bluuebunny/crossref_metadata_2025 huggingface dataset:
A multicenter prospective validation study of the 3-cm cut-off in stage I seminoma (S3MI-PT).
Authors: Fontes-Sousa Mario , Magalhães Helena , Leão Ricardo , Mansinho André , Malheiro Mariana , Rosinha Alina , Carrolo Margarida , Borralho Paula , Mauricio Joaquina , Brito Margarida , Passos-Coelho Jose Luis C. , Quintela Antonio
Published: March 2023

TPS435

Background: Testicular germ cell tumors (TGCT) are the most common solid malignancy in men aged 15 to 35, and Seminoma histology can account for up to half of the cases. Since the latest edition of the American Joint Committee on Cancer (AJCC) staging manual (8th edition, 2018), it is recommended that, only in pure Seminoma, the pT1 category should be subdivided according to tumor size: pT1a for tumors < 3 cm or T1b for tumors ≥ 3 cm. This change was based on large retrospective data that suggested almost a doubling of the risk of relapse at 3-years in pT1b versus pT1a, with a Hazard Ratio of 1.87, 95% confidence interval (CI) 1.15-3.06. So far, there has been no prospective validation for these staging changes and there are no known implications of its use in clinical practice. Furthermore, these changes are exclusive for AJCC since the Union for International Cancer Control (UICC), another widely used staging system, did not change from previous editions (i.e., no pT1 subdivision in pure Seminoma). Tumor size was already recognized as a risk factor for relapse (if tumor size > 4 cm) but not formally used for staging before. Of concern, these are mostly young patients, and despite exceptionally good long-term survival rates, in stage I Seminoma, the general estimation of relapse is about 15% but can surpass 30% — therefore accurate prognostic information is particularly important. This study aims to validate the 3 cm cut-off in stage I Seminoma introduced by AJCC 8th edition. Additionally, the study will allow for the evaluation for current trends of adjuvant options (namely surveillance vs active treatment). Methods: S3MI-PT, or Seminoma 3 cm cut-off Prospective Trial, is a multicenter prospective observational validation study that aims to include at least 300 patients (the estimate includes a 10% loss to follow-up rate as TGCT studies are historically difficult to accrue). Eligibility criteria: male patients ≥ 18 years old diagnosed with clinical stage I pure Seminoma histology (pT1N0M0S0), whose orchiectomy must have occurred after January 2018, the AJCC 8th ed. implementation date, who are willing to sign the informed consent. Demographic and clinical data will be collected, that includes, age at diagnosis, tumor size, rete testis invasion, values for TGCT markers, adjuvant treatment options (surveillance or active treatment) and relapse, if applicable. Exclusion criteria: non-pure Seminoma TGCT staged pT2-T4, pN1-N3, M1, S1-3. Primary endpoint is relapse-free survival at 3 years in pT1a versus pT1b, with two-sided P < 0.05 used to determine statistical significance with a 95% CI, by Kaplan-Meier method. S3MI-PT has been approved by the Ethics Committee. The study is actively enrolling, and all individuals and institutions interested in collaborating can do so by request.
A phase II study of risk-based stratification after chemotherapy combined with PD-1 antibody: Two various bladder-sparing modalities for muscle invasive bladder cancer therapy (ReBirth).
Authors: Shen Yijun , Lu Xiaolin , Ma Xuejun , Liu Wei , Ye Dingwei
Published: March 2023

TPS580

Background: Neoadjuvant chemotherapy plus radical cystectomy is the standard for cisplatin-eligible patients with cT2-4aN0M0 muscle invasive bladder cancer, however, some of them desperately need innate bladder. Developments in the last two decades suggest that well-documented Trimodal therapy(TMT) demonstrated durable oncologic control and long-term survival in selected patients. Nevertheless, personalized treatment based on responses of systematic treatment and biomarker are currently lacking. Additionally, concerning a balance between non-inferiority of hypofractionated radiation therapy in local control and late toxicity, the specified dose regimen combined with immunotherapy is worth exploring. "ReBirth" study was designed to evaluate the efficacy and tolerability of two various bladder-sparing modalities with risk-based stratification after chemotherapy combined with PD-1 antibody. Methods: This is a single-arm, phase II trial that includes cT2-4aN0-1M0 patients who aged 18-85 years and histologically confirmed bladder urothelial carcinoma. Other key inclusion criteria: no prior anti PD-(L)1 therapy; ECOG 0-2 and cisplatin eligible. The trial consists of two stages. In the first stage, eligible patients will receive tislelizumab 200 mg in day 1 (D1), cisplatin 70 mg/m2 D1, and gemcitabine 1000 mg/m2 D1 and D8 every 21 days for four cycles. Patients will then be divided into two cohorts in the second stage based on the cystoscopy, urine cytology, and imaging combined with utDNA (urine tumor DNA). Patients who achieve clinical complete response (cT0, cTa) will enter into cohort 1 and treated with tislelizumab 200 mg IV Q3 for up to 6 months, while patients who did not achieve clinical complete response will enter into cohort 2 and treated with tislelizumab 200 mg IV Q3W for up to 6 months and chemoradiotherapy for whole bladder 44Gy/16 fractionation, if lymph node is positive, it can be dosed to the maximum tolerable dose, such as tumor boost 11Gy/4fractionation, combined with DDP as radiosensitizer. The primary endpoint is BIDFS (bladder intact disease-free survival) at one year, which is defined as time from initiation of protocol therapy until the development of muscle-invasive bladder cancer recurrence, regional pelvic recurrence, distant metastases, bladder cancer-related death, or cystectomy. Secondary endpoints include metastatic free survival rate at two years, BIDFS at two years and safety graded according to CTCAE V5.0. Tissue samples will be collected for genomic profiling and utDNA will be collected and examined for biomarker exploring in this bladder preservation therapy. Till Sep.2022, 5 of planned 30 patients have been enrolled. Clinical trial information: NCT05531123 .
Phase 3 KEYNOTE-905/EV-303: Perioperative pembrolizumab (pembro) or pembro + enfortumab vedotin (EV) for muscle-invasive bladder cancer (MIBC).
Authors: Necchi Andrea , Bedke Jens , Galsky Matt D. , Shore Neal D. , Plimack Elizabeth R. , Xylinas Evanguelos , Jia Calvin , Hennika Tammy , Homet Moreno Blanca , Witjes Alfred Alfred
Published: March 2023

