The impact of physical activity and exercise interventions for physical health in people with cystic fibrosis: protocol for a systematic review

This is the accepted manuscript; the final version is available from BMC via the DOI in this record.Cystic fibrosis (CF) is a genetically inherited, life-limiting condition, affecting ~90,000 people globally. Physical activity (PA) and exercise form an integral component of CF management, and have been highlighted by the CF community as an area of interest for future research. Previous reviews have solely focused on PA or structured exercise regimens independent of one another, and thus a comprehensive assessment of the physical health benefits of all PA, including exercise, interventions, is subsequently warranted. Therefore, the purpose of this review is to evaluate the effects of both PA and exercise upon outcomes of physical health and healthcare utilisation in people with CF. Methods A systematic review has been registered and reported in line with Preferred Reporting Items for Systematic Reviews and Meta-Analysis-P guidelines. This will include randomised control trials on the effects of PA and exercise, relative to usual treatment, upon people with CF. Primary outcomes will include variables associated with fitness, PA, lung health, inflammation, body composition, glycaemic control and patient-reported outcomes. Secondary outcomes will include adverse events and healthcare utilisation. Searches will be undertaken in Ovid MEDLINE, OVID EMBASE, PsychINFO, ERIC, SPORTDiscus, ASSIA, CCTR, CINHAL and Web of Science databases, and will be searched from date of inception onwards. Two reviewers will independently screen citations and abstracts, and full-texts, for inclusion and data extraction, respectively. Methodological quality will be assessed using the Cochrane Risk of Bias-2 tool. If feasible, random-effects meta-analyses will be conducted where appropriate. Additional analyses will explore potential sources of heterogeneity, such as age, sex, and disease severity. Discussion This systematic review will build on previous research, by comprehensively assessing the impact of both PA and exercise upon physical health and healthcare utilisation in people with CF. Results of this review will be utilised to inform discussions that will ultimately result in a consensus document on the impact of physical activity and exercise for people with CF. Systematic review registration PROSPERO CRD42020184411 Cystic Fibrosus Trust (SRC #008

Limits of effective nutrient management in dairy farming: analyses of experimental farm De Marke

Key words: nutrient management, dairy, prototyping, organic matter, soil fertility, nitrogen, phosphor. Intensive dairy production in the Netherlands is associated with high farm nutrient (N and P) inputs and high losses to the environment. The Dutch government and the dairy sector stimulate farmers to reduce losses through more efficient use of N and P inputs on their farms. This study explores for a dairy farm on dry sandy soil with average Dutch production intensity (12,000 kg milk per ha) the possibilities to meet strict environmental standards related to N and P by maximizing N and P use efficiency at the level of the farm and of the soil. Moreover, the study addresses the effects of efficient nutrient management on soil fertility. The research was conducted on experimental dairy farm De Marke, that is designed to meet strict environmental standards, implemented in practice in 1989 and modified continuously to meet its targets by prototyping, i.e. a cyclic procedure of designing, implementing, testing and evaluating measures. The thesis evaluates system development since 2000, while results from 1993-1999 were used to analyse long-term developments. After implementation of the farming system in 1989, the nitrate concentration in groundwater ‘stabilized’ at a level exceeding the environmental standard: 55 mg l-1. Causes of excessive nitrate leaching were examined by relating measured nitrate concentrations to management. Grazing was associated with higher leaching in spite of careful management with rotational grazing. Leaching under permanent grassland was similar to the overall leaching in crop rotations in which grass was alternated with maize and grains. Spatial and temporal patterns of soil N mineralization were explored to improve the synchronization of N application and crop N requirements. This study indicated that fertilizing a 1st year maize crop, following grassland, is not necessary. Measures implemented since 2000 to improve nutrient efficiency, included reduced grazing, adoption of anaerobic digestion, application of manure in the rows of maize, growing spring barley as the last crop in the arable phase, and, since 2004, the abolishment of fertilizer N. These measures contributed to an increase in the manure-N utilization and to an increase in the farm-N use efficiency up to 2008 to values exceeding the value of 33% that was realized in the period 1993-1999. Farm-N use efficiency was 35% in 2000-2003, 43% in 2004-2008 and 37% in 2009-2010. Farm-P use efficiency also increased as compared to the 87% that was realized in 1993-1999, i.e., it was 103% in 2000-2003 and 91% in 2004-2008. In 2009-2010, however, the farm-P use efficiency decreased to 69%, lower than the value realized in 1993-1999. The lower N and P use efficiency in 2009-2010 can be attributed to the lower N and P yields in grassland as a delayed effect of N limitation resulting from the abolishment of fertilizer N in grassland since 2004. Hence, despite the increase in manure-N utilization, mineral-N use is not yet completely redundant. P-equilibrium fertilization seems to be compatible with highly efficient crop production, in the short and in the long term. Soil organic matter (SOM) percentage in the upper topsoil decreased by 0.03 yr-1 (average across all land uses) at a constant rate over the last 20 years. The possibilities to stop this decline by higher organic matter inputs to the soil seem conflicting with efficient nutrient use. Hence, the long term dynamics of SOM may become critical for future farm performance. It was concluded that N and P use efficiency can be enhanced substantially by on-farm nutrient management, but that efficient nutrient management may conflict with maintenance of SOM.</p

