Fixed Monthly versus Less Frequent Ranibizumab Dosing and Predictors of Visual Response in Exudative Age-Related Macular Degeneration

Purpose. To examine temporal patterns of visual acuity (VA) response to pooled 0.3 mg/0.5 mg ranibizumab treatment in patients with age-related macular degeneration and identify potential baseline predictors of response. Design. Retrospective analysis. Methods. Results from 1824 ranibizumab-treated patients receiving fixed monthly, quarterly, or as-needed dosing after three monthly loading doses in four phase III/IIIb trials (ANCHOR, MARINA, PIER, and SAILOR) were analyzed. Results. At month 3, 14.9% to 29.4% of patients had gained ≥15 letters. Not all patients achieved peak gains at month 3; many continued to have VA increases throughout treatment. After three monthly loading doses, continued monthly dosing resulted in further gains, as there were more delayed 15-letter responders at month 12 (14.7–16.1%) than with less frequent dosing (5.0–6.0%). Monthly dosing also resulted in more patients maintaining VA gains at later time points. Early 15-letter responders had lower baseline mean VA than delayed 15-letter responders in ANCHOR and MARINA; no other differences in baseline characteristics were noted. Conclusions. Although some patients have rapid improvements in VA, others do not experience peak VA until later during treatment. Continued monthly dosing resulted in a greater percentage of patients gaining ≥15 letters than with switching to less frequent dosing regimens

Transferring management practices to China: a Bourdieusian critique of ethnocentricity

This paper provides a critique of the emergent theories of human resource management in China with a view to generating new theoretical insights with particular reference to Pierre Bourdieu's social theory. It reassesses the relevance of the orthodox critique of ethnocentricity and the coherence of approaches embedded in Chinese culture. With reference to six case studies of the largest retail firms, we identify two key challenges: the reliance on headquarter human resource practices that reflect an ethnocentric ethos, i.e. country-of-origin bias, and the failure to empower local managers and the problems this creates for managers expected to implement ethnocentric practices. We examine how Bourdieu's social theory sheds light on the processes by which these firms realise their strategic objectives through the complicity of local managers whose scope for resistance is constrained by the use of normative control and in part through attractive remuneration and career prospects that generate Bourdieusian capital for these managers. We conclude with some suggestions for further research

Immune Enhancement of Skin Carcinogenesis by CD4+ T Cells

In a transgenic model of multi-stage squamous carcinogenesis induced by human papillomavirus (HPV) oncogenes, infiltrating CD4+ T cells can be detected in both premalignant and malignant lesions. The lymph nodes that drain sites of epidermal neoplasia contain activated CD4+ T cells predominantly reactive toward Staphylococcal bacterial antigens. HPV16 mice deficient in CD4+ T cells were found to have delayed neoplastic progression and a lower incidence of tumors. This delay in carcinogenesis is marked by decreased infiltration of neutrophils, and reduced activity of matrix metalloproteinase-9, an important cofactor for tumor progression in this model. The data reveal an unexpected capability of CD4 T cells, whereby, proinflammatory CD4+ T cells, apparently responding to bacterial infection of dysplastic skin lesions, can inadvertently enhance neoplastic progression to invasive cancer

The New York City Principals Pandemic Flu Survey: Are Schools Prepared?

It will be only a matter of time before another influenza pandemic occurs. Pandemic flu refers to a novel human influenza virus that causes a global outbreak, or pandemic. Researchers cannot accurately predict the timing, severity, or source of the next pandemic, but are certain it would present a myriad of issues for the public health infrastructures of our local communities. In the case of a pandemic flu outbreak, daily routine would be interrupted and school administrators would have many challenges to face. School principals in particular serve a unique role in their communities -- they are the link between their schools and the outside world, as well as a means of communication between these two sectors. It is important for individuals in this role to be seen as a clear and constant channel of communication at all times, especially during an emergency. In October of 2006, researchers from the National Center for Disaster Preparedness (NCDP), in coordination with the New York City (NYC) based Council of School Supervisors and Administrators (CSA), conducted a web based survey of NYC school principals to gauge their level of preparedness and to address the concern of principals for the many consequences that may arise for their schools if a pandemic flu outbreak is to occur. 330 of the 1260 principals responded (26.2%). Among key findings were the following: 1) 84.1% of principals did not have a pandemic flu plan; 2) Among the few schools with a plan, four out of five principals were not familiar with it; 3) The overwhelming majority of principals said their school had no process for talking with parents, and few have been involved in community level planning efforts. Schools are a resource to the safety of the community, and the well-being of schools and the community are inexorably intertwined. Recommendations for the future center on the need for schools and communities to work together to prepare for pandemic flu, as well as other emergencies. Other important recommendations include improving upon the role of the principal as a risk communicator and integrating the pandemic flu plan into the school's existing safety plan

