bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative outcomes of selective laser trabeculoplasty delivered by optometrists compared with ophthalmologists: a UK-based multicentre observational study
Authors: Lee Chan Ning , Delaney Alexander , Richardson Jay A L , Freeman Graham , Gunn Patrick J G , Harthan Stephen , Dubois Vincent , Yau Kenneth , Hemmerdinger Christopher , Harper Robert , Vallabh Neeru A
Published: October 2024

Background

Selective laser trabeculoplasty (SLT), a National Institute for Care and Health Excellence recommended first-line treatment for open-angle glaucoma and ocular hypertension, is increasingly delivered by optometrists. This retrospective multicentre observational study evaluates real-world outcomes of SLT comparing optometrist-treated to ophthalmologist-treated eyes.

Methods

Adults aged ≥40 years receiving first SLT treatment at three UK hospital eye units (Aintree, Manchester, Macclesfield) between 1 August 2018 and 1 August 2021 were analysed using anonymised local audit data. Outcomes included intraocular pressure (IOP), visual acuity (VA), drop burden, complications including post-SLT IOP spikes, and composite treatment failures including repeat laser or glaucoma surgery, evaluated at 6-monthly intervals up to 24 months. Groups were compared with parametric and non-parametric tests, accounting for intereye correlation, and Kaplan-Meier survival analysis using composite treatment failure endpoints was conducted.

Results

207 eyes (131 patients) were analysed, 84 (56 patients) optometrist-treated eyes compared with 123 ophthalmologist-treated eyes (75 patients). No statistically significant differences (p>0.05) were found in change in VA, IOP or glaucoma drops from pre-SLT baseline between optometrist and ophthalmologist-treated eyes, at all time points. More cataracts were detected in optometrist-treated eyes, however, this did not affect differences in VA or cataract surgery frequency. More optometrist-treated eyes underwent glaucoma surgery, however, ophthalmologist-treated eyes had higher drop burden and chance of composite treatment failure up to month 18.

Conclusion

Outcomes of SLT treatment by optometrists and ophthalmologists are comparable up to 24 months post-treatment. Ophthalmologist-treated eyes may have had more aggressive eye-drop treatment, preventing the need for surgery.
Quality improvement approach to reduce patient cycle time at a student-run free healthcare clinical network
Authors: Kronlage René Marcella , Stanley Amy S , Reid Miranda J , Shaw William Hudson , House Cara E , Lossius Michele N , Kulla Artenisa , Coxen Kendyll , Mackie Phillip M , Holland Carolyn K
Published: October 2024

Background

The University of Florida (UF) Equal Access Clinic Network (EACN) is the largest student-run free healthcare clinic network in Florida. The UF EACN serves those who are underinsured or uninsured in Alachua County and its surrounding area. Nationally, average total clinic time per medical visit has been established to be 84 min.

Problem

Before this project, average patient cycle time at the UF EACN was 125.3 min, and there was no established quality improvement (QI) team to implement changes to address inefficiencies.

Methods

This was a prospective QI study that recorded patient cycle times for patients who received healthcare at any of the four primary care free clinics across the UF EACN from 5 July 2022 to 6 April 2023.

Interventions

Eighteen Plan–Do–Study–Act cycles were tailored to each of the four primary care clinic’s needs with a focus on reducing patient cycle time by addressing the following identified problems: prolonged intake process, translation services, limited numbers of volunteers, and other inefficiencies and bottlenecks in workflow.

Results

The median patient cycle time at the EACN shifted from 125.3 min to 112.7 min over a nine month period. This drop of 12.6 min meant patients saw a 10.1% reduction in patient cycle time across the EACN.

Conclusion

Underserved patients at EACN are experiencing increased value by having shorter patient cycle times.
Mean platelet volume in preterm infants as a predictor of late-onset neonatal sepsis: a retrospective comparative study
Authors: Leibovitch Leah , Zohar Hagar , Gavri-Beker Ayelet , Goshen Abigail , Strauss Tzipora
Published: October 2024

Background

Neonatal sepsis remains a primary cause of morbidity and mortality among newborns. Rapid and accurate diagnosis poses a significant challenge—the non-specific clinical presentation of neonatal sepsis relies heavily on various laboratory indices for early detection and subsequent management. One such indicator under investigation is the mean platelet volume (MPV), which may serve as a predictive marker. This study aims to evaluate the association between the MPV and late-onset sepsis in preterm infants.

Methods

This retrospective study included 63 newborns born at Sheba Medical Center from 2016 to 2020 with late-onset sepsis as evidenced by positive blood cultures, and 63 newborns in the control group. We analysed blood count data at three intervals: preinfection, intrainfection and postinfection. Electronic medical records provided supplemental data. Each septic neonate was paired with a non-septic control.

Results

Our results revealed a significant elevation of MPV in septic newborns compared with non-septic controls during the days prior to the infection (9.323 and 8.876, respectively, p=0.043) and persisted up to 2 weeks postinfection (9.39 vs 8.714, p=0.025).

The MPV and the MPV-to-total platelet (PLT) count ratio exhibited significant predictive capabilities in receiver operating characteristics analysis (−0.60 and −0.57, respectively).

