Description:
Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10−8 to P = 10−190). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis and cell surface glycobiology (ABO, ASGR1, FUT2, GPLD1 and ST3GAL4), inflammation and immunity (CD276, CDH6, GCKR, HNF1A, HPR, ITGA1, RORA and STAT4) and glutathione metabolism (GSTT1, GSTT2 and GGT), as well as several genes of uncertain or unknown function (including ABHD12, EFHD1, EFNA1, EPHA2, MICAL3 and ZNF827). Our results provide new insight into genetic mechanisms and pathways influencing markers of liver function. 137 authors
Description:
Background. Epidemiological studies suggest that, following infection with influenza virus, there is a short period during which a host experiences a lower susceptibility to infection with other influenza viruses. This viral interference appears to be independent of any antigenic similarities between the viruses. We used the ferret model of human influenza to systematically investigate viral interference. Methods. Ferrets were first infected then challenged 1-14 days later with pairs of influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B viruses circulating in 2009 and 2010. Results. Viral interference was observed when the interval between initiation of primary infection and subsequent challenge was <1 week. This effect was virus specific and occurred between antigenically related and unrelated viruses. Coinfections occurred when 1 or 3 days separated infections. Ongoing shedding from the primary virus infection was associated with viral interference after the secondary challenge. Conclusions. The interval between infections and the sequential combination of viruses were important determinants of viral interference. The influenza viruses in this study appear to have an ordered hierarchy according to their ability to block or delay infection, which may contribute to the dominance of different viruses often seen in an influenza season.
Description:
Background. Epidemiological studies suggest that, following infection with influenza virus, there is a short period during which a host experiences a lower susceptibility to infection with other influenza viruses. This viral interference appears to be independent of any antigenic similarities between the viruses. We used the ferret model of human influenza to systematically investigate viral interference. Methods. Ferrets were first infected then challenged 1-14 days later with pairs of influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B viruses circulating in 2009 and 2010. Results. Viral interference was observed when the interval between initiation of primary infection and subsequent challenge was <1 week. This effect was virus specific and occurred between antigenically related and unrelated viruses. Coinfections occurred when 1 or 3 days separated infections. Ongoing shedding from the primary virus infection was associated with viral interference after the secondary challenge. Conclusions. The interval between infections and the sequential combination of viruses were important determinants of viral interference. The influenza viruses in this study appear to have an ordered hierarchy according to their ability to block or delay infection, which may contribute to the dominance of different viruses often seen in an influenza season.
Description:
The purpose of this paper is to summarise the methodology for the 5th International Consensus Conference on Concussion in Sport. The 18 months of preparation included engagement of a scientific committee, an expert panel of 33 individuals in the field of concussion and a modified Delphi technique to determine the primary questions to be answered. The methodology also involved the writing of 12 systematic reviews to inform the consensus conference and submission and review of scientific abstracts. The meeting itself followed a 2-day open format, a 1-day closed expert panel meeting and two additional half day meetings to develop the Concussion Recognition Tool 5 (Pocket CRT5), Sport Concussion Assessment Tool 5 (SCAT5) and Child SCAT5.
Trends in, projections of, and inequalities in reproductive, maternal, newborn and child health service coverage in Vietnam 2000-2030 : a Bayesian analysis at national and sub-national levels
Description:
Objective: To compare Orchard Sports Injury Classification System (OSICS-10) sports medicine diagnoses assigned by a clinical and non-clinical coder. Design: Assessment of intercoder agreement. Setting: Community Australian football. Participants: 1082 standardised injury surveillance records. Main outcome measurements: Direct comparison of the four-character hierarchical OSICS-10 codes assigned by two independent coders (a sports physician and an epidemiologist). Adjudication by a third coder (biomechanist). Results: The coders agreed on the first character 95% of the time and on the first two characters 86% of the time. They assigned the same four-digit OSICS-10 code for only 46% of the 1082 injuries. The majority of disagreements occurred for the third character; 85% were because one coder assigned a non-specific 'X' code. The sports physician code was deemed correct in 53% of cases and the epidemiologist in 44%. Reasons for disagreement included the physician not using all of the collected information and the epidemiologist lacking specific anatomical knowledge. Conclusions: Sports injury research requires accurate identification and classification of specific injuries and this study found an overall high level of agreement in coding according to OSICS-10. The fact that the majority of the disagreements occurred for the third OSICS character highlights the fact that increasing complexity and diagnostic specificity in injury coding can result in a loss of reliability and demands a high level of anatomical knowledge. Injury report form details need to reflect this level of complexity and data management teams need to include a broad range of expertise. Copyright Article author (or their employer) 2012.