Taxon-specific multiplex-PCR for quick, easy, and accurate identification of encyrtid and aphelinid parasitoid species attacking soft scale insects in California citrus groves

Citricola scale, Coccus pseudomagnoliarum Kuwana (Hemiptera: Coccidae), is a serious pest of citrus in California's San Joaquin Valley, but not in southern California where a complex of Metaphycus spp. Mercet (Hymenoptera: Encyrtidae) suppress it. This has created interest in using these (and other Metaphycus) species for biological control in the San Joaquin Valley. A critical step in assessing an organism's potential for biological control is the ability to accurately identify it. For Metaphycus spp., this currently requires slide mounted adult specimens and expert taxonomic knowledge. We present a simple, quick and accurate method to identify any life stage of the ten major parasitoids of soft scales in California citrus, based on amplification of ribosomal DNA, using the polymerase chain reaction (PCR). Three multiplex-PCR protocols amplify products of taxon-specific sizes, allowing direct diagnosis of taxa accommodated by the PCR, and reducing identification time to a fraction of that of existing methods

Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia

BACKGROUND: Most patients with familial primary pulmonary hypertension have defects in the gene for bone morphogenetic protein receptor II (BMPR2), a member of the transforming growth factor beta (TGF-beta) superfamily of receptors. Because patients with hereditary hemorrhagic telangiectasia may have lung disease that is indistinguishable from primary pulmonary hypertension, we investigated the genetic basis of lung disease in these patients. METHODS: We evaluated members of five kindreds plus one individual patient with hereditary hemorrhagic telangiectasia and identified 10 cases of pulmonary hypertension. In the two largest families, we used microsatellite markers to test for linkage to genes encoding TGF-beta-receptor proteins, including endoglin and activin-receptor-like kinase 1 (ALK1), and BMPR2. In subjects with hereditary hemorrhagic telangiectasia and pulmonary hypertension, we also scanned ALK1 and BMPR2 for mutations. RESULTS: We identified suggestive linkage of pulmonary hypertension with hereditary hemorrhagic telangiectasia on chromosome 12q13, a region that includes ALK1. We identified amino acid changes in activin-receptor-like kinase 1 that were inherited in subjects who had a disorder with clinical and histologic features indistinguishable from those of primary pulmonary hypertension. Immunohistochemical analysis in four subjects and one control showed pulmonary vascular endothelial expression of activin-receptor-like kinase 1 in normal and diseased pulmonary arteries. CONCLUSIONS: Pulmonary hypertension in association with hereditary hemorrhagic telangiectasia can involve mutations in ALK1. These mutations are associated with diverse effects, including the vascular dilatation characteristic of hereditary hemorrhagic telangiectasia and the occlusion of small pulmonary arteries that is typical of primary pulmonary hypertension

Single Cell RNA Sequencing Identifies HSPG2 and APLNR as Markers of Endothelial Cell Injury in Systemic Sclerosis Skin

Objective: The mechanisms that lead to endothelial cell (EC) injury and propagate the vasculopathy in Systemic Sclerosis (SSc) are not well understood. Using single cell RNA sequencing (scRNA-seq), our goal was to identify EC markers and signature pathways associated with vascular injury in SSc skin.Methods: We implemented single cell sorting and subsequent RNA sequencing of cells isolated from SSc and healthy control skin. We used t-distributed stochastic neighbor embedding (t-SNE) to identify the various cell types. We performed pathway analysis using Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA). Finally, we independently verified distinct markers using immunohistochemistry on skin biopsies and qPCR in primary ECs from SSc and healthy skin.Results: By combining the t-SNE analysis with the expression of known EC markers, we positively identified ECs among the sorted cells. Subsequently, we examined the differential expression profile between the ECs from healthy and SSc skin. Using GSEA and IPA analysis, we demonstrated that the SSc endothelial cell expression profile is enriched in processes associated with extracellular matrix generation, negative regulation of angiogenesis and epithelial-to-mesenchymal transition. Two of the top differentially expressed genes, HSPG2 and APLNR, were independently verified using immunohistochemistry staining and real-time qPCR analysis.Conclusion: ScRNA-seq, differential gene expression and pathway analysis revealed that ECs from SSc patients show a discrete pattern of gene expression associated with vascular injury and activation, extracellular matrix generation and negative regulation of angiogenesis. HSPG2 and APLNR were identified as two of the top markers of EC injury in SSc