An Overview of Glaucoma: Bidirectional Translation between Humans and Pre-Clinical Animal Models

Glaucoma is a multifactorial, polygenetic disease with a shared outcome of loss of retinal ganglion cells and their axons, which ultimately results in blindness. The most common risk factor of this disease is elevated intraocular pressure (IOP), although many glaucoma patients have IOPs within the normal physiological range. Throughout disease progression, glial cells in the optic nerve head respond to glaucomatous changes, resulting in glial scar formation as a reaction to injury. This chapter overviews glaucoma as it affects humans and the quest to generate animal models of glaucoma so that we can better understand the pathophysiology of this disease and develop targeted therapies to slow or reverse glaucomatous damage. This chapter then reviews treatment modalities of glaucoma. Revealed herein is the lack of non-IOP-related modalities in the treatment of glaucoma. This finding supports the use of animal models in understanding the development of glaucoma pathophysiology and treatments

Crystal structure of dichlorido(4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane)iron(III) hexafluoridophosphate

The title compound, [FeCl₂(C₁₄H₃₀N₄)]PF₆, contains Fe³⁺ coordinated by the four nitro­gen atoms of an ethyl­ene cross-bridged cyclam macrocycle and two cis chloride ligands in a distorted octa­hedral environment. In contrast to other similar compounds this is a monomer. Inter­molecular C-H...Cl inter­actions exist in the structure between the complex ions. Comparison with the mononuclear Fe²⁺ complex of the same ligand shows that the smaller Fe³⁺ ion is more fully engulfed by the cavity of the bicyclic ligand. Comparison with the μ-oxido dinuclear complex of an unsubstituted ligand of the same size demonstrates that the methyl groups of 4,11-dimethyl-1,4,8,11-tetra­aza­bicyclo­[6.6.2]hexa­decane prevent dimerization upon oxidation

Algal biomarkers as a proxy for pCO2: Constraints from late Quaternary sapropels in the eastern Mediterranean

Records of carbon dioxide concentrations (partial pressure expressed as pCO2) over Earth’s history provide trends that are critical to understand our changing world. To better constrain pCO2 estimations, here we test organic pCO2 proxies against the direct measurements of pCO2 recorded in ice cores. Based on the concept of stable carbon isotopic fractionation due to photosynthetic CO2 fixation (Ɛp), we use the stable carbon isotopic composition (δ13C) of the recently proposed biomarker phytol (from all photoautotrophs), as well as the conventionally used alkenone biomarkers (from specific species) for comparison, to reconstruct pCO2 over several Quaternary sapropel formation periods (S1, S3, S4, and S5) in the eastern Mediterranean Sea. The reconstructed pCO2 values are within error of the ice core values but consistently exceed the ice core values by ca. 100 µatm. This offset corresponds with atmospheric disequilibrium of present day CO2[aq] concentrations in the Mediterranean Sea from global pCO2, equivalent to ca. 100 µatm, although pCO2 estimates derived from individual horizons within each sapropel do not covary with the ice core values. This may possibly be due to greater variability in local CO2[aq] concentration changes in the Mediterranean, as compared with the global average pCO2, or possibly due to biases in the proxy, such as variable growth rate or carbon-concentrating mechanisms. Thus, the offset is likely a combination of physiological or environmental factors. Nevertheless, our results demonstrate that alkenone- and phytol-based pCO2 proxies yield statistically similar estimations (P-value = 0.02, Pearson’s r-value = 0.56), and yield reasonable absolute estimations although with relatively large uncertainties (± 100 µatm)

Cosmological parameters from SDSS and WMAP

We measure cosmological parameters using the three-dimensional power spectrum P(k) from over 200,000 galaxies in the Sloan Digital Sky Survey (SDSS) in combination with WMAP and other data. Our results are consistent with a ``vanilla'' flat adiabatic Lambda-CDM model without tilt (n=1), running tilt, tensor modes or massive neutrinos. Adding SDSS information more than halves the WMAP-only error bars on some parameters, tightening 1 sigma constraints on the Hubble parameter from h~0.74+0.18-0.07 to h~0.70+0.04-0.03, on the matter density from Omega_m~0.25+/-0.10 to Omega_m~0.30+/-0.04 (1 sigma) and on neutrino masses from <11 eV to <0.6 eV (95%). SDSS helps even more when dropping prior assumptions about curvature, neutrinos, tensor modes and the equation of state. Our results are in substantial agreement with the joint analysis of WMAP and the 2dF Galaxy Redshift Survey, which is an impressive consistency check with independent redshift survey data and analysis techniques. In this paper, we place particular emphasis on clarifying the physical origin of the constraints, i.e., what we do and do not know when using different data sets and prior assumptions. For instance, dropping the assumption that space is perfectly flat, the WMAP-only constraint on the measured age of the Universe tightens from t0~16.3+2.3-1.8 Gyr to t0~14.1+1.0-0.9 Gyr by adding SDSS and SN Ia data. Including tensors, running tilt, neutrino mass and equation of state in the list of free parameters, many constraints are still quite weak, but future cosmological measurements from SDSS and other sources should allow these to be substantially tightened.Comment: Minor revisions to match accepted PRD version. SDSS data and ppt figures available at http://www.hep.upenn.edu/~max/sdsspars.htm

