bluuebunny/crossref_metadata_2025 huggingface dataset:
NK Cells Are Required for Dendritic Cell–Based Immunotherapy at the Time of Tumor Challenge
Authors: Bouwer Anthea L. , Saunderson Sarah C. , Caldwell Felicity J. , Damani Tanvi T. , Pelham Simon J. , Dunn Amy C. , Jack Ralph W. , Stoitzner Patrizia , McLellan Alexander D.
Published: January 2014

Increasing evidence suggests that NK cells act to promote effective T cell–based antitumor responses. Using the B16-OVA melanoma model and an optimized Gram-positive bacteria–dendritic cell (DC) vaccination strategy, we determined that in vivo depletion of NK cells at time of tumor challenge abolished the benefit of DC immunotherapy. The contribution of NK cells to DC immunotherapy was dependent on tumor Ag presentation by DC, suggesting that NK cells act as helper cells to prime or reactivate tumor-specific T cells. The absence of NK cells at tumor challenge resulted in greater attenuation of tumor immunity than observed with selective depletion of either CD4 or CD8 T cell subsets. Although successful DC immunotherapy required IFN-γ, perforin expression was dispensable. Closer examination of the role of NK cells as helper cells in enhancing antitumor responses will reveal new strategies for clinical interventions using DC-based immunotherapy.
The Transcriptional Repressor BLIMP1 Curbs Host Defenses by Suppressing Expression of the Chemokine CCL8
Authors: Severa Martina , Islam Sabina A. , Waggoner Stephen N. , Jiang Zhaozhao , Kim Nancy D. , Ryan Glennice , Kurt-Jones Evelyn , Charo Israel , Caffrey Daniel R. , Boyartchuk Victor L. , Luster Andrew D. , Fitzgerald Katherine A.
Published: January 2014

The transcriptional repressor B lymphocyte–induced maturation protein 1 (BLIMP1) is a master regulator of B and T cell differentiation. To examine the role of BLIMP1 in innate immunity, we used a conditional knockout (CKO) of Blimp1 in myeloid cells and found that Blimp1 CKO mice were protected from lethal infection induced by Listeria monocytogenes. Transcriptome analysis of Blimp1 CKO macrophages identified the murine chemokine (C-C motif) ligand 8, CCL8, as a direct target of Blimp1-mediated transcriptional repression in these cells. BLIMP1-deficient macrophages expressed elevated levels of Ccl8, and consequently Blimp1 CKO mice had higher levels of circulating CCL8, resulting in increased neutrophils in the peripheral blood, promoting a more aggressive antibacterial response. Mice lacking the Ccl8 gene were more susceptible to L. monocytogenes infection than were wild-type mice. Although CCL8 failed to recruit neutrophils directly, it was chemotactic for γ/δ T cells, and CCL8-responsive γ/δ T cells were enriched for IL-17F. Finally, CCL8-mediated enhanced clearance of L. monocytogenes was dependent on γ/δ T cells. Collectively, these data reveal an important role for BLIMP1 in modulating host defenses by suppressing expression of the chemokine CCL8.
Upregulation of GRAIL Is Associated with Impaired CD4 T Cell Proliferation in Sepsis
Authors: Aziz Monowar , Yang Weng-Lang , Matsuo Shingo , Sharma Archna , Zhou Mian , Wang Ping
Published: January 2014

The loss of numbers and functionality of CD4 T cells is observed in sepsis; however, the mechanism remains elusive. Gene related to anergy in lymphocytes (GRAIL) is critical for the impairment of CD4 T cell proliferation. We therefore sought to examine the role of GRAIL in CD4 T cell proliferation during sepsis. Sepsis was induced in 10-wk-old male C57BL/6 mice by cecal ligation and puncture. Splenocytes were isolated and subjected to flow cytometry to determine CD4 T cell contents. CD4 T cell proliferation was assessed by CFSE staining, and the expression of GRAIL in splenocytes was measured by immunohistochemistry, real-time PCR, and flow cytometry. The expressions of IL-2 and early growth response-2 were determined by real-time PCR. As compared with shams, the numbers of CD4 T cells were significantly reduced in spleens. Septic CD4 T cells were less efficient in proliferation than shams. The IL-2 expression was significantly reduced, whereas the GRAIL expression was significantly increased in septic mice splenocytes as compared with shams. The small interfering RNA–mediated knockdown of GRAIL expression re-established the CD4 T cell proliferation ability ex vivo. Similarly, the treatment with recombinant murine IL-2 to the septic CD4 T cells restored their proliferation ability by downregulating GRAIL expression. Our findings reveal a novel association of the increased GRAIL expression with impaired CD4 T cell proliferation, implicating an emerging therapeutic tool in sepsis.
Smad and NFAT Pathways Cooperate To Induce CD103 Expression in Human CD8 T Lymphocytes
Authors: Mokrani M’Barka , Klibi Jihène , Bluteau Dominique , Bismuth Georges , Mami-Chouaib Fathia
Published: January 2014

