Topical prostaglandin analogues and conjunctival inflammation in uveitic glaucoma.

A pilot study to determine whether topical prostaglandin analogues alter the expression of conjunctival inflammatory markers in patients with uveitic glaucoma.Prospective, single-masked case series of 20 patients with uveitis and secondary raised intraocular pressure. Participants were divided into four groups of five patients dependent on their use of topical medication: (1) prostaglandin analogues only, (2) corticosteroids only, (3) both prostaglandin analogues and corticosteroids, (4) no topical medication. Conjunctival cells were harvested by impression cytology and were examined for inflammatory markers (CD3, CD54, HLA-DR, CCR4, CCR5) by flow cytometry. A tear fluid sample was also examined for inflammatory cytokines (IL-12p70, IL-2, IL-10, IL-8, IL-6, IL-4, IL-5, IFN-gamma, IL-1beta, IFN-alpha, IFN-beta) by multiplex bead arrays.All groups demonstrated increased markers of conjunctival inflammation. There was no significant difference in levels of any inflammatory markers between the four groups, suggesting that the use of topical prostaglandin analogues does not increase conjunctival levels of inflammation beyond those already seen in uveitis.The use of topical prostaglandins does not appear to induce conjunctival inflammation over that which is already present in patients with uveitic glaucoma. This supports the use of topical prostaglandin analogues in patients with uveitic glaucoma, indicating that their use is unlikely to adversely affect subsequent glaucoma filtration surgery through the induction of chronic conjunctival inflammation

Treatment of Retinitis Pigmentosa-Associated Cystoid Macular Oedema Using Intravitreal Aflibercept (Eylea) despite Minimal Response to Ranibizumab (Lucentis): A Case Report.

BACKGROUND: We present an interesting case of bilateral retinitis pigmentosa (RP)-associated cystoid macular oedema that responded on two separate occasions to intravitreal injections of aflibercept, despite previously demonstrating only minimal response to intravitreal ranibizumab. This unique case would support a trial of intravitreal aflibercept for the treatment of RP-associated cystoid macular oedema. CASE PRESENTATION: A 38-year-old man from Dubai, United Arab Emirates, presented to the UK with a 3-year history of bilateral RP-associated cystoid macular oedema. Previous treatment with topical dorzolamide, oral acetazolamide, and intravitreal ranibizumab had demonstrated only minimal reduction of cystoid macular oedema. Following re-confirmation of the diagnosis by clinical examination and optical coherence tomography imaging, bilateral loading doses of intravitreal aflibercept were given. Central macular thickness reduced and the patient returned to Dubai. After 6 months, the patient was treated with intravitreal ranibizumab due to re-accumulation of fluid and the unavailability of aflibercept in Dubai. Only minimal reduction of central macular thickness was observed. Once available in Dubai, intravitreal aflibercept was administered bilaterally with further reduction of central macular thickness observed. Visual acuity remained stable throughout. CONCLUSIONS: This is the first case report to demonstrate a reduction of RP-associated CMO following intravitreal aflibercept, despite inadequate response to ranibizumab on two separate occasions. Aflibercept may provide superior action to other anti-VEGF medications due to its intermediate size (115 kDa) and higher binding affinity. This is worthy of further investigation in a large prospective cohort over an extended time to determine the safety and efficacy of intravitreal aflibercept for use in this condition

Elastomeric porous poly(glycerol sebacate) methacrylate (PGSm) microspheres as 3D scaffolds for chondrocyte culture and cartilage tissue engineering

Cartilage defects can be difficult to treat; therefore, tissue engineering of cartilage is emerging as a promising potential therapy. One interesting area of research explores the delivery of cells to the cartilage defect via scaffold-based cell delivery vehicles and microsurgery. This study explores the use of novel poly(glycerol sebacate) methacrylate (PGSm)-polymerised high internal phase emulsion (polyHIPE) microspheres as scaffolds with embedded cells for cartilage tissue engineering. Porous microsphere scaffolds (100 µm–1 mm diameter) were produced from emulsions consisting of water and a methacrylate-based photocurable resin of poly(glycerol sebacate). These resins were used in conjunction with a T-junction fluidic device and an ultraviolet (UV) curing lamp to produce porous microspheres with a tuneable size. This technique produced biodegradable PGSm microspheres with similar mechanical properties to cartilage. We further explore these microspheres as scaffolds for three-dimensional culture of chondrocytes. The microspheres proved to be very efficient scaffolds for primary chondrocyte culture and were covered by a dense extracellular matrix (ECM) network during the culture period, creating a tissue disk. The presence of glycosaminoglycans (GAGs) and collagen-II was confirmed, highlighting the utility of the PGSm microspheres as a delivery vehicle for chondrocytes. A number of imaging techniques were utilised to analyse the tissue disk and develop methodologies to characterise the resultant tissue. This study highlights the utility of porous PGSm microspheres for cartilage tissue engineering

Chronic Fatigue Syndrome – A clinically empirical approach to its definition and study

