The evidence for beneficial effects of recommended levels of physical activity is overwhelming. However, 70% of Australians fail to meet these levels. In particular, physical activity participation ...by women falls sharply between ages 16 to 25 years. Further information about physical activity measures in young women is needed. Self-administered questionnaires are often used to measure physical activity given their ease of application, but known limitations, including recall bias, compromise the accuracy of data. Alternatives such as objective measures are commonly used to overcome this problem, but are more costly and time consuming.
To compare the output between the Modified Active Australia Survey (MAAS), the International Physical Activity Questionnaire (IPAQ), and an objective physical activity measure-the SenseWear Armband (SWA)-to evaluate the test-retest reliability of the MAAS and to determine the acceptability of the SWA among young women.
Young women from Victoria, Australia, aged 18 to 25 years who had participated in previous studies via Facebook advertising were recruited. Participants completed the two physical activity questionnaires online, immediately before and after wearing the armband for 7 consecutive days. Data from the SWA was blocked into 10-minute activity times. Follow-up IPAQ, MAAS, and SWA data were analyzed by comparing the total continuous and categorical activity scores, while concurrent validity of IPAQ and MAAS were analyzed by comparing follow-up scores. Test-retest reliability of MAAS was analyzed by comparing MAAS total physical activity scores at baseline and follow-up. Participants provided feedback in the follow-up questionnaire about their experience of wearing the armband to determine acceptability of the SWA. Data analyses included graphical (ie, Bland-Altman plot, scatterplot) and analytical (ie, canonical correlation, kappa statistic) methods to determine agreement between MAAS, IPAQ, and SWA data.
A total of 58 participants returned complete data. Comparisons between the MAAS and IPAQ questionnaires (n=52) showed moderate agreement for both categorical (kappa=.48, P<.001) and continuous data (r=.69, P<.001). Overall, the IPAQ tended to give higher scores. No significant correlation was observed between SWA and IPAQ or MAAS continuous data, for both minute-by-minute and blocked SWA data. The SWA tended to record lower scores than the questionnaires, suggesting participants tended to overreport their amount of physical activity. The test-retest analysis of MAAS showed moderate agreement for continuous outcomes (r=.44, P=.001). However, poor agreement was seen for categorical outcomes. The acceptability of the SWA to participants was high.
Moderate agreement between the MAAS and IPAQ and moderate reliability of the MAAS indicates that the MAAS may be a suitable alternative to the IPAQ to assess total physical activity in young women, due to its shorter length and consequently lower participant burden. The SWA, and likely other monitoring devices, have the advantage over questionnaires of avoiding overreporting of self-reported physical activity, while being highly acceptable to participants.
Abstract Asia Oceania includes countries from both the Asia Pacific region and Australasia, which cover very diverse geographical areas and populations as well as bearing 52% of the cervical cancer ...burden in the world. Human papillomavirus (HPV) genotype distribution in women with normal cytology varies between countries in this region, as well as with the distribution typically observed in worldwide estimates or in Western countries. HPV-16 remains the predominant oncogenic type for high-grade cervical dysplasia and cervical cancer across the region, and HPV-18 is generally among the five most common types. HPV-58 is commonly found in cervical cancer as well as in women with normal cytology, and HPV-31, 33 and 35 are relatively less frequent in these regions compared to the West. While screening programmes have been proposed and implemented in several populations, successful programmes are rather limited and the majority of countries still have no or minimal screening services. Prophylactic HPV vaccination will only be feasible when it becomes affordable, thus the current priority and the short-term goal for cervical cancer control is to identify feasible and effective screening measures, and to find the most effective way to combine vaccination with sustainable screening programmes. This Regional Report has carefully described the disease burden of HPV and cervical cancer and the current situations in cervical cancer prevention for many countries in the Asia Oceania region. These data identify the many challenges and opportunities to be considered for policy decisions for cervical cancer control. Furthermore, this report presents the results of advanced decision analytic models calibrated to countries in the region that provide early insight into what strategies are most promising and those likely to be cost-effective and affordable. It thus provides a synthesis of the available evidence-based scientific information, in the context of a significant and systematic international review, that is likely to be useful to governments and public health providers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Conventional immunoglobulin (Ig) markers have been used to define multiple myeloma (MM) responses, but assessment of marrow for minimal residual disease (MRD) may provide better information on ...disease status/prognosis (Paiva B, et al. Blood 2008; 112: 4017). We therefore initiated a national multi-center ASCT trial with the goal of producing a high rate of MRD-negativity by using bortezomib (btz)-based induction, enhancing the conditioning regimen and utilizing post-ASCT maintenance.
This phase 2 open label-trial was conducted in 10 Canadian centers. After btz-based induction (usually CyBorD) in the absence of disease progression, patients (pts) received BuMel conditioning (IV busulfan 3.2 mg/kg days -5 to -3 or days -6 to -4 + melphalan 140 mg/m2 day -2 or day -3), followed by ASCT on day 0. On day 100 post-ASCT, lenalidomide (len) 10 mg/day was commenced, escalated to 15 mg/day after 3 cycles if appropriate, and continued until disease progression.