Description:
Objective: To compare Orchard Sports Injury Classification System (OSICS-10) sports medicine diagnoses assigned by a clinical and non-clinical coder. Design: Assessment of intercoder agreement. Setting: Community Australian football. Participants: 1082 standardised injury surveillance records. Main outcome measurements: Direct comparison of the four-character hierarchical OSICS-10 codes assigned by two independent coders (a sports physician and an epidemiologist). Adjudication by a third coder (biomechanist). Results: The coders agreed on the first character 95% of the time and on the first two characters 86% of the time. They assigned the same four-digit OSICS-10 code for only 46% of the 1082 injuries. The majority of disagreements occurred for the third character; 85% were because one coder assigned a non-specific 'X' code. The sports physician code was deemed correct in 53% of cases and the epidemiologist in 44%. Reasons for disagreement included the physician not using all of the collected information and the epidemiologist lacking specific anatomical knowledge. Conclusions: Sports injury research requires accurate identification and classification of specific injuries and this study found an overall high level of agreement in coding according to OSICS-10. The fact that the majority of the disagreements occurred for the third OSICS character highlights the fact that increasing complexity and diagnostic specificity in injury coding can result in a loss of reliability and demands a high level of anatomical knowledge. Injury report form details need to reflect this level of complexity and data management teams need to include a broad range of expertise. Copyright Article author (or their employer) 2012.
Description:
This study tested the hypothesis that adverse events are associated with increased risk of onset of anxiety disorders. Data from Waves 1 (N = 43,093; 2001–2002) and 2 (N = 34,653; 2004–2005) of the National Epidemiological Survey on Alcohol and Related Conditions (NESARC) were used to assess whether adverse events at baseline are associated with increased risk of anxiety disorder onset over three years of follow up. Sixty-six percent (SE: 1.0) of respondents with an anxiety disorder in the intervening period between Waves 1 and 2 had experienced an adverse life event in the year prior to the Wave 1 interview. In logistic regression models adjusted for sociodemographic and psychiatric characteristics, adverse life events at baseline were associated with anxiety disorder onset within the three-year follow up period. The pattern of association between adverse events and anxiety disorder onset was similar across sub-types, and injury, illness or death of family or close friends consistently had the strongest association with anxiety disorder onset. These findings suggest that adverse life events play a role in the onset of anxiety disorders.
Description:
This study tested the hypothesis that adverse events are associated with increased risk of onset of anxiety disorders. Data from Waves 1 (N = 43,093; 2001–2002) and 2 (N = 34,653; 2004–2005) of the National Epidemiological Survey on Alcohol and Related Conditions (NESARC) were used to assess whether adverse events at baseline are associated with increased risk of anxiety disorder onset over three years of follow up. Sixty-six percent (SE: 1.0) of respondents with an anxiety disorder in the intervening period between Waves 1 and 2 had experienced an adverse life event in the year prior to the Wave 1 interview. In logistic regression models adjusted for sociodemographic and psychiatric characteristics, adverse life events at baseline were associated with anxiety disorder onset within the three-year follow up period. The pattern of association between adverse events and anxiety disorder onset was similar across sub-types, and injury, illness or death of family or close friends consistently had the strongest association with anxiety disorder onset. These findings suggest that adverse life events play a role in the onset of anxiety disorders.
Description:
Organized youth sports leagues attempt to meet many goals. Three primary needs for a youth sports league are to meet the participants' desires, provide quality learning experiences, and develop the competencies needed for continued participation. Possessing the ball, shooting more, and being more involved with a team's offense lead to more enjoyment and feelings of competence. Therefore, increasing the involvement of each player through more ball contacts should be a goal of youth sports leagues. Twelve male basketball players (age=15) from one high-school basketball team participated in this study. This study used paired t-tests to examine the differences between three-on-three basketball games and five-on-five basketball games that lasted for eight minutes in terms of average heart rate, moderate to vigorous intensity physical activity, vigorous intensity activity, and ball contacts. There were no significant differences between average heart rate, moderate-to-vigorous intensity activity, or vigorous intensity activity in the two conditions, but there were significantly more ball contacts on average in the three-on-three games. These results suggest that three-on-three leagues may be an appropriate sport for the initial exposure to basketball for youth players.
