Wrist Accelerometer Cut Points for Classifying Sedentary Behavior in Children.

INTRODUCTION: This study aimed to examine the validity and accuracy of wrist accelerometers for classifying sedentary behavior (SB) in children. METHODS: Fifty-seven children (5-8 and 9-12 yr) completed an ~170-min protocol, including 15 semistructured activities and transitions. Nine ActiGraph (GT3X+) and two GENEActiv wrist cut points were evaluated. Direct observation was the criterion measure. The accuracy of wrist cut points was compared with that achieved by the ActiGraph hip cut point (≤25 counts per 15 s) and the thigh-mounted activPAL3. Analyses included equivalence testing, Bland-Altman procedures, and area under the receiver operating curve (ROC-AUC). RESULTS: The most accurate ActiGraph wrist cut points (Kim; vector magnitude, ≤3958 counts per 60 s; vertical axis, ≤1756 counts per 60 s) demonstrated good classification accuracy (ROC-AUC = 0.85-0.86) and accurately estimated SB time in 5-8 yr (equivalence P = 0.02; mean bias = 4.1%, limits of agreement = -20.1% to 28.4%) and 9-12 yr (equivalence P 0.05) and classification accuracy (ROC-AUC = 0.79-0.80) was lower than for ActiGraph hip and activPAL3. CONCLUSION: The most accurate SB ActiGraph (Kim) and GENEActiv (Schaefer) wrist cut points can be applied in children with similar confidence as the ActiGraph hip cut point (≤25 counts per 15 s), although activPAL3 was generally more accurate.This study was funded by the National Heart Foundation of Australia (G11S5975). DPC is supported by an Australian Research Council Discovery Early Career Researcher Award (DE140101588). ADO is supported by a National Heart Foundation of Australia Career Development Fellowship (CR11S 6099). TH is funded by a National Health and Medical Research Council Early Career Fellowship (APP1070571). The work of UE and SB is funded by the UK Medical Research Council (MC_UU_12015/3). ST is supported by the National Health and Medical Research Council Centre of Research Excellence on Sitting Time and Chronic Disease Prevention (APP1057608)

Increasing physical activity among young children from disadvantaged communities: Study protocol of a group randomised controlled effectiveness trial

Background: Participation in regular physical activity (PA) during the early years helps children achieve healthy body weight and can substantially improve motor development, bone health, psychosocial health and cognitive development. Despite common assumptions that young children are naturally active, evidence shows that they are insufficiently active for health and developmental benefits. Exploring strategies to increase physical activity in young children is a public health and research priority. Methods: Jump Start is a multi-component, multi-setting PA and gross motor skill intervention for young children aged 3–5 years in disadvantaged areas of New South Wales, Australia. The intervention will be evaluated using a two-arm, parallel group, randomised cluster trial. The Jump Start protocol was based on Social Cognitive Theory and includes five components: a structured gross motor skill lesson (Jump In); unstructured outdoor PA and gross motor skill time (Jump Out); energy breaks (Jump Up); activities connecting movement to learning experiences (Jump Through); and a home-based family component to promote PA and gross motor skill (Jump Home). Early childhood education and care centres will be demographically matched and randomised to Jump Start (intervention) or usual practice (comparison) group. The intervention group receive Jump Start professional development, program resources, monthly newsletters and ongoing intervention support. Outcomes include change in total PA (accelerometers) within centre hours, gross motor skill development (Test of Gross Motor Development-2), weight status (body mass index), bone strength (Sunlight MiniOmni Ultrasound Bone Sonometer), self-regulation (Heads-Toes-Knees-Shoulders, executive function tasks, and proxy-report Temperament and Approaches to learning scales), and educator and parent self-efficacy. Extensive quantitative and qualitative process evaluation and a cost-effectiveness evaluation will be conducted. Discussion: The Jump Start intervention is a unique program to address low levels of PA and gross motor skill proficiency, and support healthy lifestyle behaviours among young children in disadvantaged communities. If shown to be efficacious, the Jump Start approach can be expected to have implications for early childhood education and care policies and practices, and ultimately a positive effect on the health and development across the life course

\u27Jump start\u27 childcare-based intervention to promote physical activity in pre-schoolers: six-month findings from a cluster randomised trial

BACKGROUND: Participation in adequate levels of physical activity during the early years is important for health and development. We report the 6-month effects of an 18-month multicomponent intervention on physical activity in early childhood education and care (ECEC) settings in low-income communities. METHODS: A cluster randomised controlled trial was conducted in 43 ECEC settings in disadvantaged areas of New South Wales, Australia. Three-year-old children were recruited and assessed in the first half of 2015 with follow-up 6 months later. The intervention was guided by Social Cognitive Theory and included five components. The primary outcome was minutes per hour in total physical activity during ECEC hours measured using Actigraph accelerometers. Intention-to-treat analysis of the primary outcome was conducted using a generalized linear mixed model. RESULTS: A total of 658 children were assessed at baseline. Of these, 558 (85%) had valid accelerometer data (mean age 3.38y, 52% boys) and 508 (77%) had valid accelerometry data at 6-month follow-up. Implementation of the intervention components ranged from 38 to 72%. There were no significant intervention effects on mins/hr. spent in physical activity (adjusted difference = - 0.17 mins/hr., 95% CI (- 1.30 to 0.97), p = 0.78). A priori sub-group analyses showed a greater effect among overweight/obese children in the control group compared with the intervention group for mins/hr. of physical activity (2.35mins/hr., [0.28 to 4.43], p = 0.036). CONCLUSIONS: After six-months the Jump Start intervention had no effect on physical activity levels during ECEC. This was largely due to low levels of implementation. Increasing fidelity may result in higher levels of physical activity when outcomes are assessed at 18-months

Wrist Acceleration Cut Points for Moderate-to-Vigorous Physical Activity in Youth.

PURPOSE: This study aimed to examine the validity of wrist acceleration cut points for classifying moderate (MPA), vigorous (VPA), and moderate-to-vigorous (MVPA) physical activity. METHODS: Fifty-seven children (5-12 yr) completed 15 semistructured activities. Three sets of wrist cut points (>192 mg, >250 mg, and >314 mg), previously developed using Euclidian norm minus one (ENMO192+), GENEActiv software (GENEA250+), and band-pass filter followed by Euclidian norm (BFEN314+), were evaluated against indirect calorimetry. Analyses included classification accuracy, equivalence testing, and Bland-Altman procedures. RESULTS: All cut points classified MPA, VPA, and MVPA with substantial accuracy (ENMO192+: κ = 0.72 [95% confidence interval = 0.72-0.73], MVPA: area under the receiver operating characteristic curve (ROC-AUC) = 0.85 [0.85-0.86]; GENEA250+: κ = 0.75 [0.74-0.76], MVPA: ROC-AUC = 0.85 [0.85-0.86]; BFEN314+: κ = 0.73 [0.72-0.74], MVPA: ROC-AUC = 0.86 [0.86-0.87]). BFEN314+ misclassified 19.7% non-MVPA epochs as MPA, whereas ENMO192+ and GENEA250+ misclassified 32.6% and 26.5% of MPA epochs as non-MVPA, respectively. Group estimates of MPA time were equivalent (P < 0.01) to indirect calorimetry for the BFEN314+ MPA cut point (mean bias = -1.5%, limits of agreement [LoA] = -57.5% to 60.6%), whereas estimates of MVPA time were equivalent (P < 0.01) to indirect calorimetry for the ENMO192+ (mean bias = -1.1%, LoA = -53.7% to 55.9%) and GENEA250+ (mean bias = 2.2%, LoA = -56.5% to 52.2%) cut points. Individual variability (LoA) was large for MPA (min: BFEN314+, -60.6% to 57.5%; max: GENEA250+, -42.0% to 104.1%), VPA (min: BFEN314+, -238.9% to 54.6%; max: ENMO192+, -244.5% to 127.4%), and MVPA (min: ENMO192+, -53.7% to 55.0%; max: BFEN314+, -83.9% to 25.3%). CONCLUSION: Wrist acceleration cut points misclassified a considerable proportion of non-MVPA and MVPA. Group-level estimates of MVPA were acceptable; however, error for individual-level prediction was larger

Height, selected genetic markers and prostate cancer risk:Results from the PRACTICAL consortium

