bluuebunny/crossref_metadata_2025 huggingface dataset:
El refugio en altura andalusí de Vilella (Almiserat, Valencia), un ejemplo de arquitectura defensiva rural en el ámbito centro-meridional valenciano (ca. 1150-1250)
Authors: Sánchez i Signes Miquel
Published: April 2014

Presentamos en este trabajo los resultados del estudio realizado sobre el pequeño refugio rural de Vilella (Almiserat, Valencia), construido mediante la técnica del tapial durante los últimos momentos de dominación islámica en el Sharq al-Andalus. Se analizan la planta y las defensas del recinto (sistema de ingreso y torre oeste) y, sobre todo, los distintos tipos de fábrica de tapia y las improntas constructivas asociadas a esta técnica. También se analizan otras técnicas de construcción documentadas.
Estudio histórico-arqueológico de la muralla sureste de Arcos de la Frontera (Cádiz)
Authors: Alonso-Ruiz Manuel María , García-Pulido Luis José
Published: April 2014

Con motivo del proyecto elaborado por los técnicos del Ayuntamiento de Arcos de la Frontera para la restauración del tramo de muralla medieval conservada en el sureste de esta localidad, los autores de este artículo realizaron la intervención arqueológica, documentación planimétrica y estudio de dicha cerca. Como resultado de estas actuaciones se han identificado ocho períodos edificatorios, agrupados en tres grandes ciclos. De cara a obtener una mayor comprensión del objeto de estudio, estas actuaciones se han completado con el recurso a las fuentes escritas, la prospección urbana, el estudio de la microtoponimia, la analogía con otros elementos arquitectónicos y, en menor medida, con la información aportada por los materiales arqueológicos. Los resultados de estos análisis permiten el planteamiento de una hipótesis razonable para la fundación de la muralla y la relación entre las tres puertas históricas del frente suroriental de la localidad. Las conclusiones obtenidas suponen un acercamiento a la evolución urbana de esta zona de Arcos de la Frontera desde época andalusí hasta las postrimerías de la Edad Moderna.
Factors affecting the fishing impact on cartilaginous fishes in southeastern Spain (western Mediterranean Sea)
Authors: Mendoza Manuel , Garrido Diego , Bellido Jose M.
Published: April 2014

We propose a global index of impact based on the relative vulnerability of the local population of every species and the further application of regression trees globally optimized with evolutionary algorithms to study the fishing impact on the cartilaginous fish in southeastern Spain. The fishing impact is much higher in areas of less than 40 m depth within 11 km of the Cape Palos marine reserve. The impact also depends on the state of the sea and the kind of habitat. Deep-sea habitats associated with hard substrata and sandy beds show the highest impact, and sublittoral muds and habitats associated with circa littoral rocks with moderate energy show the lowest impact. The fishing impact changes throughout the moon cycle, showing different day-scale patterns associated with different habitats and different species compositions. Finally, we show that the global optimization of the regression trees can be essential to find some important patterns and that these trees are a useful tool for determining which areas are considered to be more important in terms of protection, taking into account specifically the vulnerability of the local populations.
Importance of the Ecosystem Approach to Fisheries in Georgia
Authors: Goradze Rezo , Komakhidze Akaki , Mgeladze Marina , Goradze Irakli , Diasamidze Revaz , Komakhidze Giorgi
Published: April 2014

The economic downturn in the 1990s and early 2000s associated with the break-up of the Soviet Union had a negative impact on Georgian fisheries. Both marine and freshwater fisheries and aquaculture suffered considerable decline. The Georgian fishing fleet deteriorated. The role of state institutions in fisheries management weakened and funding of scientific research diminished. Economic and institutional problems had a negative effect on the state of aquatic bio-resources. The excessive and relentless use of living resources, use of illegal fishing gear and degradation of coastal ecosystems led to a considerable reduction in fish stocks, while the number of vulnerable and endangered species increased. Starting from the new millennium the attitude has changed. In 2004-2005 the 15-year plan for the development of the ecosystem approach to fisheries in Georgia was initiated with support from the FAO. A Georgian law on fisheries and aquaculture has been introduced. Discussions on responsible fisheries and an aquaculture code have also started, but are still pending. On the other hand, the fisheries department of the Ministry of Agriculture was abolished and the single fisheries research institute met a similar fate. Fisheries regulation came under the authority of the ministry of environment. There is still a lot to be done in order to establish an ecosystem approach to fisheries in Georgia. First of all, the legislative base must be addressed, including the Georgian law on fisheries, which would consider such issues as long-term sustainable development of fisheries, a responsible code of conduct for fishermen, monitoring and management structures at the national level, allocation of resources and application of scientific approaches in development of fisheries, aquaculture and mariculture.
Requirement of Calcineurin Aβ for the Survival of Naive T Cells
Authors: Manicassamy Santhakumar , Gupta Sonal , Huang Zhaofeng , Molkentin Jeffery D. , Shang Weirong , Sun Zuoming
Published: April 2014

