To Recognize the Use of International Standards for Making Harmonized Regulation of Medical Devices in Asia-Pacific

‘Medical Devices’ include everything from highly sophisticated, computerized, medical equipment, right down to simple wooden tongue depressors. Regulations embody the public expectations for how buildings and facilities are expected to perform and as such represent public policy. Regulators, who develop and enforce regulations, are empowered to act in the public’s interest to set this policy and are ultimately responsible to the public in this regard. Standardization contributes to the basic infrastructure that underpins society including health and environment, while promoting sustainability and good regulatory practice. The international organizations that produce International Standards are the International Electrotechnical Commission (IEC), the International Organization for Standardization (ISO), and the International Telecommunication Union (ITU). With the increasing globalization of markets, International Standards (as opposed to regional or national standards) have become critical to the trading process, ensuring a level playing field for exports, and ensuring that imports meet the internationally recognized levels of performance and safety. The development of standards is done in response to sectors and stakeholders that express a clearly established need for them. An industry sector or other stakeholder group typically communicates its requirement for standards to one of the national members. To be accepted for development, a proposed work item must receive a majority support of the participating members, who verify the global relevance of the proposed item. The regulatory authority (RA) should provide a method for the recognition of international voluntary standards and for public notification of such recognition. The process of recognition may vary from country to country. Recognition may occur by periodic publication of lists of standards that a regulatory authority has found will meet the Essential Principles. In conclusion, International standards, such as, basic standards, group standards, and product standards, are a tool for harmonizing regulatory processes, to assure the safety, quality, and performance of medical devices. Standards represent the opinion of experts from all interested parties, including industry, regulators, users, and others

Determining lines of therapy in patients with solid cancers: a proposed new systematic and comprehensive framework

The complexity of neoplasia and its treatment are a challenge to the formulation of general criteria that are applicable across solid cancers. Determining the number of prior lines of therapy (LoT) is critically important for optimising future treatment, conducting medication audits, and assessing eligibility for clinical trial enrolment. Currently, however, no accepted set of criteria or definitions exists to enumerate LoT. In this article, we seek to open a dialogue to address this challenge by proposing a systematic and comprehensive framework to determine LoT uniformly across solid malignancies. First, key terms, including LoT and ‘clinical progression of disease’ are defined. Next, we clarify which therapies should be assigned a LoT, and why. Finally, we propose reporting LoT in a novel and standardised format as LoT N (CLoT + PLoT), where CLoT is the number of systemic anti-cancer therapies (SACT) administered with curative intent and/or in the early setting, PLoT is the number of SACT given with palliative intent and/or in the advanced setting, and N is the sum of CLoT and PLoT. As a next step, the cancer research community should develop and adopt standardised guidelines for enumerating LoT in a uniform manner

Harmonized Medical Device Regulation: Need, Challenges, and Risks of not Harmonizing the Regulation in Asia

Medical device sector is one of the most complex and challenging business segments of the healthcare industry with close collaboration between science and engineering. Despite the fact that Asia has 60% of the world population providing large market potential, Asian healthcare expenditure constitutes only 15% of the global healthcare expenditure. The accelerated ageing population and increasing prevalence of chronic disease are the key drivers that contribute toward the increase in the total healthcare expenditure on medical devices in the region. Several policies clearly showed the eagerness of the government to provide better healthcare infrastructure with better medical devices and facilities. The fundamental objective of the regulatory harmonization is to improve the efficiency of national economies and their ability to adopt to change and remain competitive. After the era of liberalization and globalization, the desires of developing economies is to ensure safety and performance of the product brought to their markets and for this harmonized regulation is an important tool for strengthening the same. If we talk about the industry need, then this approach will eliminate redundant requirements that do not contribute to safety and effectiveness. In addition, Asia is diverse in many respects and with it come the various challenges to harmonizing the regulation which includes diversity in culture, politics, economy, historical issues, etc. If, by any reason, the regulation of medical devices is not harmonized and consequently, the harmonized regulation is not adopted, then it leads to serious concerns like delayed or absent access to innovative technology, continued rise in the cost of medical therapies, etc. So this issue is written to attract all stakeholders to move toward the concept of harmonization, keeping in mind their need, challenges, and risks of not harmonizing the regulation as well