TPS585

Background: Standard of care for MIBC is neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy + pelvic lymph node dissection (RC + PLND). However, a substantial proportion of patients (pts) with MIBC are ineligible to receive cisplatin-based chemotherapy. In the phase 1b/2 KEYNOTE-869/EV-103 study, promising antitumor activity was shown in cisplatin-ineligible pts with metastatic urothelial carcinoma treated with the PD-1 inhibitor pembro combined with the nectin-4–directed antibody-drug conjugate EV. This multicenter, open-label, randomized, phase 3 KEYNOTE-905/EV-303 study (NCT03924895) is designed to evaluate the efficacy and safety of perioperative pembro alone or in combination with EV compared with RC + PLND alone in pts with MIBC who are ineligible for or decline cisplatin-based treatment. Methods: Approximately 857 adults who are cisplatin ineligible or decline cisplatin-based treatment with treatment-naive MIBC (T2-T4aN0M0 or T1-T4aN1M0), have an Eastern Cooperative Oncology Group performance status score of 0-2, and have a predominant (≥50%) urothelial histology will be randomly assigned to arm A (neoadjuvant pembro 200 mg intravenously [IV] every 3 weeks [Q3W] up to 3 cycles followed by RC + PLND and adjuvant pembro 200 mg IV Q3W up to 14 cycles), arm B (RC + PLND followed by observation), or arm C (neoadjuvant EV 1.25 mg/kg + pembro 200 mg IV Q3W up to 3 cycles followed by RC + PLND and adjuvant EV + pembro up to 6 cycles and adjuvant pembro 200 mg IV Q3W up to 8 cycles). In both the neoadjuvant and adjuvant phases of arm C, pembro will be administered on day 1 and EV will be administered on days 1 and 8 of each cycle. Dual primary end points are pathologic complete response as assessed by central pathologic review and event-free survival. Secondary end points include overall survival, disease-free survival, pathologic downstaging rates, and safety and tolerability. Enrollment is ongoing in Africa, Asia, Europe, and North America. Clinical trial information: NCT03924895 .
First in human (FIH) phase 1/1b study evaluating KIN-3248, a next-generation, irreversible pan-FGFR inhibitor (FGFRi), in patients (pts) with advanced urothelial carcinoma (UC) and other solid tumors harboring FGFR2 and/or FGFR3 gene alterations.
Authors: Garmezy Benjamin , Perez Cesar Augusto , Kato Shumei , Sharma Manish , Quah Cheng Seok , Tam Betty , Severson Paul
Published: March 2023

TPS593

Background: FGFR1-4 gene alterations are infrequent across solid tumors though preclinical and clinical evidence indicate activating alterations drive oncogenesis and tumor growth. They can be found in up to 20% of patients with UC and up to 35% of upper tract UC. Reversible FGFRi are approved for the treatment of pts with locally advanced or metastatic urothelial carcinoma (UC) with susceptible FGFR2 or FGFR3 genetic alterations (erdafitinib) or metastatic CCA harboring FGFR2 gene fusions or rearrangements (pemigatinib and infigratinib). A critical limitation of current clinical-stage FGFRi is the emergence of secondary, on-target resistance mutations (mutn) that reduce duration of response, and indeed, about 70% of CCA patients pre-treated with FGFRi exhibit secondary FGFR2 kinase domain resistance mutn at the time of relapse. KIN-3248 is a next-generation, selective, irreversible, small molecule pan-FGFRi, structurally designed to inhibit primary FGFR oncogenic alterations as well as secondary kinase domain mutn associated with disease progression. Preclinically, KIN-3248 has favorable pharmaceutical properties, is well-tolerated with continuous, daily oral administration in GLP toxicology studies and is efficacious against primary FGFR2 and FGFR3 oncogenic driver alterations as well as secondary FGFR2 resistance mutn (e.g., gatekeeper and molecular brake) in human cancer cell and PDX models. Methods: This is a FIH, multicenter, non-randomized Ph1 study of KIN-3248 in adult pts with advanced and metastatic solid tumors (AMST) harboring FGFR2 and/or FGFR3 gene alterations. KIN-3248 is given PO QD continuously in 28-day cycles until drug intolerance or disease progression. Part A is a dose-escalation assessing single agent KIN-3248 via a BOIN design to determine the MTD/RP2D. Part B will evaluate a selected dose of KIN-3248 in 3 cohorts of pts (UC, CCA, or other AMST), each driven by specified FGFR alterations—FGFRi-naïve and -pretreated pts are eligible in both parts. Enrollment criteria include ECOG PS 0-1, intact organ function, prior receipt of standard treatment or medical judgment that such is not appropriate. Pts may have measurable or evaluable disease. Key exclusion criteria include known active brain metastases and active/uncontrolled HBV/HCV. Planned sample size is ~120 pts. Primary endpoints are safety/tolerability (Part A), and preliminary antitumor activity: objective response rate, disease control rate, duration of response, & duration of stable disease (Part B). Secondary objectives include pharmacokinetic and pharmacodynamic assessments including measures of FGFR pathway modulation. The study is actively enrolling patients in the US and globally. Clinical trial information: NCT05242822 .
Neutralizing GDF-15 in muscle-invasive bladder cancer (MIBC): A neoadjuvant immunotherapy trial of visugromab (CTL-002) in combination with the anti-PD1 antibody nivolumab (NEO-GDFATHER).
Authors: Necchi Andrea , Iacovelli Roberto , Di Maio Massimo , Gontero Paolo , Fettes Petra , Klar Kathrin , Hermann Frank , Leo Eugen
Published: March 2023

