We take a new, scenario-based look at evaluation in information visualization. Our seven scenarios, evaluating visual data analysis and reasoning, evaluating user performance, evaluating user ...experience, evaluating environments and work practices, evaluating communication through visualization, evaluating visualization algorithms, and evaluating collaborative data analysis were derived through an extensive literature review of over 800 visualization publications. These scenarios distinguish different study goals and types of research questions and are illustrated through example studies. Through this broad survey and the distillation of these scenarios, we make two contributions. One, we encapsulate the current practices in the information visualization research community and, two, we provide a different approach to reaching decisions about what might be the most effective evaluation of a given information visualization. Scenarios can be used to choose appropriate research questions and goals and the provided examples can be consulted for guidance on how to design one's own study.
We propose incremental logarithmic time-series technique as a way to deal with time-based representations of large and dynamic event data sets in limited space. Modern data visualization problems in ...the domains of news analysis, network security and financial applications, require visual analysis of incremental data, which poses specific challenges that are normally not solved by static visualizations. The incremental nature of the data implies that visualizations have to necessarily change their content and still provide comprehensible representations. In particular, in this paper we deal with the need to keep an eye on recent events together with providing a context on the past and to make relevant patterns accessible at any scale. Our technique adapts to the incoming data by taking care of the rate at which data items occur and by using a decay function to let the items fade away according to their relevance. Since access to details is also important, we also provide a novel distortion magnifying lens technique which takes into account the distortions introduced by the logarithmic time scale to augment readability in selected areas of interest. We demonstrate the validity of our techniques by applying them on incremental data coming from online news streams in different time frames.
Autophagy is emerging as a key regulatory process during skeletal muscle development, regeneration and homeostasis, and deregulated autophagy has been implicated in muscular disorders and age-related ...muscle decline. We have monitored autophagy in muscles of mdx mice and human Duchenne muscular dystrophy (DMD) patients at different stages of disease. Our data show that autophagy is activated during the early, compensatory regenerative stages of DMD. A progressive reduction was observed during mdx disease progression, in coincidence with the functional exhaustion of satellite cell-mediated regeneration and accumulation of fibrosis. Moreover, pharmacological manipulation of autophagy can influence disease progression in mdx mice. Of note, studies performed in regenerating muscles of wild-type mice revealed an essential role of autophagy in the activation of satellite cells upon muscle injury. These results support the notion that regeneration-associated autophagy contributes to the early compensatory stage of DMD progression, and interventions that extend activation of autophagy might be beneficial in the treatment of DMD. Thus, autophagy could be a 'disease modifier' targeted by interventions aimed to promote regeneration and delay disease progression in DMD.
Abstract The motor skills of patients with spinal muscular atrophy, type I (SMA-I) are very limited. It is difficult to quantify the motor abilities of these patients and as a result there is ...currently no validated measure of motor function that can be utilized as an outcome measure in clinical trials of SMA-I. We have developed the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (“CHOP INTEND”) to evaluate the motor skills of patients with SMA-I. The test was developed following the evaluation of 26 infants with SMA-I mean age 11.5 months (1.4–37.9 months) with the Test of Infant Motor Performance and The Children’s Hospital of Philadelphia Test of Strength in SMA, a newly devised motor assessment for SMA. Items for the CHOP INTEND were selected by an expert panel based on item mean and standard deviation, item frequency distribution, and Chronbach’s alpha. Intra-rater reliability of the resulting test was established by test–retest of 9 infants with SMA-I over a 2 month period; Intraclass correlation coefficient (ICC) (3,1) = 0.96. Interrater reliability was by video analysis of a mixed group of infants with neuromuscular disease by 4 evaluators; ICC (3,4) = 0.98 and in a group of 8 typically developing infants by 5 evaluators ICC (3,5) = 0.93. The face validity of the CHOP INTEND is supported by the use of an expert panel in item selection; however, further validation is needed. The CHOP INTEND is a reliable measure of motor skills in patients with SMA-I and neuromuscular disorders presenting in infancy.
The use and creation of machine‐learning‐based solutions to solve problems or reduce their computational costs are becoming increasingly widespread in many domains. Deep Learning plays a large part ...in this growth. However, it has drawbacks such as a lack of explainability and behaving as a black‐box model. During the last few years, Visual Analytics has provided several proposals to cope with these drawbacks, supporting the emerging eXplainable Deep Learning field. This survey aims to (i) systematically report the contributions of Visual Analytics for eXplainable Deep Learning; (ii) spot gaps and challenges; (iii) serve as an anthology of visual analytical solutions ready to be exploited and put into operation by the Deep Learning community (architects, trainers and end users) and (iv) prove the degree of maturity, ease of integration and results for specific domains. The survey concludes by identifying future research challenges and bridging activities that are helpful to strengthen the role of Visual Analytics as effective support for eXplainable Deep Learning and to foster the adoption of Visual Analytics solutions in the eXplainable Deep Learning community. An interactive explorable version of this survey is available online at https://aware‐diag‐sapienza.github.io/VA4XDL.
This survey systematically reports the contributions of Visual Analytics for eXplainable Deep Learning, spots gaps, serves as an anthology of visual analytical solutions ready to be exploited by the Deep Learning community, proves the degree of maturity, ease of integration, results for specific domains and finally identifies future research challenges.