Bone marrow aspirate (BMA) samples were shipped centrally for MRD analysis by 15-color multiparameter flow cytometry (MFC) before any therapy, prior to ASCT, on day 100 post-ASCT, every 3 mos for the 1st year and every 6 mos thereafter until progression.
Between 03/2013 - 07/2014, 99 newly diagnosed MM pts provided untreated BMA samples for MRD analysis. To date, 42 of a planned target of 78 pts have completed induction therapy have undergone ASCT and 39 are evaluable so far. 25 of the 99 (25%) who provided initial marrow samples did not meet criteria for enrollment: 3 (3%) had poor BMA samples; 3 (3%) did not have confirmed MM; 6 (6%) did not proceed with ASCT (1 due to progression); 1 (1%) had received dexamethasone prior to MRD analysis; 1 (1%) died during induction and 11 (11%) withdrew consent/opted for standard conditioning.
Median age of the 39 evaluable pts is 53 (39-67); 64% are male. Median serum β2-microglobulin level is 3.64 mg/L (1.7-20) and albumin 37 g/L (2.8-48.1); 17 pts have ISS stage I; 9 have stage II; 9 have stage III MM and 4 have missing data. Ig subtype includes IgGκ in 16 (40%), IgGλ in 4 (10%), IgAκ in 5 (13%), IgAλ in 8 (21%), IgMλ in 1 (3%), κ in 1 (3%); non-secretory in 2 (5%) and no data in 2 pts (5%).
Post-ASCT, only 4 SAEs have occurred: atrial fibrillation (2), acute kidney injury (1) and sepsis (1). There have been no ASCT-related deaths, and no pt has progressed at a median follow-up of 7.8 mos (range: 4.8-10.1).
The best Ig response post-induction in the 31 pts with available restaging data is CR in 5 (16%), VGPR in 9 (29%), PR in 13 (42%), and SD in 1 (3%). 27 pts have reached day 100 post-ASCT and 8 pts have been formally evaluated. In these 8, the Ig response is CR in 2 (25%), VGPR in 5 (63%) and PR in 1 (12%). Table 1 summarizes MRD results to date.
Table 1Comparison of conventional Ig response rates and achievement of MRD negativity# Conventional Ig Responses # MRD negativeTime point of assessment#EvaluableTotal # MRD negativeCRVGPRPRMRAfter btz-based induction3165 39 113 20Day 100 post-ASCT822 250100During len maintenance5105 100
Conclusions: 1) MFC performed on pre-therapy marrow samples to allow subsequent evaluation for MRD was successful in 97% of pts using a central lab; 2) IV BuMel was well-tolerated with few SAEs and no ASCT-related deaths; 3) MRD and conventional Ig responses may not correlate well; 4) Further F/U is required to determine the dynamics of MRD achievement and long term outcomes with this approach.
Reece:Novartis: Honoraria, Research Funding; BMS: Research Funding; Merck: Research Funding; Millennium: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Amgen: Honoraria. Off Label Use: Lenalidomide maintenance after ASCT. Venner:Celgene: Honoraria, Research Funding; Janssen: Honoraria. White:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Sebag:Novartis: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Song:Celgene: Honoraria; Otsuka: Honoraria; janssen: Honoraria. Tay:Celgene: Honoraria; Janssen: Honoraria. Kukreti:Celgene: Honoraria. Trudel:Glaxo Smith Kline: Honoraria, Research Funding; Novartis: Honoraria; Celgene: Honoraria; Oncoethix: Research Funding. Tiedemann:Celgene: Honoraria; Janssen: Honoraria. Chen:Millennium: Research Funding; Janssen: Honoraria; Celgene: Honoraria, Research Funding.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
With a vaccination program currently planned to protect Singaporean women from human papillomavirus, a need arises for assessing Singaporean women's knowledge of human papillomavirus and attitudes ...toward human papillomavirus vaccination to identify barriers to a successful program and to help inform health education campaigns. A representative sample of 2,145 women aged between 18 and 49 years were randomly selected from households throughout Singapore and interviewed with a similar questionnaire to that used in a recent study of Australian women. Although Singaporean women's knowledge of human papillomavirus was poor, with only 20% having heard of it, attitudes toward human papillomavirus vaccination were generally positive. The most trusted sources of information about human papillomavirus and vaccination were gynecologists and general practitioners. Based on our findings, an urgent need exists in Singapore for accurate and accessible information about human papillomavirus and the benefits of vaccination.