Calcineurin (Cn) is a Ca2+/calmodulin-dependent phosphatase that dephosphorylates and activates NFAT, a transcription factor essential for T cell activation. T lymphocytes predominantly express the calcineurin Aβ (CnAβ) isoform, and the deletion of the CnAβ gene results in defective T cell proliferation and IL-2 production in response to TCR stimulation. In this study, we show that CnAβ enhances the spontaneous survival of naive T cells by maintaining high levels of Bcl-2, a critical homeostatic survival factor for naive T cells. T cells obtained from CnAβ−/− mice displayed accelerated spontaneous apoptosis. The observed apoptosis of the CnAβ−/− T cells was prevented by IL-7 and IL-15, two cytokines critical for the homeostatic survival of naive T cells. Furthermore, CD4+ or CD8+ single positive CnAβ−/− thymocytes also underwent accelerated apoptosis. However, no obvious difference in the apoptosis of CD4+CD8+ double positive thymocytes was observed between CnAβ−/− and wild-type mice, suggesting a specific function of CnAβ in the survival of single positive T cells. Bcl-2 levels were found to be significantly lower in CnAβ−/− T cells. Transgenic expression of Bcl-xL restored the survival of the CnAβ−/− T cells. Thus, in addition to its role in mediating TCR signals essential for T cell activation, CnAβ is also required for the homeostatic survival of naive T cells.
Proliferating CD4+ T Cells Undergo Immediate Growth Arrest upon Cessation of TCR Signaling In Vivo
Authors: Yarke Cory A. , Dalheimer Stacy L. , Zhang Na , Catron Drew M. , Jenkins Marc K. , Mueller Daniel L.
Published: April 2014

To investigate the role of TCR signaling in the exit of CD4+ T cells from cell cycle, we took advantage of a low frequency TEa T cell adoptive transfer technique as well as the Y-Ae mAb to interrupt Ag/MHC recognition before the completion of clonal expansion. Termination of TCR signaling after 36 h of Ag exposure caused an immediate reduction in cell size and deceleration of G1—>SG2M phase cell cycle progression. As a consequence, clonal expansion in the absence of durable TCR signaling decreased by two-thirds. Thus, CD4+ T cells scan for the presence Ag throughout their clonal expansion response, and continuously adjust their rate of cell growth and G1—>S phase transition to match their intensity of TCR signaling.
Immune Modulation by the Human Cytomegalovirus-Encoded Molecule UL18, a Mystery Yet to Be Solved
Authors: Wagner Claudia S. , Ljunggren Hans-Gustaf , Achour Adnane
Published: April 2014

Human cytomegalovirus infects human populations at a high frequency worldwide. During the long coevolution of virus and host, a fine balance has developed between viral immune evasion strategies and defense mechanisms of the immune system. Human cytomegalovirus encodes multiple proteins involved in the evasion of immune recognition, among them UL18, a MHC class I homologue. Despite almost 20 years of research and the discovery of a broadly expressed inhibitory receptor for this protein, its function in immune modulation is not clear yet. Recent data suggest that besides inhibitory effects on various immune cells, UL18 may also act as an activating component during CMV infection. In this review, we provide an overview of the biology of UL18 and discuss several attempts to shed light on its function.
Human T Cells That Are Able to Produce IL-17 Express the Chemokine Receptor CCR6
Authors: Singh Satya P. , Zhang Hongwei H. , Foley John F. , Hedrick Michael N. , Farber Joshua M.
Published: April 2014

Some pathways of T cell differentiation are associated with characteristic patterns of chemokine receptor expression. A new lineage of effector/memory CD4+ T cells has been identified whose signature products are IL-17 cytokines and whose differentiation requires the nuclear receptor, RORγt. These Th17 cells are critical effectors in mouse models of autoimmune disease. We have analyzed the association between chemokine receptor expression and IL-17 production for human T cells. Activating cord blood (naive) CD4+ T cells under conditions driving Th17 differentiation led to preferential induction of CCR6, CCR9, and CXCR6. Despite these data, we found no strong correlation between the production of IL-17 and expression of CCR9 or CXCR6. By contrast, our analyses revealed that virtually all IL-17-producing CD4+ T cells, either made in our in vitro cultures or found in peripheral blood, expressed CCR6, a receptor found on ∼50% of CD4+ memory PBL. Compared with CD4+CD45RO+CCR6− cells, CD4+CD45RO+CCR6+ cells contained at least 100-fold more IL-17A mRNA and secreted 100-fold more IL-17 protein. The CCR6+ cells showed a similar enrichment in mRNA for RORγt. CCR6 was likewise expressed on all IL-17-producing CD8+ PBL. CCR6 has been associated with the trafficking of T, B, and dendritic cells to epithelial sites, but has not been linked to a specific T cell phenotype. Our data reveal a fundamental feature of IL-17-producing human T cells and a novel role for CCR6, suggesting both new directions for investigating IL-17-related immune responses and possible targets for preventing inflammatory injury.
The Inhibitory HVEM-BTLA Pathway Counter Regulates Lymphotoxin β Receptor Signaling to Achieve Homeostasis of Dendritic Cells
Authors: De Trez Carl , Schneider Kirsten , Potter Karen , Droin Nathalie , Fulton James , Norris Paula S. , Ha Suk-won , Fu Yang-Xin , Murphy Theresa , Murphy Kenneth M. , Pfeffer Klaus , Benedict Chris A. , Ware Carl F.
Published: April 2014

