Research Institute Research Articles

Advancing inclusive research (AIR) in Africa: Strengthening healthcare systems to enhance access on the continent through the Africa AIR site alliance model.

e13778 Background: While Africa makes up 17% of the total world population, it has 24% of the global disease burden. Furthermore, although Africa is rich in genomic diversity, Africans make up <4% of the patients in global pharma studies and 1% of the global genomic database. In 2020 there were only 63 African patients in Roche global clinical trials. The Africa AIR Site Alliance model was undertaken to address the growing importance of interventional clinical trials with advanced diagnostics and therapies in Africa, as well as the lack of representation of the African population in global datasets, which contribute to continued health disparities, poor outcomes and existing inequities. Methods: In countries with a legal research framework, no clinical trial holds and who have conducted at least 1 Roche clinical trial during the last 5 years potential Centers of Excellence for the Africa AIR Site Alliance were identified. For patients, sites had invoiceable services to ensure they were supported and could potentially include education about clinical trial participation, reasonable travel and accommodation, or covering the cost of missed work or childcare. Sites participated in training on how to conduct clinical trials, including opportunities to share best practices across sites. Results: Four pilot countries were selected and had Centers of Excellence identified to work as partners with Roche for global clinical trials: Morocco (Marrakech University Hospital Center), Nigeria (University College Hospital Ibadan), Kenya (University of Nairobi Institute of Tropical and Infectious Diseases) and South Africa (Limpopo Cancer Research Institute). After entering the Africa AIR Site Alliance, sites reported consistent application of standard operating procedures and manuals, trained and empowered staff, increased organization and appropriate patient support, plus knowledge and experience with industry trials. Sites are successfully participating in an increased number of global clinical trials in various therapeutic areas with 23 patients enrolled at the Africa AIR Site Alliance sites in oncology and ophthalmology studies. Conclusions: The Africa AIR Site Alliance model is a groundbreaking initiative that has the potential to revolutionize clinical research in Africa with a positive long-term impact on the African healthcare ecosystem and clinical care delivery. Limited diversity and representation in genomic, safety and efficacy data have hampered scientific and medical progress on the continent. The Africa AIR Site Alliance provides critical support, knowledge and skills for conducting clinical trials and assists in removing barriers for underrepresented patients to participate in these trials. Future work will focus on expanding to additional countries in Africa and creating a robust network of Centers of Excellence for innovative research.

Experiences of underrepresented adolescent and young adult (AYA) cancer survivors engaging in research-related activities.

10073 Background: Adolescent and young adult (AYA) cancer survivors are an age-defined cohort (15-39 years at diagnosis) confronting unique biopsychosocial needs throughout their cancer experience. Underrepresented (sexual and gender minority [SGM] and/or Black, Indigenous, and People of Color [BIPOC]) AYAs face additional challenges associated with discrimination, mistrust of providers, and culturally incongruent services. As a result, many underrepresented AYAs experience suboptimal oncological care and disparate outcomes when compared to cis-gendered heterosexual and/or white peers. This study explored the experiences of underrepresented AYA cancer survivors engaging in research-related activities. Methods: This study is part of a larger Patient Centered Outcomes Research Institute (PCORI)-funded project that is evaluating multilevel facilitators and barriers to oncological care and research for underrepresented AYA cancer survivors. With support from five academic cancer centers and five community-based organizations supporting AYAs across the US, we have assembled an intersectional community advisory panel (CAP) of 10 AYAs who identify as BIPOC and/or SGM. Together with the CAP, a semistructured interview guide was developed, and from January to February 2024, we conducted video interviews. Data were analyzed using thematic analysis of verbatim transcribed interview scripts. The CAP assisted the investigative team in the analyses and interpretation of data. Results: Of the 20 participants interviewed, roughly 70% identified as BIPOC, 40% as SGM, and 10% as both BIPOC and SGM. Participants included underrepresented AYA cancer survivors who, prior to this specific study, had or had not participated in cancer-related research. Three major themes affecting underrepresented AYAs and engagement in research-related activities were discovered, and included: 1) Layering of identities, culture, and stigma; 2) The role of trusted conduits in facilitating engagement; and 3) Beyond compensation: reasons of pursuance. Conclusions: The resultant themes illuminate multilevel facilitators and barriers to research engagement among underrepresented AYA cancer survivors. Findings will assist in guiding researchers, oncology care providers and program administrators both in academic and community settings in the design of inclusive and equitable cancer care delivery programs for underrepresented AYA cancer survivors.

