Advancing the Right to Health: The Vital Role of Law

Effective laws and an enabling legal environment are essential to a healthy society. Most public health challenges – from infectious and non-communicable diseases to injuries, from mental illness to universal health coverage – have a legal component. At global, national and local levels, law is a powerful tool for advancing the right to health. This tool is, however, often underutilized. This report aims to raise awareness about the role that public health laws can play in advancing the right to health and in creating the conditions for all people to live healthy lives. The report provides guidance about issues and requirements to be addressed during the process of developing or reforming public health laws, with case studies drawn from countries around the world to illustrate effective practices and critical features of effective public health legislation. Advancing the right to health: the vital role of law is the result of a collaboration between the World Health Organisation, the International Development Law Organisation (IDLO), the O’Neill Institute for National and Global Health Law, Washington D.C., USA, and Sydney Law School, University of Sydney. The Project Directors were: Professor Lawrence O. Gostin, Linda D. and Timothy J. O’Neill Professor of Global Health Law and University Professor, Georgetown University; Faculty Director, O’Neill Institute for National and Global Health Law, Georgetown University; Mr David Patterson, Senior Legal Expert – Health; Department of Research & Learning, International Development Law Organization; Professor Roger Magnusson, Professor of Health Law & Governance, Sydney Law School, University of Sydney; Mr Oscar Cabrera, Executive Director, O’Neill Institute for National and Global Health Law, Georgetown University Law Center; Ms Helena Nygren-Krug (2011–2013), Senior Advisor, Human Rights & Law, UNAIDS. The content and structure of the report reflect the consensus reached at the second of two international consultations in public health law that preceded the preparation of the report, hosted by WHO and IDLO in Cairo, Egypt, 26-28 April 2010. Part 1 introduces the human right to health and its role in guiding and evaluating law reform efforts, including efforts to achieve the goal of universal health coverage. Part 2 discusses the process of public health law reform. The law reform process refers to the practical steps involved in advancing the political goal of law reform, and the kinds of issues and obstacles that may be encountered along the way. Part 2 identifies some of the actors who may initiate or lead the public health law reform process, discusses principles of good governance during that process, and ways of building a consensus around the need for public health law reform. Part 3 turns from the process of reforming public health laws to the substance or content of those laws. It identifies a number of core areas of public health practice where regulation is essential in order to ensure that governments (at different levels) discharge their basic public health functions. Traditionally, these core areas of public health practice have included: the provision of clean water and sanitation, monitoring and surveillance of public health threats, the management of communicable diseases, and emergency powers. Building on these core public health functions, Part 3 goes on to consider a range of other public health priorities where law has a critical role to play. These priorities include tobacco control, access to essential medicines, the migration of health care workers, nutrition, maternal, reproductive and child health, and the role of law in advancing universal access to quality health services for all members of the population. The report includes many examples that illustrate the ways in which different countries have used law to protect the health of their populations in ways that are consistent with their human rights obligations. Countries vary widely in terms of their constitutional structure, size, history and political culture. For these reasons, the examples given are not intended to be prescriptive, but to provide useful comparisons for countries involved in the process of legislative review

Gaseous Dark Matter Detectors

Dark Matter detectors with directional sensitivity have the potential of yielding an unambiguous positive observation of WIMPs as well as discriminating between galactic Dark Matter halo models. In this article, we introduce the motivation for directional detectors, discuss the experimental techniques that make directional detection possible, and review the status of the experimental effort in this field.Comment: 19 pages, review on gaseous directional dark matter detectors submitted to New Journal of Physic

Predicting live birth, preterm and low birth weight infant after in-vitro fertilisation: a prospective study of 144018 treatment cycles

