Physiological Aspects of Genetics

A considerable amount of evidence indicates that desoxyribonucleic acid is capable of duplicating itself, a property also possessed by genes. (By a self-duplicating material, we mean one which plays some essential role in its own production.) Watson & Crick (1) have proposed a new structure for desoxyribonucleic acid which not only takes into account the existing analytical and x-ray diffraction data but also seems capable of explaining the mechanism of duplication. Their model consists of two helical chains coiled around the same axis, the purine and pyrimidine bases on the inside, the phosphate groups on the outside. The chains are held together by hydrogen bonds between the bases, the adenine residues of either chain being bonded specifically to thymine in the other, and similarly guanine to cytosine. The sequence of bases along one chain is not restricted, but once fixed the sequence along the other chain is determined. This complementarity, which is the most novel feature of the structure, suggests that duplication takes place by separation of the two chains, followed by the synthesis of its complement alongside each chain. The model is supported by recent x-ray diffraction studies (2, 3)

Facts for a Friendly Frankenstein

Research in tissue transplantation points the way to a used-parts market for the human body

Gender-related differences in outcomes and attrition on antiretroviral treatment among an HIV-infected patient cohort in Zimbabwe: 2007-2010.

OBJECTIVES: To determine (1) gender-related differences in antiretroviral therapy (ART) outcomes, and (2) gender-specific characteristics associated with attrition. METHODS: This was a retrospective patient record review of 3919 HIV-infected patients aged ≥15 years who initiated ART between 2007 and 2009 in 40 randomly selected ART facilities countrywide. RESULTS: Compared to females, males had more documented active tuberculosis (12% vs. 9%; p60kg), initiating ART at an urban health facility, and care at central/provincial or district/mission hospitals vs. primary healthcare facilities. CONCLUSIONS: Our findings show that males presented late for ART initiation compared to females. Similar to other studies, males had higher patient attrition and mortality compared to females and this may be attributed in part to late presentation for HIV treatment and care. These observations highlight the need to encourage early HIV testing and enrolment into HIV treatment and care, and eventually patient retention on ART, particularly amongst men

Global health partnerships: building multi-national collaborations to achieve lasting improvements in maternal and neonatal health

Abstract Background In response to health care challenges worldwide, extensive funding has been channeled to the world’s most vulnerable health systems. Funding alone is not sufficient to address the complex issues and challenges plaguing these health systems. To see lasting improvement in maternal and infant health outcomes in the developing world, a global commitment to the sharing of knowledge and resources through international partnerships is critical. But partnerships that merely introduce western medical techniques and protocols to low resource settings, without heeding the local contexts, are misguided and unsustainable. Forming partnerships with mutual respect, shared vision, and collaborative effort is needed to ensure that all parties, irrespective of whether they belong to resource rich or resource poor settings, learn from each other so that meaningful and sustained system strengthening can take place. Methods In this paper, we describe the partnership building model of an international NGO, Kybele, which is committed to achieving childbirth safety through sustained partnerships in low resource settings. The Kybele model adapts generic stages of successful partnerships documented in the literature to four principles relevant to Kybele’s work. A multiple-case study approach is used to demonstrate how the model is applied in different country settings. Results The four principle of Kybele’s partnership model are robust drivers of successful partnerships in diverse country settings. Conclusions Much has been written about the need for multi-country partnerships to achieve sustainable outcomes in global health, but few papers in the literature describe how this has been achieved in practice. A strong champion, support and engagement of stakeholders, co-creation of solutions with partners, and involvement of partners in the delivery of solutions are all requirements for successful and sustained partnerships

A Compensatory Mutation Provides Resistance to Disparate HIV Fusion Inhibitor Peptides and Enhances Membrane Fusion

Fusion inhibitors are a class of antiretroviral drugs used to prevent entry of HIV into host cells. Many of the fusion inhibitors being developed, including the drug enfuvirtide, are peptides designed to competitively inhibit the viral fusion protein gp41. With the emergence of drug resistance, there is an increased need for effective and unique alternatives within this class of antivirals. One such alternative is a class of cyclic, cationic, antimicrobial peptides known as θ-defensins, which are produced by many non-human primates and exhibit broad-spectrum antiviral and antibacterial activity. Currently, the θ-defensin analog RC-101 is being developed as a microbicide due to its specific antiviral activity, lack of toxicity to cells and tissues, and safety in animals. Understanding potential RC-101 resistance, and how resistance to other fusion inhibitors affects RC-101 susceptibility, is critical for future development. In previous studies, we identified a mutant, R5-tropic virus that had evolved partial resistance to RC-101 during in vitro selection. Here, we report that a secondary mutation in gp41 was found to restore replicative fitness, membrane fusion, and the rate of viral entry, which were compromised by an initial mutation providing partial RC-101 resistance. Interestingly, we show that RC-101 is effective against two enfuvirtide-resistant mutants, demonstrating the clinical importance of RC-101 as a unique fusion inhibitor. These findings both expand our understanding of HIV drug-resistance to diverse peptide fusion inhibitors and emphasize the significance of compensatory gp41 mutations. © 2013 Wood et al

Using online adverts to increase the uptake of cervical screening amongst "real Eastenders": an opportunistic controlled trial.

