COUNTERMOVEMENT JUMP PERFORMANCE IS NOT AFFECTED DURING AN IN-SEASON TRAINING MICROCYCLE IN ELITE YOUTH SOCCER PLAYERS

This study examined the change in countermovement jump (CMJ) performance across a microcycle of training in professional soccer players during the in-season period. Nine elite youth soccer players performed a CMJ test pre and post four consecutive soccer training sessions of an in-season weekly microcycle. Training load was quantified using global positioning systems (GPS), heart rate (HR) and rating of perceived exertion (RPE). Absolute change (pre to post training) in CMJ height across each training session was analysed using one-way repeated measures analysis of variance (ANOVA). Magnitude of effects was reported with the effect size (ES) statistic. Correlation analyses assessed the relationships between training load measures and the absolute change in CMJ height. Training load remained similar on all training days apart from a significant decrease in training load (all variables except high speed distance) on the last training session (P 0.05). This study revealed no significant change in CMJ performance across the in-season microcycle. This suggests that soccer players are able to maintain CMJ performance across an in-season training microcycle

Hearing the Voice of a Shadow Child: Healthy Siblings Experience of Cystic Fibrosis and Other Life-Threatening Conditions.

Cystic fibrosis (CF) is a chronic, life-threatening disease, similar to other chronic life-disrupting pediatric conditions, and this creates physical and psychosocial problems for parents and the healthy sibling/s of the sick child, who often become sibling carers. It is feared that, despite good intentions, professionals fail to hear the authentic voice of those intimately involved, especially these sibling carers, who can feel they became a "shadow child." This study is a partnership between an academic and a former CF sibling carer, who wrote a "fairy story" for his children about the Uncle they never knew. It is an effort to hear the "voice of shadow children" who can feel left behind and unseen as families and professionals focus upon their ill sibling

Loss and dispersion of superficial white matter in Alzheimer's disease: a diffusion MRI study

Pathological cerebral white matter changes in Alzheimer’s disease have been shown using diffusion tensor imaging. Superficial white matter changes are relatively understudied despite their importance in cortico-cortical connections. Measuring superficial white matter degeneration using diffusion tensor imaging is challenging due to its complex organizational structure and proximity to the cortex. To overcome this, we investigated diffusion MRI changes in young-onset Alzheimer’s disease using standard diffusion tensor imaging and Neurite Orientation Dispersion and Density Imaging to distinguish between disease-related changes that are degenerative (e.g. loss of myelinated fibres) and organizational (e.g. increased fibre dispersion). Twenty-nine young-onset Alzheimer’s disease patients and 22 healthy controls had both single-shell and multi-shell diffusion MRI. We calculated fractional anisotropy, mean diffusivity, neurite density index, orientation dispersion index and tissue fraction (1-free water fraction). Diffusion metrics were sampled in 15 a priori regions of interest at four points along the cortical profile: cortical grey matter, grey/white boundary, superficial white matter (1 mm below grey/white boundary) and superficial/deeper white matter (2 mm below grey/white boundary). To estimate cross-sectional group differences, we used average marginal effects from linear mixed effect models of participants’ diffusion metrics along the cortical profile. The superficial white matter of young-onset Alzheimer’s disease individuals had lower neurite density index compared to controls in five regions (superior and inferior parietal, precuneus, entorhinal and parahippocampus) (all P < 0.05), and higher orientation dispersion index in three regions (fusiform, entorhinal and parahippocampus) (all P < 0.05). Young-onset Alzheimer’s disease individuals had lower fractional anisotropy in the entorhinal and parahippocampus regions (both P < 0.05) and higher fractional anisotropy within the postcentral region (P < 0.05). Mean diffusivity was higher in the young-onset Alzheimer’s disease group in the parahippocampal region (P < 0.05) and lower in the postcentral, precentral and superior temporal regions (all P < 0.05). In the overlying grey matter, disease-related changes were largely consistent with superficial white matter findings when using neurite density index and fractional anisotropy, but appeared at odds with orientation dispersion and mean diffusivity. Tissue fraction was significantly lower across all grey matter regions in young-onset Alzheimer’s disease individuals (all P < 0.001) but group differences reduced in magnitude and coverage when moving towards the superficial white matter. These results show that microstructural changes occur within superficial white matter and along the cortical profile in individuals with young-onset Alzheimer’s disease. Lower neurite density and higher orientation dispersion suggests underlying fibres undergo neurodegeneration and organizational changes, two effects previously indiscernible using standard diffusion tensor metrics in superficial white matter

