Can videos affect learning outcomes? Evidence from an actual learning environment.

We examine the effect of an innovation in an educational context, a class of 500 + first-year economics students at a well-known Australian university. We study whether introducing content in the form of a multimedia presentation has a detectable effect on specific categories of student knowledge. The multimedia presentation has a narrator presenting concepts with images, words, and worked examples. Our key outcome measure is the probability of answering questions correctly on a mid-term test. A quasi-experimental design is followed to offer a causal interpretation of the results. We find that the multimedia presentation markedly increases students' academic outcomes on the test compared to those that did not view the presentation, especially in regards to procedural and evaluative knowledge. An additional survey reveals gains in students' metacognitive knowledge. These findings suggest that multimedia presentations contribute to improved student learning outcomes and offer valuable options at a time of increased online course delivery. The findings also highlight the relevance of investing in education and resources to develop the necessary design skills among academics and staff. Supplementary Information: The online version of this article contains supplementary material available 10.1007/s11423-022-10147-3.

Competing risks analysis with missing cause-of-failure-penalized likelihood estimation of cause-specific Cox models.

Competing risks models are attractive tools to analyze time-to-event data where several causes of an event are competing. However, a complexity may arise when, for instance, some subjects experience the event of interest but the causes are not known. Assuming that unknown causes of events are missing at random, we developed a novel constrained maximum penalized likelihood method for fitting semi-parametric cause-specific Cox regression models. Here, penalty functions were used to smooth the baseline hazards. An appealing feature of this approach is that all the relevant estimands in competing risks models are estimated including cause-specific hazard ratios, cause-specific baseline hazards, and cumulative incidence functions. Asymptotic results for these estimators were also developed, allowing for direct inferences. The proposed method was compared with some existing methods through a simulation study. A real data example was analyzed using the new method to evaluate the association of age at diagnosis with melanoma-death and non-melanoma-death in patients diagnosed with thin melanoma (tumour thickness ≤1.0 mm). An R function for our proposed method is currently available on GitHub and will be included in the R package "survivalMPL" at CRAN.

Machine Learning for the Prediction of Molecular Markers in Glioma on Magnetic Resonance Imaging: A Systematic Review and Meta-Analysis.

BACKGROUND: Molecular characterization of glioma has implications for prognosis, treatment planning, and prediction of treatment response. Current histopathology is limited by intratumoral heterogeneity and variability in detection methods. Advances in computational techniques have led to interest in mining quantitative imaging features to noninvasively detect genetic mutations. OBJECTIVE: To evaluate the diagnostic accuracy of machine learning (ML) models in molecular subtyping gliomas on preoperative magnetic resonance imaging (MRI). METHODS: A systematic search was performed following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines to identify studies up to April 1, 2020. Methodological quality of studies was assessed using the Quality Assessment for Diagnostic Accuracy Studies (QUADAS)-2. Diagnostic performance estimates were obtained using a bivariate model and heterogeneity was explored using metaregression. RESULTS: Forty-four original articles were included. The pooled sensitivity and specificity for predicting isocitrate dehydrogenase (IDH) mutation in training datasets were 0.88 (95% CI 0.83-0.91) and 0.86 (95% CI 0.79-0.91), respectively, and 0.83 to 0.85 in validation sets. Use of data augmentation and MRI sequence type were weakly associated with heterogeneity. Both O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation and 1p/19q codeletion could be predicted with a pooled sensitivity and specificity between 0.76 and 0.83 in training datasets. CONCLUSION: ML application to preoperative MRI demonstrated promising results for predicting IDH mutation, MGMT methylation, and 1p/19q codeletion in glioma. Optimized ML models could lead to a noninvasive, objective tool that captures molecular information important for clinical decision making. Future studies should use multicenter data, external validation and investigate clinical feasibility of ML models.

Patient functional outcomes and quality of life after surgery for unruptured brain arteriovenous malformation.

BACKGROUND: Studies have questioned the effectiveness of surgery for the management of unruptured brain arteriovenous malformation (ubAVM). Few studies have examined functional outcomes and quality of life (QOL) prior and 12 months after surgical repair of ubAVM. OBJECTIVE: This study examined the effectiveness of surgical management of ubAVM by measuring patients' perceived QOL and their ability to perform everyday activities. METHODS: Between 2011 and 2016, patients diagnosed with an unbAVM were assessed using the Quality Metric Short Form 36 (SF36), the DriveSafe component of the off-road driver screening tool DriveSafeDriveAware (DSDA), the modified Barthel Index (mBI) and the modified Rankin Scale (mRS). Reassessments were conducted at the 6-week post-operative follow-up for surgical patients and at 12-month follow-up for surgical and conservatively managed patients. RESULTS: Forty-five patients enrolled in the study, of which 35 (78%) had their ubAVM surgically treated. Patients undergoing surgery had a significantly lower ubAVM Spetzler-Ponce Class (SPC). There was no significant difference 12 months after presentation in function or QOL for either the conservative or surgical group. The surgical group had significantly higher QOL of life scores from pre-surgery to 12 months post-surgery (PCS p < 0.01; MCS p = 0.02). Higher SP grade ubAVM was significantly related to poorer function in the surgical group (SP C compared with SP A; p = 0.04, mean difference - 12.4, 95%CI - 24.3 to - 0.4). CONCLUSION: Function and QOL are not diminished after surgical treatment of low Spetzler-Ponce Class unruptured brain arteriovenous malformations. QOL is higher 12 months after surgery for ubAVM than for those who do not have treatment for their ubAVM.