The interaction of integrin αE(CD103)β7, often expressed on tumor-infiltrating T lymphocytes, with its cognate ligand, the epithelial cell marker E-cadherin on tumor cells, plays a major role in antitumor CTL responses. CD103 is induced on CD8 T cells upon TCR engagement and exposure to TGF-β1, abundant within the tumor microenvironment. However, the transcriptional mechanisms underlying the cooperative role of these two signaling pathways in inducing CD103 expression in CD8 T lymphocytes remain unknown. Using a human CTL system model based on a CD8+/CD103− T cell clone specific of a lung tumor–associated Ag, we demonstrated that the transcription factors Smad2/3 and NFAT-1 are two critical regulators of this process. We also identified promoter and enhancer elements of the human ITGAE gene, encoding CD103, involved in its induction by these transcriptional regulators. Overall, our results explain how TGF-β1 can participate in CD103 expression on locally TCR-engaged Ag-specific CD8 T cells, thus contributing to antitumor CTL responses and cancer cell destruction.
Leukotriene B4 Enhances the Generation of Proinflammatory MicroRNAs To Promote MyD88-Dependent Macrophage Activation
Authors: Wang Zhuo , Filgueiras Luciano Ribeiro , Wang Soujuan , Serezani Ana Paula Moreira , Peters-Golden Marc , Jancar Sonia , Serezani C. Henrique
Published: January 2014

MicroRNAs are known to control TLR activation in phagocytes. We have shown that leukotriene (LT) B4 (LTB4) positively regulates macrophage MyD88 expression by decreasing suppressor of cytokine signaling-1 (SOCS-1) mRNA stability. In this study, we investigated the possibility that LTB4 control of MyD88 expression involves the generation of microRNAs. Our data show that LTB4, via its receptor B leukotriene receptor 1 (BLT1) and Gαi signaling, increased macrophage expression of inflammatory microRNAs, including miR-155, miR-146b, and miR-125b. LTB4-mediated miR-155 generation was attributable to activating protein-1 activation. Furthermore, macrophage transfection with antagomirs against miR-155 and miR-146b prevented both the LTB4-mediated decrease in SOCS-1 and increase in MyD88. Transfection with miR-155 and miR-146b mimics decreased SOCS-1 levels, increased MyD88 expression, and restored TLR4 responsiveness in both wild type and LT-deficient macrophages. To our knowledge, our data unveil a heretofore unrecognized role for the GPCR BLT1 in controlling expression of microRNAs that regulate MyD88-dependent activation of macrophages.
Le Compartiment Centrasiatique Et Azerbaïdjanais Du Champ
Authors: de Tapia Stéphane
Published: January 2014

Depuis la fin des années 1950, l’émigration turque a construit un champ migratoire complexe, qui s’est d’abord construit en Europe, avant de s’étendre à l’Amérique du Nord, à l’Océanie puis dans les années 1970 aux pays arabes producteurs d’hydrocarbures. Au tournant des années 1990, les changements géopolitiques ont fait de l’Asie centrale et le Caucase de nouvelles destinations pour les migrants turcs, associant ambitions économiques, « retrouvailles » turciques et stratégies politiques. Aujourd’hui, la présence turque en Asie centrale est notamment liée à l’activité d’entreprises du BTP valorisant leur expérience dans le monde arabe et musulman et à l’engagement de petits investisseurs, par exemple dans le commerce, la restauration ou l’éducation. Elle prend donc des formes variées et participe à l’essor et à la diversification des relations entre l’Asie centrale et la Turquie. Pourtant, les sources documentaires sur ce nouveau compartiment du champ migratoire turc restent parcellaires, parfois contradictoires selon leur origine, malgré la publication de nombreux travaux.
On the Dispersive Estimate for the Dirichlet Schrödinger Propagator and Applications to Energy Critical NLS
Authors: Li Dong , Xu Guixiang , Zhang Xiaoyi
Published: January 2014

We consider the obstacle problem for the Schrödinger evolution in the exterior of the unit
ball with Dirichlet boundary condition. Under radial symmetry we compute explicitly the fundamental solution for the linear Dirichlet Schrödinger propagator and give a robust algorithm to prove sharp L1 → L∞ dispersive estimates. We showcase the analysis in dimensions n = 5, 7. As an application, we obtain global well–posedness and scattering for defocusing energy-critical NLS on with Dirichlet boundary condition and radial data in these dimensions.
Geometric Spectra and Commensurability
Authors: McReynolds D. B.
Published: January 2014

The work of Reid, Chinburg–Hamilton–Long–Reid, Prasad–Rapinchuk, and the author
with Reid have demonstrated that geodesics or totally geodesic submanifolds can sometimes be used to determine the commensurability class of an arithmetic manifold. The main results of this article show that generalizations of these results to other arithmetic manifolds will require a wide range of data. Specifically, we prove that certain incommensurable arithmetic manifolds arising from the semisimple Lie groups of the form
(SL(d, R)) r(SL(d, C))s have the same commensurability classes of totally geodesic submanifolds coming from a fixed field. This construction is algebraic and shows the failure of determining, in general, a central simple algebra from subalgebras over a fixed field. This, in turn, can be viewed in terms of forms of SLd and the failure of determining the form via certain classes of algebraic subgroups.
Fourier Coefficients of Vector-valued Modular Forms of Dimension 2
Authors: Franc Cameron , Mason Geoffrey
Published: January 2014

We prove the following theorem. Suppose that F = ( f1, f2) is a 2-dimensional, vectorvalued modular form on SL2(ℤ) whose component functions f1, f2 have rational Fourier coefficients with bounded denominators. Then f1, f2 are classical modular forms on a congruence subgroup of the modular group.
On Mutually m-permutable Products of Smooth Groups
Authors: Elkholy A. M. , Abd El-Latif M. H.
Published: January 2014

Let G be a finite group and H, K two subgroups of G. A group G is said to be a mutually m-permutable product of H and K if G = HK and every maximal subgroup of H permutes with K and every maximal subgroup of K permutes with H. In this paper, we investigate the structure of a finite group that is a mutually m-permutable product of two subgroups under the assumption that its maximal subgroups are totally smooth.
On the Hereditary Paracompactness of Locally Compact, Hereditarily Normal Spaces
Authors: Larson Paul , Tall Franklin D.
Published: January 2014

