Rate of Diabetic Vitrectomy in a Defined Geographical Part of North East England

Purpose: To assess the yearly incidence of vitrectomy for proliferative diabetic retinopathy (PDR) over an 11-year period, in a geographically defined part of North East England. The time period covered the introduction of diabetic retinopathy screening. Methods: All patients undergoing vitrectomy for diabetic retinopathy in the Sunderland and South Tyneside area were recorded from 2000 to 2010. Incidence rates of vitrectomy specifically for the complications of PDR for the observed diabetic population, the estimated diabetic population and the population with known PDR were calculated. Results: There was a gradual and significant decline in the vitrectomy rate from 157 (95% confidence interval, CI, 135–187) to 103 (95% CI 98–109) per 100,000 of the observed diabetic population in 2000 and 2010 respectively. The rate in the estimated diabetic population showed no significant change at 68 (95% CI 48–87) in 2002 and 77 (95% CI 55–103) in 2010. The rate in the PDR population, which comprised 2.4% of the known diabetic population in 2002 and 1.8% in 2010, declined significantly from 7.7% in 2002 to 5.7% in 2010. Conclusion: This study evaluated vitrectomy rates for PDR in an area of North East England. There were apparent declining rates of vitrectomy for PDR following the introduction of diabetic retinopathy screening but these have to be interpreted in the light of several confounding factors

Disentangling and quantifying contributions of distinct forcing factors to the observed global sea level pressure field

Variations of the global sea level pressure (SLP) field reflect atmospheric and oceanic influences and have a profound influence on temperature, precipitation and the global carbon cycle. The impact of various forcing factors on this field was investigated mainly based on numerical simulations. Alternatively, here we identify and quantify the influences of various forcing factors on observational, reanalysis and simulated SLP fields. By applying canonical correlation analysis (CCA) on the aforementioned data sets, we separated and quantified the impact of increase CO2 concentration, El Ni\~o--Southern Oscillation (ENSO), Atlantic Multidecadal Oscillation (AMO), Arctic Oscillation (AO) and solar forcing on the global SLP field, based on their associations with known footprints on the sea surface temperature (SST). Together, their corresponding SLP spatial structures explainþinspace~þinspace60% of the observed variance. Whereas the atmospheric CO2 concentration has the most prominent impact on the global SLP field, explaining 28% of variance, ENSO and AO account for 9% each. The solar forcing and AMO explain 7%, respectively 6% of global SLP variance. Similar spatial structures corresponding to the same forcing factors are identified based on the reanalysis SLP data. CCA applied on simulated SLP fields derived from six CMIP5 model simulations captures only the spatial structures of atmospheric CO2 concentration, ENSO, AAO and AO. Such a decomposition of the global pressure field based on a linear combination of coupled SST-SLP pairs provide a reference against which one could validate the performance of general circulation models in simulating the lower atmosphere dynamics

An association study of PITX2 polymorphism in a cohort of patients with primary open angle glaucoma and considerations on the genetics of glaucoma

