Clinical comparison of flat versus alignment fitting philosophies

A clinical study of twenty-three subjects was conducted to compare corneal changes and patient responses observed with flat versus alignment fitting philosophies. Corneal changes were assessed by comparison of initial and endpoint data gathered on refractive status, corneal curvature, and corneal staining. The subjective response to lens comfort was also monitored. Corneas fitted with lenses on alignment showed statistically less change in corneal astigmatism, visual acuity, and staining than lenses fitted flat

The Atacama Cosmology Telescope: Two-Season ACTPol Lensing Power Spectrum

We report a measurement of the power spectrum of cosmic microwave background (CMB) lensing from two seasons of Atacama Cosmology Telescope Polarimeter (ACTPol) CMB data. The CMB lensing power spectrum is extracted from both temperature and polarization data using quadratic estimators. We obtain results that are consistent with the expectation from the best-fit Planck LCDM model over a range of multipoles L=80-2100, with an amplitude of lensing A_lens = 1.06 +/- 0.15 (stat.) +/- 0.06 (sys.) relative to Planck. Our measurement of the CMB lensing power spectrum gives sigma_8 Omega_m^0.25 = 0.643 +/- 0.054; including baryon acoustic oscillation scale data, we constrain the amplitude of density fluctuations to be sigma_8 = 0.831 +/- 0.053. We also update constraints on the neutrino mass sum. We verify our lensing measurement with a number of null tests and systematic checks, finding no evidence of significant systematic errors. This measurement relies on a small fraction of the ACTPol data already taken; more precise lensing results can therefore be expected from the full ACTPol dataset.Comment: 17 pages, 11 figures, to be submitted to Physical Review

The Atacama Cosmology Telescope: Two-Season ACTPol Spectra and Parameters

We present the temperature and polarization angular power spectra measured by the Atacama Cosmology Telescope Polarimeter (ACTPol). We analyze night-time data collected during 2013-14 using two detector arrays at 149 GHz, from 548 deg$^2$ of sky on the celestial equator. We use these spectra, and the spectra measured with the MBAC camera on ACT from 2008-10, in combination with Planck and WMAP data to estimate cosmological parameters from the temperature, polarization, and temperature-polarization cross-correlations. We find the new ACTPol data to be consistent with the LCDM model. The ACTPol temperature-polarization cross-spectrum now provides stronger constraints on multiple parameters than the ACTPol temperature spectrum, including the baryon density, the acoustic peak angular scale, and the derived Hubble constant. Adding the new data to planck temperature data tightens the limits on damping tail parameters, for example reducing the joint uncertainty on the number of neutrino species and the primordial helium fraction by 20%.Comment: 23 pages, 25 figure

Evidence of lensing of the cosmic microwave background by dark matter halos

We present evidence of the gravitational lensing of the cosmic microwave background by 1013 solar mass dark matter halos. Lensing convergence maps from the Atacama Cosmology Telescope Polarimeter (ACTPol) are stacked at the positions of around 12 000 optically selected CMASS galaxies from the SDSS-III/BOSS survey. The mean lensing signal is consistent with simulated dark matter halo profiles and is favored over a null signal at 3.2σ significance. This result demonstrates the potential of microwave background lensing to probe the dark matter distribution in galaxy group and galaxy cluster halos

A global-scale screening of non-native aquatic organisms to identify potentially invasive species under current and future climate conditions