Contrast-Enhanced Computed Tomography Enables Quantitative Evaluation of Tissue Properties at Intrajoint Regions in Cadaveric Knee Cartilage

Objective: The aim of this study was to investigate whether the concentration of the anionic contrast agent ioxaglate, as quantitated by contrast-enhanced computed tomography (CECT) using a clinical cone-beam CT (CBCT) instrument, reflects biochemical, histological, and biomechanical characteristics of articular cartilage imaged in an ex vivo, intact human knee joint. Design: An osteoarthritic human cadaveric knee joint (91 years old) was injected with ioxaglate (36 mg I/mL) and imaged using CBCT over 61 hours of ioxaglate diffusion into cartilage. Following imaging, the joint surfaces were excised, rinsed to remove contrast agent, and compressive stiffness (equilibrium and instantaneous compressive moduli) was measured via indentation testing (n = 17 sites). Each site was sectioned for histology and assessed for glycosaminoglycan content using digital densitometry of Safranin-O stained sections, Fourier transform infrared spectroscopy for collagen content, and morphology using both the Mankin and OARSI semiquantitative scoring systems. Water content was determined using mass change after lyophilization. Results: CECT attenuation at all imaging time points, including those <1 hour of ioxaglate exposure, correlated significantly (P < 0.05) with cartilage water and glycosaminoglycan contents, Mankin score, and both equilibrium and instantaneous compressive moduli. Early time points (<30 minutes) also correlated (P < 0.05) with collagen content and OARSI score. Differences in cartilage quality between intrajoint regions were distinguishable at diffusion equilibrium and after brief ioxaglate exposure. Conclusions: CECT with ioxaglate affords biochemical and biomechanical measurements of cartilage health and performance even after short, clinically relevant exposure times, and may be useful in the clinic as a means for detecting early signs of cartilage pathology

The NASA AfriSAR campaign: Airborne SAR and lidar measurements of tropical forest structure and biomass in support of current and future space missions

International audienceIn 2015 and 2016, the AfriSAR campaign was carried out as a collaborative effort among international space and National Park agencies (ESA, NASA, ONERA, DLR, ANPN and AGEOS) in support of the upcoming ESA BIOMASS, NASA-ISRO Synthetic Aperture Radar (NISAR) and NASA Global Ecosystem Dynamics Initiative (GEDI) missions. The NASA contribution to the campaign was conducted in 2016 with the NASA LVIS (Land Vegetation and Ice Sensor) Lidar, the NASA L-band UAVSAR (Uninhabited Aerial Vehicle Synthetic Aperture Radar). A central motivation for the AfriSAR deployment was the common AGBD estimation requirement for the three future spaceborne missions, the lack of sufficient airborne and ground calibration data covering the full range of ABGD in tropical forest systems, and the intercomparison and fusion of the technologies. During the campaign, over 7000 km2 of waveform Lidar data from LVIS and 30,000 km2 of UAVSAR data were collected over 10 key sites and transects. In addition, field measurements of forest structure and biomass were collected in sixteen 1-hectare sized plots. The campaign produced gridded Lidar canopy structure products, gridded aboveground biomass and associated uncertainties, Lidar based vegetation canopy cover profile products, Polarimetric Interferometric SAR and Tomographic SAR products and field measurements. Our results showcase the types of data products and scientific results expected from the spaceborne Lidar and SAR missions; we also expect that the AfriSAR campaign data will facilitate further analysis and use of waveform lidar and multiple baseline polarimetric SAR datasets for carbon cycle, biodiversity, water resources and more applications by the greater scientific community

Tick-, Mosquito-, and Rodent-Borne Parasite Sampling Designs for the National Ecological Observatory Network [Special Feature: NEON Design]

Parasites and pathogens are increasingly recognized as significant drivers of ecological and evolutionary change in natural ecosystems. Concurrently, transmission of infectious agents among human, livestock, and wildlife populations represents a growing threat to veterinary and human health. In light of these trends and the scarcity of long-term time series data on infection rates among vectors and reservoirs, the National Ecological Observatory Network (NEON) will collect measurements and samples of a suite of tick-, mosquito-, and rodent-borne parasites through a continental-scale surveillance program. Here, we describe the sampling designs for these efforts, highlighting sampling priorities, field and analytical methods, and the data as well as archived samples to be made available to the research community. Insights generated by this sampling will advance current understanding of and ability to predict changes in infection and disease dynamics in novel, interdisciplinary, and collaborative ways

Refined histopathological predictors of BRCA1 and BRCA2 mutation status: A large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Methods: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the