Wiley最新文献

Early oral language interventions boost children's language skills, yet we know strikingly little about whether these gains endure. The handful of long-term follow-up studies available suggest that even high-quality language interventions show substantial fade-out. This gap in our evidence base has real consequences for families and for policy, especially as demand for language support continues to rise. We suggest that long-term impact might depend on three levels: characteristics of the intervention (e.g. breadth, instructional approach, and fidelity), features of the learning environment (e.g. classroom ethos, continuity of support, and language resources available) and child-specific factors (e.g. children's cognitive profiles). We call on funders and researchers to prioritise the routine capture of long-term outcomes and to invest in identifying the mechanisms and tools that could drive sustained improvement (e.g. regular booster sessions). We feel this is a critical priority for future research, as it would help us design support that genuinely shifts developmental trajectories.

Secondary electrospray ionization (SESI) and extractive electrospray ionization (EESI), as derivative technologies of electrospray ionization (ESI), have empowered the real-time analysis of trace compounds residing in gases and aerosols. Over the past three decades, SESI and EESI have demonstrated remarkable potential in a wide spectrum of applications, spanning disease diagnosis, drug detection, food safety, and environmental surveillance. Concurrently, the strides made in deciphering the ionization mechanisms of SESI and EESI have spurred the creation of diverse ion source configurations that are characterized by enhanced sensitivity and diminished background noise. This comprehensive review encapsulates the ionization mechanisms inherent in SESI and EESI processes, with particular emphasis on the impact of analyte characteristics (such as proton affinity, dipole moment, polarizability, and solubility) and ion source operational parameters (encompassing temperature, humidity, voltage, flow rate and electrospray composition) on ionization efficiency. Additionally, it delves into the progression of SESI and EESI sources, highlights recent breakthroughs, and probes into future trajectories, furnishing novel perspectives for the development of both technologies and the associated instruments.

There are no clinically meaningful differences between bio-originators (BO) and their biosimilars (BS) in safety and efficacy. However, differences in pharmaceutical properties, such as volume and excipient, can occur. This study aimed to compare outcomes between patients transitioning from the modernized adalimumab BO (0.4 mL/no citrate) to BS1 (0.8 mL/citrate) and from BS1 to BS2 (0.4 mL/no citrate) and outcomes for new starters. In this retrospective exploratory cohort study of RA, PsA, and axial SpA patients receiving adalimumab, the (adjusted) 12-month drug survival rates were compared between the transition from the modernized BO to BS1 (Cohort 1, 2021) and from BS1 to BS2 (Cohort 2, 2023) in existing users, and for adalimumab-naïve new starters of the originator and BS1 and BS2 (Cohorts 3 to 5). Subanalyses included drug survival separately for inefficacy and intolerability. In existing users, 983 patients transitioned to BS1, 1082 patients to BS2, with 659 patients in both cohorts. Drug survival rates at 12 months were 73% (95% CI: 70-76) and 90% (95% CI: 88-92), respectively (P < 0.001), adjusted hazard rate ratio (HRR) 0.32 (95% CI: 0.26-0.40) in favor of BS2. The HRR for discontinuation due to inefficacy and tolerability were 0.50 (95% CI: 0.37-0.67) and 0.20 (95% CI: 0.14-0.28), respectively, both favoring BS2. In adalimumab-naïve new starters also, better survival for the originator and BS2 were seen compared with BS1. In conclusion, adalimumab BS1 showed a significantly lower drug survival than BS2, primarily due to lower tolerability. These findings suggest that pharmaceutical differences can have an important impact on drug survival.

Whether letermovir benefits high-risk HLA-mismatched allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly with GIAC-based conditioning, is not well studied. In this retrospective real-world analysis, we evaluated the clinical benefits of letermovir in CMV IgG-positive recipients undergoing HLA-mismatched allo-HSCT (year 2011-2022) using overlap propensity score (OPS) weighting, with a prespecified subgroup included haploidentical HSCT (haplo-HSCT) with modified GIAC (mGIAC). Among 411 transplants, 105 received letermovir, including 39 of 132 patients following the mGIAC protocol. Letermovir significantly reduced day + 180 CMV DNAemia (43.4% vs 83.2%; P < 0.001) and CMV DNAemia/disease (44.7% vs 83.4%; HR 0.33; P < 0.001), with a nonsignificant decrease in CMV disease (4.7% vs 14.2%; P = 0.101). Day + 180 and +360 survival did not differ between groups. In mGIAC haplo-HSCT, letermovir likewise lowered day + 180 CMV DNAemia (47.5% vs 82.3%; P = 0.023) and CMV DNAemia/disease (50.9% vs 83.0%; HR 0.40; P = 0.028) without reducing CMV disease. On multivariable analyses, age ≥ 45 years and nonuse of letermovir independently increased CMV DNAemia/disease risk in both the overall and mGIAC haplo-HSCT cohorts. Overall survival and non-relapse mortality (NRM) were unaffected by letermovir, probably reflecting effective preemptive management and the study's overlap-weighted design. Based on our results, letermovir prophylaxis can effectively reduce CMV DNAemia/disease in HLA-mismatched and mGIAC haplo-HSCT, and may serve as a standard of care for these high-risk patients.