We establish that if it is consistent that there is a supercompact cardinal, then it is consistent that every locally compact, hereditarily normal space that does not include a perfect pre-image of ω1 is hereditarily paracompact.
The role of urban boundary layer investigated with high-resolution models and ground-based observations in Rome area: a step towards understanding parameterization potentialities
Authors: Pichelli E. , Ferretti R. , Cacciani M. , Siani A. M. , Ciardini V. , Di Iorio T.
Published: January 2014

Abstract. The urban forcing on thermodynamical conditions can greatly influence the local evolution of the atmospheric boundary layer. Heat stored in an urban environment can produce noteworthy mesoscale perturbations of the lower atmosphere. The new generation of high-resolution numerical weather prediction models (NWP) is nowadays often applied also to urban areas. An accurate representation of cities is key role because of the cities' influence on wind, temperature and water vapor content of the planetary boundary layer (PBL). The Advanced Weather Research and Forecasting model WRF (ARW) has been used to reproduce the circulation in the urban area of Rome. A sensitivity study is performed using different PBL and surface schemes. The significant role of the surface forcing in the PBL evolution has been investigated by comparing model results with observations coming from many instruments (lidar, sodar, sonic anemometer and surface stations). The impact of different urban canopy models (UCMs) on the forecast has also been investigated. One meteorological event will be presented, chosen as statistically relevant for the area of interest. The WRF-ARW model shows a tendency to overestimate the vertical transport of horizontal momentum from upper levels to low atmosphere if strong large-scale forcing occurs. This overestimation is partially corrected by a local PBL scheme coupled with an advanced UCM. Moreover, a general underestimation of vertical motions has been verified.
Performance of a mobile car platform for mean wind and turbulence measurements
Authors: Belušić D. , Lenschow D. H , Tapper N. J.
Published: January 2014

Abstract. The lack of adequate near-surface observations of the stable atmospheric boundary layer spatial structure motivated the development of an instrumented car for mobile turbulence measurements. The calibration and validation of the car measurements are performed using controlled field experiments and a comparison with an instrumented tower. The corrections required to remove the effects of the car motion are shown to be smaller and simpler than the corrections for research aircraft measurements. A car can therefore satisfactorily measure near-surface turbulence using relatively low-cost equipment. Other natural advantages of a car, such as the ability to drive on any road at any time of day or night and follow the terrain slope, as well as its low cost of operation, make it applicable to observations of a variety of flow regimes that cannot be achieved with the usual platforms, such as research aircraft or networks of flux towers.
Biomass uptake and fire as controls on groundwater solute evolution on a southeast Australian granite: aboriginal land management hypothesis
Authors: Dean J. F. , Webb J. A. , Jacobsen G. , Chisari R. , Dresel P. E.
Published: January 2014

Abstract. The chemical composition of groundwater and surface water is often considered to be dominated by water–rock interactions, particularly weathering; however, it has been increasingly realised that plant uptake can deplete groundwater and surface water of nutrient elements. Here we show, using geochemical mass balance techniques that at our study site in Southwest Victoria, Australia, water–rock interactions do not control the hydrochemistry. Instead the chemical species provided by rainfall are depleted by plant biomass uptake and exported, predominantly through fire. Regular landscape burning by Aboriginal land users is hypothesized to have caused the depletion of chemical species in groundwater for at least the past 20 000 yr by accelerating the export of elements that would otherwise have been stored within the local biomass. These findings are likely to be representative of southeast Australia, as well as similar climatic regions elsewhere in the globe, and contrast with Northern Hemisphere studies of groundwater and surface water chemistry, where water–rock interactions are the dominant hydrochemical control.
Hydrological model calibration for derived flood frequency analysis using stochastic rainfall and probability distributions of peak flows
Authors: Haberlandt U. , Radtke I.
Published: January 2014

Abstract. Derived flood frequency analysis allows the estimation of design floods with hydrological modeling for poorly observed basins considering change and taking into account flood protection measures. There are several possible choices regarding precipitation input, discharge output and consequently the calibration of the model. The objective of this study is to compare different calibration strategies for a hydrological model considering various types of rainfall input and runoff output data sets and to propose the most suitable approach. Event based and continuous, observed hourly rainfall data as well as disaggregated daily rainfall and stochastically generated hourly rainfall data are used as input for the model. As output, short hourly and longer daily continuous flow time series as well as probability distributions of annual maximum peak flow series are employed. The performance of the strategies is evaluated using the obtained different model parameter sets for continuous simulation of discharge in an independent validation period and by comparing the model derived flood frequency distributions with the observed one. The investigations are carried out for three mesoscale catchments in northern Germany with the hydrological model HEC-HMS (Hydrologic Engineering Center's Hydrologic Modeling System). The results show that (I) the same type of precipitation input data should be used for calibration and application of the hydrological model, (II) a model calibrated using a small sample of extreme values works quite well for the simulation of continuous time series with moderate length but not vice versa, and (III) the best performance with small uncertainty is obtained when stochastic precipitation data and the observed probability distribution of peak flows are used for model calibration. This outcome suggests to calibrate a hydrological model directly on probability distributions of observed peak flows using stochastic rainfall as input if its purpose is the application for derived flood frequency analysis.
Balancing ecosystem services with energy and food security – assessing trade-offs for reservoir operation and irrigation investment in Kenya's Tana basin
Authors: Hurford A. P. , Harou J. J.
Published: January 2014