Conclusions

High MPV in combination with PLT decrement might be predictive for the diagnosis of late-onset sepsis. Future studies should be conducted in order to better understand the underlying pathophysiology and the potential clinical applications of these findings.
Australian women’s experiences and perceptions of interconception care: a qualitative descriptive study
Authors: Kodavaluru Sarmitha , Appuhamy Mudiyanselage Isini , Mazza Danielle , James Sharon
Published: October 2024

Background

Interconception, the time between pregnancies, is an opportunity to improve the health outcomes of women, infants and subsequent pregnancies. Interconception care involves the assessment of previous pregnancy outcomes, management of maternal risk factors, advice regarding optimal pregnancy spacing, and postpartum contraception provision. However, there is no consistent provision of interconception care, and limited understanding of consumer perspectives. This study aims to describe Australian women’s perceptions and experiences of interconception care.

Methods

A qualitative descriptive semi-structured interview study was undertaken in July 2022 with women of reproductive age who had given birth to at least one child with intention to have another child. Reflexive thematic analysis was conducted and the standards for reporting qualitative research informed the writing of this study.

Results

From 15 participants, analysis identified two major themes: (1) women’s lack of engagement with interconception care services; and (2) difficulties accessing interconception care. All participants were unfamiliar with interconception terminology, but most perceived it as a distinct care need, largely accessed in primary healthcare settings. Participants wanted further support to be initiated by healthcare professionals about issues such as breastfeeding, postpartum care and lifestyle risk reduction. Interconception care availability and content was perceived as inconsistent, ineffective and provided opportunistically. Participants outlined the need for improved consumer and healthcare professional interconception care awareness, education, and woman-centred continuity of care.

Conclusions

Interconception care awareness is needed by women and healthcare professionals to better meet the needs of women during this life stage.
Influences on ethnic minority women’s experiences and access to contraception in the UK: a systematic qualitative evidence synthesis
Authors: Cory Ryan James , Mawson Rebecca , Linton Emma , Al-Bazz Dalal Y , Fryer Kate , Ma Richard , Mitchell Caroline Anne
Published: October 2024

Background

Accessible contraception is critical for promoting the health and well-being of women and their families. In the UK, contraception is free at the point of access, but only 55% of pregnancies are planned, with negative implications for maternal and infant outcomes. In general, women from ethnic minorities use contraceptives less than white women. Barriers to the uptake of contraceptives have been identified, including perceived poor information from healthcare professionals and concerns about side effects. However, most studies do not include representative proportions of women from ethnic minorities. Evidence suggests that ethnic minority (EM) women feel targeted and coerced by healthcare professionals regarding contraception.

Methods

A systematic search of Medline, Embase, and PsycINFO via Ovid, CINAHL, and Web of Science was conducted to identify primary qualitative and mixed-methods studies exploring ethnic minority women’s experience of contraception in the UK. The data were charted using thematic analysis, using both summary and synthesis.

Results and conclusions

16 studies met the inclusion criteria, including the perspectives of 717 participants from an ethnic minority. Four overarching themes were developed: contraceptive knowledge, beliefs, family, and services. Similar to women in general, ethnic minority women have concerns about side effects, especially infertility, value the perspectives of their peers and male partners, and express a preference for female healthcare professionals. Novel perspectives included conflicting ideas about the influence of religion and stereotyping of ethnic minority women. Culturally competent consultations and a better understanding of hormonal hesitancy are essential.
Multiomics of the intestine-liver-adipose axis in multiple studies unveils a consistent link of the gut microbiota and the antiviral response with systemic glucose metabolism
Authors: Castells-Nobau Anna , Moreno-Navarrete José Maria , de la Vega-Correa Lisset , Puig Irene , Federici Massimo , Sun Jiuwen , Burcelin Remy , Guzylack-Piriou Laurence , Gourdy Pierre , Cazals Laurent , Arnoriaga-Rodríguez María , Frühbeck Gema , Seoane Luisa Maria , López-Miranda José , Tinahones Francisco J , Dieguez Carlos , Dumas Marc-Emmanuel , Pérez-Brocal Vicente , Moya Andrés , Perakakis Nikolaos , Mingrone Geltrude , Bornstein Stefan , Rodriguez Hermosa Jose Ignacio , Castro Ernesto , Fernández-Real Jose Manuel , Mayneris-Perxachs Jordi
Published: October 2024

Background

The microbiota is emerging as a key factor in the predisposition to insulin resistance and obesity.

Objective

To understand the interplay among gut microbiota and insulin sensitivity in multiple tissues.

Design

Integrative multiomics and multitissue approach across six studies, combining euglycaemic clamp measurements (used in four of the six studies) with other measurements of glucose metabolism and insulin resistance (glycated haemoglobin (HbA1c) and fasting glucose).

Results

Several genera and species from the Proteobacteria phylum were consistently negatively associated with insulin sensitivity in four studies (ADIPOINST, n=15; IRONMET, n=121, FLORINASH, n=67 and FLOROMIDIA, n=24). Transcriptomic analysis of the jejunum, ileum and colon revealed T cell-related signatures positively linked to insulin sensitivity. Proteobacteria in the ileum and colon were positively associated with HbA1c but negatively with the number of T cells. Jejunal deoxycholic acid was negatively associated with insulin sensitivity. Transcriptomics of subcutaneous adipose tissue (ADIPOMIT, n=740) and visceral adipose tissue (VAT) (ADIPOINST, n=29) revealed T cell-related signatures linked to HbA1c and insulin sensitivity, respectively. VAT Proteobacteria were negatively associated with insulin sensitivity. Multiomics and multitissue integration in the ADIPOINST and FLORINASH studies linked faecal Proteobacteria with jejunal and liver deoxycholic acid, as well as jejunal, VAT and liver transcriptomic signatures involved in the actin cytoskeleton, insulin and T cell signalling. Fasting glucose was consistently linked to interferon-induced genes and antiviral responses in the intestine and VAT. Studies in
Drosophila melanogaster
validated these human insulin sensitivity-associated changes.

