Circulating Glycated Albumin and Glomerular Anionic Charges

Aiming to discern the mechanisms by which circulating glycated albumin alters the glomerular filtration properties that lead to glomerular dysfunction in diabetes, the authors studied the distribution and densities of anionic charges through the rat glomerular wall upon intravascular infusion of Amadori products, as well as in various conditions of increased glomerular permselectivity. Polylysine-gold was used as the probe to reveal the anionic charges. The study was carried on renal tissue sections of bovine serum albumin (BSA)- and glycated BSA–injected, normoglycemic animals. Results were generated through morphometrical evaluations of the gold labeling. Changes in glomerular anionic distribution were corroborated on renal tissue sections of short- and long-term diabetic rats and of normal newborn rats, situations known for abnormal glomerular filtration. Altered renal function in these conditions was clearly associated with changes in glomerular anionic charges. On the other hand, the infusion of glycated albumin in the circulation of normal rats, though altering glomerular filtration properties, did not modify the distribution and density of the polylysine-gold labeling through the glomerular basement membrane. Thus, anionic charges seem not to be the factor involved in the early changes of glomerular permeability induced by circulating glycated albumin

Are changes in self-rated health associated with memory decline in older adults?

OBJECTIVE: The association between patterns of change in self-rated health (SRH) and memory trajectories in older adults was examined using a systematic approach. METHOD: Data from the Health and Retirement Study (n = 6,016) and the English Longitudinal Study of Ageing (n = 734) were analyzed. Individuals were grouped into five categories according to their pattern of change in SRH over 8 years: stable excellent/very good/good, stable fair/poor, improvement, decline, and fluctuating pattern without a trend. Memory was measured using immediate and delayed recall tests. Kruskal–Wallis, chi-squares tests, and linear mixed models were used to examine the association. RESULTS: Different rates of decline in memory can be identified in the different patterns of change in SRH. Those who had a stable excellent/very good/good pattern had the slowest rate of decline. DISCUSSION: Our findings suggest that SRH status and patterns of change could be used as a marker of cognitive decline in prevention screening programs

Multimorbidity patterns and memory trajectories in older adults: Evidence from the English Longitudinal Study of Ageing

Background: We aimed to examine the multimorbidity patterns within a representative sample of UK older adults and their association with concurrent and subsequent memory. Methods: Our sample consisted of 11,449 respondents (mean age at baseline was 65.02) from the English Longitudinal Study of Ageing (ELSA). We used fourteen health conditions and immediate and delayed recall scores (IMRC and DLRC) over 7 waves (14 years of follow up). Latent class analyses were performed to identify the multimorbidity patterns and linear mixed models were estimated to explore their association with their memory trajectories. Models were adjusted by socio-demographics, BMI and health behaviors. Results: Results showed 8 classes: Class 1:Heart Disease/Stroke (26%), Class 2:Asthma/Lung Disease (16%), Class 3:Arthritis/Hypertension (13%), Class 4:Depression/Arthritis (12%), Class 5:Hypertension/Cataracts/Diabetes (10%), Class 6:Psychiatric Problems/Depression (10%), Class 7:Cancer (7%) and Class 8:Arthritis/Cataracts (6%). At baseline, Class 4 was found to have lower IMRC and DLRC scores and Class 5 in DLRC, compared to the no multimorbidity group (n=6380, 55.72% of total cohort). For both tasks, in unadjusted models, we found an accelerated decline in Classes 1, 3 and 8; and, for DLRC, also in Classes 2 and 5. However, it was fully attenuated after adjustments. Conclusions: These findings suggest that individuals with certain combinations of health conditions are more likely to have lower levels of memory compared those with no multimorbidity and their memory scores tend to differ between combinations. Socio-demographics and health behaviours have a key role to understand who is more likely to be at risk of an accelerated decline

The Traveling Tournament Problem

In this thesis we study the Traveling Tournament problem (TTP) which asks to generate a feasible schedule for a sports league such that the total travel distance incurred by all teams throughout the season is minimized. Throughout our three technical chapters a wide range of topics connected to the TTP are explored. We begin by considering the computational complexity of the problem. Despite existing results on the NP-hardness of TTP, the question of whether or not TTP is also APX-hard was an unexplored area in the literature. We prove the affirmative by constructing an L-reduction from (1,2)-TSP to TTP. To reach the desired result, we show that given an instance of TSP with a solution of cost K, we can construct an instance of TTP with a solution of cost at most 20m(m+1)cK where m = c(n-1)+1, n is the number of teams, and c > 5, c ∈ ℤ is fixed. On the other hand, we show that given a feasible schedule to the constructed TTP instance, we can recover a tour on the original TSP instance. The next chapter delves into a popular variation of the problem, the mirrored TTP, which has the added stipulation that the first and second half of the schedule have the same order of match-ups. Building upon previous techniques, we present an approximation algorithm for constructing a mirrored double round-robin schedule under the constraint that the number of consecutive home or away games is at most two. We achieve an approximation ratio on the order of 3/2 + O(1)/n. Lastly, we present a survey of local search methods for solving TTP and discuss the performance of these techniques on benchmark instances

Cognition in informal caregivers: evidence from an English population study

BACKGROUND AND OBJECTIVES: The relationship between caregiving and cognition remains unclear. We investigate this association comparing four cognitive tasks and exploring the role of potential explanatory pathways such as healthy behaviours (healthy caregiver hypothesis) and depression (stress process model).D RESEARCH AND DESIGN METHODS: Respondents were from English Longitudinal Study of Ageing (ELSA) (N = 8910). Cognitive tasks included immediate and delayed word recall, verbal fluency and serial 7 subtraction. Series of hierarchical linear regressions were performed. Adjustments included socio-demographics, health related variables, health behaviours and depression. RESULTS: Being a caregiver was positively associated with immediate and delayed recall, verbal fluency but not with serial 7. For immediate and delayed recall, these associations were partially attenuated when adjusting for health behaviours, and depression. For verbal fluency, associations were partially attenuated when adjusting for depression but fully attenuated when adjusting for health behaviours. No associations were found for serial 7. DISCUSSIONS AND IMPLICATIONS: Our findings show that caregivers have higher level of memory and executive function compared to non-caregivers. For memory, we found that although health behaviours and depression can have a role in this association, they do not fully explain it. However, health behaviours seem to have a clear role in the association with executive function. Public health and policy do not need to target specifically cognitive function but other areas as the promotion of healthy behaviours and psychological adjustment such as preventing depression and promoting physical activity in caregivers

NO NORMALIDAD Y HETEROGENEIDAD DE VARIANZA EN EL MODELO LINEALMIXTO (MLM) EN DISEÑOS SPLIT-PLOTCON MUESTRAS PEQUEÑAS

Los datos provenientes de investigaciones de tipo longitudinal en psicología suelen reflejar condiciones características de este ámbito de estudio, como son los tamaños muestrales reducidos, distribuciones no normales, violaciones de los supuestos de esfericidad y homogeneidad de varianza. Actualmente, el modelo lineal mixto (MLM) es uno de los procedimientos más recomendados cuando los supuestos en los que se basan los procedimientos tradicionales no se cumplen. Cuando los tamaños muestrales son reducidos se suele utilizar algún procedimiento de ajuste de los grados de libertad que mejore las propiedades del MLM, como el propuesto por Kenward y Roger (KR; 1997). El objetivo de este estudio fue ampliar el estudio realizado por Arnau et al. (2011) evaluando la robustez de KR con diseños split-plot de muestras pequeñas ante violaciones de la normalidad en diferente grado en los distintos grupos, violaciones de la esfericidad y de la homogeneidad de varianza. Se realiza un estudio de simulación Monte Carlo considerando un diseño split-plot con 3 grupos y 4 ocasiones de medidas repetidas, con tamaños muestrales totales de 36 y 42 individuos, asumiendo una matriz de covarianza no estructurada en la generación de datos. Se han manipulado las siguientes condiciones: a) con grupos balanceados y no balanceados; b) homogeneidad y heterogeneidad de la matriz de covarianza; c) emparejamiento nulo, positivo o negativo entre el tamaño de grupo y la matriz de covarianza y d) esfericidad de 0,57 ó 0,75. Los resultados muestran que KR es robusto cuando los diseños son equilibrados, independientemente de la violación de los supuestos de esfericidad y/o de homogeneidad de varianza. Sin embargo, cuando los diseños no son equilibrados, se halla una tendencia a la liberalidad, especialmente cuando el emparejamiento de las matrices de covarianza y el tamaño de los grupos es negativo. Los resultados de este estudio van en la línea con los obtenidos en estudios previos.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Proyecto de Investigación PSI2012-32662 Ministerio Economía y Competitividad