Background The extent to which baseline couple characteristics affect the probability of live birth and adverse perinatal outcomes after assisted conception is unknown. Methods and Findings We utilised the Human Fertilisation and Embryology Authority database to examine the predictors of live birth in all in vitro fertilisation (IVF) cycles undertaken in the UK between 2003 and 2007 (n = 144,018). We examined the potential clinical utility of a validated model that pre-dated the introduction of intracytoplasmic sperm injection (ICSI) as compared to a novel model. For those treatment cycles that resulted in a live singleton birth (n = 24,226), we determined the associates of potential risk factors with preterm birth, low birth weight, and macrosomia. The overall rate of at least one live birth was 23.4 per 100 cycles (95% confidence interval [CI] 23.2–23.7). In multivariable models the odds of at least one live birth decreased with increasing maternal age, increasing duration of infertility, a greater number of previously unsuccessful IVF treatments, use of own oocytes, necessity for a second or third treatment cycle, or if it was not unexplained infertility. The association of own versus donor oocyte with reduced odds of live birth strengthened with increasing age of the mother. A previous IVF live birth increased the odds of future success (OR 1.58, 95% CI 1.46–1.71) more than that of a previous spontaneous live birth (OR 1.19, 95% CI 0.99–1.24); p-value for difference in estimate <0.001. Use of ICSI increased the odds of live birth, and male causes of infertility were associated with reduced odds of live birth only in couples who had not received ICSI. Prediction of live birth was feasible with moderate discrimination and excellent calibration; calibration was markedly improved in the novel compared to the established model. Preterm birth and low birth weight were increased if oocyte donation was required and ICSI was not used. Risk of macrosomia increased with advancing maternal age and a history of previous live births. Infertility due to cervical problems was associated with increased odds of all three outcomes—preterm birth, low birth weight, and macrosomia. Conclusions Pending external validation, our results show that couple- and treatment-specific factors can be used to provide infertile couples with an accurate assessment of whether they have low or high risk of a successful outcome following IVF

The AMANDA Neutrino Telescope and the Indirect Search for Dark Matter

With an effective telescope area of order 10^4 m^2, a threshold of ~50 GeV and a pointing accuracy of 2.5 degrees, the AMANDA detector represents the first of a new generation of high energy neutrino telescopes, reaching a scale envisaged over 25 years ago. We describe its performance, focussing on the capability to detect halo dark matter particles via their annihilation into neutrinos.Comment: Latex2.09, 16 pages, uses epsf.sty to place 15 postscript figures. Talk presented at the 3rd International Symposium on Sources and Detection of Dark Matter in the Universe (DM98), Santa Monica, California, Feb. 199

Sequential gene promoter methylation during HPV-induced cervical carcinogenesis

We aimed to link DNA methylation events occurring in cervical carcinomas to distinct stages of HPV-induced transformation. Methylation specific-multiplex ligation-dependent probe amplification (MS-MLPA) analysis of cervical carcinomas revealed promoter methylation of 12 out of 29 tumour suppressor genes analysed, with MGMT being most frequently methylated (92%). Subsequently, consecutive stages of HPV16/18-transfected keratinocytes (n=11), ranging from pre-immortal to anchorage-independent phenotypes, were analysed by MS-MLPA. Whereas no methylation was evident in pre-immortal cells, progression to anchorage independence was associated with an accumulation of frequent methylation events involving five genes, all of which were also methylated in cervical carcinomas. TP73 and ESR1 methylation became manifest in early immortal cells followed by RARβ and DAPK1 methylation in late immortal passages. Complementary methylation of MGMT was related to anchorage independence. Analysis of nine cervical cancer cell lines, representing the tumorigenic phenotype, revealed in addition to these five genes frequent methylation of CADM1, CDH13 and CHFR. In conclusion, eight recurrent methylation events in cervical carcinomas could be assigned to different stages of HPV-induced transformation. Hence, our in vitro model system provides a valuable tool to further functionally address the epigenetic alterations that are common in cervical carcinomas

Ribosome Display Selection of a Murine IgG1 Fab Binding Affibody Molecule Allowing Species Selective Recovery Of Monoclonal Antibodies

Affinity reagents recognizing constant parts of antibody molecules are invaluable tools in immunotechnology applications, including purification, immobilization, and detection of immunoglobulins. In this article, murine IgG1, the primary isotype of monoclonal antibodies (mAbs) was used as target for selection of novel binders from a combinatorial ribosome display (RD) library of 1011 affibody molecules. Four rounds of selection using three different mouse IgG1 mAbs as alternating targets resulted in the identification of binders with broad mIgG1 recognition and dissociation constants (KD) in the low nanomolar to low micromolar range. For one of the binders, denoted Zmab25, competition in binding to full length mIgG1 by a streptococcal protein G (SPG) fragment and selective affinity capture of mouse IgG1 Fab fragments after papain cleavage of a full mAb suggest that an epitope functionally overlapping with the SPG-binding site in the CH1 domain of mouse IgG1 had been addressed. Interestingly, biosensor-based binding experiments showed that neither human IgG1 nor bovine Ig, the latter present in fetal bovine serum (FBS) was recognized by Zmab25. This selective binding profile towards murine IgG1 was successfully exploited in species selective recovery of two different mouse mAbs from complex samples containing FBS, resembling a hybridoma culture supernatant