Background: Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a possible role for its association with the risk of aggressive prostate cancer. Methods: We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases and 6016 controls and a subset of high grade cases (2480 cases). We explored height, polymorphisms in genes related to growth processes as main effects and their possible interactions. Results: The results suggest that height is associated with high-grade prostate cancer risk. Men with height 4180cm are at a 22% increased risk as compared to men with height o173cm (OR 1.22, 95% CI 1.01–1.48). Genetic variants in the growth pathway gene showed an association with prostate cancer risk. The aggregate scores of the selected variants identified a significantly increased risk of overall prostate cancer and high-grade prostate cancer by 13% and 15%, respectively, in the highest score group as compared to lowest score group. Conclusions: There was no evidence of gene-environment interaction between height and the selected candidate SNPs. Our findings suggest a role of height in high-grade prostate cancer. The effect of genetic variants in the genes related to growth is seen in all cases and high-grade prostate cancer. There is no interaction between these two exposures.</p

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Chemokine - Chemokine receptors in cancer immunotherapy

A surge in interest in the chemokine-chemokine receptor network is probably related to the expanding roles that chemokines have now been identified to play in human biology, particularly immunity. Specific tissue microenvironments express distinct chemokines and both hematopoietic and nonhematopoietic cells have receptor expression profiles that permit the coordinated trafficking and organization of cells within these specific tissues. Since the chemokine network plays critical roles in both the function of the immune system and the progression of cancer, it is an attractive target for therapeutic manipulation. This review will focus on chemokine and chemokine receptor network-related therapeutic interventions that utilize host-tumor interactions particularly involving the immune system

Improving cancer immunotherapy by targeting tumor-induced immune suppression

The status of a host's immune response influences both the development and progression of a malignancy such that immune responses can have both pro- and anti-tumorigenic effects. Cancer immunotherapy is a form of treatment that aims to improve the ability of a cancer-bearing individual to reject the tumor immunologically. However, antitumor immunity elicited by the host or by immunotherapeutic strategies, can be actively attenuated by mechanisms that limit the strength and/or duration of immune responses, including the presence of immunoregulatory cell types or the production of immunosuppressive factors. As our knowledge of tumor-induced immune suppression increases, it has become obvious that these mechanisms are probably a major barrier to effective therapy. The identification of multiple mechanisms of tumor-induced immune suppression also provides a range of novel targets for new cancer therapies. Given the vital role that a host's immune response is known to play in cancer progression, therapies that target immune suppressive mechanisms have the potential to enhance anticancer immune responses thus leading to better immune surveillance and the limitation of tumor escape. In this review, mechanisms of tumor-associated immune suppression have been divided into four forms that we have designated as (1) regulatory cells; (2) cytokines/chemokines; (3) T cell tolerance/exhaustion and (4) metabolic. We discuss select mechanisms representing each of these forms of immunosuppression that have been shown to aid tumors in evading host immune surveillance and overview therapeutic strategies that have been recently devised to "suppress these suppressors.

Sensitivity of a novel model of mammary cancer stem cell-like cells to TNF-related death pathways

Cancer stem cells (CSC) are resistant to radiation and chemotherapy and play a significant role in cancer recurrence and metastatic disease. It is therefore important to identify alternative strategies, such as immunotherapies that can be used to control this refractory population. A CD44?CD24-/low subpopulation of cells within the B6 PyMT-MMTV transgenic mouse-derived AT-3 mammary carcinoma cell line was identified, which had CSC-like characteristics, including pluripotency and a resistance to chemo- and radiotherapy. Therefore, unlike xenograph models that require immunocompromised settings, this novel system may provide a means to study immune-mediated responses against CSC-like cells. The immunobiology of the AT-3 CSC-like cell population was studied by their surface molecule expression profile and their sensitivity to specified cell death pathways. Comparable levels of Rae-1, CD155, CD54 and higher levels of Fas and DR5 were expressed on the AT-3 CSC-like cells compared to non-CSC-like tumor cells. Expression correlated with an in vitro sensitivity to cell death by NK cells or through the ligation of the death receptors (Fas or DR5), by their ligands or anti-Fas and anti-DR5 mAbs. Indeed, compared to the rest of the AT-3 tumor cells, the CD44?CD24-/low subpopulation of cells were more sensitive to both Fas- and TRAIL-mediated cell death pathways. Therefore, despite the refractory nature of CSC to other conventional therapies, these CSC-like cells were not inherently resistant to specified forms of immune-mediated cell death. These results encourage the continued investigation into immunotherapeutic strategies as a means of controlling breast CSC, particularly through their cell death pathways