A serious games platform for cognitive rehabilitation with preliminary evaluation

In recent years Serious Games have evolved substantially, solving problems in diverse areas. In particular, in Cognitive Rehabilitation, Serious Games assume a relevant role. Traditional cognitive therapies are often considered repetitive and discouraging for patients and Serious Games can be used to create more dynamic rehabilitation processes, holding patients' attention throughout the process and motivating them during their road to recovery. This paper reviews Serious Games and user interfaces in rehabilitation area and details a Serious Games platform for Cognitive Rehabilitation that includes a set of features such as: natural and multimodal user interfaces and social features (competition, collaboration, and handicapping) which can contribute to augment the motivation of patients during the rehabilitation process. The web platform was tested with healthy subjects. Results of this preliminary evaluation show the motivation and the interest of the participants by playing the games.- This work has been supported by FCT - Fundacao para a Ciencia e Tecnologia in the scope of the projects: PEst-UID/CEC/00319/2015 and PEst-UID/CEC/00027/2015. The authors would like to thank also all the volunteers that participated in the study

An algorithm for classifying tumors based on genomic aberrations and selecting representative tumor models

<p>Abstract</p> <p>Background</p> <p>Cancer is a heterogeneous disease caused by genomic aberrations and characterized by significant variability in clinical outcomes and response to therapies. Several subtypes of common cancers have been identified based on alterations of individual cancer genes, such as HER2, EGFR, and others. However, cancer is a complex disease driven by the interaction of multiple genes, so the copy number status of individual genes is not sufficient to define cancer subtypes and predict responses to treatments. A classification based on genome-wide copy number patterns would be better suited for this purpose.</p> <p>Method</p> <p>To develop a more comprehensive cancer taxonomy based on genome-wide patterns of copy number abnormalities, we designed an unsupervised classification algorithm that identifies genomic subgroups of tumors. This algorithm is based on a modified genomic Non-negative Matrix Factorization (gNMF) algorithm and includes several additional components, namely a pilot hierarchical clustering procedure to determine the number of clusters, a multiple random initiation scheme, a new stop criterion for the core gNMF, as well as a 10-fold cross-validation stability test for quality assessment.</p> <p>Result</p> <p>We applied our algorithm to identify genomic subgroups of three major cancer types: non-small cell lung carcinoma (NSCLC), colorectal cancer (CRC), and malignant melanoma. High-density SNP array datasets for patient tumors and established cell lines were used to define genomic subclasses of the diseases and identify cell lines representative of each genomic subtype. The algorithm was compared with several traditional clustering methods and showed improved performance. To validate our genomic taxonomy of NSCLC, we correlated the genomic classification with disease outcomes. Overall survival time and time to recurrence were shown to differ significantly between the genomic subtypes.</p> <p>Conclusions</p> <p>We developed an algorithm for cancer classification based on genome-wide patterns of copy number aberrations and demonstrated its superiority to existing clustering methods. The algorithm was applied to define genomic subgroups of three cancer types and identify cell lines representative of these subgroups. Our data enabled the assembly of representative cell line panels for testing drug candidates.</p

The Effects of Time Varying Curvature on Species Transport in Coronary Arteries

Alterations in mass transport patterns of low-density lipoproteins (LDL) and oxygen are known to cause atherosclerosis in larger arteries. We hypothesise that the species transport processes in coronary arteries may be affected by their physiological motion, a factor which has not been considered widely in mass transfer studies. Hence, we numerically simulated the mass transport of LDL and oxygen in an idealized moving coronary artery model under both steady and pulsatile flow conditions. A physiological inlet velocity and a sinusoidal curvature waveform were specified as velocity and wall motion boundary conditions. The results predicted elevation of LDL flux, impaired oxygen flux and low wall shear stress (WSS) along the inner wall of curvature, a predilection site for atherosclerosis. The wall motion induced changes in the velocity and WSS patterns were only secondary to the pulsatile flow effects. The temporal variations in flow and WSS due to the flow pulsation and wall motion did not affect temporal changes in the species wall flux. However, the wall motion did alter the time-averaged oxygen and LDL flux in the order of 26% and 12% respectively. Taken together, these results suggest that the wall motion may play an important role in coronary arterial transport processes and emphasise the need for further investigation

Analysis of osteoarthritis in a mouse model of the progeroid human DNA repair syndrome trichothiodystrophy

