ORPHAN DRUGS: THE CURRENT GLOBAL AND INDIAN SCENARIO

ABSTRACTIt was not until a few decades ago that orphan drugs, still enjoyed†the status of pharmaceutical touch-me-not entities. However, the past two decadeshave witnessed a radical shift in the approach of global pharmaceutical industry toward orphan drugs. This has stemmed from an apparent innovationcrisis in the domain of common diseases, progressively increasing stringency in the regulations, and the decline of the blockbuster business model.Further, the success stories of a few orphan drugs, for instance, eculizumab has gone a long way in breaking the myth of non-profitability associatedwith orphan drug development endeavor. This combined with the high degree of incentivization attached with orphan drug development makes it avery lucrative avenue for further investment by the pharmaceutical industry. Sadly, the Indian scenario with respect to orphan drugs is a throwbackto the dark ages.†The progress seen across the developed nations, for instance, the United States of America has not permeated into the Indianmarket. India, with its huge population base, stands to provide a hugely lucrative market for orphan drug development. However, this point seemsto have escaped the notice of the Indian authorities and the pharmaceutical sector in India. Thus, with the various patient advocacy groups and nongovernmentorganizationschampioning the cause of orphan diseased patientsin India, the time is ripe forthe concerned authoritiesand the pharmasectorin India totakecognizance of this gapinglacuna in the health-careservices and undertakemeasurestoaddressthis situation.Keywords: Pharmaceutical touch-me-not, Orphan, Indian scenario.Â

Finding Pairwise Intersections Inside a Query Range

We study the following problem: preprocess a set O of objects into a data structure that allows us to efficiently report all pairs of objects from O that intersect inside an axis-aligned query range Q. We present data structures of size $O(n({\rm polylog} n))$ and with query time $O((k+1)({\rm polylog} n))$ time, where k is the number of reported pairs, for two classes of objects in the plane: axis-aligned rectangles and objects with small union complexity. For the 3-dimensional case where the objects and the query range are axis-aligned boxes in R^3, we present a data structures of size $O(n\sqrt{n}({\rm polylog} n))$ and query time $O((\sqrt{n}+k)({\rm polylog} n))$. When the objects and query are fat, we obtain $O((k+1)({\rm polylog} n))$ query time using $O(n({\rm polylog} n))$ storage

Frequency stabilization in nonlinear micromechanical oscillators

Mechanical oscillators are present in almost every electronic device. They mainly consist of a resonating element providing an oscillating output with a specific frequency. Their ability to maintain a determined frequency in a specified period of time is the most important parameter limiting their implementation. Historically, quartz crystals have almost exclusively been used as the resonating element, but micromechanical resonators are increasingly being considered to replace them. These resonators are easier to miniaturize and allow for monolithic integration with electronics. However, as their dimensions shrink to the microscale, most mechanical resonators exhibit nonlinearities that considerably degrade the frequency stability of the oscillator. Here we demonstrate that, by coupling two different vibrational modes through an internal resonance, it is possible to stabilize the oscillation frequency of nonlinear self-sustaining micromechanical resonators. Our findings provide a new strategy for engineering low-frequency noise oscillators capitalizing on the intrinsic nonlinear phenomena of micromechanical resonators.Fil: Antonio, Dario. Argonne National Laboratory. Center for Nanoscale Materials; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zanette, Damian Horacio. Comisión Nacional de Energía Atómica. Gerencia del Area de Investigación y Aplicaciones No Nucleares. Gerencia de Física (centro Atómico Bariloche); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: López, Daniel . Argonne National Laboratory. Center for Nanoscale Materials; Estados Unido

Alcohol Production as an Adaptive Livelihood Strategy for Women Farmers in Tanzania and Its Potential for Unintended Consequences on Women's Reproductive Health.

Although women occupy a central position in agriculture in many developing countries, they face numerous constraints to achieving their full potential including unequal access to assets and limited decision-making authority. We explore the intersection of agricultural livelihoods, food and economic security, and women's sexual and reproductive health in Iringa Region, Tanzania. Our goal was to understand whether the benefits of supporting women in the agricultural sector might also extend to more distal outcomes, including sexual and reproductive health. Using the Sustainable Livelihoods Framework to guide data collection, we conducted 13 focus group discussions (FGD) with female (n = 11) and male farmers (n = 2) and 20 in-depth interviews with agricultural extension officers (n = 10) and village agro-dealers (n = 10). Despite providing the majority of agricultural labor, women have limited control over land and earned income and have little bargaining power. In response to these constraints, women adopt adaptive livelihood strategies, such as alcohol production, that allow them to retain control over income and support their households. However, women's central role in alcohol production, in concert with the ubiquitous nature of alcohol consumption, places them at risk by enhancing their vulnerability to unsafe or transactional sex. This represents a dangerous confluence of risk for female farmers, in which alcohol plays an important role in income generation and also facilitates high-risk sexual behavior. Alcohol production and consumption has the potential to both directly and indirectly place women at risk for undesirable sexual and reproductive health outcomes. Group formation, better access to finance, and engaging with agricultural extension officers were identified as potential interventions for supporting women farmers and challenging harmful gender norms. In addition, joint, multi-sectoral approaches from health and agriculture and alternative income-generating strategies for women might better address the complexities of achieving safe and sustainable livelihoods for women in this context

