Utility of corneal confocal microscopy for assessing mild diabetic neuropathy: baseline findings of the LANDMark study

Background:  For those in the field of managing diabetic complications, the accurate diagnosis and monitoring of diabetic peripheral neuropathy (DPN) continues to be a challenge. Assessment of sub-basal corneal nerve morphology has recently shown promise as a novel ophthalmic marker for the detection of DPN. Methods:  Two hundred and thirty-one individuals with diabetes with predominantly mild or no neuropathy and 61 controls underwent evaluation of diabetic neuropathy symptom score, neuropathy disability score, testing with 10 g monofilament, quantitative sensory testing (warm, cold, vibration detection) and nerve conduction studies. Corneal nerve fibre length, branch density and tortuosity were measured using corneal confocal microscopy. Differences in corneal nerve morphology between individuals with and without DPN and controls were investigated using analysis of variance and correlations were determined between corneal morphology and established tests of, and risk factors for, DPN. Results:  Corneal nerve fibre length was significantly reduced in diabetic individuals with mild DPN compared with both controls (p < 0.001) and diabetic individuals without DPN (p = 0.012). Corneal nerve branch density was significantly reduced in individuals with mild DPN compared with controls (p = 0.032). Corneal nerve fibre tortuosity did not show significant differences. Corneal nerve fibre length and corneal nerve branch density showed modest correlations to most measures of neuropathy, with the strongest correlations to nerve conduction study parameters (r = 0.15 to 0.25). Corneal nerve fibre tortuosity showed only a weak correlation to the vibration detection threshold. Corneal nerve fibre length was inversely correlated to glycated haemoglobin (r = -0.24) and duration of diabetes (r = -0.20). Conclusion:  Assessment of corneal nerve morphology is a non-invasive, rapid test capable of showing differences between individuals with and without DPN. Corneal nerve fibre length shows the strongest associations with other diagnostic tests of neuropathy and with established risk factors for neuropathy.

Longitudinal assessment of neuropathy in type 1 diabetes using novel ophthalmic markers (LANDMark) : study design and baseline characteristics

Aims Corneal nerve morphology and corneal sensation threshold have recently been explored as potential surrogate markers for the evaluation of diabetic neuropathy. We present the baseline findings of the ‘Longitudinal Assessment of Neuropathy in type 1 Diabetes using novel ophthalmic Markers’(LANDMark) study. Methods The LANDMark study is a 4-year, two-site, natural history study of three participant groups: type 1 diabetes with neuropathy (T1W), type 1 diabetes without neuropathy (T1WO) and control participants without diabetes or neuropathy. All participants undergo a detailed annual assessment of neuropathy including corneal nerve parameters measured using corneal confocal microscopy and corneal sensitivity measured using non-contact corneal aesthesiometry. Results 76 T1W, 166 T1WO and 154 control participants were enrolled into the study. Corneal sensation threshold (mbars) was significantly higher (i.e. sensitivity was lower) in T1W (1.0 ± 1.1) than T1WO (0.7 ± 0.7) and controls (0.6 ± 0.4) (p < 0.001), with no difference between T1WO and controls. Corneal nerve fibre length was lower in T1W (14.0 ± 6.4 mm/mm2) compared to T1WO (19.1 ± 5.8 mm/mm2) and controls (23.2 ± 6.3 mm/mm2) (p < 0.001). Corneal nerve fibre length was lower in T1WO compared to controls. Conclusions The LANDMark baseline findings confirm a reduction in corneal sensitivity only in Type 1 patients with neuropathy. However, corneal nerve fibre length is reduced even in Type 1 patients without neuropathy with an even greater deficit in Type 1 patients with neuropathy.

Research update: LANDMark study: Longitudinal assessment of neuropathy in diabetes using novel ophthalmic MARKers

The eye is a simple, non-invasive location for screening, diagnosing and follow up of diabetic peripheral neuropathy.

Longitudinal assessment of neuropathy in diabetes using novel ophthalmic markers (LANDMark) : baseline findings