Abstract. Competition for water between key economic sectors and the environment means agreeing on allocation is challenging. Managing releases from the three major dams in Kenya's Tana River basin with its 4.4 million inhabitants, 567 MW of installed hydropower capacity, 33 000 ha of irrigation and ecologically important wetlands and forests is a pertinent example. This research seeks to identify and help decision-makers visualise reservoir management strategies which result in the best possible (Pareto-optimal) allocation of benefits between sectors. Secondly we seek to show how trade-offs between achievable benefits shift with the implementation of new proposed rice, cotton and biofuel irrigation projects. To identify the Pareto-optimal trade-offs we link a water resources management model to a multi-criteria search algorithm. The decisions or "levers" of the management problem are volume dependent release rules for the three major dams and extent of investment in new irrigation schemes. These decisions are optimised for objectives covering provision of water supply and irrigation, energy generation and maintenance of ecosystem services which underpin tourism and local livelihoods. Visual analytic plots allow decision makers to assess multi-reservoir rule-sets by understanding their impacts on different beneficiaries. Results quantify how economic gains from proposed irrigation schemes trade-off against disturbance of the flow regime which supports ecosystem services. Full implementation of the proposed schemes is shown to be Pareto-optimal, but at high environmental and social cost. The clarity and comprehensiveness of "best-case" trade-off analysis is a useful vantage point from which to tackle the interdependence and complexity of water-energy-food "nexus" challenges.
Using the Nordic Geodetic Observing System for land uplift studies
Authors: Nordman M. , Poutanen M. , Kairus A. , Virtanen J.
Published: January 2014

Abstract. Geodetic observing systems have been planned and developed during the last decade. An ideal observing system consists of a network of geodetic observing stations with several techniques at the same site, publicly accessible databases, and as a product delivers data time series, combination of techniques or some other results obtained from the datasets. Globally, there is the IAG GGOS (Global Geodetic Observing System), and there are ongoing attempts to create also regional observing systems. In this paper we introduce one regional system, NGOS (Nordic Geodetic Observing System) hosted by the Nordic Geodetic Commission (NKG). Data availability and accessibility are one of the major issues today. We discuss on general data-related topics, and introduce a pilot database project of NGOS. As a demonstration of the use of such database, we apply it for postglacial rebound studies in the Fennoscandian area. We compare land uplift values from three techniques, GNSS, tide gauges and absolute gravimeter, with the Nordic NKG2005LU land uplift model. The purpose is to evaluate the data obtained from different techniques and different sources and get the most reliable values for the uplift using publicly available data. It is also important to consider the relation between geodetic observing systems and specific projects like DynaQlim (Upper Mantle Dynamics and Quaternary Climate in Cratonic Areas) or EPOS (European Plate Observing System). The natural aim of observing systems will be to produce data and other products needed by such multidisciplinary projects, but their needs may currently exceed the scope of an observing system. We discuss what requirements the projects pose to observing systems and their development.
Response of ice cover on shallow lakes of the North Slope of Alaska to contemporary climate conditions (1950–2011): radar remote-sensing and numerical modeling data analysis
Authors: Surdu C. M. , Duguay C. R. , Brown L. C. , Fernández Prieto D.
Published: January 2014

Abstract. Air temperature and winter precipitation changes over the last five decades have impacted the timing, duration, and thickness of the ice cover on Arctic lakes as shown by recent studies. In the case of shallow tundra lakes, many of which are less than 3 m deep, warmer climate conditions could result in thinner ice covers and consequently, in a smaller fraction of lakes freezing to their bed in winter. However, these changes have not yet been comprehensively documented. The analysis of a 20 yr time series of European remote sensing satellite ERS-1/2 synthetic aperture radar (SAR) data and a numerical lake ice model were employed to determine the response of ice cover (thickness, freezing to the bed, and phenology) on shallow lakes of the North Slope of Alaska (NSA) to climate conditions over the last six decades. Given the large area covered by these lakes, changes in the regional climate and weather are related to regime shifts in the ice cover of the lakes. Analysis of available SAR data from 1991 to 2011, from a sub-region of the NSA near Barrow, shows a reduction in the fraction of lakes that freeze to the bed in late winter. This finding is in good agreement with the decrease in ice thickness simulated with the Canadian Lake Ice Model (CLIMo), a lower fraction of lakes frozen to the bed corresponding to a thinner ice cover. Observed changes of the ice cover show a trend toward increasing floating ice fractions from 1991 to 2011, with the greatest change occurring in April, when the grounded ice fraction declined by 22% (α = 0.01). Model results indicate a trend toward thinner ice covers by 18–22 cm (no-snow and 53% snow depth scenarios, α = 0.01) during the 1991–2011 period and by 21–38 cm (α = 0.001) from 1950 to 2011. The longer trend analysis (1950–2011) also shows a decrease in the ice cover duration by ~24 days consequent to later freeze-up dates by 5.9 days (α = 0.1) and earlier break-up dates by 17.7–18.6 days (α = 0.001).
Excimer Laser Mushroom Penetrating Keratoplasty: New Technique
Authors: Della Valle Vincenzo , Bonci Paolo
Published: January 2014

Purpose:

To evaluate retrospectively the outcomes of 15 consecutive mushroom-shaped penetrating keratoplasties performed by using excimer laser for both the recipient bed and the fresh donor corneas.

Methods:

Fifteen eyes of 14 patients who underwent excimer laser mushroom-shaped penetrating keratoplasty from October 13, 2010, to October 14, 2011, were included in our retrospective study. Eight were men and 6 were women, with a mean age of 31.45 ± 6.52 (range 27-65) years. Eleven (73.3%) had postinfective central deep corneal scar; 4 (26.7%) had severe keratoconus with Descemet opacity.