Test-retest reliability of touchscreen DriveSafe DriveAware.

INTRODUCTION: This prospective study examines the test-retest reliability of touchscreen DriveSafe DriveAware (DSDA). In a future study, the authors intend assessing the usefulness of DSDA to measure progress of patients undergoing treatment for neurological conditions. Evidence of test-retest reliability is required first. METHODS: Australian adults with current driver's licences (N = 39) aged 20 to 91 years (Mage  = 58) recruited from a convenience sample were assessed with DSDA. The assessment was repeated 6 weeks, 6 months, and 12 months later to match planned assessments of patients undergoing neurosurgical treatment in future research. DSDA classification, DriveSafe subtest score, and DriveAware subtest scores were analysed as a whole sample, and in three age groups. RESULTS: DSDA classification and DriveAware scores were consistent over repeated tests. DriveSafe scores increased between test 1 and 2 (p = .006), and thereafter no significant change from test 2 to 4. DriveSafe scores of older participants (70+ years) increased between test 1 and 2 more notably than younger participants' scores. No DriveSafe scores decreased over time. CONCLUSION: DSDA classification and DriveAware scores demonstrated test-retest reliability for all age groups. DriveSafe scores did not demonstrate test-retest reliability between test 1 and 2 for participants 70+ years. However, DriveSafe scores demonstrated test-retest reliability after test 2, possibly indicating an initial learning effect for the DriveSafe score only. The authors posit that this result may have been influenced by older adults' reduced familiarity with iPad technology at first assessment. Further longitudinal research is required to confirm whether these results are consistent in a sample population with diagnosed cognitive impairment. Future research will assess whether repeated assessment of DSDA may be useful for monitoring and screening cognitive fitness to drive in patients who have undergone neurosurgical treatment and whether declining scores may indicate cognitive changes in ability to drive.

Functional outcomes and quality of life after microsurgical clipping of unruptured intracranial aneurysms: a prospective cohort study.

OBJECTIVE :Few studies have examined patients' ability to drive and quality of life (QOL) after microsurgical repair for unruptured intracranial aneurysms (uIAs). However, without a strong evidentiary basis, jurisdictional road transport authorities have recommended driving restrictions following brain surgery. In the present study, authors examined the outcomes of the microsurgical repair of uIAs by measuring patients' perceived QOL and cognitive abilities related to driving. METHODS: Between January 2011 and January 2016, patients with a new diagnosis of uIA were prospectively enrolled in this study. Assessments were performed at referral, before surgery, and at 6 weeks and 12 months after surgery in those undergoing microsurgical repair and at referral and at 12 months in conservatively managed patients. Assessments included the Physical Component Summary (PCS) and Mental Component Summary (MCS) of the SF-36, the off-road driver-screening instrument DriveSafe (DS), the modified Barthel Index (mBI), and the modified Rankin Scale (mRS). RESULTS: One hundred sixty-nine patients were enrolled in and completed the study, and 112 (66%) of them had microsurgical repair of their aneurysm. In the microsurgical group, there was a trend for improved DS scores: from a mean (± standard deviation) score of 108 ± 10.7 before surgery to 111 ± 9.7 at 6 weeks after surgery to 112 ± 10.2 at 12 months after surgery (p = 0.05). Two percent of the microsurgical repair group and 4% of the conservatively managed group whose initial scores indicated competency to drive according to the DS test subsequently had 12-month scores deemed as not competent to drive; the difference between these 2 groups was not statistically significant (p > 0.99). Factors associated with a decline in the DS score among those who had a license at the time of initial assessment were an increasing age (p < 0.01) and mRS score > 0 at one of the assessments (initial, 6 weeks, or 12 months; p < 0.01). Mean PCS scores in the microsurgical repair group were 52 ± 8.1, 46 ± 6.8, and 52 ± 7.1 at the initial, 6-week, and 12-month assessments, respectively (p < 0.01). These values represented a significant decline in the mean PCS score at 6 weeks that recovered by 12 months (p < 0.01). There were no significant changes in the MCS, mBI, or mRS scores in the surgical group. CONCLUSIONS: Overall, QOL at 12 months for the microsurgical repair group had not decreased and was comparable to that in the conservatively managed group. Furthermore, as assessed by the DS test, the majority of patients were not affected in their ability to drive.