Background: Glaucoma is a major cause of blindness world-wide. There is a need for methods to identify individuals at risk of developing glaucoma, so that early treatment can prevent visual loss. Genetic screening tests offer the prospect of pre-symptomatic diagnosis of at risk individuals. There is now strong evidence that a number of different genes are associated with glaucoma susceptibility. Mutations in the PITX2 homeobox transcription factor gene disrupt normal development of the anterior segment and cause overt structural abnormalities. It is possible that, as yet undetected mutations/polymorphisms in PITX2 may produce subtle and undetected abnormalities in anterior segment structure and function that could predispose to glaucoma. Purpose: The aim of this thesis is two fold: 1. Screening for the presence of single nucleotide polymorphisms in PITX2 gene in a cohort of 100 unrelated primary open angle glaucoma/ ocular hypertension patients, 10 Posterior embryotoxon subjects and 100 age and ethnically matched controls to establish the mutation spectrum. 2. Identification, phenotyping and recruitment for genetic studies of primary open angle glaucoma patients with strong family history of glaucoma. Materials and methods: 1. 100 primary open angle glaucoma patients and 60 age and ethnically matched controls were enrolled in the study. Patients and controls were phenotyped and a blood sample for DNA extraction collected. PITX2 exon-specific primers were used to PCR amplify patient and control DNA. Direct sequencing was used to screen for sequence alterations in the entire coding sequence of PITX2 gene. Concurrently, polymorphic sites reported in the PITX2 gene were identified from the NCBI and Ensemble databases and the frequency of polymorphic sites was investigated. The SHEsis and UNPHASED software packages were used for statistical analysis. 2. Patients diagnosed with glaucoma and strong family history were identified from Glaucoma Unit at Sunderland Eye Infirmary, phenotyped and enrolled in the study. The pedigrees were constructed and interested relatives enrolled in the study and phenotyped. A sample of blood for DNA extraction was collected from all people enrolled in the study. Results: 1. Direct sequencing did not identify any sequence variation in the coding region. 26 PITX2 polymorphic sites were identified from the internet databases, including five in the coding sequence. Sixteen non coding SNPs were confirmed within our study group and SNP frequencies were examined. None of the coding sequence SNPs was identified in our cohort, demonstrating a high degree of sequence conservation. Also, none of the SNPs confirmed in this study group showed an increased frequency in the primary open angle glaucoma group compared with the control group. 2. Thirty-three pedigrees were identified with strong family of glaucoma during the time allowed for patient recruitment. Of these, twenty-two agreed to take part in the study. Thirteen pedigrees are presented in this study, mostly demonstrating autosomal dominant inheritance. Conclusion: There is ample evidence to suggest that genetics play an important role in unravelling the pathogenesis of glaucoma. Identification and recruitment of patients for genetic studies is an essential step and the role of the clinician in this process is paramount. Also, developmental glaucoma genes are an important group of genes to be screened in primary open angle glaucoma/ocular hypertension patients, as they may play a role in the pathogenesis of this preventable blinding disease.EThOS - Electronic Theses Online ServiceRoyal College of Surgeons, Edinburgh : Glaucoma Research and Development at Sunderland (GRAD@S) fund : Pfizer OphthalmicGBUnited Kingdo

Visual and refractive outcome of one-site phacotrabeculectomy compared with temporal approach phacoemulsification

Background We aimed to compare visual and refractive outcome following phacoemulsification and intraocular lens implant (IOL) and combined one-site phacotrabeculectomy. Method We performed a retrospective study of case records of patients who had temporal incision phacoemulsification with IOL or one-site phacotrabeculectomy, between June 1997 and June 2001. The patients were matched for age group, operating list and IOL type. All patients were operated on under local anesthesia by the same surgeon. Each arm of the study had 90 patients, age range 60 to 75 years. We collected pre- and postoperative visual acuity, pre- and postoperative refraction within six months after surgery, and intended refraction. The intraocular pressure control was not recorded, as it was not the aim of our study. Results In the phacotrabeculectomy group, 76.6% of patients achieved aimed spherical equivalent, 15.5% of patients had against-the-rule (ATR) astigmatism induced by the surgery, and 90% of the patients had best corrected visual acuity (BCVA) more than 6/12. In the temporal incision phacoemulsification group, 81.1% of patients achieved aimed spherical equivalent, 10% of the patients had induced ATR by the surgery and 95.55% of patients achieved BCVA more than 6/12. Conclusion In this study the visual outcome of the phacotrabeculectomy group did not differ significantly from the visual outcome of temporal approach phacoemulsification

Examining the Eastern European extreme summer temperatures of 2023 from a long-term perspective: the role of natural variability vs. anthropogenic factors