Results:

The mean follow-up was 11.9 ± 2.7 months. The mean preoperative best-corrected visual acuity (BCVA) was 0.15 ± 0.16; the postoperative BCVA was 0.69 ± 0.24 after 12 months with a mean refractive astigmatism of 1.8 ± 1.1 D. The mean preoperative endothelial cell count of the donor corneas was 2297.0 ± 189.7 cells/mm2; after 12 months, it was 1906.5 ± 165.8 with a decrease of 17.0%. No intraoperative complications occurred.

Conclusions:

Our results showed that excimer laser mushroom penetrating keratoplasty is safe. Furthermore, it does not appear to influence the visual outcomes of the penetrating keratoplasty surgery. This technique is useful for those who use an excimer laser.
Cytomegalovirus Retinitis in Patients with AIDS before and after Introduction of HAART in China
Authors: Sun Hui Yu , Peng Xiao Yan , Li Dan , Mao Fei Fei , You Qi Sheng , Jonas Jost B.
Published: January 2014

Purpose:

To determine the prevalence of cytomegalovirus retinitis (CMVR) and other fundus lesions in subjects with acquired immunodeficiency syndrome (AIDS) before and after the introduction of highly active antiretroviral therapy (HAART) in China.

Methods:

The retrospective study included subjects with AIDS who consecutively attended a third referral center in Beijing before and after HAART was introduced. Comprehensive systemic and ophthalmic examinations, including CD4+ T-cell count, ophthalmoscopy, and fundus photography, were carried out.

Results:

A total of 173 HIV-infected, HAART-naive individuals and 267 people undergoing HAART were included in the study. The HAART-naive group as compared with the HAART group was significantly older (39.5 ± 11.5 years versus 36.7 ± 11.2 years; p = 0.02) and included significantly more men (p = 0.045). Prevalence of CMVR, microvascular retinopathy, and optic neuropathy in the HAART group (9.0 ± 1.8%, 7.9 ± 1.7%, and 4.9 ± 1.3%, respectively) were significantly (all p≤0.001) lower than in the HAART-naive group (20.2 ± 3.1%, 31.2 ± 3.5%, and 13.9 ± 2.6%, respectively). Microvascular retinopathy was significantly associated with HAART-naive status (p<0.001; odds ratio [OR] 0.20; 95% confidence interval [CI] 0.12, 0.36) and higher age (p = 0.002; OR 1.04; 95% CI 1.10, 1.06). Cytomegalovirus retinitis was significantly associated with CD4+ cell count <50 cells/μL (p = 0.001; OR 5.50; 95% CI 1.95, 15.5), HAART-naive status (p = 0.02; OR 0.23; 95% CI 0.07, 0.79), and lower best-corrected visual acuity (p<0.001; OR 5.44; 95% CI 2.11, 14.0).

Conclusions:

As in Western countries, prevalence of CMVR and microvascular retinopathy in Chinese subjects with AIDS were significantly associated with a low CD4+ cell count and a HAART-naive status as the 2 major risk factors.
The Effect of an Artificial Tear Combining Hyaluronic Acid and Tamarind Seeds Polysaccharide in Patients with Moderate Dry Eye Syndrome: A New Treatment for Dry Eye
Authors: Barabino Stefano , Rolando Maurizio , Nardi Marco , Bonini Stefano , Aragona Pasquale , Traverso Carlo Enrico
Published: January 2014

Purpose:

Synergistic interactions between hyaluronic acid (HA) and tamarind seed polysaccharide (TS-polysaccharide) have been demonstrated by means of nuclear magnetic resonance spectroscopy. This study was designed to investigate the potential clinical benefit of a combination of HA and TS-polysaccharide in managing dry eye disease (DED).

Methods:

A total of 49 subjects with moderate DED, confirmed by Ocular Surface Disease Index (OSDI) questionnaire score between 10 and 25, tear break-up time (BUT) <10 seconds, or Schirmer I test <5.5 mm after 5 minutes, and lissamine green staining of the ocular surface >2 according to National Eye Institute score system, were enrolled into this multicenter, randomized, double-masked study to receive either combination of HA and TS-polysaccharide or carmellose sodium for 3 months, both instilled 4 times per day. The assessments included OSDI questionnaire, tear film stability (BUT), tear production (Schirmer I test), and corneal and conjunctival staining.

Results:

Patients treated with HA and TS-polysaccharide showed a statistically significant improvement in the OSDI score at the end of the study compared to the baseline and control groups. The HA and TS-polysaccharide and carmellose sodium were equally effective in reducing BUT and the extent of injury assessed by corneal and conjunctival staining. Non-significant changes were recorded for Schirmer I test.

Conclusions:

Based on the results of this clinical trial, the combination of HA and TS-polysaccharide appears to be effective in improving the symptoms of dry eye, opening new scenarios in possible treatment of the disease by combining different molecules.
Imaging in Retina Units: Changes Observed during the Last 12 Years
Authors: Cohen Salomon Y. , Weber Michel , Oubraham Hassiba , Gaudric Alain , Quentel Gabriel , Tadayoni Ramin
Published: January 2014

Purpose:

The last decade has seen many improvements in the imaging of the choroids, retina, and vitreous. However, there are no available data about changes in the practice of imaging in retina units. The present study was therefore undertaken to document the 12-year changes in this practice in retina units in France, particularly the relative changes in the distribution of the different imaging methods.

