Non-invasive techniques for imaging in-vivo human corneal sub basal nerve mapping and migration rate in diabetic neuropathy

Purpose Corneal confocal microscopy (CCM) is a rapid non-invasive ophthalmic technique, which has been shown to diagnose and stratify the severity of diabetic neuropathy. Current morphometric techniques assess individual static images of the subbasal nerve plexus; this work explores the potential for non-invasive assessment of the wide-field morphology and dynamic changes of this plexus in vivo. Methods In this pilot study, laser scanning CCM was used to acquire maps (using a dynamic fixation target and semi-automated tiling software) of the central corneal sub-basal nerve plexus in 4 diabetic patients with and 6 without neuropathy and in 2 control subjects. Nerve migration was measured in an additional 7 diabetic patients with neuropathy, 4 without neuropathy and in 2 control subjects by repeating a modified version of the mapping procedure within 2-8 weeks, thus facilitating re-identification of distinctive nerve landmarks in the 2 montages. The rate of nerve movement was determined from these data and normalised to a weekly rate (µm/week), using customised software. Results Wide-field corneal nerve fibre length correlated significantly with the Neuropathy Disability Score (r = -0.58, p < 0.05), vibration perception (r = -0.66, p < 0.05) and peroneal conduction velocity (r = 0.67, p < 0.05). Central corneal nerve fibre length did not correlate with any of these measures of neuropathy (p > 0.05 for all). The rate of corneal nerve migration was 14.3 ± 1.1 µm/week in diabetic patients with neuropathy, 19.7 ± 13.3µm/week in diabetic patients without neuropathy, and 24.4 ± 9.8µm/week in control subjects; however, these differences were not significantly different (p = 0.543). Conclusions Our data demonstrate that it is possible to capture wide-field images of the corneal nerve plexus, and to quantify the rate of corneal nerve migration by repeating this procedure over a number of weeks. Further studies on larger sample sizes are required to determine the utility of this approach for the diagnosis and monitoring of diabetic neuropathy.

Exploring Retinal Markers of Diabetic Neuropathy

Purpose : To investigate the application of retinal nerve fibre layer (RNFL) thickness as a marker for severity of diabetic peripheral neuropathy (DPN) in people with Type 2 diabetes. Methods : This was a cross-sectional study whereby 61 participants (mean age 61 [41-75 years], mean duration of diabetes 14 [1-40 years], 70% male) with Type 2 diabetes and DPN underwent optical coherence tomography (OCT) scans. Global and 4 quadrant (TSNI) RNFL thicknesses were measured at 3.45mm around the optic nerve head of one eye. Neuropathy disability score (NDS) was used to assess the severity of DPN on a 0 to 10 scale. Participants were divided into three age-matched groups representing mild (NDS=3-5), moderate (NDS=6-8) and severe (NDS=9-10) neuropathy. Two regression models were fitted for statistical analysis: 1) NDS scores as co-variate for global and quadrant RNFL thicknesses, 2) NDS groups as a factor for global RNFL thickness only. Results : Mean (SD) RNFL thickness (µm) was 103(9) for mild neuropathy (n=34), 101(10) for moderate neuropathy (n=16) and 95(13) in the group with severe neuropathy (n=11). Global RNFL thickness and NDS scores were statistically significantly related (b=-1.20, p=0.048). When neuropathy was assessed across groups, a trend of thinner mean RNFL thickness was observed with increasing severity of neuropathy; however, this result was not statistically significant (F=2.86, p=0.065). TSNI quadrant analysis showed that mean RNFL thickness reduction in the inferior quadrant was 2.55 µm per 1 unit increase in NDS score (p=0.005). However, the regression coefficients were not statistically significant for RNFL thickness in the superior (b=-1.0, p=0.271), temporal (b=-0.90, p=0.238) and nasal (b=-0.99, p=0.205) quadrants. Conclusions : RNFL thickness was reduced with increasing severity of DPN and the effect was most evident in the inferior quadrant. Measuring RNFL thickness using OCT may prove to be a useful, non-invasive technique for identifying severity of DPN and may also provide additional insight into common mechanisms for peripheral neuropathy and RNFL damage.

Editorial: Research reporting: Clarity and accuracy improve quality

Research publication is one of the final steps in the research process, which begins with development of a research idea. Moving through the process of bringing together collaborators, design of the study protocol, securing of grant or study funding, and obtaining ethic(s) approval to conduct the research, and implementation of the research, analysis and drawing of conclusions based on the data leads to publication of the study results. Although a final step in the research process entails dissemination of the results, many studies go unreported or are improperly reported. Indeed, reviewers have suggested that many randomized controlled trials, observational studies, and qualitative studies lack crucial methodological features or details that lend credibility to study results (Simera et al., 2010).