Description:
Organized youth sports leagues attempt to meet many goals. Three primary needs for a youth sports league are to meet the participants' desires, provide quality learning experiences, and develop the competencies needed for continued participation. Possessing the ball, shooting more, and being more involved with a team's offense lead to more enjoyment and feelings of competence. Therefore, increasing the involvement of each player through more ball contacts should be a goal of youth sports leagues. Twelve male basketball players (age=15) from one high-school basketball team participated in this study. This study used paired t-tests to examine the differences between three-on-three basketball games and five-on-five basketball games that lasted for eight minutes in terms of average heart rate, moderate to vigorous intensity physical activity, vigorous intensity activity, and ball contacts. There were no significant differences between average heart rate, moderate-to-vigorous intensity activity, or vigorous intensity activity in the two conditions, but there were significantly more ball contacts on average in the three-on-three games. These results suggest that three-on-three leagues may be an appropriate sport for the initial exposure to basketball for youth players.
Description:
Runs of homozygosity (ROHs) are recognized signature of recessive inheritance. Contributions of ROHs to the genetic architecture of coronary artery disease and regulation of gene expression in cells relevant to atherosclerosis are not known. Our combined analysis of 24,320 individuals from 11 populations of white European ethnicity showed an association between coronary artery disease and both the count and the size of ROHs. Individuals with coronary artery disease had approximately 0.63 (95% CI: 0.4-0.8) excess of ROHs when compared to coronary-artery-disease-free control subjects (p = 1.49 x 10
Description:
It is well known that the mutations in BRCA1 or BRCA2 gene can cause the hereditary breast cancer. However, it is a tedious and expensive task to identify the mutant genes that impact breast cancer due to the large number of genes and very small number of samples. Furthermore, the expressive energy of the subset of genes in comparison to that of one individual gene at a time is considered to have a profound influence in case of breast cancer. In this paper 7 tumors with BRCA1 mutation and 8 tumors with BRCA2 mutation have been used to identify the subset of discriminative genes. A combination of a non-parametric supervised and an unsupervised statistical method is introduced to analyze the gene expressions and the distinctive genes among the highly expressed genes are identified. The most important genes are filtered using the area under the curve (AUC) measure. These filtered genes are then used to build a hidden Markov model (HMM) to analyse their inter-relationship and identify the best subset among them. In addition, Protein-Protein interaction network is generated to analyse the pathways of the identified genes and their link with BRCA1 or BRCA2. Transcription Factors are identified and Gene Set Enrichment Analysis (GSEA) is calculated for the identified genes subset and the results are compared with the results mentioned in other cancer literature. Experimental results suggest that only 8 genes have been identified out of 3226 genes by the proposed hybrid method. Out of the 8 identified genes, 5 have been linked with breast cancer by other studies. Moreover, 7 genes have been associated with numerous diseases that may result in breast cancer. Furthermore, 8 transcription factors were identified that cover the identified genes and BRCA1 and BRCA2. Lastly, GSEA enrichment score of 0.52 is calculated for the identified genes and it is comparatively better considering the small subset of identified genes.
Description:
Introduction and Aims Treatment of opioid dependence through opioid replacement therapy is widely recognised as effective. Nonetheless, while there has been a community-based program in the state of Victoria for over two decades, consumer experiences have received little attention. This study aimed to describe the experiences of opioid replacement therapy consumers living in rural and regional areas of the state. Design and Methods A qualitative design employed an interpretative phenomenological approach. Sixteen consumers were interviewed. Thematic analysis was conducted by the researchers to examine the phenomena of consumers ' experiences and findings were verified by a stakeholder group. Results Findings centred on themes of consumers ' experience of becoming recipients; consumer perceptions of pharmacists and pharmacy settings and psychosocial impacts on consumers. A majority of participants believed opioid replacement therapy brought increased normality to their life, however systemic and psychosocial barriers impacted on well-being. The pharmacy setting itself as a public dosing space commonly provoked feelings of stigma and discrimination among consumers. Other barriers prominently reported were restrictions on number of takeaways, cost of dispensing and lack of access to medical practitioners and allied supports. Discussion and Conclusions There were psychosocial impacts on opioid replacement therapy consumers relating to financial and social burdens, stigma and discrimination. Access to medical care and a choice of pharmacy appeared to be restricted in rural regions. The findings suggest a need to address, in particular, the financial and dispensing point burdens experienced by consumers to facilitate program retention.