First-Principles Study of the Electronic and Magnetic Properties of Defects in Carbon Nanostructures

Understanding the magnetic properties of graphenic nanostructures is instrumental in future spintronics applications. These magnetic properties are known to depend crucially on the presence of defects. Here we review our recent theoretical studies using density functional calculations on two types of defects in carbon nanostructures: Substitutional doping with transition metals, and sp$^3$-type defects created by covalent functionalization with organic and inorganic molecules. We focus on such defects because they can be used to create and control magnetism in graphene-based materials. Our main results are summarized as follows: i)Substitutional metal impurities are fully understood using a model based on the hybridization between the $d$ states of the metal atom and the defect levels associated with an unreconstructed D$_{3h}$ carbon vacancy. We identify three different regimes, associated with the occupation of distinct hybridization levels, which determine the magnetic properties obtained with this type of doping; ii) A spin moment of 1.0 $\mu_B$ is always induced by chemical functionalization when a molecule chemisorbs on a graphene layer via a single C-C (or other weakly polar) covalent bond. The magnetic coupling between adsorbates shows a key dependence on the sublattice adsorption site. This effect is similar to that of H adsorption, however, with universal character; iii) The spin moment of substitutional metal impurities can be controlled using strain. In particular, we show that although Ni substitutionals are non-magnetic in flat and unstrained graphene, the magnetism of these defects can be activated by applying either uniaxial strain or curvature to the graphene layer. All these results provide key information about formation and control of defect-induced magnetism in graphene and related materials.Comment: 40 pages, 17 Figures, 62 References; Chapter 2 in Topological Modelling of Nanostructures and Extended Systems (2013) - Springer, edited by A. R. Ashrafi, F. Cataldo, A. Iranmanesh, and O. Or

Basal cell carcinoma of the vulva: a case report and systematic review of the literature

The vulva is an unusual site for basal cell carcinoma (BCC). Vulvar BCC accounts for <1% of all BCCs and <5% of all vulvar malignancies. We report the case of an 83 year‐old woman who presented with a 2‐month history of a tender labial growth, with histopathology confirming nodular BCC. We conducted a systematic literature review of the characteristics of reported cases of vulvar BCCs. A comprehensive systematic review of articles indexed for MEDLINE and Embase yielded 96 reports describing 437 patients with 446 BCCs of the vulva. The mean age at presentation was 70 (range 20–100). Most women had no underlying vulvar disease. Approximately 60% of cases were of the nodular subtype. Treatment approach varied widely with over half of cases treated with wide local or local excision. Mohs micrographic surgery (MMS) for vulvar BCC was first reported in 1988 with seven total MMS cases reported. Twenty‐three cases of recurrence have been reported; 21 of these cases after local excision but none following MMS. Vulvar BCC is a rarely reported cancer that affects older women predominantly. MMS represents a promising treatment for BCC in this anatomic location.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150570/1/ijd14307.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150570/2/ijd14307_am.pd

Exclusive ρ0\rho^0 electroproduction on the proton at CLAS

The $e p\to e^\prime p \rho^0$ reaction has been measured, using the 5.754 GeV electron beam of Jefferson Lab and the CLAS detector. This represents the largest ever set of data for this reaction in the valence region. Integrated and differential cross sections are presented. The $W$, $Q^2$ and $t$ dependences of the cross section are compared to theoretical calculations based on $t$-channel meson-exchange Regge theory on the one hand and on quark handbag diagrams related to Generalized Parton Distributions (GPDs) on the other hand. The Regge approach can describe at the $\approx$ 30% level most of the features of the present data while the two GPD calculations that are presented in this article which succesfully reproduce the high energy data strongly underestimate the present data. The question is then raised whether this discrepancy originates from an incomplete or inexact way of modelling the GPDs or the associated hard scattering amplitude or whether the GPD formalism is simply inapplicable in this region due to higher-twists contributions, incalculable at present.Comment: 29 pages, 29 figure

