Mining unexpected temporal associations: Applications in detecting adverse drug reactions

Copyright © 2008 IEEEIn various real-world applications, it is very useful mining unanticipated episodes where certain event patterns unexpectedly lead to outcomes, e.g., taking two medicines together sometimes causing an adverse reaction. These unanticipated episodes are usually unexpected and infrequent, which makes existing data mining techniques, mainly designed to find frequent patterns, ineffective. In this paper, we propose unexpected temporal association rules (UTARs) to describe them. To handle the unexpectedness, we introduce a new interestingness measure, residual-leverage, and develop a novel case-based exclusion technique for its calculation. Combining it with an event-oriented data preparation technique to handle the infrequency, we develop a new algorithm MUTARC to find pairwise UTARs. The MUTARC is applied to generate adverse drug reaction (ADR) signals from real-world healthcare administrative databases. It reliably shortlists not only six known ADRs, but also another ADR, flucloxacillin possibly causing hepatitis, which our algorithm designers and experiment runners have not known before the experiments. TheMUTARC performs much more effectively than existing techniques. This paper clearly illustrates the great potential along the new direction of ADR signal generation from healthcare administrative databases.Huidong (Warren) Jin, Jie Chen, Member, Hongxing He, Graham J. Williams, Chris Kelman and Christine M. O’Keef

Intermediate statistics in quantum maps

We present a one-parameter family of quantum maps whose spectral statistics are of the same intermediate type as observed in polygonal quantum billiards. Our central result is the evaluation of the spectral two-point correlation form factor at small argument, which in turn yields the asymptotic level compressibility for macroscopic correlation lengths

DNA Methylation of the ABO Promoter Underlies Loss of ABO Allelic Expression in a Significant Proportion of Leukemic Patients

Background: Loss of A, B and H antigens from the red blood cells of patients with myeloid malignancies is a frequent occurrence. Previously, we have reported alterations in ABH antigens on the red blood cells of 55% of patients with myeloid malignancies. Methodology/Principal Findings: To determine the underlying molecular mechanisms of this loss, we assessed ABO allelic expression in 21 patients with ABH antigen loss previously identified by flow cytometric analysis as well as an additional 7 patients detected with ABH antigen changes by serology. When assessing ABO mRNA allelic expression, 6/12 (50%) patients with ABH antigen loss detected by flow cytometry and 5/7 (71%) of the patients with ABH antigen loss detected by serology had a corresponding ABO mRNA allelic loss of expression. We examined the ABO locus for copy number and DNA methylation alterations in 21 patients, 11 with loss of expression of one or both ABO alleles, and 10 patients with no detectable allelic loss of ABO mRNA expression. No loss of heterozygosity (LOH) at the ABO locus was observed in these patients. However in 8/11 (73%) patients with loss of ABO allelic expression, the ABO promoter was methylated compared with 2/10 (20%) of patients with no ABO allelic expression loss (P = 0.03). Conclusions/Significance: We have found that loss of ABH antigens in patients with hematological malignancies is associated with a corresponding loss of ABO allelic expression in a significant proportion of patients. Loss of ABO allelic expression was strongly associated with DNA methylation of the ABO promoter.Tina Bianco-Miotto, Damian J. Hussey, Tanya K. Day, Denise S. O'Keefe and Alexander Dobrovi

Deposition of Cerium-Based Conversion Coatings on Aluminum Alloy 380

Cerium-based conversion coatings were deposited on as-cast aluminum alloy 380 substrates by a spontaneous immersion process. In this study, the effects of rinsing temperature prior to immersion in the coating deposition solution were studied with respect to the surface morphology, electrochemical response, and corrosion resistance of the coatings. Panels rinsed at 25°C prior to coating had large cracks and holes in the coating. In contrast, panels rinsed at 100°C prior to coating had a uniform coating morphology with fewer, smaller cracks. Electrochemical testing revealed that coatings deposited on substrates rinsed at 100°C had higher impedance (~80 kΩ·cm2) and lower corrosion current (~0.34 μA/cm2) compared to coatings deposited on substrates rinsed at 25°C, which had 10 kΩ·cm2 impedance and 2.7 μA/cm2 corrosion current. Finally, ASTM B117 salt spray testing showed that rinsing at 100°C prior to coating resulted in cerium-based conversion coatings that could resist the formation of salt tails for at least 8 days

A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families

HARS2 encodes mitochondrial histidyl-tRNA synthetase (HARS2), which links histidine to its cognate tRNA in the mitochondrial matrix. Biallelic variants in HARS2 are associated with Perrault syndrome, a rare recessive condition characterized by sensorineural hearing loss in both sexes and primary ovarian insufficiency in 46,XX females. Some individuals with Perrault syndrome have a broader phenotypic spectrum with neurological features, including ataxia and peripheral neuropathy. Here, we report a recurrent variant in HARS2 in association with sensorineural hearing loss. In affected individuals from three unrelated families, the variant HARS2 c.1439G>A p.(Arg480His) is present as a heterozygous variant in trans to a putative pathogenic variant. The low prevalence of the allele HARS2 c.1439G>A p.(Arg480His) in the general population and its presence in three families with hearing loss, confirm the pathogenicity of this variant and illustrate the presentation of Perrault syndrome as nonsyndromic hearing loss in males and prepubertal females

