Migrating a Large Scale Legacy Application to SOA: Challenges and Lessons Learned

Abstract—This paper presents the findings of a case study of a large scale legacy to service-oriented architecture migration process in the payments domain of a Dutch bank. The paper presents the business drivers that initiated the migration, and describes a 4-phase migration process. For each phase, the paper details benefits of using the techniques, best practices that contribute to the success, and possible challenges that are faced during migration. Based on these observations, the findings are discussed as lessons learned, including the implications of using reverse engineering techniques to facilitate the migration process, adopting a pragmatic migration realization approach, emphasizing the organizational and business perspectives, and harvesting knowledge of the system throughout the system’s life cycle. I

Incidence of and predictors for antiseizure medication gaps in Medicare beneficiaries with epilepsy: a retrospective cohort study.

BACKGROUND For the two-thirds of patients with epilepsy who achieve seizure remission on antiseizure medications (ASMs), patients and clinicians must weigh the pros and cons of long-term ASM treatment. However, little work has evaluated how often ASM discontinuation occurs in practice. We describe the incidence of and predictors for sustained ASM fill gaps to measure discontinuation in individuals potentially eligible for ASM withdrawal. METHODS This was a retrospective cohort of Medicare beneficiaries. We included patients with epilepsy by requiring International Classification of Diseases codes for epilepsy/convulsions plus at least one ASM prescription each year 2014-2016, and no acute visit for epilepsy 2014-2015 (i.e., potentially eligible for ASM discontinuation). The main outcome was the first day of a gap in ASM supply (30, 90, 180, or 360 days with no pills) in 2016-2018. We displayed cumulative incidence functions and identified predictors using Cox regressions. RESULTS Among 21,819 beneficiaries, 5191 (24%) had a 30-day gap, 1753 (8%) had a 90-day gap, 803 (4%) had a 180-day gap, and 381 (2%) had a 360-day gap. Predictors increasing the chance of a 180-day gap included number of unique medications in 2015 (hazard ratio [HR] 1.03 per medication, 95% confidence interval [CI] 1.01-1.05) and epileptologist prescribing physician (≥25% of that physician's visits for epilepsy; HR 2.37, 95% CI 1.39-4.03). Predictors decreasing the chance of a 180-day gap included Medicaid dual eligibility (HR 0.75, 95% CI 0.60-0.95), number of unique ASMs in 2015 (e.g., 2 versus 1: HR 0.37, 95% CI 0.30-0.45), and greater baseline adherence (> 80% versus ≤80% of days in 2015 with ASM pill supply: HR 0.38, 95% CI 0.32-0.44). CONCLUSIONS Sustained ASM gaps were rarer than current guidelines may suggest. Future work should further explore barriers and enablers of ASM discontinuation to understand the optimal discontinuation rate

Mixture models for analysis of melting temperature data

<p>Abstract</p> <p>Background</p> <p>In addition to their use in detecting undesired real-time PCR products, melting temperatures are useful for detecting variations in the desired target sequences. Methodological improvements in recent years allow the generation of high-resolution melting-temperature (T_m) data. However, there is currently no convention on how to statistically analyze such high-resolution T_mdata.</p> <p>Results</p> <p>Mixture model analysis was applied to T_mdata. Models were selected based on Akaike's information criterion. Mixture model analysis correctly identified categories in T_mdata obtained for known plasmid targets. Using simulated data, we investigated the number of observations required for model construction. The precision of the reported mixing proportions from data fitted to a preconstructed model was also evaluated.</p> <p>Conclusion</p> <p>Mixture model analysis of T_mdata allows the minimum number of different sequences in a set of amplicons and their relative frequencies to be determined. This approach allows T_mdata to be analyzed, classified, and compared in an unbiased manner.</p

The human cytomegalovirus-encoded G protein- coupled receptor UL33 exhibits oncomodulatory properties