Glomerular Basement Membrane Selective Permeability in Short-term Streptozotocin-induced Diabetic Rats

In diabetes, the glomerular basement membrane undergoes thickening and structural alterations with loss of glomerular permselectivity properties. However, the onset of the alterations at early phases of diabetes is unclear. Aiming to determine the functional and structural alterations of the glomerular wall in the early stages of diabetes, we have studied the distribution of endogenous circulating albumin and type IV collagen in the glomerular basement membrane, using the immunocytochemical approach. The streptozotocin-injected hyperglycemic rat was our animal model. Renal tissues were examined after 10 days, 2, 4 and 6 months of hyperglycemia. Upon immunogold labelings, changes in the glomerular permeability to endogenous albumin were found altered as early as upon ten days of hyperglycemia. In contrast, no structural modifications were detected at this time point. Indeed, glomerular basement membrane thickening and an altered type IV collagen labeling distribution were only observed after four months of hyperglycemia, suggesting that functional alterations take place early in diabetes prior to any structural modification. In order to evaluate the reversibility of the glomerular alterations, two-month-old diabetic animals were treated with insulin. These animals showed a significant restoring of their glomerular permselectivity. Our results suggest a link between glycemic levels and alteration of glomerular permeability in early stages of diabetes, probably through high levels of glycated serum proteins

Expression and distribution of adenosine diphosphate-ribosylation factors in the rat kidney111Present address is: Renal Unit & Program in Membrane Biology, Massachusetts General Hospital, Harvard Medical School, 149, 13th Street, 8th Floor, Boston, MA, 02129, USA

Expression and distribution of adenosine diphosphate-ribosylation factors in the rat kidney.BackgroundAdenosine diphosphate (ADP)-ribosylation factors (ARFs) are small guanosine triphosphatases involved in membrane traffic regulation. Aiming to explore the possible involvement of ARF1 and ARF6 in the reabsorptive properties of the nephron, we evaluated their distribution along the different renal epithelial segments.MethodsARFs were detected by immunofluorescence and immunogold cytochemistry on renal sections, using specific anti-ARF antibodies.ResultsARF1 was detected in proximal and distal tubules, thick ascending limbs of Henle's loops, and cortical and medullary collecting ducts. By immunofluorescence, labeling was mostly localized to the cell cytoplasm, particularly in Golgi areas. By electron microscopy, the Golgi apparatus and the endosomal compartment of proximal and distal tubular cells were labeled. ARF6 immunofluorescence was observed in brush border membranes and the cytoplasm of proximal convoluted tubular cells, whereas it was restricted to the apical border of proximal straight tubules. ARF6 immunogold labeling was detected over microvilli and endocytic compartments of proximal tubular cells.ConclusionsThis study demonstrates the following: (a) the heterogeneous distributions of ARF1 and ARF6 along the nephron, (b) the existence of cytosolic and membrane-bound forms for both ARFs, and (c) their association with microvilli and endocytic compartments, suggesting an active participation in renal reabsorption

MedCATTrainer: A biomedical free text annotation interface with active learning and research use case specific customisation

We present MedCATTrainer1 an interface for building, improving and customising a given Named Entity Recognition and Linking (NER+L) model for biomedical domain text. NER+L is often used as a first step in deriving value from clinical text. Collecting labelled data for training models is difficult due to the need for specialist domain knowledge. MedCATTrainer offers an interactive web-interface to inspect and improve recognised entities from an underlying NER+L model via active learning. Secondary use of data for clinical research often has task and context specific criteria. MedCATTrainer provides a further interface to define and collect supervised learning training data for researcher specific use cases. Initial results suggest our approach allows for efficient and accurate collection of research use case specific training data