bluuebunny/crossref_metadata_2025 huggingface dataset:
Whose Expression Is It Anyway? Videogames and the Freedom of Expression
Authors: Jørgensen Kristine , Mortensen Torill Elvira
Published: March 2022

In debates concerning videogames and the freedom of expression, two lines of argumentation have traditionally been put forward: That games express ideas and for this reason are entitled to the same protection as other expressive media or that their interactive nature makes them different in how they reflect the world compared to other media. This paper adds nuance to this discussion through two arguments. First, we argue that videogames cannot be understood as mainly expressive or interactive, but that these characteristics must be understood in tandem if we are to understand the role of videogames in culture and society, connected by the player. Second, we argue that play and playfulness are ignored in debates about videogames and the freedom of expression, and that attention towards the playful aspects offers a better view of how videogames differ from other media and what this means for the status of expressions in videogames.
Cochrane Effective Practice and Organisation of Care (EPOC) Qualitative Evidence Syntheses, Differences From Reviews of Intervention Effectiveness and Implications for Guidance
Authors: Glenton Claire , Lewin Simon , Downe Soo , Paulsen Elizabeth , Munabi-Babigumira Susan , Agarwal Smisha , Ames Heather , Cooper Sara , Daniels Karen , Houghton Catherine , Karimi‐Shahanjarini Akram , Moloi Hlengiwe , Odendaal Willem , Shakibazadeh Elham , Vasudevan Lavanya , Xyrichis Andreas , Bohren Meghan A.
Published: February 2022

Systematic reviews of qualitative research (‘qualitative evidence syntheses’) are increasingly popular and represent a potentially important source of information about people’s views, needs and experiences. Since 2013, Cochrane has published qualitative evidence syntheses, and the Cochrane Effective Practice and Organisation of Care group has been involved in the majority of these reviews. But more guidance is needed on how to prepare these reviews in an environment that is more familiar with reviews of quantitative research. In this paper, we describe and reflect on how Cochrane qualitative evidence syntheses differ from reviews of intervention effectiveness and how these differences have influenced the guidance developed by the EPOC group. In particular, we discuss how it has been important to display to end users, firstly, that qualitative evidence syntheses are carried out with rigour and transparency, and secondly, that these quality standards need to reflect qualitative research traditions. We also discuss lessons that reviews of effectiveness might learn from qualitative research.
Illuminating the Role of Reflexivity Within Qualitative Pilot Studies: Experiences From a Scholarship of Teaching and Learning Project
Authors: Lees Amanda B. , Walters Simon , Godbold Rosemary
Published: March 2022

Pilot studies within qualitative inquiry are crucial yet often hidden aspects of research design. In this article, we argue for pilots to have greater visibility. We explore the role of a pilot in providing a foundation for enhancing ethical reflexivity, drawing on a recent pilot study within a tertiary healthcare education setting. The Scholarship of Teaching and Learning (SoTL) presents a unique environment with complex stakeholder relationships. There is a lack of consensus nationally and internationally on whether all SoTL projects require consideration by institutional ethics review bodies. A pilot study offers an opportunity for ethical steerage of a research project, reflecting ethics in practice whilst augmenting any procedural ethics review requirements. We propose that a qualitative pilot study, as a design strategy, can enhance ethical conduct by researchers. Within SoTL specifically, the pilot can provide an opportunity for researchers to demonstrate a commitment to a pedagogy of care spanning the project’s duration, signifying a commitment to enduring teacher-student relationships within the broader learning environment. Beyond tertiary settings, we believe the pilot study, as a space for ethical reflexivity, has applicability to research settings where caring for and being seen to care for the wider participant community is a critical ethical consideration.
A Psychology of Ideology: Unpacking the Psychological Structure of Ideological Thinking
Authors: Zmigrod Leor
Published: March 2022

The psychological study of ideology has traditionally emphasized the content of ideological beliefs, guided by questions about what people believe, such as why people believe in omniscient gods or fascist worldviews. This theoretical focus has led to siloed subdisciplines separately dealing with political, religious, moral, and prejudiced attitudes. The fractionation has fostered a neglect of the cognitive structure of ideological worldviews and associated questions about why ideologies—in all their forms—are so compelling to the human mind. Here I argue that it is essential to consider the nature of ideological cognition across a multitude of ideologies. I offer a multidimensional, empirically tractable framework of ideological thinking, suggesting it can be conceptualized as a style of thinking that is rigid in its adherence to a doctrine and resistance to evidence-based belief-updating and favorably oriented toward an in-group and antagonistic to out-groups. The article identifies the subcomponents of ideological thinking and highlights that ideological thinking constitutes a meaningful psychological phenomenon that merits direct scholarly investigation and analysis. By emphasizing conceptual precision, methodological directions, and interdisciplinary integration across the political and cognitive sciences, the article illustrates the potential of this framework as a catalyst for developing a rigorous domain-general psychology of ideology.
Mycobacterium tuberculosis infection and disease in healthcare workers in a tertiary referral hospital in Bandung, Indonesia
Authors: Apriani Lika , McAllister Susan , Sharples Katrina , Nurul Aini Isni , Nurhasanah Hanifah , Ruslami Rovina , Menzies Dick , Hill Philip C , Alisjahbana Bachti
Published: March 2022

Background

Healthcare workers (HCWs), especially in high tuberculosis (TB) incidence countries, are at risk of Mycobacterium tuberculosis infection and TB disease, likely due to greater exposure to TB cases and variable implementation of infection control measures.