Methods:

This retrospective study was performed in 4 different retina units considered to be representative of retina units in France. They comprise 2 departments of ophthalmology in university-based hospitals in Paris and Nantes, one in a non-university-based general hospital in Orleans, and one private tertiary care clinical center located in Paris. The annual numbers for the different retinal imaging methods performed in the 4 units between 2000 and 2011 were recorded, analyzed, and compared.

Results:

The total of images performed increased during the last decade, from 16,084 in 2000 to 76,318 in 2011. The distribution of the imaging techniques performed each year changed significantly during this period (p<0.0001, χ2 test): the share of fluorescein angiography decreased from 78.7% in 2000 to 7.0% in 2011. During this period, the share of indocyanine green angiography also dropped from 11.3% to 1.3%. The share of optical coherence tomography increased from 26.4% in 2003 to 53.4% in 2012.

Conclusions:

The present study documents the increasing share of noninvasive imaging and the decreasing share of angiography in retina units over the last 12 years.
Bilateral Superior Oblique Palsy: Etiology and Therapeutic Options
Authors: Merino Pilar S. , Rojas Pilar L. , Gómez De Liaño Pilar S. , Fukumitsu Hideki M. , Yáñez Jacobo M.
Published: January 2014

Purpose:

To study the causes of bilateral superior oblique palsy (BSOP), treatment with botulinum toxin and/or surgery, and outcome of treatment.

Methods:

This was an 11-year retrospective study of patients with BSOP treated with injections of botulinum toxin (Botox), surgery, or both. Treatment was considered successful when anomalous head turn and diplopia in primary gaze position and downgaze resolved.

Results:

Bilateral superior oblique palsy was diagnosed in 12 patients (8 male; mean age, 29.5 years). Palsy was secondary to a neoplasm in 3 cases and to head trauma in 2. In 2 cases, it was ischemic, in 2 it was congenital; the remaining cases were iatrogenic (hydrocephalus secondary to meningitis, 1), hemorrhagic ( 1 ), and idiopathic ( 1 ). The clinical manifestations recorded were diplopia ( 10 ), anomalous head posture ( 9 ), V pattern ( 12 ), subjective excyclotorsion ( 8 ), and objective excyclotorsion ( 6 ). Recovery was spontaneous in 1 case with neoplastic disease. Botox was injected in 8 cases (inferior oblique and/or inferior rectus muscles [successful in 2]), and subsequent surgery was required in 6. Two patients underwent surgery without prior injection of Botox. The most common surgical technique was recession of the inferior oblique muscle (6 patients), either as the only operation or associated with other procedures. The final result was good in 72.72% (8/11). Mean follow-up was 62.6 months (range 9-99 months).

Conclusions:

Causes of BSOP were varied (most frequently neoplastic). Botox was effective as the only treatment in 25% (2/8). Outcome was good in a high percentage of cases with Botox, surgery, or both.
Prognostic Factors and Visual Outcomes of Ruptured and Lacerated Globe Injuries
Authors: Fabian Ido Didi , Eliashiv Sivan , Moisseiev Joseph , Tryfonides Christos , Alhalel Amir
Published: January 2014

Purpose:

To identify prognostic factors related to ruptured and lacerated globes and compare the visual outcomes of these 2 mechanisms of injury.

Methods:

Medical records of patients with open-globe injuries referred to the Goldschleger Eye Institute between 2004 and 2010 were reviewed. Clinical parameters were summarized as defined by the ocular trauma score (OTS). All cases were classified as either ruptured or lacerated globes and a statistical analysis was performed in order to identify prognostic factors.

Results:

Medical records of 73 patients (55 male) were reviewed. Mean age of male injured patients was 33 years and of female injured patients was 64 years. Thirty-three percent of injuries were classified as ruptured globes. Males were mostly injured by a lacerating mechanism, compared to females (79.6% and 33.3%, respectively; p = 0.01). Mean logMAR at presentation after lacerated and ruptured globes was 1.42 ± 1.01 and 2.02 ± 0.91, respectively. Mean logMAR at the final follow-up visit after lacerated and ruptured globes was 0.65 ± 0.85 and 1.69 ± 1.10, respectively. Mean logMAR of the lacerated globes improved to a better extent compared to the ruptured ones (p = 0.046). The OTS was found to be a significant predictor of final mean logMAR for the lacerated globes (p<0.001), whereas mean logMAR at presentation was found to be the only predictive measure for ruptured globes (p<0.001).

Conclusions:

Ruptured and lacerated globes differ from each other in regard to prognostic factors and visual outcomes. We recommend distinguishing these 2 injury types in clinical practice as different open-globe injuries.
Recrudescent Meibomian Gland Carcinoma Treated with Xeloda: Case Report
Authors: Liang Yi-chen , Zhang Tao , Chen Sheng , Yu Dan-dan , Wu Hong-ge
Published: January 2014

Purpose:

To observe the curative effect of Xeloda in meibomian gland carcinoma.

Methods:

We treated a 53-year-old woman, who had recrudescent meibomian gland carcinoma, with Xeloda.

Results:

The mass was much smaller with decreased amount of overflow pus after 4 cycles of chemotherapy with Xeloda.

