Ethics Standards (HRPP) and Public Partnership (PARTAKE) to Address Clinical Research Concerns in India: Moving Toward Ethical, Responsible, Culturally Sensitive, and Community-Engaging Clinical Research.

Like other emerging economies, India's quest for independent, evidence-based, and affordable healthcare has led to robust and promising growth in the clinical research sector, with a compound annual growth rate (CAGR) of 20.4% between 2005 and 2010. However, while the fundamental drivers and strengths are still strong, the past few years witnessed a declining trend (CAGR -16.7%) amid regulatory concerns, activist protests, and sponsor departure. And although India accounts for 17.5% of the world's population, it currently conducts only 1% of clinical trials. Indian and international experts and public stakeholders gathered for a 2-day conference in June 2013 in New Delhi to discuss the challenges facing clinical research in India and to explore solutions. The main themes discussed were ethical standards, regulatory oversight, and partnerships with public stakeholders. The meeting was a collaboration of AAHRPP (Association for the Accreditation of Human Research Protection Programs)-aimed at establishing responsible and ethical clinical research standards-and PARTAKE (Public Awareness of Research for Therapeutic Advancements through Knowledge and Empowerment)-aimed at informing and engaging the public in clinical research. The present article covers recent clinical research developments in India as well as associated expectations, challenges, and suggestions for future directions. AAHRPP and PARTAKE provide etiologically based solutions to protect, inform, and engage the public and medical research sponsors

The absolute position of a resonance peak

It is common practice in scattering theory to correlate between the position of a resonance peak in the cross section and the real part of a complex energy of a pole of the scattering amplitude. In this work we show that the resonance peak position appears at the absolute value of the pole's complex energy rather than its real part. We further demonstrate that a local theory of resonances can still be used even in cases previously thought impossible

A HIERARCHY OF GAUGED GRASSMANIAN MODELS IN 4p4p DIMENSIONS WITH SELF-DUAL INSTANTONS

We present a hierarchy of gauged Grassmanian models in $4p$ dimensions, where the gauge field takes its values in the $2^{2p- 1}\times 2^{2p-1}$ chiral representation of SO(4p). The actions of all these models are absolutely minimised by a hierarchy of self-duality equations, all of which reduce to a single pair of coupled ordinary differential equations when subjected to $4p$ dimensional spherical symmetry.Comment: latex file, 13 page

Effects of dopamine D2/D3 receptor antagonism on human planning and spatial working memory

Psychopharmacological studies in humans suggest important roles for dopamine (DA) D2 receptors in human executive functions, such as cognitive planning and spatial working memory (SWM). However, studies that investigate an impairment of such functions using the selective DA D2/3 receptor antagonist sulpiride have yielded inconsistent results, perhaps because relatively low doses were used. We believe we report for the first time, the effects of a higher (800 mg p.o.) single dose of sulpiride as well as of genetic variation in the DA receptor D2 gene (DA receptor D2 Taq1A polymorphism), on planning and working memory. With 78 healthy male volunteers, we apply a between-groups, placebo-controlled design. We measure outcomes in the difficult versions of the Cambridge Neuropsychological Test Automated Battery One-Touch Stockings of Cambridge and the self-ordered SWM task. Volunteers in the sulpiride group showed significant impairments in planning accuracy and, for the more difficult problems, in SWM. Sulpiride administration speeded response latencies in the planning task on the most difficult problems. Volunteers with at least one copy of the minor allele (A1+) of the DA receptor D2 Taq1A polymorphism showed better SWM capacity, regardless of whether they received sulpiride or placebo. There were no effects on blood pressure, heart rate or subjective sedation. In sum, a higher single dose of sulpiride impairs SWM and executive planning functions, in a manner independent of the DA receptor D2 Taq1A polymorphism.This research work was funded by a Core Award from the Medical Research Council and the Wellcome Trust to the Behavioural and Clinical Neuroscience Institute (MRC Ref G1000183; WT Ref 093875/Z/10/Z). Also supported by a Wellcome Trust Senior Investigator Award (104631/Z/14/Z) awarded to TWR. CE was supported by the Swiss National Science Foundation (PA00P1_134135) and the Vienna Science and Technology Fund (WWTF VRG13-007)

Doping a semiconductor to create an unconventional metal

Landau Fermi liquid theory, with its pivotal assertion that electrons in metals can be simply understood as independent particles with effective masses replacing the free electron mass, has been astonishingly successful. This is true despite the Coulomb interactions an electron experiences from the host crystal lattice, its defects, and the other ~1022/cm3 electrons. An important extension to the theory accounts for the behaviour of doped semiconductors1,2. Because little in the vast literature on materials contradicts Fermi liquid theory and its extensions, exceptions have attracted great attention, and they include the high temperature superconductors3, silicon-based field effect transistors which host two-dimensional metals4, and certain rare earth compounds at the threshold of magnetism5-8. The origin of the non-Fermi liquid behaviour in all of these systems remains controversial. Here we report that an entirely different and exceedingly simple class of materials - doped small gap semiconductors near a metal-insulator transition - can also display a non-Fermi liquid state. Remarkably, a modest magnetic field functions as a switch which restores the ordinary disordered Fermi liquid. Our data suggest that we have finally found a physical realization of the only mathematically rigourous route to a non-Fermi liquid, namely the 'undercompensated Kondo effect', where there are too few mobile electrons to compensate for the spins of unpaired electrons localized on impurity atoms9-12.Comment: 17 pages 4 figures supplemental information included with 2 figure