Conclusion

These data provide comprehensive insights into the microbiome-gut-adipose-liver axis and its impact on systemic insulin action, suggesting potential therapeutic targets.
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Bullying victimisation and perpetration of foster and kinship youth in the USA
Authors: Helton Jesse J , Hong Jun Sung , Kong Vibol
Published: October 2024

Background

Childhood bullying can result in serious injury. Our objective was to compare bullying victimisation and perpetration of school-aged youth from 2018 to 2022 in different households: foster care, kinship care and birth families. A second objective examined correlations between bullying and adverse childhood experiences, child gender, age and race while stratifying by household type.

Methods

The 2018–2022 samples of the National Surveys of Children’s Health were used. Bullying victimisation and perpetration were reported by caregivers and ranged from none, yearly, monthly to weekly or daily. Adversities include parental separation, death or incarceration; witnessing or experiencing violence; living with an adult with a substance problem or severe mental illness; or racial discrimination. Pearson χ2and ordinal logistic regression models were used.

Results

Pre-COVID-19, 69% of foster youth were victimised compared with 44% of kinship and 48% of birth-family youth, and 57% of foster youth perpetrated compared with 21% of kinship and 20% of birth-family youth. During COVID-19, the relative risk of both victimisation and perpetration flipped between groups: 25% of fosters were victimised compared with 34% of both kinship and birth youth, and 24% of fosters perpetrated compared with 35% of kinship and 33% of birth youth. In 2022, younger foster youth were at a higher risk of victimisation and perpetration, while males were at risk of perpetration.

Discussion and conclusions

Foster youth are at high risk for victimisation and perpetration compared with youth living with kinship or birth families. Results indicate that prevention efforts in school settings may be the most effective.
Answering the call for better science: an update on SAVIR’s efforts to advance antiracism in injury and violence research
Authors: Ranapurwala Shabbar I , Cruz Theresa H , Hohl Bernadette , Murray Regan , Rexing Christen , Villarreal Silvia , Rose Dominique M , Brooks-Russell Ashley
Published: October 2024

In response to the call for better science that the Society for Advancement of Violence and Injury Research (SAVIR) put out 4 years ago, SAVIR established its Anti-racism Interest Group (AIG) and charged it to lead antiracism efforts at SAVIR. The SAVIR AIG has led SAVIR’s efforts to actively integrate antiracism principles and frameworks into injury and violence prevention (IVP) education, research, methods, dissemination and implementation as a field, and more specifically into each of SAVIR committee activities and strategies. In this article, we detail those efforts and outline the immediate next steps of a vision that is developing and the course we are taking. But we acknowledge that these efforts are only the beginning on the long road ahead to fully rid ourselves (as a society), our science and our field of IVP of the scourge that racism is.
Novel bispecific antibody-drug conjugate targeting PD-L1 and B7-H3 enhances antitumor efficacy and promotes immune-mediated antitumor responses
Authors: Dong Yijun , Zhang Zongliang , Luan Siyuan , Zheng Meijun , Wang Zeng , Chen Yongdong , Chen Xiaoting , Tong Aiping , Yang Hui
Published: October 2024

Background

Antibody-drug conjugates (ADCs) offer a promising approach, combining monoclonal antibodies with chemotherapeutic drugs to target cancer cells effectively while minimizing toxicity.

Methods

This study examined the therapeutic efficacy and potential mechanisms of a bispecific ADC (BsADC) in laryngeal squamous cell carcinoma. This BsADC selectively targets the immune checkpoints programmed cell death ligand-1 (PD-L1) and B7-H3, and the precise delivery of the small-molecule toxin monomethyl auristatin E.

Results

Our findings demonstrated that the BsADC outperformed its bispecific antibody and PD-L1 or B7-H3 ADC counterparts, particularly in terms of in vitro/in vivo tumor cytotoxicity, demonstrating remarkable immune cytotoxicity. Additionally, we observed potent activation of tumor-specific immunity and significant induction of markers of immunogenic cell death (ICD) and potential endoplasmic reticulum stress.

Conclusion

In conclusion, this novel BsADC, through immune checkpoint inhibition and promotion of ICD, amplified durable tumor immune cytotoxicity, providing novel insights and potential avenues for future cancer treatments and overcoming resistance.
Gal-3 blocks the binding between PD-1 and pembrolizumab
Authors: Greisen Stinne Ravn , Bendix Mia , Nielsen Morten Aagaard , Pedersen Kathrine , Jensen Nina Haunstrup , Hvid Malene , Mikkelsen Jakob Hauge , Drace Taner , Boesen Thomas , Steiniche Torben , Schmidt Henrik , Deleuran Bent
Published: October 2024

Introduction

Immune checkpoint inhibitors (ICI) have revolutionized the treatment of metastatic malignant melanoma (MM) and improved long-term survival. Despite the impressive results, some patients still have progressive disease, and the search for biomarkers predicting response to ICI treatment is ongoing. In this search, galectin-3 (Gal-3) has been suggested as a molecule of interest, both as a marker of treatment response and as a treatment target to potentiate ICI therapy. We have previously demonstrated the binding between programmed cell death 1 (PD-1) and Gal-3, and here, we investigated the interaction between PD-1, pembrolizumab, and Gal-3 in metastatic MM patients.