The prevalence of RCTs in PARP and immune-checkpoint blockade combination trials: An appraisal of clinical evidence generation in oncology.

e23006 Background: PARP-inhibitors were developed to promote lethal genomic instability in cancers with homologous recombination repair (HRR) defects, ultimately receiving approval for patients with BRCA gene mutations. At the tumor microenvironment, DNA instability is linked to higher expression of immune activating signals such as PDL1. PDL1 is one of the primary targets for immune-checkpoint inhibitors (ICIs), receiving approval for numerous cancer types. In-vitro studies support mechanisms of possible synergy for PARP and ICIs in combination. Despite both therapy classes being available to oncologists for nearly a decade, the clinical benefit for these agents together remains unclear. Our study aims to appraise the global clinical trial landscape for trials testing combination PARP and PD1/PDL1 regimens. Methods: Search terms for all known approved or unapproved PD1/PDL1 and PARP inhibitors associated with trials registered on the National Library of Medicine’s website, clinicaltrials.gov, were included in the cohort as long as one interventional arm administered both agents. Qualitative and quantitative trial data features were collected from the Cancer Research Institute (CRI) Immuno-Oncology Intelligence Database and complemented with manually sourced information from trial registries and publications. Contribution of Effect (COE) was defined as trials with two or more arms that compare our combination regimen of interest to PARP or an ICI alone. The presence of randomization, eligibility for randomized-controlled trial (RCT) status as well as COE was determined by three reviewers separately with disagreements settled by committee decision. Results: In total, we found 188 clinical trials that enrolled 39,268 patients. A minority of 17 trials were phase I not considered as RCTs, leaving 37,827 patients across 171 trials for enrollment in phase II trials and beyond. Of these 171 trials, 80 (47 %) were single-arm studies without active comparator. Forty-nine (29%) used randomized assortment, 40 (23%) met criteria for an RCT and 33 (19%) met criteria for RCT with COE. In total, these 33 trials enrolled 14,803 patients. Of the 33, 17 (10%) enrolled patients with cancers that are approved for PARP blockade by the FDA and 11 (6%) employed genetic testing for HRR defects. Sponsorship ranged from 16 trials by industry, 6 by cooperative oncology group, 6 by academic institutions and 5 by the National Cancer Institute. Conclusions: Our study results highlight that the global clinical trial apparatus directs significant resources and patients towards trials with lower standards of evidence generation. Across sponsor types, there was a considerable number of trials that met the rigor of an RCT with COE. These findings show both promise and areas of improvement within the trial landscape to generate evidence relevant to the use of PARP and ICIs in combination.

Cardio-Oncology Awareness: A multidisciplinary survey amongst health care trainees and practicing professionals at academic institutions.

e24023 Background: The awareness of cancer therapy-related adverse cardiac effects is incited by recent literature on cardiotoxicity incidence and detection strategies. Despite availability of guidelines, cardiotoxicity monitoring and treatment are not structurally performed across institutions. Aim: Assessing knowledge of health care professionals’ cardiac complications of cancer treatments, current perspectives on cardio-oncology ultimately to determine an agenda for improvements in practice. Methods: A web-based survey (Google Forms) was adapted from that of Ottawa Hospital Research Institute’s survey, consisting of 45 questions organized into 7 sections, modified according to our local needs and circulated to cardiologists, oncologists (radiation, medical) practicing or training in a multi-disciplinary setup and academic centers. Fortnightly reminders were sent for to receive a maximum response. The survey enquired about implementing respondent’s perception of cardio-oncology, availability of cardio-oncology services at the respondent’s institution, opinions towards current practice. A descriptive statistical analysis was carried out. Results: Fifty-five professionals completed the survey, of which 12 were cardiologists, 31 radiation oncologists, and 12 medical oncologists. Majority, 31 (54.5%) were trainees and only 1.8% had some formal training in cardio-oncology while 20% respondents reported to have a formal cardio-oncology training programme. Nearly 90% understood cardio-oncology as a stream to be able to identify side-effects and refer for treatment to the cardiologists while 84% felt that timely referral would improve outcomes.72% recognized follow-up and 67.3% felt patient education to be important component. Awareness of cardio-oncology guidelines was reported by 38.2% respondents. In the setting of metastatic cancer, there was a difference in risk tolerance for cardiotoxicity with the majority accepting 1-5% risk in curative setting and 56% accepting > 5% risk of cardiotoxicity in the metastatic setting. None of the institutions reported on having a formal training programme. Limited infrastructure (54.5%) and limited interest (47.3%) were cited the most common reasons. Conclusions: This survey identified that professionals recognize cardio-oncology services to be an important component of cancer treatment. Lack of formal training and awareness about guidelines was reported. There is a felt need for collaboration between cardiologists and oncologists to improve cardiovascular outcomes of cancer patients.

Cross-Sectional Analysis of Exome Sequencing Diagnosis in Patients With Neurologic Phenotypes Facing Barriers to Clinical Testing.