Proliferation of dendritic cells (DC) in the spleen is regulated by positive growth signals through the lymphotoxin (LT)-β receptor; however, the countering inhibitory signals that achieve homeostatic control are unresolved. Mice deficient in LTα, LTβ, LTβR, and the NFκB inducing kinase show a specific loss of CD8− DC subsets. In contrast, the CD8α− DC subsets were overpopulated in mice deficient in the herpesvirus entry mediator (HVEM) or B and T lymphocyte attenuator (BTLA). HVEM- and BTLA-deficient DC subsets displayed a specific growth advantage in repopulating the spleen in competitive replacement bone marrow chimeric mice. Expression of HVEM and BTLA were required in DC and in the surrounding microenvironment, although DC expression of LTβR was necessary to maintain homeostasis. Moreover, enforced activation of the LTβR with an agonist Ab drove expansion of CD8α− DC subsets, overriding regulation by the HVEM-BTLA pathway. These results indicate the HVEM-BTLA pathway provides an inhibitory checkpoint for DC homeostasis in lymphoid tissue. Together, the LTβR and HVEM-BTLA pathways form an integrated signaling network regulating DC homeostasis.
Cutting Edge: Engagement of NKG2A on CD8+ Effector T Cells Limits Immunopathology in Influenza Pneumonia
Authors: Zhou Jing , Matsuoka Mitsuo , Cantor Harvey , Homer Robert , Enelow Richard I.
Published: April 2014

Influenza pneumonia results in considerable lung injury, a significant component of which is mediated by CD8+ T cell Ag recognition in the distal airways and alveoli. TNF-α produced by Ag-specific CD8+ T cells appears primarily responsible for this immunopathology, and we have examined the negative regulation of CD8+ TNF production by CD94/NKG2A engagement with its receptor, Qa-1b. TNF production by antiviral CD8+ T cells was significantly enhanced by NKG2A blockade in vitro, and mice deficient in the NKG2A ligand, Qa-1b, manifested significantly greater pulmonary pathology upon CD8+ T cell-mediated clearance in influenza pneumonia. Furthermore, blockade of NKG2A ligation resulted in the enhancement of lung injury induced by CD8+ effector cell recognition of alveolar Ag in vivo in the absence of infectious virus. These data demonstrate that CD94/NKG2A transduces a biologically important signal in vivo to activated CD8+ T cells that limits immunopathology in severe influenza infection.
Hyperacute Rejection by Anti-Gal IgG1, IgG2a, and IgG2b Is Dependent on Complement and Fc-γ Receptors
Authors: Ding Jin Wen , Zhou Tingting , Zeng Huasong , Ma Lianli , Verbeek J. Sjef , Yin Dengping , Shen Jikun , Chong Anita S.
Published: April 2014

We have previously reported that anti-Gal-α1,3Gal (Gal) IgG3 mAbs mediate a classical complement-dependent hyperacute rejection (HAR), while anti-Gal IgG1 mAbs mediate HAR that is dependent on complement, the Fc-γ receptors FcγRII/III (CD32/CD16), and NK cells. IgG2a and IgG2b subclasses can activate complement and have FcγR binding properties in vitro. Whether these IgG subclasses can mediate HAR in vivo and the mechanisms by which they would do so are not known. In this study, we isolated spontaneous IgG switch mutants from an anti-Gal IgG1 hybridoma. In vitro complement-mediated hemolytic assays with mouse complement indicate that both anti-Gal IgG2a and IgG2b mAbs were more potent compared with the parent anti-Gal IgG1. In vivo administration of anti-Gal IgG2a and IgG2b mAbs into Gal−/− mice induced HAR of rat cardiac xenografts. HAR induced by anti-Gal IgG2a and IgG2b was dependent on complement activation and the presence of NK cells. Using FcγRIII-deficient (Gal−/−CD16−/−) recipients, we observed that HAR mediated by different anti-Gal IgG subclasses was variably dependent on FcγRIII, with IgG1 > IgG2b ≫ IgG2a = IgG3. Using FcγRI-deficient (Gal−/−CD64−/−) recipients, we observed that HAR mediated by anti-Gal IgG1, IgG2a, and IgG2b, but not by anti-Gal IgG3, was dependent on FcγRI. Collectively, these studies demonstrate the necessity and sufficiency of complement in IgG3-mediated HAR and the necessity of both complement and FcγR, especially FcγRI, in IgG1-, IgG2a-, and IgG2b-mediated HAR.
IL-15 Treatment during Acute Simian Immunodeficiency Virus (SIV) Infection Increases Viral Set Point and Accelerates Disease Progression despite the Induction of Stronger SIV-Specific CD8+ T Cell Responses
Authors: Mueller Yvonne M. , Do Duc H. , Altork Susan R. , Artlett Carol M. , Gracely Edward J. , Katsetos Christos D. , Legido Agustin , Villinger Francois , Altman John D. , Brown Charles R. , Lewis Mark G. , Katsikis Peter D.
Published: April 2014

In this study, we examined the effect of in vivo treatment of acutely SIV-infected Mamu-A*01+ rhesus macaques with IL-15. IL-15 treatment during acute infection increased viral set point by 3 logs and accelerated the development of simian AIDS in two of six animals with one developing early minimal lesion SIV meningoencephalitis. Although IL-15 induced a 2- to 3-fold increase in SIV-specific CD8+ T cell and NK cell numbers at peak viremia and reduced lymph node (LN) SIV-infected cells, this had no impact on peak viremia and did not lower viral set point. At viral set point, however, activated SIV-specific CD8+ T cells and NK cells were reduced in the blood of IL-15-treated animals and LN SIV-infected cells were increased. Week 30 LN from IL-15-treated animals had significantly increased Gag-specific CD8+ T cell numbers, whereas total cell, lymphocyte, and CD4+ T cell numbers were reduced. IL-15 treatment significantly reduced anti-SIV Ab concentrations at week 3 and viral set point. IL-15 increased Ki-67+CD4+ T cells at week 1 of treatment and reduced blood CCR5+ and CD45RA−CD62L− CD4+ T cells. The frequency of day 7 Ki-67+CD4+ T cells strongly correlated with viral set point. These findings suggest that CD4+ T cell activation during acute infection determines subsequent viral set point and IL-15 treatment by increasing such activation elevates viral set point. Finally, IL-15-treated acutely SIV-infected primates may serve as a useful model to investigate the poorly understood mechanisms that control viral set point and disease progression in HIV infection.
Maintenance of Long-Lived Plasma Cells and Serological Memory Despite Mature and Memory B Cell Depletion during CD20 Immunotherapy in Mice
Authors: DiLillo David J. , Hamaguchi Yasuhito , Ueda Yoshihiro , Yang Kaiyong , Uchida Junji , Haas Karen M. , Kelsoe Garnett , Tedder Thomas F.
Published: April 2014

