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Perceptions over biologics for psoriasis after 5 years of access in Brazil: a cross-sectional study
No full textBiologic therapies have transformed psoriasis management, and their incorporation into Brazil’s public healthcare system (SUS) in 2019 expanded access nationwide. However, real-world utilization and perceptions remain incompletely understood. To evaluate perceptions, barriers, and prescription patterns regarding biologic therapy among Brazilian dermatologists and patients five years after universal incorporation, while quantifying the prevalence of undertreatment. We conducted two independent cross-sectional online surveys throughout 2024 among dermatologists (n = 225) and patients with psoriasis or psoriatic arthritis (n = 1,001). Data on demographics, clinical characteristics, and perceived barriers were analyzed. Overall, 64.9% of dermatologists prescribed biologics, with higher prescribing rates among younger physicians (p = 0.022), those with fewer years of practice (p = 0.013), higher patient volumes (p < 0.001), and practice in tertiary centers (p = 0.001). Only 25.5% of patients were receiving biologics, strongly associated with psoriatic arthritis (p < 0.001), with no difference between public and private care. Key barriers included perceptions that conventional therapies are sufficient (59.5%), insufficient training (38.0%), and administrative burden (45.5%), while patients mainly reported safety (45.7%) and cost (30.9%) concerns. Undertreatment was prevalent, affecting over 50% of patients with moderate-to-severe disease. While 71.3% of non-users were willing to start biologics, only 28.0% had received a medical recommendation. Persistent educational and structural barriers continue to limit optimal biologic use despite formal availability, highlighting the need for targeted education, streamlined care pathways, and improved physician–patient communication to achieve equitable outcomes
Synthesis, SAR, and biophysical mechanism of action of cyclopropabenzindole-pyridinobenzodiazepine (CBI-PDD) guanine-adenine DNA cross-linking agents
Get PDFThis study investigates the Structure–Activity Relationship (SAR) and biophysical mechanism of action of a series of novel Cyclopropabenzindole-Pyridinobenzodiazepine (CBI-PDD) agents designed to alkylate adenine and guanine bases in the DNA minor groove. A library of 18 analogs was synthesized using a modular approach to vary linker length, rigidity and the CBI and PDD core structures. Structural modifications included alkyl, aromatic, heteroaromatic and sterically constrained linkers, as well as prodrug variants. Several compounds demonstrated potent in vitro cytotoxicity, with lead analogs achieving IC50 values in the low picomolar range across multiple human tumor cell lines. Control compounds with inactivated electrophilic groups in either or both pharmacophores showed markedly reduced activity, confirming the necessity of dual alkylation for optimal cytotoxic potency. Fluorescence-based thermal denaturation (ΔTm up to 34 °C) and gel-based assays were used to assess DNA binding and provide mechanistic insights into the DNA sequence requirements for mono-alkylation and interstrand cross-linking. The study also includes a scalable synthesis of a linker-payload construct suitable for Antibody–Drug Conjugate (ADC) applications based on these agents. Overall, these findings support the use of CBI-PDDs as a promising class of sequence-selective DNA cross-linking agents for targeted cancer therapies.</p
China’s Securities Law Reform: Market Practice, Regulatory Innovation, and Global Integration
No full textThis article examines the development of China’s capital markets and assesses key securities and corporate law reforms introduced in the 2010s and 2020s to build a more transparent, market-oriented system with stronger investor protection. First, it analyses the expansion of China’s multi-layered capital markets, focusing on the establishment of the Shanghai STAR Market (2019) and the Beijing Stock Exchange (2021), which were created to meet the diverse financing needs of companies across different sizes, industries, and development stages, while aligning with the varied risk appetites of investors. Second, it evaluates core legal reforms, particularly the PRC Securities Law 2020 and PRC Company Law 2023. A pivotal change is the shift from an approval-based to a registration-based IPO system, which reduces administrative discretion, strengthens information disclosure, increases penalties for financial misconduct, and improves investor protection through collective and class action mechanisms. The Company Law further introduces dual-class share structures, more flexible board governance, clearer directors’ duties, stronger accountability, and enhanced private enforcement. Third, the article explores China’s internationalisation strategies through Chinese Depositary Receipts (CDRs) and cross-border Stock Connect schemes such as the Shanghai–London Stock Connect, which facilitate global capital flows and enable overseas-listed Chinese firms to access domestic markets. The article argues that China’s securities law reforms strike a balance between market efficiency and investor protection, regulatory modernisation and stability, and domestic development and international integration
Lifestyle intervention is more effective in high 1-hour post-load glucose than in prediabetes for restoring β-cell function, reducing ectopic fat, and preventing type 2 diabetes
Get PDFBackground High 1-h-post-load plasma glucose (1 h-PG) is an early diabetes risk marker. We hypothesized that isolated high 1 h-PG represents an intermediate state between normal glucose regulation (NGR) and impaired glucose regulation (IGR) and is amendable to greater lifestyle intervention (LI) benefit. Methods In the Tübingen Lifestyle Intervention Program, 317 people with either NGR, IGR or isolated high 1 h-PG without IGR underwent LI for 9 months to achieve ≥5 % weight loss. Results Before LI initiation, insulin sensitivity and β-cell function declined progressively from NGR ( n = 106) to high 1 h-PG ( n = 96) and to IGR ( n = 115). Visceral adipose tissue (VAT) volume and liver fat content increased from NGT to high 1 h-PG and to IGR. LI improved insulin sensitivity and ß-cell function in the high 1 h-PG group to levels observed in NGR together with a marked reduction in hepatic fat content. Compared to the IGR group, T2D risk was reduced by 80 % (37–96 %, p = 0.005) in the high 1 h-PG group during a 12-year follow-up period. The odds of remission to complete normoglycemia were doubled in the high 1 h-PG group compared to the IGR group (2.18 [1.13–4.28], p = 0.021). Conclusion High 1 h-PG indicates an intermediate metabolic state with pathophysiological changes more severe than in NGR but milder than in IGR. In people with high 1 h-PG, LI significantly improved insulin sensitivity and β-cell function and reduced ectopic lipid deposition and the risk of developing T2D compared to IGR. These findings highlight the value of 1 h-PG as a clinically useful biomarker, providing a critical window for early intervention to reverse core metabolic defects driving prediabetes and T2D.</p
Impact of electronic correlations on the superconductivity of high-pressure CeH9
Get PDFRare-earth superhydrides have attracted considerable attention because of their high critical superconducting temperature under extreme pressures. They are known to have localized valence electrons, implying strong electronic correlations. However, such many-body effects are rarely included in first-principles studies of rare-earth superhydrides because of the complexity of their high-pressure phases. In this work, we use a combined density functional theory and dynamical mean-field theory approach to study both electrons and phonons in the prototypical rare-earth superhydride CeH9, shedding light on the impact of electronic correlations on its critical temperature for phonon-mediated superconductivity. Our findings indicate that electronic correlations result in a larger electronic density at the Fermi level, a bigger superconducting gap, and softer vibrational modes associated with hydrogen atoms. Together, the inclusion of these correlation signatures increases the Migdal-Eliashberg superconducting critical temperature from 47 K to 96 K, close to the measured 95 K. Our results reconcile experimental observations and theoretical predictions for CeH9 and herald a path towards the quantitative modeling of phonon-mediated superconductivity for interacting electron systems
Prescribing of high-cost targeted therapies in England is diverging by region
No full textObjectives To examine regional variation in the prescribing of targeted therapies for chronic inflammatory disorders in England between 2019 and 2025. Study design Retrospective observational study. Methods This study analysed Secondary Care Medicines Data from all NHS hospitals in England to evaluate time-trends in prescribing rates of targeted therapies by Integrated Care Board (ICB). Results Substantial and increasing regional variation in prescribing rates for targeted therapies was observed between 2019 and 2025. The disparity between the highest and lowest prescribing ICBs increased over time, with rates ranging from 2.0 to 6.5 per 1000 people in 2019 and 3.4 to 14.2 per 1000 people in 2025. Conclusions There is marked and growing regional variation in the prescribing of targeted therapies across England. Further research should explore the reasons for this divergence to ensure equitable access to these highly effective treatments for patients with chronic inflammatory disorders, irrespective of geography.</p
Theories with no superluminal signaling have greater information-processing power than theories with no superluminal causation
Get PDFA central goal in the foundations of physics is to understand the structure of physical theories, such as quantum theory, from physical principles. This is often explored by considering various information-theoretic principles. Here, we initiate a similar approach considering relativistic causality principles. No superluminal causation (NSC) and no superluminal signaling (NSS) are distinct relativistic principles, requiring respectively that causal influence/the ability of agents to signal are within the future lightcone. After formalizing their distinction, we investigate how well theories constrained by NSC and NSS perform in a task that involves generating nonclassical correlations. We find a spacetime configuration in which this task cannot be achieved in any theory (classical, quantum, or postquantum) satisfying NSC. However, we show that theories violating NSC but satisfying NSS can perfectly achieve the task. We give a protocol that would, in a world allowing superluminal causation, enable its operational certification without violating NSS, in general spacetimes. In the case of (1 + 1)-dimensional Minkowski spacetime, the task remains achievable in a configuration where measurement outcomes occur arbitrarily earlier in time than the settings, allowing a form of certifiable retrocausality without violating NSS. We illustrate our results by linking two different types of nonclassical postquantum resources: PR boxes and jamming. Our work offers insights into the role of different relativistic causality principles in fundamental physics and paves the way for characterizing the information-theoretic structure of theories obeying such principles.</p
Can Whole-Family interventions target violence and parenting in families experiencing Domestic Violence and Abuse?:A longitudinal study of the For Baby’s Sake Programme
No full textBackground: This study aimed to assess the potential for a whole-family intervention for domestic violence and abuse (DVA) – the For Baby's Sake programme – to address both parenting and abusive behaviours in families experiencing DVA. This objective is achieved by investigating parents’ perspective. This trauma-informed programme works separately with mothers and fathers and is intended to start in pregnancy and continue for two years.Methods: Three sets of individual interviews were conducted with mothers and fathers both at the start of the programme (during pregnancy); one year after programme enrolment and at programme end. Reflexive Thematic Analysis was employed. 26 mothers and 13 fathers participated with a total of 83 interviewsResults: Parents reported perceived improvements in parenting knowledge and behaviours, notably through psychoeducation on child development and feedback on video recordings of parent-child interactions. Mothers acknowledged experiences of DVA, and found psychoeducation, insights into intergenerational transmission, and safety planning activities beneficial. Some fathers acknowledged perpetration of violent behaviours. Fathers embraced change by addressing their own Adverse Childhood Experiences (ACEs), acquiring emotional regulation skills, and committing to anger management. Both fathers and mothers stressed the importance of a non-judgmental environment and a desire to enhance parenting as motivating factors for acknowledging DVA and committing to change.Conclusions: The findings suggest that whole-family approach interventions – such as the For Baby's Sake programme – holds promise in addressing both parenting and abusive behaviours in families experiencing DVAKey words Domestic violence and abuse, whole-family approach, parenting, intervention, trauma, intergenerational transmissio
Labour-intensive geographies and support for radical right parties
Get PDFDoes variation in local economic environments help explain why some areas exhibit systematically higher support for radical-right parties? To address this question, I focus on two drivers related to the type of industry where individuals work and socially interact. First, in contrast to knowledge-based industries, labour-intensive industries are characterised by clustering of individuals with high job vulnerability and low education. Second, when they coincide spatially, these two socioeconomic characteristics give rise to nativist preferences and exclusionary attitudes, which drive support for radical-right parties. I test these claims with two empirical strategies. In geographical municipal-level data from Spain, I confirm that support for radical-right parties is determined by exposure to labour-intensive activities such as certain sectors of agriculture and tourism. In addition, survey data from 17 European democracies confirm that working in labour-intensive industries boosts the roles of job vulnerability and education in developing and expressing exclusionary political behaviours
Correlated decoherence and thermometry with mobile impurities in a one-dimensional Fermi gas
No full textWe theoretically investigate the correlated decoherence dynamics of two mobile impurities trapped within a gas of ultracold fermionic atoms. We use a mean-field approximation to self-consistently describe the effect of impurity-gas collisions on impurity motion, while decoherence of the impurities' internal state is computed exactly within a functional determinant approach. At equilibrium, we find that the impurities undergo bath-induced localization as the impurity-gas interaction strength is increased. We then study the nonequilibrium dynamics induced by a sudden change of the impurities' internal state, which can be experimentally probed by Ramsey interferometry. Our theoretical approach allows us to investigate the effect of impurity motion on decoherence dynamics, finding strong deviations from the universal behavior associated with Anderson's orthogonality catastrophe when the mass imbalance between impurity and gas atoms is small. Finally, we show that mobile impurities can be used as thermometers of their environment, and that bath-mediated correlations can be beneficial for thermometric performance at low temperatures, even in the presence of nontrivial impurity motion. Our results showcase the interesting open quantum dynamics of mobile impurities dephasing in a common environment, and they can help to provide more precise temperature estimates of ultracold fermionic mixtures