Methods

The binding between PD-1, pembrolizumab and Gal-3 was investigated by surface plasmon resonance (SPR) and cryogenic electron microscopy (cryo-EM). The function was studied in in vitro cultures and soluble levels of both PD-1 and Gal-3 were measured in metastatic MM patients, treated with pembrolizumab.

Results

By SPR, we demonstrated that Gal-3 can block the binding between PD-1 and pembrolizumab, and further visualized a steric inhibition using cryo-EM. T cells cultured with Gal-3 had reduced pro-inflammatory cytokine production, which could not be rescued by pembrolizumab. In patients with metastatic MM, high levels of Gal-3 in plasma were found in patients with a longer progression-free survival in the study period, whereas high Gal-3 expression in the tumor was seen in patients with disease progression. Soluble PD-1 levels in plasma increased after treatment with pembrolizumab and correlated with disease progression.

Conclusion

We demonstrate that the interaction between PD-1 and Gal-3 interferes with the binding of pembrolizumab, supporting that an immune suppression induced by Gal-3 in the tumor microenvironment cannot be rescued by pembrolizumab.
Classification ofPTENgermline non-truncating variants: a new approach to interpretation
Authors: Margot Henri , Jones Natalie , Matis Thibaut , Bonneau Dominique , Busa Tiffany , Bonnet Françoise , Conrad Solene , Crivelli Louise , Monin Pauline , Fert-Ferrer Sandra , Mortemousque Isabelle , Raad Sabine , Lacombe Didier , Caux Frédéric , Sevenet Nicolas , Bubien Virginie , Longy Michel
Published: October 2024

Background

PTEN hamartoma tumour syndrome (PHTS) encompasses distinct syndromes, including Cowden syndrome resulting fromPTENpathogenic variants. Missense variants account for 30% of PHTS cases, but their classification remains challenging. To address these difficulties, guidelines were published by the Clinical Genome Resource PTEN Variant Curation Expert Panel.

Methods

Between 2010 and 2020, the Bergonie Institute reference laboratory identified 76 different non-truncatingPTENvariants in 166 patients, 17 of which have not previously been reported. Variants were initially classified following the current guidelines. Subsequently, a new classification method was developed based on four main criteria: functional exploration, phenotypic features and familial segregation, in silico modelling, and allelic frequency.

Results

This new method of classification is more discriminative and reclassifies 25 variants, including 8 variants of unknown significance.

Conclusion

This report proposes a revision of the currentPTENvariant classification criteria which at present rely on functional tests evaluating only the phosphatase activity of PTEN and apply a particularly stringent clinical PHTS score.The classification of non-truncating variants ofPTENis facilitated by taking into consideration protein stability for variants with intact phosphatase activity, clinical and segregation criteria adapted to the phenotypic variability of PHTS and by specifying the allelic frequency of variants in the general population. This novel method of classification remains to be validated in a prospective cohort.
Novel therapies in CIDP
Authors: Mair Devan , Madi Heba , Eftimov Filip , Lunn Michael P , Keddie Stephen
Published: October 2024

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a heterogeneous but clinically well-described disease within circumscribed parameters. It is immunologically mediated through several poorly understood mechanisms. First-line therapies with steroids, intravenous immunoglobulin (IVIG) or plasma exchange are each effective in about two-thirds of patients. These treatments are seldom associated with complete resolution or cure, and often pose considerable practical, financial and medical implications.

Our understanding of many of the key pathological processes in autoimmune diseases is expanding, and novel targeted therapeutics are being developed with promise in several autoimmune neurological disorders.

This narrative review looks first at detailing key pathogenic mechanisms of disease in CIDP, followed by an in-depth description of potential novel therapies and the current evidence of their application in clinical practice.
Post COVID-19 syndrome among 5248 healthcare workers in England: longitudinal findings from NHS CHECK
Authors: Dempsey Brendan , Blake Helen A , Madan Ira , Stevelink Sharon A M , Greenberg Neil , Raine Rosalind , Rafferty Anne-Marie , Bhundia Rupa , Wessely Simon , Lamb Danielle
Published: October 2024

Objectives

The objectives of this study were to examine post COVID-19 syndrome (PCS) among healthcare workers (HCWs) in England and explore risk factors for the condition.

Methods

Data were collected by National Health Service (NHS) CHECK, a longitudinal study exploring HCWs’ mental and physical well-being during and after the COVID-19 pandemic. NHS CHECK collected data at four timepoints: the baseline survey between April 2020 and January 2021, and then three follow-up surveys at approximately 6, 12 and 32 months post baseline. PCS data were collected at 12 and 32 months, while risk factor data were from baseline. HCWs were asked what COVID-19 symptoms they experienced and for how long and were classified as having PCS if they had any symptom for ≥12 weeks. Multilevel regressions were used to examine risk factors for PCS.

Results

This study included 5248 HCWs. While 33.6% (n=1730) reported prolonged COVID-19 symptoms consistent with PCS, only 7.4% (n=385) reported a formal diagnosis of PCS. Fatigue, difficult concentrating, insomnia and anxiety or depression were the most common PCS symptoms. Baseline risk factors for reporting PCS included screening for common mental disorders, direct contact with COVID-19 patients, pre-existing respiratory illnesses, female sex and older age.