CD20 mAb-mediated B cell depletion is an effective treatment for B cell malignancies and some autoimmune diseases. However, the full effects of B cell depletion on natural, primary, and secondary Ab responses and the maintenance of Ag-specific serum Ig levels are largely unknown. The relationship between memory B cells, long-lived plasma cells, and long-lived humoral immunity also remains controversial. To address the roles of B cell subsets in the longevity of humoral responses, mature B cells were depleted in mice using CD20 mAb. Peritoneal B cell depletion reduced natural and Ag-induced IgM responses. Otherwise, CD20+ B cell depletion prevented humoral immune responses and class switching and depleted existing and adoptively transferred B cell memory. Nonetheless, B cell depletion did not affect serum Ig levels, Ag-specific Ab titers, or bone marrow Ab-secreting plasma cell numbers. Coblockade of LFA-1 and VLA-4 adhesion molecules temporarily depleted long-lived plasma cells from the bone marrow. CD20+ B cell depletion plus LFA-1/VLA-4 mAb treatment significantly prolonged Ag-specific plasma cell depletion from the bone marrow, with a significant decrease in Ag-specific serum IgG. Collectively, these results support previous claims that bone marrow plasma cells are intrinsically long-lived. Furthermore, these studies now demonstrate that mature and memory B cells are not required for maintaining bone marrow plasma cell numbers, but are required for repopulation of plasma cell-deficient bone marrow. Thereby, depleting mature and memory B cells does not have a dramatic negative effect on preexisting Ab levels.
Targeting HIV-1 Gag into the Defective Ribosomal Product Pathway Enhances MHC Class I Antigen Presentation and CD8+ T Cell Activation
Authors: Goldwich Andreas , Hahn Sabine S. C. , Schreiber Sandra , Meier Stefanie , Kämpgen Eckhart , Wagner Ralf , Lutz Manfred B. , Schubert Ulrich
Published: April 2014

The main source for endogenous peptides presented by the MHC class I (MHC-I) pathway are de novo-synthesized proteins which are degraded via the ubiquitin proteasome pathway. Different MHC-I Ag pools can be distinguished: first, short-lived defective ribosomal products, which are degraded in concert with or shortly after their synthesis, and, second, functional proteins that enter the standard protein life cycle. To compare the contribution of these two Ag sources to the generation of MHC-I-presented peptides, we established murine cell lines which express as a model Ag the HIV-1 Gag polyprotein fused to ubiquitin (Ub) carrying the epitope SIINFEKL (SL). Gag was expressed either in its wild-type form (UbMGagSL) or as a variant UbRGagSL harboring an N-end rule degron signal. Although UbRGagSL displayed wild-type protein stability, its inherent defective ribosomal products rate observed after proteasome shutdown was increased concomitant with enhanced presentation of the SL epitope. In addition, UbRGagSL induces enhanced T cell stimulation of SL-specific B3Z hybridoma cells as measured in vitro and of adoptively transferred TCR-transgenic OT-1 T cells in vivo. Furthermore, an elevated frequency of SL-specific T cells was detected by IFN-γ ELISPOT after immunization of naive C57BL/6 mice with UbRGagSL/EL4 cells. These results further underline the role of the defective ribosomal product pathway in adaptive immunity.
TLR9 Contributes to Antiviral Immunity during Gammaherpesvirus Infection
Authors: Guggemoos Simone , Hangel Doris , Hamm Svetlana , Heit Antje , Bauer Stefan , Adler Heiko
Published: April 2014

The human gammaherpesviruses Kaposi’s sarcoma-associated herpesvirus and EBV cause important infections. As pathogenetic studies of the human infections are restricted, murine gammaherpesvirus 68 serves as a model to study gammaherpesvirus pathogenesis. TLRs are a conserved family of receptors detecting microbial molecular patterns. Among the TLRs, TLR9 recognizes unmethylated CpG DNA motifs present in bacterial and viral DNA. The aim of this study was to assess the role of TLR9 in gammaherpesvirus pathogenesis. Upon stimulation with murine gammaherpesvirus 68, Flt3L-cultured bone marrow cells (dendritic cells) from TLR9−/− mice secreted reduced levels of IL-12, IFN-α, and IL-6, when compared with dendritic cells from wild-type mice. Intranasal infection of TLR9−/− and wild-type mice did not reveal any differences during lytic and latent infection. In contrast, when infected i.p., TLR9−/− mice showed markedly higher viral loads both during lytic and latent infection. Thus, we show for the first time that TLR9 is involved in gammaherpesvirus pathogenesis and contributes to organ-specific immunity.
Cutting Edge: Mechanism of Enhancement of In Vivo Cytokine Effects by Anti-Cytokine Monoclonal Antibodies
Authors: Phelan James D. , Orekov Tatyana , Finkelman Fred D.
Published: April 2014

