Expression of human adenosine deaminase in nonhuman primates after retrovirus-mediated gene transfer.

Primate bone marrow cells were infected with a retroviral vector carrying the genes for human adenosine deaminase (h-ADA) and bacterial neomycin resistance (neor). The infected cells were infused back into the lethally irradiated donor animals. Several monkeys fully reconstituted and were shown to express the h-ADA and neor genes at low levels in their recirculating hematopoietic cells for short periods of time

Scanning-probe spectroscopy of semiconductor donor molecules

Semiconductor devices continue to press into the nanoscale regime, and new applications have emerged for which the quantum properties of dopant atoms act as the functional part of the device, underscoring the necessity to probe the quantum structure of small numbers of dopant atoms in semiconductors[1-3]. Although dopant properties are well-understood with respect to bulk semiconductors, new questions arise in nanosystems. For example, the quantum energy levels of dopants will be affected by the proximity of nanometer-scale electrodes. Moreover, because shallow donors and acceptors are analogous to hydrogen atoms, experiments on small numbers of dopants have the potential to be a testing ground for fundamental questions of atomic and molecular physics, such as the maximum negative ionization of a molecule with a given number of positive ions[4,5]. Electron tunneling spectroscopy through isolated dopants has been observed in transport studies[6,7]. In addition, Geim and coworkers identified resonances due to two closely spaced donors, effectively forming donor molecules[8]. Here we present capacitance spectroscopy measurements of silicon donors in a gallium-arsenide heterostructure using a scanning probe technique[9,10]. In contrast to the work of Geim et al., our data show discernible peaks attributed to successive electrons entering the molecules. Hence this work represents the first addition spectrum measurement of dopant molecules. More generally, to the best of our knowledge, this study is the first example of single-electron capacitance spectroscopy performed directly with a scanning probe tip[9].Comment: In press, Nature Physics. Original manuscript posted here; 16 pages, 3 figures, 5 supplementary figure

Toward optimal implementation of cancer prevention and control programs in public health: A study protocol on mis-implementation

Abstract Background Much of the cancer burden in the USA is preventable, through application of existing knowledge. State-level funders and public health practitioners are in ideal positions to affect programs and policies related to cancer control. Mis-implementation refers to ending effective programs and policies prematurely or continuing ineffective ones. Greater attention to mis-implementation should lead to use of effective interventions and more efficient expenditure of resources, which in the long term, will lead to more positive cancer outcomes. Methods This is a three-phase study that takes a comprehensive approach, leading to the elucidation of tactics for addressing mis-implementation. Phase 1: We assess the extent to which mis-implementation is occurring among state cancer control programs in public health. This initial phase will involve a survey of 800 practitioners representing all states. The programs represented will span the full continuum of cancer control, from primary prevention to survivorship. Phase 2: Using data from phase 1 to identify organizations in which mis-implementation is particularly high or low, the team will conduct eight comparative case studies to get a richer understanding of mis-implementation and to understand contextual differences. These case studies will highlight lessons learned about mis-implementation and identify hypothesized drivers. Phase 3: Agent-based modeling will be used to identify dynamic interactions between individual capacity, organizational capacity, use of evidence, funding, and external factors driving mis-implementation. The team will then translate and disseminate findings from phases 1 to 3 to practitioners and practice-related stakeholders to support the reduction of mis-implementation. Discussion This study is innovative and significant because it will (1) be the first to refine and further develop reliable and valid measures of mis-implementation of public health programs; (2) bring together a strong, transdisciplinary team with significant expertise in practice-based research; (3) use agent-based modeling to address cancer control implementation; and (4) use a participatory, evidence-based, stakeholder-driven approach that will identify key leverage points for addressing mis-implementation among state public health programs. This research is expected to provide replicable computational simulation models that can identify leverage points and public health system dynamics to reduce mis-implementation in cancer control and may be of interest to other health areas

Reprogramming of orientation columns in visual cortex : a domino effect

Abstract : Cortical organization rests upon the fundamental principle that neurons sharing similar properties are co-located. In the visual cortex, neurons are organized into orientation columns. In a column, most neurons respond optimally to the same axis of an oriented edge, that is, the preferred orientation. This orientation selectivity is believed to be absolute in adulthood. However, in a fully mature brain, it has been established that neurons change their selectivity following sensory experience or visual adaptation. Here, we show that after applying an adapter away from the tested cells, neurons whose receptive fields were located remotely from the adapted site also exhibit a novel selectivity in spite of the fact that they were not adapted. These results indicate a robust reconfiguration and remapping of the orientation domains with respect to each other thus removing the possibility of an orientation hole in the new hypercolumn. These data suggest that orientation columns transcend anatomy, and are almost strictly functionally dynamic