Description:
Abandoned historical gold mining wastes often exist as geographically extensive, unremediated, and poorly contained deposits that contain elevated levels of As and other potentially toxic elements (PTEs). One of the key variables governing human exposure to PTEs in mine waste is particle size. By applying a size-resolved approach to mine waste characterisation, this study reports on the proportions of mine waste relevant to human exposure and mobility, as well as their corresponding PTE concentrations, in four distinct historical mine wastes from the gold province in Central Victoria, Australia. To the best of our knowledge, such a detailed investigation and comparison of historical mining wastes has not been conducted in this mining-affected region. Mass distribution analysis revealed notable proportions of waste material in the readily ingestible size fraction (aecurrency sign250 A mu m; 36.1-75.6 %) and the dust size fraction (aecurrency sign100 A mu m; 5.9-45.6 %), suggesting a high potential for human exposure and dust mobilisation. Common to all mine waste types were statistically significant inverse trends between particle size and levels of As and Zn. Enrichment of As in the finest investigated size fraction (aecurrency sign53 A mu m) is of particular concern as these particles are highly susceptible to long-distance atmospheric transport. Human populations that reside in the prevailing wind direction from a mine waste deposit may be at risk of As exposure via inhalation and/or ingestion pathways. Enrichment of PTEs in the finer size fractions indicates that human health risk assessments based on bulk contaminant concentrations may underestimate potential exposure intensities.
Description:
Background. Antibody titres and vaccine effectiveness decline within 6 months after influenza vaccination in older adults. Biannual vaccination may be necessary to provide year-round protection in the tropics, where influenza circulates throughout the year. Methods. Tropical Influenza Control Strategies (TROPICS1) was a single-center, 1:1 randomized, observer-blinded, active-comparator- controlled, superiority study in 200 community-resident adults aged ≥65 years. Participants received a standard-dose trivalent inactivated influenza vaccination (IIV3) at enrollment, and either tetanus-diphtheria-pertussis vaccination or IIV3 6 months later. The primary outcome was the proportion of participants with haemagglutination-inhibition (HI) geometric mean titre (GMT) ≥1:40 1 month after the second vaccination (month 7). Secondary outcomes included GMTs to month 12, the incidence of influenza- like illness (ILI), and adverse reactions after vaccination. Results. At month 7, the proportion of participants with an HI tire ≥1:40 against A/H1N1 increased by 21.4% (95% confidence interval [CI] 8.6-33.4) in the semiannual vaccination group. This proportion was not significantly higher for A/H3N2 (4.3, 95% CI -1.1-10.8) or B (2.1, 95% CI -2.0-7.3). Semiannual vaccination significantly increased GMTs against A/H1N1 and A/H3N2, but not B, at month 7. Participants receiving a repeat vaccination of IIV3 reported a significantly lower incidence of ILI in the 6 months after the second vaccination (relative vaccine effectiveness 57.1%, 95% CI 0.6-81.5). The frequency of adverse events was similar after the first and second influenza vaccinations. Conclusions. Semiannual influenza vaccination in older residents of tropical countries has the potential to improve serological measures of protection against infection. Alternative vaccination strategies should also be studied.
Description:
Dietary nitrate supplementation has been shown to increase nitric oxide (NO) metabolites, reduce blood pressure (BP) and enhance exercise performance. Acute exposure to ultraviolet (UV)-A light also increases NO bioavailability and reduces BP. We conducted a randomized, counterbalanced placebo-controlled trial to determine the effects of UV-A light alone and in combination with nitrate on the responses to sub-maximal steady-state exercise and time trial (TT) performance. Nine cyclists (VO2max 53.1 +/- 4.4 ml/kg/min) completed five performance trials comprising 10 min submaximal steady-state cycling followed by a 16.1 km TT. Following a familiarization the final four trials were preceded, in random order, by either (1) Nitrate gels (NIT) + UV-A, (2) Placebo (PLA) + UV-A, (3) NIT + Sham light (SHAM) and (4) PLA + SHAM (control). The NIT gels (2 x 60 ml gels, ~8.1 mmol nitrate) or a low-nitrate PLA were ingested 2.5 h prior to the trial. The light exposure consisted of 20 J/cm(2) whole body irradiation with either UV-A or SHAM light. Plasma nitrite was measured pre- and post-irradiation and VO2 was measured continuously during steady-state exercise. Plasma nitrite was higher for NIT + SHAM (geometric mean (95% CI), 332 (292-377) nM; P = 0.029) and NIT + UV-A (456 (312-666) nM; P = 0.014) compared to PLA + SHAM (215 (167-277) nM). Differences between PLA + SHAM and PLA + UV-A (282 (248-356) nM) were small and non-significant. During steady-state exercise VO2 was reduced following NIT + UVA (P = 0.034) and tended to be lower in NIT + SHAM (P = 0.086) but not PLA + UV-A (P = 0.381) compared to PLA + SHAM. Performance in the TT was significantly faster following NIT + UV-A (mean +/- SD 1447 +/- 41 s P = 0.005; d = 0.47), but not PLA + UV-A (1450 +/- 40 s; d = 0.41) or NIT + SHAM (1455 +/- 47 s; d = 0.28) compared to PLA + SHAM (1469 +/- 52 s). These findings demonstrate that exposure to UV-A light alone does not alter the physiological responses to exercise or improve performance in a laboratory setting. A combination of UV-A and NIT, however, does improve cycling TT performance in this environment, which may be due to a larger increase in NO availability.