Quality of life and disability 12 months after surgery vs. conservative management for unruptured brain arteriovenous malformations: Scottish population-based and Australian hospital-based studies.

BACKGROUND: Few data are available on disability and quality of life (QOL) after surgery versus conservative management for unruptured brain arteriovenous malformations (uAVMs). OBJECTIVE: The aim of this study was to test the hypothesis that QOL and disability are worse after surgery ± preoperative embolisation for uAVM compared with conservative management. METHODS: We included consecutive patients diagnosed with uAVM from a prospective population-based study in Scotland (1999-2003; 2006-2010) and a prospective hospital-based series in Australia (2011-2015). We assessed outcomes on the modified Rankin Scale (mRS) and the Short Form (SF)-36 at ~ 12 months after surgery or conservative treatment and compared these groups using continuous ordinal regression in the two cohorts separately. RESULTS: Surgery was performed for 29% of all uAVM cases diagnosed in Scotland and 84% of all uAVM referred in Australia. There was no statistically significant difference between surgery and conservative management at 12 months among 79 patients in Scotland (mean SF-36 Physical Component Score (PCS) 39 [SD 14] vs. 39 [SD 13]; mean SF-36 Mental Component Score (MCS) 38 [SD 14] vs. 39 [SD 14]; mRS > 1, 24 vs. 9%), nor among 37 patients in Australia (PCS 51 [SD 10] vs. 49 [SD 6]; MCS 48 [SD 12] vs. 49 [SD 10]; mRS > 1, 19 vs. 30%). In the Australian series, there was no statistically significant change in the MCS and PCS between baseline before surgery or conservative management and 12 months. CONCLUSIONS: We did not find a statistically significant difference between surgery ± preoperative embolisation and conservative management in disability or QOL at 12 months.

How to analyze the Visual Analogue Scale: Myths, truths and clinical relevance.

BACKGROUND AND AIMS: The Visual Analogue Scale (VAS) is a popular tool for the measurement of pain. A variety of statistical methods are employed for its analysis as an outcome measure, not all of them optimal or appropriate. An issue which has attracted much discussion in the literature is whether VAS is at a ratio or ordinal level of measurement. This decision has an influence on the appropriate method of analysis. The aim of this article is to provide an overview of current practice in the analysis of VAS scores, to propose a method of analysis which avoids the shortcomings of more traditional approaches, and to provide best practice recommendations for the analysis of VAS scores. METHODS: We report on the current usage of statistical methods, which fall broadly into two categories: those that assume a probability distribution for VAS, and those that do not. We give an overview of these methods, and propose continuous ordinal regression, an extension of current ordinal regression methodology, which is appropriate for VAS at an ordinal level of measurement. We demonstrate the analysis of a published data set using a variety of methods, and use simulation to compare the power of the various methods to detect treatment differences, in differing pain situations. RESULTS: We demonstrate that continuous ordinal regression provides the most powerful statistical analysis under a variety of conditions. CONCLUSIONS AND IMPLICATIONS: We recommend that in the situation in which no covariates besides treatment group are included in the analysis, distribution-free methods (Wilcoxon, Mann-Whitney) be used, as their power is indistinguishable from that of the proposed method. In the situation in which there are covariates which affect VAS, the proposed method is optimal. However, in this case, if the VAS scores are not concentrated around either extreme of the scale, normal-distribution methods (t-test, linear regression) are almost as powerful, and are recommended as a pragmatic choice. In the case of small sample size and VAS skewed to either extreme of the scale, the proposed method has vastly superior power to other methods.

Ordinal regression models for continuous scales.

Ordinal regression analysis is a convenient tool for analyzing ordinal response variables in the presence of covariates. In this paper we extend this methodology to the case of continuous self-rating scales such as the Visual Analog Scale (VAS) used in pain assessment, or the Linear Analog Self-Assessment (LASA) scales in quality of life studies. These scales measure subjects' perception of an intangible quantity, and cannot be handled as ratio variables because of their inherent nonlinearity. We express the likelihood in terms of a function connecting the scale with an underlying continuous latent variable and approximate this function either parametrically or non-parametrically. Then a general semi-parametric regression framework for continuous scales is developed. Two data sets have been analyzed to compare our method to the standard discrete ordinal regression model, and the parametric to the non-parametric versions of the model. The first data set uses VAS data from a study on the efficacy of low-level laser therapy in the treatment of chronic neck pain; the second comes from a study on chemotherapy treatments in advanced breast cancer and looks at the impact of different drugs on patients' quality of life. The continuous formulation of the ordinal regression model has the advantage of no loss of precision due to categorization of the scores and no arbitrary choice of the number and boundaries of categories. The semi-parametric form of the model makes it a flexible method for analysis of continuous ordinal scales.

