Avoiding URL Reference Degradation in Scientific Publications

Arguments are presented concerning the deposit of Internet-based information into the Internet Archive, a digital library of Internet sites and other digital dat

Beyond ‘witnessing’: children’s experiences of coercive control in domestic violence and abuse

Children’s experiences and voices are underrepresented in academic literature and professional practice around domestic violence and abuse. The project ‘Understanding Agency and Resistance Strategies’ addresses this absence, through direct engagement with children. We present an analysis from interviews with 21 children in the United Kingdom (12 girls and 9 boys, aged 8-18 years), about their experiences of domestic violence and abuse, and their responses to this violence. These interviews were analysed using interpretive interactionism. Three themes from this analysis are presented: a) ‘Children’s experiences of abusive control’, which explores children’s awareness of controlling behaviour by the adult perpetrator, their experience of that control, and its impact on them; b) ‘Constraint’, which explores how children experience the constraint associated with coercive control in situations of domestic violence, and c) ‘Children as agents’ which explores children’s strategies for managing controlling behaviour in their home and in family relationships. The paper argues that, in situations where violence and abuse occurs between adult intimate partners, children are significantly impacted, and can be reasonably described as victims of abusive control. Recognising children as direct victims of domestic violence and abuse would produce significant changes in the way professionals respond to them, by 1) recognising children’s experience of the impact of domestic violence and abuse; 2) recognising children’s agency, undermining the perception of them as passive ‘witnesses’ or ‘collateral damage’ in adult abusive encounters; and 3) strengthening professional responses to them as direct victims, not as passive witnesses to violence

Business Continuity Management in Micro Enterprises: Perception, Strategies, and Use of ICT

Small and medium-sized enterprises (SMEs) represent 99% of enterprises in Germany and more than 95% in the European Union. Given the recent increase of natural disasters and man-made crises and emergencies, it seems an important economic goal to ascertain that SMEs are capable of maintaining their work, revenue and profit at an acceptable level. According to ISO 22301, business continuity management (BCM) is a holistic management process which identifies potential threats and their impact to an organization and serves as a framework to increase organizational resilience and response capabilities. Prior research identified that BCM is under-represented in SMEs and that their security level is partially in an uneconomical range. This article presents the analysis of interviews with 19 independent micro enterprises highlighting findings on their low crisis awareness, varying technical dependency, existing action strategies and communication strategies and proposing a categorization of micro enterprises as preventive technicians, data-intensive chains or pragmatic jumpers

Reactogenicity and safety of second trimester maternal tetanus, diphtheria and acellular pertussis vaccination in the Netherlands

Background: Maternal tetanus-diphtheria-and-acellular-pertussis (Tdap) vaccination is offered to all pregnant women during their second trimester in the Netherlands since December 2019. We assessed second trimester Tdap vaccination reactogenicity and compared with third trimester data from a similar study. For safety assessment, adverse pregnancy outcomes were compared with national data from 2018, before Tdap vaccine-introduction. Methods: Pregnant women were included between August 2019-December 2021 and received Tdap vaccination between 20 and 24w gestational age (GA). Participants completed a questionnaire on solicited local reactions and systemic adverse events (AEs) within one week after vaccination. Results were compared with historical data on reactogenicity from women vaccinated between 30 and 33w GA (n = 58). Regarding safety-related outcomes, each participant was matched to four unvaccinated pregnant women from the Dutch Perinatal Registry, based on living area, parity and age. Results: Among 723 participants who completed the questionnaire, 488 (67.5 %) experienced ≥ 1 local reaction with pain at the injection site as most reported reaction (62.3 %), and 460 (63.6 %) experienced ≥ 1 systemic AE with stiffness in muscles/joints (38.9 %), fatigue (28.9 %), headache (14.5 %) and common cold-like symptoms (11.0 %) most frequently reported. 4 women (0.6 %) reported fever (≥38.0˚C). Symptoms were considered mild and transient within days. No difference in AEs were found between vaccination at 20-24w versus 30-33w GA. 723 participants were matched to 2,424 unvaccinated pregnant women with no increased rates of premature labor, small-for-gestational-age, or other adverse pregnancy outcomes. Conclusions: Second trimester maternal Tdap vaccination appears safe and well-tolerated. Comparison between second versus third trimester vaccination yielded no reactogenicity concerns

La vesícula extracelular TGF-β basal es un biomarcador predictivo de la respuesta a los inhibidores del punto de control inmunitario y de la supervivencia en el cáncer de pulmón no microcítico