Conclusions

While a third of HCWs reported prolonged COVID-19 symptoms consistent with PCS, a smaller percentage reported a formal diagnosis of the condition. We replicate findings that direct contact with COVID-19 patients, older age, female sex, pre-existing respiratory illness and symptoms of common mental disorders are associated with increased risk of PCS.
Development of a web-based ecological momentary assessment tool to measure day-to-day variability of the symptoms in patients with Sjögren’s disease
Authors: Georgel Laurie , Benyoussef Anas-Alexis , Berrouiguet Sofian , Guellec Dewi , Carvajal Alegria Guillermo , Marhadour Thierry , Jousse-Joulin Sandrine , Cochener-Lamard Béatrice , Labetoulle Marc , Gottenberg Jacques-Eric , Bourcier Tristan , Nocturne Gaétane , Saraux Alain , Mariette Xavier , Consigny Maëlys , Gravey Michel , Devauchelle-Pensec Valérie , Seror Raphaele , Cornec Divi
Published: October 2024

Objectives

To develop and validate a web-based ecological momentary assessment (EMA) tool to enhance symptoms monitoring among patients with Sjögren’s disease (SjD).

Methods

Consecutive adults with SjD were enrolled in this pilot observational study. Participants used the WebApp over a 3-month period, for the daily collection of individual EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) scales and separate assessment of eyes and mouth dryness, using 0–10 numerical scales. Primary outcome was the measure of the interdaily variability of symptoms. Data collected through the WebApp were compared with those obtained with paper-based questionnaires administered during a final visit, using distinct approaches (predicted error, maximum negative error and maximum positive error). User experience was assessed using the System Usability Scale (SUS) score.

Results

Among the 45 participants, 41 (91.1%) were women. Median age was 57 years (IQR: 49–66). Daily variability of symptoms ranged between 0.5 and 0.8 points across the scales. Over the 3-month period, the predicted error ranged between −1.2 and −0.3 points of the numerical scales. The greatest differences were found for fatigue (−1.2 points (IQR: −2.3 to −0.2)) and ESSPRI score (−1.2 points (IQR: −1.7 to −0.3)). Over the last 2 weeks, the predicted error ranged between – 1.2 and 0.0 points. Maximum negative error ranged between −2.0 and −1.0 points, and maximum positive error between −0.3 and 0.0 points. Median SUS score was 90 (IQR: 85–95).

Conclusion

Our results demonstrate the usability and the relevance of our web-based EMA tool for capturing data that closely reflects daily experiences of patients with SjD.
An evaluation of an online STI service across London: reviewing uptake, utility and outcomes over a 4-year period
Authors: Tittle Victoria , Day Sara Louise , Tostevin Anna , Kelly Adrian M , Spate Jonathan , Burns Fiona , Gibbs Jo , Howarth Alison , Sullivan Ann
Published: October 2024

Objectives

Since 2018, Sexual Health London (SHL) has provided remote sexually transmitted infection (STI) testing services to London residents over 16 years of age. SHL was an asymptomatic screening service. In 2020, SHL widened access to non-urgent symptomatic testing. We undertook a 4-year evaluation on the uptake of SHL’s online testing pathway and outcomes, including the association of positive chlamydia and gonorrhoea nucleic acid amplification test (NAAT) outcomes with user demographics and user utility.

Methods

This is a retrospective data analysis of routine SHL clinical data from 8 January 2018 to 31 March 2022 of all STI test kit orders, focusing on HIV, chlamydia and gonorrhoea outcomes. Descriptive analysis on uptake of each stage of SHL’s clinical care pathway is provided, including HIV testing outcomes. Binary logistic regression was used to examine the association between SHL user-completed online consultation information, SHL uptake and chlamydia and gonorrhoea NAAT results (negative or positive).

Results

During the evaluation period, there were 1 476 187 orders made by 670 293 unique users. The return rate for chlamydia and gonorrhoea NAATs was 79.5% and 67.6% for HIV blood samples. The positivity rate from sufficient samples was 4.5% for chlamydia, 1.6% for gonorrhoea and 0.3% reactivity for HIV. There were increased odds of a positive chlamydia and gonorrhoea NAAT result in non-cisgender women, those with a high number of STI orders, non-UK born and those who collected an STI test kit from a clinic-based service.

Conclusions

To date, this is the largest number of orders in an evaluation of online postal sexual health infection testing in the UK, and highest return rate of samples, suggesting acceptability of SHL for STI testing. Positivity rates for chlamydia and gonorrhoea NAAT tests are lower than national figures, which may reflect asymptomatic screening prior to 2020 and testing of non-urgent symptoms since 2020.
Advance Consent for participation in Acute Stroke Trials (ACTION): protocol for a feasibility study
Authors: Udoh Ubong , Seeger Rena , Dewar Brian , Cummings Emma , Gocan Sophia , Nicholls Stuart , Fedyk Mark , Shepherd Victoria , Perry Jeff , Fahed Robert , Ramsay Tim , Brehaut Jamie , Hill Michael D , Poppe Alexandre Y , Menon Bijoy K , Swartz Richard H , Dowlatshahi Dar , Shamy Michel
Published: October 2024

Introduction

Obtaining informed consent for research from patients in medical emergencies remains a challenge, particularly in acute stroke care as treatment must be administered quickly and patients often arrive in the hospital in a state of incapacitation. Adaptations to standard consenting approaches—such as the use of surrogate consent or deferral of consent—have significant limitations. This feasibility study aims to test a new consenting approach in acute stroke care that we call advance consent. Advance consent has the potential to render emergency trial enrolment faster, fairer and more transparent, leading to more generalisable results.