A field synopsis on low-penetrance variants in DNA repair genes and cancer susceptibility.

BACKGROUND: Several genes encoding for DNA repair molecules implicated in maintaining genomic integrity have been proposed as cancer-susceptibility genes. Although efforts have been made to create synopses for specific fields that summarize the data from genetic association studies, such an overview is not available for genes involved in DNA repair. METHODS: We have created a regularly updated database of studies addressing associations between DNA repair gene variants (excluding highly penetrant mutations) and different types of cancer. Using 1087 datasets and publicly available data from genome-wide association platforms, meta-analyses using dominant and recessive models were performed on 241 associations between individual variants and specific cancer types that had been tested in two or more independent studies. The epidemiological strength of each association was graded with Venice criteria that assess amount of evidence, replication, and protection from bias. All statistical tests were two-sided. RESULTS: Thirty-one nominally statistically significant (ie, P < .05 without adjustment for multiple comparisons) associations were recorded for 16 genes in dominant and/or recessive model analyses (BRCA2, CCND1, ERCC1, ERCC2, ERCC4, ERCC5, MGMT, NBN, PARP1, POLI, TP53, XPA, XRCC1, XRCC2, XRCC3, and XRCC4). XRCC1, XRCC2, TP53, and ERCC2 variants were each nominally associated with several types of cancer. Three associations were graded as having "strong" credibility, another four had modest credibility, and 24 had weak credibility based on Venice criteria. Requiring more stringent P values to account for multiplicity of comparisons, only the associations of ERCC2 codon 751 (recessive model) and of XRCC1 -77 T>C (dominant model) with lung cancer had P

Exposure to the tobacco smoke constituent 4-aminobiphenyl induces chromosomal instability in human cancer cells.

The relationships between environmental factors and the genetic abnormalities that drive carcinogenesis are supported by experimental and epidemiologic evidence but their molecular basis has not been fully elucidated. At the genomic level, most human cancers display either chromosomal (CIN) or microsatellite (MIN) instability. The molecular mechanisms through which normal cells acquire these forms of instability are largely unknown. The arylamine 4-aminobiphenyl (4-ABP) is a tobacco smoke constituent, an environmental contaminant, and a well-established carcinogen in humans. Among others, bladder, lung, colon, and breast cancers have been associated with 4-ABP. We have investigated the effects of 4-ABP and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on genetically stable colorectal (HCT116) and bladder (RT112) cancer cells. Cells were treated with carcinogens to generate resistant clones that were then subjected to genetic analysis to assess whether they displayed either CIN or MIN. We found that 50% to 60% of cells treated with 4-ABP developed CIN but none developed MIN as confirmed by their ability to gain and lose chromosomes. In contrast, all MNNG-treated clones (12/12) developed MIN but none developed CIN as shown by the microsatellite assay. The mismatch repair protein expression analysis suggests that the acquired mechanism of MIN resistance in the HCT116 MNNG-treated cells is associated with the reduction or the complete loss of MLH1 expression. By providing a mechanistic link between exposure to a tobacco constituent and the development of CIN, our results contribute to a better understanding of the origins of genetic instability, one of the remaining unsolved problems in cancer research.

XRCC3 and XPD/ERCC2 single nucleotide polymorphisms and the risk of cancer: a HuGE review.

Hundreds of polymorphisms in DNA repair genes have been identified; however, for many of these polymorphisms, the impact on repair phenotype and cancer susceptibility remains uncertain. In this review, the authors focused on the x-ray repair cross-complementing protein group 3 (XRCC3) and xeroderma pigmentosum group D (XPD)/excision repair cross-complementing rodent repair deficiency (ERCC2) genes, because they are among the most extensively studied but no final conclusion has yet been drawn about their role in cancer occurrence. XRCC3 participates in DNA double-strand break/recombinational repair through homologous recombination to maintain chromosome stability. XPD/ERCC2 is a helicase involved in the nucleotide excision repair pathway, which recognizes and repairs many structurally unrelated lesions, such as bulky adducts and thymidine dimers. The authors identified a sufficient number of epidemiologic studies on cancer to perform meta-analyses for XPD/ERCC2 variants in codons 156, 312, and 751 and XRCC3 variants in codon 241. The authors evaluated all cancer sites to investigate whether DNA repair is likely to take place in a rather nonspecific manner for different carcinogens and different cancers. For the most part, the authors found no association between these genes and the cancer sites investigated, except for some statistically significant associations between XPD/ERCC2 single nucleotide polymorphisms and skin, breast, and lung cancers.