Outcomes of 23-gauge pars plana vitrectomy in combined scleral buckling and vitrectomy for complex rhegmatogenous retinal detachments

Rhegmatogenous retinal detachments associated with proliferative vitreoretinopathy, giant retinal tears, ocular trauma, proliferative diabetic retinopathy, or necrotizing retinitis are considered more complex than those without these factors. The aim of the current review is to address the surgical outcomes and complications of 23-gauge pars plana vitrectomy with scleral buckling (23GPPV/SB) for repair of these complex retinal detachments. This retrospective study involved 54 eyes of 53 patients who underwent 23GPPV/SB between July 2007 and September 2009. Preoperative diagnosis, surgical technique, preoperative and postoperative visual acuities, intraoperative and postoperative complications, and anatomic reattachment rates were examined. Fifty-four eyes of 53 patients were reviewed in this study and indications for surgery varied. Mean logarithm of the minimal angle of resolution (logMAR) pre- and post-operative visual acuities were 1.166 (20/293) and 0.780 (20/120), respectively, which led to a statistically significant improvement in logMAR (P=0.0165). Single operation and final reattachment rates were 87% (47 of 54 eyes) and 100%, respectively. Postoperative complications included choroidal effusion/hemorrhage (14.8%, 8 of 54 eyes) and vitreous hemorrhage (11.1%, 6 of 54 eyes). Other more infrequent complications included hyphema (9.3%, 5 of 54 eyes), hypotony (5.6%, 3 of 54 eyes) and ocular hypertension > 35 mmHg (3.7%, 2 of 54 eyes). A total of 31.5% (17 of 54 eyes) of patients had a complication in the postoperative time period, but 58.8% of these resolved spontaneously without requiring an intervention. 23GPPV/SB may be considered for complex retinal detachment repair with good anatomic reattachment rates, but with relatively high complication rates

Tumor Growth Enhances Cross-Presentation Leading to Limited T Cell Activation without Tolerance

Using a tumor model of spontaneously arising insulinomas expressing a defined tumor-associated antigen, we investigated whether tumor growth promotes cross-presentation and tolerance of tumor-specific T cells. We found that an advanced tumor burden enhanced cross-presentation of tumor-associated antigens to high avidity tumor-specific T cells, inducing T cell proliferation and limited effector function in vivo. However, contrary to other models, tumor-specific T cells were not tolerized despite a high tumor burden. In fact, in tumor-bearing mice, persistence and responsiveness of adoptively transferred tumor-specific T cells were enhanced. Accordingly, a potent T cell–mediated antitumor response could be elicited by intravenous administration of tumor-derived peptide and agonistic anti-CD40 antibody or viral immunization and reimmunization. Thus, in this model, tumor growth promotes activation of high avidity tumor-specific T cells instead of tolerance. Therefore, the host remains responsive to T cell immunotherapy

Big Data and AI – A transformational shift for government: So, what next for research?

Big Data and artificial intelligence will have a profound transformational impact on governments around the world. Thus, it is important for scholars to provide a useful analysis on the topic to public managers and policymakers. This study offers an in-depth review of the Policy and Administration literature on the role of Big Data and advanced analytics in the public sector. It provides an overview of the key themes in the research field, namely the application and benefits of Big Data throughout the policy process, and challenges to its adoption and the resulting implications for the public sector. It is argued that research on the subject is still nascent and more should be done to ensure that the theory adds real value to practitioners. A critical assessment of the strengths and limitations of the existing literature is developed, and a future research agenda to address these gaps and enrich our understanding of the topic is proposed

A Threshold Model for T-Cell Activation in the Era of Checkpoint Blockade Immunotherapy

Continued discoveries of negative regulators of inflammatory signaling provide detailed molecular insights into peripheral tolerance and anti-tumor immunity. Accumulating evidence indicates that peripheral tolerance is maintained at multiple levels of immune responses by negative regulators of proinflammatory signaling, soluble anti-inflammatory factors, inhibitory surface receptors & ligands, and regulatory cell subsets. This review provides a global overview of these regulatory machineries that work in concert to maintain peripheral tolerance at cellular and host levels, focusing on the direct and indirect regulation of T cells. The recent success of checkpoint blockade immunotherapy (CBI) has initiated a dramatic shift in the paradigm of cancer treatment. Unprecedented responses to CBI have highlighted the central role of T cells in both anti-tumor immunity and peripheral tolerance and underscored the importance of T cell exhaustion in cancer. We discuss the therapeutic implications of modulating the negative regulators of T cell function for tumor immunotherapy with an emphasis on inhibitory surface receptors & ligands—central players in T cell exhaustion and targets of checkpoint blockade immunotherapies. We then introduce a Threshold Model for Immune Activation—the concept that these regulatory mechanisms contribute to defining a set threshold of immunogenic (proinflammatory) signaling required to elicit an anti-tumor or autoimmune response. We demonstrate the value of the Threshold Model in understanding clinical responses and immune related adverse events in the context of peripheral tolerance, tumor immunity, and the era of Checkpoint Blockade Immunotherapy