Sleepy driving and drink driving: attitudes, behaviours, and perceived legitimacy of enforcement of younger and older drivers

Sleepy driving and drink driving are two risky driving behaviours that substantially contribute to road crashes. Several studies demonstrate equivalent levels of impairment from both sleepy and drink driving. Yet, drivers perceive sleepy and drink driving distinctly different, with younger and older drivers engaging in these two risky driving behaviours at different rates. The current study sought to examine the sleepy and drink driving behaviours and perceptions in a sample of 114 younger (17-29 years) and 177 older (30+ years) drivers. Compared to older drivers, younger drivers reported more positive attitudes toward sleepy and drink driving behaviours, as well as more negative views regarding perceived legitimacy of sleepy driving enforcement. Younger drivers were also more likely to report performing sleepy driving behaviours than older drivers. Younger drivers reported greater likelihood to drive while sleepy, lower perceptions of legitimacy for sleepy driving, and more positive attitudes towards sleepy driving when compared to drink driving and the same pattern was found for older drivers as well. Subsequently, the self-reported likelihood of driving while sleepy was greater than drink driving in both age groups. Overall, the results suggest that sleepy driving is not viewed as equally dangerous as drink driving with younger drivers’ perceptions being more lenient than older drivers’ perceptions. It is likely that change is needed regarding the perceptions of dangerousness of sleepy driving with a particular focus on younger drivers seemingly needed.

Long-term variation of tropical rock lobster panulirus ornatus (decapoda, palinuridae) growth inTorres Strait, Australia

This analysis of all carapace length measurements collected between 1989 and 2009, during scientific surveys, describes the variation of tropical rock lobster, Panulirus ornatus, somatic growth in Torres Strait. Multiple models of carapace length frequency distributions were compared by maximum likelihood to determine which hypotheses were most supported by the data. The best model assumed sex and cohort-specific Von Bertalanffy's parameters. These estimates are consistent with results derived from tagging data collected in the 1980s and provide new information on parameters' uncertainty. In the past two decades, growth rates have fluctuated inter-annually without displaying any distinctive trend. Associated uncertainties are large, suggesting that sampling will need to be intensified in order to detect an effect of climate change.

Additional information on the length-weight relationship of skipjack tuna from the Eastern Tropical Pacific Ocean

ENGLISH: Results of a study of the length-weight relationships of yellowfin (Neothunnus macropterus) and skipjack (Katsuwonus pelamis) tuna from several fishing areas of the Eastern Tropical Pacific Ocean have been published by Chatwin (1959). In that report, a very low exponential value of 2.6261 was obtained for skipjack from Area 14 (off northern Chile, see Chatwin, Figure 1). It was pointed out, however, that this estimate was based on two samples of fish with a very narrow range of total lengths, not representative of the range in the catch, and that it would be desirable to obtain a further estimate based on a larger range of total lengths. In addition, there proved to be significantly large differences among exponents for the areas sampled, precluding use of a single regression equation for all areas. Two important fishing areas remained unsampled (Areas 10 and 13, see Chatwin, Figure 1), and it appeared desirable to collect length-weight measurement data from them, so that estimating equations would be available for all areas. Subsequent to publication of Chatwin's study, samples of skipjack length-weight measurements were obtained from the desired areas. Estimates derived from these data, and their effects on the previous analysis are presented herein. SPANISH:Los resultados de un estudio sobre las relaciones entre la longitud y el peso del atún aleta amarilla (Neothunnus macropterus) y del barrilete (Katsuwonus pelamis) de las diferentes áreas de pesca en el Pacífico Oriental Tropical ya han sido publicados por Chatwin (1959). En ese informe se obtuvo un valor exponencial muy bajo de 2.626 para el barrilete del Area 14 (frente a la costa norte de Chile, ver Chatwin, Figura 1). Se hizo hincapié, sin embargo, en que esta estimación se basaba en dos muestras de peces con una amplitud muy estrecha de longitudes totales, no representativa de la amplitud en la pesca, y que sería deseable obtener una estimación adicional basada en una amplitud mayor de longitudes totales. Además, se comprobó que habian diferencias significativamente grandes entre los exponentes de las áreas muestreadas lo que impedía el usa de una sola ecuación de regresión para todas las áreas. Se quedaron sin muestrear dos importantes áreas de pesca (Areas 10 y 13, ver Chatwin, Figura 1) y pareció deseable recolectar datos de medidas de longitud y peso de estas áreas, de tal manera que hubiesen disponibles ecuaciones estimadoras para todas las áreas. Después de la publicación del estudio de Chatwin, so obtuvieron muestras de medidas de longitud y peso de barriletes de las áreas deseadas. Las estimaciones derivadas de estos datos y sus efectos sabre el análisis previo se dan en el presente informe.

