Cloud computing is a disruptive technology with profound implications not only for Internet services but also for the IT sector as a whole. Its emergence promises to streamline the on-demand ...provisioning of software, hardware, and data as a service, achieving economies of scale in IT solutions' deployment and operation. This issue's articles tackle topics including architecture and management of cloud computing infrastructures, SaaS and IaaS applications, discovery of services and data in cloud computing infrastructures, and cross-platform interoperability. Still, several outstanding issues exist, particularly related to SLAs, security and privacy, and power efficiency. Other open issues include ownership, data transfer bottlenecks, performance unpredictability, reliability, and software licensing issues. Finally, hosted applications' business models must show a clear pathway to monetizing cloud computing. Several companies have already built Internet consumer services such as search, social networking, Web email, and online commerce that use cloud computing infrastructure. Above all, cloud computing's still unknown "killer application" will determine many of the challenges and the solutions we must develop to make this technology work in practice.
The deployment of wireless sensor networks in many application areas requires self-organization of the network nodes into clusters. Clustering is a network management technique, since it creates a ...hierarchical structure over a flat network. Quite a lot of node clustering techniques have appeared in the literature, and roughly fall into two families: those based on the construction of a dominating set and those which are based solely on energy considerations. The former family suffers from the fact that only a small subset of the network nodes are responsible for relaying the messages, and thus cause rapid consumption of the energy of these nodes. The latter family uses the residual energy of each node in order to decide about whether it will elect itself as a leader of a cluster or not. This family’s methods ignore topological features of the nodes and are used in combination with the methods of the former family. We propose an energy-efficient distributed clustering protocol for wireless sensor networks, based on a metric for characterizing the significance of a node, w.r.t. its contribution in relaying messages. The protocol achieves small communication complexity and linear computation complexity. Experimental results attest that the protocol improves network longevity.
In the PORTEC-3 trial, women with high-risk endometrial cancer (HR-EC) were randomised to receive pelvic radiotherapy (RT) with or without concurrent and adjuvant chemotherapy (two cycles of ...cisplatin 50 mg/m2 in weeks 1 and 4 of RT, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2). Pathology review was required before patient enrolment. The aim of this analysis was to evaluate the role of central pathology review before randomisation.
A total of 1295 cases underwent pathology review to confirm HR-EC in the Netherlands (n = 395) and the UK (n = 900), and for 1226/1295 (95%) matching review and original reports were available. In total, 329 of these patients were enrolled in the PORTEC-3 trial: 145 in the Netherlands and 184 in the UK, comprising 48% of the total PORTEC-3 cohort of 686 participants. Areas of discrepancies were evaluated, and inter-observer agreement between original and review opinion was evaluated by calculating the kappa value (κ).
In the 1226 pathology reviews, 6356 selected items were evaluable for both original and review pathology. In 43% of cases at least one pathology item changed after review. For 102 patients (8%), this discrepancy led to ineligibility for the PORTEC-3 trial, most frequently due to differences in the assessment of histological type (34%), endocervical stromal involvement (27%) and histological grade (19%). Lowest inter-observer agreement was found for histological type (κ = 0.72), lymph-vascular space invasion (κ = 0.72) and histological grade (κ = 0.70).
Central pathology review by expert gynaeco-pathologists changed histological type, grade or other items in 43% of women with HR-EC, leading to ineligibility for the PORTEC-3 trial in 8%. Upfront pathology review is essential to ensure enrolment of the target trial-population, and to avoid over- or undertreatment, especially when treatment modalities with substantial toxicity are involved.
This study is registered with ISRCTN (ISRCTN14387080, www.controlled-trials.com) and with ClinicalTrials.gov (NCT00411138).