Conclusions:

Xeloda played a significant role in treating recrudescent meibomian gland carcinoma in this patient.
Luminal Subtypes Predict Improved Survival Following Central Nervous System Metastasis in Patients With Surgically Managed Metastatic Breast Carcinoma
Authors: Wiens Andrea L. , Martin Sarah E. , Bertsch Elizabeth C. , Vance Gail H. , Stohler Ryan A. , Cheng Liang , Badve Sunil , Hattab Eyas M.
Published: January 2014

Context.—Metastatic breast cancer to the central nervous system (CNS) is second only to lung cancer metastasis to the CNS in frequency. Patients with triple-negative primary breast cancer and those with human epidermal growth factor receptor 2 (HER2)–positive primary breast cancer are at an increased risk for metastasis. Very little is known about predictive or prognostic variables once patients develop CNS metastases. Currently, therapeutic options are limited, with surgery generally offered primarily to those with solitary lesions.

Context.—To determine the influence of molecular subtypes of metastatic breast cancer on survival from the time of CNS metastasis and to aid in the prognostic stratification of these patients.

Design.—We identified 59 cases of metastatic breast cancer to the CNS and analyzed them for various demographic and clinicopathologic parameters. Tumors were categorized into molecular subtypes using immunohistochemical methods: luminal A [estrogen receptor (ER)+/Ki67low], luminal B (ER+/Ki67 high), intrinsic HER2 (ER−/HER2+), and triple-negative. Survival after CNS metastasis for each group was plotted using a Kaplan-Meier curve, and multivariate analysis was performed.

Results.—Patients with metastases from luminal tumors had a statistically significant survival advantage when compared with those of the triple-negative phenotype. Importantly, survival among patients with luminal A and luminal B tumors was not significantly different. Similarly, patient's age, histologic grade, and number of lesions did not contribute to determining outcomes.

Conclusions.—Estrogen receptor positivity (ie, luminal phenotype) of tumors appears to determine outcomes after development of metastases. In contrast, proliferation rate had little or no effect on the long-term survival. Understanding the biology of metastases can help stratify patients into prognostically meaningful categories and tailor treatment regimens for individual patients.
Differentiation of Pancreatic Ductal Adenocarcinoma From Chronic Pancreatitis by PAM4 Immunohistochemistry
Authors: Shi Chanjuan , Merchant Nipun , Newsome Guy , Goldenberg David M. , Gold David V.
Published: January 2014

Context.—PAM4 is a monoclonal antibody that shows high specificity for pancreatic ductal adenocarcinoma (PDAC) and its neoplastic precursor lesions. A PAM4-based serum immunoassay is able to detect 71% of early-stage patients and 91% with advanced disease. However, approximately 20% of patients diagnosed with chronic pancreatitis (CP) are also positive for circulating PAM4 antigen. The specificity of the PAM4 antibody is critical to the interpretation of the serum-based and immunohistochemical assays for detection of PDAC.

Objective.—To determine whether PAM4 can differentiate PDAC from nonneoplastic lesions of the pancreas.

Design.—Tissue microarrays of PDAC (N = 43) and surgical specimens from CP (N = 32) and benign cystic lesions (N = 19) were evaluated for expression of the PAM4 biomarker, MUC1, MUC4, CEACAM5/6, and CA19-9.

Results.—PAM4 and monoclonal antibodies (MAbs) to MUC1, MUC4, CEACAM5/6, and CA19-9 were each reactive with the majority of PDAC cases; however, PAM4 was the only monoclonal antibody not to react with adjacent, nonneoplastic parenchyma. Although PAM4 labeled 19% (6 of 32) of CP specimens, reactivity was restricted to pancreatic intraepithelial neoplasia associated with CP; inflamed tissues were negative in all cases. In contrast, MUC1, MUC4, CEACAM5/6, and CA19-9 were detected in 90%, 78%, 97%, and 100% of CP, respectively, with reactivity also present in nonneoplastic inflamed tissue.

Conclusions.—PAM4 was the only monoclonal antibody able to differentiate PDAC (and pancreatic intraepithelial neoplasia precursor lesions) from benign, nonneoplastic tissues of the pancreas. These results suggest the use of PAM4 for evaluation of tissue specimens, and support its role as an immunoassay for detection of PDAC.
Approach to Lung Biopsies From Patients With Pneumothorax
Authors: Schneider Frank , Murali Rajmohan , Veraldi Kristen L. , Tazelaar Henry D. , Leslie Kevin O.
Published: January 2014

Context.—Patients with pneumothorax occasionally require limited lung resections to control persistent air leaks. In some patients, especially smokers, histopathologic findings suggest that a ruptured bulla or bleb caused the pneumothorax. Other patients only exhibit histopathologic changes related to the physical trauma of acute, and likely occult recurrent, peripheral lung injury in the setting of “spontaneous,” or idiopathic, lung rupture. Sometimes, pneumothorax occurs secondary to an underlying localized or diffuse parenchymal lung disease. A comprehensive description of the morphologic findings that may be seen in these specimens will help the surgical pathologist distinguish patients with more common and indolent occurrences of pneumothorax from those requiring additional workup or treatment.

Objective.—To develop a diagnostic approach for surgical pathologists encountering lung specimens obtained in the context of pneumothorax repair.

Data Sources.—Literature review and consultation experience of the authors.