Inhibitory anti-cytokine mAbs are used to treat cytokine-mediated disorders. Recently, however, S4B6, an anti-IL-2 mAb that blocks IL-2 binding to IL-2Rα, a receptor component that enhances affinity but is not required for signaling, was shown to enhance IL-2 agonist effects in vivo. We evaluated how S4B6 enhances IL-2 effects and whether a similar mechanism allows mAbs to IL-4 to enhance IL-4 effects. Induction of T cell proliferation by IL-2/S4B6 complexes did not require complex dissociation and was IL-2Rα independent. S4B6 increased IL-2 agonist effects by increasing in vivo half-life, not by focusing IL-2 onto cells through Fc receptors. In contrast to IL-2/S4B6 complexes, anti-IL-4 mAb enhancement of in vivo IL-4 effects required IL-4/anti-IL-4 mAb complex dissociation. Thus, agonist effects observed with high doses of anti-IL-2 mAb are most likely only applicable for mAbs that maintain cytokine half-life without blocking binding to receptor signaling components.
Neutrophils Clear Bacteria Associated with Parasitic Nematodes Augmenting the Development of an Effective Th2-Type Response
Authors: Pesce John T. , Liu Zhugong , Hamed Hossein , Alem Farhang , Whitmire Jeanette , Lin Hongxia , Liu Qian , Urban Joseph F. , Gause William C.
Published: April 2014

Infection with the parasitic nematode Nippostrongylus brasiliensis induces a potent Th2 response; however, little is known about early stages of the innate response that may contribute to protective immunity. To examine early events in this response, chemokine expression in the draining lymph node was examined after N. brasiliensis inoculation. Pronounced increases of several chemokines, including CCL2, were observed. Compared with wild-type mice, elevations in a Gr-1bright population in the draining lymph node was significantly decreased in CCL2−/− mice after N. brasiliensis inoculation. Further flow cytometric and immunofluorescent analysis showed that in wild-type mice, Gr-1+ cells transiently entered and exited the draining lymph node shortly after N. brasiliensis inoculation. The Gr-1bright population was comprised of neutrophils expressing TGF-β and TNF-α. Following Gr-1+ cell depletion, N. brasiliensis infection resulted in transient, but significantly increased levels of IFN-γ, increased serum IgG2a, reduced Th2 cytokines and serum IgE, greatly increased mortality, and delayed worm expulsion. Furthermore, bacteria were readily detected in vital organs. Infection of Gr-1+ cell-depleted mice with N. brasiliensis larvae that were pretreated with antibiotics prevented bacterial dissemination, Th1 inflammatory responses, and decreases in host survival. This study indicates that parasitic nematodes can be an important vector of potentially harmful bacteria, which is typically controlled by CCL2-dependent neutrophils that ensure the optimal development of Th2 immune responses and parasite resistance.
A Role for Macrophage Migration Inhibitory Factor in the Neonatal Respiratory Distress Syndrome
Authors: Kevill Katharine A. , Bhandari Vineet , Kettunen Mika , Leng Lin , Fan Juan , Mizue Yuka , Dzuira James D. , Reyes-Mugica Miguel , McDonald Courtney L. , Baugh John A. , O’Connor Christine L. , Aghai Zubair H. , Donnelly Seamas C. , Bazzy-Asaad Alia , Bucala Richard J.
Published: April 2014

Using a mouse model of neonatal respiratory distress syndrome (RDS), we demonstrate a central role for macrophage migration inhibitory factor (MIF) in lung maturation at the developmental stage when human neonates are most susceptible to RDS. We prematurely delivered mouse pups at embryonic day 18, during the early saccular stage of pulmonary development. Only 8% of the prematurely delivered pups genetically deficient in MIF survived 8 h vs 75% of wild-type controls (p < 0.001). This phenotype was corrected when pups of all genotypes were bred from dams heterozygote for MIF deficiency. Local production of MIF in the lung increased at embryonic day 18, continued until full-term at embryonic day 19.5, and decreased in adulthood, thus coinciding with this developmental window. The lungs of pups genetically deficient in MIF were less mature upon histological evaluation, and demonstrated lower levels of vascular endothelial growth factor and corticosterone – two factors that promote fetal lung maturation. In vitro studies support a role for MIF in surfactant production by pulmonary epithelial cells. In a cohort of human neonates with RDS, higher intrapulmonary MIF levels were associated with a lower likelihood of developing bronchopulmonary dysplasia, a sequelae of RDS (p < 0.03). This study demonstrates for the first time a role for MIF in lung maturation, and supports a protective role for MIF in newborn lung disease.
Critical but Overlapping Role of FcγRIII and FcγRIV in Activation of Murine Neutrophils by Immobilized Immune Complexes
Authors: Jakus Zoltán , Németh Tamás , Verbeek J. Sjef , Mócsai Attila
Published: April 2014

Immune complex-induced activation of neutrophils through cell surface FcRs plays a central role in the pathogenesis of autoimmune inflammatory diseases. These diseases are often modeled using genetically modified mice. However, in contrast to the number of studies on human cells, the identity of FcRs involved in immune complex activation of murine neutrophils is at present unknown. Furthermore, little is known about the cellular functions mediated by the recently identified murine FcγRIV. In this study, we tested the identity of FcRs involved in the activation of neutrophils by plate-bound immune complexes, using various knockout mouse strains, function-blocking mAbs, or the combination of both approaches. Activation of murine neutrophils by immobilized IgG immune complexes was abrogated in FcR γ-chain-deficient cells, but not by the single or combined deficiency of the γ-chain-associated FcγRI and FcγRIII, or by blocking Abs against either FcγRIII or FcγRIV alone. However, treatment of FcγRIII-deficient neutrophils with FcγRIV-blocking Abs or simultaneous blocking of FcγRIII and FcγRIV in wild-type cells completely inhibited the immune complex-induced cellular responses. In parallel studies, activation of human neutrophils by immobilized immune complexes was abrogated by blocking Abs against either FcγRIIA or FcγRIIIB alone. Taken together, neutrophil activation by immobilized immune complexes requires the murine FcγRIII/FcγRIV or the human FcγRIIA/FcγRIIIB molecules. Although both of the two human receptors are required for this response, the two murine receptors play overlapping, redundant roles. These results promote our understanding of autoimmune diseases and identify an IgG-dependent cellular function of FcγRIV.
Suffering in the perspective of God’s governance, eschatology and God’s council
Authors: Van de Beek Abraham
Published: April 2014

From the beginning of Christian theology, theologians have struggled with the question of how suffering in the world is related to God’s providence. A classic response to this question is that, ultimately, God’s governance is beyond human understanding. More recently an eschatological solution has been preferred: God is involved in a historical process and he will finally overcome evil. This article argued that both responses have their own problems. In the first God is a hidden mystery, and in the latter either the outcome of history is uncertain or God is waiting unnecessarily long. On the other hand, both provide consolation to human beings in times of suffering. Which one of the two answers is more helpful, depends on culture and context. Therefore, they are both acceptable responses to the question. At a deeper level, one can argue that both refer to eternity − one in a spatial model (above) and the other in a temporal model (hereafter). Both space and time are metaphors in this context. That is also the case when we speak of ‘before’ with regard to God’s eternal council. Ultimately, from a perspective of eternity, God’s council, God’s governance and God’s final judgment coincide. In Christian theology these concepts can only be understood in the paradigm of God’s revelation in Christ, who is the expression of the mystery of creation − as is especially indicated in the letters to the Ephesians and Colossians. Vanaf het begin van het Christendom hebben theologen geworsteld met de vraag hoe het lijden in de wereld zich verhoudt tot Gods voorzienigheid. Een klassiek antwoord daarop is dat ten laatste Gods bestuur het menselijk begrip te boven gaat. Tegenwoordig wordt eerder de voorkeur gegeven aan een eschatologische oplossing: God is betrokken in een proces door de geschiedenis waarin Hij uiteindelijk het kwaad zal overwinnen. De auteur betoogt dat beide benaderingen hun eigen problemen hebben. In het eerste geval is God een onkenbaar mysterie en in het tweede geval is de afloop onzeker of wacht God onnodig lang met zijn overwinning. Aan de andere kant bieden beide antwoorden mensen troost in lijdenssituaties. Welke van de twee antwoorden het beste is, hangt af van cultuur en context. Daarom zijn beide aanvaardbaar als antwoord op het probleem van Gods voorzienigheid. Op een dieper niveau kan men betogen dat beide verwijzen naar de eeuwigheid, het eerste antwoord in een ruimtelijk model (‘te boven’) en het tweede in een tijdsmodel (‘hierna’). Zowel ruimte als tijd zijn hier metaforisch gebruikt. Dat is ook het geval als we spreken over ‘vóór’ met betrekking tot Gods eeuwige raad. Uiteindelijk zijn, vanuit het perspectief van de eeuwigheid, Gods raad, Gods beleid en Gods laatste oordeel identiek. In de christelijke theologie kunnen deze concepten alleen worden verstaan in het paradigma van Gods openbaring in Christus, die de expressie van het geheimenis van de schepping is, zoals met name de brieven aan de Efeziërs en aan de Kolossenzen aangeven.
Breaking bad news of cancer diagnosis – Perception of the cancer patients in a rural community in Malaysia
Authors: Bain Mathew Gabriel , Lian Cheah Whye , Thon Chang Ching
Published: April 2014

Context: Breaking of bad news is an important component in the management of cancer patients. Aims: This study aimed to assess the perceptions of breaking bad news of cancer diagnosis. Settings and Design: It was a cross-sectional study using Breaking Bad News Assessment Schedule (BAS) questionnaire on cancer patients in Serian district. Materials and Methods: Using snowballing sampling method, a total of 134 patients were interviewed face-to-face after the consent was obtained from each of the respondents. Statistical Analysis Used: Data was entered and analyzed using SPSS version 19.0. Results: Majority were comfortable with the current method of breaking bad news. The main aspects found to be the areas of concern were the importance of the usage of body language, management of time and identifying patients′ key area of concerns. There were significant difference between sex and "information giving" (P = 0.028) and "general consideration" (P = 0.016) and also between "the age and setting the scene" (P = 0.042). Significant difference was also found between the types of cancer and "the setting of scene" (P = 0.018), "breaking bad news technique" (P = 0.010), "eliciting concerns" (P = 0.003) and "information giving" (P = 0.004). Conclusion: Good and effective communication skill of breaking bad news is vital in the management of cancer patients. As the incidence of new cases of cancer increase every year, breaking of bad news has become a pertinent to the medical professionals′ role. Specific aspects of communication skills based on local characteristics should be more emphasized in the formulation of training for doctors.
Barriers for early detection of cancer amongst Indian rural women
Authors: Tripathi Neha , Kadam Yugantara R. , Dhobale Randhir V. , Gore Alka D.
Published: April 2014