IGF-1 Induction by Acylated Steryl β-Glucosides Found in a Pre-Germinated Brown Rice Diet Reduces Oxidative Stress in Streptozotocin-Induced Diabetes

BACKGROUND: The pathology of diabetic neuropathy involves oxidative stress on pancreatic β-cells, and is related to decreased levels of Insulin-like growth factor 1 (IGF-1). Acylated steryl β-glucoside (PR-ASG) found in pre-germiated brown rice is a bioactive substance exhibiting properties that enhance activity of homocysteine-thiolactonase (HTase), reducing oxidative stress in diabetic neuropathy. The biological importance of PR-ASG in pancreatic β-cells remains unknown. Here we examined the effects of PR-ASG on IGF-1 and glucose metabolism in β-cells exposed to oxidative stress. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, a pre-germinated brown rice (PR)-diet was tested in streptozotocin (STZ)-induced diabetic rats. Compared with diabetic rats fed control diets, the PR-diet fed rats showed an improvement of serum metabolic and neurophysiological parameters. In addition, IGF-1 levels were found to be increased in the serum, liver, and pancreas of diabetic rats fed the PR-diet. The increased IGF-1 level in the pancreas led us to hypothesize that PR-ASG is protective for islet β-cells against the extensive injury of advanced or severe diabetes. Thus we examined PR-ASG to determine whether it showed anti-apoptotic, pro-proliferative effects on the insulin-secreting β-cells line, INS-1; and additionally, whether PR-ASG stimulated IGF-1 autocrine secretion/IGF-1-dependent glucose metabolism. We have demonstrated for the first time that PR-ASG increases IGF-1 production and secretion from pancreatic β-cells. CONCLUSION/SIGNIFICANCE: These findings suggest that PR-ASG may affect pancreatic β-cells through the activation of an IGF-1-dependent mechanism in the diabetic condition. Thus, intake of pre-germinated brown rice may have a beneficial effect in the treatment of diabetes, in particular diabetic neuropathy

Lrp Acts as Both a Positive and Negative Regulator for Type 1 Fimbriae Production in Salmonella enterica Serovar Typhimurium

Leucine-responsive regulatory protein (Lrp) is known to be an indirect activator of type 1 fimbriae synthesis in Salmonella enterica serovar Typhimurium via direct regulation of FimZ, a direct positive regulator for type 1 fimbriae production. Using RT-PCR, we have shown previously that fimA transcription is dramatically impaired in both lrp-deletion (Δlrp) and constitutive-lrp expression (lrpC) mutant strains. In this work, we used chromosomal PfimA-lacZ fusions and yeast agglutination assays to confirm and extend our previous results. Direct binding of Lrp to PfimA was shown by an electrophoretic mobility shift assay (EMSA) and DNA footprinting assay. Site-directed mutagenesis revealed that the Lrp-binding motifs in PfimA play a role in both activation and repression of type 1 fimbriae production. Overproduction of Lrp also abrogates fimZ expression. EMSA data showed that Lrp and FimZ proteins independently bind to PfimA without competitive exclusion. In addition, both Lrp and FimZ binding to PfimA caused a hyper retardation (supershift) of the DNA-protein complex compared to the shift when each protein was present alone. Nutrition-dependent cellular Lrp levels closely correlated with the amount of type 1 fimbriae production. These observations suggest that Lrp plays important roles in type 1 fimbriation by acting as both a positive and negative regulator and its effect depends, at least in part, on the cellular concentration of Lrp in response to the nutritional environment