Leaf anatomy is a key factor determining plant ecology. Cell size and number are related to leaf size in tracheophytes, but this has been little studied in bryophytes, which never reach large leaf sizes. We studied the main anatomical factors determining leaf size in mosses, and how this is related to their ecology. We measured cell and leaf dimensions in 287 moss species, as well as cell density, cell wall thickness and midrib length. These measurements were contrasted against different traits, highlighting growth form and genome size, and correlations among traits. Moss leaf size was positively correlated with cell size but negatively correlated with cell density. The longest moss leaves were always supported by midribs reaching or surpassing the leaf apex. Genome size was positively correlated with cell and, especially, leaf size. All these relationships were stronger in acrocarpous mosses. Leaf size in mosses is limited by the mechanical support provided by cell turgor and the midrib. Both mechanical support and effect of genome size were more important in acrocarpous mosses. Our findings suggest anatomy as a key linking factor between genome size and plant ecology.

Ionization and fragmentation are at the core of mass spectrometry. But they are not necessarily separated in space, as in-source fragmentation can also occur. Here, we survey the literature published since our 2005 review on the internal energy and fragmentation in electrospray ionization sources. We present new thermometer molecules to diagnose and quantify source heating, provide tables of recommended threshold (E₀) and appearance energies (E_app) for the survival yield method, and attempt to compare the softness of a variety of ambient pressure ionization sources. The droplet size distribution and desolvation dynamics play a major role: lower average internal energies are obtained when the ions remain protected by a solvation shell and spend less time nakedly exposed to activating conditions in the transfer interface. Methods based on small droplet formation without charging can thus be softer than electrospray. New dielectric barrier discharge sources can gas-phase ionize small molecules while conferring barely more internal energy than electrospray ionization. However, the tuning of the entire source interface often has an even greater influence on ion internal energies and fragmentation than on the ionization process itself. We hope that this review will facilitate further research to control and standardize in-source ion activation conditions, and to ensure the transferability of data and research results in mass spectrometry.

Pretreatment with direct oral anticoagulants (DOACs) may increase bleeding risk after intravenous thrombolysis (IVT) for acute ischemic stroke, but the comparative safety of tenecteplase vs. alteplase remains uncertain. We conducted a real-world retrospective cohort study using the TriNetX Global Network (queried October 2025). Patients with acute ischemic stroke who received IVT were identified and matched 1:1 by propensity scores. Cox proportional hazard models estimated hazard ratios (HRs); a time-split Cox model assessed time-varying effects. The primary composite outcome comprised nontraumatic intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), transfusion, gastrointestinal bleeding, and mortality; secondary outcomes were the individual components. Outcomes were assessed from the day of IVT through days 1, 7, 14, and 21. A total of 1636 patients receiving tenecteplase and 25,370 receiving alteplase were identified, yielding 1634 matched patients per group. Tenecteplase was associated with higher risks of composite outcomes (Day 1: 13.6% vs. 7.4%; HR 1.87, P < 0.001; Day 21: HR 1.36, P = 0.002), ICH (Day 1: 9.1% vs 2.8%; HR 3.26, P < 0.001; Day 21: HR 3.23, P < 0.001), SAH (Day 1: 3.2% vs 1.1%; HR 2.84, P < 0.001; Day 21: HR 2.78, P < 0.001). Mortality was greater with tenecteplase at Day 1 (2.6% vs 1.3%; HR 2.01, P = 0.009) and Day 7 (HR 1.38, P = 0.020). Time-split Cox analysis confirmed that excess risk was confined to the first 24 hours. Among patients pretreated with DOACs, tenecteplase was associated with higher early risk of hemorrhagic transformation and mortality than alteplase, underscoring the need for vigilance during the first 24 hours after treatment.