The time-dependent expression of keratins 5 and 13 during the reepithelialization of human skin wounds

The time-dependent reepithelialization of 55 human surgical skin wounds with a wound age between 8h and more than 2 months was investigated by the immunohistochemical localization of cytokeratins 5 and 13. A complete, rebuilt epidermal layer over the wound area was first detectable in a 5-day-old wound, while all wounds of more than 18 days duration contained a completely reepithelialized wound area. Between 5 and 18 days the basal layer of keratinocytes showed — in contrast to normal skin — only some cells positive for cytokeratin 5. In some, but not all lesions with a wound age of 13 days or more, a basal cell layer completely staining for cytokeratin 5 was demonstrable. This staining pattern was found in all skin wounds with a wound age of more than 23 days. The immunohistochemical detection of cytokeratin 13 which can be observed regularly in non-cornifying squamous epithelia provides no information for the time-estimation of human skin wounds, since no significant temporary expression of this polypeptide seems to occur during the healing of human skin wounds

Event-based camera refractory period characterization and initial clock drift evaluation

Event-based camera (EBC) technology provides high-dynamic range operation and shows promise for efficient capture of spatio-temporal information, producing a sparse data stream and enabling consideration of nontraditional data processing solutions (e.g., new algorithms, neuromorphic processors, etc.). Given the fundamental difference in camera architecture, the EBC response and noise behavior differ considerably compared to standard CCD/CMOS framing sensors. These differences necessitate the development of new characterization techniques and sensor models to evaluate hardware performance and elucidate the trade-space between the two camera architectures. Laboratory characterization techniques reported previously include noise level as a function of static scene light level (background activity) and contrast responses referred to as S-curves. Here we present further progress on development of basic characterization methods and test capabilities for commercial-off-the-shelf (COTS) visible EBCs, with a focus on measurement of pixel deadtime (refractory period) including results for the 4th-generation sensor from Prophesee and Sony. Refractory period is empirically determined from analysis of the interspike intervals (ISIs), and results visualized using log-histograms of the minimum per-pixel ISI values for a subset of pixels activated by a controlled dynamic scene. Our tests of the Prophesee gen4 EVKv2 yield refractory period estimates ranging from 6.1 msec to 6.8 μsec going from the slowest (20) to fastest (100) settings of the relevant bias parameter, bias_refr. We also introduce and demonstrate the concept of pixel bandwidth measurement from data captured while viewing a static scene – based on recording data at a range of refractory period setting and then analyzing noise-event statistics. Finally, we present initial results for estimating and correcting EBC clock drift using a GPS PPS signal to generate special timing events in the event-list data streams generated by the DAVIS346 and DVXplorer EBCs from iniVation

Cyber security fear appeals:unexpectedly complicated

Cyber security researchers are starting to experiment with fear appeals, with a wide variety of designs and reported efficaciousness. This makes it hard to derive recommendations for designing and deploying these interventions. We thus reviewed the wider fear appeal literature to arrive at a set of guidelines to assist cyber security researchers. Our review revealed a degree of dissent about whether or not fear appeals are indeed helpful and advisable. Our review also revealed a wide range of fear appeal experimental designs, in both cyber and other domains, which confirms the need for some standardized guidelines to inform practice in this respect. We propose a protocol for carrying out fear appeal experiments, and we review a sample of cyber security fear appeal studies, via this lens, to provide a snapshot of the current state of play. We hope the proposed experimental protocol will prove helpful to those who wish to engage in future cyber security fear appeal research

Human autoantibodies against desmoplakins in paraneoplastic pemphigus.

Recently, a previously unrecognized autoantibody mediated blistering disease, paraneoplastic pemphigus has been described. Paraneoplastic pemphigus is associated with lymphoid malignancies, thymomas, and poorly differentiated sarcomas. Serum of affected patients contain pathogenic autoantibodies that immunoprecipitate from normal keratinocytes a characteristic complex of four polypeptides with M(r) of 250, 230, 210, and 190 kD. As our preliminary studies indicated that the 250-kD and the 210-kD antigens comigrated with desmoplakins I and II, we investigated the possibility that autoantibodies against the desmoplakins were a component of this autoimmune syndrome. 11 sera from affected patients were tested by indirect immunofluorescence against desmosome containing tissues, immunoprecipitation of metabolically labeled keratinocytes, and Western immunoblotting of desmoplakins I and II that had been purified to homogeneity from pig tongue epithelium. By indirect immunofluorescence, 9 of 11 sera showed strong binding to epithelial and nonepithelial desmosomes, and 2 were weakly reactive. All 11 immunoprecipitated 250- and 210-kD bands of variable intensity that comigrated with bands identified by a murine monoclonal antidesmoplakin antibody, and immunoblotting confirmed binding of the serum autoantibodies to purified desmoplakins. This demonstrates that paraneoplastic pemphigus is the first human autoimmune syndrome in which autoantibodies against the desmoplakins are a prominent component of the humoral autoimmune response