Bibliometric analysis of authorship trends and collaboration dynamics over the past three decades of BONE's publication history

The existence of a gender gap in academia has been a hotly debated topic over the past several decades. It has been argued that due to the gender gap, it is more difficult for women to obtain higher positions. Manuscripts serve as an important measurement of one's accomplishments within a particular field of academia. Here, we analyzed, over the past 3 decades, authorship and other trends in manuscripts published in BONE, one of the premier journals in the field of bone and mineral metabolism. For this study, one complete year of manuscripts was evaluated (e.g. 1985, 1995, 2005, 2015) for each decade. A bibliometric analysis was then performed of authorship trends for those manuscripts. Analyzed fields included: average number of authors per manuscript, numerical position of the corresponding author, number of institutions collaborating on each manuscript, number of countries involved with each manuscript, number of references, and number of citations per manuscript. Each of these fields increased significantly over the 30-year time frame (p < 10− 6). The gender of both the first and corresponding authors was identified and analyzed over time and by region. There was a significant increase in the percentage of female first authors from 23.4% in 1985 to 47.8% in 2015 (p = 0.001). The percentage of female corresponding authors also increased from 21.2% in 1985 to 35.4% in 2015 although it was not significant (p = 0.07). With such a substantial emphasis being placed on publishing in academic medicine, it is crucial to comprehend the changes in publishing characteristics over time and geographical region. These findings highlight authorship trends in BONE over time as well as by region. Importantly, these findings also highlight where challenges still exist

Effective Control of Schistosoma haematobium Infection in a Ghanaian Community following Installation of a Water Recreation Area

BackgroundUrogenital schistosomiasis caused by Schistosoma haematobium was endemic in Adasawase, Ghana in 2007. Transmission was reported to be primarily through recreational water contact.MethodsWe designed a water recreation area (WRA) to prevent transmission to school-aged children. The WRA features a concrete pool supplied by a borehole well and a gravity-driven rainwater collection system; it is 30 m2 and is split into shallow and deep sections to accommodate a variety of age groups. The WRA opened in 2009 and children were encouraged to use it for recreation as opposed to the local river. We screened children annually for S. haematobium eggs in their urine in 2008, 2009, and 2010 and established differences in infection rates before (2008–09) and after (2009–10) installation of the WRA. After each annual screening, children were treated with praziquantel and rescreened to confirm parasite clearance.Principal FindingsInitial baseline testing in 2008 established that 105 of 247 (42.5%) children were egg-positive. In 2009, with drug treatment alone, the pre-WRA annual cumulative incidence of infection was 29 of 216 (13.4%). In 2010, this incidence rate fell significantly (p<0.001, chi-squared) to 9 of 245 (3.7%) children after installation of the WRA. Logistic regression analysis was used to determine correlates of infection among the variables age, sex, distance between home and river, minutes observed at the river, low height-for-age, low weight-for-age, low Body Mass Index (BMI)-for-age, and previous infection status.Conclusion/SignificanceThe installation and use of a WRA is a feasible and highly effective means to reduce the incidence of schistosomiasis in school-aged children in a rural Ghanaian community. In conjunction with drug treatment and education, such an intervention can represent a significant step towards the control of schistosomiasis. The WRA should be tested in other water-rich endemic areas to determine whether infection prevalence can be substantially reduced.Author SummaryUrogenital schistosomiasis is a disease caused by the parasite Schistosoma haematobium; it is often characterized by bloody urine and tends to disproportionately affect school-aged children in rural tropical regions. The parasite is transmitted via skin contact with surface water that is contaminated by human waste. The disease was endemic in Adasawase, a rural Ghanaian community, in 2007. Transmission occurred mainly through recreational water contact. We collaborated with community members to design a water recreation area (WRA) featuring a concrete pool supplied by a borehole well and a rainwater collection system. We opened the pool in 2009 and local officials encouraged children to use the WRA for recreation. We screened local children annually (2008, 2009, 2010) for S. haematobium infection. After each screening, children were treated with praziquantel and rescreened. Baseline testing in 2008 established that at least 105 of 247 (42.5%) children were infected. In 2009, 29 of 216 (13.4%) children were infected, reflecting annual cumulative incidence. In 2010, a significantly smaller percentage of children (9 of 245, 3.7%) were infected. We conclude that the WRA effectively reduced infection in Adasawase, and that it should be tested in other water-rich endemic areas

High resolution melting analysis for rapid and sensitive EGFR and KRAS mutation detection in formalin fixed paraffin embedded biopsies