Exome sequencing (ES) demonstrates a 20-50 percent diagnostic yield for patients with a suspected monogenic neurologic disease. Despite the proven efficacy in achieving a diagnosis for such patients, multiple barriers for obtaining exome sequencing remain. This study set out to assess the efficacy of ES in patients with primary neurologic phenotypes who were appropriate candidates for testing but had been unable to pursue clinical testing. A total of 297 patients were identified from the UCLA Clinical Neurogenomics Research Center Biobank, and ES was performed, including bioinformatic assessment of copy number variation and repeat expansions. Information regarding demographics, clinical indication for ES, and reason for not pursuing ES clinically were recorded. To assess diagnostic efficacy, variants were interpreted by a multidisciplinary team of clinicians, bioinformaticians, and genetic counselors in accordance with the American College of Medical Genetics and Genomics variant classification guidelines. We next examined the specific barriers to testing for these patients, including how frequently insurance-related barriers such as coverage denials and inadequate coverage of cost were obstacles to pursuing exome sequencing. The cohort primarily consisted of patients with sporadic conditions (n = 126, 42.4%) of adult-onset (n = 239, 80.5%). Cerebellar ataxia (n = 225, 75.8%) was the most common presenting neurologic phenotype. Our study found that in this population of mostly adult patients with primary neurologic phenotypes that were unable to pursue exome sequencing clinically, 47 (15.8%) had diagnostic results while an additional 24 patients (8.1%) had uncertain results. Of the 297 patients, 206 were initially recommended for clinical exome but 88 (42.7%) could not pursue ES because of insurance barriers, of whom 14 (15.9%) had diagnostic findings, representing 29.8% of all patients with diagnostic findings. In addition, the incorporation of bioinformatic repeat expansion testing was valuable, identifying a total of 8 pathogenic repeat expansions (17.0% of all diagnostic findings) including 3 of the common spinocerebellar ataxias and 2 patients with Huntington disease. These findings underscore the importance and value of clinical ES as a diagnostic tool for neurogenetic disease and highlight key barriers that prevent patients from receiving important clinical information with potential treatment and psychosocial implications for patients and family members.

The utility of HPV16 E6 as a potential biomarker for HPV-related cancers in HIV-infected men who have sex with men.

10526 Background: The burden of HPV-related cancers, including oropharyngeal and anal cancers, poses a significant challenge. Although recent advancements in screening for anal cancer have been made for HIV-infected men who have sex with men (HIV-MSM), establishing effective screening protocols for oropharyngeal cancer remains ongoing. The early oncoprotein HPV16 E6 presents as a promising biomarker for the detection of HPV-associated cancers in this population as well. We investigated the utility of HPV16 E6 in HIV-MSM. Methods: We conducted a retrospective study using an HIV cohort at the AIDS Clinical Center of the National Center for Global Health and Medicine. Participants were all HIV-MSM and included those with HPV-related cancers or precancerous lesions such as oropharyngeal cancer, anal cancer, anal high-grade squamous intraepithelial lesions (aHSIL), and anal low-grade squamous intraepithelial lesions (aLSIL). All cancers and precancerous lesions were histologically confirmed. Frozen plasma samples taken at the time of diagnosis were evaluated. Additionally, when available, samples were retrospectively analyzed up to four years pre- and post-diagnosis. These specimens were sent to the German Cancer Research Center (DKFZ, Heidelberg, Germany) for analysis of antibodies against the early oncoproteins of carcinogenic mucosal HPV types, particularly HPV16 and other high-risk HPVs. Results: One hundred thirty-seven patients living with HIV (PWH) were included in the analysis. The distribution of PWH diagnosed with oropharyngeal cancer, anal cancer, aHSIL, and aLSIL was 6, 14, 96, and 9 respectively. Regarding HPV16 E6 seropositivity, 100% of patients with oropharyngeal cancer tested positive (6/6). Seropositivity rates for anal cancer, aHSIL, and aLSIL were 28.6% (4/14), 12.5% (12/96), and 11.1% (1/9) respectively (Table). Patients with oropharyngeal cancer exhibited the highest titer of HPV16 E6. Among the six patients with oropharyngeal cancer, one demonstrated persistent positivity from four years prior, and four showed positivity from one year prior. Two patients were not assessed as they were newly diagnosed at the time of the study. After chemoradiation treatment, their titers decreased but did not fall below the cutoff level during the follow-up period. In two cases of relapse, the titers, which had initially decreased with chemoradiation, increased again at least one year before the relapse diagnosis. Conclusions: The study demonstrated that screening for HPV16 E6 seropositivity is highly effective for the detection of oropharyngeal cancer in HIV-MSM. This could potentially contribute to early diagnosis and treatment of HPV-related cancers. [Table: see text]

Improving the quality of performing in-service inspections using manipulators

Many in-service inspections, mainly carried out by the ultrasonic method, were until recently carried out manually or semi-automated with the use of encoders. These types of inspections usually lack data recording and are dependent on the experience of the operator performing these inspections. For these reasons, in recent years one of the important activities carried out within the Research Centre Rez has been the development and production of manipulators for non-destructive testing. This article will describe in more detail the manipulators used for ultrasonic testing of the reactor head nozzles, nozzles of the emergency power supply system of steam generators treated with weld overlay, inspection of low-pressure blade dovetails and others. The developed manipulators will make it possible to refine and improve the repeatability of inspections that were previously carried out manually (more precise guidance of probes, etc.) or were not carried out at all due to inaccessibility for operators. Among other examples of the use of manipulators is in conditions where manual testing is not possible. One of the applications can be measurement using the phased array technique on pipelines during service, when the temperature on the surface of the pipeline can be up to 320°C (the maximum temperature of the primary pipeline of a nuclear power plant).

