scholarly journals The meaning of significant mean group differences for biomarker discovery

2021 ◽  
Vol 17 (11) ◽  
pp. e1009477
Author(s):  
Eva Loth ◽  
Jumana Ahmad ◽  
Chris Chatham ◽  
Beatriz López ◽  
Ben Carter ◽  
...  
Keyword(s):  
Effect Size ◽  
Biomarker Discovery ◽  
Psychiatric Research ◽  
Group Differences ◽  
Nonnormal Distributions ◽  
Autism Research ◽  
Diagnosis And Prognosis ◽  
Autistic People ◽  
Statistical Sense ◽  
Psychiatric Conditions

Over the past decade, biomarker discovery has become a key goal in psychiatry to aid in the more reliable diagnosis and prognosis of heterogeneous psychiatric conditions and the development of tailored therapies. Nevertheless, the prevailing statistical approach is still the mean group comparison between “cases” and “controls,” which tends to ignore within-group variability. In this educational article, we used empirical data simulations to investigate how effect size, sample size, and the shape of distributions impact the interpretation of mean group differences for biomarker discovery. We then applied these statistical criteria to evaluate biomarker discovery in one area of psychiatric research—autism research. Across the most influential areas of autism research, effect size estimates ranged from small (d = 0.21, anatomical structure) to medium (d = 0.36 electrophysiology, d = 0.5, eye-tracking) to large (d = 1.1 theory of mind). We show that in normal distributions, this translates to approximately 45% to 63% of cases performing within 1 standard deviation (SD) of the typical range, i.e., they do not have a deficit/atypicality in a statistical sense. For a measure to have diagnostic utility as defined by 80% sensitivity and 80% specificity, Cohen’s d of 1.66 is required, with still 40% of cases falling within 1 SD. However, in both normal and nonnormal distributions, 1 (skewness) or 2 (platykurtic, bimodal) biologically plausible subgroups may exist despite small or even nonsignificant mean group differences. This conclusion drastically contrasts the way mean group differences are frequently reported. Over 95% of studies omitted the “on average” when summarising their findings in their abstracts (“autistic people have deficits in X”), which can be misleading as it implies that the group-level difference applies to all individuals in that group. We outline practical approaches and steps for researchers to explore mean group comparisons for the discovery of stratification biomarkers.

scholarly journals Do animated triangles reveal a marked difficulty among autistic people with reading minds?

Autism ◽  
2021 ◽  
pp. 136236132198915
Author(s):  
Alexander C Wilson
Keyword(s):  
Effect Size ◽  
Meta Analysis ◽  
General Information ◽  
Medium Effect ◽  
Group Differences ◽  
Social Challenges ◽  
Autistic People ◽  
The Social ◽  
Small Effect Size ◽  
The Difference

This meta-analysis tested whether autistic people show a marked, isolated difficulty with mentalising when assessed using the Frith -Happé Animations, an advanced test of mentalising (or ‘theory of mind’). Effect sizes were aggregated in multivariate meta-analysis from 33 papers reporting data for over 3000 autistic and non-autistic people. Relative to non-autistic individuals, autistic people underperformed, with a small effect size on the non-mentalising control conditions and a medium effect size on the mentalising condition. This indicates that studies have reliably found mentalising to be an area of challenge for autistic people, although the group differences were not large. It remains to be seen how important mentalising difficulties are in accounting for the social difficulties diagnostic of autism. As autistic people underperformed on the control conditions as well as the mentalising condition, it is likely that group differences on the test are partly due to domain-general information processing differences. Finally, there was evidence of publication bias, suggesting that true effects on the Frith -Happé Animations may be somewhat smaller than reported in the literature. Lay abstract Autistic people are thought to have difficulty with mentalising (our drive to track and understand the minds of other people). Mentalising is often measured by the Frith -Happé Animations task, where individuals need to interpret the interactions of abstract shapes. This review article collated results from over 3000 people to assess how autistic people performed on the task. Analysis showed that autistic people tended to underperform compared to non-autistic people on the task, although the scale of the difference was moderate rather than large. Also, autistic people showed some difficulty with the non-mentalising as well as mentalising aspects of the task. These results raise questions about the scale and specificity of mentalising difficulties in autism. It also remains unclear how well mentalising difficulties account for the social challenges diagnostic of autism.

What is taken for granted in autism research?