Antecedentes: Los inhibidores de los puntos de control inmunitarios (ICI) son una estrategia terapéutica eficaz que mejora la supervivencia de los pacientes con cáncer de pulmón en comparación con los tratamientos convencionales. terapéutica eficaz que mejora la supervivencia de los pacientes con cáncer de pulmón en comparación con los tratamientos convencionales. Sin embargo, se necesitan biomarcadores predictivos novedosos para estratificar qué pacientes obtienen un beneficio clínico, ya que el histológico PD-L1, actualmente utilizado y altamente heterogéneo, ha mostrado una baja precisión. La biopsia líquida es el análisis de biomarcadores en fluidos corporales y representa una herramienta mínimamente invasiva que puede utilizarse para monitorizar la evolución del tumor y los efectos del tratamiento, reduciendo potencialmente los sesgos asociados a la heterogeneidad tumoral asociada a las biopsias de tejidos. En este contexto citoquinas, como el factor de crecimiento transformante-β (TGF-β), pueden encontrarse libres en circulación en la sangre y empaquetadas en vesículas extracelulares (VE), que tienen un tropismo de administración específico y pueden afectar a la interacción entre el tumor y el sistema inmunitario. El TGF-β es una citocina inmunosupresora que desempeña un papel crucial en el escape inmunitario de los tumores, la resistencia al tratamiento y la metástasis. Así pues, nuestro objetivo era evaluar el valor predictivo predictivo del TGF-β circulante y EV en pacientes con cáncer de pulmón no microcítico que reciben ICI.Background: Immune‐checkpoint inhibitors (ICIs) are an effective therapeutic strategy, improving the survival of patients with lung cancer compared with conventional treatments. However, novel predictive biomarkers are needed to stratify which patients derive clinical benefit because the currently used and highly heterogenic histological PD‐L1 has shown low accuracy. Liquid biopsy is the analysis of biomarkers in body fluids and represents a minimally invasive tool that can be used to monitor tumor evolution and treatment effects, potentially reducing biases associated with tumor heterogeneity associated with tissue biopsies. In this context, cytokines, such as transforming growth factor‐β (TGF‐β), can be found free in circulation in the blood and packaged into extracellular vesicles (EVs), which have a specific delivery tropism and can affect in tumor/immune system interaction. TGF‐β is an immunosuppressive cytokine that plays a crucial role in tumor immune escape, treatment resistance, and metastasis. Thus, we aimed to evaluate the predictive value of circulating and EV TGF‐β in patients with non–small‐cell lung cancer receiving ICIs

Hermansky-Pudlak syndrome type 1 causes impaired anti-microbial immunity and inflammation due to dysregulated immunometabolism

Hermansky-Pudlak syndrome (HPS) types 1 and 4 are caused by defective vesicle trafficking. The mechanism for Crohn's disease-like inflammation, lung fibrosis, and macrophage lipid accumulation in these patients remains enigmatic. The aim of this study is to understand the cellular basis of inflammation in HPS-1. We performed mass cytometry, proteomic and transcriptomic analyses to investigate peripheral blood cells and serum of HPS-1 patients. Using spatial transcriptomics, granuloma-associated signatures in the tissue of an HPS-1 patient with granulomatous colitis were dissected. In vitro studies were conducted to investigate anti-microbial responses of HPS-1 patient macrophages and cell lines. Monocytes of HPS-1 patients exhibit an inflammatory phenotype associated with dysregulated TNF, IL-1α, OSM in serum, and monocyte-derived macrophages. Inflammatory macrophages accumulate in the intestine and granuloma-associated macrophages in HPS-1 show transcriptional signatures suggestive of a lipid storage and metabolic defect. We show that HPS1 deficiency leads to an altered metabolic program and Rab32-dependent amplified mTOR signaling, facilitated by the accumulation of mTOR on lysosomes. This pathogenic mechanism translates into aberrant bacterial clearance, which can be rescued with mTORC1 inhibition. Rab32-mediated mTOR signaling acts as an immuno-metabolic checkpoint, adding to the evidence that defective bioenergetics can drive hampered anti-microbial activity and contribute to inflammation

Validation of the numerical rating scale for pain intensity and unpleasantness in pediatric acute postoperative pain: sensitivity to change over time

This study evaluates the construct validity (including sensitivity to change) of the numerical rating scale (NRS) for pain intensity (I) and unpleasantness (U) and participant pain scale preferences in children/adolescents with acute postoperative pain. Eighty-three children aged 8 to 18 years (mean = 13.8, SD = 2.4) completed 3 pain scales including NRS, Verbal Rating Scale (VRS), and faces scales (Faces Pain Scale-Revised [FPS-R] and Facial Affective Scale [FAS], respectively) for pain intensity (I) and unpleasantness (U) 48 to 72 hours after major surgery, and the NRS, VRS and Functional Disability Index (FDI) 2 weeks after surgery. As predicted, the NRSI correlated highly with the VRSI and FPS-R and the NRSU correlated highly with the VRSU and FAS 48 to 72 hours after surgery. The FDI correlated moderately with the NRS at both time points. Scores on the NRSI and NRSU at 48 to 72 hours were significantly higher than at 2 weeks after surgery. Children found the faces scales the easiest to use while the VRS was liked the least and was the hardest to use. The NRS has adequate evidence of construct validity including sensitivity for both pain intensity and unpleasantness. This study further supports the validity of the NRS as a tool to measure both intensity and unpleasantness of acute pain in children

Micronutrient status during pregnancy is associated with child immune status in rural Bangladesh.

