IoT Forensics: Amazon Echo as a Use Case Li, Shancang; Choo, Kim-Kwang Raymond; Sun, Qindong ...
IEEE internet of things journal,
08/2019, Letnik:
6, Številka:
4
Journal Article
Odprti dostop
Internet of Things (IoT) are increasingly common in our society, and can be found in civilian settings as well as sensitive applications, such as battlefields and national security. Given the ...potential of these devices to be targeted by attackers, they are a valuable source in digital forensic investigations. In addition, incriminating evidence may be stored on an IoT device (e.g., Amazon Echo in a home environment and Fitbit worn by the victim or an accused person). In comparison to IoT security and privacy literature, IoT forensics is relatively under-studied. IoT forensics is also challenging in practice, particularly due to the complexity, diversity, and heterogeneity of IoT devices and ecosystems. In this paper, we present an IoT-based forensic model that supports the identification, acquisition, analysis, and presentation of potential artifacts of forensic interest from IoT devices and the underpinning infrastructure. Specifically, we use the popular Amazon Echo as a use case to demonstrate how our proposed model can be used to guide forensics analysis of IoT devices.
First-generation EGFR tyrosine kinase inhibitors (EGFR TKI) provide significant clinical benefit in patients with advanced EGFR-mutant (EGFRm(+)) non-small cell lung cancer (NSCLC). Patients ...ultimately develop disease progression, often driven by acquisition of a second T790M EGFR TKI resistance mutation. AZD9291 is a novel oral, potent, and selective third-generation irreversible inhibitor of both EGFRm(+) sensitizing and T790M resistance mutants that spares wild-type EGFR. This mono-anilino-pyrimidine compound is structurally distinct from other third-generation EGFR TKIs and offers a pharmacologically differentiated profile from earlier generation EGFR TKIs. Preclinically, the drug potently inhibits signaling pathways and cellular growth in both EGFRm(+) and EGFRm(+)/T790M(+) mutant cell lines in vitro, with lower activity against wild-type EGFR lines, translating into profound and sustained tumor regression in EGFR-mutant tumor xenograft and transgenic models. The treatment of 2 patients with advanced EGFRm(+) T790M(+) NSCLC is described as proof of principle.
We report the development of a novel structurally distinct third-generation EGFR TKI, AZD9291, that irreversibly and selectively targets both sensitizing and resistant T790M(+) mutant EGFR while harboring less activity toward wild-type EGFR. AZD9291 is showing promising responses in a phase I trial even at the first-dose level, with first published clinical proof-of-principle validation being presented.
Membrane transporters in drug development Giacomini, Kathleen M; Huang, Shiew-Mei; Tweedie, Donald J ...
Nature reviews. Drug discovery,
03/2010, Letnik:
9, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Membrane transporters can be major determinants of the pharmacokinetic, safety and efficacy profiles of drugs. This presents several key questions for drug development, including which transporters ...are clinically important in drug absorption and disposition, and which in vitro methods are suitable for studying drug interactions with these transporters. In addition, what criteria should trigger follow-up clinical studies, and which clinical studies should be conducted if needed. In this article, we provide the recommendations of the International Transporter Consortium on these issues, and present decision trees that are intended to help guide clinical studies on the currently recognized most important drug transporter interactions. The recommendations are generally intended to support clinical development and filing of a new drug application. Overall, it is advised that the timing of transporter investigations should be driven by efficacy, safety and clinical trial enrolment questions (for example, exclusion and inclusion criteria), as well as a need for further understanding of the absorption, distribution, metabolism and excretion properties of the drug molecule, and information required for drug labelling.