The increasing average age in developed societies is paralleled by an increase in the prevalence of many age-related diseases such as osteoarthritis (OA), which is characterized by deformation of the joint due to cartilage damage and increased turnover of subchondral bone. Consequently, deficiency in DNA repair, often associated with premature aging, may lead to increased pathology of these two tissues. To examine this possibility, we analyzed the bone and cartilage phenotype of male and female knee joints derived from 52- to 104-week-old WT C57Bl/6 and trichothiodystrophy (TTD) mice, who carry a defect in the nucleotide excision repair pathway and display many features of premature aging. Using micro-CT, we found bone loss in all groups of 104-week-old compared to 52-week-old mice. Cartilage damage was mild to moderate in all mice. Surprisingly, female TTD mice had less cartilage damage, proteoglycan depletion, and osteophytosis compared to WT controls. OA severity in males did not significantly differ between genotypes, although TTD males had less osteophytosis. These results indicate that in premature aging TTD mice age-related changes in cartilage were not more severe compared to WT mice, in striking contrast with bone and many other tissues. This segmental aging character may be explained by a difference in vasculature and thereby oxygen load in cartilage and bone. Alternatively, a difference in impact of an anti-aging response, previously found to be triggered by accumulation of DNA damage, might help explain why female mice were protected from cartilage damage. These findings underline the exceptional segmental nature of progeroid conditions and provide an explanation for pro- and anti-aging features occurring in the same individual

Relationship of metabolic syndrome and its components with -844 G/A and HindIII C/G PAI-1 gene polymorphisms in Mexican children

<p>Abstract</p> <p>Background</p> <p>Several association studies have shown that -844 G/A and <it>HindIII </it>C/G <it>PAI-1 </it>polymorphisms are related with increase of PAI-1 levels, obesity, insulin resistance, glucose intolerance, hypertension and dyslipidemia, which are components of metabolic syndrome. The aim of this study was to analyze the allele and genotype frequencies of these polymorphisms in <it>PAI-1 </it>gene and its association with metabolic syndrome and its components in a sample of Mexican mestizo children.</p> <p>Methods</p> <p>This study included 100 children with an age range between 6-11 years divided in two groups: a) 48 children diagnosed with metabolic syndrome and b) 52 children metabolically healthy without any clinical and biochemical alteration. Metabolic syndrome was defined as the presence of three or more of the following criteria: fasting glucose levels ≥ 100 mg/dL, triglycerides ≥ 150 mg/dL, HDL-cholesterol < 40 mg/dL, obesity BMI ≥ 95^thpercentile, systolic blood pressure (SBP) and diastolic blood pressure (DBP) ≥ 95^thpercentile and insulin resistance HOMA-IR ≥ 2.4. The -844 G/A and <it>HindIII </it>C/G <it>PAI-1 </it>polymorphisms were analyzed by PCR-RFLP.</p> <p>Results</p> <p>For the -844 G/A polymorphism, the G/A genotype (OR = 2.79; 95% CI, 1.11-7.08; <it>p </it>= 0.015) and the A allele (OR = 2.2; 95% CI, 1.10-4.43; <it>p </it>= 0.015) were associated with metabolic syndrome. The -844 G/A and A/A genotypes were associated with increase in plasma triglycerides levels (OR = 2.6; 95% CI, 1.16 to 6.04; <it>p </it>= 0.02), decrease in plasma HDL-cholesterol levels (OR = 2.4; 95% CI, 1.06 to 5.42; <it>p </it>= 0.03) and obesity (OR = 2.6; 95% CI, 1.17-5.92; <it>p </it>= 0.01). The C/G and G/G genotypes of the <it>HindIII </it>C/G polymorphism contributed to a significant increase in plasma total cholesterol levels (179 vs. 165 mg/dL; <it>p </it>= 0.02) in comparison with C/C genotype.</p> <p>Conclusions</p> <p>The -844 G/A <it>PAI-1 </it>polymorphism is related with the risk of developing metabolic syndrome, obesity and atherogenic dyslipidemia, and the <it>HindIII </it>C/G <it>PAI-1 </it>polymorphism was associated with the increase of total cholesterol levels in Mexican children.</p

Computational Models of Classical Conditioning guest editors’ introduction

In the present special issue, the performance of current computational models of classical conditioning was evaluated under three requirements: (1) Models were to be tested against a list of previously agreed-upon phenomena; (2) the parameters were fixed across simulations; and (3) the simulations used to test the models had to be made available. These requirements resulted in three major products: (a) a list of fundamental classical-conditioning results for which there is a consensus about their reliability; (b) the necessary information to evaluate each of the models on the basis of its ordinal successes in accounting for the experimental data; and (c) a repository of computational models ready to generate simulations. We believe that the contents of this issue represent the 2012 state of the art in computational modeling of classical conditioning and provide a way to find promising avenues for future model development