Construção do pensamento autoritário anticomunista no Exército brasileiro nas páginas da revista Nação Armada (1939-1947)

Através da análise da revista Nação Armada, publicação de caráter civil-militar dedicada a Segurança Nacional, publicada pelo Exército brasileiro entre 1939 e 1947, o presente trabalho tem como objetivo compreender o processo de construção de um pensamento autoritário e anticomunista no Exército brasileiro neste período, e medir a contribuição do periódico Nação Armada neste processo. Utilizando a Nação Armada como fio condutor, procuramos remontar as formas de pensamento dos homens da época, tendo o mesmo cuidado em analisar conceitos como o de autoritarismo. Metodologicamente, adotamos primeiramente uma abordagem hermenêutica, quando todos os dados relacionados à publicação da Nação Armada (editores, tiragem, formato, autores, artigos, etc.), foram exaustivamente levantados e organizados, e em seguida passamos a uma abordagem heurística, quando passamos à crítica interna do conteúdo da Nação Armada, analisando os conceitos e discursos mais recorrentes. Contextualizamos nossa circunscrição temporal e temática à Era Vargas, e ao momento internacional. Trouxemos à discussão fatos históricos pontuais e locais, cronologicamente anteriores à publicação de Nação Armada, como a Intentona Comunista de 1935, bem como processos mais abrangentes e internacionais como a crise do sistema político liberal, a Segunda Guerra Mundial e o comunismo. Autores como Azevedo Amaral, Francisco Campos e Oliveira Vianna nos forneceram um arcabouço primordial para o entendimento de uma ideologia autoritária no Brasil na primeira metade do século XX. Dentre as várias ramificações que o presente trabalho apresentou, em virtude de período tão rico e transformador da história nacional e mundial, adotamos uma hipótese principal, que vai ao sentido de um processo contínuo de elaboração de ideário anticomunista e autoritário no Exército brasileiro através de construções simbólicas, e de tradições inventadas.

Face recognition from video

In spite of over two decades of intense research, illumination and pose invariance remain prohibitively challenging aspects of face recognition for most practical applications. The objective of this work is to recognize faces using video sequences both for training and recognition input, in a realistic, unconstrained setup in which lighting, pose and user motion pattern have a wide variability and face images are of low resolution. In particular there are three areas of novelty: (i) we show how a photometric model of image formation can be combined with a statistical model of generic face appearance variation, learnt offline, to generalize in the presence of extreme illumination changes; (ii) we use the smoothness of geodesically local appearance manifold structure and a robust same-identity likelihood to achieve invariance to unseen head poses; and (iii) we introduce an accurate video sequence "reillumination" algorithm to achieve robustness to face motion patterns in video. We describe a fully automatic recognition system based on the proposed method and an extensive evaluation on 171 individuals and over 1300 video sequences with extreme illumination, pose and head motion variation. On this challenging data set our system consistently demonstrated a nearly perfect recognition rate (over 99.7%), significantly outperforming state-of-the-art commercial software and methods from the literature. © Springer-Verlag Berlin Heidelberg 2006.

Achieving robust face recognition from video by combining a weak photometric model and a learnt generic face invariant

In spite of over two decades of intense research, illumination and pose invariance remain prohibitively challenging aspects of face recognition for most practical applications. The objective of this work is to recognize faces using video sequences both for training and recognition input, in a realistic, unconstrained setup in which lighting, pose and user motion pattern have a wide variability and face images are of low resolution. The central contribution is an illumination invariant, which we show to be suitable for recognition from video of loosely constrained head motion. In particular there are three contributions: (i) we show how a photometric model of image formation can be combined with a statistical model of generic face appearance variation to exploit the proposed invariant and generalize in the presence of extreme illumination changes; (ii) we introduce a video sequence re-illumination algorithm to achieve fine alignment of two video sequences; and (iii) we use the smoothness of geodesically local appearance manifold structure and a robust same-identity likelihood to achieve robustness to unseen head poses. We describe a fully automatic recognition system based on the proposed method and an extensive evaluation on 323 individuals and 1474 video sequences with extreme illumination, pose and head motion variation. Our system consistently achieved a nearly perfect recognition rate (over 99.7% on all four databases). © 2012 Elsevier Ltd All rights reserved.