Background Topotecan has single-agent activity in recurrent ovarian cancer. It was evaluated in a novel combination compared with standard frontline therapy. Methods Women aged 75 years or younger ...with newly diagnosed stage IIB or greater ovarian cancer, Eastern Cooperative Oncology Group Performance Status of 1 or less, were stratified by type of primary surgery and residual disease, treatment center, and age; then randomly assigned to one of the two 21-day intravenous regimens. Patients in arm 1 (n = 409) were administered four cycles of cisplatin 50 mg/m2 on day 1 and topotecan 0.75 mg/m2 on days 1–5, then four cycles of paclitaxel 175 mg/m2 over 3 hours on day 1 followed by carboplatin (area under the curve = 5) on day 1. Patients in arm 2 (n = 410) were given paclitaxel plus carboplatin as in arm 1 for eight cycles. We compared progression-free survival (PFS), overall survival, and cancer antigen-125 normalization rates in the two treatment arms. A stratified log-rank test was used to assess the primary endpoint, PFS. All statistical tests were two-sided. Results A total of 819 patients were randomly assigned. At baseline, the median age of the patients was 57 years (range = 28–78); 81% had received debulking surgery, and of these, 55% had less than 1 cm residual disease; 66% of patients were stage III and 388 (47.4%) patients had measurable disease. After a median follow-up of 43 months, 650 patients had disease progression or died without documented progression and 406 had died. Patients in arm 1 had more hematological toxicity and hospitalizations than patients in arm 2; PFS was 14.6 months in arm 1 vs 16.2 months in arm 2 (hazard ratio = 1.10, 95% confidence interval = 0.94 to 1.28, P = .25). Among patients with elevated baseline cancer antigen-125, fewer in arm 1 than in arm 2 had levels return to normal by 3 months after random assignment (51.6% vs 63.3%, P = .007) Conclusions Topotecan and cisplatin, followed by carboplatin and paclitaxel, were more toxic than carboplatin and paclitaxel alone, but without improved efficacy. Carboplatin plus paclitaxel remains the standard of care for advanced epithelial ovarian cancer.
The benefits of migrating business software applications to the cloud is a dominant IT topic among consultants, software managers, and executives. The broad interest in cloud computing is motivated ...by the prospect of quick, painless deployment and maintenance of applications that are now a burden of the enterprise. The authors propose an analytical method for deciding whether the features and cost of a cloud solution are appropriate to the business IT problem and whether the risks are reasonable and manageable.
Discrete sequence modeling and prediction is an important goal and a challenge for pervasive computing. Mobile clients' data request forecasting and location tracking in wireless cellular networks ...are characteristic application areas of sequence prediction in pervasive computing. This article presents information-theoretic techniques for discrete sequence prediction. It surveys, classifies, and compares the state-of-the-art solutions, suggesting routes for further research by discussing the critical issues and challenges of prediction in wireless networks.
Background: Self-injection of biologics is a mainstay of chronic disease treatment, yet the process of self-injection often causes persistent apprehension and anxiety, distinct from needle phobia. ...While literature alludes to the role that routines and rituals play in self-injection, there is no comprehensive study on the routines and rituals self-injectors employ, nor of the process by which they are discovered and ingrained. Methods: We conducted a mixed-method, observational pilot ethnography study of 27 patients with plaque psoriasis, psoriatic arthritis, or ankylosing spondylitis with and without prior biologic self-injection experience. Patients submitted self-made videos, photos, and projective exercises of an actual biologic self-injection and completed validated instruments to assess burden of treatment. Videos and photos containing routine and ritual elements were thematically categorized based on functional and emotional benefit, and analyzed for differences based on current biologic, dosing frequency, time on current biologic, and burden of treatment measures. Results: During patients' initial at-home injections, training gaps became apparent, leading to a process of experimentation aimed at reducing pain/anxiety, increasing confidence, and building a consistent injection process. Routines were present in 27/27 (100%) patients and anchored the time, place, and process for injection, and incorporated approved use steps for the injection device. Ritual elements served as emotional coping strategies for patients and were present in 21/27 (77.8%) of patients. Conclusion: Our findings suggest that providing patients device training using adult learning principles, teaching routines and rituals concurrently, and providing at-home opportunities for practice with a device trainer may be useful strategies to reduce anxiety, avoid unnecessary experimentation, and improve adherence to injection therapy. While further studies are needed to generalize our findings, we posit that routine and ritual elements can be incorporated into existing patient-clinician interactions or novel digital interventions through mobile medical applications, smart training devices, and connected injection ecosystems. Keywords: training, drug delivery device, combination product, patient support, routines, rituals, burden of treatment, chronic disease, injection trainer, mixed methods research
Hypersensitivity reactions (HSRs) to platinum are an important issue in the treatment of patients (pts) with ovarian cancer (OC). Germline BRCA mutations have been proposed as a risk factor. We aimed ...at evaluating the incidence and severity of HSRs to platinum in OC pts. with known BRCA status.
We retrospectively analyzed 432 pts. from 5 Italian Centers. In addition, we performed a systematic review and meta-analysis of published series.