Geographical information system and predictive risk maps of urinary schistosomiasis in Ogun State, Nigeria

<p>Abstract</p> <p>Background</p> <p>The control of urinary schistosomiasis in Ogun State, Nigeria remains inert due to lack of reliable data on the geographical distribution of the disease and the population at risk. To help in developing a control programme, delineating areas of risk, geographical information system and remotely sensed environmental images were used to developed predictive risk maps of the probability of occurrence of the disease and quantify the risk for infection in Ogun State, Nigeria.</p> <p>Methods</p> <p>Infection data used were derived from carefully validated morbidity questionnaires among primary school children in 2001–2002, in which school children were asked among other questions if they have experienced "blood in urine" or urinary schistosomiasis. The infection data from 1,092 schools together with remotely sensed environmental data such as rainfall, vegetation, temperature, soil-types, altitude and land cover were analysis using binary logistic regression models to identify environmental features that influence the spatial distribution of the disease. The final regression equations were then used in Arc View 3.2a GIS software to generate predictive risk maps of the distribution of the disease and population at risk in the state.</p> <p>Results</p> <p>Logistic regression analysis shows that the only significant environmental variable in predicting the presence and absence of urinary schistosomiasis in any area of the State was Land Surface Temperature (LST) (B = 0.308, p = 0.013). While LST (B = -0.478, p = 0.035), rainfall (B = -0.006, p = 0.0005), ferric luvisols (B = 0.539, p = 0.274), dystric nitosols (B = 0.133, p = 0.769) and pellic vertisols (B = 1.386, p = 0.008) soils types were the final variables in the model for predicting the probability of an area having an infection prevalence equivalent to or more than 50%. The two predictive risk maps suggest that urinary schistosomiasis is widely distributed and occurring in all the Local Government Areas (LGAs) in State. The high-risk areas (≥ 50% prevalence) however, are confined to scatter foci in the north western part of the State. The model also estimated that 98.99% of schools aged children (5–14 years) are living in areas suitable for urinary schistosomiasis transmission and are at risk of infection.</p> <p>Conclusion</p> <p>The risk maps developed will hopefully be useful to the state health officials, by providing them with detailed distribution of urinary schistosomiasis, help to delineate areas for intervention, assesses population at risk thereby helping in optimizing scarce resources.</p

Atrophy and partial volume related bias in cortical region of interest NODDI metrics

Background: Neurite Orientation Dispersion and Density Imaging (NODDI) provides in-vivo indices of neurite density (NDI) and orientation dispersion (ODI) within the tissue compartment of each voxel. However, NDI and ODI are treated equally when calculating region of interest (ROI) means, despite tissue fraction (TF) varying within regions undergoing neurodegeneration. Covariation between TF and cortical NODDI measures bias these conventional means and we recommend using tissue-weighted averages to address this. Method: In this study, we included 22 healthy controls and 33 individuals affected by Young-Onset Alzheimer’s disease (YOAD, see Table 1 for demographics) with suitable diffusion-weighted and T1-weighted 3T MR images. Diffusion data were corrected for eddy currents, motion and susceptibility artefacts before fitting the NODDI model to produce NDI, ODI, isotropic volume fraction (ISO) and TF maps (TF=1-ISO). T1w images were parcellated into cortical ROIs using Geodesic Information Flow (Cardoso et al., IEEE Trans.Med.Im.; 34:1976-1988, 2015). Five bilateral ROIs expected to undergo neurodegeneration were analysed (Precuneus, Fusiform Gyrus, Superior Parietal, Middle and Inferior Temporal cortex). ROIs were resampled into native diffusion space and two regional measures calculated: 1) conventional, unweighted NDI and ODI averages and 2) tissue-weighted averages using voxel TF as weights. Within-participant differences between conventional and tissue-weighted measures were calculated. Spearman’s rank tested correlations and Wilcoxon tests evaluated within- and between-participant differences (Bonferroni adjusted for multiple comparisons). Result: TF positively correlated with GM volume (rs range=0.33-0.68,p<0.05) in all ROIs except the left fusiform gyrus (rs=0.31,p=0.06) (Figure 1). YOAD individuals had lower TF than healthy controls in all ROIs (Figure 2a), and lower volumes in all ROIs except the right fusiform gyrus (W=475,p=0.27) (Figure 2b). NDI showed small positive/negative biases in six of the ten ROIs (Figure 3a), while ODI showed significant positive biases across all ROIs (Figure 3b). Biases decreased as TF increased towards its maximum of one (Figure 4a-4b). Conclusion: Lower cortical volumes in YOAD were associated with lower TF and higher bias, suggesting a greater risk for misestimation of cortical region NODDI metrics in studies involving neurodegenerative disease. We recommend tissue-weighted averages to account for varying intra-regional TF in NODDI measures