BACKGROUND: Poor immune function increases childrens risk of infection and mortality. Several maternal factors during pregnancy may affect infant immune function during the postnatal period. OBJECTIVES: We aimed to evaluate whether maternal micronutrients, stress, estriol, and immune status during the first or second trimester of pregnancy were associated with child immune status in the first two years after birth. METHODS: We conducted observational analyses within the water, sanitation, and hygiene (WASH) Benefits Bangladesh randomized controlled trial. We measured biomarkers in 575 pregnant women and postnatally in their children. Maternal biomarkers measured during the first and second trimester of pregnancy included nutrition status via vitamin D (25-hydroxy-D [25(OH)D]), ferritin, soluble transferrin receptor (sTfR), and retinol-binding protein (RBP); cortisol; estriol. Immune markers were assessed in pregnant women at enrollment and their children at ages 14 and 28 mo, including C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), and 13 cytokines (including IFN-γ). We generated a standardized sum score of log-transformed cytokines. We analyzed IFN-γ individually because it is a critical immunoregulatory cytokine. All outcomes were prespecified. We used generalized additive models and reported the mean difference and 95% confidence intervals at the 25th and 75th percentiles of exposure distribution. RESULTS: At child age 14 mo, concentrations of maternal RBP were inversely associated with the cytokine sum score in children (-0.34 adjusted difference between the 25th and 75th percentile [95% confidence interval -0.61, -0.07]), and maternal vitamin A deficiency was positively associated with the cytokine sum score in children (1.02 [0.13, 1.91]). At child age of 28 mo, maternal RBP was positively associated with IFN-γ in children (0.07 [0.01, 0.14]), whereas maternal vitamin A deficiency was negatively associated with child AGP (-0.07 [-0.13, -0.02]). Maternal iron deficiency was associated with higher AGP concentrations in children at age 14 mo (0.13 [0.04, 0.23]), and maternal sTfR concentrations were positively associated with child CRP concentrations at age 28 mo (0.18 [0, 0.36]). CONCLUSION: Maternal deficiencies in vitamin A or iron during the first 2 trimesters of pregnancy may shape the trajectory of a childs immune status

Consistency, completeness and external validity of ethnicity recording in NHS primary care records: a cohort study in 25 million patients’ records at source using OpenSAFELY

Background: Ethnicity is known to be an important correlate of health outcomes, particularly during the COVID-19 pandemic, where some ethnic groups were shown to be at higher risk of infection and adverse outcomes. The recording of patients’ ethnic groups in primary care can support research and efforts to achieve equity in service provision and outcomes; however, the coding of ethnicity is known to present complex challenges. We therefore set out to describe ethnicity coding in detail with a view to supporting the use of this data in a wide range of settings, as part of wider efforts to robustly describe and define methods of using administrative data. Methods: We describe the completeness and consistency of primary care ethnicity recording in the OpenSAFELY-TPP database, containing linked primary care and hospital records in > 25 million patients in England. We also compared the ethnic breakdown in OpenSAFELY-TPP with that of the 2021 UK census. Results: 78.2% of patients registered in OpenSAFELY-TPP on 1 January 2022 had their ethnicity recorded in primary care records, rising to 92.5% when supplemented with hospital data. The completeness of ethnicity recording was higher for women than for men. The rate of primary care ethnicity recording ranged from 77% in the South East of England to 82.2% in the West Midlands. Ethnicity recording rates were higher in patients with chronic or other serious health conditions. For each of the five broad ethnicity groups, primary care recorded ethnicity was within 2.9 percentage points of the population rate as recorded in the 2021 Census for England as a whole. For patients with multiple ethnicity records, 98.7% of the latest recorded ethnicities matched the most frequently coded ethnicity. Patients whose latest recorded ethnicity was categorised as Other were most likely to have a discordant ethnicity recording (32.2%). Conclusions: Primary care ethnicity data in OpenSAFELY is present for over three quarters of all patients, and combined with data from other sources can achieve a high level of completeness. The overall distribution of ethnicities across all English OpenSAFELY-TPP practices was similar to the 2021 Census, with some regional variation. This report identifies the best available codelist for use in OpenSAFELY and similar electronic health record data