Aim

We aimed to estimate the prevalence of tuberculin skin test (TST) positivity, history of TB and to identify associated risk factors in HCWs employed at a tertiary referral hospital in Bandung, Indonesia.

Methods

A cross-sectional study was conducted from April to August 2018. A stratified sample of the HCWs were recruited, screened by TST, assessed for TB symptoms, history of TB disease and possible risk factors. Prevalence of positive TST included diagnosis with TB after starting work. HCWs with TB disease diagnosed earlier were excluded. Survey weights were used for all analyses. Possible risk factors were examined using logistic regression; adjusted odds ratios and 95% confidence intervals (CI) are presented.

Results

Of 455 HCWs recruited, 42 reported a history of TB disease (25 after starting work) and 395 had a TST result. The prevalence of positive TST was 76.9% (95% CI 72.6–80.8%). The odds increased by 7% per year at work (95% CI 3–11%) on average, with a rapid rise in TST positivity up to 10 years of work and then a plateau with around 80% positive.

Discussion

A high proportion of HCWs had a history of TB or were TST positive, increasing with longer duration of work. A package of TB infection control measures is needed to protect HCWs from Mycobacterium tuberculosis infection.
Impact of Blood Glucose Monitoring System Accuracy on Clinical Decision Making for Diabetes Management
Authors: Eichenlaub Manuel , Pleus Stefan , Shaginian Rimma , Richardson James , Pardo Scott , Stuhr Andreas , Freckmann Guido
Published: March 2022

Background:

The accuracy of blood glucose monitoring systems (BGMS) is crucial for the safe and effective management of diabetes mellitus. Despite standardization of accuracy assessment procedures and requirements, various studies have shown that the accuracy of BGMS on the market can vary considerably. This article therefore provides health care professionals and users with an intuitive illustration of the impact of BGMS accuracy on clinical decision making.

Material and Methods:

Several hypothetical patient scenarios based on blood glucose (BG) levels in the low, normal, and high BG range are devised. Using data from a recent BGMS accuracy study, a method for calculating the expected range of BG readings from four examined BGMS at the selected BG levels is introduced. Based on these ranges, it is illustrated how clinical decisions and subsequent outcomes of the hypothetical patients are affected by the expected inaccuracies of the BGMS.

Results:

The range of expected BGMS readings for the same true BG level can vary considerably between different BGMS. The discussion of hypothetical patient scenarios revealed that the use of some BGMS could be associated with an increased risk of adverse events such as failure to detect hypoglycemia, driving with an unsafe BG level, delay of treatment intervention in diabetes during pregnancy, or the failure to prevent diabetic ketoacidosis.

Conclusions:

This article can support both health care professionals and patients to understand the impact of BGMS accuracy in a relatable, clinical context. Furthermore, it is suggested that current accuracy requirements might be insufficient for the prevention of adverse clinical outcomes in certain circumstances.
What’s Phase 2? Crafting the Value Proposition for Applied and Clinical Sociology
Authors: David Gary C.
Published: March 2022

In the 2018 President Address provided by Gary David, he discusses the need for new approaches to how applied and clinical sociology is branded. He explores business approaches to how we can leverage our passion for sociology with the unique skills we have with clear messaging around what it is we do and why we do it.
Management of Giant Cell Tumor of Talus With Extended Intralesional Curettage and Reconstruction Using Polymethylmethacrylate Cement
Authors: Ilyas Muhammad Saad , Akram Rizwan , Zehra Uruj , Aziz Amer
Published: March 2022

An 18-year-old man presented with complaints of pain and swelling around the left ankle region. Local examination revealed diffuse, hard, mildly tender swelling with ill-defined margins over the medial aspect of the left ankle joint just below the medial malleolus. Radiographic and computed tomographic assessment revealed osteolytic lesion with moderately defined margins. Provisional diagnosis of Campanacci grade 2 giant cell tumor was made, which was later confirmed on histopathology. Extended intralesional curettage and reconstruction with polymethylmethacrylate cement was done under spinal anesthesia. Full weight bearing was allowed at 4 weeks when the below knee back slab was removed. Radiographic assessment was done every 3 months during the first year of follow-up and then every 6 months. No evidence of recurrence of tumor, collapse of talus, or avascular necrosis was found during follow-up. Managing such rare form of bone tumors with extended intralesional curettage and bone cement is an appropriate treatment and gives good functional results.

