Quantifying and leveraging predictive uncertainty for medical image assessment

The interpretation of medical images is a challenging task, often complicated by the presence of artifacts, occlusions, limited contrast and more. Most notable is the case of chest radiography, where there is a high inter-rater variability in the detection and classification of abnormalities. This is largely due to inconclusive evidence in the data or subjective definitions of disease appearance. An additional example is the classification of anatomical views based on 2D Ultrasound images. Often, the anatomical context captured in a frame is not sufficient to recognize the underlying anatomy. Current machine learning solutions for these problems are typically limited to providing probabilistic predictions, relying on the capacity of underlying models to adapt to limited information and the high degree of label noise. In practice, however, this leads to overconfident systems with poor generalization on unseen data. To account for this, we propose a system that learns not only the probabilistic estimate for classification, but also an explicit uncertainty measure which captures the confidence of the system in the predicted output. We argue that this approach is essential to account for the inherent ambiguity characteristic of medical images from different radiologic exams including computed radiography, ultrasonography and magnetic resonance imaging. In our experiments we demonstrate that sample rejection based on the predicted uncertainty can significantly improve the ROC-AUC for various tasks, e.g., by 8% to 0.91 with an expected rejection rate of under 25% for the classification of different abnormalities in chest radiographs. In addition, we show that using uncertainty-driven bootstrapping to filter the training data, one can achieve a significant increase in robustness and accuracy. Finally, we present a multi-reader study showing that the predictive uncertainty is indicative of reader errors.     

The apex angle of the rocker sole affects the posture and gait stability of healthy individuals

BackgroundRocker sole (RS) shoes have been linked to impaired postural control. However, which features of RS design affect balance is unclear.Research questionWhich RS design features affect standing balance and gait stability?MethodsThis study utilized an intervention and cross-over design. Twenty healthy young adults (10 males and 10 females) participated in this study. Standing balance and gait stability were measured using a single force platform and three-dimensional motion analysis system, respectively. The experimental conditions included the control shoe and five RS shoes in the combination of apex position (%) and apex angle (degree) for RS50-95, RS60-95, RS70-95, RS60-70, and RS60-110. The main outcome measures were the area surrounding the maximal rectangular amplitude, mean path length, average displacement of the center of pressure along the lateral and anterior/posterior directions, and maximal center of pressure excursion as the standing balance and lateral margin of stability as the gait stability. Statistical analyses were conducted using a two-way split-plot analysis of variance with repeated measures (with RS design as the within-subject factor and sex as the between-subject factor) and the Bonferroni post hoc test (α = .05).ResultsRegarding the mean path length, RS60-70 was significantly longer than the control shoe, and it showed a significantly increased lateral margin of stability. Thus, RS60-70 was shown to affect standing balance, limit of stability, and gait stability of the frontal plane during gait.SignificanceThese results suggest that the apex angle of the RS design feature affects standing balance and gait stability, and RS60-70 is detrimental to stability. Therefore, when RS with a small apex angle is prescribed, it is necessary to consider the patient’s balance ability.     

The rise of stem cells in skin rejuvenation: A new frontier

Stem cells have recently garnered increased attention, especially pertaining to their use in cutaneous rejuvenation. Their popularity has continued to grow with patients and consumers alike, which has followed the substantial marketing bolstering them. Although limited, studies have begun to demonstrate promise in the field of esthetics. We review the prominent studies in the literature to shed more light on the use of stem cells for cosmetic practitioners.     

Preparation and identification of multifunctional mesoporous silica nanoparticles for in vitro and in vivo dual-mode imaging,theranostics, and targeted tracking

Mesoporous silica nanoparticles (MSNs) can provide a structural foundation for a new generation of nanocarriers with a broad range of functionalities. Multifunctional MSNs can serve as all-in-one diagnostic and therapeutic tools that can be used to simultaneously visualize and treat various diseases, such as cancer. This research study is the first time that two lanthanide-based imaging systems have been combined to incorporate controlled drug release and targeted tracing into a single MSN-based nano-platform for a novel theranostic drug delivery system. Doping lanthanide ions, i.e., europium (Eu) and gadolinium (Gd) ions, into an MSN structure (EuGd-MSNs) imparts fluorescence and magnetism to the nanostructure that can be used to develop magnetic resonance imaging (MRI) and biological fluorescence tools. Current cancer research has revealed that most human cancer cells express a large number of folate receptors on their surface. Grafting folic acid (FA) onto the EuGd-MSN surface (EuGd-FA-MSNs) imparts a targeting function to the MSN because of the specificity of the binding of FA to cell surface receptors. Furthermore, grafting anticancer drugs, such as camptothecin (CPT), onto the surface of these MSNs by forming disulfide bonds (EuGd-SS-CPT-FA-MSNs) enables intracellular controlled drug release. A high concentration of intracellular glutathione cleaves the disulfide bond to release the drug and treat the disease. The results of in vitro and in vivo studies show that the functionalized MSNs can be successfully used as a platform to integrate dual-imaging, targeting, and therapeutic treatment in multifunctional diagnosis drug delivery systems.     