Declining Rates in Male Circumcision amidst Increasing Evidence of its Public Health Benefit

BACKGROUND: Recent experimental evidence has demonstrated the benefits of male circumcision for the prevention of human immunodeficiency virus (HIV) infection. Studies have also shown that male circumcision is cost-effective and reduces the risk for certain ulcerative sexually transmitted diseases (STDs). The epidemiology of male circumcision in the United States is poorly studied and most prior reports were limited by self-reported measures. The study objective was to describe male circumcision trends among men attending the San Francisco municipal STD clinic, and to correlate the findings with HIV, syphilis and sexual orientation. METHODS AND FINDINGS: A cross sectional study was performed by reviewing all electronic records of males attending the San Francisco municipal STD clinic between 1996 and 2005. The prevalence of circumcision over time and by subpopulation such as race/ethnicity and sexual orientation were measured. The findings were further correlated with the presence of syphilis and HIV infection. Circumcision status was determined by physical examination and disease status by clinical evaluation with laboratory confirmation. Among 58,598 male patients, 32,613 (55.7%, 95% Confidence Interval (CI) 55.2-56.1) were circumcised. Male circumcision varied significantly by decade of birth (increasing between 1920 and 1950 and declining overall since the 1960's), race/ethnicity (Black: 62.2%, 95% CI 61.2-63.2, White: 60.0%, 95% CI 59.46-60.5, Asian Pacific Islander: 48.2%, 46.9-49.5 95% CI, and Hispanic: 42.2%, 95% CI 41.3-43.1), and sexual orientation (gay/bisexual: 73.0%, 95% CI 72.6-73.4; heterosexual: 66.0%, 65.5-66.5). Male circumcision may have been modestly protective against syphilis in HIV-uninfected heterosexual men (PR 0.92, 95% C.I. 0.83-1.02, P = 0.06). CONCLUSIONS: Male circumcision was common among men seeking STD services in San Francisco but has declined substantially in recent decades. Male circumcision rates differed by race/ethnicity and sexual orientation. Given recent studies suggesting the public health benefits of male circumcision, a reconsideration of national male circumcision policy is needed to respond to current trends

Collective Excitations of Holographic Quantum Liquids in a Magnetic Field

We use holography to study N=4 supersymmetric SU(Nc) Yang-Mills theory in the large-Nc and large-coupling limits coupled to a number Nf << Nc of (n+1)-dimensional massless supersymmetric hypermultiplets in the Nc representation of SU(Nc), with n=2,3. We introduce a temperature T, a baryon number chemical potential mu, and a baryon number magnetic field B, and work in a regime with mu >> T,\sqrt{B}. We study the collective excitations of these holographic quantum liquids by computing the poles in the retarded Green's function of the baryon number charge density operator and the associated peaks in the spectral function. We focus on the evolution of the collective excitations as we increase the frequency relative to T, i.e. the hydrodynamic/collisionless crossover. We find that for all B, at low frequencies the tallest peak in the spectral function is associated with hydrodynamic charge diffusion. At high frequencies the tallest peak is associated with a sound mode similar to the zero sound mode in the collisionless regime of a Landau Fermi liquid. The sound mode has a gap proportional to B, and as a result for intermediate frequencies and for B sufficiently large compared to T the spectral function is strongly suppressed. We find that the hydrodynamic/collisionless crossover occurs at a frequency that is approximately B-independent.Comment: 45 pages, 8 png and 47 pdf images in 22 figure

Regional differences in psychiatric disorders in Chile

BACKGROUND: Psychiatric epidemiological surveys in developing countries are rare and are frequently conducted in regions that are not necessarily representative of the entire country. In addition, in large countries with dispersed populations national rates may have low value for estimating the need for mental health services and programs. METHODS: The Chile Psychiatric Prevalence Study using the Composite International Diagnostic Interview was conducted in four distinct regions of the country on a stratified random sample of 2,978 people. Lifetime and 12-month prevalence and service utilization rates were estimated. RESULTS: Significant differences in the rates of major depressive disorder, substance abuse disorders, non-affective psychosis, and service utilization were found across the regions. The differential prevalence rates could not be accounted by socio-demographic differences between sites. CONCLUSIONS: Regional differences across countries may exist that have both implications for prevalence rates and service utilization. Planning mental health services for population centers that span wide geographical areas based on studies conducted in a single region may be misleading, and may result in areas with high need being underserved

What is the easier and more reliable dose calculation for iv Phenytoin in children at risk of developing convulsive status epilepticus, 18 mg/kg or 20 mg/kg?

