Prediction-based classification for longitudinal biomarkers

Assessment of circulating CD4 count change over time in HIV-infected subjects on antiretroviral therapy (ART) is a central component of disease monitoring. The increasing number of HIV-infected subjects starting therapy and the limited capacity to support CD4 count testing within resource-limited settings have fueled interest in identifying correlates of CD4 count change such as total lymphocyte count, among others. The application of modeling techniques will be essential to this endeavor due to the typically nonlinear CD4 trajectory over time and the multiple input variables necessary for capturing CD4 variability. We propose a prediction-based classification approach that involves first stage modeling and subsequent classification based on clinically meaningful thresholds. This approach draws on existing analytical methods described in the receiver operating characteristic curve literature while presenting an extension for handling a continuous outcome. Application of this method to an independent test sample results in greater than 98% positive predictive value for CD4 count change. The prediction algorithm is derived based on a cohort of $n=270$ HIV-1 infected individuals from the Royal Free Hospital, London who were followed for up to three years from initiation of ART. A test sample comprised of $n=72$ individuals from Philadelphia and followed for a similar length of time is used for validation. Results suggest that this approach may be a useful tool for prioritizing limited laboratory resources for CD4 testing after subjects start antiretroviral therapy.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS326 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Water bears dominated cryoconite hole ecosystems : densities, habitat preferences and physiological adaptations of Tardigrada on an alpine glacier

We investigated the Forni Glacier and the surrounding area in the Alps in terms of habitat preferences, densities, dispersal and desiccation tolerance of glacier tardigrades, which are one of the most common faunal representatives and top consumers in supraglacial ecosystems. To do so, we sampled supraglacial environments (cryoconite holes, debris from ice surface, dirt cones and moraine, mosses from supraglacial stones) and non-glacial habitats (mosses, freshwater sediments and algae), and we installed air traps on the glacier and the nearby area. We found that cryoconite holes on the Forni Glacier are exclusively dominated by one metazoan group of tardigrades, representing one species, Hypsibius klebelsbergi (identified by morphological and molecular approaches). Tardigrades were found in 100% of cryoconite holes and wet supraglacial sediment samples and reached up to 172 ind./ml. Additionally, we found glacier tardigrades in debris from dirt cones and sparsely in supraglacial mosses. Glacier tardigrades were absent from freshwater and terrestrial samples collected from non-glacial habitats. Despite the fact that H. klebelsbergi is a typical aquatic species, we showed it withstands desiccation in sediments, but in low temperatures only. Treatments conducted in higher temperatures and water only showed low or no recovery. We suspect successful dispersal with wind might have taken place only when tardigrades desiccated in sediments and were passively transported by cold wind. Limited ability to withstand high temperatures and desiccation may be potential barriers preventing glacier tardigrades inhabiting new, even apparently suitable high mountain water bodies like temporary rock pools

Mesoscopic phase separation in Nax_xCoO2_2 (0.65≤x≤0.750.65\leq x\leq 0.75)

NMR, EPR and magnetization measurements in Na$_x$CoO$_2$ for $0.65\leq x\leq 0.75$ are presented. While the EPR signal arises from Co$^{4+}$ magnetic moments ordering at $T_c\simeq 26$ K, $^{59}$Co NMR signal originates from cobalt nuclei in metallic regions with no long range magnetic order and characterized by a generalized susceptibility typical of strongly correlated metallic systems. This phase separation in metallic and magnetic insulating regions is argued to occur below $T^*(x)$ ($220 - 270$ K). Above $T^*$ an anomalous decrease in the intensity of the EPR signal is observed and associated with the delocalization of the electrons which for $T<T^*$ were localized on Co$^{4+}$ $d_{z^2}$ orbitals. It is pointed out that the in-plane antiferromagnetic coupling $J\ll T^*$ cannot be the driving force for the phase separation.Comment: 14 figure

Post-Depositional Biodegradation Processes of Pollutants on Glacier Surfaces

Glaciers are important fresh-water reservoirs for our planet. Although they are often located at high elevations or in remote areas, glacial ecosystems are not pristine, as many pollutants can undergo long-range atmospheric transport and be deposited on glacier surface, where they can be stored for long periods of time, and then be released into the down-valley ecosystems. Understanding the dynamics of these pollutants in glaciers is therefore important for assessing their environmental fate. To this aim, it is important to study cryoconite holes, small ponds filled with water and with a layer of sediment, the cryoconite, at the bottom, which occur on the surface of most glaciers. Indeed, these environments are hotspots of biodiversity on glacier surface as they host metabolically active bacterial communities that include generalist taxa able to degrade pollutants. In this work, we aim to review the studies that have already investigated pollutant (e.g., chlorpyrifos and polychlorinated-biphenyls (PCBs)) degradation in cryoconite holes and other supraglacial environmental matrices. These studies have revealed that bacteria play a significant role in pollutant degradation in these habitats and can be positively selected in contaminated environments. We will also provide indication for future research in this field

Modeling an Industrial Revolution: How to Manage Large-Scale, Complex IoT Ecosystems?