Quantification of the effects of antibodies on the extra- and intracellular dynamics of Salmonella enterica.

Antibodies are known to be essential in controlling Salmonella infection, but their exact role remains elusive. We recently developed an in vitro model to investigate the relative efficiency of four different human immunoglobulin G (IgG) subclasses in modulating the interaction of the bacteria with human phagocytes. Our results indicated that different IgG subclasses affect the efficacy of Salmonella uptake by human phagocytes. In this study, we aim to quantify the effects of IgG on intracellular dynamics of infection by combining distributions of bacterial numbers per phagocyte observed by fluorescence microscopy with a mathematical model that simulates the in vitro dynamics. We then use maximum likelihood to estimate the model parameters and compare them across IgG subclasses. The analysis reveals heterogeneity in the division rates of the bacteria, strongly suggesting that a subpopulation of intracellular Salmonella, while visible under the microscope, is not dividing. Clear differences in the observed distributions among the four IgG subclasses are best explained by variations in phagocytosis and intracellular dynamics. We propose and compare potential factors affecting the replication and death of bacteria within phagocytes, and we discuss these results in the light of recent findings on dormancy of Salmonella.

Grooming and hygienic behaviours of the honey bee (Apis mellifera) toward the parasitic mite Varroa destructor

Despite a multitude of environmental stressors, the Varroa mite is still regarded as the greatest cause of honey bee mortality in its invaded range. Breeding honey bees that are resistant to the mite is an important area of research. This thesis aimed to gain a better understanding of the grooming and hygienic behaviours of Russian honey bees (RHB). The effect of a break in the synchrony of a mite’s life cycle on reproductive success was tested through brood inoculation experiments. Mites released by hygienic behaviour and forced to enter a new cell are less likely to lay male offspring. Through laboratory cage assays it was found that daughter mites are more susceptible to grooming behaviour. A new method of marking Varroa mites was developed which would enable a single cohort of mites to be followed after inoculation. A strong brood removal trait was noticed in RHB colonies, therefore they were tested for Varroa sensitive hygienic (VSH) behaviour. RHB demonstrated levels of VSH as high as the USDA line bred specifically for this behaviour. In addition the same QTL found to be responsible for the trait in VSH bees, was associated with VSH in RHB stock. Previous work showed that the ratio of older mites to total trapped mites (O/T) in the debris of honey bee colonies demonstrated the strongest association with colony infestation. This research showed that O/T is associated with VSH and brood removal behaviour. In addition, bees that displayed high levels of VSH in this study were also more likely to spend a longer amount of time grooming in laboratory assays. This indicates that both grooming and hygienic behaviours play important roles in the resistance of RHB stock. Their likelihood to be expressed by other stocks is discussed and recommendations for further research are provided.

Sequential anomaly detection in the presence of noise and limited feedback

This paper describes a methodology for detecting anomalies from sequentially observed and potentially noisy data. The proposed approach consists of two main elements: 1) filtering, or assigning a belief or likelihood to each successive measurement based upon our ability to predict it from previous noisy observations and 2) hedging, or flagging potential anomalies by comparing the current belief against a time-varying and data-adaptive threshold. The threshold is adjusted based on the available feedback from an end user. Our algorithms, which combine universal prediction with recent work on online convex programming, do not require computing posterior distributions given all current observations and involve simple primal-dual parameter updates. At the heart of the proposed approach lie exponential-family models which can be used in a wide variety of contexts and applications, and which yield methods that achieve sublinear per-round regret against both static and slowly varying product distributions with marginals drawn from the same exponential family. Moreover, the regret against static distributions coincides with the minimax value of the corresponding online strongly convex game. We also prove bounds on the number of mistakes made during the hedging step relative to the best offline choice of the threshold with access to all estimated beliefs and feedback signals. We validate the theory on synthetic data drawn from a time-varying distribution over binary vectors of high dimensionality, as well as on the Enron email dataset. © 1963-2012 IEEE.