Context: Breast and cervical cancer are the most common causes of cancer mortality among women worldwide, but actually they are largely preventable diseases. Healthcare providers in developing countries regularly see women with advanced, incurable cancers. Health of a rural Indian women and her access to health facility is compromised due to sociocultural, economical, and environmental factors. Aims: To know the problems associated with early detection of cancers in rural women. Settings and Design: Rural area and cross-sectional. Subjects and Methods: Study subject: Women of 35 years and above. Exclusion criteria: Not willing to participate. Sample size: All eligible women of selected villages. Sampling Technique: Random selection of villages. Study duration: 2 months. Study tools: Pretested questionnaire. Statistical Analysis Used: Percentages, χ2 test, analysis of variance (ANOVA), multivariate analysis. Results: Awareness about symptoms, possibility of early detection, available tests, possibility of cure of disease was low. Main barrier for screening was cognitive, that is, ′don′t know′ answer by 83.99% women for cancer cervix, 84.93%, for cancer breast, and 67.26% for oral cancer. Awareness score was significantly associated with age (χ2 = 17.77, P = 0.001), education (χ2 = 34.62, P = 0.000), and income (χ2 = 16.72, P = 0.002); while attitude score with age (χ2 = 16.27, P = 0.012) and education (χ2 = 25.16, P = 0.003). Practice score was significantly associated with age (χ2 = 11.28, P = 0.023), education (χ2 = 32.27, P = 0.003), and occupation (χ2 = 10.69, P = 0.03). Awareness, attitude, and practice score of women having history of cancer in family or relative was significantly high than women without history. Conclusions: Cognitive barrier was the important barrier which has to be taken care of.
Hospital Information System Satisfaction in Brazil: Background and Moderating Effects
Authors: Nunes Gadelha Socorro , Javier Miranda González Francisco
Published: April 2014

In the last years, hospitals in Brazil have made significant investments in adopting and implementing new hospital information system (HIS). Whether these investments will prove beneficial for these organizations depends on the support that will be provided to ensure the effective use of the information systems (IS) implemented and also on the satisfaction of its users.

The purpose of this study is to propose a conceptual model, appropriate for the intention to use HIS, by adopting the system, service, and information qualities covered in the Information System Success Model proposed by DeLone and Mclean.

In the present study, structural analysis applied to data from a sample of 393 HIS users showed the variables service quality, information quality, system quality and satisfaction to act as antecedents of HIS success. A novel finding of the study was the importance of the user's aptitude with respect to computer moderating the relationships of the model.

Managerial implications are provided accordingly. Suggestions for introducing healthcare information system are then provided as well.

How to cite this article

Nunes GS, Javier MGF. Hospital Information System Satisfaction in Brazil: Background and Moderating Effects. Int J Res Foundation Hosp Healthc Adm 2014;2(1):1-9.
Impact of Healthcare Marketing and Branding on Hospital Services
Authors: Kumar P Naveen , Jacob Anil , Thota Smruthi
Published: April 2014

Healthcare is one of the many human-centered services offered, the other being legal services, hospitality services, transport services, etc. The healthcare is also the foremost in all of these personal services. Every section of the healthcare experience must embody and convey the message that the hospital is the center of health and wellness in the community. The connection between healthcare provider and patient needs to be developed to improve the delivery model.

However with the rise of healthcare costs to providers, increase in operating costs, informative and knowledgeable customers; hospitals need branding to drive strategies, convey their expanding range of services, make an emotional connection with customers and create lasting relationships thereby generating profits.

Companies are losing out because there is often little or no integration between Corporate Social Responsibility (CSR) and marketing departments and their respective strategies. This misses brand building opportunities and may also confuse as well as disenfranchise company stakeholders.

Unless CSR becomes central to the marketing director's agenda, it will not have the desired effect and can potentially create a backlash. The nature of the business — category, customers, competitors — should dictate how much and in which ways, a company should promote its CSR-related activities.

Here, it lies the importance of developing a more strategic, distinct, sustainable and well defined brand platform. It is ultimately the hospital's brand and the customers’ ability to trust that will aid in the decision-making process between competitive healthcare hospitals. Patient expectations and desires are changing, altering the competitive landscape. Employees are a hospital's most vital force and communication medium. Thus, the brand is the greatest asset for uniting employees around a singular culture and mission. This study highlights a conceptual framework that can be used for healthcare organizations to develop the revenues based on branding.

How to cite this article

Kumar PN, Jacob A, Thota S. Impact of Healthcare Marketing and Branding on Hospital Services. Int J Res Foundation Hosp Healthc Adm 2014;2(1):19-24.
Patient Rights: Awareness and Practice in a Tertiary Care Indian Hospital
Authors: Fernandes Alphonsa B , D'Cunha Sweta , Suresh Sucharita
Published: April 2014

Aim and objectives

To study the awareness and practice of Patient rights and to compare the same between general and private ward hospitalized patients of a selected hospital.

Materials and methods

Descriptive research approach was adopted wherein data was collected from 120 hospitalized patients, i.e. 60 from general and 60 from private ward using a structured questionnaire. It was then analyzed by frequency, percentage and significance test to interpret the awareness and practice of patient rights in the hospital.

Results

The study reveals that awareness of patient rights was high in most of the cases. There was 71% awareness about the right to confidentiality, 67% awareness of the right to grievance redressal, 65% awareness about the right to be informed, 58% awareness of the right of access to healthcare and 55% awareness about the patient's right to choice of care and decision making. But low (39%) awareness was noted in case of patient's right to informed consent.

With regards to practice of patient rights, it was seen that certain rights were well-practiced like 95% practice of the right of access to healthcare, 89% practice of the right to confidentiality and 64% practice of the right to choice of care and decision making. But relatively lower percentage of practice was observed for right to be informed (49%), right to informed consent (44%) and the right to grievance redressal (21%). There was significant difference in the level of awareness and practice of patient rights among private and general ward patients in most of the rights.