Background: With the Convulsive Status Guidelines due for renewal, we wondered if a phenytoin dose of ‘20 mg/kg’ would be easier to calculate correctly and therefore safer than the current ‘18 mg/kg’. An educational exercise in dose calculation was therefore undertaken to assess ease of calculation. Method: A standard question paper was prepared, comprising five clinical scenarios with children of varying ages and estimated body weights. Medical students, trainee doctors at registrar and senior house officer level, and consultant paediatricians were asked to complete the exercise, in private, by one of two medical students (SD, PS). Calculations were done with and without a calculator, for 18 mg/kg and for 20 mg/kg in randomised order. Speed and errors (greater than 10%) were determined. The data analysis was performed using SPSS version 18. Results: All answered all 20 scenarios, giving a total of 300 answers per doctor/student group, and 300 answers per type of calculation. When comparing the 2 doses, the numbers of errors more than 10% were significantly less in 20 mg/kg dose (0.33%) as compared to the 18 mg/kg dose (9.3%) (p<0.0001). Speed off calculation was significantly decreased in 20 mg/kg dose when compared with 18 mg/kg dose, with (p<0.001) or without (p<0.0001) the calculator. Speed was more than halved and errors were much less frequent by using a calculator, for the 18 mg/kg dose but no difference with or without the calculator for 20 mg/kg dose. Conclusion: We recommend that the future guidelines should suggest iv Phenytoin at 20 mg/kg rather than 18 mg/kg. This will make the calculation easier and reduce the risk of significant errors

Ecological Release and Venom Evolution of a Predatory Marine Snail at Easter Island

BACKGROUND:Ecological release is coupled with adaptive radiation and ecological diversification yet little is known about the molecular basis of phenotypic changes associated with this phenomenon. The venomous, predatory marine gastropod Conus miliaris has undergone ecological release and exhibits increased dietary breadth at Easter Island. METHODOLOGY/PRINCIPAL FINDINGS:We examined the extent of genetic differentiation of two genes expressed in the venom of C. miliaris among samples from Easter Island, American Samoa and Guam. The population from Easter Island exhibits unique frequencies of alleles that encode distinct peptides at both loci. Levels of divergence at these loci exceed observed levels of divergence observed at a mitochondrial gene region at Easter Island. CONCLUSIONS/SIGNIFICANCE:Patterns of genetic variation at two genes expressed in the venom of this C. miliaris suggest that selection has operated at these genes and contributed to the divergence of venom composition at Easter Island. These results show that ecological release is associated with strong selection pressures that promote the evolution of new phenotypes

Zircon ages in granulite facies rocks: decoupling from geochemistry above 850 °C?

Granulite facies rocks frequently show a large spread in their zircon ages, the interpretation of which raises questions: Has the isotopic system been disturbed? By what process(es) and conditions did the alteration occur? Can the dates be regarded as real ages, reflecting several growth episodes? Furthermore, under some circumstances of (ultra-)high-temperature metamorphism, decoupling of zircon U–Pb dates from their trace element geochemistry has been reported. Understanding these processes is crucial to help interpret such dates in the context of the P–T history. Our study presents evidence for decoupling in zircon from the highest grade metapelites (> 850 °C) taken along a continuous high-temperature metamorphic field gradient in the Ivrea Zone (NW Italy). These rocks represent a well-characterised segment of Permian lower continental crust with a protracted high-temperature history. Cathodoluminescence images reveal that zircons in the mid-amphibolite facies preserve mainly detrital cores with narrow overgrowths. In the upper amphibolite and granulite facies, preserved detrital cores decrease and metamorphic zircon increases in quantity. Across all samples we document a sequence of four rim generations based on textures. U–Pb dates, Th/U ratios and Ti-in-zircon concentrations show an essentially continuous evolution with increasing metamorphic grade, except in the samples from the granulite facies, which display significant scatter in age and chemistry. We associate the observed decoupling of zircon systematics in high-grade non-metamict zircon with disturbance processes related to differences in behaviour of non-formula elements (i.e. Pb, Th, U, Ti) at high-temperature conditions, notably differences in compatibility within the crystal structure