Purpose Over the past decade, corneal nerve morphology and corneal sensation threshold have been explored as potential surrogate markers for the evaluation of diabetic neuropathy. We present the baseline findings of a Longitudinal Assessment of Neuropathy in Diabetes using novel ophthalmic Markers (LANDMark). Methods The LANDMark Study is a 5-year, two-site, natural history (observational) study of individuals with Type 1 diabetes stratified into those with (T1W) and without (T1WO) neuropathy according to the Toronto criteria, and control subjects. All study participants undergo detailed annual assessment of neuropathy including corneal nerve parameters measured using corneal confocal microscopy and corneal sensitivity measured using non-contact corneal esthesiometry. Results 396 eligible individuals (208 in Brisbane and 188 in Manchester) were assessed: 76 T1W, 166 T1WO and 154 controls. Corneal sensation threshold (mbars) was significantly higher in T1W (1.0 ± 1.1) than T1WO (0.7 ± 0.7) and controls (0.6 ± 0.4) (P=0.002); post-hoc analysis (PHA) revealed no difference between T1WO and controls (Tukey HSD, P=0.502). Corneal nerve fiber length (mm/mm2) (CNFL) was lower in T1W (13.8 ± 6.4) than T1WO (19.1 ± 5.8) and controls (23.2 ± 6.3) (P<0.001); PHA revealed CNFL to be lower in T1W than T1WO, and lower in both of these groups than controls (P<0.001). Corneal nerve branch density (branches/mm2) (CNBD) was significantly lower in T1W (40 ± 32) than T1WO (62 ± 37) and controls (83 ± 46) (P<0.001); PHA showed CNBD was lower in T1W than T1WO, and lower in both groups than controls (P<0.001). Alcohol and cigarette consumption did not differ between groups, although age, BMI, BP, waist circumference, HbA1c, albumin-creatinine ratio, and cholesterol were slightly greater in T1W than T1WO (p<0.05). Some site differences were observed. Conclusions The LANDMark baseline findings confirm that corneal sensitivity and corneal nerve morphometry can detect differences in neuropathy status in individuals with Type 1 diabetes and healthy controls. Corneal nerve morphology is significantly abnormal even in diabetic patients ‘without neuropathy’ compared to control participants. Results of the longitudinal trial will assess the capability of these tests for monitoring change in these parameters over time as potential surrogate markers for neuropathy.

Longitudinal Assessment of Neuropathy in Diabetes using novel ophthalmic MARKers (LANDMark): Baseline findings

Purpose:Over the past decade, corneal nerve morphology and corneal sensation threshold have been explored as potential surrogate markers for the evaluation of diabetic neuropathy. We present the baseline findings of a Longitudinal Assessment of Neuropathy in Diabetes using novel ophthalmic Markers (LANDMark). Methods:The LANDMark Study is a 5-year, two-site, natural history (observational) study of individuals with Type 1 diabetes stratified into those with (T1W) and without (T1WO) neuropathy according to the Toronto criteria, and control subjects. All study participants undergo detailed annual assessment of neuropathy including corneal nerve parameters measured using corneal confocal microscopy and corneal sensitivity measured using non-contact corneal esthesiometry. Results:396 eligible individuals (208 in Brisbane and 188 in Manchester) were assessed: 76 T1W, 166 T1WO and 154 controls. Corneal sensation threshold (mbars) was significantly higher in T1W (1.0 ± 1.1) than T1WO (0.7 ± 0.7) and controls (0.6 ± 0.4) (P=0.002); post-hoc analysis (PHA) revealed no difference between T1WO and controls (Tukey HSD, P=0.502). Corneal nerve fiber length (mm/mm2) (CNFL) was lower in T1W (13.8 ± 6.4) than T1WO (19.1 ± 5.8) and controls (23.2 ± 6.3) (P<0.001); PHA revealed CNFL to be lower in T1W than T1WO, and lower in both of these groups than controls (P<0.001). Corneal nerve branch density (branches/mm2) (CNBD) was significantly lower in T1W (40 ± 32) than T1WO (62 ± 37) and controls (83 ± 46) (P<0.001); PHA showed CNBD was lower in T1W than T1WO, and lower in both groups than controls (P<0.001). Alcohol and cigarette consumption did not differ between groups, although age, BMI, BP, waist circumference, HbA1c, albumin-creatinine ratio, and cholesterol were slightly greater in T1W than T1WO (p<0.05). Some site differences were observed. Conclusions:The LANDMark baseline findings confirm that corneal sensitivity and corneal nerve morphometry can detect differences in neuropathy status in individuals with Type 1 diabetes and healthy controls. Corneal nerve morphology is significantly abnormal even in diabetic patients ‘without neuropathy’ compared to control participants. Results of the longitudinal trial will assess the capability of these tests for monitoring change in these parameters over time as potential surrogate markers for neuropathy.

A rare view: Barbara Hatley’s new book documents a career-long study of, and passion for performance in Central Java

Javanese Performances on an Indonesian Stage: Contesting Culture, Embracing Change, is Barbara Hatley’s first book about the performing arts in Indonesia, a topic that piqued her interest while undergoing a masters program at Yale University in the late 1960s. In this sense, it is a landmark study, for Hatley has since become very well known in Indonesianist circles, especially among those with an interest in matters of culture, popular and elite. Until recently, her writings on Indonesian performing arts have only been available in the form of journal articles and book chapters...

A Glorious Work in the World : Welsh Methodism and the International Evangelical Revival, 1735-1750

Jones, David, A Glorious Work in the World: Welsh Methodism and the International Evangelical Revival, 1735-1750 (Cardiff: University of Wales Press, 2004), pp.xiv+386 RAE2008

The evolution of the UK charity Statement of Recommended Practice: The influence of key stakeholders

In the early 1980s, a landmark study identified significant poor reporting practice in UK charities. As a consequence, a journey was commenced with the aim of improving accounting and reporting as a basis for enhancing accountability by charities. Much of this change has been effected through the publication of evolving Statements of Recommended Practice (SORPs) on accounting and reporting by charities. This paper analyses the evolution of the SORP through time using insights from stakeholder theory, and argues that the key stakeholders influencing the evolving SORP have been government and the accounting profession.