TPS595

Background: Neoadjuvant chemotherapy (NACT) is a well-established treatment modality in MIBC but suffers from limited activity and significant toxicity. Recently, neoadjuvant immunotherapy (I/O) has demonstrated clinical safety and efficacy in various solid tumor indications including MIBC, with potentially less toxicity. Results from previous studies of single-agent I/O indicated a proportion of pathologic complete responses (ypT0N0) similar to that reported with NACT. Therefore, improving ypT0N0 responses remains a major task for successful treatment of MIBC in the future. Increasing evidence has emerged that Growth and Differentiation Factor 15 (GDF-15) plays a critical local immunosuppressive. Apart from blocking immune-cell entry into tissues GDF-15 also has major impact on the formation of the immune synapse. Many tumors overexpress GDF-15 and have hijacked this mechanism to block I/O therapy success. Various translational research efforts have indicated that GDF-15 may play a significant role for immunosuppression and T-cell exclusion in urothelial carcinoma (UC). Visugromab (CTL-002) is a GDF-15 neutralizing IgG4 monoclonal antibody that has demonstrated in Phase 1 a favorable safety profile and promising clinical activity with durable and deep responses in PD-1/PD-L1 relapsed/refractory metastatic solid tumors in combination with the anti-PD1 antibody Nivolumab (Nivo)*. This clinical trial is intended to investigate the combination of Visugromab with Nivo vs. Nivo monotherapy as neoadjuvant therapy for MIBC in patients (pts) who are ineligible for or elect not to undergo NACT. Primary endpoints are the complete pathologic response rate and radiologic response. Methods: This is a multi-center, parallel-cohorts and single-blinded Phase 2 study of neoadjuvant therapy in pts planned for radical cystectomy (RC). A total number of 30 subjects with stage T2-T4N0M0 MIBC will be enrolled and assigned 1:1 to receive either Nivo + Visugromab or Nivo + Placebo after stratification for CPS PD-L1 expression and cT-stage. No statistical assumptions have been undertaken at this stage. Treatment consists of three 4-week cycles [i.v., Q4Wk], and RC is planned 4-8 weeks after last dose of study drug. After RC, pts will follow standard recommendations according to EAU guidelines. Primary endpoints are the proportion of ypT0N0 response and radiologic response rate. Secondary endpoints comprise additional efficacy parameter, surgical and medical safety, PK and PD assessments. Translational research includes evaluation of immunologic parameters in the tumor, other immune-correlates and molecular profiles, as well as evaluation of treatment-emergent cytokine and chemokine profiles in peripheral blood. * Melero et al., Annals of Oncology (2022) 33 (suppl_7): S331-S355.
A phase 1, open-label trial to evaluate feasibility and safety of intramural injection of belzupacap sarotalocan (AU-011) in non-muscle–invasive bladder cancer (NMIBC).
Authors: Lerner Seth P. , Bivalacqua Trinity , Kim Isaac Yi , Murray Carrie , Rich Cadmus Collins , Agarwal Piyush K. , Shore Neal D.
Published: March 2023

TPS596

Background: A high unmet medical need exists for new therapies in NMIBC to reduce common risks of recurrence, progression and, ultimately, cystectomy. Belzupacap sarotalocan, a novel investigational virus-like drug conjugate (VDC), has a dual mechanism of action designed to provide 1) selective binding to malignant cells, causing acute necrosis upon light activation, and 2) long-term anti-tumor immunity as demonstrated in pre-clinical models. This Phase 1 trial is designed to evaluate the feasibility and safety of intramural injection with or without intratumoral injection of belzupacap sarotalocan for treatment of NMIBC. The hypothesis is that after near infrared light activation, targeted distribution of belzupacap sarotalocan at high concentrations at the tumor base could necrose the tumor where it is most likely to be invasive. In turn, the tumor targeted pro-immunogenic cell death could potentially lead to an anti-tumor immune response preventing the risk for recurrence, progression and metastasis. Methods: This is an actively enrolling “window of opportunity” trial (NCT05483868) in low, medium or high risk NMIBC subjects scheduled to undergo TURBT or cystectomy per standard of care. A pre-treatment biopsy will be performed in up to 23 adult subjects enrolled in 4 cohorts, who will be given belzupacap sarotalocan +/- laser as shown in the table. The primary endpoint is incidence and severity of treatment-related adverse events, serious adverse events regardless of attribution, and incidence of dose-limiting toxicities. Each cohort will have a safety review for the injection procedure and laser (as needed), after 3 subjects have been treated and followed for 28 days. Secondary endpoints are based on histopathology and include assessment of local biodistribution of belzupacap sarotalocan measured via immunohistochemical staining, tumor necrosis, and evidence of an immune response via comparison of pre-treatment biopsy to TURBT/cystectomy samples after treatment. Statistical analysis plan includes descriptive statistics for the above endpoints. Clinical trial information: NCT05483868 . [Table: see text]
Phase 2, multicenter, open-label basket trial of nab-sirolimus for patients with malignant solid tumors harboring pathogenic inactivating alterations in TSC1 or TSC2 genes (PRECISION I).
Authors: Iyer Gopa , Demeure Michael J. , Deming Dustin A. , Federman Noah , McKean Meredith , Lee Elizabeth Katherine , Spira Alexander I. , Kwiatkowski David J. , Hussein Maen A. , Gordon Erlinda Maria , Crockett David G. , Ganjoo Kristen N. , Schulte Brian , Cranmer Lee D. , Schmid Anita N. , Navarro Willis H. , Itri Loretta Marie
Published: March 2023

