‘ISOLATED IN OUR OWN NEIGHBOURHOOD’: ANALYSIS ON THE PROPOSAL TO REGULATE PEER-TO-PEER ACCOMMODATION SERVICES IN MALAYSIA

Peer-to-Peer Accommodation services (P2PA) are mushrooming worldwide due to the expansion of digital services and Internet access. Since P2PA services operate fully online, small establishments utilise disruptive technology and surpass traditional hoteliers by surprise. In the first part of this article, we examine the problems caused by P2PA for ‘playing on an uneven field’, avoiding necessary taxes, skipping regulatory and safety requirements, and causing loss of tranquillity to the neighbourhood. Due to these problems, a proposal was moved by the government to regulate P2PA in Malaysia via a self-regulatory guideline, as analysed in the second part of the article. However, due to its non-binding status, the proposal will arguably lead to irregularities in regulatory mechanisms at the state level when enforced. P2PA hosts were asked to comply with regulatory requirements similar to hoteliers, but the platform providers have arguably avoided any P2PA related liability nor responsibility as they operate offshore. Applying qualitative research methods via content analysis and semi-structured interviews, the article concludes by proposing a legal framework to regulate the P2PA platform providers, including hosts and agents, which is deemed timely and necessary for Malaysia to safeguard the interests of both tourists and stakeholders.

Physical Model Testing Of An Experimental Vortex Device For Controlling Total Suspended Solids In Stormwater

In highly urbanized area, lack of space limits the application of most stormwater quality treatment technologies. Oil/Grit Separators (OGSs) are preferred in these cases due to their compact size and reasonable solids removal efficiency. The objective of this research is to identify the challenges and practical potential solutions of solids treatment performance testing on a full-scaled experimental vortex device (EVD) adopting TRCA’s regulatory guideline titled the “Procedure for Laboratory Testing of Oil/Grit Separators” (referred to in this paper as the Procedure) which stipulates the standards of sediments and oil removal tests in Canada. The test results indicated that: (1) TSS treatment efficiency of EVD was observed to decline with the particle size and flow rate; and (2) the average overall TSS treatment efficiency decreased from 52% to 44% as the flow rate doubled.

Physical Model Testing Of An Experimental Vortex Device For Controlling Total Suspended Solids In Stormwater

In highly urbanized area, lack of space limits the application of most stormwater quality treatment technologies. Oil/Grit Separators (OGSs) are preferred in these cases due to their compact size and reasonable solids removal efficiency. The objective of this research is to identify the challenges and practical potential solutions of solids treatment performance testing on a full-scaled experimental vortex device (EVD) adopting TRCA’s regulatory guideline titled the “Procedure for Laboratory Testing of Oil/Grit Separators” (referred to in this paper as the Procedure) which stipulates the standards of sediments and oil removal tests in Canada. The test results indicated that: (1) TSS treatment efficiency of EVD was observed to decline with the particle size and flow rate; and (2) the average overall TSS treatment efficiency decreased from 52% to 44% as the flow rate doubled.

Thresholds and Endocrine Disruptors: An Endocrine Society Policy Perspective

The concept of a threshold of adversity in toxicology is neither provable nor disprovable. As such, it is not a scientific question but a theoretical one. Yet, the belief in thresholds has led to traditional ways of interpreting data derived from regulatory guideline studies of the toxicity of chemicals. This includes, for example, the use of standard “uncertainty factors” when a “No Adverse Effect Level” (or similar “benchmark dose”) is either observed, or not observed. In the context of endocrine-disrupting chemicals (EDCs), this approach is demonstrably inappropriate. First, the efficacy of a hormone on different endpoints can vary by several orders of magnitude. This feature of hormone action also applies to EDCs that can interfere with that hormone. For this reason, we argue that the choice of endpoint for use in regulation is critical, but note that guideline studies were not designed with this in mind. Second, the biological events controlled by hormones in development not only change as development proceeds but are different from events controlled by hormones in the adult. Again, guideline endpoints were also not designed with this in mind, especially since the events controlled by hormones can be both temporally and spatially specific. The Endocrine Society has laid out this logic over several years and in several publications. Rather than being extreme views, they represent what is known about hormones and the chemicals that can interfere with them.