Conclusions.—Two general categories of histopathologic changes can be identified: (1) nonspecific changes, reflecting the lung's acute and chronic response to localized injury, and (2) changes suggesting an underlying lung disease that may have played an etiologic role in the development of pneumothorax. The latter changes are important to recognize because they may require additional workup or treatment of clinically occult lung disease. Difficulty arises when nonspecific histopathologic changes overlap with those of an underlying lung disease. Awareness of these diagnostic challenges and pitfalls, together with clinicoradiographic correlation, is essential in these situations and will help guide the surgical pathologist toward an accurate diagnosis and the appropriate management of clinically occult disease.
Transplantation of Photoreceptors Derived From Human Müller Glia Restore Rod Function in the P23H Rat
Authors: Jayaram Hari , Jones Megan F. , Eastlake Karen , Cottrill Phillippa B. , Becker Silke , Wiseman Joseph , Khaw Peng T. , Limb G. Astrid
Published: January 2014

Müller glia possess stem cell characteristics that have been recognized to be responsible for the regeneration of injured retina in fish and amphibians. Although these cells are present in the adult human eye, they are not known to regenerate human retina in vivo. Human Müller glia with stem cell characteristics (hMSCs) can acquire phenotypic and genotypic characteristics of rod photoreceptors in vitro, suggesting that they may have potential for use in transplantation strategies to treat human photoreceptor degenerations. Much work has been undertaken in rodents using various sources of allogeneic stem cells to restore photoreceptor function, but the effect of human Müller glia-derived photoreceptors in the restoration of rod photoreceptor function has not been investigated. This study aimed to differentiate hMSCs into photoreceptor cells by stimulation with growth and differentiation factors in vitro to upregulate gene and protein expression of CRX, NR2E3, and rhodopsin and various phototransduction markers associated with rod photoreceptor development and function and to examine the effect of subretinal transplantation of these cells into the P23H rat, a model of primary photoreceptor degeneration. Following transplantation, hMSC-derived photoreceptor cells migrated and integrated into the outer nuclear layer of the degenerated retinas and led to significant improvement in rod photoreceptor function as shown by an increase in a-wave amplitude and slope using scotopic flash electroretinography. These observations suggest that hMSCs can be regarded as a cell source for development of cell-replacement therapies to treat human photoreceptor degenerations and may also offer potential for the development of autologous transplantation.
Environmental Justice and Human Rights on the Mining Wastelands of the Witwatersrand Gold Fields
Authors: Humby Tracy-Lynn
Published: January 2014

In South Africa, the constitutional and statutory framework seemingly establishes a strong synergy between environmental rights and environmental justice. A prevailing notion of transformative constitutionalism additionally positions law as the foundation for large-scale social change through non-violent political processes. A case study of the Tudor Shaft Informal settlement on the Witwatersrand goldfields elucidates the ambiguities in the notion of environmental justice and the tensions between claims based on the environmental right and socio-economic rights. By highlighting the existence of local moral orders—political alliances based on access to resources that frequently employ violence to achieve political ends—it also suggests the limited reach of the constitutional order and the project of transformative constitutionalism.
International and Domestic Law Dimensions of Climate Justice for Arctic Indigenous Peoples
Authors: Kronk Warner Elizabeth Ann , Abate Randall S.
Published: January 2014

The Arctic region is in crisis from the effects of climate change. The impacts of climate change pose a particular threat to Arctic indigenous communities. Because of the disproportionate impacts of climate change, these indigenous communities are environmental justice communities. Part I of this article discusses how indigenous nations are environmental justice communities and discusses the unique factors that may apply to environmental justice claims arising in Indian country. The article then presents two case studies to explore how, if at all, these concepts have been previously applied to environmental justice claims brought by various Arctic indigenous communities. Part II addresses the Inuit Circumpolar Conference’s petition to the Inter-American Commission on Human Rights. Part III considers the Native Village of Kivalina’s lawsuit against numerous private emitters of greenhouse gases. These case studies underscore the failure of international and domestic forums’ consideration of the special situation of Arctic indigenous peoples as environmental justice communities.
Une archéologie philosophique des normes environnementales : biopolitique et droit des peuples autochtones
Authors: Bertrand Aliènor
Published: January 2014

Cet article décrit la dialectique qui oppose les droits des peuples autochtones et les normes de protection de la nature. Il défend l’hypothèse selon laquelle ces normes sont un instrument de biopouvoir. Dessinant une nouvelle archéologie philosophique, il discute et renverse la périodisation proposée par Foucault en distinguant trois grandes formes de biopolitique ayant rythmé successivement l’histoire de l’expansion occidentale : la biopolitique esclavagiste, la biopolitique sanitaire et la biopolitique environnementale. La combinaison de cette nouvelle périodisation avec l’anthropologie de la nature de Philippe Descola permet une réinterprétation puissante des dispositifs de pouvoir qui se sont succédé depuis le début de l’époque moderne. Réinscrites dans une perspective de longue durée, les normes environnementales apparaissent alors comme un outil majeur de l’imposition au monde du socle anthropologique de l’Occident moderne. Mais les dynamiques historiques d’opposition ou de synergie entre les systèmes de droit coutumier, les édifices juridiques de souveraineté et les gouvernementalités biopolitiques montrent aussi que le droit naissant des peuples autochtones ouvre une double voie de résistance au pouvoir des États et à la normativité environnementale néolibérale.
Putting Property in its Place: Relational Theory, Environmental Rights and Land Use Planning
Authors: Van Wagner Estair
Published: January 2014

This paper examines the complex web of legal, social and ecological relationships engaged by contemporary land use disputes. In particular, it considers the role of non-owners in decision-making processes about the use of private land. Combining critical perspectives on property theory with relational approaches to rights, it examines recent conflicts around the siting of aggregate quarries in Southwestern Ontario. Three decisions of the Ontario Municipal Board and the Joint Board are analyzed to demonstrate how aggregate disputes present opportunities for the strategic advancement of non-ownership interests in land. Jennifer Nedelsky’s four-step relational approach to dispute resolution and Nicole Graham’s theory of reciprocal person-place relations are applied to the cases to show how a shift away from the ownership model of property can lead to better social and ecological outcomes in land use planning.