Level of Evidence: Level V
Child marriage and sexularism in Sweden: Constructing the nation racializing migrants
Authors: Manga Edda
Published: March 2022

This article investigates the discourse on child marriage as reflected in the entire corpus of official investigations Statens Offentliga Utredningar (SOU) and government bills (Prop.) proposing legislative measures against child marriage in Sweden since the first motions on the issue were drafted in 2001. It analyzes them as instances of sexularism: a form of secularism where the secular is construed in relation to sexual emancipation and gender equality rather than in relation to politics or the public sphere. It then connects the effects of legislation against child marriage on the right to family reunification to the racialization of migrant populations and religious minorities in Sweden.
No pain, no gain! The uncertainty-to-win effect on customer experience quality through gamified interaction
Authors: Leclercq Thomas
Published: March 2022

Offering customers a high-quality experience has become critical for companies. Scholars have therefore emphasized the opportunity to use gamification. However, despite the increasing popularity of such an approach, prior studies report mixed results. This research aims to reconcile these findings by identifying under which conditions gamification leads to a better experience. Drawing on uncertainty-resolution theory, we examine how uncertainty-to-win affects customer experience quality. The results from six studies, combining a field study and experiments, demonstrate the benefits of uncertainty-to-win for customer experience quality. We find that the uncertainty-to-win effect persists even after people are informed of a win/lose decision. Moreover, we highlight that losing the contest stresses the uncertainty-to-win effect, and consequently counter the harmful effect of loss. Conversely, we suggest that reward value mitigates the positive impact of uncertainty-to-win by focusing customers’ attention on a prize instead of on their experience. Our findings move the literature forward by underscoring how uncertainty-to-win is a condition that explains gamification’s ability to deliver a high-quality experience.
GripAble: An accurate, sensitive and robust digital device for measuring grip strength
Authors: Mace Michael , Mutalib Sharah Abdul , Ogrinc Matjaz , Goldsmith Nicola , Burdet Etienne
Published: March 2022

Introduction

Grip strength is a reliable biomarker of overall health and physiological well-being. It is widely used in clinical practice as an outcome measure. This paper demonstrates the measurement characteristics of GripAble, a wireless mobile handgrip device that measures grip force both isometrically and elastically-resisted for assessment and training of hand function.

Methods

A series of bench tests were performed to evaluate GripAble's grip force measurement accuracy and sensitivity. Measurement robustness was evaluated through repeated drop tests interwoven with error verification test phases.

Results

GripAble's absolute measurement error at the central position was under 0.81 and 1.67 kg (95th percentiles; N = 47) when measuring elastically and isometrically, respectively, providing similar or better accuracy than the industry-standard Jamar device. Sensitivity was measured as 0.062 ± 0.015 kg (mean ± std; 95th percentiles: [0.036, 0.089] kg; N = 47), independent of the applied force. There was no significant performance degradation following impact from 30 drops from a height >1.5 m.

Conclusion

GripAble is an accurate and reliable grip strength dynamometer. It is highly sensitive and robust, which in combination with other novel features (e.g. portability, telerehabilitation and digital data tracking) enable broad applicability in a range of clinical caseloads and environments.
Cracking the Hip: Does Protocol Matter? A Retrospective Cohort Study Investigating the Effect of Protocol Implementation
Authors: Levi Amelia R , Coste Marine , Warshowsky Ethan , Shah Neil V , Suneja Nishant , Schwartz Jeffrey M. , Roudnitsky Valery
Published: February 2022

Introduction

Approximately 300 000 hip fractures occur annually in the USA in patients >65 years old. Early intervention is key in reducing morbidity and mortality. Our institution implemented a collaborative hip fracture protocol, streamlining existing processes to reduce time to OR (TTO) and hospital length of stay (LOS). Our aim was to determine if this protocol improved these outcomes.

Study Design

We conducted a retrospective cohort study using our level-1 trauma center’s trauma registry, comparing outcomes for patients >60 years old with isolated hip fractures pre-and post-hip protocol implementation in May 2018. Our primary outcomes were TTO and in-hospital mortality. Secondary outcomes included LOS and postoperative complications. Univariate analysis was done using chi-square and T-test.

Results

We identified 176 patients with isolated hip fractures: 69 post- and 107 pre-protocol. Comparing post- to pre-protocol, TTO decreased by 18hrs (39 vs 57h; P = .013) and patients had fewer postoperative complications (9 vs 23%; P = .016) despite post-protocol patients being more likely to have diabetes (42 vs 27%, P < .05), elevated BMI (22 vs 25; P < .001), and to be current smokers (9 vs 2%; P < .05). LOS and in-hospital mortality also decreased (11 vs 20d; P = .312, 4.3 vs 7.5%; P = .402). Post-protocol patients were more likely to go to the OR within 24hrs of presentation (39 vs 16%; P < .001) and to go straight from ED to OR (32 vs 4%; P < .001).

Conclusion

TTO, LOS, and postoperative complications for isolated hip fracture patients were lower post-protocol. Though not all statistically significant, this trend indicates that the protocol was helpful in improving hip fracture outcomes but may require further improvement and institution-wide education.
The Utility of ‘Minimal Access and Separation Surgery’ in the Management of Metastatic Spine Disease
Authors: Kumar Naresh , Tan Jiong H. , Thomas Andrew C. , Tan Joel Y. H. , Madhu Sirisha , Shen Liang , Lopez Keith G. , Hey Dennis H. W. , Liu Gabriel , Wong HeeKit
Published: March 2022

Study Design

Retrospective cohort study.

