An investigation into the pedestrianisation of city streets : a move towards pedestrain friendly spaces and their economic effects in the City of Cape Town

Includes abstract.Includes bibliographical references.During December (2007), Cape Town’s peak tourism season, a pilot pedestrianisation project was run in the City of Cape Town. The 300 year old Greenmarket Square was pedestrianised and stakeholders on the square were surveyed six months after the implementation of the scheme to access the economic benefits, as well as the perception of predestination by the traders. A SATURN dynamic assignment model was used to simulate the effect of certain road closures to traffic as part of an extension to the pedestrian network. These road are vital to start forming a formalise pedestrian network within the CBD. From the results, a pedestrian network for the Cape Town CBD has been proposed

Approach to lower back pain

Lower back pain is one of the most common symptoms – and the most common musculoskeletal problem –  seen by general practitioners. It is also a common cause of disability and an expensive condition in terms of  economic impact because of absenteeism. This article discusses an approach to this common symptom and how to distinguish the benign, mechanical type of back pain from the more sinister, but less frequently  encountered, inflammatory back pain

Challenging Patronage Networks and Corruption in Iraq: A social accounting matrix analysis of citizen-based oil revenue distribution

Iraq is a country with exceptional natural resource wealth, but also consistent political turbulence manifested by high levels of state corruption, patronage networks, weak governance, poor institutional quality, civil unrest and sectarian conflict, all of which have undermined the sovereignty of its vast petroleum wealth and limited its potential for economic prosperity. As a mechanism for reducing the high levels of corruption and patronage networks as well as stimulating economic activity, this dissertation proposes the use of citizen-based direct distribution of oil revenues and studies the economic impacts of this policy using Social Accounting Matrix analysis. The methodology for this analysis includes testing the policy at different levels of per capita distribution, as well as with three variations in the design of the distribution programs. These variations include a universal cash transfer funded by oil revenue surpluses, a targeted cash transfer funded by oil revenue surpluses and a universal cash transfer funded by the reallocation of funding from the existing food subsidy system. The results illustrate that in each of the scenario variations, cash transfers are shown to have a significant positive impact on household incomes, producing activities and aggregate demand in the economy. The results also illustrate a net welfare gain to households when replacing the existing food subsidy system with cash transfers. In the comparison of distribution variations, targeted programs are shown to have the largest effect on the economy, primarily as lower-income households were allocated a greater proportion of income and subsequently also spend a greater proportion of their income on goods with lower leakages. Higher-income households, who are non-recipients in the targeted programs, benefit from targeted programs through the indirect/induced effects, which are largest in comparison to the other distribution variations. The results also show increased consumption on essential goods & services, primarily agricultural produce, which would ease concerns that cash transfers may generate increased consumption on non-essential/temptation goods

The Genetic Determinants of Axial Length: From Microphthalmia to High Myopia in Childhood

The axial length of the eye is critical for normal visual function by enabling light to precisely focus on the retina. The mean axial length of the adult human eye is 23.5 mm, but the molecular mechanisms regulating ocular axial length remain poorly understood. Underdevelopment can lead to microphthalmia (defined as a small eye with an axial length of less than 19 mm at 1 year of age or less than 21 mm in adulthood) within the first trimester of pregnancy. However, continued overgrowth can lead to axial high myopia (an enlarged eye with an axial length of 26.5 mm or more) at any age. Both conditions show high genetic and phenotypic heterogeneity associated with significant visual morbidity worldwide. More than 90 genes can contribute to microphthalmia, and several hundred genes are associated with myopia, yet diagnostic yields are low. Crucially, the genetic pathways underpinning the specification of eye size are only now being discovered, with evidence suggesting that shared molecular pathways regulate under- or overgrowth of the eye. Improving our mechanistic understanding of axial length determination will help better inform us of genotype-phenotype correlations in both microphthalmia and myopia, dissect gene-environment interactions in myopia, and develop postnatal therapies that may influence overall eye growth

Sparse scalp hair and vision loss: think hypotrichosis with juvenile macular dystrophy

Here, we report the diagnostic challenge of a female patient of Russian descent with autosomal recessive hypotrichosis with juvenile macular dystrophy (HJMD). She presented to dermatology age one and a half years with sparse hair growth on her scalp, her parents were reassured this would grow, but it never manifested. She was found to be hypermetropic and prescribed glasses from age 2 but no retinal findings were noted. At age 23 years, the patient undertook an internet search and discovered the association of symptoms pointing towards HJMD. She sought genetic testing, revealing a homozygous missense mutation in Cadherin-3 (CDH3) gene. The patient presented to our Genetic Eye Disease Service at Moorfields Eye Hospital age 27 years, with reduced colour, central distance and near vision. Fundus examination and imaging confirmed atrophic macular changes. Currently, HJMD has no treatment, she wears a wig, UV-protected sunglasses in sunlight and maintains a healthy balanced diet

Retinol dehydrogenase 12 (RDH12): Role in vision, retinal disease and future perspectives

Retinol dehydrogenase 12 (RDH12) is an NADPH-dependent retinal reductase, which is expressed in the inner segments of the photoreceptors. It functions as part of the visual cycle, which is a series of enzymatic reactions required for the regeneration of the visual pigment, and has also been implicated in detoxification of lipid peroxidation products. Mutations in RDH12 have been linked to Leber congenital amaurosis (LCA) and autosomal dominant retinitis pigmentosa. A number of in-vitro studies have shown that mutations in RDH12 result in little or no enzyme activity. Knockout mouse models however do not recapitulate the severe phenotype observed in patients, resulting in a limited understanding of the disease mechanisms. With gene replacement and small molecule drugs emerging for inherited retinal dystrophies, herein we provide a review of RDH12 structure, its role in vision and the current understanding of disease mechanisms linked to clinical phenotype to support therapeutic development