Methods and design

We will conduct a five-part study at The Ottawa Hospital, a quaternary care stroke centre: (1) administering questionnaires in the Ottawa Hospital Stroke Prevention Clinic that will examine patients’ perspectives on research participation and advance consent; (2) inviting participants to consent in advance to any or both currently enrolling acute stroke trials; (3) tracking patient enrolment into these trials over 1 year; (4) administering a follow up questionnaire to participants at 1 year and (5) administering a questionnaire to participating hospital staff in order to interrogate their experiences with advance consent. Outcomes include but are not limited to eligibility rate, recruitment rate, withdrawal rate and the proportion of patients whose advance consent results in trial enrolment.

Conclusion

This study will test the feasibility of enrolling patients at risk of stroke into acute stroke trials using advance consent.
Definitions of white matter hyperintensity change: impact on estimates of progression and regression
Authors: Jochems Angela C C , Muñoz Maniega Susana , Clancy Una , Arteaga Reyes Carmen , Jaime Garcia Daniela , Valdés Hernández Maria del C. , Chappell Francesca M , Barclay Gayle , Jardine Charlotte , McIntyre Donna , Gerrish Iona , Wiseman Stewart , Stringer Michael S , Thrippleton Michael J , Doubal Fergus , Wardlaw Joanna M
Published: October 2024

Background

White matter hyperintensity (WMH) progression is well documented; WMH regression is more contentious, which might reflect differences in defining WMH change. We compared four existing WMH change definitions in one population to determine the effect of definition on WMH regression.

Methods

We recruited patients with minor non-disabling ischaemic stroke who underwent MRI 1–3 months after stroke and 1 year later. We assessed WMH volume (in absolute mL and % intracranial volume) and applied four different definitions, including two thresholds (based on SD or mL), percentile and quintile approaches.

Results

In 198 participants, mean age 65.5 (SD=11.13), baseline WMH volume was 15.46 mL (SD=19.2), the mean net WMH volume change was 0.98 mL (SD=2.84), range −7.98 to +12.84 mL. Proportion regressing/stable/progressing WMH were threshold 1 (SD), 29.8%/55.6%/14.6%; threshold 2(mL), 29.8%/16.7%/53.5%; percentile approach, 28.3%/21.2%/50.5%. The quintile approach includes five groups with quintile 3 reflecting no change (N=40), quintiles 1 and 2 any WMH decrease (N=80) and quintiles 4 and 5 any WMH increase (N=78).

Conclusions

Different WMH change definitions cause big differences in how participants are categorised; additionally, non-normal WMH distribution precludes use of some definitions. Consistent use of an appropriate definition would facilitate data comparisons, particularly in clinical trials of potential WMH treatments.
Exosomes-mediated delivery of miR-486-3p alleviates neuroinflammation via SIRT2-mediated inhibition of mitophagy after subarachnoid hemorrhage
Authors: Sheng Bin , Gao Sen , Chen XiangXin , Liu Yang , Lai Niansheng , Dong Jin , Sun Jiaqing , Zhou Yan , Wu Lingyun , Hang Chun-Hua , Li Wei
Published: October 2024

Background

Neuroinflammation participates in the pathogenesis of subarachnoid haemorrhage (SAH); however, no effective treatments exist. MicroRNAs regulate several aspects of neuronal dysfunction. In a previous study, we found that exosomal miR-486-3p is involved in the pathophysiology of SAH. Targeted delivery of miR-486-3p without blood-brain barrier (BBB) restriction to alleviate SAH is a promising neuroinflammation approach.

Methods

In this study, we modified exosomes (Exo) to form an RVG-miR-486-3p-Exo (Exo/miR) to achieve targeted delivery of miR-486-3p to the brain. Neurological scores, brain water content, BBB damage, flow cytometry and FJC staining were used to determine the effect of miR-486-3p on SAH. Western blot analysis, ELISA and RT-qPCR were used to measure relevant protein and mRNA levels. Immunofluorescence staining and laser confocal detection were used to measure the expression of mitochondria, lysosomes and autophagosomes, and transmission electron microscopy was used to observe the level of mitophagy in the brain tissue of mice after SAH.

Results

Tail vein injection of Exo/miR improved targeting of miR-486-3p to the brains of SAH mice. The injection reduced levels of neuroinflammation-related factors by changing the phenotype switching of microglia, inhibiting the expression of sirtuin 2 (SIRT2) and enhancing mitophagy. miR-486-3p treatment alleviated neurobehavioral disorders, brain oedema, BBB damage and neurodegeneration. Further research found that the mechanism was achieved by regulating the acetylation level of peroxisome proliferator-activated receptor γ coactivator l alpha (PGC-1α) after SIRT2 enters the nucleus.