Objectives

To compare outcomes of percutaneous pedicle screw fixation (PPSF) to open posterior stabilization (OPS) in spinal instability patients and minimal access separation surgery (MASS) to open posterior stabilization and decompression (OPSD) in metastatic spinal cord compression (MSCC) patients.

Methods

We analysed patients who underwent surgery for thoracolumbar metastatic spine disease (MSD) from Jan 2011 to Oct 2017. Patients were divided into minimally invasive spine surgery (MISS) and open spine surgery (OSS) groups. Spinal instability patients were treated with PPSF/OPS with pedicle screws. MSCC patients were treated with MASS/OPSD. Outcomes measured included intraoperative blood loss, operative time, duration of hospital stay and ASIA-score improvement. Time to initiate radiotherapy and perioperative surgical/non-surgical complications was recorded. Propensity scoring adjustment analysis was utilised to address heterogenicity of histological tumour subtypes.

Results

Of 200 eligible patients, 61 underwent MISS and 139 underwent OSS for MSD. There was no significant difference in baseline characteristics between MISS and OSS groups. In the MISS group, 28 (45.9%) patients were treated for spinal instability and 33 (54.1%) patients were treated for MSCC. In the OSS group, 15 (10.8%) patients were treated for spinal instability alone and 124 (89.2%) were treated for MSCC. Patients who underwent PPSF had significantly lower blood loss (95 mL vs 564 mL; P < .001) and surgical complication rates( P < .05) with shorter length of stay approaching significance (6 vs 19 days; P = .100) when compared to the OPS group. Patients who underwent MASS had significantly lower blood loss (602 mL vs 1008 mL) and shorter length of stay (10 vs 18 days; P = .098) vs the OPSD group.

Conclusion

This study demonstrates the benefits of PPSF and MASS over OPS and OPSD for the treatment of MSD with spinal instability and MSCC, respectively.
Elements of Medieval Town in Indian and Pakistan City Borders: Case of Amritsar and Lahore
Authors: Sahni Sakshi
Published: March 2022

The article presents various elements of the medieval cities of Lahore and Amritsar which are at an approximate distance of 51 km. These two-share various similar characteristics and patterns and were part of one state, Punjab. Although, the borders have been divided in India–Pakistan partition of 1947, still the urban fabric of both cities remains the same, and they share common features and elements. The common pattern and themes will be discussed by the author. This article briefly analyses the elements of both cities and attempts to bring out the similarity between the two.
The Digital Divide Exacerbates Disparities in Latinx Recruitment for Alzheimer’s Disease and Related Dementias Online Education During COVID-19
Authors: Gutiérrez Ángela , Cain Rosalba , Nadine Diaz  , Aranda María P.
Published: March 2022

Latinx adults experience a high burden of dementia. Given that modifiable factors drive dementia disparities, engaging Latinxs in Alzheimer’s disease and related dementias (ADRD) education is critical to address dementia burden among this aging population. Yet, no studies have documented the role of the COVID-19 pandemic on dementia education among Latinxs. This study: (1) elucidates the recruitment and retention processes targeting Latinxs for online educational events during the pandemic; (2) describes facilitators/barriers to participation; and (3) offers lessons learned. We developed online dementia-focused workshops (English and Spanish) and employed a cold-calling approach to invite Latinx participants enrolled in clinical studies ( N = 209). Bivariate tests assessed demographic and cognitive differences between those who recruiters did ( n = 60) and did not ( n = 149) successfully engage. Frequency counts assessed participants’ technological access. Only 8/209 attended the online events; all held university degrees, most reported English as their primary language, and none experienced cognitive impairment. Results underscore how educational attainment, cognitive impairment, language preference, and age intersect to shape recruitment in dementia-focused online education. To promote healthy aging and to ameliorate dementia disparities, barriers to online engagement among older Spanish-speaking Latinxs with cognitive impairment and low educational attainment must be addressed.
Business as Usual? The Post-Brexit Impacts on UK and UAE Relations
Authors: Gibbins Justin
Published: March 2022

Since the formal leaving of the United Kingdom from the European Union on January 31, 2020, much discussion has focused on the consequences for British foreign policy. Predictions broadly fit into two outcomes: internationalism, echoed in the “global Britain” mantra, and isolationism, with a Britain struggling to be heard on the world stage. As British foreign and trade policies are being shaped by a desire to seek out new friends, and reaffirm contacts with old ones, the United Arab Emirates, a Gulf Cooperation Council country with a palpable set of linkages to the UK, will be impacted. Military, diplomatic and economic ties are robust, but the UAE’s position, particularly in light of its rising-power regional status, requires investigation. With some believing British influence will be stymied by its non-EU status, and with a UAE that has reversed its traditional nonintervention status to become more regionally resurgent, what would this mean for future UK–UAE relations? This article seeks to provide an early snapshot of the post-Brexit relationship between the two.
Process evaluation protocol for the BeST? Services trial
Authors: Kainth Gary , Turner Fiona , Crawford Karen , Watson Nicholas , Dundas Ruth , Minnis Helen
Published: March 2022

