Validation of a parent-proxy quality of life questionnaire for paediatric chronic cough (PC-QOL)

Background Quality of life (QOL) measures are an important patient-relevant outcome measure for clinical studies. Currently there is no fully validated cough-specific QOL measure for paediatrics. The objective of this study was to validate a cough-specific QOL questionnaire for paediatric use. Method 43 children (28 males, 15 females; median age 29 months, IQR 20–41 months) newly referred for chronic cough participated. One parent of each child completed the 27-item Parent Cough-Specific QOL questionnaire (PC-QOL), and the generic child (Pediatric QOL Inventory 4.0 (PedsQL)) and parent QOL questionnaires (SF-12) and two cough-related measures (visual analogue score and verbal category descriptive score) on two occasions separated by 2–3 weeks. Cough counts were also objectively measured on both occasions. Results Internal consistency for both the domains and total PC-QOL at both test times was excellent (Cronbach alpha range 0.70–0.97). Evidence for repeatability and criterion validity was established, with significant correlations over time and significant relationships with the cough measures. The PC-QOL was sensitive to change across the test times and these changes were significantly related to changes in cough measures (PC-QOL with: verbal category descriptive score, rs=−0.37, p=0.016; visual analogue score, rs=−0.47, p=0.003). Significant correlations of the difference scores for the social domain of the PC-QOL and the domain and total scores of the PedsQL were also noted (rs=0.46, p=0.034). Conclusion The PC-QOL is a reliable and valid outcome measure that assesses QOL related to childhood cough at a given time point and measures changes in cough-specific QOL over time.

Toward understanding the (lack of?) significance of dialogue to the practice of public relations

The public relations literature has tended to present dialogue as an idealised concept, with a focus on how it should, could, or ought to be carried out in public relations practice. There is little in extant literature that considers the significance of dialogue to the actual practice of public relations. This paper presents the findings of a qualitative study of public relations practitioners’ day-to-day work. It concludes that dialogue does not – and arguably, cannot – occur in public relations practice and instead articulates an empirically-based practitioner perspective on two-way communication, which displays pragmatic characteristics that significantly distinguish it from dialogue.

Predicting movie ratings from audience behaviors

We propose a method of representing audience behavior through facial and body motions from a single video stream, and use these features to predict the rating for feature-length movies. This is a very challenging problem as: i) the movie viewing environment is dark and contains views of people at different scales and viewpoints; ii) the duration of feature-length movies is long (80-120 mins) so tracking people uninterrupted for this length of time is still an unsolved problem, and; iii) expressions and motions of audience members are subtle, short and sparse making labeling of activities unreliable. To circumvent these issues, we use an infrared illuminated test-bed to obtain a visually uniform input. We then utilize motion-history features which capture the subtle movements of a person within a pre-defined volume, and then form a group representation of the audience by a histogram of pair-wise correlations over a small-window of time. Using this group representation, we learn our movie rating classifier from crowd-sourced ratings collected by rottentomatoes.com and show our prediction capability on audiences from 30 movies across 250 subjects (> 50 hrs).

MMP-14 is expressed in preeclamptic placentas and mediates release of soluble endoglin

Soluble endoglin is an anti-angiogenic protein that is released from the placenta and contributes to both maternal endothelial dysfunction and the clinical features of severe preeclampsia. The mechanism through which soluble endoglin is released from the placenta is currently unknown; however, recent work in colorectal cancer identified matrix metalloproteinase 14 (MMP-14) as the cleavage protease of endoglin. To determine whether this is also the mechanism responsible for soluble endoglin release in preeclampsia, we investigated the expression of MMP-14 within the placenta and the effects of its inhibition on soluble endoglin release. Placentas were obtained from severe, early onset preeclamptic pregnancies (n = 8) and gestationally matched preterm controls (n = 8). MMP-14 was predominately localized to the syncytiotrophoblast. Results from a proximity ligation assay showed protein interactions between endogenous MMP-14 and endoglin within the preeclamptic placenta. To demonstrate that this interaction produces soluble endoglin, we treated trophoblastic BeWo cells with either a broad-spectrum MMP inhibitor (GM6001) or MMP-14 siRNA. Both treatments produced a decrease in soluble endoglin (P ≤ 0.05). Treatment of mice bearing BeWo xenografts with GM6001 decreased circulating soluble endoglin levels in mouse serum (P ≤ 0.05). These findings indicate that MMP-14 is the likely cleavage protease of endoglin in the setting of preeclampsia. This approach provides a novel method for the development of potential therapeutics to reduce circulating soluble endoglin and ameliorate the clinical features of severe preeclampsia.