Đặc điểm lâm sàng và hiệu quả điều trị của liệu pháp oxy cao áp ở bệnh nhân chóng mặt ngoại biên

This paper presents “Clinical characteristics and therapeutic efficacy of hyperbaric oxygen therapy in patients with peripheral vertigo” to determine the clinical features of peripheral vertigo and its therapeutic efficacy. The study was carried out at Hyperbaric Oxygen Center (Southern Branch of Joint Vietnam-Russia Tropical Science and Technology Research Center) from October 2021 to December 2022, with 60 patients, divided into 2 groups. Group 1 consisted of 30 patients was treated with hyperbaric oxygen therapy (HBOT) and group 2 consisted of 30 patients was treated with HBOT and drugs (vestibular inhibitors, antiemetics and brain tonics). The results showed that: vertigo often occured when changing head position, vertigo accompanied by nausea, loss of balance. After the treatment, the group treated with HBOT and drugs, the patient's condition improved better, the level gradually increased with HBOT. In the group treated with HBOT and drugs, the mean score before treatment was 12.5 points, after 10 days of treatment was 4.37 points, after 20 days of treatment decreased to 0.63 points and after 30 days of treatment to 0.27 points. Particularly, in the group treated with HBOT, this rate was 12.33 points, respectively; 6.37 points; 2.1 points and 0.97 points (p < 0.05).

Some bats are here: Reducing the Wallacean shortfall of bats in the amazon.

The Amazon rainforest has approximately 23% of its sampled area dedicated to bats, making it one of the least sampled and most diverse regions for bats in Brazil. The lack of sampling results in a lack of knowledge regarding the accurate geographical distribution of bat species. This lack is referred to as the Wallacean shortfall, which should be addressed with primary data obtained from insitu collections. However, the use of Species Distribution Models (SDMs) can help alleviate this gap. The states of Pará and Acre are located in the Brazilian Amazon. So, our objective is to decrease the Wallacean shortfall concerning Amazonian bat species. To achieve this, we provide (i) a list of bat species sampled in the states of Pará and Acre in the last 5 years (2017 to 2022); (ii) the potential distribution of species considered as new occurrences for the region; and (iii) the potential distribution of species classified as Data Deficient (DD) and Near Threatened (NT) according to the IUCN classification. With 96 nights of collection and 129,600 m2h of mist netting, we obtained 75 bat species, with an estimated total of 94.78 species. Additionally, 21 species were considered as range extensions. The Brazilian Amazon region has a vast geographic expanse and few established research centers, resulting in a limited sampling of bats and other biological groups. Furthermore, we draw attention to the significant number of bat species with expanded geographical distributions, with 21 out of the 75 sampled species. This should be a reminder that primary biogeographic data is still necessary for the neotropical region.

Time to treatment initiation: An assessment of trends in delays in patients with lung cancer across Missouri.

11186 Background: Lung cancer is a major health challenge globally. Missouri's incidence rate of 68.1% exceeds the national rate of 54.0% indicating a significant disease burden. It is the 2nd most common malignancy in men and women in the state. Timely treatment can significantly improve while delays can worsen outcomes. The Institute of Medicine strongly recommends efforts promoting timely care in lung cancer. The RAND Cooperation suggests treatment should begin within 6 weeks after diagnosis. These priorities align with the Healthy People 2030 Initiative which aims to reduce lung cancer incidence and mortality through enhanced screening and early treatment. The U.S. National Committee on Health Care identified a goal of 60% of lung cancer patients receiving treatment within 30-days of diagnosis. Our primary objective was to assess delays in treatment initiation post-diagnosis and to investigate Missouri’s adherence to treatment delay guidelines in lung cancer patients. Methods: Study population included adults (age>18) with a diagnosis of Lung Cancer, identified using ICD-10 codes C50.0-C50.9. Records were retrieved from the Missouri Cancer Registry and Research Center database for the years 2012-2022. Data for 2022 had a completion rate of 90%, all others had at least 95% completeness. We used the RAND guidelines 42-day treatment delay rule and the Missouri Cancer Action Plan's (MCAP) 30 day treatment delay metric as our benchmarks. Treatment delay was determined by subtracting the Date of Initial Diagnosis from the Date of First Course Treatment. Records with missing or incomplete dates were excluded. Data processing and analyses were performed using Python 3.11. Results: Of the 68,293 adult lung cancer patients in the database, 7,882 were excluded due to missing or incomplete data. Among the eligible 60,411 patients, 89.5% were Caucasian, median age was 69 (range 18-105), gender distribution was nearly equal with males accounting for 51.3% of the total. Average time from diagnosis to treatment was 36.8 days, with a median of 27 days. About 31.2% of patients had a gap over 42 days from diagnosis to first treatment. This delay has risen from 26.3% in 2012 to 42.6% in 2022, marking a 16.3% increase. In terms of adherence to the MCAP’s 30 day treatment delay metric, 45.6% of patients experienced more than a 30-day gap between diagnosis and treatment. The trend shows an increase in delays, from 40.4% in 2012 to 58.1% in 2022, reflecting a 17.7% rise. Conclusions: Despite the declining incidence rate of lung cancer in Missouri over the years, our analysis revealed a surprising increase in treatment initiation delays over the years. The average time from diagnosis to treatment and the percentage of patients experiencing delays exceed the RAND guideline and the MCAP's treatment delay metric and with a rising trend from 2012 to 2022. Further analysis into factors causing delay in treatment initiation is needed and being planned.