Cortical microstructure in young onset Alzheimer's disease using neurite orientation dispersion and density imaging

Alzheimer's disease (AD) is associated with extensive alterations in grey matter microstructure, but our ability to quantify this in vivo is limited. Neurite orientation dispersion and density imaging (NODDI) is a multi-shell diffusion MRI technique that estimates neuritic microstructure in the form of orientation dispersion and neurite density indices (ODI/NDI). Mean values for cortical thickness, ODI, and NDI were extracted from predefined regions of interest in the cortical grey matter of 38 patients with young onset AD and 22 healthy controls. Five cortical regions associated with early atrophy in AD (entorhinal cortex, inferior temporal gyrus, middle temporal gyrus, fusiform gyrus, and precuneus) and one region relatively spared from atrophy in AD (precentral gyrus) were investigated. ODI, NDI, and cortical thickness values were compared between controls and patients for each region, and their associations with MMSE score were assessed. NDI values of all regions were significantly lower in patients. Cortical thickness measurements were significantly lower in patients in regions associated with early atrophy in AD, but not in the precentral gyrus. Decreased ODI was evident in patients in the inferior and middle temporal gyri, fusiform gyrus, and precuneus. The majority of AD-related decreases in cortical ODI and NDI persisted following adjustment for cortical thickness, as well as each other. There was evidence in the patient group that cortical NDI was associated with MMSE performance. These data suggest distinct differences in cortical NDI and ODI occur in AD and these metrics provide pathologically relevant information beyond that of cortical thinning

Not all voxels are created equal: Reducing estimation bias in regional NODDI metrics using tissue-weighted means

Data and code availability: Code used in calculating the tissue-weighting mean is available here: https://github.com/tdveale/NODDI-tissue-weighting-tool. ROI data and other scripts used in this analysis are available on request and without restriction by contacting the corresponding author. Acquired or processed NIfTI images are not available due to patient confidentiality agreements.Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdfAppendix: Table A1 available at https://www.sciencedirect.com/science/article/pii/S1053811921010211?via%3Dihub#tbl0001 ; Appendix B. Supplementary materials available at https://ars.els-cdn.com/content/image/1-s2.0-S1053811921010211-mmc1.docx (Word document (3MB)).Copyright © 2021 The Authors. Neurite orientation dispersion and density imaging (NODDI) estimates microstructural properties of brain tissue relating to the organisation and processing capacity of neurites, which are essential elements for neuronal communication. Descriptive statistics of NODDI tissue metrics are commonly analyzed in regions-of-interest (ROI) to identify brain-phenotype associations. Here, the conventional method to calculate the ROI mean weights all voxels equally. However, this produces biased estimates in the presence of CSF partial volume. This study introduces the tissue-weighted mean, which calculates the mean NODDI metric across the tissue within an ROI, utilising the tissue fraction estimate from NODDI to reduce estimation bias. We demonstrate the proposed mean in a study of white matter abnormalities in young onset Alzheimer's disease (YOAD). Results show the conventional mean induces significant bias that correlates with CSF partial volume, primarily affecting periventricular regions and more so in YOAD subjects than in healthy controls. Due to the differential extent of bias between healthy controls and YOAD subjects, the conventional mean under- or over-estimated the effect size for group differences in many ROIs. This demonstrates the importance of using the correct estimation procedure when inferring group differences in studies where the extent of CSF partial volume differs between groups. These findings are robust across different acquisition and processing conditions. Bias persists in ROIs at higher image resolution, as demonstrated using data obtained from the third phase of the Alzheimer's disease neuroimaging initiative (ADNI); and when performing ROI analysis in template space. This suggests that conventional ROI means of NODDI metrics are biased estimates under most contemporary experimental conditions, the correction of which requires the proposed tissue-weighted mean. The tissue-weighted mean produces accurate estimates of ROI means and group differences when ROIs contain voxels with CSF partial volume. In addition to NODDI, the technique can be applied to other multi-compartment models that account for CSF partial volume, such as the free water elimination method. We expect the technique to help generate new insights into normal and abnormal variation in tissue microstructure of regions typically confounded by CSF partial volume, such as those in individuals with larger ventricles due to atrophy associated with neurodegenerative disease.CP and GZ were funded by the Wellcome Trust (Collaborative Award 200181/Z/15/Z). TV was funded by an Alzheimer's Research UK PhD scholarship (ARUK-PhD2018–009). MB was supported by a Fellowship award from the Alzheimer's Society, UK (AS-JF-19a-004–517). MB's work was also supported by the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. IM was supported by Alzheimer's Research UK (ARUK-PG2014–1946, ARUK-PG2017–1946) and the Wolfson Foundation (PR/ylr/18575). DLT was supported by the UCL Leonard Wolfson Experimental Neurology Centre (PR/ylr/18575), UCLH NIHR Biomedical Research Centre and the Wellcome Trust (Centre award 539208). JMS acknowledges the support of the National Institute for Health Research University College London Hospitals Biomedical Research Centre, Wolfson Foundation, Alzheimer's Research UK, Brain Research UK, Weston Brain Institute, Medical Research Council, British Heart Foundation, UK Dementia Research Institute and Alzheimer's Association. DMC was supported by the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK, as well as Alzheimer's Research UK (ARUK‐PG2017‐1946) and the UCL/UCLH NIHR Biomedical Research Centre. We would also like to acknowledge Prof. Nick Fox who is a senior NIHR investigator for his role in conceiving the initial YOAD study preceding this work. The authors would like to thank all research participants who made this study possible, as well as Alzheimer's Research UK and Iceland Foods Charitable Foundation for funding the Young-Onset Alzheimer's disease study. The Dementia Research Centre is supported by Alzheimer's Research UK, Brain Research Trust, and The Wolfson Foundation. They also thank Kirsty Lu, Amelia Carton, Timothy Shakespeare, Keir Yong, Aida Suarez Gonzalez and Silvia Primativo for assistance with neuropsychology assessments