Simple matrix models for random Bergman metrics

Recently, the authors have proposed a new approach to the theory of random metrics, making an explicit link between probability measures on the space of metrics on a Kahler manifold and random matrix models. We consider simple examples of such models and compute the one and two-point functions of the metric. These geometric correlation functions correspond to new interesting types of matrix model correlators. We study a large class of examples and provide in particular a detailed study of the Wishart model.Comment: 23 pages, IOP Latex style, diastatic function Eq. (22) and contact terms in Eqs. (76, 95) corrected, typos fixed. Accepted to JSTA

Influence of subretinal fluid in advanced stage retinopathy of prematurity on proangiogenic response and cell proliferation

Purpose The clinical phenotype of advanced stage retinopathy of prematurity (ROP, stages 4 and 5) cannot be replicated in an animal model. To dissect the molecular events that can lead up to advanced ROP, we examined subretinal fluid (SRF) and surgically dissected retrolental membranes from patients with advanced ROP to evaluate its influences on cell proliferation, angiogenic properties, and macrophage polarity. Methods: We compared our findings to SRF collected from patients with uncomplicated rhegmatogenous retinal detachment (RD) without proliferative vitreoretinopathy and surgically dissected epiretinal membrane from eyes with macular pucker. All subretinal fluid samples were equalized for protein. The angiogenic potential of SRF from ROP eyes was measured using a combination of capillary cord formation in a fibrin clot assay, and its proliferative effect was tested with a DNA synthesis of human retinal microvascular endothelial cells. Findings were compared with SRF collected from participants with uncomplicated rhegmatogenous RD without proliferative vitreoretinopathy. The ability of SRF to induce nitric oxide production was measured in vitro using murine J774A.1 macrophages. Cytokine profiles of SRF from ROP and RD eyes were measured using a multienzyme-linked immunosorbent assay (ELISA). Fluorescent immunohistochemistry of retrolental membranes from ROP was performed to detect the presence of leukocytes and the composition of tissue macrophages using markers for M1 and M2 differentiation. Results: The cytokine composition in SRF revealed that in ROP, not only were several proangiogenic factors were preferentially elevated but also the profile of proinflammatory factors was also increased compared to the RD eyes. SRF from ROP eyes supported cell proliferation and endothelial cord formation while SRF from RD eyes had inhibitory effects. SRF from eyes with ROP but not RD robustly induced nitric oxide production in macrophages. Furthermore, fluorescent immunostaining revealed a preponderance of M1 over M2 macrophages in retrolental fibrous membranes from ROP eyes. The cytokine profile and biologic properties of SRF in ROP promote a proangiogenic environment, which supports the maintenance and proliferation of fibrous membranes associated with advanced stages of ROP. In contrast, SRF from RD eyes exhibits a suppressive environment for endothelial cell proliferation and angiogenesis. Conclusions: Our investigation demonstrates that the microenvironment in advanced ROP eyes is proangiogenic and proinflammatory. These findings suggest that management of advanced ROP should not be limited to the surgical removal of the fibrovascular membranes and antiangiogenic therapy but also directed to anti-inflammatory therapy and to promote M2 activation over M1 activity

Random matrix theory and symmetric spaces

In this review we discuss the relationship between random matrix theories and symmetric spaces. We show that the integration manifolds of random matrix theories, the eigenvalue distribution, and the Dyson and boundary indices characterizing the ensembles are in strict correspondence with symmetric spaces and the intrinsic characteristics of their restricted root lattices. Several important results can be obtained from this identification. In particular the Cartan classification of triplets of symmetric spaces with positive, zero and negative curvature gives rise to a new classification of random matrix ensembles. The review is organized into two main parts. In Part I the theory of symmetric spaces is reviewed with particular emphasis on the ideas relevant for appreciating the correspondence with random matrix theories. In Part II we discuss various applications of symmetric spaces to random matrix theories and in particular the new classification of disordered systems derived from the classification of symmetric spaces. We also review how the mapping from integrable Calogero--Sutherland models to symmetric spaces can be used in the theory of random matrices, with particular consequences for quantum transport problems. We conclude indicating some interesting new directions of research based on these identifications.Comment: 161 pages, LaTeX, no figures. Revised version with major additions in the second part of the review. Version accepted for publication on Physics Report

Bose Glass in Large N Commensurate Dirty Boson Model

The large N commensurate dirty boson model, in both the weakly and strongly commensurate cases, is considered via a perturbative renormalization group treatment. In the weakly commensurate case, there exists a fixed line under RG flow, with varying amounts of disorder along the line. Including 1/N corrections causes the system to flow to strong disorder, indicating that the model does not have a phase transition perturbatively connected to the Mott Insulator-Superfluid (MI-SF) transition. I discuss the qualitative effects of instantons on the low energy density of excitations. In the strongly commensurate case, a fixed point found previously is considered and results are obtained for higher moments of the correlation functions. To lowest order, correlation functions have a log-normal distribution. Finally, I prove two interesting theorems for large N vector models with disorder, relevant to the problem of replica symmetry breaking and frustration in such systems.Comment: 16 pages, 7 figure