Background: Outcomes for children who have been received into state care due to maltreatment or neglect are very poor in comparison to the general population. A mental health focussed intervention is being trialled in the UK which seeks to improve outcomes for such children. Although the main study is concerned with outcome evaluation (child mental health measures), a robust process evaluation adds nuance to the findings by examining the relationship between the interventions, the participants and the context-thereby determining what works, for whom and in what context. This paper sets out the protocol for that process evaluation. Methods: The process evaluation is embedded within a Randomised Control Trial and uses Realist Evaluation as its theoretical framework. It sets out the mechanisms of change that are used to effect positive outcomes and outlines the various aspects of the context (including service provision and the legal system that provides the statutory basis for involvement with families). Data collection is primarily qualitative and takes place with a large group of stakeholders. The analysis of the interplay between context, mechanisms and outcomes will provide a richer understanding of the main trial outcomes. Discussion: The nature of the interaction between the social, legal and practice context is complex. The use of a variety of methods including case studies, focus groups and analysis of routine data are justified and it is argued that they will provide for greater understanding of the nature of the interactions within such a challenging context.
Incidence and Type of Right Ventricular Diastolic Dysfunction in Postoperative Tetralogy of Fallot Pediatric Patients
Authors: Kidwai Mohammad Moaaz , Azad Sushil , Radhakrishnan Sitaraman , Garg Ankit
Published: March 2022

Objective:

Assessment of right ventricular (RV) diastolic function in postoperative Tetralogy of Fallot (TOF) patients is not routinely done during intermediate follow-up. We have done this study to assess the incidence and type of RV diastolic dysfunction in these patients.

Method:

Ninety patients who were less than 18 years and underwent total correction for TOF were analyzed in this study. The incidence and type of RV diastolic dysfunction was measured and the effect of degree of pulmonary regurgitation on RV diastolic function was also seen.

Results:

The total number of patients with RV diastolic dysfunction was 46 (51.1%). Restrictive RV physiology was seen in 8 patients (8.8%) and the most common type of RV diastolic dysfunction seen was pseudonormal filling, seen in 23 (25.6%) patients.

Conclusion:

Subclinical RV diastolic dysfunction is present in almost half of the postoperative TOF patients of pediatric age group. The most prevalent form of diastolic dysfunction was pseudonormal filling during intermediate follow-up.
Triceps Tendon Repair
Authors: Yalcin Sercan , Maier Jacob , Schickendantz Mark
Published: March 2022

Background:

Triceps tendon tear has a low incidence. Therefore, surgical repair of the triceps tendon is performed only by a small number of orthopedic surgeons.

Indications:

To provide information regarding the current treatment algorithm and surgical technique.

Technique Description:

The triceps tendon is exposed through a posterior approach. The tendon is then longitudinally split to expose the deep degenerated tissue. The degenerated tissue and any existing osteophytes are removed. The superficial layer of the tendon is sewn back down to the deeper layer of the tendon. The tendon is advanced distally, and the split incision is closed. This is followed by double–row repair with suture anchors.

Results:

Excellent clinical outcomes have been reported with re–rupture rates of around 7% at a 4–year follow–up.

Discussion/Conclusion:

Partial and complete ruptures of the triceps tendon require surgical treatment. Current surgical treatment options yield excellent clinical outcomes.
Evidence supporting a role for the immune checkpoint protein B7-H3 in NK cell-mediated cytotoxicity against AML
Authors: Tyagi Anudishi , Ly Stanley , El-Dana Fouad , Yuan Bin , Jaggupilli Appalaraju , Grimm Sabrina , Konopleva Marina , Bühring Hans-Jörg , Battula V. Lokesh
Published: March 2022

We observed that the immune checkpoint protein B7-H3 is overexpressed in acute myeloid leukemia (AML) patients with poor treatment outcomes. Inhibition of B7-H3 expression or blocking of its activity using a novel monoclonal antibody (T-1A5) in AML cells significantly enhanced natural killer (NK) cell-mediated cytotoxicity in AML cells in vitro and in vivo. Moreover, a human-mouse chimera of this antibody (ChT-1A5) induced antibody-dependent cell-mediated cytotoxicity (ADCC) in B7-H3+ primary AML cells, but not in normal hematopoietic cells, suggesting the specify of this antibody for AML cells. Epitope mapping studies identified that both T-1A5 and ChT-1A5 antibodies bind to the FG-loop region of B7-H3, which is known to regulate the immunosuppressive function of B7-H3. Furthermore, treatment with ChT-1A5 in combination with human NK cells significantly prolonged survival in AML patient-derived xenograft (PDX) models. Our results suggest that the ChT-1A5 antibody can inhibit the immunosuppressive function of B7-H3 protein as well as induce ADCC in B7-H3+ AML.
A novel salt-tolerant strain Trichoderma atroviride HN082102.1 isolated from marine habitat alleviates salt stress and diminishes cucumber root rot caused by Fusarium oxysporum
Authors: Zhang Chongyuan , Wang Weiwei , Hu Yihui , Peng Zhongpin , Ren Sen , Xue Ming , Liu Zhen , Hou Jumei , Xing Mengyu , Liu Tong
Published: March 2022

Background

Salt stress threaten the growth of plants, and even aggravate plant disease. In this article, salt-tolerant Trichoderma strain was isolated, and its potential to alleviate salt stress and diminish cucumber root rot caused by Fusarium oxysporum was evaluated.

Results

Twenty-seven Trichoderma isolates were isolated from samples of sea muds and algae collected from the South Sea of China. Among these, the isolate HN082102.1 showed the most excellent salt tolerance and antagonistic activity against F. oxysporum causing root rot in cucumber and was identified as T. atroviride. Its antagonism ability may be due to mycoparasitism and inhibition effect of volatile substances. The application of Trichoderma mitigated the adverse effects of salt stress and promoted the growth of cucumber under 100 mM and 200 mM NaCl, especially for the root. When T. atroviride HN082102.1 was applied, root fresh weights increased by 92.55 and 84.86%, respectively, and root dry weights increased by 75.71 and 53.31%, respectively. Meanwhile, the application of HN082102.1 reduced the disease index of cucumber root rot by 63.64 and 71.01% under 100- and 0-mM saline conditions, respectively, indicating that this isolate could inhibit cucumber root rot under salt stress.

Conclusions

This is the first report of salt-tolerant T. atroviride isolated from marine habitat showing antagonistic activity to F. oxysporum, and the results provide evidence for the novel strain T. atroviride HN082102.1 in alleviating salt stress and diminishing cucumber root rot, indicating that T. atroviride strain HN082102.1 can be used as biological control agent in saline alkali land.
Bayesian identification of structural coefficients in causal models and the causal false-positive risk of confounders and colliders in linear Markovian models
Authors: Kelter Riko
Published: February 2022

Background

Causal inference has seen an increasing popularity in medical research. Estimation of causal effects from observational data allows to draw conclusions from data when randomized controlled trials cannot be conducted. Although the identification of structural causal models (SCM) and the calculation of structural coefficients has received much attention, a key requirement for valid causal inference is that conclusions are drawn based on the true data-generating model.

Methods

It remains widely unknown how large the probability is to reject the true structural causal model when observational data from it is sampled. The latter probability – the causal false-positive risk – is crucial, as rejection of the true causal model can induce bias in the estimation of causal effects. In this paper, the widely used causal models of confounders and colliders are studied regarding their causal false-positive risk in linear Markovian models. A simulation study is carried out which investigates the causal false-positive risk in Gaussian linear Markovian models. Therefore, the testable implications of the DAG corresponding to confounders and colliders are analyzed from a Bayesian perspective. Furthermore, the induced bias in estimating the structural coefficients and causal effects is studied.

Results

Results show that the false-positive risk of rejecting a true SCM of even simple building blocks like confounders and colliders is substantial. Importantly, estimation of average, direct and indirect causal effects can become strongly biased if a true model is rejected. The causal false-positive risk may thus serve as an indicator or proxy for the induced bias.

Conclusion

While the identification of structural coefficients and testable implications of causal models have been studied rigorously in the literature, this paper shows that causal inference also must develop new concepts for controlling the causal false-positive risk. Although a high risk cannot be equated with a substantial bias, it is indicative of the induced bias. The latter fact calls for the development of more advanced risk measures for committing a causal type I error in causal inference.
Enrichment Bayesian design for randomized clinical trials using categorical biomarkers and a binary outcome
Authors: Vinnat Valentin , Chevret Sylvie
Published: February 2022

Background

Adaptive clinical trials have been increasingly commonly employed to select a potential target population for one trial without conducting trials separately. Such enrichment designs typically consist of two or three stages, where the first stage serves as a screening process for selecting a specific subpopulation.

Methods

We propose a Bayesian design for randomized clinical trials with a binary outcome that focuses on restricting the inclusion to a subset of patients who are likely to benefit the most from the treatment during trial accrual. Several Bayesian measures of efficacy and treatment-by-subset interactions were used to dictate the enrichment, either based on Gail and Simon’s or Millen’s criteria. A simulation study was used to assess the performance of our design. The method is exemplified in a real randomized clinical trial conducted in patients with respiratory failure that failed to show any benefit of high flow oxygen supply compared with standard oxygen.

Results

The use of the enrichment rules allowed the detection of the existence of a treatment-by-subset interaction more rapidly compared with Gail and Simon’s criteria, with decreasing proportions of enrollment in the whole sample, and the proportions of enrichment lower, in the presence of interaction based on Millen’s criteria. In the real dataset, this may have allowed the detection of the potential interest of high flow oxygen in patients with a SOFA neurological score ≥ 1.