Reading Disability as a Condition of Family Stability

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72295/1/j.1545-5300.1964.00066.x.pd

Changing relationships between multinational companies and their host regions? A case study of Aberdeen and the international oil industry

There has been a revival of interest in recent years in the relationships between multinational corporations (hereafter MNCs) and the host regions in which they operate. The branch plant thesis which generally views inward investment by MNCs in a negative light - as reinforcing power relations between core and peripheral regions - has been challenged, with the suggestion that such developments can play a key role in linking up local economies to important flows of knowledge and information in a global economy. It has also been suggested that MNC branch plant activities are in practice often upgraded over time, leading to the development of important competitive advantage's for host regions. In this paper, such claims are investigated through a case study of the Aberdeen oil region in the north east of Scotland. The changing position of Aberdeen within the oil industry's corporate division of labour is evaluated in terms of the wider theoretical debate

Antigen loading of MHC class I molecules in the endocytic tract

Major histocompatibility complex (MHC) class I molecules bind antigenic peptides that are translocated from the cytosol into the endoplasmic reticulum by the transporter associated with antigen processing. MHC class I loading independent of this transporter also exists and involves peptides derived from exogenously acquired antigens. Thus far, a detailed characterization of the intracellular compartments involved in this pathway is lacking. In the present study, we have used the model system in which peptides derived from measles virus protein F are presented to cytotoxic T cells by B-lymphoblastoid cells that lack the peptide transporter. Inhibition of T cell activation by the lysosomotropic drug ammoniumchloride indicated that endocytic compartments were involved in the class I presentation of this antigen. Using immunoelectron microscopy, we demonstrate that class I molecules and virus protein F co-localized in multivesicular endosomes and lysosomes. Surprisingly, these compartments expressed high levels of class II molecules, and further characterization identified them as MHC class II compartments. In addition, we show that class I molecules co-localized with class II molecules on purified exosomes, the internal vesicles of multivesicular endosomes that are secreted upon fusion of these endosomes with the plasma membrane. Finally, dendritic cells, crucial for the induction of primary immune responses, also displayed class I in endosomes and o

Single-cell resolution imaging of retinal ganglion cell apoptosis in vivo using a cell-penetrating caspase-activatable peptide probe

Peptide probes for imaging retinal ganglion cell (RGC) apoptosis consist of a cell-penetrating peptide targeting moiety and a fluorophore-quencher pair flanking an effector caspase consensus sequence. Using ex vivo fluorescence imaging, we previously validated the capacity of these probes to identify apoptotic RGCs in cell culture and in an in vivo rat model of N-methyl- D-aspartate (NMDA)-induced neurotoxicity. Herein, using TcapQ488, a new probe designed and synthesized for compatibility with clinically-relevant imaging instruments, and real time imaging of a live rat RGC degeneration model, we fully characterized time- and dose-dependent probe activation, signal-to-noise ratios, and probe safety profiles in vivo. Adult rats received intravitreal injections of four NMDA concentrations followed by varying TcapQ488 doses. Fluorescence fundus imaging was performed sequentially in vivo using a confocal scanning laser ophthalmoscope and individual RGCs displaying activated probe were counted and analyzed. Rats also underwent electroretinography following intravitreal injection of probe. In vivo fluorescence fundus imaging revealed distinct single-cell probe activation as an indicator of RGC apoptosis induced by intravitreal NMDA injection that corresponded to the identical cells observed in retinal flat mounts of the same eye. Peak activation of probe in vivo was detected 12 hours post probe injection. Detectable fluorescent RGCs increased with increasing NMDA concentration; sensitivity of detection generally increased with increasing TcapQ488 dose until saturating at 0.387 nmol. Electroretinography following intravitreal injections of TcapQ488 showed no significant difference compared with control injections. We optimized the signal-to-noise ratio of a caspase-activatable cell penetrating peptide probe for quantitative non-invasive detection of RGC apoptosis in vivo. Full characterization of probe performance in this setting creates an important in vivo imaging standard for functional evaluation of future probe analogues and provides a basis for extending this strategy into glaucoma-specific animal models