Amidst unprecedented rising global temperatures, this study investigates the historical context of heat wave (HW) events in Eastern Europe. The record-breaking 2023 summer, featuring a HW lasting for 19 d in the southeastern part of Romania, extending up to Ukraine, necessitates a deeper understanding of past extreme events. Utilizing statistical methods on long-term station data spanning from 1885 to 2023, we aim to detect and analyze historical HWs, particularly focusing on events predating 1960. This extended time frame allows for a more comprehensive assessment of noteworthy extremes compared to recent decades. We used both a percentile-based threshold and a fixed absolute temperature threshold to identify HW events. Our analysis identifies two critical periods with increased HW frequency and intensity: 1920-1965 and 1980-2023, respectively, highlighting the most extreme events in August 1946, August 1952, July 2012, June 2019, and August 2023. Furthermore, reanalysis data show that historical HWs, similar to the 2023 event, were associated with large-scale European heat extremes linked to high-pressure systems, and they were accompanied by extreme drought, thus leading to compound extreme events. We find that while a clear trend emerges towards more frequent HWs from the 1980s onward, the analysis also uncovers substantial HW activity on daily timescales throughout the 1885-1960 period. Moreover, we highlight the intertwined impacts of climate change and multidecadal internal variability on HW patterns, with evidence suggesting that both contribute to the increasing frequency and intensity of these extreme events. Attribution analysis reveals that the extreme summer temperatures observed in 2023 would not have been possible in the absence of anthropogenic climate change. Regardless of future warming levels, such temperatures will occur every year by the end of the century. Our research highlights the value of extending the historical record for a more nuanced understanding of HW behavior and suggests that extreme heat events, comparable to those experienced in recent decades, have occurred throughout the analyzed period

Aminobenzofuran-containing analogues of proximicins exhibit higher antiproliferative activity against human UG-87 glioblastoma cells compared to temozolomide

A new series of proximicin analogues containing a benzofuran moiety as the replacement of the di-furan scaffold of the parent compound were synthesised and evaluated for their anti-proliferative activities against human glioblastoma cells U-87 MG. Proximicins A, B, and C are secondary metabolites produced by Verrucosispora Fiedleri MG-37, a Gram-positive actinomycete isolated from deep-sea sediment. Proximicins exhibit significant cytotoxic and apoptotic effects in a number of tumour cell lines, although further investigations on these natural products biological activity are hampered by the challenging synthesis of their constitutive di-furan unit. Therefore, the easily-synthesisable benzofuran ring was elected as a replacement of the di-furan platform, and a library of proximicin analogues was prepared in which different substituents were introduced at both the N-terminus and C-terminus of the benzofuran core unit. The novel compounds were tested against U-87 MG, as it was previously found that proximicins targeted this cancerous cell line, and the human healthy cell line WI-38. Temozolomide, the chemotherapeutic agent of choice for the treatment of glioblastoma, was used as a control. Analysis of growth inhibitory concentration values revealed that a number of furan-benzofuran-containing proximicin analogues, including 23(16) (IC50 U-87 MG = 6.54 μg mL-1) exhibited higher antiproliferative activity against glioblastoma cells compared to both proximicins A-C and temozolomide (IC50 U-87 MG = 29.19 μg mL-1) in U-87 MG

Interplay of anthropogenic and natural drivers of observed coupled sea surface temperature - Arctic sea ice variability

Arctic sea ice plays a pivotal role in shaping the climate system at high latitudes, acting as both an indicator and driver of climate change processes in this sensitive region. Its seasonal variability and long-term decline have far-reaching implications for global climate dynamics, regional ecosystems, and human activities. While climate models indicate clear evidence of human-induced sea ice decline, quantification of the relative contributions of forcing factors in relation to climate-system internal processes remains uncertain. Here, we tackle this uncertainty by employing a combination of statistical analyses on observational data, highlighting the distinct fingerprints of increased atmospheric CO2 concentration as external forcing, the Atlantic Multidecadal Oscillation (AMO) as well as the North Atlantic Oscillation (NAO), as modes of internal variability, on global sea surface temperature (SST) and Arctic sea ice concentration (SIC) since 1950. Our analyses reveal that rising atmospheric CO2 concentrations are by far the dominant causal factor for SIC variability, while AMO and NAO also play a significant role in either exacerbating or mitigating sea ice loss. Since mid-1980s, the positive trend of the AMO has amplified the declining trend in Arctic sea ice, with its effects being roughly half as large as the effect of rising CO2 concentrations. Linear regression analyses shed light on the physical processes linking the drivers of Arctic sea ice decline both during phases of sea-ice accumulation and melting. Causal links between increasing atmospheric CO2 concentrations, the AMO, the NAO, on the one hand, and observed global SST—Arctic SIC patterns on the other are also established. Observation-based coupled SST-SIC interactions underline the past evolution of Arctic sea ice and emphasize the important roles of these drivers in shaping its current and future evolution