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IJS, NUK, UL, UM, UPUK, VSZLJ
This paper aims to provide evidence-based recommendations for health professionals, to develop a comprehensive cervical cancer program for a clinic, a community, or a country. Ensuring access to ...healthcare is the responsibility of all societies, and the Asia Oceania Research Organisation in Genital Infections and Neoplasia (AOGIN) is committed to working collaboratively with governments and health professionals to facilitate prevention programs, to protect girls and women from cervical cancer, a disease that globally affects 500,000 and kills nearly 300,000 women annually, just over half of whom are in the Asia Oceania region. We share the vision that a comprehensive program of vaccination, screening, and treatment should be made accessible to all girls and women in the world. The primary purpose of these guidelines is to provide information on scientific evidence on the different modalities and approaches of cervical cancer prevention programs, for high resource and low resource settings. The secondary purpose is to provide an overview of the current situation of cervical cancer control and prevention in various Asian Oceania countries: their views of an ideal program, identified obstacles, and suggestions to overcome them are discussed.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract Most approaches to transplant tolerance involve treatment of the recipient to prevent rejection. This study investigates donor treatment with IL-4 for its effect on subsequent rat liver ...allograft survival. Rat orthotopic liver transplants were performed in rejecting (PVG donor to Lewis recipient) or spontaneously tolerant (PVG to DA) strain combinations. Donors were untreated or injected intraperitoneally with IL-4 (30,000 U/day) for 5 days. Tissue infiltrates and gene expression were examined by immunohistochemistry and real-time quantitative PCR. IL-4 induced a marked leukocyte infiltrate in donor livers prior to transplant. Macrophages comprised the major population, although B cells, T cells and natural killer (NK) cells also increased. IL-4-induced liver macrophages had an alternatively activated phenotype with increased expression of mannose receptor but not inducible nitric oxide synthase (NOS2). IL-4 also induced IDO and IFN-gamma expression by NK cells. Donor IL-4-treatment converted rejection to acceptance in the majority of Lewis recipients (median survival time > 96 days) and did not prevent acceptance in DA recipients. Acceptance in Lewis recipients was associated with increased donor cell migration to recipient spleens and increased splenic IL-2, IFN-gamma and IDO expression 24 h after transplantation. Donor IL-4-treatment increased leukocytes in the donor liver including potentially immunosuppressive populations of alternatively activated macrophages and IDO-expressing NK cells. Donor treatment led to long-term acceptance of most livers in association with early immune activation in recipient lymphoid tissues.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
High estradiol (E
) levels are linked to an increased risk of venous thromboembolism; however, the underlying molecular mechanism(s) remain poorly understood. We previously identified an E
...-responsive microRNA (miR), miR-494-3p, that downregulates protein S expression, and posited additional coagulation factors, such as tissue factor, may be regulated in a similar manner via miRs.
To evaluate the coagulation capacity of cohorts with high physiological E
, and to further characterize novel E
-responsive miR and miR regulation on tissue factor in E
-related hypercoagulability.
Ceveron Alpha thrombin generation assay (TGA) was used to assess plasma coagulation profile of three cohorts. The effect of physiological levels of E
, 10 nM, on miR expression in HuH-7 cells was compared using NanoString nCounter and validated with independent assays. The effect of tissue factor-interacting miR was confirmed by dual-luciferase reporter assays, immunoblotting, flow cytometry, biochemistry assays, and TGA.
Plasma samples from pregnant women and women on the contraceptive pill were confirmed to be hypercoagulable (compared with sex-matched controls). At equivalent and high physiological levels of E
, miR-365a-3p displayed concordant E
downregulation in two independent miR quantification platforms, and tissue factor protein was upregulated by E
treatment. Direct interaction between miR-365a-3p and
3'UTR was confirmed and overexpression of miR-365a-3p led to a decrease of (1) tissue factor mRNA transcripts, (2) protein levels, (3) activity, and (4) tissue factor-initiated thrombin generation.
miR-365a-3p is a novel tissue factor regulator. High E
concentrations induce a hypercoagulable state via a miR network specific for coagulation factors.
BackgroundMolybdenum cofactor deficiency (MoCD) (OMIM# 252150) is an autosomal-recessive disorder caused by mutations in four genes involved in the molybdenum cofactor (MOCO) biosynthesis ...pathway.ObjectivesWe report a milder phenotype in a patient with MOCS1 gene mutation who presented with a Leigh-like presentation.Case reportWe present the case of a 10-year-old boy who was symptomatic at the age of 5 months with sudden onset of dyskinesia, nystagmus, and extrapyramidal signs following a febrile illness. Initial biochemical, radiological, and histopathological findings a Leigh syndrome-like phenotype; however, whole-exome sequencing detected compound heterozygous mutations in MOCS1 gene, c.1133 G>C and c.217C>T, confirming an underlying MoCD. This was biochemically supported by low uric acid level of 80 (110-282 mmol/L) and low cystine level of 0 (3-49), and a urine S-sulfocysteine at 116 (0-15) mmol/mol creatinine. The patient was administered methionine- and cystine-free formulas. The patient has remained stable, with residual intellectual, speech, and motor sequelae.ConclusionThis presentation expands the phenotypic variability of late-onset MoCD A and highlights the role of secondary mitochondrial dysfunction in its pathogenesis.
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