The threat posed by invasive non-native species worldwide requires a global approach to identify which introduced species are likely to pose an elevated risk of impact to native species and ecosystems. To inform policy, stakeholders and management decisions on global threats to aquatic ecosystems, 195 assessors representing 120 risk assessment areas across all six inhabited continents screened 819 non-native species from 15 groups of aquatic organisms (freshwater, brackish, marine plants and animals) using the Aquatic Species Invasiveness Screening Kit. This multi-lingual decision-support tool for the risk screening of aquatic organisms provides assessors with risk scores for a species under current and future climate change conditions that, following a statistically based calibration, permits the accurate classification of species into high-, medium-and low-risk categories under current and predicted climate conditions. The 1730 screenings undertaken encompassed wide geographical areas (regions, political entities, parts thereof, water bodies, river basins, lake drainage basins, and marine regions), which permitted thresholds to be identified for almost all aquatic organismal groups screened as well as for tropical, temperate and continental climate classes, and for tropical and temperate marine ecoregions. In total, 33 species were identified as posing a 'very high risk' of being or becoming invasive, and the scores of several of these species under current climate increased under future climate conditions, primarily due to their wide thermal tolerances. The risk thresholds determined for taxonomic groups and climate zones provide a basis against which area-specific or climate-based calibrated thresholds may be interpreted. In turn, the risk rankings help decision-makers identify which species require an immediate 'rapid' management action (e.g. eradication, control) to avoid or mitigate adverse impacts, which require a full risk assessment, and which are to be restricted or banned with regard to importation and/or sale as ornamental or aquarium/fishery enhancement. Decision support tools AS-ISK Hazard identification Non-native species Risk analysis Climate changepublishedVersio

A global-scale screening of non-native aquatic organisms to identify potentially invasive species under current and future climate conditions

The threat posed by invasive non-native species worldwide requires a global approach to identify which introduced species are likely to pose an elevated risk of impact to native species and ecosystems. To inform policy, stakeholders and management decisions on global threats to aquatic ecosystems, 195 assessors representing 120 risk assessment areas across all six inhabited continents screened 819 non-native species from 15 groups of aquatic organisms (freshwater, brackish, marine plants and animals) using the Aquatic Species Invasiveness Screening Kit. This multi-lingual decision-support tool for the risk screening of aquatic organisms provides assessors with risk scores for a species under current and future climate change conditions that, following a statistically based calibration, permits the accurate classification of species into high-, medium- and low-risk categories under current and predicted climate conditions. The 1730 screenings undertaken encompassed wide geographical areas (regions, political entities, parts thereof, water bodies, river basins, lake drainage basins, and marine regions), which permitted thresholds to be identified for almost all aquatic organismal groups screened as well as for tropical, temperate and continental climate classes, and for tropical and temperate marine ecoregions. In total, 33 species were identified as posing a ‘very high risk’ of being or becoming invasive, and the scores of several of these species under current climate increased under future climate conditions, primarily due to their wide thermal tolerances. The risk thresholds determined for taxonomic groups and climate zones provide a basis against which area-specific or climate-based calibrated thresholds may be interpreted. In turn, the risk rankings help decision-makers identify which species require an immediate ‘rapid’ management action (e.g. eradication, control) to avoid or mitigate adverse impacts, which require a full risk assessment, and which are to be restricted or banned with regard to importation and/or sale as ornamental or aquarium/fishery enhancement.publishedVersio

Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology

Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p <1 x 10(-4)) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.Peer reviewe

Pancreatic β-Cell Death in Response to Pro-Inflammatory Cytokines Is Distinct from Genuine Apoptosis

A reduction in functional β-cell mass leads to both major forms of diabetes; pro-inflammatory cytokines, such as interleukin-1beta (IL-1β) and gamma-interferon (γ-IFN), activate signaling pathways that direct pancreatic β-cell death and dysfunction. However, the molecular mechanism of β-cell death in this context is not well understood. In this report, we tested the hypothesis that individual cellular death pathways display characteristic phenotypes that allow them to be distinguished by the precise biochemical and metabolic responses that occur during stimulus-specific initiation. Using 832/13 and INS-1E rat insulinoma cells and isolated rat islets, we provide evidence that apoptosis is unlikely to be the primary pathway underlying β-cell death in response to IL-1β+γ-IFN. This conclusion was reached via the experimental results of several different interdisciplinary strategies, which included: 1) tandem mass spectrometry to delineate the metabolic differences between IL-1β+γ-IFN exposure versus apoptotic induction by camptothecin and 2) pharmacological and molecular interference with either NF-κB activity or apoptosome formation. These approaches provided clear distinctions in cell death pathways initiated by pro-inflammatory cytokines and bona fide inducers of apoptosis. Collectively, the results reported herein demonstrate that pancreatic β-cells undergo apoptosis in response to camptothecin or staurosporine, but not pro-inflammatory cytokines

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P &lt; 0.001) and PARP inhibitor therapy (P &lt; 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P &lt; 0.018) and WEE1 inhibitor (P &lt; 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P &lt; 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy