"mismatch" between positive DWI and negative FLAIR allows the identification of patients that are highly likely to be within the 3-hour time window. Within the first 6 hours of stroke, the sensitivity of FLAIR sequences for acute ischemic lesions increases with time from symptom onset elapsing, approximating 100% after 3 to 6 hours.

ObjectiveSystemic sclerosis (SSc) is a rare and clinically heterogeneous autoimmune disorder characterised by fibrosis and microvascular obliteration of the skin and internal organs. Organ involvement mostly manifests after a variable period of the onset of Raynaud's phenomenon (RP). We aimed to map the incidence and predictors of pulmonary, cardiac, gastrointestinal (GI) and renal involvement in the early course of SSc.MethodsIn the EUSTAR cohort, patients with early SSc were identified as those who had a visit within the first year after RP onset. Incident SSc organ manifestations and their risk factors were assessed using Kaplan-Meier methods and Cox regression analysis.ResultsOf the 695 SSc patients who had a baseline visit within 1 year after RP onset, the incident non-RP manifestations (in order of frequency) were: skin sclerosis (75%) GI symptoms (71%), impaired diffusing capacity for monoxide<80% predicted (65%), DU (34%), cardiac involvement (32%), FVC<80% predicted (31%), increased PAPsys>40mmHg (14%), and renal crisis (3%). In the heart, incidence rates were highest for diastolic dysfunction, followed by conduction blocks and pericardial effusion. While the main baseline risk factor for a short timespan to develop FVC impairment was diffuse skin involvement, for PAPsys>40mmHg it was higher patient age. The main risk factors for incident cardiac manifestations were anti-topoisomerase autoantibody positivity and older age. Male sex, anti-RNA-polymerase-III positivity, and older age were risk factors associated with incident renal crisis.ConclusionIn SSc patients presenting early after RP onset, approximately half of all incident organ manifestations occur within 2 years and have a simultaneous rather than a sequential onset. These findings have implications for the design of new diagnostic and therapeutic strategies aimed to ‘widen' the still very narrow ‘window of opportunity'. They may also enable physicians to counsel and manage patients presenting early in the course of SSc more accurately.

Background: Osteoporotic vertebral fractures (OVFs) have become increasingly common, and previous nonrandomized and randomized controlled trials (RCTs) have compared the effects of cement augmentation versus nonoperative management on the clinical outcome. This meta-analysis focuses on RCTs and the calculated differences between cement augmentation techniques and nonsurgical management in outcome (e.g., pain reduction, adjacent-level fractures, and quality of life [QOL]). Methods: A systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, and the following scientific search engines were used: MEDLINE, Embase, Cochrane, Web of Science, and Scopus. The inclusion criteria included RCTs that addressed different treatment strategies for OVF. The primary outcome was pain, which was determined by a visual analog scale (VAS) score; the secondary outcomes were the risk of adjacent-level fractures and QOL (as determined by the EuroQol-5 Dimension [EQ-5D] questionnaire, the Oswestry Disability Index [ODI], the Quality of Life Questionnaire of the European Foundation for Osteoporosis [QUALEFFO], and the Roland-Morris Disability Questionnaire [RDQ]). Patients were assigned to 3 groups according to their treatment: vertebroplasty (VP), kyphoplasty (KP), and nonoperative management (NOM). The short-term (weeks), midterm (months), and long-term (>1 year) effects were compared. A random effects model was used to summarize the treatment effect, including I 2 for assessing heterogeneity and the revised Cochrane risk-of-bias 2 (RoB 2) tool for assessment of ROB. Funnel plots were used to assess risk of publication bias. The log of the odds ratio (OR) between treatments is reported. Results: After screening of 1,861 references, 53 underwent full-text analysis and 16 trials (30.2%) were included. Eleven trials (68.8%) compared VP and NOM, 1 (6.3%) compared KP and NOM, and 4 (25.0%) compared KP and VP. Improvement of pain was better by 1.31 points (95% confidence interval [CI], 0.41 to 2.21; p < 0.001) after VP when compared with NOM in short-term follow-up. Pain effects were similar after VP and KP (midterm difference of 0.0 points; 95% CI, −0.25 to 0.25). The risk of adjacent-level fractures was not increased after any treatment (log OR, −0.16; 95% CI, −0.83 to 0.5; NOM vs. VP or KP). QOL did not differ significantly between the VP or KP and NOM groups except in the short term when measured by the RDQ. Conclusions: This meta-analysis provides evidence in favor of the surgical treatment of OVFs. Surgery was associated with greater improvement of pain and was unrelated to the development of adjacent-level fractures or QOL. Although improvements in sagittal balance after surgery were poorly documented, surgical treatment may be warranted if pain is a relevant problem. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

The process of cell-sorting is essential for development and maintenance of tissues. Mathematical modeling can provide the means to analyze the consequences of different hypotheses about the underlying mechanisms. With the Differential Adhesion Hypothesis, Steinberg proposed that cell-sorting is determined by quantitative differences in cell-type-specific intercellular adhesion strengths. An implementation of the Differential Adhesion Hypothesis is the Differential Migration Model by Voss-Böhme and Deutsch. There, an effective adhesion parameter was derived analytically for systems with two cell types, which predicts the asymptotic sorting pattern. However, the existence and form of such a parameter for more than two cell types is unclear. Here, we generalize analytically the concept of an effective adhesion parameter to three and more cell types and demonstrate its existence numerically for three cell types based on in silico time-series data that is produced by a cellular-automaton implementation of the Differential Migration Model. Additionally, we classify the segregation behavior using statistical learning methods and show that the estimated effective adhesion parameter for three cell types matches our analytical prediction. Finally, we demonstrate that the effective adhesion parameter can resolve a recent dispute about the impact of interfacial adhesion, cortical tension and heterotypic repulsion on cell segregation.