BACKGROUND: Cervical screening uptake has increased as a result of occurrences of cervical cancer in TV 'soap operas' and in real life celebrities such as Jade Goody. Media analysis at the time of Jade Goody's death suggested the NHS did not take sufficient advantage of this opportunity to improve cervical screening rates. Google AdWords has been used to recruit and raise awareness of health but we were not aware of its use to supplement media events. METHODS: This was an opportunistic service evaluation to accompany a cervical cancer storyline in Eastenders (a TV 'soap opera'). We ran an AdWords campaign based on keywords such as 'Eastenders', and 'cervical cancer' in a one mile radius in East London, linked to one webpage giving details of 10 practices and other links on cervical cancer. We recorded costs of adverts and setting up the webpage. We used routine statistics from Tower Hamlets, City and Hackney, and Newham Primary Care Trusts (PCTs) of the number of smears, eligible populations, and coverage by practice by month from September 2010 to January 2012 to compare the ten intervention practices with controls. RESULTS: Eight people per day in the target area viewed the project webpage. The cost of setting up the website and running Google AdWords was £1320 or £1.88 per person viewing the webpage. Unlike Jade Goody's death, there was no major impact from the Eastenders' storyline on Google searches for cervical cancer. There was considerable monthly variation in the number of smear tests in the 3 PCTs. The AdWords campaign may have had some effect on smear rates but this showed, at best, a marginal statistical difference. Assuming a 'real' effect, the intervention may have resulted in 110 'extra' women being screened but there was no change in coverage. CONCLUSIONS: Although the Eastenders storyline seemed to have no effect on interest in cervical cancer or screening, the AdWords campaign may have had some effect. Given the small scale exploratory nature of the study this was not statistically significant but the relatively modest cost of advertising suggests a larger study may be worthwhile. An outline of a possible study is described

All-sky search for periodic gravitational waves in LIGO S4 data

We report on an all-sky search with the LIGO detectors for periodic gravitational waves in the frequency range 50-1000 Hz and with the frequency's time derivative in the range -1.0E-8 Hz/s to zero. Data from the fourth LIGO science run (S4) have been used in this search. Three different semi-coherent methods of transforming and summing strain power from Short Fourier Transforms (SFTs) of the calibrated data have been used. The first, known as "StackSlide", averages normalized power from each SFT. A "weighted Hough" scheme is also developed and used, and which also allows for a multi-interferometer search. The third method, known as "PowerFlux", is a variant of the StackSlide method in which the power is weighted before summing. In both the weighted Hough and PowerFlux methods, the weights are chosen according to the noise and detector antenna-pattern to maximize the signal-to-noise ratio. The respective advantages and disadvantages of these methods are discussed. Observing no evidence of periodic gravitational radiation, we report upper limits; we interpret these as limits on this radiation from isolated rotating neutron stars. The best population-based upper limit with 95% confidence on the gravitational-wave strain amplitude, found for simulated sources distributed isotropically across the sky and with isotropically distributed spin-axes, is 4.28E-24 (near 140 Hz). Strict upper limits are also obtained for small patches on the sky for best-case and worst-case inclinations of the spin axes.Comment: 39 pages, 41 figures An error was found in the computation of the C parameter defined in equation 44 which led to its overestimate by 2^(1/4). The correct values for the multi-interferometer, H1 and L1 analyses are 9.2, 9.7, and 9.3, respectively. Figure 32 has been updated accordingly. None of the upper limits presented in the paper were affecte

Search for gravitational waves from binary inspirals in S3 and S4 LIGO data

We report on a search for gravitational waves from the coalescence of compact binaries during the third and fourth LIGO science runs. The search focused on gravitational waves generated during the inspiral phase of the binary evolution. In our analysis, we considered three categories of compact binary systems, ordered by mass: (i) primordial black hole binaries with masses in the range 0.35 M(sun) < m1, m2 < 1.0 M(sun), (ii) binary neutron stars with masses in the range 1.0 M(sun) < m1, m2 < 3.0 M(sun), and (iii) binary black holes with masses in the range 3.0 M(sun)< m1, m2 < m_(max) with the additional constraint m1+ m2 < m_(max), where m_(max) was set to 40.0 M(sun) and 80.0 M(sun) in the third and fourth science runs, respectively. Although the detectors could probe to distances as far as tens of Mpc, no gravitational-wave signals were identified in the 1364 hours of data we analyzed. Assuming a binary population with a Gaussian distribution around 0.75-0.75 M(sun), 1.4-1.4 M(sun), and 5.0-5.0 M(sun), we derived 90%-confidence upper limit rates of 4.9 yr^(-1) L10^(-1) for primordial black hole binaries, 1.2 yr^(-1) L10^(-1) for binary neutron stars, and 0.5 yr^(-1) L10^(-1) for stellar mass binary black holes, where L10 is 10^(10) times the blue light luminosity of the Sun.Comment: 12 pages, 11 figure

Searching for gravitational waves from known pulsars

We present upper limits on the amplitude of gravitational waves from 28 isolated pulsars using data from the second science run of LIGO. The results are also expressed as a constraint on the pulsars' equatorial ellipticities. We discuss a new way of presenting such ellipticity upper limits that takes account of the uncertainties of the pulsar moment of inertia. We also extend our previous method to search for known pulsars in binary systems, of which there are about 80 in the sensitive frequency range of LIGO and GEO 600.Comment: Accepted by CQG for the proceeding of GWDAW9, 7 pages, 2 figure