The relative safety (or otherwise) of silicone gel filled breast implants remains a controversial issue. The Dark Agouti (DA) rat has been shown recently to have a high susceptibility for developing ...arthritis. This study determined the arthritogenic potential of silicone gel, silicone oil, and the low molecular weight octamethylcyclotetrasiloxane (D4), by either mixing it with bovine collagen II (BII) or by injecting silicone gel alone in DA rats. Three separate experiments were performed using 110 female DA rats with 10 rats per treatment group. The incidence of collagen induced arthritis was as follows: Experiment I (6
μg BII)-PBS=0/10, silicone gel=4/10, and IFA=8/9; Experiment II (125
μg BII)-PBS=0/10, silicone gel=7/10, IFA=10/10, 1,000
cs silicone oil=3/10, D4=0/10, and 1% D4 in 1,000
cs silicone oil=1/10; Experiment III (adjuvant alone)-IFA=8/10, silicone gel=0/10. Anti-BII antibodies were formed in most of the rats treated with either silicone gel or IFA mixed with BII and these groups of rats showed a positive DTH reaction. The PBS treated rats were negative for both anti-BII antibodies and DTH reaction. Silicone gel taken from a commercial breast implant thus is capable of mediating collagen induced arthritis in the DA rat. However, silicone gel alone does not appear to be arthritogenic.
Evolving treatments, disease phenotypes, and biology, together with a changing drug development environment, have created the need to revise castration-resistant prostate cancer (CRPC) clinical trial ...recommendations to succeed those from prior Prostate Cancer Clinical Trials Working Groups.
An international expert committee of prostate cancer clinical investigators (the Prostate Cancer Clinical Trials Working Group 3 PCWG3) was reconvened and expanded and met in 2012-2015 to formulate updated criteria on the basis of emerging trial data and validation studies of the Prostate Cancer Clinical Trials Working Group 2 recommendations.
PCWG3 recommends that baseline patient assessment include tumor histology, detailed records of prior systemic treatments and responses, and a detailed reporting of disease subtypes based on an anatomic pattern of metastatic spread. New recommendations for trial outcome measures include the time to event end point of symptomatic skeletal events, as well as time to first metastasis and time to progression for trials in the nonmetastatic CRPC state. PCWG3 introduces the concept of no longer clinically benefiting to underscore the distinction between first evidence of progression and the clinical need to terminate or change treatment, and the importance of documenting progression in existing lesions as distinct from the development of new lesions. Serial biologic profiling using tumor samples from biopsies, blood-based diagnostics, and/or imaging is also recommended to gain insight into mechanisms of resistance and to identify predictive biomarkers of sensitivity for use in prospective trials.
PCWG3 moves drug development closer to unmet needs in clinical practice by focusing on disease manifestations most likely to affect prognosis adversely for therapeutics tested in both nonmetastatic and metastatic CRPC populations. Consultation with regulatory authorities is recommended if a trial is intended to seek support for drug approval.
The ability of the myocyte to maintain an ionic concentration gradient is perhaps the best indication of myocardial viability. We studied the relationship of 23Na MRI intensity to viability and ...explored the potential of fast-imaging techniques to reduce 23Na imaging times in rabbits and dogs.
Eighteen rabbits underwent in situ coronary artery occlusion and reperfusion. The hearts were then either imaged following isolation and perfusion with cardioplegic solution (n = 6), imaged in vivo (n = 6), or analyzed for 23Na content and relaxation times (n = 12). Normal rabbits (n = 6) and dogs (n = 4) were imaged to examine the effect of animal size on 23Na image quality. 23Na imaging times were 7, 11, and 4 minutes for isolated rabbits, in vivo rabbits, and in vivo dogs, respectively. Infarcted, reperfused regions, identified by triphenyltetrazolium chloride staining, showed a significant elevation in 23Na image intensity compared with viable regions (isolated, 42 +/- 5%, P < .02; in vivo, 95 +/- 6%, P < .001), consistent with increased tissue sodium content. Similarly, 23Na MR spectroscopy showed that Na+ was higher in nonviable than viable myocardium (isolated, 99 +/- 4 versus 61 +/- 2 mmol/L; in vivo, 91 +/- 2 versus 38 +/- 1 mmol/L; P < .001 for both). Image signal-to-noise ratios were higher in dogs than rabbits despite shorter imaging times, primarily due to larger voxels.
Following acute infarction with reperfusion, a regional increase in 23Na MR image intensity is associated with nonviable myocardium. Fast gradient-echo imaging techniques reduce 23Na imaging times to a few minutes, suggesting that 23Na MR imaging has the potential to become a useful experimental and clinical tool.
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