diagnosis or ART following treatment completion does not seem to be associated with detrimental prognostic effect in young women with breast cancer, including among patients with hormone receptor-positive disease and those receiving neoadjuvant chemotherapy. Study funding/competing interest(s): Partially supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC; grant number MFAG 2020 ID 24698) and the Italian Ministry of Health-5 7 1000 funds 2017 (no grant number). M.L. acted as consultant for Roche, Pfizer, Novartis, Lilly, AstraZeneca, MSD, Exact Sciences, Gilead, Seagen and received speaker honoraria from Roche, Pfizer, Novartis, Lilly, Ipsen, Takeda, Libbs, Knight, Sandoz outside the submitted work. F.S. acted as consultant for Novartis, MSD, Sun Pharma, Philogen and Pierre Fabre and received speaker honoraria from Roche, Novartis, BMS, MSD, Merck, Sun Pharma, Sanofi and Pierre Fabre outside the submitted work. I.D. has acted as a consultant for Roche, has received research grants from Roche and Ferring, has received reagents for academic clinical trial from Roche diagnostics, speaker's fees from Novartis, and support for congresses from Theramex and Ferring outside the submitted work. L.D.M. reported honoraria from Roche, Novartis, Eli Lilly, MSD, Pfizer, Ipsen, Novartis and had an advisory role for Roche, Eli Lilly, Novartis, MSD, Genomic Health, Pierre Fabre, Daiichi Sankyo, Seagen, AstraZeneca, Eisai outside the submitted work. The other authors declare no conflict of interest. The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript and decision to submit the manuscript for publication. Registration number: N/A

326peffectiveness of trastuzumab emtansine tdm1 in patients with her2 positive advanced breast cancer abc progressing after taxane plus pertuzumab plus trastuzumab

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Influence of HER2 expression on prognosis in metastatic triple-negative breast cancer—results from an international, multicenter analysis coordinated by the AGMT Study Group

Background: Triple-negative breast cancer (TNBC) is associated with poor prognosis, and new treatment options are urgently needed. About 34%-39% of primary TNBCs show a low expression of human epidermal growth factor receptor 2 (HER2-low), which is a target for new anti-HER2 drugs. However, little is known about the frequency and the prognostic value of HER2-low in metastatic TNBC. Patients and methods: We retrospectively included patients with TNBC from five European countries for this international, multicenter analysis. Triple-negativity had to be shown in a metastatic site or in the primary breast tumor diagnosed simultaneously or within 3 years before metastatic disease. HER2-low was defined as immunohistochemically (IHC) 1+ or 2+ without ERBB2 gene amplification. Survival probabilities were calculated by the Kaplan-Meier method, and multivariable hazard ratios (HRs) were estimated by Cox regression models. Results: In total, 691 patients, diagnosed between January 2006 and February 2021, were assessable. The incidence of HER2-low was 32.0% [95% confidence interval (CI) 28.5% to 35.5%], with similar proportions in metastases (n = 265; 29.8%) and primary tumors (n = 425; 33.4%; P = 0.324). The median overall survival (OS) in HER2-low and HER2-0 TNBC was 18.6 and 16.1 months, respectively (HR 1.00; 95% CI 0.83-1.19; P = 0.969). Similarly, in multivariable analysis, HER2-low had no significant impact on OS (HR 0.95; 95% CI 0.79-1.13; P = 0.545). No difference in prognosis was observed between HER2 IHC 0/1+ and IHC 2+ tumors (HR 0.89; 95% CI 0.69-1.17; P = 0.414). Conclusions: In this large international dataset of metastatic TNBC, the frequency of HER2-low was 32.0%. Neither in univariable nor in multivariable analysis HER2-low showed any influence on OS.info:eu-repo/semantics/publishedVersio

Understanding coastal morphodynamic patterns from depth-averaged sediment concentration

This review highlights the important role of the depth-averaged sediment concentration (DASC) to understand the formation of a number of coastal morphodynamic features that have an alongshore rhythmic pattern: beach cusps, surf zone transverse and crescentic bars, and shoreface-connected sand ridges. We present a formulation and methodology, based on the knowledge of the DASC (which equals the sediment load divided by the water depth), that has been successfully used to understand the characteristics of these features. These sand bodies, relevant for coastal engineering and other disciplines, are located in different parts of the coastal zone and are characterized by different spatial and temporal scales, but the same technique can be used to understand them. Since the sand bodies occur in the presence of depth-averaged currents, the sediment transport approximately equals a sediment load times the current. Moreover, it is assumed that waves essentially mobilize the sediment, and the current increases this mobilization and advects the sediment. In such conditions, knowing the spatial distribution of the DASC and the depth-averaged currents induced by the forcing (waves, wind, and pressure gradients) over the patterns allows inferring the convergence/divergence of sediment transport. Deposition (erosion) occurs where the current flows from areas of high to low (low to high) values of DASC. The formulation and methodology are especially useful to understand the positive feedback mechanisms between flow and morphology leading to the formation of those morphological features, but the physical mechanisms for their migration, their finite-amplitude behavior and their decay can also be explored

Sea ripple formation: the turbulent boundary layer case

This study presents a predictive theory of ripple formation beneath sea waves. The theory is based on a linear stability analysis of a flat sandy bottom subject to an oscillatory flow. The flow regime in the bottom boundary layer is assumed to be turbulent; hence previous works on the subject, which considered a laminar flow, are extended in a more relevant range of the Reynolds number. The turbulent stresses are described by means of the constant eddy viscosity model proposed by Sleath in 1991 and a two time-scale approach is used to decouple fluid motion from bottom time development. A closed form solution is found for the turbulent oscillatory how over a fixed wavy wall and the time development of the bottom perturbation is determined by means of sediment continuity equation. The conditions for ripple appearance are determined along with their wavelength as they form. A comparison between theoretical findings and experimental data supports the validity of the present approach

Sea ripple formation: the heterogenous sediment case

Ripple formation beneath sea waves is analyzed both by experimental and analytical means when the bottom is made up of a mixture of sands. An oscillatory flow is obtained in a closed duct by the oscillations of two rigidly connected pistons located at the ends of the duct. The amplitude and period of the oscillations can be continuously varied. A fixed tray, located at the bottom of the duct and filled with different types of sediments, allows ripple formation to be observed. The presence of graded sediments is found to have a stabilizing effect and causes longer ripples to appear. Moreover a selective sediment transport is observed and quantified which tends to pile up the coarse grains at ripple crests leaving the fine ones in the troughs. As in the companion paper, the theory is based on a linear stability analysis of a flat sandy bottom subject to an oscillatory flow. Because of the presence of a mixture, a modified version of Exner equation is used and an \u201chiding\u201d factor should be inserted in the sediment transport rate formula. The flow regime in the bottom boundary layer is assumed to be turbulent. The conditions for ripple appearance are determined along with their wavelengths as they form. Good agreement is found between experimental data and theoretical findings