Herpesviruses can rewire cellular signaling in host cells by expressing viral G protein- coupled receptors (GPCRs). These viral receptors exhibit homology to human chemokine receptors, but some display constitutive activity and promiscuous G protein coupling. Human cytomegalovirus (HCMV) has been detected in multiple cancers, including glioblastoma, and its genome encodes four GPCRs. One of these receptors, US28, is expressed in glioblastoma and possesses constitutive activity and oncomodulatory properties. UL33, another HCMV-encoded GPCR, also displays constitutive signaling via Gαq, Gαi, and Gαs proteins. However, little is known about the nature and functional effects of UL33-driven signaling. Here, we assessed UL33's signaling repertoire and oncomodulatory potential. UL33 activated multiple proliferative, angiogenic, and inflammatory signaling pathways in HEK293T and U251 glioblastoma cells. Notably, upon infection, UL33 contributed to HCMV-mediated STAT3 activation. Moreover, UL33 increased spheroid growth in vitro and accelerated tumor growth in different in vivo tumor models, including an orthotopic glioblastoma xenograft model. UL33-mediated signaling was similar to that stimulated by US28; however, UL33-induced tumor growth was delayed. Additionally, the spatiotemporal expression of the two receptors only partially overlapped in HCMV-infected glioblastoma cells. In conclusion, our results unveil that UL33 has broad signaling capacity and provide mechanistic insight into its functional effects. UL33, like US28, exhibits oncomodulatory properties, elicited via constitutive activation of multiple signaling pathways. UL33 and US28 might contribute to HCMV's oncomodulatory effects through complementing and converging cellular signaling, and hence UL33 may represent a promising drug target in HCMV-associated malignancies

Comparison of two protective lung ventilatory regimes on oxygenation during one-lung ventilation: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>The efficacy of protective ventilation in acute lung injury has validated its use in the operating room for patients undergoing thoracic surgery with one-lung ventilation (OLV). The purpose of this study was to investigate the effects of two different modes of ventilation using low tidal volumes: pressure controlled ventilation (PCV) vs. volume controlled ventilation (VCV) on oxygenation and airway pressures during OLV.</p> <p>Methods</p> <p>We studied 41 patients scheduled for thoracoscopy surgery. After initial two-lung ventilation with VCV patients were randomly assigned to one of two groups. In one group OLV was started with VCV (tidal volume 6 mL/kg, PEEP 5) and after 30 minutes ventilation was switched to PCV (inspiratory pressure to provide a tidal volume of 6 mL/kg, PEEP 5) for the same time period. In the second group, ventilation modes were performed in reverse order. Airway pressures and blood gases were obtained at the end of each ventilatory mode.</p> <p>Results</p> <p>PaO₂, PaCO₂and alveolar-arterial oxygen difference did not differ between PCV and VCV. Peak airway pressure was significantly lower in PCV compared with VCV (19.9 ± 3.8 cmH₂O vs 23.1 ± 4.3 cmH₂O; p < 0.001) without any significant differences in mean and plateau pressures.</p> <p>Conclusions</p> <p>In patients with good preoperative pulmonary function undergoing thoracoscopy surgery, the use of a protective lung ventilation strategy with VCV or PCV does not affect the oxygenation. PCV was associated with lower peak airway pressures.</p

Clinical outcomes in typhoid fever: adverse impact of infection with nalidixic acid-resistant Salmonella typhi

BACKGROUND: Widespread use of fluoroquinolones has resulted in emergence of Salmonella typhi strains with decreased susceptibility to fluoroquinolones. These strains are identifiable by their nalidixic acid-resistance. We studied the impact of infection with nalidixic acid-resistant S. typhi (NARST) on clinical outcomes in patients with bacteriologically-confirmed typhoid fever. METHODS: Clinical and laboratory features, fever clearance time and complications were prospectively studied in patients with blood culture-proven typhoid fever, treated at a tertiary care hospital in north India, during the period from November 2001 to October 2003. Susceptibility to amoxycillin, co-trimoxazole, chloramphenicol, ciprofloxacin and ceftriaxone were tested by disc diffusion method. Minimum inhibitory concentrations (MIC) of ciprofloxacin and ceftriaxone were determined by E-test method. RESULTS: During a two-year period, 60 patients (age [mean ± SD]: 15 ± 9 years; males: 40 [67%]) were studied. All isolates were sensitive to ciprofloxacin and ceftriaxone by disc diffusion and MIC breakpoints. However, 11 patients had clinical failure of fluoroquinolone therapy. Infections with NARST isolates (47 [78%]) were significantly associated with longer duration of fever at presentation (median [IQR] 10 [7-15] vs. 4 [3-6] days; P = 0.000), higher frequency of hepatomegaly (57% vs. 15%; P = 0.021), higher levels of aspartate aminotransferase (121 [66–235] vs. 73 [44–119] IU/L; P = 0.033), and increased MIC of ciprofloxacin (0.37 ± 0.21 vs. 0.17 ± 0.14 μg/mL; P = 0.005), as compared to infections with nalidixic acid-susceptible isolates. All 11 patients with complications were infected with NARST isolates. Total duration of illness was significantly longer in patients who developed complications than in patients who did not (22 [14.8–32] vs. 12 [9.3–20.3] days; P = 0.011). Duration of prior antibiotic intake had a strong positive correlation with the duration of fever at presentation (r = 0.61; P = 0.000) as well as the total duration of illness (r = 0.53; P = 0.000). CONCLUSION: Typhoid fever caused by NARST infection is associated with poor clinical outcomes, probably due to delay in initiating appropriate antibiotic therapy. Fluoroquinolone breakpoints for S. typhi need to be redefined and fluoroquinolones should no longer be used as first-line therapy, if the prevalence of NARST is high