2019 ◽  
Vol 42 ◽  
Author(s):  
Michele Ilana Friedner
Keyword(s):  
Research Methodologies ◽  
Communicative Practices ◽  
Autism Research ◽  
Autistic People ◽  
The Social ◽  
New Research

Abstract This commentary focuses on three points: the need to consider semiotic ideologies of both researchers and autistic people, questions of commensurability, and problems with “the social” as an analytical concept. It ends with a call for new research methodologies that are not deficit-based and that consider a broad range of linguistic and non-linguistic communicative practices.

scholarly journals Propensity Scores: Method for Matching on Multiple Variables in Down Syndrome Research

2009 ◽  
Vol 47 (5) ◽  
pp. 348-357 ◽  
Author(s):  
Jennifer Urbano Blackford
Keyword(s):  
Down Syndrome ◽  
Propensity Score ◽  
Effect Size ◽  
Propensity Scores ◽  
Group Differences ◽  
Typically Developing ◽  
Children With Down Syndrome ◽  
Confounding Variables ◽  
Multiple Variables ◽  
Birth Data

Abstract Confounding variables can affect the results from studies of children with Down syndrome and their families. Traditional methods for addressing confounders are often limited, providing control for only a few confounding variables. This study introduces propensity score matching to control for multiple confounding variables. Using Tennessee birth data as an example, newborns with Down syndrome were compared with a group of typically developing infants on birthweight. Three approaches to matching on confounders—nonmatched, covariate matched, and propensity matched—were compared using 8 potential confounders. Fewer than half of the newborns with Down syndrome were matched using covariate matching, and the matched group was differed from the unmatched newborns. Using propensity scores, 100% of newborns with Down syndrome could be matched to a group of comparison newborns, a decreased effect size was found on newborn birthweight, and group differences were not statistically significant.

The magnitude of neurocognitive impairment is overestimated in depression: the role of motivation, debilitating momentary influences, and the overreliance on mean differences

2022 ◽  
pp. 1-11
Author(s):  
Steffen Moritz ◽  
Jingyuan Xie ◽  
Danielle Penney ◽  
Lisa Bihl ◽  
Niklas Hlubek ◽  
...  
Keyword(s):  
Effect Size ◽  
Neurocognitive Impairment ◽  
Self Report ◽  
Medium Effect ◽  
Group Differences ◽  
Neurocognitive Deficits ◽  
Performance Deficits ◽  
Impact Performance ◽  
The Impact ◽  
Performance Scale

Abstract Background Meta-analyses agree that depression is characterized by neurocognitive dysfunctions relative to nonclinical controls. These deficits allegedly stem from impairments in functionally corresponding brain areas. Increasingly, studies suggest that some performance deficits are in part caused by negative task-taking attitudes such as poor motivation or the presence of distracting symptoms. A pilot study confirmed that these factors mediate neurocognitive deficits in depression. The validity of these results is however questionable given they were based solely on self-report measures. The present study addresses this caveat by having examiners assess influences during a neurocognitive examination, which were concurrently tested for their predictive value on performance. Methods Thirty-three patients with depression and 36 healthy controls were assessed on a battery of neurocognitive tests. The examiner completed the Impact on Performance Scale, a questionnaire evaluating mediating influences that may impact performance. Results On average, patients performed worse than controls at a large effect size. When the total score of the Impact on Performance Scale was accounted for by mediation analysis and analyses of covariance, group differences were reduced to a medium effect size. A total of 30% of patients showed impairments of at least one standard deviation below the mean. Conclusions This study confirms that neurocognitive impairment in depression is likely overestimated; future studies should consider fair test-taking conditions. We advise researchers to report percentages of patients showing performance deficits rather than relying solely on overall group differences. This prevents fostering the impression that the majority of patients exert deficits, when in fact deficits are only true for a subgroup.

scholarly journals Fifth metatarsal stress fracture in elite male football players: an on-field analysis of plantar loading

2018 ◽  
Vol 4 (1) ◽  
pp. e000377 ◽  
Author(s):  
Athol Thomson ◽  
Richard Akenhead ◽  
Rodney Whiteley ◽  
Pieter D'Hooghe ◽  
Ken Van Alsenoy ◽  
...  
Keyword(s):  
Stress Fracture ◽  
Effect Size ◽  
Field Analysis ◽  
Group Differences ◽  
Football Players ◽  
Vertical Force ◽  
Primary Stress ◽  
Straight Line ◽  
Plantar Force ◽  
To Receive

ObjectiveEvaluate plantar loading during ‘on-field’ common football movements in players after fifth metatarsal (MT-5) stress fracture and compare with matched healthy players.MethodsFourteen elite male soccer players participated in the study conducted on a natural grass playing surface using firm ground football boots. Seven players who had suffered a primary stress fracture (MT-5 group) and seven matched healthy players (controls, CON) performed three common football movements while in-shoe plantar loading data were collected.ResultsLarge between-group differences exist for maximal vertical force normalised to bodyweight (Fmax) at the lateral toes (2-5) of the stance leg during a set-piece kick (MT-5: 0.2±0.06 bodyweight (BW), CON: 0.1±0.05 BW, effect size (ES) 1.4) and the curved run where the MT-5 group showed higher Fmaxwith very large effect size at the lateral forefoot of the injured (closest to curve) limb when running a curve to receive a pass (MT-5 injured−CON=0.01 BW, ES 1.5). Small between-group differences were evident during straight-line running. However, between-limb analysis of MT-5 group showed significant unloading of the lateral forefoot region of the involved foot.ConclusionsElite male football players who have returned to play after MT-5 stress fracture display significantly higher maximum plantar force at the lateral forefoot and lateral toes (2-5) compared with healthy matched control players during two football movements (kick and curved run) with the magnitude of these differences being very large. These findings may have important implications for manipulating regional load during rehabilitation or should a player report lateral forefoot prodromal symptoms.