A novel generation design dipole magnet power supply of booster to storage ring transport line in NSRRC

The Taiwan Light Source (TLS) is a synchrotron radiation facility located in Taiwan. The booster ring at TLS injects electrons into the storage ring, which then circulates the electrons to produce synchrotron radiation for various experiments. The Taiwan Light Source (TLS) has been in service for more than 20 years, and some of the power supplies used in the facility are old and hard to maintain repair and the component are phase-out. The upgrade is specifically aimed at replacing the power supply for the BTS (Booster to Storage ring) transmission line with a new machine. During the regular shunt down time, dipole magnet power supply replacements were completed. The main reason for using the Chroma 62075H-30E power supply is commonality, for this machine is widely used in Taiwan Photon Source (TPS), and the output current of the power supply is paralleled to a dipole magnet. Therefore, a total of 17 power supplies are used in this upgrade planned to be executed. This novel generation upgrade design is important because the power supply for the BTS transmission line is critical for the operation of the facility, as it is responsible for maintaining the electron beam at a stable energy level as it is injected from the booster ring into the storage ring. A more reliable and efficient power supply can help improve the stability and quality of the electron beam, leading to better experimental results and more efficient use of the facility. Overall, this novel generation upgrade design is part of the ongoing effort to modernize and improve the infrastructure of the TLS, ensuring that it remains a state-of-the-art research facility for years to come.

Bibliometric analysis of the association between periodontal disease and cardiovascular disease

PurposeConduct a bibliometric analysis to review the knowledge structure and research trends regarding the association between periodontal disease and cardiovascular disease (CVD). MethodsThe Web of Science Core collection database was searched for retrieving publications related to periodontitis and CVD between January 1, 2003 and December 31, 2022. The VOSviewer, CiteSpace, and R software package “bibliometrix” were employed for the bibliometric analysis. ResultsIn total, 3447 articles were collected from 98 countries over the past 20 years, with the United States (1,003), Japan (377), and China (321) contributing the most publications. The literature in this field exhibited exponential growth. The University of Helsinki (n = 125, 1.37 %) holds the distinction of being the research institution with the highest number of publications, with a predominant representation from institutions in the United States. Notably, the Journal of Periodontology emerges as the most popular journal in the field, whereas the Journal of Clinical Periodontology takes the lead in terms of citations. These publications originated from 15,236 authors, with Pussinen (n = 40) having the highest number of published papers and Tonetti (n = 976) garnering the most citations. The visualization analysis of keywords identified “oral microbiome,” “inflammation,” and “porphyromonas gingivalis” as emerging research hotspots in exploring the relationship between periodontitis and CVDs. ConclusionThrough a comprehensive bibliometric analysis, this study posits that periodontitis may heighten the risk of cardiovascular events, offering valuable academic references for scholars investigating the link between periodontitis and CVDs.

연구기관 재직자의 심리적 임파워먼트 연구: 성별의 다양성을 중심으로

by exploring the latent psychological empowerment profiles of research institution employees and examining the differences between groups according to gender. The quality of psychological empowerment vary among employees depending not only on individual factors but also on relational and institutional factors. Since psychological empowerment is directly linked to the personal growth and career development of employees, it is essential to examine the factors that influence it. We conducted a latent profile analysis to examine how psychological empowerment profiles differ. First, we identified five profiles based on the extent of research control and overall psychological empowerment in male samples, while four profiles were identified in female samples. Second, the quality of the social network, perceived career development support, and knowledge sharing significantly influenced the probability of belonging to each profile, particularly when the perceptions of these predictor variables are high, this suggests a higher likelihood of belonging to a group with high psychological empowerment. Finally, the group with high psychological empowerment, regardless of gender, was perceived as having higher organizational commitment, career satisfaction, and technical orientation. Based on these results, we discuss the implications for enhancing the psychological empowerment of employees at research institutions and aligning their individual career development with the organization's objectives.