Mapping Proprioception across a 2D Horizontal Workspace

Relatively few studies have been reported that document how proprioception varies across the workspace of the human arm. Here we examined proprioceptive function across a horizontal planar workspace, using a new method that avoids active movement and interactions with other sensory modalities. We systematically mapped both proprioceptive acuity (sensitivity to hand position change) and bias (perceived location of the hand), across a horizontal-plane 2D workspace. Proprioception of both the left and right arms was tested at nine workspace locations and in 2 orthogonal directions (left-right and forwards-backwards). Subjects made repeated judgments about the position of their hand with respect to a remembered proprioceptive reference position, while grasping the handle of a robotic linkage that passively moved their hand to each judgement location. To rule out the possibility that the memory component of the proprioceptive testing procedure may have influenced our results, we repeated the procedure in a second experiment using a persistent visual reference position. Both methods resulted in qualitatively similar findings. Proprioception is not uniform across the workspace. Acuity was greater for limb configurations in which the hand was closer to the body, and was greater in a forward-backward direction than in a left-right direction. A robust difference in proprioceptive bias was observed across both experiments. At all workspace locations, the left hand was perceived to be to the left of its actual position, and the right hand was perceived to be to the right of its actual position. Finally, bias was smaller for hand positions closer to the body. The results of this study provide a systematic map of proprioceptive acuity and bias across the workspace of the limb that may be used to augment computational models of sensory-motor control, and to inform clinical assessment of sensory function in patients with sensory-motor deficits

Human cytomegalovirus immediate-early 1 protein rewires upstream STAT3 to downstream STAT1 signaling switching an IL6-type to an IFNγ-like response

MN and CP were supported by the Wellcome Trust (www.wellcome.ac.uk) Institutional Strategic Support Fund and CP was supported by the Deutsche Forschungsgemeinschaft (PA 815/2-1; www.dfg.de).The human cytomegalovirus (hCMV) major immediate-early 1 protein (IE1) is best known for activating transcription to facilitate viral replication. Here we present transcriptome data indicating that IE1 is as significant a repressor as it is an activator of host gene expression. Human cells induced to express IE1 exhibit global repression of IL6- and oncostatin M-responsive STAT3 target genes. This repression is followed by STAT1 phosphorylation and activation of STAT1 target genes normally induced by IFNγ. The observed repression and subsequent activation are both mediated through the same region (amino acids 410 to 445) in the C-terminal domain of IE1, and this region serves as a binding site for STAT3. Depletion of STAT3 phenocopies the STAT1-dependent IFNγ-like response to IE1. In contrast, depletion of the IL6 receptor (IL6ST) or the STAT kinase JAK1 prevents this response. Accordingly, treatment with IL6 leads to prolonged STAT1 instead of STAT3 activation in wild-type IE1 expressing cells, but not in cells expressing a mutant protein (IE1dl410-420) deficient for STAT3 binding. A very similar STAT1-directed response to IL6 is also present in cells infected with a wild-type or revertant hCMV, but not an IE1dl410-420 mutant virus, and this response results in restricted viral replication. We conclude that IE1 is sufficient and necessary to rewire upstream IL6-type to downstream IFNγ-like signaling, two pathways linked to opposing actions, resulting in repressed STAT3- and activated STAT1-responsive genes. These findings relate transcriptional repressor and activator functions of IE1 and suggest unexpected outcomes relevant to viral pathogenesis in response to cytokines or growth factors that signal through the IL6ST-JAK1-STAT3 axis in hCMV-infected cells. Our results also reveal that IE1, a protein considered to be a key activator of the hCMV productive cycle, has an unanticipated role in tempering viral replication.Publisher PDFPeer reviewe