Association of genetic variants at MYP10 and MYP15 with high myopia in a Han Chinese population

Background: Previous genome-wide association study (GWAS) has revealed the association between MYP10 at 8p23 and MYP15 at 10q21.1 and high myopia (HM) in a French population. This study is managed to discover the connection between some single nucleotide polymorphism (located at MYP10 and MYP15) and Han Chinese HM.

Methods and Results: This case-control association study contained 1673 samples, including 869 ophthalmic patients and 804 controls. Twelve tag SNPs have been selected from the MYP10 and MYP15 loci and genotyped by SNaPshot method. Among 12 SNPs, rs4840437 and rs6989782 in TNKS gene were found significant association with HM. Carriers of rs4840437G allele and rs4840437GG genotype created a low risk of high myopia (P = .036, OR = 0.81, 95%CI = 0.71–0.93; P = .016, OR = 0.73, 95%CI = 0.56–0.96; respectively). Carriers of rs6989782T allele and rs6989782TT+CT genotype also had a decreased risk of high myopia (P = .048, OR = 0.82, 95%CI = 0.71–0.94; P = .006, OR = 0.74, 95%CI = 0.59–0.92; respectively). Other 10 SNPs displaced nonsignificant association with HM. Additionally, the risk haplotype AC and the protective haplotype GT, generated by two SNPs in TNKS, were considerably more likely to be association with HM (for AC, P = .002 and OR = 1.26; for GT, P = .027 and OR = 0.84).

Conclusions: Our results demonstrated that some heritable variants in the TNKS gene are associated with HM in the Han population. The possible functions of TNKS in the development and pathogenesis of hereditary high myopia still require further researches to identify.     

Adverse childhood experiences,inflammation, and depressive symptoms in later life: a prospective cohort study

BackgroundExposure to adverse childhood experiences (ACEs) has been associated with both inflammation and depression. However, little research has examined the potential mediational role of inflammation in the link between ACEs and depression using longitudinal data. Therefore, we investigated the direct and indirect effects of ACEs on inflammation, depression, and their change trajectories over time.MethodsWe used data from the English Longitudinal Study of Ageing. Four ACE categories were assessed retrospectively at wave 3 (2006–07): abuse (physical or sexual abuse or physical assault), family dysfunction (parent arguments, parent mental illness or substance abuse, or parent separation or divorce), poor parent–child bonding (maternal or paternal), and loss of an attachment figure (separation from mother for >6 months, parent death, foster care or adoption, or institutionalisation). A cumulative ACE score was calculated representing the total number of ACEs experienced by the participants. Concentration of C-reactive protein (CRP), an inflammatory marker, was measured at waves 2 (2004–05), 4 (2008–09), and 6 (2012–13). Depressive symptoms were ascertained using the 8-item Centre for Epidemiological Studies Depression Scale from waves 6 to 8 (2016–17). The longitudinal direct and indirect effects of ACEs were estimated using parallel process latent growth curve modelling. All analyses were adjusted for relevant confounders. Missing data were estimated using multiple imputation.ResultsAmong the study sample (N=4382; mean age 70 years; 56% female), 24% of participants reported one ACE and 13% had two or three ACEs. The percentage of participants with three or more depressive symptoms was 21% at baseline. Greater cumulative exposure to ACEs was associated with increased CRP concentration (β=0·042, p=0·010) and depressive symptoms (β=0·164, p<0·0001) at baseline and predicted a steeper increase in these outcomes throughout the study (β_CRP=0·074, p=0·011; β_Depression=0·338, p<0·0001). However, indirect effects of ACEs on depression mediated by CRP were not observed, with only weak associations between CRP and depressive symptoms (β_iDepression=0·032, p=0·173; β_sDepression=0·067, p=0·240). Sensitivity analyses using only somatic depressive symptoms as the outcome revealed a positive association between CRP and somatic symptoms at baseline (β_iDepression=0·068, p=0·008), although the indirect effects remained non-significant in this model.InterpretationBiological mechanisms other than inflammation might underlie the relationship between ACEs and depression. Psychosocial interventions to reduce the negative effects of ACEs on children's development could help to reduce the risk of depression and of other medical conditions linked to inflammation.FundingEconomic and Social Research Council–Biotechnology and Biological Sciences Research Council Soc-B Centre for Doctoral Training (ES/P000347/1).