Impact of El Niño on Staple Food Prices in East and Southern Africa

Demand and Price Analysis,

Disparity-driven vs blur-driven models of accommodation and convergence in binocular vision and intermittent strabismus

Background. Current models of concomitant, intermittent strabismus, heterophoria, convergence and accommodation anomalies are either theoretically complex or incomplete. We propose an alternative and more practical way to conceptualize clinical patterns. Methods. In each of three hypothetical scenarios (normal; high AC/A and low CA/C ratios; low AC/A and high CA/C ratios) there can be a disparity-biased or blur-biased “style”, despite identical ratios. We calculated a disparity bias index (DBI) to reflect these biases. We suggest how clinical patterns fit these scenarios and provide early objective data from small illustrative clinical groups. Results. Normal adults and children showed disparity bias (adult DBI 0.43 (95%CI 0.50-0.36), child DBI 0.20 (95%CI 0.31-0.07) (p=0.001). Accommodative esotropes showed less disparity-bias (DBI 0.03). In the high AC/A and low CA/C scenario, early presbyopes had mean DBI of 0.17 (95%CI 0.28-0.06), compared to DBI of -0.31 in convergence excess esotropes. In the low AC/A and high CA/C scenario near exotropes had mean DBI of 0.27, while we predict that non-strabismic, non-amblyopic hyperopes with good vision without spectacles will show lower DBIs. Disparity bias ranged between 1.25 and -1.67. Conclusions. Establishing disparity or blur bias, together with knowing whether convergence to target demand exceeds accommodation or vice versa explains clinical patterns more effectively than AC/A and CA/C ratios alone. Excessive bias or inflexibility in near-cue use increases risk of clinical problems. We suggest clinicians look carefully at details of accommodation and convergence changes induced by lenses, dissociation and prisms and use these to plan treatment in relation to the model

Determining the relative contribution of retinal disparity and blur cues to ocular accommodation in Down syndrome

Individuals with Down syndrome (DS) often exhibit hypoaccommodation alongside accurate vergence. This study investigates the sensitivity of the two systems to retinal disparity and blur cues, establishing the relationship between the two in terms of accommodative-convergence to accommodation (AC/A) and convergence-accommodation to convergence (CA/C) ratios. An objective photorefraction system measured accommodation and vergence under binocular conditions and when retinal disparity and blur cues were removed. Participants were aged 6–16 years (DS n = 41, controls n = 76). Measures were obtained from 65.9% of participants with DS and 100% of controls. Accommodative and vergence responses were reduced with the removal of one or both cues in controls (p < 0.007). For participants with DS, removal of blur was less detrimental to accommodative responses than removal of disparity; accommodative responses being significantly better when all cues were available or when blur was removed in comparison to when proximity was the only available cue. AC/A ratios were larger and CA/C ratios smaller in participants with DS (p < 0.00001). This study demonstrates that retinal disparity is the main driver to both systems in DS and illustrates the diminished influence of retinal blur. High AC/A and low CA/C ratios in combination with disparity-driven responses suggest prioritisation of vergence over accurate accommodation

Fabry disease: progression of nephropathy, and prevalence of cardiac and cerebrovascular events before enzyme replacement therapy

Background. In Fabry disease, progressive glycolipid accumulation leads to organ damage and early demise, but the incidence of renal, cardiac and cerebrovascular events has not been well characterized

Standardising clinical outcomes measures for adult clinical trials in Fabry Disease: A global Delphi Consensus