<p>Abstract</p> <p>Background</p> <p>Epithelial growth factor receptor (<it>EGFR</it>) and <it>KRAS </it>mutation status have been reported as predictive markers of tumour response to <it>EGFR </it>inhibitors. High resolution melting (HRM) analysis is an attractive screening method for the detection of both known and unknown mutations as it is rapid to set up and inexpensive to operate. However, up to now it has not been fully validated for clinical samples when formalin-fixed paraffin-embedded (FFPE) sections are the only material available for analysis as is often the case.</p> <p>Methods</p> <p>We developed HRM assays, optimised for the analysis of FFPE tissues, to detect somatic mutations in <it>EGFR </it>exons 18 to 21. We performed HRM analysis for <it>EGFR </it>and <it>KRAS </it>on DNA isolated from a panel of 200 non-small cell lung cancer (NSCLC) samples derived from FFPE tissues.</p> <p>Results</p> <p>All 73 samples that harboured <it>EGFR </it>mutations previously identified by sequencing were correctly identified by HRM, giving 100% sensitivity with 90% specificity. Twenty five samples were positive by HRM for <it>KRAS </it>exon 2 mutations. Sequencing of these 25 samples confirmed the presence of codon 12 or 13 mutations. <it>EGFR </it>and <it>KRAS </it>mutations were mutually exclusive.</p> <p>Conclusion</p> <p>This is the first extensive validation of HRM on FFPE samples using the detection of <it>EGFR </it>exons 18 to 21 mutations and <it>KRAS </it>exon 2 mutations. Our results demonstrate the utility of HRM analysis for the detection of somatic <it>EGFR </it>and <it>KRAS </it>mutations in clinical samples and for screening of samples prior to sequencing. We estimate that by using HRM as a screening method, the number of sequencing reactions needed for <it>EGFR </it>and <it>KRAS </it>mutation detection can be reduced by up to 80% and thus result in substantial time and cost savings.</p

Polymorphisms in the RNASE3 Gene Are Associated with Susceptibility to Cerebral Malaria in Ghanaian Children

BACKGROUND: Cerebral malaria (CM) is the most severe outcome of Plasmodium falciparum infection and a major cause of death in children from 2 to 4 years of age. A hospital based study in Ghana showed that P. falciparum induces eosinophilia and found a significantly higher serum level of eosinophil cationic protein (ECP) in CM patients than in uncomplicated malaria (UM) and severe malaria anemia (SA) patients. Single nucleotide polymorphisms (SNPs) have been described in the ECP encoding-gene (RNASE3) of which the c.371G>C polymorphism (rs2073342) results in an arginine to threonine amino acid substitution p.R124T in the polypeptide and abolishes the cytotoxicity of ECP. The present study aimed to investigate the potential association between polymorphisms in RNASE3 and CM. METHODOLOGY/PRINCIPAL FINDINGS: The RNASE3 gene and flanking regions were sequenced in 206 Ghanaian children enrolled in a hospital based malaria study. An association study was carried out to assess the significance of five SNPs in CM (n=45) and SA (n=56) cases, respectively. The two severe case groups (CM and SA) were compared with the non-severe control group comprising children suffering from UM (n=105). The 371G allele was significantly associated with CM (p=0.00945, OR=2.29, 95% CI=1.22-4.32) but not with SA. Linkage disequilibrium analysis demonstrated significant linkage between three SNPs and the haplotype combination 371G/*16G/*94A was strongly associated with susceptibility to CM (p=0.000913, OR=4.14, 95% CI=1.79-9.56), thus, defining a risk haplotype. The RNASE3 371GG genotype was found to be under frequency-dependent selection. CONCLUSIONS/SIGNIFICANCE: The 371G allele of RNASE3 is associated with susceptibility to CM and forms part of a risk associated haplotype GGA defined by the markers: rs2073342 (G-allele), rs2233860 (G-allele) and rs8019343 (A-allele) respectively. Collectively, these results suggest a hitherto unrecognized role for eosinophils in CM pathogenesis

Fear and loathing in the Caribbean: three studies of fear and cancer screening in Brooklyn's immigrant Caribbean subpopulations