Four hundred nine pts. received at least one prior platinum-based treatment line: 314 were BRCA wild type (77%) and 95 were BRCA mutated (23%). There was no statistical difference in exposure to platinum. Incidence of any grade HSRs was higher among BRCA mutated pts. 9% vs 18%, p = 0.019 and the time-to-HSRs curves show that the risk increases with the duration of platinum exposure, in BRCA mutated pts. more than in BRCA wild type. A multivariable analysis showed that harboring a germline BRCA mutation was related to a higher incidence of HSRs (HR: 1.84, 95% CI 1.00–3.99, p = 0.05) while having received pegylated liposomal doxorubicin (PLD) was related to a lower incidence of HSRs (HR: 0.03 95% CI 0.004–0.22, p = 0.001). The systematic review confirmed the higher incidence of HSRs in BRCA mutated pts., though heterogeneity among series was significant.
In OC pts. with BRCA mutations, there is a significantly higher incidence of HSRs to carboplatin, not justified by longer drug exposure. On the other hand, PLD exerted a protective role in our series.
•Hypersensitivity reactions (HSRs) to carboplatin are frequent in pretreated ovarian cancer (OC) patients (pts).•The role of BRCA mutations (mut) as a risk factor has been suggested.•We demonstrate that BRCAmut pts. have an increased risk of HSRs which is not justified by longer drug exposure only.•Receiving pegylated liposomal doxorubicin was a protective factor in our series.•The meta-analysis of literature, though results are heterogeneous, confirms the role of BRCAmut in increasing HSRs risk.
Background: The efficacy and tolerability of the regimen containing paclitaxel and cisplatin (TP) in the neo-adjuvant treatment of locally advanced squamous cell cervical cancer are unknown. The TIP ...regimen (TP plus ifosfamide) showed high efficacy but high toxicity and it is used as an internal control. Patients and methods: In all, 154 patients were randomized to TP (paclitaxel 175 mg/m2 + cisplatin 75 mg/m2; n = 80) or TIP (TP + ifosfamide 5 g/m2; n = 74), three cycles, followed by radical surgery. Pathological response to chemotherapy was classified as optimal no residual tumor (complete response) or residual disease with ≤3 mm stromal invasion (PR1) or suboptimal response. Results: Patient characteristics (TP/TIP): stage IB2 (56%/64%), IIA (18%/14%), IIB (20%/19%), III–IVA (5%/4%) and median age (42 years/45 years). The optimal response rate in the TP group was 25%, 95% confidence interval (CI) = 16% to 37% and 43%, 95% CI = 31% to 55% in the TIP group. Grades 3–4 leukopenia (6%/53%) and neutropenia (26%/76%) were significantly more frequent on TIP. Conclusion: TP performance was below expectation since the lower 95% confidence limit of the optimal response rate failed to reach the prespecified minimum requirement of efficacy, i.e. 22%. The TIP regimen confirmed its activity but was associated with higher haematological toxicity than TP.
Insulin-like growth factor-II (IGF-II) may be a prognostic marker in ovarian cancer, and its intronic single nucleotide polymorphism (SNP) rs4320932 has been associated with risk of the disease. We ...determined whether rs4320932 is associated with IGF-II expression and patient survival in ovarian cancer, and explored whether the SNP variation affects DNA conformation both in the absence of and presence of carboplatin. IGF-II genotype (rs4320932) and phenotype were analyzed in 212 primary invasive epithelial ovarian cancer tissue samples with Taqman® SNP genotyping assays, quantitative reverse transcription-polymerase chain reaction and commercial enzyme-linked immunosorbent assay. DNA conformation was evaluated by circular dichroism (CD) spectra. Kaplan-Meier survival curves and Cox proportional hazard regression models were used to analyze the SNP associations with patient survival. The C allele of rs4320932, previously associated with decreased risk of ovarian cancer development, was here associated with significantly elevated risks of relapse (Ptrend = 0.0002) and death (Ptrend = 0.0006), remaining significant in multivariate analyses. The adjusted hazard ratios were 3.05 (95% confidence interval CI: 1.47-6.37) for relapse and 3.28 (95% CI: 1.64-6.57) for death, respectively. The variant was also significantly associated with chemotherapy response, but not with other clinicopathologic variables or with IGF-II expression. DNA with genotypes TT and CC had distinct CD spectra in both the absence of and presence of carboplatin. These findings suggest that the intronic SNP rs4320932 affects patient survival and chemotherapy response via alteration of DNA conformation, but not through regulation of IGF-II expression. This novel finding may have implications in individualized medicine for the design of specific molecules targeting DNA of specific conformations.
PDF