Ukrainian NPP Seismic Resistance Assessment Using Provisions of Regulatory Guideline NP 306.2.208-2016

Since November 2016, the new Regulatory Guideline NP 306.2.208-2016 “Requirements for Seismic Resistance Design and for Evaluation of Seismic Safety of Ukrainian NPPs” [1] has been in force in Ukraine. This Guideline was developed to improve requirements for NPP site seismic hazard assessment, NPP seismic resistance design and assessment/review of Ukrainian NPP seismic safety. Energoatom developed the Organizational and Technical Measures for Implementation of NP 306.2.208-2016 [2] approved by State Nuclear Regulatory Inspectorate of Ukraine to perform NP 306.2.208-2016 [1] requirements. The paper considers the status of Energoatom in implementation of the main organizational and technical measures [2] on increasing seismic resistance of Ukrainian NPP units according to NP 306.2.208-2016 [1]. In particular, these measures are the following: specification of NPP site seismicity considering results of new studies; introduction of changes into classification (seismic categorization) of systems and components; analysis of necessity to consider additional load combinations with seismic loads, specification of assessing seismic resistance of structures, systems and components; seismic probabilistic safety assessment of NPP units.

Validated LC-MS/MS Method for Simultaneous Quantitation of SAFit-1 and SAFit-2 in Mice Plasma: Application to a Pharmacokinetic Study

SAFit-1 and SAFit-2 are selective FKBP51 (FK506-binding protein 51) ligands. In this paper, we present the development and validation data of an LC-MS/MS method for the simultaneous quantitation of SAFit-1 and SAFit-2 in mice plasma as per FDA regulatory guideline. SAFit-1 and SAFit-2 along with internal standard were extracted from mice plasma using liquid-liquid extraction method. Chromatographic resolution of SAFit-1, SAFit-2 and the internal standard (warfarin) was achieved on an X-Terra phenyl column using 0.2% formic acid:acetonitrile (20:80, v/v) as an eluent, which was delivered at a flow-rate of 0.9 mL/min. The MS/MS ion transitions monitored were m/z 748.4→420.4, 803.7→384.3 and 309.2 →163.2 for SAFit-1, SAFit-2 and the internal standard, respectively. The linearity range was 2.45–2446 ng/mL for both SAFit-1 and SAFit-2. The intra- and inter-day accuracy and intra- and inter-day precision were in the range of 0.90–1.07 and 2.38–10.8%, respectively for SAFit-1; 0.97–1.15 and 0.23–12.5%, respectively for SAFit-2. Both SAFit-1 and SAFit-2 were found to be stable in stability studies (up to three freeze-thaw cycles and for long-term at −80°C for 30 days) and processed (bench-top for 3 h and in in-injector for 16 h) samples. The application of the validated method was shown in a pharmacokinetic study in mice.

Validated HPLC Method for Quantification of a Novel Trk Inhibitor, Larotrectinib in Mice Plasma: Application to a Pharmacokinetic Study

Larotrectinib, is an orally active novel small molecule approved for the treatment of solid tumors in pediatrics and adult patients. It acts by inhibiting tropomyosin receptor kinase. In this paper, we report the development and validation of a high-performance liquid chromatography (HPLC) method for the quantitation of larotrectinib in mice plasma as per the FDA regulatory guideline. Plasma samples processing was accomplished through simple protein precipitation using acetonitrile enriched with internal standard (IS, enasidenib). The chromatographic analysis was performed using a gradient mobile phase comprising 10 mM ammonium acetate and acetonitrile at a flow-rate of 0.8 mL/min on an X-Terra Phenyl column. The UV detection wave length was set at λmax 262 nm. Larotrectinib and the IS eluted at 3.85 and 6.60 min, respectively with a total run time of 8.0 min. The calibration curve was linear over a concentration range of 0.20–5.00 μg/mL (r2=≥0.992). The intra- and inter-day precision and accuracy results were within the acceptable limits. Results of stability studies indicated that larotrectinib was stable on bench-top, in auto-sampler, up to three freeze/thaw cycles and long-term storage at −80°C. The validated HPLC method was successfully applied to a pharmacokinetic study in mice.

