关键词： Subpolar North Atlantic cold blob   Air-sea interaction   Surface heat flux   Surface-subsurface ocean thermal coupling   Storminess  

摘要： A well-known exception to rising sea surface temperatures (SST) across the globe is the subpolar North Atlantic, where SST has been declining at a rate of 0.39 (+/-} 0.23) K century(-1) during the 1900-2017 period. This cold blob has been hypothesized to result from a slowdown of the Atlantic Meridional Overturning Circulation (AMOC). Here, observation-based evidence is used to suggest that local atmospheric forcing can also contribute to the century-long cooling trend. Specifically, a 100-year SST trend simulated by an idealized ocean model forced by historical atmospheric forcing over the cold blob region matches 92% (+/- 77%) of the observed cooling trend. The data-driven simulations suggest that 54% (+/- 77%) of the observed cooling trend is the direct result of increased heat loss from the ocean induced by the overlying atmosphere, while the remaining 38% is due to strengthened local convection. An analysis of surface wind eddy kinetic energy suggests that the atmosphere-induced cooling may be linked to a northward migration of the jet stream, which exposes the subpolar North Atlantic to intensified storminess.

关键词： Anterior cruciate ligament   Fascia lata   Iliotibial band   MacIntosh  

摘要： Purpose Despite encouraging clinical, biomechanical and histological results, ACL reconstruction using the ITB was slowly abandoned. The hypothesis was that the current literature supports the use of ITB as the graft of choice for ACL reconstruction because of its good outcomes. Methods A systematic search of the literature was performed in the PubMed, MEDLINE, Cochrane, and Ovid databases to identify published clinical studies relevant to ACL reconstruction with ITB autograft and studies comparing ITB autograft with bone-patellar tendon-bone (BPTB) and hamstring (HT) autografts (none were found). The results of the eligible studies were analyzed in terms of graft failure, instrumented knee laxity measurements, Lachman test, pivot-shift test, Lysholm score, objective and subjective International Knee Documentation committee (IKDC) scores, Tegner activity score, return to sports rate, return to sports at pre-injury level and complications. Results Nineteen clinical studies including 1,210 patients with ACL reconstruction met the inclusion criteria. Graft failure occurred after ITB autograft in 4.2% of patients. Postoperative mean side-to-side laxity was 1.41 mm with 21% of patients having greater than 3 mm side-to-side difference. Lachman test and pivot-shift test were negative (grade 0) in 57% and 85%, respectively, and were grade 0 or 1 in 95% and 97%, respectively. Functional outcomes were satisfactory in 84% of patients with good to excellent results (Lysholm score > 84). Mean postoperative Lysholm score was 93.3 and 84% of patients had an objective IKDC grade of A or B. Mean postoperative Tegner score was 6.8. The return to sports rate was 89% and 61% of patients returned to their pre-injury level. A comparison of 89 ITB versus 80 BPTB autografts revealed no significant differences in graft failure (n.s.), instrumented mean side-to-side knee laxity difference (n.s.) or Tegner score (n.s.). Conclusion The graft survival rate and clinical and functional outcomes f

关键词： cell therapy   irrigation   mesenchymal stem   stromal cells   non-healing wounds  

摘要： The application of mesenchymal stem/stromal cells (MSC) in regenerative medicine offers hope for the effective treatment of incurable or difficult-to-heal diseases. However, it requires the development of unified protocols for both safe and efficient cell acquisition and clinical usage. The therapeutic effect of fat grafts (containing stem cells) in non-healing wounds has been discussed in previous studies, although the application requires local or general anaesthesia. The treatment of MSC derived from adipose tissue (ASC) could be a less invasive method, and efficient delivery could lead to more favourable outcomes, which should encourage clinicians to use such therapeutic approaches more frequently. Therefore, the aim of this study was to optimise the methods of ASC isolation, culture and administration while maintaining their high survival, proliferation and colonisation potential. The ASC were isolated by an enzymatic method and were characterised according to International Society for Cellular Therapy and International Federation for Adipose Therapeutics and Science guidelines. To assess the opportunity to obtain a sufficient number of cells for transplantation, long-term cell cultures in two oxygen concentrations (5% vs. 21%) were conducted. For these cultures, the population doubling time, the cumulative time for cell population doublings and the rate of cell senescence were estimated. In a developed and pre-defined protocol, ASC can be efficiently cultured at physiological oxygen concentrations (5%), which leads to faster proliferation and slower cell senescence. Subsequently, to select the optimal and minimally invasive methods of ASC transplantation, direct cell application with an irrigator or with skin dressings was analysed. Our results confirmed that both the presented methods of cell application allow for the safe delivery of isolated ASC into wounds without losing their vitality. Cells propagated in the described conditions and applied in non-invasi

关键词： Magnesium-lithium alloys   Accumulative roll bonding   Bimodal grain structure   Texture   Strain hardening   Mechanical properties  