BACKGROUND: The lack of standardized criteria for defining chronic fatigue syndrome (CFS) has constrained research. The objective of this study was to apply the 1994 CFS criteria by standardized reproducible criteria. METHODS: This population-based case control study enrolled 227 adults identified from the population of Wichita with: (1) CFS (n = 58); (2) non-fatigued controls matched to CFS on sex, race, age and body mass index (n = 55); (3) persons with medically unexplained fatigue not CFS, which we term ISF (n = 59); (4) CFS accompanied by melancholic depression (n = 27); and (5) ISF plus melancholic depression (n = 28). Participants were admitted to a hospital for two days and underwent medical history and physical examination, the Diagnostic Interview Schedule, and laboratory testing to identify medical and psychiatric conditions exclusionary for CFS. Illness classification at the time of the clinical study utilized two algorithms: (1) the same criteria as in the surveillance study; (2) a standardized clinically empirical algorithm based on quantitative assessment of the major domains of CFS (impairment, fatigue, and accompanying symptoms). RESULTS: One hundred and sixty-four participants had no exclusionary conditions at the time of this study. Clinically empirical classification identified 43 subjects as CFS, 57 as ISF, and 64 as not ill. There was minimal association between the empirical classification and classification by the surveillance criteria. Subjects empirically classified as CFS had significantly worse impairment (evaluated by the SF-36), more severe fatigue (documented by the multidimensional fatigue inventory), more frequent and severe accompanying symptoms than those with ISF, who in turn had significantly worse scores than the not ill; this was not true for classification by the surveillance algorithm. CONCLUSION: The empirical definition includes all aspects of CFS specified in the 1994 case definition and identifies persons with CFS in a precise manner that can be readily reproduced by both investigators and clinicians

Evaluating Forecasting Methods

Ideally, forecasting methods should be evaluated in the situations for which they will be used. Underlying the evaluation procedure is the need to test methods against reasonable alternatives. Evaluation consists of four steps: testing assumptions, testing data and methods, replicating outputs, and assessing outputs. Most principles for testing forecasting methods are based on commonly accepted methodological procedures, such as to prespecify criteria or to obtain a large sample of forecast errors. However, forecasters often violate such principles, even in academic studies. Some principles might be surprising, such as do not use R-square, do not use Mean Square Error, and do not use the within-sample fit of the model to select the most accurate time-series model. A checklist of 32 principles is provided to help in systematically evaluating forecasting methods

Complementarities between IT and Organizational Structure: The Role of Corporate Exploration and Exploitation

The decentralization of organizational decision authority has been shown to be complementary to Information Technology (IT) in prior research. We draw from the information processing view of organizations, the IT and de/centralization debate, and organizational learning theory to argue that IT payoffs can also be improved by greater centralization of decision authority, contingent on a firm’s corporate learning type. We argue that an exploratory learning type is best pursued with a decentralized organization design, while an exploitative learning type requires a centralized organization design. We hypothesize that under corporate exploration, IT payoffs are enhanced through greater decentralization, whereas under corporate exploitation, returns to IT are improved by greater centralization. Our study uses a novel multi‐source panel on the IT capital, the degree of de/centralization, and the performance of almost 260 German manufacturing firms. We estimate production functions to assess the contribution of combning IT with de/centralization to firmlevel productivity under different corporate learning types. Our results strongly support our hypotheses and hold up to a variety of robustness tests

The clinical utility of new combination phenylephrine/ketorolac injection in cataract surgery

Lola Elizabeth Lawuyi, Avinash Gurbaxani Moorfields Eye Hospital Dubai, Dubai, UAE Abstract: The maintenance of mydriasis throughout cataract extraction surgery and the control of ocular inflammation are crucial for successful surgical outcomes. The development of miosis during cataract surgery compromises the visualization of the surgical field and working space for surgeons. This may lead to complications that include posterior capsular tear and associated vitreous loss, longer surgical time, and postoperative inflammation. Postoperative inflammation is often uncomfortable and frustrating for patients. It causes pain, redness, and photophobia. This compromises the best-uncorrected vision following surgery and often leads to multiple clinic visits. This article examines the literature published on the current treatments used to manage mydriasis, pain, and inflammation in cataract extraction surgery. Combination phenylephrine/ketorolac injection offers an exciting new class of medication for use in cataract surgery. With the recent approval of Omidria™ (combination of phenylephrine 1% and ketorolac 0.3%) by the US Food and Drug Administration (FDA) for intraocular use, we review the clinical utility of this new combination injection in cataract surgery. PubMed, MEDLINE, and conference proceedings were searched for the relevant literature using a combination of the following search terms: cataract extraction surgery, pupil dilation (mydriasis), miosis, phenylephrine, ketorolac, Omidria™, intracameral mydriatic. Relevant articles were reviewed and their references checked for further relevant literature. All abstracts were reviewed and full texts retrieved where available. Keywords: cataract extraction surgery, ketorolac, mydriasis, miosis, Omidria™, phenylephrin