Validated LC-MS/MS Method for Simultaneous Quantitation of Enasidenib and its Active Metabolite, AGI-16903 in Small Volume Mice Plasma: Application to a Pharmacokinetic Study

Enasidenib is a selective mutant isocitrate dehydrogenase 2 inhibitor approved for the treatment of relapsed and refractory acute myeloid leukemia patients. A sensitive and rapid method has been developed and validated as per regulatory guideline for the simultaneous quantitation of enasidenib and its active metabolite, AGI-16903 in mice plasma using an LC-MS/MS. Enasidenib and AGI-16903 along with internal standard were extracted from mice plasma using simple protein precipitation method. Chromatographic resolution of enasidenib, AGI-16903 and the internal standard (close analogue of AGI-16903) was achieved on a Chromolith RP-18e column using 0.2% formic acid:acetonitrile (15:85, v/v) as an eluent, which was delivered at a flow-rate of 1.2 mL/min. The MS/MS ion transitions monitored were m/z 474.1→267.2, 402.1→188.1 and 421.0→146.1 for enasidenib, AGI-16903 and the internal standard, respectively. The linearity range was 1.01–3023 ng/mL for both enasidenib and AGI-16903. The within-run and between-run accuracy and within-run and between-run precision were in the range of − 2.29 to 2.72 (as one value is in negative side). and 4.65–9.82%, respectively for enasidenib; 0.19–10.3 and 3.22–9.22%, respectively for AGI-16903. Both enasidenib and AGI-16903 were found to be stable in stability (up to three freeze-thaw cycles and for long-term at −80°C for 30 days) and processed (bench-top for 6 h and in in-injector for 24 h) samples. Application of the validated method was shown in a pharmacokinetic study in mice.

Validated LC-ESI-MS/MS method for the determination of ivosidenib in 10 µL mice plasma: application to a pharmacokinetic study

A simple, selective and rapid LC-ESI-MS/MS method has been developed and validated for the quantification of ivosidenib in mice plasma using warfarin as an internal standard (I.S.) as per regulatory guideline. Sample preparation was accomplished through a simple protein precipitation process. Chromatography of ivosidenib and the I.S. was achieved on an Atlantis dC18 column using an isocratic mobile phase comprising 0.2 % formic acid in water and acetonitrile (25:75, v/v) delivered at a flow rate of 1.0 mL/min. LC-MS/MS was operated under the multiple reaction-monitoring mode (MRM) using the electrospray ionization technique in positive ion mode and the transitions of m/z 583.1→186.1 and m/z 309.2→251.3 were used to quantitate ivosidenib and the I.S, respectively. The total chromatographic run time was 2.0 min. Linearity was established in the concentration range of 1.10-3293 ng/mL (r2>0.99). The intra- and inter-day accuracy and precision for ivosidenib in mice plasma were in the range of 5.72-9.91 and 5.90-10.7 %, respectively. Ivosidenib was found to be stable on bench-top for 6 h, up to three freeze-thaw cycles, in in-injector for 24 h and for one month at -80 °C. The applicability of the validated method has been demonstrated in a mice pharmacokinetic study. Following intravenous (2 mg/kg) and oral (5 mg/kg) administration of ivosidenib to mice, concentrations were quantifiable up to 24 and 48 h, respectively. The bioavailability was 61 %.