scholarly journals Methodological Approaches to Study Extracellular Vesicle miRNAs in Epstein–Barr Virus-Associated Cancers

2018 ◽  
Vol 19 (9) ◽  
pp. 2810 ◽  
Author(s):  
Li Sun ◽  
David Meckes
Keyword(s):  
Epstein Barr Virus ◽  
Biomarker Discovery ◽  
Immune Escape ◽  
Human Cancer ◽  
Biological Fluids ◽  
Extracellular Vesicle ◽  
Cellular Mirnas ◽  
Barr Virus ◽  
Diagnosis And Prognosis ◽  
Epstein Barr

Epstein Barr-virus (EBV) was the first virus identified to be associated with human cancer in 1964 and is found ubiquitously throughout the world’s population. It is now established that EBV contributes to the development and progression of multiple human cancers of both lymphoid and epithelial cell origins. EBV encoded miRNAs play an important role in tumor proliferation, angiogenesis, immune escape, tissue invasion, and metastasis. Recently, EBV miRNAs have been found to be released from infected cancer cells in extracellular vesicles (EVs) and regulate gene expression in neighboring uninfected cells present in the tumor microenvironment and possibly at distal sites. As EVs are abundant in many biological fluids, the viral and cellular miRNAs present within EBV-modified EVs may serve as noninvasion markers for cancer diagnosis and prognosis. In this review, we discuss recent advances in EV isolation and miRNA detection, and provide a complete workflow for EV purification from plasma and deep-sequencing for biomarker discovery.

Scapular exercise combined with cognitive functional therapy is more effective at reducing chronic neck pain and kinesiophobia than scapular exercise alone: a randomized controlled trial

2020 ◽  
Vol 34 (12) ◽  
pp. 1485-1496 ◽  
Author(s):  
Norollah Javdaneh ◽  
Amir Letafatkar ◽  
Sadredin Shojaedin ◽  
Malihe Hadadnezhad
Keyword(s):  
Randomized Controlled Trial ◽  
Neck Pain ◽  
Pain Intensity ◽  
Effect Size ◽  
Controlled Trial ◽  
Chronic Neck Pain ◽  
Secondary Outcome ◽  
Group Differences ◽  
Functional Therapy ◽  
Randomized Controlled

Objective: The aim of this study was to compare the effectiveness of scapular exercises alone and combined with cognitive functional therapy in treating patients with chronic neck pain and scapular downward rotation impairment. Design: Single-blind randomized controlled trial. Setting: Outpatient. Subjects: A total of 72 patients (20–45 years old) with chronic neck pain were studied. Intervention: Allocation was undertaken into three groups: scapular exercise ( n = 24), scapular exercise with cognitive functional therapy ( n = 24) and control ( n = 24) groups. Each programme lasted three times a week for six weeks. Main outcomes: The primary outcome measure was pain intensity measured by the visual analogue scale scores. The secondary outcome measures included kinesiophobia and muscles activity. Results: Statistically significant differences in pain intensity were found when multidisciplinary physiotherapy group including a cognitive functional approach was compared with the scapular exercise alone group at six weeks (effect size (95% CI) = −2.56 (−3.32 to −1.80); P = 0.019). Regarding kinesiophobia, a significant between-group difference was observed at six-week (effect size (95% CI) = −2.20 (−2.92 to −1.49); P = 0.005), with the superiority of effect in multidisciplinary physiotherapy group. A significant between-group differences was observed in muscle activity. Also, there were significant between-group differences favouring experimental groups versus control. Conclusion: A group-based multidisciplinary rehabilitation programme including scapular exercise plus cognitive functional therapy was superior to group-based scapular exercise alone for improving pain intensity, kinesiophobia and muscle activation in participants with chronic neck pain.

Diagnostic Prediction and Prognosis

2013 ◽  
Author(s):  
Michael A. Bishop ◽  
J. D. Trout
Keyword(s):  
Psychiatric Diagnosis ◽  
Diagnostic Method ◽  
Ethical Issues ◽  
Moral Issues ◽  
Diagnosis And Prognosis ◽  
Psychiatric Conditions ◽  
Conceptual Problems ◽  
The Many ◽  
The Individual ◽  
Individual Clinician

Psychiatric diagnosis and prognosis is fraught with important philosophical and conceptual problems. This chapter focuses on some epistemological issues (What evidence justifies the belief that a course of treatment is effective?) and moral issues (What is a just distribution of scarce psychiatric resources given the many people with psychiatric conditions whose suffering could be alleviated with treatment?) that arise in contemporary psychiatric practice. It examines various clinical and actuarial techniques for psychiatric diagnosis, ordered very loosely in terms of how "structured" or "automated" they are (or, put another way, ordered according to how much freedom the individual clinician has in carrying out the diagnostic method). The chapter makes the case for assessing psychiatric treatments with controlled experiments, raises several epistemological dangers that arise from relying on uncontrolled investigations, and considers some of the unique methodological and ethical issues that arise when trying to assess talk therapy.

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