Conclusion

The study was vital in finding that most respondents were aware of patient rights. So also, most of the patient rights were practiced in the hospital in varying degrees, while a few needed immediate rectification and management action.

How to cite this article

Fernandes AB, D'Cunha S, Suresh S. Patient Rights: Awareness and Practice in a Tertiary Care Indian Hospital. Int J Res Foundation Hosp Healthc Adm 2014;2(1):25-30.
A Study of Prescribing Practices in Outpatient Department of an Apex Tertiary Care Institute of India
Authors: Gupta Shakti Kumar , Siddharth V , Arya S
Published: April 2014

Introduction

Poor quality prescriptions, besides affecting patient safety, have a deleterious impact on the restricted purse of sick persons, especially those belonging to lower socioeconomic strata.

Objective

To study the prescribing practices in outpatient departments of an apex tertiary care institute of India.

Methodology

Descriptive and observational study of randomly taken sample of 300 prescriptions from pharmacy was carried out. Parameters for analysis were selected based on review of literature.

Observations

Of the total samples analyzed, OPD registration number, date of registration, patients name, gender and department were mentioned in 99.3% of prescriptions. Patient name was mentioned in all the prescriptions and gender was present in 99% prescriptions. Address of the patient was present in only 64.7% (194) prescriptions. 93.7% of the prescriptions were legible. Ninety-seven percent of the prescriptions carried diagnosis or presenting complaints. An average of 2.82 ± 1.77 (median – 3) drugs were prescribed per patient. Only 1.63% (14) prescribed drugs were generic. In our study, antacids (26.33%) followed by the vitamins (24%), analgesics (23.3%), antibiotics (22.8%) and antipyretics (18%) were the most commonly prescribed drugs. Drug strength, drug frequency and drug administration route was mentioned in only 62, 89 and 89% of the total prescriptions. Fifty percent did not carry the duration and mean duration of prescription was 17.75 ± 24.18 days. Signature, name, designation, address, stamp and medical registration number of the physician was mentioned only in 96.7, 7.3, 6.7, 2.7, 0.7 and 0% of the prescriptions respectively.

Conclusion

The study has brought out the need for sensitization and awareness programes for doctors to improve the quality of prescription-writing and periodic review of prescriptions.

How to cite this article

Siddharth V, Arya S, Gupta SK. A Study of Prescribing Practices in Outpatient Department of an Apex Tertiary Care Institute of India. Int J Res Foundation Hosp Healthc Adm 2014;2(1):31-35.
Ice particle habit and surface roughness derived from PARASOL polarization measurements
Authors: Cole B. H. , Yang P. , Baum B. A. , Riedi J. , C.-Labonnote L.
Published: April 2014

Abstract. Ice clouds are an important element in the radiative balance of the earth's climate system, but their microphysical and optical properties still are not well constrained, especially ice particle habit and the degree of particle surface roughness. In situ observations have revealed common ice particle habits and evidence for surface roughness, but these observations are limited. An alternative is to infer the ice particle shape and surface roughness from satellite observations of polarized reflectivity since they are sensitive to both particle shape and degree of surface roughness. In this study an adding–doubling radiative transfer code is used to simulate polarized reflectivity for nine different ice habits and one habit mixture, along with 17 distinct levels of the surface roughness. A lookup table (LUT) is constructed from the simulation results and used to infer shape and surface roughness from PARASOL satellite polarized reflectivity data over the ocean. Globally, the retrievals yield a compact aggregate of columns as the most commonly retrieved ice habit. Analysis of PARASOL data from the tropics results in slightly more aggregates than in midlatitude or polar regions. Some level of surface roughness is inferred in nearly 70% of PARASOL data, with mean and median roughness near σ = 0.2 and 0.15, respectively. Tropical region analyses have 20% more pixels retrieved with particle surface roughness than in midlatitude or polar regions. The global asymmetry parameter inferred at a wavelength of 0.865 μm has a mean value of 0.77 and a median value of 0.75.
Comparing the cloud vertical structure derived from several methods based on measured atmospheric profiles and active surface measurements
Authors: Costa-Surós M. , Calbó J. , González J. A. , Long C. N.
Published: April 2014

Abstract. The cloud vertical distribution and especially the cloud base height, which is linked to cloud type, is an important characteristic in order to describe the impact of clouds on climate. In this work several methods to estimate the cloud vertical structure (CVS) based on atmospheric sounding profiles are compared, considering number and position of cloud layers, with a ground based system which is taken as a reference: the Active Remote Sensing of Clouds (ARSCL). All methods establish some conditions on the relative humidity, and differ on the use of other variables, the thresholds applied, or the vertical resolution of the profile. In this study these methods are applied to 193 radiosonde profiles acquired at the ARM Southern Great Plains site during all seasons of year 2009 and endorsed by GOES images, to confirm that the cloudiness conditions are homogeneous enough across their trajectory. The perfect agreement (i.e. when the whole CVS is correctly estimated) for the methods ranges between 26–64%; the methods show additional approximate agreement (i.e. when at least one cloud layer is correctly assessed) from 15–41%. Further tests and improvements are applied on one of these methods. In addition, we attempt to make this method suitable for low resolution vertical profiles, like those from the outputs of reanalysis methods or from the WMO's Global Telecommunication System. The perfect agreement, even when using low resolution profiles, can be improved up to 67% (plus 25% of approximate agreement) if the thresholds for a moist layer to become a cloud layer are modified to minimize false negatives with the current data set, thus improving overall agreement.