TPS597

Background: Albumin-bound ( nab)-sirolimus, a novel mTOR inhibitor (mTORi) that utilizes nanoparticle technology to preferentially target tumors, is approved in the US for the treatment of adults with malignant PEComa. In an exploratory analysis of the AMPECT registrational trial of nab-sirolimus in advanced malignant PEComa (NCT02494570), 8/9 (89%) and 1/5 (20%) patients with TSC1 and TSC2 inactivating alterations, respectively, had confirmed response (Wagner, J Clin Oncol. 2021). Importantly, both TSC1 and TSC2 alterations have been observed in patients with various gastrointestinal cancers (Table). Overall, most treatment-related adverse events (TRAEs) in AMPECT were grade 1/2 and manageable for long-term treatment; no grade ≥4 TRAEs occurred. Methods: PRECISION I (NCT05103358) is a phase 2, open-label, multi-institutional basket trial evaluating efficacy and safety of nab-sirolimus in patients with alterations in TSC1 (Arm A) and TSC2 (Arm B). Patients ≥12 years old with malignant solid tumors harboring pathogenic inactivating alterations in TSC1 or TSC2 (confirmed by central review of next-generation sequencing reports) who have progressed on standard therapies and are mTORi-naïve are eligible. nab-Sirolimus 100 mg/m2 will be administered weekly as an intravenous infusion over 30 minutes on Days 1 and 8 of each 21-day cycle. The primary endpoint is overall response rate determined by independent review using RECIST v1.1; other endpoints include duration of response, disease control rate, time to response progression-free survival by independent radiographic review, overall survival, patient-reported quality of life, and safety. Enrollment is ongoing. The most frequent tumor types expected in this tissue-agnostic trial are bladder, hepatobiliary, endometrial, soft tissue sarcoma, ovarian, and esophagogastric based on the prevalence of TSC1 or TSC2 alterations (Table). Clinical trial information: NCT05103358 . [Table: see text]
Spin and angular momentum in quaternionic quantum mechanics
Authors: Giardino Sergio
Published: March 2023

We present two novel solutions of real Hilbert state quaternionic quantum mechanics

. Firstly, we observe that the angular momentum operator admits two different classes of physically non-equivalent free particles. As a second result, we study the Larmor precession to observe that it has a quaternionic solution where a novel phenomenological interpretation is possible, as well as a different spin is possible, and these results may encourage experimental and theoretical investigations of the quaternionic theory.
Το κοιμητήριο στον χώρο και στον χρόνο
Authors: Πολυμενίδης Ιωάννης
Published: March 2023

Το κοιμητήριο ήταν πάντα ένας «ζωντανός» χώρος της πόλης και συμμετείχε ενεργά στην αστική ζωή. Ωστόσο η στάση του δυτικού κόσμου απέναντι στο θάνατο, επηρέασε και συνεχίζει να επηρεάζει την αντίληψη του τοπίου και της θέσης του κοιμητηρίου. Το αντικείμενο της διατριβής είναι η θεώρηση των χώρων ταφής και γενικότερα διαχείρισης νεκρών, από χωρική, πολιτισμική, ανθρωπολογική, ιστορική, οικονομική, πολιτική σκοπιά και η διαχρονική επιρροή αυτής της πολυποίκιλης θεώρησης στην χωρική τους διάσταση και στην σχέση τους με τον περιβάλλοντα χώρο, αστικό και εξωαστικό.Σήμερα, η στάση της κοινωνίας απέναντι στο θάνατο έχει μετατρέψει τους χώρους ταφής, από πολυδιάστατους αστικούς χώρους, σε λησμονημένα τοπία κατ' ανάγκη αποδεκτά και υποβαθμισμένο ως προς τις πολιτιστικές αξίες της σύγχρονης αστικής ζωής. Οι μελετητές του χώρου, θεωρώντας το κοιμητήριο ως «ιερό», αλλά και απαγορευμένο χώρο το αντιμετωπίζουν ως μια λειτουργία σε συγκρουσιακή σχέση γης σε σχέση με τις άλλες και κυρίως με την κατοικία και προσπαθούν να την απομακρύνουν και να την απομονώνουν, συνεπικουρούμενοι από το ισχύον θεσμικό πλαίσιο.Η παρούσα διατριβή, μέσα από την ευρεία βιβλιογραφική έρευνα που καλύπτει το χρονικό διάστημα από την αρχαιότητα μέχρι σήμερα και χωρίζεται σε τέσσερις χρονικές περιόδους, αναλύει και αξιολογεί τα θετικά και αρνητικά στοιχεία της ιστορικής πορείας του κοιμητηρίου και απαντά στις σημερινές προκλήσεις μέσω της σύνταξης συγκεκριμένης πρότασης για την «δεύτερη» επιστροφή του στον σημερινό αστικό ιστό, μετά την πρώτη του 6ου αιώνα μ.Χ.. Η πρωτοτυπία της διατριβής έγκειται στην αναλυτική κάλυψη όλων των διαστάσεων χωρικής ταυτότητας και λειτουργίας του χώρου διαχείρισης νεκρών, στην διερεύνηση των μεταξύ τους σχέσεων και επιρροών, στην διαμόρφωση πλαισίου κανόνων και προϋποθέσεων χωροθέτησης αυτής της αμφιλεγόμενης χρήσης γης στον αστικό χώρο, σε συνδυασμό με κατευθύνσεις αναθεώρησης του ισχύοντος θεσμικού πλαισίου.
DE LA ENSEÑANZA A LA EVALUACIÓN DE LENGUAS CON LA AYUDA DE RECURSOS TECNOLÓGICOS: LOS ESTUDIANTES DE EDUCACIÓN SUPERIOR Y LA PRODUCCIÓN ORAL.
Authors: Senra Silva Inmaculada
Published: March 2023