Initial evaluation of measurement properties of the Work Environment Impact Questionnaire (WEIQ) - using Rasch analysis

BackgroundTo provide both preventive and rehabilitative conditions in a workplace, one must understand how employees experience work demands. Such an understanding can be obtained from each individual with valid and quality-assured questionnaires. The Work Environment Impact Questionnaire (WEIQ) is a new questionnaire for measuring employees’ self-perceived work ability in relation to their specific workplace environment. The purpose of this study was to assess the measurement properties in terms of construct validity of the WEIQ.MethodsA cross-sectional survey study was conducted with 288 respondents from three different workplaces involving assisted living personnel, vocational rehabilitation personnel and personnel at a research institute. The measurement properties of the WEIQ were assessed according to Rasch Measurement Theory (RMT), including assessment of item-to-sample targeting, threshold ordering, item fit statistics, unidimensionality and reliability.ResultsItem fit, i.e., fit residuals, item characteristic curves (ICC) and chi square values, were all satisfactory, and no disordered thresholds were present after collapsing the lowest response categories. However, issues with local dependent (LD) item correlations was present in 7.6% cases, four items showed statistically significant differential item functioning (DIF), where 11% of the respondents had person fit residuals outside the recommended range of ± 2.5 and the t-test for unidimensionality did not meet the criterion of 5%. Scale-to-sample targeting and reliability (0.92) were good. LD could be resolved with testlets and at the same time maintaining fit and improving dimensionality, but then the reliability decreased to 0.82.ConclusionsThis study provides an initial validation of the WEIQ to be used for assessing employees’ self-perceived work ability. Most measurement properties were acceptable, but further exploration of LD, DIF and unidimensionality in additional work settings and with larger sample sizes is warranted.Trial registrationNot applicable.

Oversight of Dual-Use Research: What Role for Ethics Committees?

The World Health Organization (WHO) Global Guidance Framework for the Responsible Use of the Life Sciences addresses the governance of biorisks, including dual-use research, for countries. It emphasizes engaging multisectoral stakeholders such as governments, scientific bodies, health and research institutes, standard-setting organizations, funding bodies, and others. Ethics constitutes a key component of the framework. Given the high social impact of such research and the importance of trust, risk, and benefit, national ethics committees could make a valuable contribution by providing ethical guidance in the decisionmaking process. The purpose of this study was to examine the role of national ethics committees in the context of governance and oversight of dual-use research at the national level. We conducted a landscape analysis of the activities of ethics committees in dual-use research oversight. We also searched the WHO database on National Ethics Committees for publications related to dual-use research and/or misuse of life sciences research and gathered additional documentation from national ethics committees websites and through author contacts. Results showed that in the context of the wide range of oversight mechanisms for dual-use research in countries, national ethics committees have contributed to guiding policy and assessing dual-use research risks in only a limited number of countries. Recommendations from those countries include establishing a multistakeholder, coordinated oversight mechanism at the country level; strengthening international linkages to guide, harmonize, and reinforce national and international efforts; and involving ethics committees as an expert resource in the governance and oversight process.

Self-reported removal and expulsion of the dapivirine vaginal ring: qualitative reports from female ring users and their male partners in the Ring Study (IPM 027)

Background/aimsThe dapivirine vaginal ring is a self-administered, women-initiated, discreet, long-acting HIV-1 prevention option for women. It was found to be safe and effective in healthy HIV-negative women who adhered to product use instructions, and has been approved for use in women aged 18 and older in some African countries. A qualitative study was conducted to explore participants’ and their male partners’ discussions on accidental/purposeful vaginal ring removals during The Ring Study (IPM 027 clinical trial).MethodsData were collected via in-depth interviews and focus group discussions with female trial participants and their male partners, from seven research centres in South Africa and Uganda. Data were thematically analysed using NVivo.ResultsMore participants reported purposeful ring removals than accidental expulsions. Various factors influenced purposeful ring removal – including individual (discomfort during use/sex and to clean it), partner (to show them, because of discomfort during sex, to test if partners could feel it, and concerns of harm), organisational (doctor’s request), and socio-cultural (rumours about sickness and infertility). Some described their own ring use removal, others discussed why other participants removed their rings.ConclusionsVaginal ring adherence is critical to improve and support product efficacy. Counselling on vaginal anatomy, vaginal ring insertion and importance of adherence is important to minimise vaginal ring removal. Couples counselling is also important to facilitate support and long-term vaginal ring adherence behaviour. Understanding factors influencing vaginal ring adherence is important for tailoring and targeting messages to support correct and consistent vaginal ring use as it is made available to the public.