Background: Recent years have witnessed a considerable increase in clinical trials of new investigational agents for Fabry disease (FD). Several trials investigating different agents are currently in progress; however, lack of standardisation results in challenges to interpretation and comparison. To facilitate the standardisation of investigational programs, we have developed a common framework for future clinical trials in FD. Methods and findings: A broad consensus regarding clinical outcomes and ways to measure them was obtained via the Delphi methodology. 35 FD clinical experts from 4 continents, representing 3389 FD patients, participated in 3 rounds of Delphi procedure. The aim was to reach a consensus regarding clinical trial design, best treatment comparator, clinical outcomes, measurement of those clinical outcomes and inclusion and exclusion criteria. Consensus results of this initiative included: the selection of the adaptative clinical trial as the ideal study design and agalsidase beta as ideal comparator treatment due to its longstanding use in FD. Renal and cardiac outcomes, such as glomerular filtration rate, proteinuria and left ventricular mass index, were prioritised, whereas neurological outcomes including cerebrovascular and white matter lesions were dismissed as a primary or secondary outcome measure. Besides, there was a consensus regarding the importance of patient-related outcomes such as general quality of life, pain, and gastrointestinal symptoms. Also, unity about lysoGb3 and Gb3 tissue deposits as useful surrogate markers of the disease was obtained. The group recognised that cardiac T1 mapping still has potential but requires further development before its widespread introduction in clinical trials. Finally, patients with end-stage renal disease or renal transplant should be excluded unless a particular group for them is created inside the clinical trial. Conclusion: This consensus will help to shape the future of clinical trials in FD. We note that the FDA has, coincidentally, recently published draft guidelines on clinical trials in FD and welcome this contribution

Renal outcomes of agalsidase beta treatment for Fabry disease: role of proteinuria and timing of treatment initiation

BACKGROUND: The purpose of this study was to identify determinants of renal disease progression in adults with Fabry disease during treatment with agalsidase beta. METHODS: Renal function was evaluated in 151 men and 62 women from the Fabry Registry who received agalsidase beta at an average dose of 1 mg/kg/2 weeks for at least 2 years. Patients were categorized into quartiles based on slopes of estimated glomerular filtration rate (eGFR) during treatment. Multivariate logistic regression analyses were used to identify factors associated with renal disease progression. RESULTS: Men within the first quartile had a mean eGFR slope of -0.1 mL/min/1.73m(2)/year, whereas men with the most rapid renal disease progression (Quartile 4) had a mean eGFR slope of -6.7 mL/min/1.73m(2)/year. The risk factor most strongly associated with renal disease progression was averaged urinary protein:creatinine ratio (UP/Cr) ≥1 g/g (odds ratio 112, 95% confidence interval (95% CI) 4-3109, P = 0.0054). Longer time from symptom onset to treatment was also associated with renal disease progression (odds ratio 19, 95% CI 2-184, P = 0.0098). Women in Quartile 4 had the highest averaged UP/Cr (mean 1.8 g/g) and the most rapid renal disease progression: (mean slope -4.4 mL/min/1.73m(2)/year). CONCLUSIONS: Adults with Fabry disease are at risk for progressive loss of eGFR despite enzyme replacement therapy, particularly if proteinuria is ≥1 g/g. Men with little urinary protein excretion and those who began receiving agalsidase beta sooner after the onset of symptoms had stable renal function. These findings suggest that early intervention may lead to optimal renal outcomes

The management and survival outcomes of nasopharyngeal cancer in the Nordic countries

Peer reviewe

A case-control study of GST polymorphisms and arsenic related skin lesions

BACKGROUND: Polymorphisms in GSTT1, GSTM1 and GSTP1 impact detoxification of carcinogens by GSTs and have been reported to increase susceptibility to environmentally related health outcomes. Individual factors in arsenic biotransformation may influence disease susceptibility. GST activity is involved in the metabolism of endogenous and exogenous compounds, including catalyzing the formation of arsenic-GSH conjugates. METHODS: We investigated whether polymorphisms in GSTT1, GSTP1 and GSTM1 were associated with risk of skin lesions and whether these polymorphisms modify the relationship between drinking water arsenic exposure and skin lesions in a case control study of 1200 subjects frequency matched on age and gender in community clinics in Pabna, Bangladesh in 2001–2002. RESULTS AND DISCUSSION: GSTT1 homozygous wildtype status was associated with increased odds of skin lesions compared to the null status (OR1.56 95% CI 1.10–2.19). The GSTP1 GG polymorphism was associated with greater odds of skin lesions compared to GSTP1 AA, (OR 1.86 (95%CI 1.15–3.00). No evidence of effect modification by GSTT1, GSTM1 or GSTP1 polymorphisms on the association between arsenic exposure and skin lesions was detected. CONCLUSION: GSTT1 wildtype and GSTP1 GG are associated with increased risk of skin lesions