Conclusion

Exo/miR treatment attenuates neuroinflammation after SAH by inhibiting SIRT2 expression and stimulating mitophagy, suggesting potential clinical applications.
Effect of spacing of grid PHD on performance of combined PHD–PVD vacuum preloading method for treatment of clayey slurry
Authors: Pan Yu , Song Ding-Bao , Yin Zhen-Yu , Yin Jian-Hua
Published: October 2024

A novel ground improvement method that combines grid prefabricated horizontal drains (PHDs) with prefabricated vertical drain (PVD) assisted by vacuum preloading is proposed for the beneficial reuse of dredged clayey slurry for reclamation purpose. To assess the feasibility of this innovative method, physical model tests are designed and conducted using high-water content Hong Kong marine deposits as the clayey slurry material. Furthermore, the impact of the spacing configuration of the grid PHD on the effectiveness of the proposed method is investigated through a series of model tests. A test without the installation of PVD was set, and in this case, two phases of vacuum preloading are applied sequentially through the PHD layer installed in stage. The other three tests involve three phases, with the addition of a vacuum preloading stage through PVD and variations in arrangement pattern of grid PHD layer. Results show that this proposed approach yields a final average undrained shear strength of soil of approximately 30 kPa, meanwhile reducing the average water content to around 50%. Furthermore, it is observed that decreasing the vertical spacing of grid PHDs results in growing final settlement. Reducing the horizontal spacing has less impact on the final settlement.
Characterizing diameter distribution of Pinus nigra stands in Türkiye with a Weibull distribution
Authors: Alkan Onur , Cao Quang V. , Özçelik Ramazan
Published: October 2024

The objective of this study was to identify the most effective system for predicting parameters of the Weibull function that characterize diameter distributions of black pine ( Pinus nigra Arn.) stands in Türkiye. We examined three Parameter Recovery methods: the Moment Recovery method, based on diameter moments (diameter variance and quadratic mean diameter), the Percentile Recovery method, relying on diameter percentiles (the 31st and 63rd percentiles), and the Hybrid method, which combines elements of both approaches. Within each of the three methods, we derived regression coefficients from four estimation approaches: Seemingly Unrelated Regression (SUR), Cumulative Distribution Function Regression (CDFR), Maximum Likelihood Estimator Regression (MLER), and Stand Table Regression (STR). Our findings demonstrated that the Moment Recovery method exhibited superior performance compared to the Percentile Recovery and Hybrid methods. Additionally, the MLER approach surpassed the other three estimation techniques. Notably, the Moment Recovery method, coupled with regression coefficients estimated through MLER, emerged as the top-performing combination overall. These results hold significant implications for the development of a diameter distribution growth and yield model tailored to black pine stands in Türkiye.
Responses of needle terpene concentrations and characteristics of resin canals to different warming treatments in Scots pine and Norway spruce seedlings grown in a field experiment
Authors: Kivimäenpää Minna , Virjamo Virpi , Nissinen Katri , Pikkarainen Laura , Ghimire Rajendra P. , Julkunen-Tiitto Riitta , Peltola Heli
Published: October 2024

We studied responses of needle terpene concentrations and resin canal characteristics to warming in Scots pine ( Pinus sylvestris) and Norway spruce ( Picea abies) seedlings grown in a controlled field set-up in eastern Finland. Warming was simulated during the growing seasons using infrared heaters that increased air temperature in study 1 (2016–2019) by 1 °C and in study 2 (2019–2020) by 2 and 4 °C, compared to ambient conditions. Terpenes were sampled in study 1 from non-matured current year and matured previous year needles in June 2019, and study 2 from mature current year needles in August 2020. In study 1, we also studied resin canal anatomy. We found that 1 °C elevation of temperature caused two-fold increase in concentrations of total terpenes, oxygenated monoterpenes, and sesquiterpenes of non-matured current year needles of Norway spruce. Further, it caused 1.3–1.8-fold increases in sesquiterpene concentrations both in unmatured and matured needles of Scots pine. It also decreased resin canal diameter of mature needles in Norway spruce. In study 2, the stronger warming treatments did not affect terpene concentrations of matured current year needles in either species. Based on our findings, even minor elevation of temperature may affect terpene concentrations of non-mature needles in boreal conifers.
Reducing Leakage Effects and Measurement Time in Low-frequency Noise Measurements
Authors: Scandurra Graziella , Ciofi Carmine
Published: October 2024

We propose a modified approach for DFT-based spectra and cross-spectra estimation that allows to significantly reduce the problem of spectral leakage at very low frequencies. This results in the ability to select larger resolution bandwidths that, in turn, allow for reduced measurement time for a given maximum level of statistical error in spectral points at very low frequencies.
On automorphisms of affine superspaces
Authors: Shu Bin
Published: October 2024

In this paper, we propose a super version of Jacobian conjecture on the automorphisms of affine superspaces over an algebraically closed field [Formula: see text] of characteristic [Formula: see text], which predicts that for a homomorphism [Formula: see text] of the polynomial superalgebra [Formula: see text] over [Formula: see text], if [Formula: see text] satisfies the super version of Jacobian condition (SJ for short), then [Formula: see text] gives rise to an automorphism of the affine superspace [Formula: see text]. We verify the conjecture if additionally, the set [Formula: see text] of maximal [Formula: see text]-homogeneous ideals of [Formula: see text] is assumed to be preserved under [Formula: see text]. The statement is actually proved in any characteristic, i.e. a homomorphism [Formula: see text] gives rise to an automorphism of [Formula: see text] if SJ is satisfied with [Formula: see text] and the set [Formula: see text] is preserved under [Formula: see text] for an algebraically closed field [Formula: see text] of any characteristic.
Weighted analytic regularity for the integral fractional Laplacian in polyhedra
Authors: Faustmann Markus , Marcati Carlo , Melenk Jens Markus , Schwab Christoph
Published: October 2024