Conclusion

Enrichment designs that handle the uncertainty in treatment efficacy by focusing on the target population offer a promising balance for trial efficiency and ease of interpretation.
Distributional regression in clinical trials: treatment effects on parameters other than the mean
Authors: Heller Gillian Z. , Robledo Kristy P. , Marschner Ian C.
Published: February 2022

Background

The classical linear model is widely used in the analysis of clinical trials with continuous outcomes. However, required model assumptions are frequently not met, resulting in estimates of treatment effect that can be inefficient and biased. In addition, traditional models assess treatment effect only on the mean response, and not on other aspects of the response, such as the variance. Distributional regression modelling overcomes these limitations. The purpose of this paper is to demonstrate its usefulness for the analysis of clinical trials, and superior performance to that of traditional models.

Methods

Distributional regression models are demonstrated, and contrasted with normal linear models, on data from the LIPID randomized controlled trial, which compared the effects of pravastatin with placebo in patients with coronary heart disease. Systolic blood pressure (SBP) and the biomarker midregional pro-adrenomedullin (MR-proADM) were analysed. Treatment effect was estimated in models that used response distributions more appropriate than the normal (Box-Cox-t and Johnson’s Su for MR-proADM and SBP, respectively), applied censoring below the detection limit of MR-proADM, estimated treatment effect on distributional parameters other than the mean, and included random effects for longitudinal observations. A simulation study was conducted to compare the performance of distributional regression models with normal linear regression, under conditions mimicking the LIPID study. The R package gamlss (Generalized Additive Models for Location, Scale and Shape), which implements maximum likelihood estimation for distributional regression modelling, was used throughout.

Results

In all cases the distributional regression models fit the data well, in contrast to poor fits obtained for traditional models; for MR-proADM a small but significant treatment effect on the mean was detected by the distributional regression model and not the normal model; and for SBP a beneficial treatment effect on the variance was demonstrated. In the simulation study distributional models strongly outperformed normal models when the response variable was non-normal and heterogeneous; and there was no disadvantage introduced by the use of distributional regression modelling when the response satisfied the normal linear model assumptions.

Conclusions

Distributional regression models are a rich framework, largely untapped in the clinical trials world. We have demonstrated a sample of the capabilities of these models for the analysis of trials. If interest lies in accurate estimation of treatment effect on the mean, or other distributional features such as variance, the use of distributional regression modelling will yield superior estimates to traditional normal models, and is strongly recommended.

Trial registration

The LIPID trial was retrospectively registered on ANZCTR on 27/04/2016, registration number ACTRN12616000535471.
Locating and testing the healthy context paradox: examples from the INCLUSIVE trial
Authors: Melendez-Torres G. J. , Warren Emily , Ukoumunne Obioha C , Viner Russell , Bonell Chris
Published: February 2022

Background

The healthy context paradox, originally described with respect to school-level bullying interventions, refers to the generation of differences in mental wellbeing amongst those who continue to experience bullying even after interventions successfully reduce victimisation. Using data from the INCLUSIVE trial of restorative practice in schools, we relate this paradox to the need to theorise potential harms when developing interventions; formulate the healthy context paradox in a more general form defined by mediational relationships and cluster-level interventions; and propose two statistical models for testing the healthy context paradox informed by multilevel mediation methods, with relevance to structural and individual explanations for this paradox.

Methods

We estimated two multilevel mediation models with bullying victimisation as the mediator and mental wellbeing as the outcome: one with a school-level interaction between intervention assignment and the mediator; and one with a random slope component for the student-level mediator-outcome relationship predicted by school-level assignment. We relate each of these models to contextual or individual-level explanations for the healthy context paradox.

Results

Neither model suggested that the INCLUSIVE trial represented an example of the healthy context paradox. However, each model has different interpretations which relate to a multilevel understanding of the healthy context paradox.

Conclusions

Greater exploration of intervention harms, especially when those accrue to population subgroups, is an essential step in better understanding how interventions work and for whom. Our proposed tests for the presence of a healthy context paradox provide the analytic tools to better understand how to support development and implementation of interventions that work for all groups in a population.

Trial registration

Current Controlled Trials,ISRCTN10751359.
Feasibility of an online training and support program for dementia carers: results from a mixed-methods pilot randomized controlled trial
Authors: Teles Soraia , Ferreira Ana , Paúl Constança
Published: March 2022

Background

iSupport is an online program developed by the World Health Organization to provide education, skills training, and social support to informal carers of persons with dementia. This pilot study examines the feasibility of the protocol for a main effectiveness trial of iSupport-Portugal and explores how the intervention and control arms compare over time on well-being outcomes.

Methods

A mixed-methods experimental parallel between-group design with two arms is followed. Participants were recruited nationwide, by referral or advertising, through the National Alzheimer’s Association. Inclusion criteria are being Portuguese adults, providing e-consent, providing unpaid care to someone with dementia for at least 6 months, experiencing relevant scores on burden (≥ 21 on ZBI) or depression or anxiety (≥ 8 on HADS), and using webpages autonomously. Participants were consecutively randomized to receive iSupport-Portugal or an education-only e-book and were not blinded to group assignment. Data were collected online with self-administered instruments, at baseline, 3 and 6 months after. Outcomes comprise caregiver burden, depression, anxiety, QoL, positive aspects of caregiving, and self-efficacy. Generalized estimating equations were used to estimate group, time, and group-by-time effects. Intervention engagement data were extracted from iSupport’s platform. Semi-structured interviews were conducted.

Results

Forty-two participants were allocated to the intervention (N = 21) and control (N = 21) arms. Participation (78.1%) and retention rates (73.8%) were fair. More carers in the control arm completed the study (N = 20, 95.2%) than in the intervention arm (N = 11; 52.4%) (χ2 = 9.98,p = .002). Non-completers were younger, spent less time caring, and scored higher on anxiety. Among carers in the intervention arm, the average attendance rate was of 53.7%. At post-test 38.9% of participants still used iSupport; the remainder participants interrupted use within 2 weeks (Mdn). For per-protocol analyses, significant group-by-time interaction effects favouring the intervention were found for anxiety (Wald χ2 = 6.17,p = .046) and for environmental QoL (Waldχ2 = 7.06,p = .029). Those effects were not observed in intention-to-treat analyses adjusted for age. Interviewees from the intervention arm (N = 12) reported positive results of iSupport on knowledge and on experiencing positive feelings. No adverse effects were reported.

Conclusions

This study provides information for a forthcoming full-scale effectiveness trial, as on the acceptability and potential results of iSupport-Portugal. iSupport is suggested as a relevant resource for Portuguese carers.

Trial registration

ClinicalTrials.gov,NCT04104568. 26/09/2019.
Gender differences in the association of obesity-related measures with multi-morbidity among older adults in India: evidence from LASI, Wave-1
Authors: Muhammad T. , Boro Bandita , Kumar Manish , Srivastava Shobhit
Published: March 2022

Background

Co-existence of multiple chronic diseases is increasingly becoming a norm among ageing population. The study aims to investigate the prevalence of multimorbidity and the association between anthropometric measures of obesity and multimorbidity among men and women aged 60 years and above in India.

Methods

The present study is based on the first wave of the Longitudinal Aging Study in India. The analytical sample size for the study was 28,050 older adults aged 60 years and above. Descriptive statistics and multivariable analysis using logistic regression models were conducted.

Results

Body Mass Index (BMI) based-obesity is more prevalent among older women than men (26.3% vs. 17.6%). Similarly, higher proportion of older women was at high-risk waist circumference (37.1% vs 8.9%) and waist-hip ratio (78.5 vs 75.4%) than men respectively. In Model-I, after controlling for several covariates, older adults with overweight/obesity were 1.6 times more likely to have multi-morbidity than non-obese older adults (Adjusted OR = 1.61; 95% CI: 1.48–1.74). Similarly, older adults with high-risk waist circumference [Adjusted OR: 1.66; 95% CI: 1.52–1.80] and waist-hip ratio [Adjusted OR: 1.45; 95% CI: 1.33–1.59] also had higher odds of having multi-morbidity in reference to their counterparts. In model-3 it was found that females with high-risk waist-hip ratio had 14% lower odds of multimorbidity than males with high-risk waist-hip ratio [Adjusted OR: 0.86; 95%CI: 0.78–0.94].

Conclusion

The findings of the study show significant gender difference in the prevalence of multimorbidity, men being at increased risk in the multivariate analysis which is uncommon in the existing epidemiological research. Interactive effect of male gender with anthropometric measures on multimorbidity reported in our study probably due to increased unhealthy behaviours among men requires further research.
A multi-level intervention to eliminate hepatitis C from the Region of Southern Denmark: the C-Free-South project
Authors: Dröse Sandra , Øvrehus Anne Lindebo Holm , Holm Dorte Kinggaard , Madsen Lone Wulff , Mössner Belinda Klemmensen , Søholm Jacob , Hansen Janne Fuglsang , Røge Birgit Thorup , Christensen Peer Brehm
Published: March 2022

Denmark has signed the WHO strategy to eliminate hepatitis C virus (HCV). In the absence of a national strategy for elimination, a local action plan was developed in the Region of Southern Denmark (RSD). The aim of the strategy is to diagnose 90% of HCV-infected persons and treat 80% of those diagnosed by 2025. The strategy was developed by reviewing Danish data on HCV epidemiology and drug use to identify key populations for screening, linkage to care, and treatment. Based on available published data from 2016, an estimated 3028 persons in the RSD were HCV-RNA positive (population prevalence 0.21%). Of these, 1002 were attending clinical care, 1299 were diagnosed but not in clinical care, and 727 were undiagnosed. Three different interventions targeting the HCV-infected population and two interventions for HCV surveillance are planned to achieve elimination. The “C-Free-South” strategy aims to eliminate HCV in our region by identifying (90%) and treating (80%) of infected persons by the end of 2025, 5 years earlier than the WHO elimination target date.