Senator Elizabeth Warren fights the White House over the secret Trans-Pacific Partnership #TPP #TPPA

In his visit to the G20 in Brisbane, President Barack Obama sought to promote his ambitious Pacific Rim trade agreement — the Trans-Pacific Partnership (TPP). He told an audience at the University of Queensland: We’ll keep leading the effort to realize the Trans-Pacific Partnership to lower barriers, open markets, export goods, and create good jobs for our people. But with the 12 countries of the TPP making up nearly 40 percent of the global economy, this is also about something bigger. It is our chance to put in place new, high standards for trade in the 21st century that uphold our values. So, for example, we are pushing new standards in this trade agreement, requiring countries that participate to protect their workers better and to protect the environment better, and protect intellectual property that unleashes innovation, and baseline standards to ensure transparency and rule of law.

Measurement of disordered eating in Latina college women

The Eating Disorder Risk Composite (EDRC) comprises the Drive for Thinness, Bulimia, and Body Dissatisfaction subscales of the Eating Disorder Inventory, Third Edition (EDI-3, Garner, 2004). Past research conducted with Latina college women (LCW) has found older versions of the EDRC subscales to be reliable, but the EDI-3's EDRC factor structure has yet to be studied among LCW. The present study investigated the pattern of responses to and the factor structure of the EDRC in LCW. It was hypothesized that eating pathology would be present and that a factor analysiswould find some discrepancies between the original factor structure of the EDRC and the factor structure from LCW. Analyses of data on a 6-point Likert scale indicate that drive for thinness and body dissatisfaction are far more prevalent than is bulimic symptomology in LCW. Principal Axis Factoring with promax rotation was used to extract three factors very similar to the original EDRC. Some discrepancies in the item loadings were observed, most notably that half of the items from the original Body Dissatisfaction subscale did not load together on one factor. Overall, the EDRC appears to be a goodmeasurement of eating- and body-related phenomena among LCW. Implications, limitations, and future directions are discussed.

Genetics of rheumatoid arthritis contributes to biology and drug discovery

A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)1. Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ~10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2, 3, 4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation5, cis-acting expression quantitative trait loci6 and pathway analyses7, 8, 9—as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes—to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.

Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10−8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10−4, Bonferroni corrected), of which six reached P < 5 × 10−8, including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1–3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region4, 5, 6, 7, 8, 9, 10, 11. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods—recursive partitioning and regression...

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: Quantifying the epidemiological transition

Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5–89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.

Transition of self: Repositioning the celebrity brand through social media—The case of Elizabeth Gilbert

Transitioning the personal brand from one representation to another is sometimes necessary, particularly within the public eye. Marketing literature regarding celebrities focuses on brand endorsement (see for example Till, 1998 or Erdogan, 1999), rather than the positioning of a celebrity brand. Furthermore, the role of social media in strengthening the celebrity brand has received limited attention in the literature outside of political marketing (see for example Crawford, 2009 and Grant, Moon and Grant, 2010). This study focuses on the brand of “Elizabeth Gilbert,” author of the bestseller memoir, Eat, Pray, Love (2006). Through critical discourse analysis, the way the author has used social media to reposition her celebrity brand at the time of the launch of her new novel, ‘The Signature of All Things’ (2013) is examined. This study focuses on the use of social media by celebrities to strengthen the celebrity brand.

J.W.Lindt’s Colonial man and Aborigine image from the GRAFTON ALBUM : “On chemistry and optics all does not depend, art must with these in triple union blend”

J.W.Lindt’s Colonial man and Aborigine image from the GRAFTON ALBUM: “On chemistry and optics all does not depend, art must with these in triple union blend” (text from J.W. Lindt’s photographic backing card) In this paper, I follow an argument that Lindt held a position in his particular colonial environment where he was simultaneously both an insider and an outsider and that such a position may be considered prerequisite in stimulating exchange. A study of the transition of J.W. Lindt in Grafton, N.S.W. in the 1860s from a traveller to a migrant and subsequently to a professional photographer, as well as Lindt’s photographic career, which evolved through strategic action and technical approaches to photography, bears witness to his cultural relativity. One untitled photograph from this period of work constructs a unique commentary of Australian colonial life that illustrates a non-hegemonic position, particularly as it was included in one of the first albums of photographs of Aborigines that Lindt gifted to an illustrious person (in this case the Mayor of Grafton). As in his other studio constructions, props and backdrops were arranged and sitters were positioned with care, but this photograph is the only one in the album that includes a non-Aborigine in a relationship to an Aborigine. An analysis of the props, technical details of the album and the image suggests a reconciliatory aspect that thwarts the predominant attitudes towards Aborigines in the area at that time.

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10−8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.