摘要： To improve comprehensive mechanical properties of Mg-Li alloy, alternative alpha/beta Mg-Li composite sheets with a bimodal-grained structure were prepared by accumulative roll bonding (ARB). The microstructure, texture, mechanical properties and strain hardening behavior of the alternative alpha/beta Mg-Li composite sheets were studied. The bimodal grain structure, with ultrafine grains (about 0.79 mu m) in the alpha alloy and coarse grains (about 53.28 mu m) in the beta alloy, can be observed in the composite sheet. The dominant texture of alpha-Mg and beta-Li alloys is {0002} basal texture and {110} texture, respectively. In the alpha alloy, the basal texture decreases gradually with the increase of ARB pass, and the non-basal texture is formed in the sheet processed by 5-pass ARB. The dislocation density of the composite sheet gradually increases and approaches saturation after 3-pass ARB process due to the balance between dislocation accumulation in the ARB process and dislocation annihilation in dynamic recovery. The sheet processed by 3-pass ARB has the preferable strength and plasticity, with yield strength, ultimate tensile strength, elongation of 204 MPa, 216 MPa, 22.73%, respectively. Compared with the as-annealed alloys before ARB, the strain hardening rate of the ARB composite sheets increases gradually at low stress (stage II). Mg-Li sheets produced by ARB process remain a high plasticity because of the longer softening stage (stage III), which is mainly contributed to the synergistic effect of the bimodal grain structure and the activation of non-basal texture.

关键词： cirrhosis   hepatocellular carcinoma   imaging   screening   visualisation  

摘要： LINKED CONTENT This article is linked to Huang et al papers. To view these articles, visit https://***/10.1111/apt.16844 and https://***/10.1111/apt.16887

关键词： Glioblastoma   Recurrence   ATM   ATR   Radioresistant  

摘要： Primary treatment modality for glioblastoma (GBM) post-surgery is radiation therapy. Due to increased DNA damage repair capacity of resistant residual GBM cells, recurrence is inevitable in glioblastoma and unfortunately the recurrent tumours are resistant to the conventional therapy. Here we used our previously described in vitro radiation survival model generated from primary GBM patient samples and cell lines, which recapitulates the clinical scenario of therapy resistance and relapse. Using the parent and recurrent GBM cells from these models, we show that similar to parent GBM, the recurrent GBM cells also elicit a competent DNA damage response (DDR) post irradiation. However, the use of apical DNA damage repair sensory kinase (ATM and/or ATR) is different in the recurrent cells compared to parent cells. Consistently, we demonstrate that there is a differential clonogenic response of parent and recurrent GBM cells to the ATM and ATR kinase inhibitors with recurrent samples switching between these sensory kinases for survival emphasizing on the underlying heterogeneity within and across GBM samples. Taken together, here we report that recurrent tumours utilize an alternate DDR kinase to overcome radiation induced DNA damage. Since there is no effective treatment specifically for recurred GBM patients, these findings provide a rationale for developing newer treatment option to sensitize recurrent GBM samples by detecting in clinics the ability of cells to activate a DNA damage repair kinase different from their parent counterparts.

摘要： LINKED CONTENT This article is linked to Huang et al papers. To view these articles, visit https://***/10.1111/apt.16844 and https://***/10.1111/apt.16908

关键词： modelling and simulation   monoclonal antibodies   pharmacodynamics  

摘要： Aims Addition of isatuximab (Isa) to pomalidomide/dexamethasone (Pd) significantly improved progression-free survival (PFS) in patients with relapsed/refractory multiple myeloma (RRMM). We aimed to characterize the relationship between serum M-protein kinetics and PFS in the phase 3 ICARIA-MM trial (NCT02990338), and to evaluate an alternative dosing regimen of Isa by simulation. Methods Data from the ICARIA-MM trial comparing Isa 10 mg/kg weekly for 4 weeks then every 2 weeks (QW-Q2W) in combination with Pd versus Pd in 256 evaluable RRMM patients were used. A joint model of serum M-protein dynamics and PFS was developed. Trial simulations were then performed to evaluate whether efficacy is maintained after switching to a monthly dosing regimen. Results The model identified instantaneous changes (slope) in serum M-protein as the best on-treatment predictor for PFS and baseline patient characteristics impacting serum M-protein kinetics (albumin and beta 2-microglobulin on baseline levels, non-IgG type on growth rate) and PFS (presence of plasmacytomas). Trial simulations demonstrated that switching to a monthly Isa regimen at 6 months would shorten median PFS by 2.3 weeks and induce 42.3% patients to progress earlier. Conclusions Trial simulations supported selection of the approved Isa 10 mg/kg QW-Q2W regimen and showed that switching to a monthly regimen after 6 months may reduce clinical benefit in the overall population. However, patients with good prognostic characteristics and with a stable, very good partial response may switch to a monthly regimen after 6 months without compromising the risk of disease progression. This hypothesis will be tested in a prospective clinical trial.