CORRELATION OF CARDIAC MARKERS WITH THYROID STIMULATING HORMONE IN SUBCLINICAL HYPOTHYROIDELDERLY

Cardiac markers (CPK-MB and TroponinT (TnT)) are often used to differentiate between cardiac and non cardiac chest pain. Subclinical hypothyroidism (SCH) has increased incidence of cardiovascular risk factors and disease. Elderly have an increased incidence of SCH. However, no study has specifically examined the association between cardiac markers and SCH in elderly population. Aims and Objectives: To determine the association of cardiac markers with thyroid stimulating hormone (TSH) in elderly patientswith subclinical hypothyroids and euthyroid. Method: The present study was designed as a retrospective cross-sectional study conducted in Biochemistry department of Adesh institute of medical sciences and research (AIMSR) Bathinda from a period of May 2023 to April 2024.The data was obtained from the lab computers and the subjects were divided into four groups. Group 1 included patients who had MI and SCH. Group 2 consisted of patients who had MI and were euthyroid. Group 3 were those who presented with chest pain only (no MI) and SCH. Group 4 were those who had acute chest pain (no MI) and were found to be euthyroid. Results:Our study showed significant correlation of TSH with CPK-MB (r=0.69, p=0.001)and Troponin T ( r=0.201, p= 0.04) in Group 1 while a non significant correlation was found in Group 2, CPK-MB (r=0.06, p=0.67) and Troponin T (r= 0.156, p= 0.57). There was a significant correlation of TSH with CPK-MB (r=0.71, p=0.02) and Troponin T (r=0.84, p= 0.001) in Group 3. A nonsignificant correlation was found in Group 4, between TSH and CPK-MB (r=0.116, p=0.68) and Troponin T (r= 0.001, p= 0.99). Conclusion: Elevations of TSH levels may cause a significant rise in the cardiac markers in SCH elderly as compared to euthyroid.

Environmental Blindspots: Identification and Mitigation using Technologies, Education, and Policies

Objectives:“Environmental Blindspots” are newly defined as a type of social problem within the realm of various environmental pollution and climate issues, wherein they are pushed down in priority due to factors such as corporate profit, consumer preferences, and government regulations, consequently remaining unresolved. This ultimately leads citizens to experience a sense of guilt. Despite the significant influence they wield on the welfare of current and future generations, various environmental social issues characterized by environmental blindspots (such as micro-hazardous substances like microplastics and environmental hormones) fail to become major considerations in societal decision-making. Consequently, they are not actively discussed within the social community. This absence of social consensus on these issues reflects the current situation. As a result, citizens repeatedly make choices that do not prioritize environmental values due to a perception of powerlessness stemming from the absence of environmentally friendly options, the belief that the issue is too immense to tackle individually, and lack of knowledge about specific actions to take for environmental problem-solving, among other factors. In this process, they experience involuntary and deliberate emotions of guilt. Since environmental blindspots are issues collectively experienced by the societal community comprising citizens, businesses, and government, solutions must also be derived collectively through collective thinking. This review has endeavored to incorporate such efforts.Methods:In this review, to develop a more effective interdisciplinary research methodology for addressing the previously mentioned environmental social issues, ten interdisciplinary researchers from the Environmental Engineering and Social Sciences fields at the center for convergence research (SEBIS) collaborated, leveraging their respective expertise to document literature survey results. Firstly, they reported on the environmental behavior, toxicity, distribution, and regulatory status of micro-hazardous substances, namely (micro)plastics and volatile organic compounds, which are the research subjects of the Environmental Blindspot Research Center. Secondly, they compiled relevant treatment technologies. Subsequently, they described the socio-structural causes of environmental blindspots and various solutions to environmental social issues through social science methodologies.Results and Discussion:To address the environmental blindspots, a key environmental social issue, it is necessary to advance various environmental technologies alongside responsible production by businesses and the enhancement of citizen environmental awareness. It is crucial for the government to institutionalize policies in the public domain to achieve this. Understanding the structural roles of citizens, businesses, and government is essential. It requires ethical consumer awareness and active participation, public campaigns and education, as well as effective government environmental policies to incentivize environmental friendly technological innovations by companies.Conclusion:In this review, the issue of environmental blindspots as an environmental social issue is being addressed comprehensively for the first time. Through this, we aim to establish an effective communication and cooperation system among social entities to explore solutions to environmental blindspots, and to propagate this ability to address social issues to future academic generations.

Optimisation of dose level and vaccination schedule for the VLA15 Lyme borreliosis vaccine candidate among healthy adults: two randomised, observer-blind, placebo-controlled, multicentre, phase 2 studies.