Background: Anxiety, worry, and fear are among the most common emotional responses to the threat of disease and several studies have linked various fears to cancer preventive and detection behaviors. Cancer-related worry and fears about screening or its consequences are also characteristics that vary across ethnic groups and may be differentially linked to screening outcomes 1. Limiting the utility of this growing literature are at least two key considerations. First, little attention has been paid to documenting variation in cancer-related fears among subpopulations of persons of African descent, despite evidence that (a) rates of screening may vary among both male 2 and female 3 immigrants from islands in the Caribbean living in the United States and (b) incidence rates for cancers such as those of the prostate may be very high in men from Jamaica 4, Guadaloupe 5 and Trinidad and Tobago 6, as well as in immigrant groups in both the United Kingdom 7 and United States 8. Second, findings regarding the relations anxiety, cancer worry, and screening fear hold with screening behavior seen thus far have been inconsistent, in our view because anxieties stemming from different sources have different relations with behavior. In the emotions theory view, understanding the role of fear in health behavior in diverse groups is predicated on understanding the object or source of the fear 91011 for the simple reason that anxiety motivates avoidance of particular elicitors 1012. Research conducted within the U54 Comprehensive Cancer Partnership between Long Island University and Columbia University has produced several studies documenting differences in breast and prostate cancer screening frequencies among Caribbean subpopulations living in Brooklyn, New York 11213. A major concentration in this program of behavioral research has investigated whether trait anxiety, cancer worry, and screening-related fears vary across Caribbean subpopulations and whether these highly differentiated emotional responses independently predict screening behavior in multivariate models 12121314. Consistent with theory, we expected that fears pertaining to the screening context (e.g., fear of pain or the psychological implications of certain screens), would predict avoidance of the fear-inducing situation and thus be associated with less frequent screening. Conversely, where fears relate to the disease itself, greater fear should predict more frequent screening. Methods: Because of our overarching interest in the links between cancer and cancer-screening-related fears and cancer screening behaviors among the diverse groups of men and women living in Brooklyn, New York, we combined data from three community-based studies. Although measures and samples varied somewhat across studies, each study investigated the link between emotions and screening outcome in ethnic groups that included immigrants from islands in the Caribbean. Because of our interest in examining differences within traditional racial categories, we used a combination of (a) self-categorization based on a the traditional racial categories offered in the US Census together with (b) information regarding country of origin. Allowing a combination of self-reported racial categorization (tapping aspects of identity and minority status) in concert with shared birthplace to influence groupings increases the likelihood that participants share cultural and developmental characteristics thought to form part of ethnicity 15. We distinguished between Black men born in the United States (hereafter, U.S.-born African Americans), and those originating from countries in the English-speaking Caribbean (e.g., Trinidad & Tobago, Jamaica, Barbados). Immigrant and non-immigrant minority groups were contrasted with men self-identifying as "European or White/Non-Hispanic" who were born in the United States (hereafter, U.S.-born European American). In Study 1, stratified cluster-sampling was used to recruit 1364 women (aged between 50–70 years) from six ethnic groups: US-born African American, US-born European American, immigrants from islands in the English-speaking Caribbean (Jamaica, Barbados, Trinidad and Tobago), the Dominican Republic, Haiti, and Eastern Europe 1. In Study 2, 180 US-born African American, US-born European American and immigrant Jamaican men (aged between 40–70 years) were recruited using convenience sampling 13. In Study 3, 533 men (aged between 45–70 years) from four groups – US-born African American, US-born European American, and immigrant men from Jamaica and from Trinidad and Tobago – were recruited 12. In each study, participants provided background data, reported on screening history for either breast or prostate cancer, and completed a measure of trait anxiety, cancer worry, and/or screening fears. Results: As expected, we found differences among groups of African descent from the United States and the Caribbean. Although women from all groups screened at rates below those recommended, data from Study 1 showed that English-speaking Caribbean, Haitian and Dominican women screened less frequently than US-born African Americans and European Americans and that immigrant Eastern European women were also infrequent screeners (see Figure 1). Conversely, however, there were no differences in rates of self-reported prostate screening among men from the English-speaking Caribbean, US-born African Americans, or US-born European Americans in either Study 2 or Study 3. As expected, cancer-related emotional characteristics also varied across subpopulations (see Figure 2). Cancer worry was generally lower among women from the various Caribbean immigrant groups (Study 1) than it was among US-born African Americans or US-born European Americans. Fears regarding screening, however, varied somewhat differently. Fear of screening was higher among US-born African Americans and immigrant men from the English-speaking Caribbean (Studies 2 and 3) than among US-born European Americans. Consistent with the need to carefully measure fear-related constructs in the context of cancer behavior, however, our data also demonstrated that a specific fear related to concerns regarding threats to masculinity in the context of male screening strongly characterized the attitudes of men from the English-speaking Caribbean compared to the views of US-born European and US-born African Americans (Study 2). Finally, a combination of multiple regression and ANOVAs in each study showed that emotional characteristics independently predicted screening, in most cases even when background characteristics were controlled. Across studies, greater cancer worry predicted more frequent screening while fear of screening predicted less frequent screening. Figure 1 Number of cancer screens in prior 10 years Number of cancer screens in prior 10 years. DRE = digital rectal examination, PSA = prostate specific antigen test, Mamm = mammogram, CBE = clinical breast exam. Figure 2 Emotion characteristics related to screening Emotion characteristics related to screening. Trait = trait anxiety, Worry = cancer worry, Scr. Fr. = screening fear, and Em. Con. = emasculation concern. Conclusion: Data from three large-scale studies in Brooklyn, New York suggest that members of immigrant Caribbean subpopulations screen for breast and prostate cancer at very low rates; in most cases lower than those of either US-born African or US-born European Americans. Groups of Caribbean men and women also vary in the emotions they report regarding cancer and the screening process, generally revealing a pattern that is predictive of poorer screening. Coupled with the fact that emotion characteristics predicted screening outcomes even when controlling for other factors, data from these three studies suggest that the emotional responses Caribbean groups place them at risk for poor screening. Interventions that address these responses may offer the prospect of improving screening frequency in these disadvantaged groups. Competing interests: The authors declare that they have no competing interests. Authors' contributions: NSC and CM was involved in study design, analysis, interpretation/write up and critical revision of the manuscript. BA and DH in the analysis, interpretation and write up. AKJ, TU and LNB were involved in the interpretation and write up. PMR was part of the study design, analysis and interpretation/write up. JMM and AIN had part in the study design, analysis and critical revision whilst JSJ took part in critical revision

Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation.

Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.This work was supported by NIH fellowship F32 GM106584 (AG), NIH grants R01 MH101244(A.G.), R01 CA188392 (B.P.), U01 CA194393(B.P.), R01 GM107427 (M.L.F.), R01 CA193910 (M.L.F./M.P.) and Prostate Cancer Foundation Challenge Award (M.L.F./M.P.). This study makes use of data generated by the Wellcome Trust Case Control Consortium and the Wellcome Trust Sanger Institute. A full list of the investigators who contributed to the generation of the Wellcome Trust Case Control Consortium data is available on www.wtccc.org.uk. Funding for the Wellcome Trust Case Control Consortium project was provided by the Wellcome Trust under award 076113. This study makes use of data generated by the UK10K Consortium. A full list of the investigators who contributed to the generation of the data is available online (http://www.UK10K.org). The PRACTICAL consortium was supported by the following grants: European Commission's Seventh Framework Programme grant agreement n° 223175 (HEALTH-F2-2009-223175), Cancer Research UK Grants C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, C16913/A6135 and The National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative Grant: no. 1 U19 CA 148537-01 (the GAME-ON initiative); Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007 and C5047/A10692), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112—the GAME-ON initiative), the Department of Defense (W81XWH-10-1-0341), A Linneus Centre (Contract ID 70867902), Swedish Research Council (grant no K2010-70X-20430-04-3), the Swedish Cancer Foundation (grant no 09-0677), grants RO1CA056678, RO1CA082664 and RO1CA092579 from the US National Cancer Institute, National Institutes of Health; US National Cancer Institute (R01CA72818); support from The National Health and Medical Research Council, Australia (126402, 209057, 251533, 396414, 450104, 504700, 504702, 504715, 623204, 940394 and 614296); NIH grants CA63464, CA54281 and CA098758; US National Cancer Institute (R01CA128813, PI: J.Y. Park); Bulgarian National Science Fund, Ministry of Education and Science (contract DOO-119/2009; DUNK01/2–2009; DFNI-B01/28/2012); Cancer Research UK grants [C8197/A10123] and [C8197/A10865]; grant code G0500966/75466; NIHR Health Technology Assessment Programme (projects 96/20/06 and 96/20/99); Cancer Research UK grant number C522/A8649, Medical Research Council of England grant number G0500966, ID 75466 and The NCRI, UK; The US Dept of Defense award W81XWH-04-1-0280; Australia Project Grant [390130, 1009458] and Enabling Grant [614296 to APCB]; the Prostate Cancer Foundation of Australia (Project Grant [PG7] and Research infrastructure grant [to APCB]); NIH grant R01 CA092447; Vanderbilt-Ingram Cancer Center (P30 CA68485); Cancer Research UK [C490/A10124] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge; Competitive Research Funding of the Tampere University Hospital (9N069 and X51003); Award Number P30CA042014 from the National Cancer Institute.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/0.1038/ncomms1097

Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation.

Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa