搜索结果：castles

All patients born with anorectal malformations (ARMs) deserve high-quality healthcare, including appropriate neonatal screening, perioperative management, and long-term follow-up. This study examined global pediatric surgical practices for ARM management, identifying areas of consensus and variability in perioperative care and reported outcomes. A multi-center survey distributed by The Hendren Project (a global networked community of pediatric surgeons) invited surgeons to retrospectively review their ten most recent primary ARM reconstructions, excluding reoperations. Data were compared by country/continent and World Bank income. A total of 144 surgeons from 90 hospitals in 50 countries reported outcomes for 900 patients. Sacral radiographs were inconsistently obtained, with 34.2% lacking lateral views and 21.9% missing anterior-posterior views. The complication rate after PSARP was 27.2%, including dehiscence (11.7%), wound infection (7.4%), and stricture (6.9%). Divided stomas were more common than loop colostomies (66.3% versus 28.8%). Postoperative anal dilations were performed by 92.6% of surgeons. Reported complication rates did not differ significantly by region or income category. This global survey demonstrates wide regional and income-based variability in ARM perioperative care, spanning screening, operative strategy, timing, and postoperative management. Inconsistent sacral and spinal screening, especially in low-resource settings, highlights needs for standardized pathways and context-aware quality improvement efforts worldwide.

School principals are prone to mental health problems due to work demands. During the COVID-19 pandemic, school principals were additionally tasked with managing challenging responsibilities, i.e. implementing hygiene regulations, communicating frequent policy updates, and transitioning to online teaching. This international study aimed to assess school principals' COVID-19 health literacy (HL) levels as a resource during the pandemic and to examine associations with well-being and psychosomatic complaints. The COVID-19 Health Literacy School Principal Survey was jointly conducted in 11 countries during 2021 and 2022. N = 8644 school or vice principals completed the online survey. Well-being was assessed using the WHO-5 Well-Being Index, psychosomatic complaints with a subscale of the Burnout Assessment Tool and self-reported COVID-19 HL through the HLS-COVID-Q22. HL levels were computed using Rasch analysis. Multiple linear regression analysis was conducted to investigate the association of school principals' COVID-19 HL with well-being and psychosomatic complaints while controlling for sociodemographic and school-level factors. Overall, 0.1% of school principals had insufficient COVID-19 HL, 3.3% problematic, 65.7% sufficient, and 30.9% excellent. COVID-19 HL significantly predicted well-being and psychosomatic complaints even after controlling for sex, age, position, school type, teaching load, and working hours. Despite the small explained variance, the findings emphasize a need to invest in school principals' HL as a resource during times of crisis and beyond. Health promotion interventions should be developed to enhance HL and hence health, especially of female and younger school principals, who reported lower well-being and more frequent psychosomatic complaints.

We aimed to capture UK medical students' preferences regarding skin color terminology in medical education and in relation to how they describe their own skin tone, to better understand how we can develop more inclusive, diverse medical language for both educational and clinical settings.

Atopic dermatitis (AD) is a chronic inflammatory dermatosis requiring multifaceted treatment. Poor adherence to topical therapy hinders symptom management, highlighting the need to identify barriers influencing adherence among adults with AD. Identify factors influencing adherence to topical therapy among adults with AD and outline strategies to improve adherence. We conducted a systematic review following PRISMA guidelines and with PROSPERO registration (CRD42023488557). PubMed and EMBASE were searched in December 2023 for articles with relevant terms published from 2000 to 2023, and the search was updated in April 2025. Eligible studies reported original data on adherence to topical therapy in adults with AD and findings were categorized using the World Health Organization's adherence dimensions. A total of 50 studies involving 17,124 adults across 17 countries were analyzed. Patient-related barriers included patient forgetfulness, knowledge about AD and treatment options, as well as topical corticosteroid phobia. Therapy-related factors included regimen complexity, vehicle preparation, and symptom perception. Cost and advice from family, friends, and the internet were frequent socioeconomic concerns. Healthcare system factors included clinician communication, time constraints, and inconsistent guidance. Condition-related factors including disease severity and chronicity also shaped adherence. Topical therapy adherence among adults with AD is influenced by several modifiable barriers including patient forgetfulness, education, treatment duration, and vehicle preparation. Future work should standardize adherence measurement tools and definitions. Proposed strategies may integrate patient-centered education, simplified regimens, reminder tools, cost reduction, and strong therapeutic relationships to support sustained adherence and improve long-term outcomes.

Real-world performance of the Tandem Mobi insulin pump with Control-IQ+ technology has been evaluated in small early access studies, but data from larger populations with long-term use has yet to be presented, especially with the use of newer sensors and newly indicated populations. The Tandem Mobi insulin pump with Control-IQ+ technology paired with the Dexcom G7 continuous glucose monitor (CGM) was evaluated in 29,265 users of the combined system, for a median of 5.1&#x2009;months of use per user. Users had to have at least 30&#x2009;days of use of the combined system in the Tandem Source web application to be included in the analysis. Customer service check-in surveys that were performed as part of routine postmarket surveillance activities were also analyzed. CGM availability exceeded 95% for all age groups, with an overall median 97.8%. Median time in closed loop was 94.1%, demonstrating strong reliability of the CGM connection in real-world settings. Median time in range 3.9-10.0&#x2009;mmol/L was 70.8% for adults, 62.3% for children age 6-17&#x2009;years old and 59.5% for children 2-5&#x2009;years old. Time <3.9&#x2009;mmol/L was low at 1.4%. Postmarket surveillance surveys completed by 1941 of these users reported high satisfaction with pump usability, CGM connectivity and the automated insulin delivery algorithm. These findings demonstrate safe and effective use of the Tandem Mobi insulin pump with Control-IQ+ technology paired with the Dexcom G7 sensor in the at-home, unsupervised setting.

Using the James Lind Alliance (JLA) methodology, we established a Priority Setting Partnership (PSP) to identify the most important unanswered research questions in childhood food allergy. This approach places those directly affected, those with food allergy, their parents/carers, and healthcare professionals at the centre of the process. A multidisciplinary steering group (n&#x2009;=&#x2009;19 people) oversaw the PSP. Research uncertainties were collected through a UK-wide online survey distributed to children, young people and adults with food allergy, their parents/carers, and healthcare professionals working in food allergy. A focus group was conducted with seven children aged 8-11&#x2009;years with food allergy to ensure inclusion of their perspectives. Submitted questions were reviewed, combined into summary questions, and checked against existing evidence to confirm that they represented genuine uncertainties. An interim prioritisation survey was used to rank questions, with equal weighting given to each stakeholder group. A final facilitated workshop used a nominal group technique to agree on the top 10 research priorities. In total, 916 respondents submitted 2563 questions. After removing out-of-scope and already answered questions, an interim prioritisation survey was completed by 1087 participants. The final workshop involved 29 participants, including young people (n&#x2009;=&#x2009;3), young adults (n&#x2009;=&#x2009;4), parents (n&#x2009;=&#x2009;7) and multidisciplinary healthcare professionals (n&#x2009;=&#x2009;15), who agreed on the top 10 questions. These cover prevention, early diagnosis, treatment, causes, eating out, safety in care settings, impact, emergency treatment, and awareness of food allergy. There was strong consensus from the final workshop across all attendees that prevention should be the number one priority. Using a rigorous, transparent, and person-centred approach, we have identified the most important research priorities in childhood food allergy. They highlight the depth and breadth of research required to improve the prevention, diagnosis, treatment, and broader impacts of food allergy on children, families, and carers who live with this condition.

暂无摘要（点击查看详情）

Grapevine downy mildew (GDM), caused by Plasmopara viticola, is managed largely through repeated fungicide applications, yet evaluating spray-program performance is difficult because field infections are spatially heterogeneous. However, host physiological changes can precede visible symptom development. We tested whether standardized, high-throughput VNIR hyperspectral imaging of field-grown grapevine leaf discs can capture early optical changes associated with infection and discriminate program-linked mitigation. Leaves were collected from a 2025 vineyard trial in Geneva, NY (cv. La Crescent) managed under three spray programs (conventional fungicides, biofungicides, and untreated control). Leaf discs (&#x2248;87 per program) were excised, inoculated with P. viticola, and imaged at 0.5, 1.5, and 3.5 days post inoculation (dpi) using a custom built, automated, hyperspectral imaging microscopy platform (400-980 nm). No visible sporulation occurred at 0.5 or 1.5 dpi; sporulation was first observed at 3.5 dpi and occurred only in the untreated control, whereas no discs from either treated program sporulated. Multivariate spectral analyses showed significant separation by spray program and dpi, and disease-related spectral indices exhibited program-dependent trajectories, with treated discs showing attenuated optical change relative to the control. A random-forest classifier trained on pre-sporulation spectra (0.5 and 1.5 dpi; N = 169) predicted subsequent sporulation with 0.78 accuracy and 0.77 ROC-AUC (95% CI 0.68-0.85), highlighting informative bands across visible, red-edge, and near-infrared regions. Together, these results support outcome-linked, replicate-rich hyperspectral phenotyping of vineyard spray programs using field-derived material under standardized acquisition conditions.

The gut microbiome is increasingly recognized as a modulator of cancer immunotherapy efficacy, including responses to immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell (CAR-T) therapy. Recent clinical trials of microbiome-targeted interventions such as fecal microbiome transplantation (FMT) and live biotherapeutic products (LBPs) suggest the potential to enhance antitumor immunity and improve clinical outcomes. Yet responses remain heterogeneous and are not fully explained by engraftment of donor taxa alone. We integrate evidence from interventional trials, observational cohort studies, and principles from gut microbial ecology to develop a model hypothesis on how microbiome-targeted therapies may shape response to immunotherapy, with potential to inform future trial design, analyses, and interpretation. Drawing on the available evidence, we propose that therapeutic perturbation of the gut microbiome may augment immunotherapy efficacy through two parallel axes: (1) elimination of immunosuppressive pathobionts that restrain CD8+ T-cell activation and promote myeloid-mediated immunosuppression, and (2) functional restoration of the gut ecosystem through engraftment of taxa that provide metabolites, structural cues, and immunoregulatory signals required for effective antitumor immunity. The success of both axes appears to depend on ecological processes governed by predator-prey dynamics, including colonization resistance, resilience of the resident microbiota, and the ability of administered organisms to displace entrenched dysbiotic communities. This ecological lens may help to explain discrepancies across trial designs, donor types, and intervention modalities, and suggests that complete donor engraftment is neither necessary nor sufficient for clinical benefit. A dual-mechanism model of pathobiont elimination and functional microbial restoration may help explain microbiome-mediated enhancement of cancer immunotherapy, highlighting a balanced immune permissive gut ecosystem as a key determinant of therapeutic success.

Generalized myasthenia gravis (gMG) is a chronic autoimmune disorder that causes muscle weakness. This human factors (HF) validation study aimed to demonstrate that use of a prefilled syringe with needle safety device (PFS-SD) or autoinjector (AI) is safe and effective for patients with gMG, caregivers, and healthcare professionals (HCPs) to administer injectable medication in the intended use environments without preventable use errors. Patients with gMG, caregivers, and HCPs were randomized to the PFS-SD or AI. No training on either device use was provided. The safety and usability of both devices were assessed using simulated use scenarios, knowledge-based questions, and participant feedback. The simulated use scenario was successfully completed by 94% and 96% of participants using the PFS-SD and AI, respectively, while 90% and 87% of participants, respectively, successfully administered their assigned dose. Device acceptability was reported by 93% and 100% of patient participants for the PFS-SD and AI, respectively. This HF validation study demonstrated that the PFS-SD and AI are safe and effective for use by patients with gMG, caregivers, and HCPs in the intended use environments.

Inhaled pathogens, pollutants and therapeutics interact with the dynamic architecture of the alveoli, yet how individual particles move and deposit at cellular resolution remains unclear. Here, utilizing the crystal ribcage platform, we track aerosol transport in ex vivo, actively ventilated lungs using real-time fluorescence imaging with single-particle resolution, capturing droplet trajectories, free-flight motion, impact orientation and deposition timescales within functional alveoli. These measurements show that intra-alveolar transport is directional and shaped by airway-guided flow and tissue motion. At larger scales, aerosols do not disperse uniformly throughout the lung's volume but instead concentrate into geometrically constrained clusters of alveoli, forming a conserved mosaic-like compartmentalization while neighbouring alveoli remain largely unexposed. The pattern persists across particle types and species and varies with particle properties and lung age. In models of emphysema, fibrosis and metastasis, airway remodelling alters both the geometry and amount of deposition. These multiscale insights reveal how single-particle transport and airway structure together shape alveolar exposure, immune activation, development and therapeutic accessibility.

Atopic dermatitis is a common inflammatory disorder affecting the skin, often associated with a strong disease burden and a long-term impact on patients' quality of life. Although most treatments for atopic dermatitis have been mainly focusing on alleviating symptoms, emerging therapies and approaches may offer the potential to modify the disease course, thereby leading to off-treatment remission and prevention of comorbidities. However, a consensus on the definition of disease modification in atopic dermatitis is yet to be reached. The aim of this article is to review the concept of disease modification in atopic dermatitis and its different dimensions, including underlying pathophysiology, disease control, atopic and nonatopic comorbidities, subclinical biomarkers, and the importance of early therapeutic intervention. Ultimately, identifying therapies with long-lasting effects on atopic dermatitis progression could alleviate the global health burden of atopic diseases.

Wildfires in California's Sierra Nevada during 2020-2021 killed giant sequoias (Sequoiadendron giganteum) at rates unseen for millennia, underscoring the vulnerability of highly fire-adapted trees to ongoing environmental change. Following a century of fire exclusion and fuel accumulation, the effectiveness of prescribed burns in reducing giant sequoia mortality from wildfire remained poorly quantified. Here we estimate mortality outcomes for 26,403 giant sequoias across 19 groves in Sequoia and Kings Canyon national parks following the Castle (2020) and KNP Complex (2021) wildfires using a Bayesian framework. We map tree mortality using a deep learning classifier integrating 3 m PlanetScope imagery, airborne lidar, and field observations. From an estimated 7,974 sequoia deaths (95% Bayesian credible interval (CI): 7,555-8,430), corresponding to 30.2% mortality (CI: 28.6-31.9%), we find previous prescribed burns (&#x2264;10 years prior) reduced mortality odds by 77% (CI: 69-83%), making treated trees nearly four times more likely to survive. Counterfactual simulations suggest that prescribed burns prevented at least 1,888 (CI: 1,487-2,302) deaths, and universal treatment would have saved an additional 3,888 (CI: 3,236-4,580) giant sequoias. These results show that prescribed burns substantially improve survival during extreme wildfires, offering guidance for conserving long-lived, fire-adapted forests under intensifying fire regimes.

Large biliary stones (>25 mm) present significant therapeutic challenges, with standard endoscopic techniques frequently failing to achieve complete ductal clearance. Conventional 3F electrohydraulic lithotripsy (EHL) probes often require multiple sessions or result in incomplete fragmentation. We present a novel approach using a 4.5F EHL probe (Walz Elektronik GmbH, Rohrdorf, Germany) for successful management of large refractory biliary stones. Three female patients (aged 57, 59, and 67 years) with large biliary stones (35-45 mm) previously refractory to standard techniques underwent direct cholangioscopy with a 4.5F EHL probe fragmentation using an 11F cholangioscope (eyeMAX; Micro-Tech, Ann Arbor, Mich, USA). The 4.5F probe delivers energy up to 950 mJ with greater surface area contact than standard 3F probes. Complete ductal clearance was achieved in all 3 cases within a single session, with successful fragmentation where conventional techniques had failed. Procedure durations ranged from 49 to 94 minutes. No adverse events occurred in any case. The 4.5F EHL probe represents a significant advancement for managing large refractory biliary stones, potentially reducing repeat procedures and obviating surgical intervention.

To assess the effectiveness of canakinumab (CAN) in controlling clinical and laboratory inflammation by achieving complete control of cardinal disease manifestations and full normalization of laboratory inflammatory markers. Data were obtained from the international AutoInflammatory Disease Alliance (AIDA) network registry, dedicated to monogenic autoinflammatory diseases. The assessment included both retrospective and prospective real-world data. In total, 158 FMF patients treated with CAN were enrolled. Complete clinical-laboratory response was observed in 45.6% of patients at 3&#x2009;months, 58.6% at 12&#x2009;months, and 55.2% at the last follow-up, after a mean treatment duration of 45&#x2009;months. Partial response occurred in 16.5%, 12.5%, and 16.8% at the same timepoints, respectively. Complete absence of clinical manifestations was observed in&#x2009;>&#x2009;80% of patients at each timepoint. Inflammatory markers normalized significantly by the 3-month assessment. The probability of achieving and maintaining complete response and full laboratory control appeared higher in patients reaching these outcomes by 3&#x2009;months, although it remained substantial in other patients as well. Complete response was associated with a relapsing-remitting disease course and fewer annual attacks. Nearly all patients maintained stable organ damage scores, and therapy discontinuation due to inefficacy was rare (&#x2264;6%). CAN is effective in achieving rapid and sustained clinical and laboratory control in FMF, including stringent endpoints of complete response. Early effectiveness may favour better long-term outcomes, but delayed achievement of complete response and full laboratory control is not uncommon. This study confirms CAN as an effective, and durable therapeutic option in FMF.

Integration of electronic health data from patients with heart failure into process mining could provide insights to the patient journey. However, the current approaches have challenges in addressing all aspects of patient care. A retrospective cohort study of 234 patients with heart failure who were admitted to an outpatient heart failure clinic was conducted. We developed a two-stage pipeline to integrate multidimensional data aspects, such as patient-reported outcome measures, biomarkers, medication changes and reasons for hospitalization. The pipeline consists of: (1) Data Enrichment, where we derive indicators from disparate sources like outpatient visits and self-reported data and we structure this information into an event log; and (2) Supervised Event Abstraction where low-level events are translated into clinically meaningful concepts using a knowledge graph. We demonstrate the practical integration of clinical event enrichment and knowledge-graph-based abstraction for exploratory heart failure pathway analysis. We identified four clusters based on patients' backgrounds. Group A included older, multi-morbid patients with advanced HF and more frequent HF hospitalizations and renal-function worsening, while Groups B, C, and D represented ischemic, arrhythmia-associated, and younger lower-comorbidity profiles with simpler care pathways. These findings demonstrate that this process mining approach offers a practical framework to better understand specific patient pathways and identify mitigation strategies for adverse disease trajectories and mortality. It allows for a more granular understanding of patient journeys and the identification of at-risk cohorts by integrating clinical and patient-reported outcomes. This is a significant step towards more data-driven, patient-centered healthcare.

To evaluate whether oral Age-Related Eye Disease Study (AREDS/2) supplementation is associated with structural or functional disease progression over 24 months in patients with Macular Telangiectasia Type 2 (MacTel). This post hoc analysis included 208 participants enrolled in two 24-month Phase 3 clinical trials of revakinagene taroretcel-lwey for MacTel (sham,&#xa0;n&#xa0;= 98; treated,&#xa0;n&#xa0;= 110). Consistent AREDS/2 exposure was defined by documented intake at baseline and month 24. The primary outcome was 24-month change in ellipsoid zone (EZ) area loss. Secondary outcomes included changes in reading speed, best-corrected visual acuity (BCVA), and aggregate retinal sensitivity. Non-randomized exposure was adjusted using a doubly robust framework combining inverse probability of treatment weighting (IPTW) and multivariable survey-weighted linear regression. In the sham cohort, AREDS/2 supplementation was not associated with statistically significant differences in 24-month EZ area loss (P&#xa0;= 0.258). In the treated cohort, an initial association with greater EZ area loss among AREDS/2 users (P = 0.032) became non-significant after full multivariable adjustment for age, sex, and diabetes status (P&#xa0;= 0.577). Secondary functional metrics showed no significant differences between groups across either cohort. AREDS/2 supplementation was not associated with meaningful differences in structural or functional MacTel progression over a 24-month period. These findings do not provide evidence that routine AREDS/2 supplementation slows EZ area loss or preserves visual function in this population. WHAT IS KNOWN : Depletion of macular pigments is a hallmark structural feature of Macular Telangiectasia Type 2 (MacTel), leading to the hypothesis that oral antioxidant supplementation might offer therapeutic benefit. A prior retrospective study reported structural stabilization of the ellipsoid zone (EZ) with off-label AREDS supplementation, although findings were limited by linear rather than area-based OCT measurements. Utilizing a doubly robust statistical framework across two highly characterized clinical trial cohorts, long-term AREDS/2 supplementation was not associated with a statistically significant difference in 24 months anatomical EZ area loss. Secondary functional outcomes&#x2014;including reading speed, aggregate retinal sensitivity, and best-corrected visual acuity&#x2014;demonstrated no significant difference between AREDS/2 users and non-users over 24 months. The lack of structural or functional efficacy observed in this study may indicate that macular pigment loss is a downstream consequence of M&#xfc;ller cell dysfunction rather than a primary driver of disease progression that can be mitigated by oral antioxidants but this requires future validation with larger longitudinal trials.

This study aims to translate and adapt the University of California San Diego Performance-Based Skills Assessment Extended Range (UPSA-2-ER) to Chinese for assessing independent living skills of people with severe mental illness in Hong Kong. An expert panel was conducted to evaluate the translation, content validity, and cultural relevance. The UPSA-2ER (HK) was administered to 30 Hong Kong Chinese with severe mental illness (SMI) to examine the inter-rater reliability and 210 more to examine the internal consistency, structural validity and predictive validity. Sixty-six participants also completed the Chinese Functional Needs Assessment (CFNA) for concurrent validity. Good content validity was established with modifications of items to address cultural relevance. Both inter-rater reliability (ICC ranged from 0.98 to 0.99) and internal consistency (Cronbach's &#x3b1;&#xa0;=&#xa0;0.97) of total score were excellent, while internal consistency of sub-domains ranged from fair to excellent (Cronbach's &#x3b1; ranged from 0.76 to 0.96). In Rasch analysis, raw variance explained by measures &#x2265;40% was interpreted as good in terms of unidimensionality (Sumintono & Widhiarso, 2015), study results provided modest evidence that the UPSA-2ER(HK) has a unidimensional structure, as the variance explained by the items was 43.5% and the unexplained variance in the 1st contrast was 4.4%. Classification & regression tree analysis showed that the UPSA-2ER(HK) correctly classified 78.5% of the 210 participants into their residential status of independent living, halfway house or long stay care home. For concurrent validity, the UPSA-2ER(HK) demonstrated high correlation with the local golden standard, CFNA (r&#xa0;=&#xa0;0.82). The results showed that the instrument has satisfactory psychometric properties for assessing capacity to perform community living tasks.

Rotator cuff repair aims to achieve stable tendon-to-bone healing while restoring the anatomic footprint and minimizing tension. Although single-row and double-row constructs are widely used, double-row repairs have showed biomechanical advantages, including broader footprint coverage, improved force distribution, and reduced gap formation. These benefits have translated to lower retear rates and improved functional outcomes in certain populations. This technique describes an arthroscopic one-to-one anchor, double-row construct designed for small, crescent-shaped tears. By providing multiple points of fixation with fewer implants, the construct distributes load evenly across the repair and maximizes footprint restoration.