Rising Lyme borreliosis incidence rates, potential for severe outcomes, and limitations in accurate and timely diagnosis for treatment initiation suggest the need for a preventive vaccine; however, no vaccine is currently available for human use. We performed two studies in adults to optimise the dose level and vaccination schedule for VLA15, an investigational Lyme borreliosis vaccine targeting outer surface protein A (OspA) serotypes 1-6, which are associated with the most common pathogenic Borrelia species in Europe and North America. Both randomised, observer-blind, placebo-controlled, multicentre phase 2 studies included participants aged 18-65 years without recent history of Lyme borreliosis or tick bites. Study one was conducted at nine clinical research and study centre sites in the USA (n=6), Germany (n=2), and Belgium (n=1); study two was conducted at five of the study one US sites. Based on a randomisation list created by an unmasked statistician for each study, participants were randomly assigned via an electronic case report form randomisation module to receive 90 μg (study one only), 135 μg, or 180 μg VLA15 or placebo by intramuscular injection at months 0, 1, and 2 (study one) or 0, 2, and 6 (study two). Study one began with a run-in phase to confirm safety, after which the Data Safety Monitoring Board recommended the removal of the 90 μg group and continuation of the study. In the study one run-in phase, randomisation was stratified by study site, whereas in the study one main phase and in study two, randomisation was stratified by study site, age group, and baseline B burgdorferi (sensu lato) serostatus. All individuals were masked, other than staff involved in randomisation, vaccine preparation or administration, or safety data monitoring. The primary endpoint for both studies was OspA-specific IgG geometric mean titres (GMTs) at 1 month after the third vaccination and was evaluated in the per-protocol population. Safety endpoints were evaluated in the safety population: all participants who received at least one vaccination. Both studies are registered at ClinicalTrials.gov (study one NCT03769194 and study two NCT03970733) and are completed. For study one, 573 participants were screened and randomly assigned to treatment groups between Dec 21, 2018, and Sept, 26, 2019. For study two, 248 participants were screened and randomly assigned between June 26 and Sept 3, 2019. In study one, 29 participants were assigned to receive 90 μg VLA15, 215 to 135 μg, 205 to 180 μg, and 124 to placebo. In study two, 97 participants were assigned to receive 135 μg VLA15, 100 to 180 μg, and 51 to placebo. At 1 month after the third vaccination (ie, month 3), OspA-specific IgG GMTs in study one ranged from 74·3 (serotype 1; 95% CI 46·4-119·0) to 267·4 units per mL (serotype 3; 194·8-367·1) for 90 μg VLA15, 101·9 (serotype 1; 87·1-119·4) to 283·2 units per mL (serotype 3; 248·2-323·1) for 135 μg, and 115·8 (serotype 1; 98·8-135·7) to 308·6 units per mL (serotype 3; 266·8-356·8) for 180 μg. In study two, ranges at 1 month after the third vaccination (ie, month 7) were 278·5 (serotype 1; 214·9-361·0) to 545·2 units per mL (serotype 2; 431·8-688·4) for 135 μg VLA15 and 274·7 (serotype 1; 209·4-360·4) to 596·8 units per mL (serotype 3; 471·9-754·8) for 180 μg. Relative to placebo, the VLA15 groups had more frequent reports of solicited local adverse events (study one: 94%, 95% CI 91-96 vs 26%, 19-34; study two: 96%, 93-98 vs 35%, 24-49 after any vaccination) and solicited systemic adverse events (study one: 69%, 65-73 vs 43%, 34-52; study two: 74%, 67-80 vs 51%, 38-64); most were mild or moderate. In study one, unsolicited adverse events were reported by 52% (48-57) of participants in the VLA15 groups and 52% (43-60) of those in the placebo groups; for study two these were 65% (58-71) and 69% (55-80), respectively. Percentages of participants reporting serious unsolicited adverse events (study one: 2%, 1-4; study two: 4%, 2-7) and adverse events of special interest (study one: 1%, 0-2; study two: 1%, 0-3) were low across all groups. A single severe, possibly related unsolicited adverse event was reported (worsening of pre-existing ventricular extrasystoles, which resolved after change of relevant concomitant medication); no related serious adverse events or deaths were reported. VLA15 was safe, well tolerated, and elicited robust antibody responses to all six OspA serotypes. These findings support further clinical development of VLA15 using the 180 μg dose and 0-2-6-month schedule, which was associated with the greatest immune responses. Valneva.

Using Data to Sustain and Measure Student Success Initiatives

This is a follow-up to an earlier case study [Faudree, J. 2021. Courage by experiment, rescue by data. PRIMUS. 31(3–5): 483–491.] describing one Math Department's attempt to improve pass rates in Calculus I by implementing the recommendations from national studies of successful calculus programs [Bressoud, D. and C. Rasmussen. 2015. Seven characteristics of successful calculus programs. Notices of the American Mathematical Society. 62(2): 144–146; Rasmussen, C., J. Ellis, and D. Zazkis. 2014. Lessons learned from case studies of successful calculus programs at five doctoral degree granting institutions. In Proceedings of the 17th Annual Conference on Research in Undergraduate Mathematics Education, pp. 999–1005. Denver, CO.]. This article, along with the earlier one, provide concrete, detailed strategies for promoting departmental change. We describe how the collection and analysis of baseline data has formed the backbone of a sustained, department-driven effort to improve outcomes for undergraduate students and one that weathered the pandemic. For context, our public university is the major research institution of the state, but it is also open-admissions, small (7500 undergraduates) and physically isolated. The effort described here started in 2016 with few resources: no faculty with expertise in mathematics education at the post-secondary level, no support from administration, and no external funding.