En este artículo se presentan los resultados de un estudio realizado con el fin de evaluar las habilidades de producción oral de estudiantes de educación a distancia matriculados en una carrera universitaria, así como su experiencia con los recursos digitales para producir las tareas de evaluación. La práctica de comunicación oral en una lengua extranjera así como la evaluación de las habilidades de producción oral suponen un reto importante que a menudo encuentra dificultades metodológicas y tecnológicas en los entornos tradicionales de aprendizaje presencial, pero particularmente en los de aprendizaje a distancia. Tras analizar las necesidades y peculiaridades de los estudiantes provenientes de un contexto de educación a distancia, se ha llevado a cabo una investigación para probar y proponer una actividad donde los estudiantes individualmente diseñan y producen un video en el que explican un tema de su elección como tarea de evaluación continua. Seguidamente reciben la retroalimentación del docente a través de una rúbrica que les permite mejorar su aprendizaje al mismo tiempo que permite a los profesores obtener información valiosa sobre su progreso en cuanto a habilidades productivas orales se refiere. Los resultados del estudio muestran cómo los estudiantes pueden mejorar sus habilidades de producción oral con el autoaprendizaje y cómo la preparación de esta actividad de evaluación tiene un efecto positivo en su dominio global del idioma, así como en su competencia digital.
Osteoporosis: prevention and management
Authors: Walker Jennie
Published: March 2023

Osteoporosis is a common skeletal condition that is characterised by low bone mass, increased bone fragility and an increased risk of fracture. It is important to understand who may be at risk of developing osteoporosis and sustaining fragility fractures so that appropriate steps can be taken to minimise any modifiable risk factors. Simple lifestyle changes, such as increasing physical activity, stopping smoking and ensuring adequate nutritional intake, can improve musculoskeletal health and reduce fracture risk.
Employees' rights when businesses transfer
Authors: Bernstein Adam
Published: March 2023

Adam Bernstein discusses the rights of employees when a business is bought, sold or transferred and what rules the employer must observe.
Challenges facing social care and the impact on the NHS in Wales
Authors: Hughes Darren
Published: March 2023

With pressures across the health and care system being higher than ever before, leaders are examining what can be done to alleviate them – including improving patient flow. The Welsh NHS Confederation, the national membership body representing all the organisations that make up the NHS in Wales, surveyed 52 NHS leaders to examine the impact that the challenges facing social care is having on the NHS and, ultimately, on patients. The survey also explored leaders' views on the most effective way to move forward and ease system-wide pressures. The challenges in social care are longstanding and require immediate and sustained government action to support better integration. Steps are being taken to alleviate pressures, but these are not having a great enough impact to make a meaningful difference to patient flow, patient outcomes and wider system pressures at scale. Without an increase in long-term investment in social care from governments across the UK, the most vulnerable members of society will continue to experience worse outcomes.
Bracken and horsetail poisoning
Authors: Bates Nicola
Published: March 2023

Bracken (Pteridium spp.) and horsetail (Equisetum spp.) are ancient plants that contain thiaminase. Chronic grazing by monogastric animals, such as horses, results in an induced deficiency of thiamine (vitamin B1). This manifests as ataxia, lack of co-ordination (‘bracken staggers’), loss of condition and stumbling. As the disease progresses, there is weakness, inability to stand, muscle tremors, coma and convulsions. In addition, haemolytic anaemia and haemoglobinuria may occur. Diagnosis of bracken or horsetail toxicosis is based on clinical signs and history of exposure. Post-mortem findings are generally non-specific. Treatment is supportive with prompt removal of the plants, and provision of good quality forage and nursing care. Supplementation with thiamine can be effective. Prevention of poisoning involves ensuring adequate forage is available, and preventing access to the plants. Clearing the bracken or horsetail can be difficult and in the case of bracken, specialist advice should be sought.
Identification of protective and ‘at risk’ HLA genotypes for the development of pseudotumours around metal-on-metal hip resurfacings
Authors: Sheridan Gerard A. , Hanlon Michael , Welch-Phillips Adanna , Spratt Karen , Hagan Richard , O'Byrne John M. , Kenny Patrick J. , Kurmis Andrew P. , Masri Bassam A. , Garbuz Donald S. , Hurson Conor J.
Published: March 2023

Aims

Hip resurfacing remains a potentially valuable surgical procedure for appropriately-selected patients with optimised implant choices. However, concern regarding high early failure rates continues to undermine confidence in use. A large contributor to failure is adverse local tissue reactions around metal-on-metal (MoM) bearing surfaces. Such phenomena have been well-explored around MoM total hip arthroplasties, but comparable data in equivalent hip resurfacing procedures is lacking. In order to define genetic predisposition, we performed a case-control study investigating the role of human leucocyte antigen (HLA) genotype in the development of pseudotumours around MoM hip resurfacings.

Methods

A matched case-control study was performed using the prospectively-collected database at the host institution. In all, 16 MoM hip resurfacing 'cases' were identified as having symptomatic periprosthetic pseudotumours on preoperative metal artefact reduction sequence (MARS) MRI, and were subsequently histologically confirmed as high-grade aseptic lymphocyte-dominated vasculitis-associated lesions (ALVALs) at revision surgery. ‘Controls’ were matched by implant type in the absence of evidence of pseudotumour. Blood samples from all cases and controls were collected prospectively for high resolution genetic a nalysis targeting 11 separate HLA loci. Statistical significance was set at 0.10 a priori to determine the association between HLA genotype and pseudotumour formation, given the small sample size.