On polytopal domains in [Formula: see text], we prove weighted analytic regularity of solutions to the Dirichlet problem for the shifted integral fractional Laplacian with analytic right-hand side. Employing the Caffarelli–Silvestre extension allows one to localize the problem and to decompose the regularity estimates into results on vertex, edge, face, vertex-edge, vertex-face, edge-face and vertex-edge-face neighborhoods of the boundary. Using tangential differentiability of the extended solutions, a bootstrapping argument based on Caccioppoli inequalities on dyadic decompositions of the neighborhoods provides weighted, analytic control of higher-order solution derivatives.
Analysis of the Vibration Effect on the Trailing Edge Noise for Wind Turbine Applications
Authors: da Silva Junior Francisco Ilson , de Sousa Felipe Martins
Published: October 2024

The noise emitted is a factor in determining the location for installing wind turbines. It can be a concern for people living near wind farms due to the nuisance and health problems caused by noise emissions. Therefore, noise estimation is one of the most relevant aspects of wind turbine design. Aerodynamic noise can be caused by air motion around the turbine blades. This can create a swooshing or whooshing sound as the blades pass through the air. Aerodynamic noise tends to be more prominent at higher wind speeds when the turbine is operating at full capacity. The trailing edge noise is the main source of wind turbine aerodynamic noise. In this work, semi-analytical solutions for modeling this effect are used. The Ffowcs Williams and Hawkings (FW-H) acoustic analogy is used to predict far-field noise generated by wind turbine blades moving in the air. The equations of the rotor–tower–nacelle structure are obtained by the classical finite element method for a typical onshore wind turbine to predict the blade vibration signal. This new formulation is applied to rotating sources and statistical analysis of broadband trailing edge noise. The novelty of this work is to model the acoustic–structure interaction between the wind flow and the blade structure vibration. In this context, the acoustic far-field pressure emissions are modified by source vibration. In this point, this work compares the acoustic pressure values from rigid and flexible sources. Once the relationship between acoustic emission and wind turbine structural vibration is determined, the potential application of this research is, for example, to provide valuable information about the health and integrity of the blades. Thus, the goal of this work is to predict the aerodynamic noise of a typical large wind turbine taking into account its structural behavior. Therefore, Formulation 1A is used to calculate the far-field noise radiated from the trailing edge of wind turbine blades in a low Mach number flow. The vibration effects are input variables to evaluate the intensity and acoustic pressure values. Some computational aspects are discussed and the numerical model is clarified. The acoustic predictions are validated with analytical results and experimental measurements that are available in the scientific literature. The numerical results of the FW-H acoustic analogy demonstrate that the aerodynamic noise value is predominantly low frequency in the sections closest to the source.
Completion and Conditionality: A Parsimonious Analysis of IMF Programs
Authors: Bird Graham , Baldovino Harvey , Rowlands Dane
Published: October 2024

A feature of IMF programs is the relatively large proportion that are not carried through to completion. One explanation is that excessive conditionality undermines ownership and commitment to IMF-favored policy reform. The IMF’s “streamlining” initiative in the early 2000s was intended to limit conditionality and thereby improve the completion rate. This paper empirically investigates the relationship between conditionality and completion. For the full period, 1980–2019, it discovers no statistically significant relationship between them at the aggregate level. It goes on to examine the ways in which this result can be interpreted and discusses the implications for reform.
Strong convergence of the empirical spectral distribution of a unified matrix model
Authors: Li Xiangchao , Han Xiao , Yang Qing
Published: October 2024

Let [Formula: see text] is a positive definite matrix and [Formula: see text] with [Formula: see text] being independent and identically distributed (i.i.d.) centered real random variables. Consider the matrix [Formula: see text] where [Formula: see text] and [Formula: see text] are two projection matrices (deterministic or random) satisfying [Formula: see text] and [Formula: see text]. Additionally, if [Formula: see text] and [Formula: see text] are random matrices, they are independent of [Formula: see text]. In this paper, we demonstrate that the empirical spectral distribution of [Formula: see text] converges almost surely to a non-random distribution when [Formula: see text] and [Formula: see text], assuming [Formula: see text] has finite second moment.
Efficient Distance Queries on Non-point Data
Authors: Michalopoulos Achilleas , Tsitsigkos Dimitrios , Bouros Panagiotis , Mamoulis Nikos , Terrovitis Manolis
Published: October 2024

Distance queries, including distance-range queries,
k
-nearest neighbors search, and distance joins, are very popular in spatial databases. However, they have been studied mainly for point data. Inspired by a recent approach on indexing non-point objects for rectangular range queries, we propose a secondary partitioning approach for space-partitioning indices, which is appropriate for distance queries. Our approach classifies the contents of each primary partition into 16 secondary partitions, taking into consideration the begin and end values of objects with respect to the spatial extent of the primary partition. Based on this, we define algorithms for three popular spatial query types, that avoid duplicate results and skip unnecessary computations. We compare our approach to the previous secondary partitioning method and to state-of-the-art data-partitioning indexing and find that it has a significant performance advantage.