Applications of Direct Injection Soft Chemical Ionisation-Mass Spectrometry for the Detection of Pre-blast Smokeless Powder Organic Additives

Analysis of smokeless powders is of interest from forensics and security perspectives. This article reports the detection of smokeless powder organic additives (in their pre-detonation condition), namely the stabiliser diphenylamine and its derivatives 2-nitrodiphenylamine and 4-nitrodiphenylamine, and the additives (used both as stabilisers and plasticisers) methyl centralite and ethyl centralite, by means of swab sampling followed by thermal desorption and direct injection soft chemical ionisation-mass spectrometry. Investigations on the product ions resulting from the reactions of the reagent ions H3O+ and O2+ with additives as a function of reduced electric field are reported. The method was comprehensively evaluated in terms of linearity, sensitivity and precision. For H3O+, the limits of detection (LoD) are in the range of 41-88 pg of additive, for which the accuracy varied between 1.5 and 3.2%, precision varied between 3.7 and 7.3% and linearity showed R20.9991. For O2+, LoD are in the range of 72 to 1.4 ng, with an accuracy of between 2.8 and 4.9% and a precision between 4.5 and 8.6% and R20.9914. The validated methodology was applied to the analysis of commercial pre-blast gun powders from different manufacturers.(VLID)4826148Accepted versio

Intervention planning and modification of the BUMP intervention: a digital intervention for the early detection of raised blood pressure in pregnancy

Background: Hypertensive disorders in pregnancy, particularly pre-eclampsia, pose a substantial health risk for both maternal and foetal outcomes. The BUMP (Blood Pressure Self-Monitoring in Pregnancy) interventions are being tested in a trial. They aim to facilitate the early detection of raised blood pressure through self-monitoring. This article outlines how the self-monitoring interventions in the BUMP trial were developed and modified using the person-based approach to promote engagement and adherence. Methods: Key behavioural challenges associated with blood pressure self-monitoring in pregnancy were identified through synthesising qualitative pilot data and existing evidence, which informed guiding principles for the development process. Social cognitive theory was identified as an appropriate theoretical framework. A testable logic model was developed to illustrate the hypothesised processes of change associated with the intervention. Iterative qualitative feedback from women and staff informed modifications to the participant materials. Results: The evidence synthesis suggested women face challenges integrating self-monitoring into their lives and that adherence is challenging at certain time points in pregnancy (for example, starting maternity leave). Intervention modification included strategies to address adherence but also focussed on modifying outcome expectancies, by providing messages explaining pre-eclampsia and outlining the potential benefits of self-monitoring. Conclusions: With an in-depth understanding of the target population, several methods and approaches to plan and develop interventions specifically relevant to pregnant women were successfully integrated, to address barriers to behaviour change while ensuring they are easy to engage with, persuasive and acceptable

Antibiotic resistance and biofilm formation ability among coagulase-negative staphylococci in healthy individuals from Portugal

In the past few years the interest in coagulase-negative staphylococci (CoNS) species has significantly increased due to their impact on human health and disease. CoNS are common bacterial colonizers of the normal human microflora and usually have a benign relationship with the host.This work was funded by Fundacao para a Ciencia e a Tecnologia (FCT) and COMPETE grants PTDC/BIA-MIC/113450/2009 and FCOMP-01-0124-FEDER-014309

Polyhedra Circuits and Their Applications

To better compute the volume and count the lattice points in geometric objects, we propose polyhedral circuits. Each polyhedral circuit characterizes a geometric region in Rd . They can be applied to represent a rich class of geometric objects, which include all polyhedra and the union of a finite number of polyhedron. They can be also used to approximate a large class of d-dimensional manifolds in Rd . Barvinok [3] developed polynomial time algorithms to compute the volume of a rational polyhedron, and to count the number of lattice points in a rational polyhedron in Rd with a fixed dimensional number d. Let d be a fixed dimensional number, TV(d,n) be polynomial time in n to compute the volume of a rational polyhedron, TL(d,n) be polynomial time in n to count the number of lattice points in a rational polyhedron, where n is the total number of linear inequalities from input polyhedra, and TI(d,n) be polynomial time in n to solve integer linear programming problem with n be the total number of input linear inequalities. We develop algorithms to count the number of lattice points in geometric region determined by a polyhedral circuit in O(nd⋅rd(n)⋅TV(d,n)) time and to compute the volume of geometric region determined by a polyhedral circuit in O(n⋅rd(n)⋅TI(d,n)+rd(n)TL(d,n)) time, where rd(n) is the maximum number of atomic regions that n hyperplanes partition Rd . The applications to continuous polyhedra maximum coverage problem, polyhedra maximum lattice coverage problem, polyhedra (1−β) -lattice set cover problem, and (1−β) -continuous polyhedra set cover problem are discussed. We also show the NP-hardness of the geometric version of maximum coverage problem and set cover problem when each set is represented as union of polyhedra