Results

Using a previously-reported ALVAL classification, the majority of pseudotumour-positive caseswere found to have intermediate-grade group 2 (n = 10; 63%) or group 3 (n = 4; 25%) histological findings. Two further patients (13%) had high-grade group 4 lesions. HLA-DQB1*05:03:01 (p = 0.0676) and HLA-DRB1*14:54:01 (p = 0.0676) alleles were significantly associated with a higher risk of pseudotumour formation, while HLA-DQA1*03:01:01 (p = 0.0240), HLA-DRB1*04:04:01 (p = 0.0453), HLA-C*01:02:01 (p = 0.0453), and HLA-B*27:05:02 (p = 0.0855) were noted to confer risk reduction.

Conclusion

These findings confirm the association between specific HLA genotypes and the risk of pseudotumour development around MoM hip resurfacings. Specifically, the two ‘at risk’ alleles (DQB1*05:03:01 and DRB1*14:54:01) may hold clinical value in preoperative screening and prospective surgical decision-making.

Cite this article: Bone Jt Open 2023;4(3):182–187.
Impact of adverse events during community-wide mass drug administration for soil-transmitted helminths on subsequent participation–a Theory of Planned Behaviour analysis
Authors: Aruldas Kumudha , Israel Gideon John , Johnson Jabaselvi , Titus Angelin , Saxena Malvika , Kaliappan Saravanakumar Puthupalayam , Ramesh Rohan Michael , Walson Judd L. , Means Arianna Rubin , Ajjampur Sitara S. R.
Published: March 2023

Background

Experiencing adverse events (AEs) during mass drug administration (MDA) could affect participation in future MDAs. This study aims to understand the potential influence of AEs during a community-wide MDA (cMDA) trial for soil-transmitted helminths (STH) in India on intention to participate in future cMDAs.

Methods

This study was conducted using a multi-method quantitative and qualitative approach among 74 participants who experienced an AE during STH cMDA and the 12 participants who subsequently refused cMDA treatment of the ongoing DeWorm3 trial. Path analysis and thematic analysis guided by the Theory of Planned Behaviour, was used.

Principal findings

Among 74 individuals who reported an AE, 12% refused treatment in the cMDA immediately subsequent to their AE and 4% refused in all subsequent cMDAs. Of these 74 individuals, 59 (80%) completed a survey and eight participated in in-depth interviews. A positive attitude towards deworming and perceived ability to participate in cMDA (perceived behavioural control) were significant predictors of intention to participate in cMDA (p<0.05). A positive attitude towards cMDA was associated with caste (χ2 = 3.83, P = 0.05), particularly among the scheduled caste/scheduled tribe (SC/ST) (62%). Perceived behavioural control in cMDA participation was associated with occupation (χ2 = 5.02, P<0.05), with higher perceived control among those engaged in skilled occupations (78%). Intention to participate in subsequent cMDAs was associated with caste and family type (χ2 = 3.83, P = 0.05 and χ2 = 7.50, P<0.05 respectively) and was higher among SC/ST (62%) and those with extended families (67%). In-depth interviews demonstrated that perceived severe AEs may lead to treatment refusal in future, particularly if children were affected.

Conclusions

Intention to participate in future STH cMDAs was associated with caste (SC/ST) and family type (extended families). Therefore, community mobilization messages about potential AEs and their management may need to intentionally target non-SC/ST households, nuclear families, and those engaged in unskilled occupations to increase cMDA participation given the possibility of AEs occurring.

Trial registration

NCT03014167, ClinicalTrials.gov.
Design and implementation of a global site assessment survey among HIV clinics participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) research consortium
Authors: Brazier Ellen , Maruri Fernanda , Wester C. William , Musick Beverly , Freeman Aimee , Parcesepe Angela , Hossmann Stefanie , Christ Benedikt , Kimmel April , Humphrey John , Freeman Esther , Enane Leslie A. , Lancaster Kathryn E. , Ballif Marie , Golub Jonathan E. , Nash Denis , Duda Stephany N. ,   on behalf of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium
Published: March 2023

Introduction

Timely descriptions of HIV service characteristics and their evolution over time across diverse settings are important for monitoring the scale-up of evidence-based program strategies, understanding the implementation landscape, and examining service delivery factors that influence HIV care outcomes.

Methods

The International epidemiology Databases to Evaluate AIDS (IeDEA) consortium undertakes periodic cross-sectional surveys on service availability and care at participating HIV treatment sites to characterize trends and inform the scientific agenda for HIV care and implementation science communities. IeDEA’s 2020 general site assessment survey was developed through a consultative, 18-month process that engaged diverse researchers in identifying content from previous surveys that should be retained for longitudinal analyses and in developing expanded and new content to address gaps in the literature. An iterative review process was undertaken to standardize the format of new survey questions and align them with best practices in survey design and measurement and lessons learned through prior IeDEA site assessment surveys.

Results

The survey questionnaire developed through this process included eight content domains covered in prior surveys (patient population, staffing and community linkages, HIV testing and diagnosis, new patient care, treatment monitoring and retention, routine HIV care and screening, pharmacy, record-keeping and patient tracing), along with expanded content related to antiretroviral therapy (differentiated service delivery and roll-out of dolutegravir-based regimens); mental health and substance use disorders; care for pregnant/postpartum women and HIV-exposed infants; tuberculosis preventive therapy; and pediatric/adolescent tuberculosis care; and new content related to Kaposi’s sarcoma diagnostics, the impact of COVID-19 on service delivery, and structural barriers to HIV care. The survey was distributed to 238 HIV treatment sites in late 2020, with a 95% response rate.