Immunological Signatures Identifying Different Stages of Latent Mycobacterium tuberculosis Infection and Discriminating Latent from Active Tuberculosis in Humans

Objectives: One third of the world population is considered latently infected with Mycobacterium tuberculosis(LTBI) and sterilizing this reservoir of bacteria that may reactivate is required for tuberculosis (TB) elimination. Thegroup of individuals with LTBI is heterogeneous with some of them being more at risk to develop TB disease thanothers. Improved diagnosis of subjects with LTBI is needed, allowing to differentiate subjects with LTBI from thosewith active TB, and to select among LTBI subjects those who are more at risk to develop active TB. We havecharacterized at the cellular level both the quantitative and qualitative T cell responses to different mycobacterialantigens in selected populations of infected subjects in order to identify new biomarkers that could help to identify M.tuberculosis-infected subjects and to stratify them in risk groups for reactivation of the infection.Methods: Lymphoblast frequencies and cytokine production (IFN-γ, TNF-α, IL-2) among CD4+ and CD8+ T cellswere analyzed by flow cytometry after in vitro stimulation with the latency antigen heparin-binding haemagglutinin(HBHA) or early-secreted antigen Target-6 (ESAT-6) of peripheral blood mononuclear cells from clinically wellcharacterized M. tuberculosis-infected humans (28 LTBI, 22 TB disease,12 controls). The LTBI group definedaccording to the Center for Disease Control guidelines was subdivided into QuantiFERON-TB Gold in-Tube (QFT)positive and negative subgroups.Results: Similar to TB patients, QFT+ LTBI subjects had higher proportions of HBHA-induced TNF-αsingle+ CD4+lymphocytes than QFT- LTBI subjects (p<0.05). Compared to LTBI subjects, TB patients had higher frequencies ofESAT-6-induced CD8+ lymphoblasts (p<0.001), higher proportions of ESAT-6-induced IFN-γ+TNF-α+ CD4+ Tlymphocytes (p<0.05), and lower proportions of HBHA-induced IFN-γ+TNF-α+IL-2+ (p<0.05) CD4+ T lymphocytes.Conclusions: These data provide new biomarkers to discriminate active TB from LTBI, and more interestingly,help to identify LTBI subjects with increased likelihood to develop TB disease.

Violence Exposure and Welfare over Time: Evidence from the Burundi Civil War

We investigate the relationship between exposure to conflict and poverty dynamics over time, using original three-waves panel data for Burundi which tracked individuals and reported local-level violence exposure from 1998 to 2012. Firstly, the data reveal that headcount poverty has not changed since 1998 while we observe multiple transitions into and out of poverty. Moreover, households exposed to the war exhibit a lower level of welfare than non-exposed households, with the difference between the two groups predicted to remain significant at least until 2017, i.e. twelve years after the conflict termination. The correlation between violence exposure and deprivation over time is confirmed in a household-level panel setting. Secondly, our empirical investigation shows how violence exposure over different time spans interacts with households' subsequent welfare. Our analysis of the determinants of households' likelihood to switch poverty status (i.e. to fall into poverty or escape poverty) combined with quantile regressions suggest that, (i) exposure during the first phase of the conflict has affected the entire distribution, and (ii) exposure during the second phase of the conflict has mostly affected the upper tail of the distribution: initially non-poor households have a higher propensity to fall into poverty while initially poor households see their propensity to pull through only slightly decrease with recent exposure to violence. Although not directly testable with the data at hand, these results are consistent with the changing nature of violence in the course of the Burundi civil war, from relatively more labour-destructive to relatively more capital-destructive.

Is hyperfiltration associated with the future risk of developing diabetic nephropathy? A meta-analysis.

Aims/hypothesis Glomerular hyperfiltration is a well established phenomenon occurring early in some patients with type 1 diabetes. However, there is no consistent answer regarding whether hyperfiltration predicts later development of nephropathy. We performed a systematic review and meta-analysis of observational studies that compared the risk of developing diabetic nephropathy in patients with and without glomerular hyperfiltration and also explored the impact of baseline GFR.

Methods A systematic review and meta-analysis was carried out. Cohort studies in type 1 diabetic participants were included if they contained data on the development of incipient or overt nephropathy with baseline measurement
of GFR and presence or absence of hyperfiltration.

Results We included ten cohort studies following 780 patients. After a study median follow-up of 11.2 years, 130 patients had developed nephropathy. Using a random effects model, the pooled odds of progression to a minimum
of microalbuminuria in patients with hyperfiltration was 2.71 (95% CI 1.20–6.11) times that of patients with normofiltration. There was moderate heterogeneity (heterogeneity test p=0.05, measure of degree of inconsistency=48%) and some evidence of funnel plot asymmetry, possibly due to publication bias. The pooled weighted mean difference in baseline GFR was 13.8 ml min-1 1.73 m-2 (95% CI 5.0–22.7) greater in the group progressing to nephropathy than in those not progressing (heterogeneity test p<0.01).

Conclusions/interpretation In published studies, individuals with glomerular hyperfiltration were at increased risk of progression to diabetic nephropathy using study level data. Further larger studies are required to explore this relationship and the role of potential confounding variables.