Refining Risk Estimates Using Models (Chapter 4)

In 2004 nineteen scientists from fourteen institutions in seven countries
collaborated in the landmark study described in chapter 2 (Thomas et al., 2004a). This chapter provides an overview of results of studies published subsequently and assesses how much, and why, new results differ from those of Thomas et al.
Some species distribution modeling (SDM) studies are directly comparable to the Thomas et al. estimates. Others using somewhat different methods nonetheless illuminate whether the original estimates were of the right order of magnitude. Climate similarity models (Williams et al., 2007; Williams and Jackson, 2007), biome, and vegetation dynamic models (Perry and Enright, 2006) have also been
applied in the context of climate change, providing interesting opportunities
for comparison and cross-validation with results from SDMs.
This chapter concludes with an assessment of whether the range of extinction risk estimates presented in 2004 can be narrowed, and whether the mean estimate should be revised upward or downward. To set the stage for these analyses, the chapter begins with brief reviews of advances in climate modeling and species modeling since 2004.

Desenlaces clínicos del cuidado perioperatorio de reemplazos articulares según grupos relacionados de diagnóstico en un hospital de cuarto nivel

Introducción Los Grupos Relacionados de Diagnóstico (GRD) se han usado para determinar la calidad de la atención en varios sistemas de salud. Esto ha llevado a que se obtengan resultados en el mejoramiento continuo de la atención y del cuidado. El objetivo de este estudio es determinar desenlaces clínicos de los pacientes a quienes se les había realizado reemplazo de articulares según la complejidad clínica definida mediante GRD. Métodos Se realizó un estudio longitudinal descriptivo en el cual se incluyeron todos los pacientes que tuvieron cirugía de reemplazo total de hombro, cadera y rodilla entre 2012 y 2014. Se realizó la estratificación de los pacientes de acuerdo a tres niveles de complejidad dados por el sistema de GRD y se determinaron las proporciones de pacientes para las variables de estancia hospitalaria, enfermedad trombo-embólica, cardiovascular e infección del sitio operatorio. Resultados Se realizaron en total 886 reemplazos articulares de los cuales 40 (4.5%) presentaron complicaciones. Los eventos más frecuentes fueron las complicaciones coronarias, con una presencia de 2.4%. El GRD1, sin complicaciones ni comorbilidades, fue el que presentó mayor número de eventos. La estancia hospitalaria fue de 3.8 a 9.3 días para todos los reemplazos. Conclusiones Contrario a lo planteado en la hipótesis de estudio, se encontró que el primer GRD presentó el mayor número de complicaciones, lo que puede estar relacionado con el tamaño del grupo. Es necesario realizar nuevas investigaciones que soporten el uso de los GRD como herramienta para evaluar desenlaces clínicos.

On increasing global temperatures: 75 years after Callendar

In 1938, Guy Stewart Callendar was the first to demonstrate that the Earth’s land surface was warming. Callendar also suggested that the production of carbon dioxide by the combustion of fossil fuels was responsible for much of this modern change in climate. This short note marks the 75th anniversary of Callendar’s landmark study and demonstrates that his global land temperature estimates agree remarkably well with more recent analyses.

River and Hillslope Response to Localized Uplift Along a Left Bend of the San Andreas Fault, Santa Cruz Mountains, CA

Studying landscape evolution of the Earthís surface is difficult because both tectonic forces and surface processes control its response to perturbation, and ultimately, its shape and form. Researchers often use numerical models to study erosional response to deformation because there are rarely natural settings in which we can evaluate both tectonic activity and topographic response over appropriate time scales (103-105 years). In certain locations, however, geologic conditions afford the unique opportunity to study the relationship between tectonics and topography. One such location is along the Dragonís Back Pressure Ridge in California, where the landscape moves over a structural discontinuity along the San Andreas Fault and landscape response to both the initiation and cessation of uplift can be observed. In their landmark study, Hilley and Arrowsmith (2008) found that geomorphic metrics such as channel steepness tracked uplift and that hillslope response lagged behind that of rivers. Ideal conditions such as uniform vegetation density and similar lithology allowed them to view each basin as a developmental stage of response to uplift only. Although this work represents a significant step forward in understanding landscape response to deformation, it remains unclear how these results translate to more geologically complex settings. In this study, I apply similar methodology to a left bend along the San Andreas Fault in the Santa Cruz Mountains, California. At this location, the landscape is translated through a zone of localized uplift caused by the bend, but vegetation, lithology, and structure vary. I examine the geomorphic response to uplift along the San Andreas Fault bend in order to determine whether predicted landscape patterns can be observed in a larger, more geologically complex setting than the Dragonís Back Pressure Ridge. I find that even with a larger-scale and a more complex setting, geomorphic metrics such as channel steepness index remain useful tools for evaluating landscape evolution through time. Steepness indices in selected streams of study record localized uplift caused by the restraining bend, while hillslope adjustment in the form of landsliding occurs over longer time scales. This project illustrates that it is possible to apply concepts of landscape evolution models to complex settings and is an important contribution to the body of geomorphological study.