Conclusion

IeDEA’s approach for site survey development has broad relevance for HIV research networks and other priority health conditions.
The archaeological potential of the northern Luangwa Valley, Zambia: The Luwumbu basin
Authors: Burke A. , Bisson M. , Schilt F. , Tolan S. , Museba J. , Drapeau M. S. M. , Aleman J. C. , Peros M. C.
Published: March 2023

The Luangwa Basin, Zambia, which forms part of the Zambezi drainage, is strategically located between the Central African plateau and the East African Rift system. The Luangwa River and major tributaries, such as the Luwumbu River, are perennial water sources supporting essential resources that sustain human communities and a rich and diverse fauna and flora. The archaeological record of Luangwa is relatively unknown, despite early archaeological exploration hinting at its potential. Recent research in the southern Luangwa valley, however, suggests that it preserves a long record of hominin occupation spanning the Early to Late Stone Age. The research described here details fieldwork carried out in northeastern Luangwa, in the Luwumbu Basin, that confirms that a relatively deep package of Quaternary deposits, containing evidence of the Stone Age occupation of the region persists in the upper piedmont zone.
Prevalence and associated factors of insomnia symptoms during the COVID-19 pandemic lockdown among Mettu town residents
Authors: Lelisho Mesfin Esayas , Wotale Teramaj Wongel , Tareke Seid Ali
Published: March 2023

Background

Insomnia is a prevalent sleep disorder that affects people all over the world. Creating suitable interventions will require a better understanding of the magnitude and determinants of insomnia. This study aimed to assess the prevalence and associated factors of insomnia symptoms among residents of Mettu town during the pandemic lockdown.

Methodology

A community-based cross-sectional study was conducted among residents of Mettu town from October 1stto October 15th, 2020. Residents who lived in Mettu town at least for six months were included. To determine the prevalence and determinants of insomnia symptoms, both descriptive and inferential analyses were used. The chi-squared test of association and logistic regression was used to identify predictors of insomnia symptoms among residents of Mettu town. We used SPSS version 25 for all statistical analyses.

Principal findings

The prevalence of depressive symptoms among residents of Mettu town was 52.6%. According to results of multivariable binary logistic regression, being female [AOR = 3.677, 95%CI: 2.124–6.365], being aged between 19 and 40 [AOR = 13.261, 95%CI: 6.953–25.291], being aged above 41 [AOR = 2.627, 95%CI: 1.120–6.159], smoking [AOR = 15.539, 95%CI: 7.961–30.329], satisfaction with information available [AOR = 0.310, 95%CI: 0.168–0.570], fear Corona Virus Disease 2019 (COVID-19), [AOR = 2.171, 95%CI: 1.262–3.733], feeling alienated from others [AOR = 3.288, 95%CI: 1.897–5.699], having somatic symptoms [AOR = 2.298, 95% CI: 1.360–3.884], having depressive symptoms [AOR = 1.841, 95% CI: 1.073–3.160], and experiencing psychological distress [AOR = 1.962, 95% CI: 1.173–3.281] were significantly associated with insomnia symptoms.

Conclusion

In this study, the prevalence of insomnia symptoms was found to be high among residents of Mettu town. Being female, being aged between 19 and 40, being aged above 41 years, smoking, fear of Corona Virus Disease 2019, feeling alienated from others, having somatic symptoms, having depressive symptoms, and experiencing psychological distress were all associated with an increased risk of developing insomnia symptoms while being satisfied with the information available decreased the risk of insomnia symptoms among residents of Mettu town. Interventions should be put in place to promote healthy sleep among residents of Mettu town.
Data quality in online human-subjects research: Comparisons between MTurk, Prolific, CloudResearch, Qualtrics, and SONA
Authors: Douglas Benjamin D. , Ewell Patrick J. , Brauer Markus
Published: March 2023

With the proliferation of online data collection in human-subjects research, concerns have been raised over the presence of inattentive survey participants and non-human respondents (bots). We compared the quality of the data collected through five commonly used platforms. Data quality was indicated by the percentage of participants who meaningfully respond to the researcher’s question (high quality) versus those who only contribute noise (low quality). We found that compared to MTurk, Qualtrics, or an undergraduate student sample (i.e., SONA), participants on Prolific and CloudResearch were more likely to pass various attention checks, provide meaningful answers, follow instructions, remember previously presented information, have a unique IP address and geolocation, and work slowly enough to be able to read all the items. We divided the samples into high- and low-quality respondents and computed the cost we paid per high-quality respondent. Prolific ($1.90) and CloudResearch ($2.00) were cheaper than MTurk ($4.36) and Qualtrics ($8.17). SONA cost $0.00, yet took the longest to collect the data.
Establishing evidence to inform culturally competent mental health services: A mixed methods study protocol
Authors: Yu Ge , Panagioti Maria , Tang Eugene Y. H. , Robinson Damian , Husain Nusrat , Lasrado Reena , Lovell Karina , Kaner Eileen , Fu Yu
Published: March 2023

Background

COVID-19 has exacerbated the significant and longstanding mental health inequalities for ethnic minorities, who were less likely to access mental health support in primary care but more likely to end up in crisis care compared to the majority ethnic group. Services were poorly offered and accessed to respond to the increased mental health challenges.

Aim

To 1) establish evidence on which changes to mental health services provided in response to COVID-19 are beneficial for ethnic minorities who experience mental health difficulties in the North of England, and 2) to inform what and how culturally competent mental health services should be routinely provided.

