Framing Expectations in Early HIV Cure Research

Language used to describe clinical research represents a powerful opportunity to educate volunteers. In the case of HIV cure research there is an emerging need to manage expectations by using the term ‘experiment’. Cure experiments are proof-of-concept studies designed to evaluate novel paradigms to reduce persistent HIV-1 reservoirs, without any expectation of medical benefit

MR Spectroscopic Imaging of Peripheral Zone in Prostate Cancer Using a 3T MRI Scanner: Endorectal versus External Phased Array Coils.

Magnetic resonance spectroscopic imaging (MRSI) detects alterations in major prostate metabolites, such as citrate (Cit), creatine (Cr), and choline (Ch). We evaluated the sensitivity and accuracy of three-dimensional MRSI of prostate using an endorectal compared to an external phased array "receive" coil on a 3T MRI scanner. Eighteen patients with prostate cancer (PCa) who underwent endorectal MR imaging and proton (1H) MRSI were included in this study. Immediately after the endorectal MRSI scan, the PCa patients were scanned with the external phased array coil. The endorectal coil-detected metabolite ratio [(Ch+Cr)/Cit] was significantly higher in cancer locations (1.667 ± 0.663) compared to non-cancer locations (0.978 ± 0.420) (P < 0.001). Similarly, for the external phased array, the ratio was significantly higher in cancer locations (1.070 ± 0.525) compared to non-cancer locations (0.521 ± 0.310) (P < 0.001). The sensitivity and accuracy of cancer detection were 81% and 78% using the endorectal 'receive' coil, and 69% and 75%, respectively using the external phased array 'receive' coil

MODIS Tree Cover Validation for the Circumpolar Taiga-Tundra Transition Zone

A validation of the 2005 500m MODIS vegetation continuous fields (VCF) tree cover product in the circumpolar taiga-tundra ecotone was performed using high resolution Quickbird imagery. Assessing the VCF's performance near the northern limits of the boreal forest can help quantify the accuracy of the product within this vegetation transition area. The circumpolar region was divided into longitudinal zones and validation sites were selected in areas of varying tree cover where Quickbird imagery is available in Google Earth. Each site was linked to the corresponding VCF pixel and overlaid with a regular dot grid within the VCF pixel's boundary to estimate percent tree crown cover in the area. Percent tree crown cover was estimated using Quickbird imagery for 396 sites throughout the circumpolar region and related to the VCF's estimates of canopy cover for 2000-2005. Regression results of VCF inter-annual comparisons (2000-2005) and VCF-Quickbird image-interpreted estimates indicate that: (1) Pixel-level, inter-annual comparisons of VCF estimates of percent canopy cover were linearly related (mean R(sup 2) = 0.77) and exhibited an average root mean square error (RMSE) of 10.1 % and an average root mean square difference (RMSD) of 7.3%. (2) A comparison of image-interpreted percent tree crown cover estimates based on dot counts on Quickbird color images by two different interpreters were more variable (R(sup 2) = 0.73, RMSE = 14.8%, RMSD = 18.7%) than VCF inter-annual comparisons. (3) Across the circumpolar boreal region, 2005 VCF-Quickbird comparisons were linearly related, with an R(sup 2) = 0.57, a RMSE = 13.4% and a RMSD = 21.3%, with a tendency to over-estimate areas of low percent tree cover and anomalous VCF results in Scandinavia. The relationship of the VCF estimates and ground reference indicate to potential users that the VCF's tree cover values for individual pixels, particularly those below 20% tree cover, may not be precise enough to monitor 500m pixel-level tree cover in the taiga-tundra transition zone

Spatio-temporal patterns in a mechanical model for mesenchymal morphogenesis

We present an in-depth study of spatio-temporal patterns in a simplified version of a mechanical model for pattern formation in mesenchymal morphogenesis. We briefly motivate the derivation of the model and show how to choose realistic boundary conditions to make the system well-posed. We firstly consider one-dimensional patterns and carry out a nonlinear perturbation analysis for the case where the uniform steady state is linearly unstable to a single mode. In two-dimensions, we show that if the displacement field in the model is represented as a sum of orthogonal parts, then the model can be decomposed into two sub-models, only one of which is capable of generating pattern. We thus focus on this particular sub-model. We present a nonlinear analysis of spatio-temporal patterns exhibited by the sub-model on a square domain and discuss mode interaction. Our analysis shows that when a two-dimensional mode number admits two or more degenerate mode pairs, the solution of the full nonlinear system of partial differential equations is a mixed mode solution in which all the degenerate mode pairs are represented in a frequency locked oscillation

Genomic Organization, Splice Variants and Expression of CGMl, a CD66-related Member of the Carcinoembryonic Antigen Gene Family

The tumor marker carcinoembryonic antigen (CEA) belongs to a family of proteins which are composed of one immunogiobulin variable domain and a varying number of immunoglobulin constant-like domains. Most of the membrane-bound members, which are anchored either by a glycosylphosphatidylinositol moiety or a transmembrane domain, have been shown to convey cell adhesion in vitro. Here we describe two splice variants of CGMI. a transmembrane member of the CEA family without immunoglobulin constant.like domains. CGM1a and CGM1c contain cytopiasmic domains of 71 and 31 amino acids, respectively, The cytoplasmic region of CGM1a is encoded by four exons (Cyt1-Cyt4). Differential splicing of the Cyt1 exon (53 bp)..