Vincristine-induced vocal cord palsy and successful re-treatment in a patient with diffuse large B cell lymphoma: a case report

Background: Vincristine, a type of vinca alkaloid, is widely used in the treatment of various childhood and adult malignancies. A well-known side effect of vincristine is its neurotoxicity and it is rarely indicted in vagus nerve involvement. Vincristine induced vocal cord palsy is a potentially reversible condition, with the mainstay of therapy being withdrawal of the offending drug. However, there are no clear guidelines regarding the possibility of re-treatment with the causative agent.CASE PRESENTATION: A 58 year old Asian male presented with constipation and abdominal distension. Diagnostic investigations revealed stage IVB diffuse large B cell lymphoma (DLBCL). The patient was subsequently started on R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone). On day twelve of receiving course four of R-CHOP, our patient presented to the hospital with a history of hoarseness of voice. Clinical and radiological examination revealed bilateral vocal cord palsy. Tracheostomy was done in view of a compromised airway. The patient subsequently went on to receive two more cycles of R-CHOP. Two weeks later Flexible laryngoscopy showed no lesion and the vocal cords were moving normally. The tracheostomy was removed. His voice has improved since and the patient is currently in remission.CONCLUSION: The occurrence of vincristine induced vocal cord palsy has been well reported in the literature. We strongly believe that our patient developed vocal cord palsy secondary to vincristine. The uniqueness of our patient\u27s case lies in successful re-treatment of our patient with the offending drug. To the best of our knowledge this is the third instance where a patient was successfully re-treated with vincristine after having developed vocal cord palsy as a result of its use

A Natural History Study of RP2-Related Retinopathy

X-linked retinitis pigmentosa (RP) is a severe form of RP, often with early macular involvement. This study aimed to characterise the natural history of patients with a diagnosis of X-linked RP due to RP2 mutations. Clinical details, best-corrected visual acuity (BCVA) and multimodal retinal imaging were retrospectively collected from patients with RP2 variants from Moorfields Eye Hospital (London, UK). Measures of the ellipsoid-zone (EZ) width, central retinal thickness (CRT), and thickness of the photoreceptor and retinal pigment epithelium complex (PR+RPE, taken between the external limiting membrane and RPE) were extracted from spectral-domain optical coherence tomography (SD-OCT) scans. A total of 47 affected males (median baseline age: 20 years, IQR: 12.5–36.5) were included, and 41 had two or more visits (median follow-up: 8.0 years, IQR: 3.2–14.5). A total of 24 RP2 variants were identified, 13 of which were novel. BCVA dropped from 0.66 LogMAR at baseline (IQR, 0.35–1.4) to 1.3 LogMAR at the most recent visit (IQR: 0.6–1.4). SD-OCT revealed a prevalent outer retinal atrophy (n = 23/35, 65.7%), and measurable EZ width at baseline in 34.3% of patients (n = 12). Age significantly affected all quantitative measures (p < 0.001) except EZ width (p = 0.58), with exponential decays of 46–49% and 12.6–33.9% per decade for BCVA and SD-OCT measures, respectively. RP2 patients exhibited rapid progression to outer retina atrophy and early macular involvement with substantial vision loss by age 30–40

The Landscape of Non-Viral Gene Augmentation Strategies for Inherited Retinal Diseases

Inherited retinal diseases (IRDs) are a heterogeneous group of disorders causing progressive loss of vision, affecting approximately one in 1000 people worldwide. Gene augmentation therapy, which typically involves using adeno-associated viral vectors for delivery of healthy gene copies to affected tissues, has shown great promise as a strategy for the treatment of IRDs. However, the use of viruses is associated with several limitations, including harmful immune responses, genome integration, and limited gene carrying capacity. Here, we review the advances in non-viral gene augmentation strategies, such as the use of plasmids with minimal bacterial backbones and scaffold/matrix attachment region (S/MAR) sequences, that have the capability to overcome these weaknesses by accommodating genes of any size and maintaining episomal transgene expression with a lower risk of eliciting an immune response. Low retinal transfection rates remain a limitation, but various strategies, including coupling the DNA with different types of chemical vehicles (nanoparticles) and the use of electrical methods such as iontophoresis and electrotransfection to aid cell entry, have shown promise in preclinical studies. Non-viral gene therapy may offer a safer and effective option for future treatment of IRDs

USH2A-retinopathy: From genetics to therapeutics

Bilallelic variants in the USH2A gene can cause Usher syndrome type 2 and non-syndromic retinitis pigmentosa. In both disorders, the retinal phenotype involves progressive rod photoreceptor loss resulting in nyctalopia and a constricted visual field, followed by subsequent cone degeneration, leading to the loss of central vision and severe visual impairment. The USH2A gene raises many challenges for researchers and clinicians due to a broad spectrum of mutations, a large gene size hampering gene therapy development and limited knowledge on its pathogenicity. Patients with Usher type 2 may benefit from hearing aids or cochlear implants to correct their hearing defects, but there are currently no approved treatments available for the USH2A-retinopathy. Several treatment strategies, including antisense oligonucleotides and translational readthrough inducing drugs, have shown therapeutic promise in preclinical studies. Further understanding of the pathogenesis and natural history of USH2A-related disorders is required to develop innovative treatments and design clinical trials based on reliable outcome measures. The present review will discuss the current knowledge about USH2A, the emerging therapeutics and existing challenges