We present three members of an Italian family affected by tubular aggregate myopathy (TAM) and congenital miosis harboring a novel missense mutation in ORAI1. All patients had a mild, late onset TAM ...revealed by asymptomatic creatine kinase (CK) elevation and congenital miosis consistent with a Stormorken‐like Syndrome, in the absence of thrombocytopathy. Muscle biopsies showed classical histological findings but ultrastructural analysis revealed atypical tubular aggregates (TAs). The whole body muscle magnetic resonance imaging (MRI) showed a similar pattern of muscle involvement that correlated with clinical severity. The lower limbs were more severely affected than the scapular girdle, and thighs were more affected than legs. Molecular analysis revealed a novel c.290C>G (p.S97C) mutation in ORAI1 in all affected patients. Functional assays in both human embryonic kidney (HEK) cells and myotubes showed an increased rate of Ca2+ entry due to a constitutive activation of the CRAC channel, consistent with a ‘gain‐of‐function’ mutation. In conclusion, we describe an Italian family harboring a novel heterozygous c.290C>G (p.S97C) mutation in ORAI1 causing a mild‐ and late‐onset TAM and congenital miosis via constitutive activation of the CRAC channel. Our findings extend the clinical and genetic spectrum of the ORAI1‐related TAM.
Background and purpose
The therapeutic scenario of X‐linked adrenoleukodystrophy (X‐ALD) is rapidly changing. Whereas the disease is well characterized in men, the condition remains to be fully ...clarified in women carrying ATP binding cassette subfamily D member 1 (ABCD1) variants. Specifically, data on clinical progression are needed, in order to recommend any appropriate management. The objective of this study was to outline the natural history of a cohort of untreated ABCD1 heterozygous female carriers.
Methods
Longitudinal data from a single‐center population of 60 carriers were retrospectively reviewed. Demographics, anthropometrics, serum very long chain fatty acid (VLCFA) levels, clinical parameters and the Adult ALD Clinical Score (AACS) were collected from every recorded visit in a 7‐year period and analyzed to define the phenotype modifications, to determine factors associated with clinical features, and to estimate the annual progression rate and the subsequent sample size for interventional trials.
Results
Thirty‐two patients were eligible for the study, and 59.4% were symptomatic at baseline. Clinical severity worsens with age which increases risk of symptom onset, the cut‐off of 41 years being crucial for phenoconversion. VLCFA levels were not predictive and did not change over time. Symptomatic carriers were followed up for 3.45 ± 2.1 years. The AACS increased at an annual rate of 0.24 points. The estimated sample size for 30% reduction in annual progression at 80% power was 272.
Conclusions
This study provides data on the natural disease progression of untreated ABCD1 heterozygous female carriers, demonstrating the relevance of aging. The estimated annual increase of the AACS will be useful for future interventional studies.
•48-week phase 3 RCT evaluating efficacy and safety of drisapersen 6 mg/kg/week.•The pre-specified analyses did not meet statistical significance.•Due to increased data variation, statistical power ...for 6MWD was reduced to 53%.•Evidence for a greater treatment benefit was seen in a selected population post-hoc.•Most common adverse events were injection-site reactions and subclinical proteinuria.
This 48-week, randomized, placebo-controlled phase 3 study (DMD114044; NCT01254019) evaluated efficacy and safety of subcutaneous drisapersen 6 mg/kg/week in 186 ambulant boys aged ≥5 years, with Duchenne muscular dystrophy (DMD) resulting from an exon 51 skipping amenable mutation. Drisapersen was generally well tolerated, with injection-site reactions and renal events as most commonly reported adverse events. A nonsignificant treatment difference (P = 0.415) in the change from baseline in six-minute walk distance (6MWD; primary efficacy endpoint) of 10.3 meters in favor of drisapersen was observed at week 48. Key secondary efficacy endpoints (North Star Ambulatory Assessment, 4-stair climb ascent velocity, and 10-meter walk/run velocity) gave consistent findings. Lack of statistical significance was thought to be largely due to greater data variability and subgroup heterogeneity. The increased standard deviation alone, due to less stringent inclusion/exclusion criteria, reduced the statistical power from pre-specified 90% to actual 53%. Therefore, a post-hoc analysis was performed in 80 subjects with a baseline 6MWD 300–400 meters and ability to rise from floor. A statistically significant improvement in 6MWD of 35.4 meters (P = 0.039) in favor of drisapersen was observed in this subpopulation. Results suggest that drisapersen could have benefit in a less impaired population of DMD subjects.
Congenital ataxias are nonprogressive neurological disorders characterized by neonatal hypotonia, developmental delay and ataxia, variably associated with intellectual disability and other ...neurological or extraneurological features. We performed trio‐based whole‐exome sequencing of 12 families with congenital cerebellar and/or vermis atrophy in parallel with targeted next‐generation sequencing of known ataxia genes (CACNA1A, ITPR1, KCNC3, ATP2B3 and GRM1) in 12 additional patients with a similar phenotype. Novel pathological mutations of ITPR1 (inositol 1,4,5‐trisphosphate receptor, type 1) were found in seven patients from four families (4/24, ∼16.8%) all localized in the IRBIT (inositol triphosphate receptor binding protein) domain which plays an essential role in the regulation of neuronal plasticity and development. Our study expands the mutational spectrum of ITPR1‐related congenital ataxia and indicates that ITPR1 gene screening should be implemented in this subgroup of ataxias.
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