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

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

Using ordinal logistic regression to evaluate the performance of laser-Doppler predictions of burn-healing time

Background Laser-Doppler imaging (LDI) of cutaneous blood flow is beginning to be used by burn surgeons to predict the healing time of burn wounds; predicted healing time is used to determine wound treatment as either dressings or surgery. In this paper, we do a statistical analysis of the performance of the technique. Methods We used data from a study carried out by five burn centers: LDI was done once between days 2 to 5 post burn, and healing was assessed at both 14 days and 21 days post burn. Random-effects ordinal logistic regression and other models such as the continuation ratio model were used to model healing-time as a function of the LDI data, and of demographic and wound history variables. Statistical methods were also used to study the false-color palette, which enables the laser-Doppler imager to be used by clinicians as a decision-support tool. Results Overall performance is that diagnoses are over 90% correct. Related questions addressed were what was the best blood flow summary statistic and whether, given the blood flow measurements, demographic and observational variables had any additional predictive power (age, sex, race, % total body surface area burned (%TBSA), site and cause of burn, day of LDI scan, burn center). It was found that mean laser-Doppler flux over a wound area was the best statistic, and that, given the same mean flux, women recover slightly more slowly than men. Further, the likely degradation in predictive performance on moving to a patient group with larger %TBSA than those in the data sample was studied, and shown to be small. Conclusion Modeling healing time is a complex statistical problem, with random effects due to multiple burn areas per individual, and censoring caused by patients missing hospital visits and undergoing surgery. This analysis applies state-of-the art statistical methods such as the bootstrap and permutation tests to a medical problem of topical interest. New medical findings are that age and %TBSA are not important predictors of healing time when the LDI results are known, whereas gender does influence recovery time, even when blood flow is controlled for. The conclusion regarding the palette is that an optimum three-color palette can be chosen 'automatically', but the optimum choice of a 5-color palette cannot be made solely by optimizing the percentage of correct diagnoses

Characterization of the seismic environment at the Sanford Underground Laboratory, South Dakota

An array of seismometers is being developed at the Sanford Underground Laboratory, the former Homestake mine, in South Dakota to study the properties of underground seismic fields and Newtonian noise, and to investigate the possible advantages of constructing a third-generation gravitational-wave detector underground. Seismic data were analyzed to characterize seismic noise and disturbances. External databases were used to identify sources of seismic waves: ocean-wave data to identify sources of oceanic microseisms, and surface wind-speed data to investigate correlations with seismic motion as a function of depth. In addition, sources of events contributing to the spectrum at higher frequencies are characterized by studying the variation of event rates over the course of a day. Long-term observations of spectral variations provide further insight into the nature of seismic sources. Seismic spectra at three different depths are compared, establishing the 4100-ft level as a world-class low seismic-noise environment.Comment: 29 pages, 16 figure