Description:
Dietary nitrate supplementation has been shown to increase nitric oxide (NO) metabolites, reduce blood pressure (BP) and enhance exercise performance. Acute exposure to ultraviolet (UV)-A light also increases NO bioavailability and reduces BP. We conducted a randomized, counterbalanced placebo-controlled trial to determine the effects of UV-A light alone and in combination with nitrate on the responses to sub-maximal steady-state exercise and time trial (TT) performance. Nine cyclists (VO2max 53.1 +/- 4.4 ml/kg/min) completed five performance trials comprising 10 min submaximal steady-state cycling followed by a 16.1 km TT. Following a familiarization the final four trials were preceded, in random order, by either (1) Nitrate gels (NIT) + UV-A, (2) Placebo (PLA) + UV-A, (3) NIT + Sham light (SHAM) and (4) PLA + SHAM (control). The NIT gels (2 x 60 ml gels, ~8.1 mmol nitrate) or a low-nitrate PLA were ingested 2.5 h prior to the trial. The light exposure consisted of 20 J/cm(2) whole body irradiation with either UV-A or SHAM light. Plasma nitrite was measured pre- and post-irradiation and VO2 was measured continuously during steady-state exercise. Plasma nitrite was higher for NIT + SHAM (geometric mean (95% CI), 332 (292-377) nM; P = 0.029) and NIT + UV-A (456 (312-666) nM; P = 0.014) compared to PLA + SHAM (215 (167-277) nM). Differences between PLA + SHAM and PLA + UV-A (282 (248-356) nM) were small and non-significant. During steady-state exercise VO2 was reduced following NIT + UVA (P = 0.034) and tended to be lower in NIT + SHAM (P = 0.086) but not PLA + UV-A (P = 0.381) compared to PLA + SHAM. Performance in the TT was significantly faster following NIT + UV-A (mean +/- SD 1447 +/- 41 s P = 0.005; d = 0.47), but not PLA + UV-A (1450 +/- 40 s; d = 0.41) or NIT + SHAM (1455 +/- 47 s; d = 0.28) compared to PLA + SHAM (1469 +/- 52 s). These findings demonstrate that exposure to UV-A light alone does not alter the physiological responses to exercise or improve performance in a laboratory setting. A combination of UV-A and NIT, however, does improve cycling TT performance in this environment, which may be due to a larger increase in NO availability.
Description:
Multilocus sequence typing (MLST) is an important tool for the global surveillance of bacterial pathogens that is performed by comparing the sequences of designated housekeeping genes. We developed and tested a novel mass spectrometry-based method for MLST of Streptococcus pneumoniae. PCR amplicons were subjected to in vitro transcription and base-specific cleavage, followed by analysis of the resultant fragments by using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Comparison of the cleavage fragment peak patterns to a reference sequence set permitted automated identification of alleles. Validation experiments using 29 isolates of S. pneumoniae revealed that the results of MALDI-TOF MS MLST matched those obtained by traditional sequence-based MLST for 99% of alleles and that the MALDITOF MS method accurately identified two single-nucleotide variations. The MADLI-TOF MS method was then used for MLST analysis of 43 S. pneumoniae isolates from Papua New Guinean children. The majority of the isolates present in this population were not clonal and contained seven new alleles and 30 previously unreported sequence types.