Interleukin-1β sequesters hypoxia inducible factor 2α to the primary cilium.

BACKGROUND: The primary cilium coordinates signalling in development, health and disease. Previously we have shown that the cilium is essential for the anabolic response to loading and the inflammatory response to interleukin-1β (IL-1β). We have also shown the primary cilium elongates in response to IL-1β exposure. Both anabolic phenotype and inflammatory pathology are proposed to be dependent on hypoxia-inducible factor 2 alpha (HIF-2α). The present study tests the hypothesis that an association exists between the primary cilium and HIFs in inflammatory signalling. RESULTS: Here we show, in articular chondrocytes, that IL-1β-induces primary cilia elongation with alterations to cilia trafficking of arl13b. This elongation is associated with a transient increase in HIF-2α expression and accumulation in the primary cilium. Prolyl hydroxylase inhibition results in primary cilia elongation also associated with accumulation of HIF-2α in the ciliary base and axoneme. This recruitment and the associated cilia elongation is not inhibited by blockade of HIFα transcription activity or rescue of basal HIF-2α expression. Hypomorphic mutation to intraflagellar transport protein IFT88 results in limited ciliogenesis. This is associated with increased HIF-2α expression and inhibited response to prolyl hydroxylase inhibition. CONCLUSIONS: These findings suggest that ciliary sequestration of HIF-2α provides negative regulation of HIF-2α expression and potentially activity. This study indicates, for the first time, that the primary cilium regulates HIF signalling during inflammation

An HLA-I signature favouring KIR-educated Natural Killer cells mediates immune control of HIV in children and contrasts with the HLA-B-restricted CD8+T-cell-mediated immune control in adults

Natural Killer (NK) cells contribute to HIV control in adults, but HLA-B-mediated T-cell activity has a more substantial impact on disease outcome. However, the HLA-B molecules influencing immune control in adults have less impact on paediatric infection. To investigate the contribution NK cells make to immune control, we studied >300 children living with HIV followed over two decades in South Africa. In children, HLA-B alleles associated with adult protection or disease-susceptibility did not have significant effects, whereas Bw4 (p = 0.003) and low HLA-A expression (p = 0.002) alleles were strongly associated with immunological and viral control. In a comparator adult cohort, Bw4 and HLA-A expression contributions to HIV disease outcome were dwarfed by those of protective and disease-susceptible HLA-B molecules. We next investigated the immunophenotype and effector functions of NK cells in a subset of these children using flow cytometry. Slow progression and better plasma viraemic control were also associated with high frequencies of less terminally differentiated NKG2A+NKp46+CD56dim NK cells strongly responsive to cytokine stimulation and linked with the immunogenetic signature identified. Future studies are indicated to determine whether this signature associated with immune control in early life directly facilitates functional cure in children