Methods

A mixed methods approach comprising 1) a rapid review to map services and models of care designed or adjusted for mental health during the pandemic, 2) an observational study of retrospective routine data to assess changes to mental health services and associated outcomes, 3) qualitative interviews to understand experiences of seeking care and factors associated with high-quality service provision, and 4) a Delphi study to establish consensus on key features of culturally competent services. From the selected areas in the North of England, adults from ethnic minorities who experience mental health difficulties will be identified from the primary, community and secondary care services and local ethnic minority communities.

Discussion

This study will identify ways to tackle health inequalities and contribute to mental health service recovery post pandemic by providing practice recommendations on equitable and effective services to ensure culturally competent and high-quality care. A list of services and features on what and how mental health services will be provided. Working with study collaborators and public and patient involvement partners, the study findings will be widely disseminated through presentations, conferences and publications and will inform the subsequent funding application for intervention development and evaluation.
Healthcare worker access to molnupiravir: A case series
Authors: O’Keeffe Jessica C. , Constable Meg , Chiang Janice , Somerville Margaret , Yerramilli Arvind , Nolan Ross , Weeks Greg , O’Brien Daniel P.
Published: March 2023

Molnupiravir, an oral antiviral shown to reduce COVID-19 severity, is available in Australia via the Pharmaceutical Benefits Scheme (PBS) for treatment of mild-moderate COVID-19. For people less than 70 years of age it is only available with risk factors for severe disease, hence the majority of healthcare workers do not qualify. Currently, Australian health services are under considerable strain due to COVID-related staff shortages. Thirty staff members of a tertiary hospital, not eligible under the PBS, were offered molnupiravir within the first five days of COVID-19 illness. Their median age was 43 years, and 73% were female. All completed treatment with rates of adverse events that were low and comparable with clinical trial data. The reported duration of illness ranged from 1–16 days with a median of four days. A negative rapid antigen test on the final day of treatment was reported in 81% of people, and 73% reported being well enough to return to work at the completion of mandatory isolation. Only 22% of people reported transmission in their household after they commenced treatment. The implementation of a policy allowing access to molnupiravir outside of PBS recommendations for healthcare workers with mild-moderate COVID-19 may have important individual benefits to workers health and wellbeing and help alleviate the acute staff shortages experienced currently by the Australian healthcare workforce.
Regional impact of aging population on economic development in China: Evidence from panel threshold regression (PTR)
Authors: Liang Yifan , Mazlan Nur Syazwani , Mohamed Azali Bin , Mhd Bani Nor Yasmin Binti , Liang Bufan
Published: March 2023

The aging population is a common problem faced by most countries in the world. This study uses 18 years (from 2002 to 2019) of panel data from 31 regions in China (excluding Hong Kong, Macao, and Taiwan Province), and establishes a panel threshold regression model to study the non-linear impact of the aging population on economic development. It is different from traditional research in that this paper divides 31 regions in China into three regions: Eastern, Central, and Western according to the classification standard of the National Bureau of Statistics of China and compares the different impacts of the aging population on economic development in the three regions. Although this study finds that the aging population promotes the economy of China’s eastern, central, and western regions, different threshold variables have dramatically different influences. When the sum of export and import is the threshold variable, the impact of the aging population on the eastern and the central region of China is significantly larger than that of the western region of China. However, when the unemployment rate is the threshold variable, the impact of the aging population on the western region of China is dramatically higher than the other regions’ impact. Thus, one of the contributions of this study is that if the local government wants to increase the positive impact of the aging population on the per capita GDP of China, the local governments of different regions should advocate more policies that align with their economic situation rather than always emulating policies from other regions.
The Age of AI: And Our Human Future
Authors: Balogh Attila
Published: March 2023

A mesterséges intelligencia egyre fontosabb és kiemelkedőbb szerephez jut napjainkban mind a magánéletben mind pedig a tudomány különböző szféráiban. Éppen ezért nem meglepő, hogy a történelem egyik leghíresebb diplomatájának, Henry Kissingernek, új könyve is ezzel a témával foglalkozik. Az Eric Schmidttel és Daniel Huttenlocherrel közösen írt The Age of AI: And Our Human Future magyar nyelven még nem elérhető a könyvesboltok polcain, viszont többek közt a Foreign Affairs elismerően nyilatkozik róla. A könyv közel 272 oldalon keresztül és hét fejezeten keresztül igyekszik bemutatni a mesterséges intelligencia rövid fejlődéstörténetét és jövőbeli potenciális alkalmazási lehetőségeit (ill. korlátait) az élet különböző területein.
Az online platform gazdaság kudarca
Authors: Balogh Attila
Published: March 2023

A Bruegel Intézet podcastot adott közre The dominance of platform economy címmel 2022. november 22-én (https://www.bruegel.org/podcast/dominance-platform-economy). A podcast műsorvezetője, Giuseppe Porcaro érdekes beszélgetésre invitálta meg kollegáját, Fabian Stephanyt és az Oxford Egyetem gazdaságszociológia professzorát, Vili Lehdonvirtát. A beszélgetés témája a mostanság hevesen vitatott online platform gazdaság egyik kulcselképzelésének kudarca és lehetséges megváltása volt.
Az űrszektor helyzete az Európai Unióban
Authors: Pókász Zoltán
Published: March 2023

Forrás: Europe, We Have a Problem, Rodrigo da Costa, Kris Peeters (2022), Project Syndicate Az űrkutatás egyre nagyobb szerepet képvisel a gazdasági versenyképességben és a hadászatban. Ennek ellenére az Európai Unióban bizonyos kritikus szektorokban messze lemaradva kullog az olyan (űr)nagyhatalmak mögött, mint az Egyesült Államok, Kína vagy akár Japán.