Precision spectroscopy with two correlated atoms

We discuss techniques that allow for long coherence times in laser spectroscopy experiments with two trapped ions. We show that for this purpose not only entangled ions prepared in decoherence-free subspaces can be used but also a pair of ions that are not entangled but subject to the same kind of phase noise. We apply this technique to a measurement of the electric quadrupole moment of the 3d D5/2 state of 40Ca+ and to a measurement of the linewidth of an ultrastable laser exciting a pair of 40Ca+ ions

Ecosystem carbon 7 dioxide fluxes after disturbance in forests of North America

Disturbances are important for renewal of North American forests. Here we summarize more than 180 site years of eddy covariance measurements of carbon dioxide flux made at forest chronosequences in North America. The disturbances included stand-replacing fire (Alaska, Arizona, Manitoba, and Saskatchewan) and harvest (British Columbia, Florida, New Brunswick, Oregon, Quebec, Saskatchewan, and Wisconsin) events, insect infestations (gypsy moth, forest tent caterpillar, and mountain pine beetle), Hurricane Wilma, and silvicultural thinning (Arizona, California, and New Brunswick). Net ecosystem production (NEP) showed a carbon loss from all ecosystems following a stand-replacing disturbance, becoming a carbon sink by 20 years for all ecosystems and by 10 years for most. Maximum carbon losses following disturbance (g C m−2y−1) ranged from 1270 in Florida to 200 in boreal ecosystems. Similarly, for forests less than 100 years old, maximum uptake (g C m−2y−1) was 1180 in Florida mangroves and 210 in boreal ecosystems. More temperate forests had intermediate fluxes. Boreal ecosystems were relatively time invariant after 20 years, whereas western ecosystems tended to increase in carbon gain over time. This was driven mostly by gross photosynthetic production (GPP) because total ecosystem respiration (ER) and heterotrophic respiration were relatively invariant with age. GPP/ER was as low as 0.2 immediately following stand-replacing disturbance reaching a constant value of 1.2 after 20 years. NEP following insect defoliations and silvicultural thinning showed lesser changes than stand-replacing events, with decreases in the year of disturbance followed by rapid recovery. NEP decreased in a mangrove ecosystem following Hurricane Wilma because of a decrease in GPP and an increase in ER

Patterns of Atopic Eczema Disease Activity from Birth through Midlife in 2 British Birth Cohorts

Importance: Atopic eczema is characterized by a heterogenous waxing and waning course, with variable age of onset and persistence of symptoms. Distinct patterns of disease activity such as early-onset/resolving and persistent disease have been identified throughout childhood; little is known about patterns into adulthood. Objective: This study aimed to identify subtypes of atopic eczema based on patterns of disease activity through mid-adulthood, to examine whether early life risk factors and participant characteristics are associated with these subtypes, and to determine whether subtypes are associated with other atopic diseases and general health in mid-adulthood. Design, Setting, and Participants: This study evaluated members of 2 population-based birth cohorts, the 1958 National Childhood Development Study (NCDS) and the 1970 British Cohort Study (BCS70). Participant data were collected over the period between 1958 and 2016. Data were analyzed over the period between 2018 and 2020. Main Outcomes and Measures: Subtypes of atopic eczema were identified based on self-reported atopic eczema period prevalence at multiple occasions. These subtypes were the outcome in models of early life characteristics and an exposure variable in models of midlife health. Results: Latent class analysis identified 4 subtypes of atopic eczema with distinct patterns of disease activity among 15939 individuals from the NCDS (51.4% male, 75.4% White) and 14966 individuals from the BCS70 (51.6% male, 78.8% White): rare/no (88% to 91%), decreasing (4%), increasing (2% to 6%), and persistently high (2% to 3%) probability of reporting prevalent atopic eczema with age. Sex at birth and early life factors, including social class, region of residence, tobacco smoke exposure, and breastfeeding, predicted differences between the 3 atopic eczema subtypes and the infrequent/no atopic eczema group, but only female sex differentiated the high and decreasing probability subtypes (odds ratio [OR], 1.99; 95% CI, 1.66-2.38). Individuals in the high subtype were most likely to experience asthma and rhinitis, and those in the increasing subtype were at higher risk of poor self-reported general (OR, 1.29; 95% CI, 1.09-1.53) and mental (OR 1.45; 95% CI, 1.23-1.72) health in midlife. Conclusions and Relevance: The findings of this cohort study suggest that extending the window of observation beyond childhood may reveal clear subtypes of atopic eczema based on patterns of disease activity. A newly identified subtype with increasing probability of activity in adulthood warrants additional attention given observed associations with poor self-reported health in midlife.

Analysis of Collectivism and Egoism Phenomena within the Context of Social Welfare

Comparative benefits provided by the basic social strategies including collectivism and egoism are investigated within the framework of democratic decision-making. In particular, we study the mechanism of growing "snowball" of cooperation.Comment: 12 pages, 5 figures. Translated from Russian. Original Russian Text published in Problemy Upravleniya, 2008, No. 4, pp. 30-3

Interrupting Antiretroviral Treatment in HIV Cure Research: Scientific and Ethical Considerations

Over the past several years there has been intense activity directed at the possibility of achieving remission or eradication of HIV infection. Current assays for the measurement of latent HIV are insufficient to demonstrate complete clearance of replication-competent HIV. Therefore, the ultimate test for assessing whether investigational interventions have resulted in HIV remission or eradication is to interrupt standard antiretroviral therapy (ART) in a carefully controlled clinical trial setting. These procedures, known as analytic treatment interruptions (ATIs), raise important scientific and ethical questions. The lack of definitive assays for measuring viral reservoirs not only makes research on HIV remission or cure challenging, it also affects the ability to assess risks from ATIs themselves. In spite of these challenges, basic ethical criteria can be met with careful study design and close monitoring. In this brief report we outline ethical standards for HIV cure research involving ATIs. These criteria should be revisited as the science evolves