Advancements around the modern digital industry gave birth to a number of closely interrelated concepts: in the age of the Internet of Things (IoT), System of Systems (SoS), Cyber-Physical Systems (CPS), Digital Twins and the fourth industrial revolution, everything revolves around the issue of designing well-understood, sound and secure complex systems while providing maximum flexibility, autonomy and dynamics.The aim of the paper is to present a concise overview of a comprehensive conceptual framework for integrated modeling and management of industrial IoT architectures, supported by actual evidence from the Arrowhead Tools project; in particular, we adopt a three-dimensional projection of our complex engineering space, from modeling the engineering process to SoS design and deployment.In particular, we start from modeling principles of the the engineering process itself. Then, we present a design-time SoS representation along with a toolchain concept aiding SoS design and deployment. This brings us to reasoning about what potential workflows are thinkable for specifying comprehensive toolchains along with their data exchange interfaces. We also discuss the potential of aligning our vision with RAMI4.0, as well as the utilization perspectives for real-life engineering use-cases

Human Papilloma Virus (HPV) status, P16INK4a and p53 overexpression in epithelial malignant and borderline ovarian neoplasms

This investigation is the first to evaluate simultaneously human papilloma virus (HPV) status, p16(INK4a), and p53 immunoreactivity in epithelial ovarian neoplasms. The results were analyzed and correlated with histological type, histological grade, and survival of patients. Subtypes considered are papillary serous and mucinous. Polymerase chain reaction (PCR) analysis, performed in our previous study, had already demonstrated a small number of HPV-positive epithelial ovarian neoplasms. No significant correlation was found between the presence of HPV DNA and subtypes of ovarian neoplasms; thus, HPV cannot be considered responsible for epithelial ovarian neoplasm. Since p16 immunoreactivity was present in many other HPV-negative cases of epithelial ovarian neoplasms, this study suggests that p16 overexpression in some neoplasms of the female genital tract is not related to HPV carcinogenesis. A higher p53 expression rate observed between borderline and malignant serous tumors and between serous and mucinous neoplasms can confirm a recent dualistic model of ovarian carcinogenesis. According to this theory, low-grade serous carcinomas (serous intraepithelial carcinomas, serous borderline neoplasm, and ovarian mucinous neoplasms) (type I tumors) develop from mutations of KAS and BRAF, while high-grade serous carcinomas (type II tumors) develop from mutation of p53. In malignant neoplasms, for univariate analysis, patient survival seems to be related to p53, strong and diffuse p16 overexpression, and the stage of development of neoplasms at the diagnosis. In multinomial logistic regression, used to evaluate the role of staging, grading, p16 and p53 immunopositivity as predictor variables of unfavorable outcome of the disease, only p16 positivity was significantly related to the poor prognosis of the cancer

Nematodes and rotifers on two Alpine debris-covered glaciers

Debris-covered glaciers (DCGs) are glaciers whose ablation area is mostly covered by a continuous layer of debris, and are considered to be among the continental glacierized environments richest in life. DCG colonization by microorganisms, plants and animals, has been investigated in a few studies, while the meiofauna (metazoans smaller than 2\uc2\ua0mm) of these environments has been neglected so far. In this study, we analyzed nematode and rotifer fauna on the two largest debris-covered glaciers of the Italian Alps: the Miage Glacier and the Belvedere Glacier. In total, we collected 38 debris samples on the glaciers in July and September 2009. All the rotifers we found belonged to the bdelloid Adineta vaga (Davis, 1873). Nematodes belonged to 19 species. Miage Glacier hosted a richer and more diverse nematode fauna than the Belvedere. The dominant genus was Plectus Bastian, 1865, a common genus in habitats at high latitude and altitude. Analysis of the feeding type of nematodes highlighted that bacterivores were dominant on Miage Glacier, while bacterivores and herbivores were more widespread on Belvedere Glacier. Predator nematodes were absent. Analysis of the food-web structure indicated that nematode assemblages on both glaciers were typical of environments with depleted food availability, probably resulting from instability of the glacier surface and the short exposure of sediments, preventing the evolution of true soil and enrichment in organic matter of the debris. The scarcity of bacterial primary producers suggests that deposition of allochthonous organic matter is the principal organic carbon source in this environment