Percutaneous Achilles Tendon Repair Using Ultrasound Guidance: An Intraoperative Ultrasound Technique

Rupture of the Achilles tendon is a common injury seen in patients of varying ages and activity levels. There are many considerations for treatment of these injuries, with both operative and nonoperative management providing satisfactory outcomes in the literature. The decision to proceed with surgical intervention should be individualized for each patient, including the patient\u27s age, future athletic goals, and comorbidities. Recently, a minimally invasive percutaneous approach to repair the Achilles tendon has been proposed as an equivalent alternative to the traditional open repair, while avoiding wound complications associated with larger incisions. However, many surgeons have been hesitant to adopt these approaches due to poor visualization, concern that suture capture in the tendon is not as robust, and the potential for iatrogenic sural nerve injury. The purpose of this Technical Note is to describe a technique using high-resolution ultrasound guidance intraoperatively during minimally invasive repair of the Achilles tendon. This technique minimizes the drawbacks of poor visualization associated with percutaneous repair, while providing the benefit of a minimally invasive approach

Common colorectal cancer risk alleles contribute to the multiple colorectal adenoma phenotype, but do not influence colonic polyposis in FAP

The presence of multiple (5-100) colorectal adenomas suggests an inherited predisposition, but the genetic aetiology of this phenotype is undetermined if patients test negative for Mendelian polyposis syndromes such as familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP). We investigated whether 18 common colorectal cancer (CRC) predisposition single-nucleotide polymorphisms (SNPs) could help to explain some cases with multiple adenomas who phenocopied FAP or MAP, but had no pathogenic APC or MUTYH variant. No multiple adenoma case had an outlying number of CRC SNP risk alleles, but multiple adenoma patients did have a significantly higher number of risk alleles than population controls (P=5.7 × 10(-7)). The association was stronger in those with ≥10 adenomas. The CRC SNPs accounted for 4.3% of the variation in multiple adenoma risk, with three SNPs (rs6983267, rs10795668, rs3802842) explaining 3.0% of the variation. In FAP patients, the CRC risk score did not differ significantly from the controls, as we expected given the overwhelming effect of pathogenic germline APC variants on the phenotype of these cases. More unexpectedly, we found no evidence that the CRC SNPs act as modifier genes for the number of colorectal adenomas in FAP patients. In conclusion, common colorectal tumour risk alleles contribute to the development of multiple adenomas in patients without pathogenic germline APC or MUTYH variants. This phenotype may have 'polygenic' or monogenic origins. The risk of CRC in relatives of multiple adenoma cases is probably much lower for cases with polygenic disease, and this should be taken into account when counselling such patients

Canta Nación con Nación: una Aproximación Comparativa entre el Son Jarocho y el Joropo Llanero

Dissertação apresentada ao Programa de Pós-Graduação Interdisciplinar em Estudos Latino-Americanos da Universidade Federal da Integração Latino-Americana, como requisito parcialà obtenção do título de Mestra em Estudos Latino-Americanos.El son jarocho de México y el Joropo llanero de Venezuela son dos expresiones musicales que muestran rasgos en común, como resultado de un proceso histórico que los hermana. Ambos tienen su raíz principal en el fandango, celebración músico-bailable que cruzó el océano atlántico de ida y vuelta, formando variadas manifestaciones musicales y danzarías durante la época colonial, tanto en América como en la Península Ibérica. En ese proceso se va conformando también el complejo genérico ternario del Caribe, el cual se subdivide y se expande en las diversas expresiones regionales que aún hoy se conocen. En el Gran Caribe ha habido siempre intercambios musicales, por lo que el flujo de estéticas ha sido permanente y la hermandad dentro del fenómeno fandanguero se viene manifestando en los aspectos musicales como el ritmo, la armonía, lo tímbrico, entre otros. Para destacar las afinidades y diferencias que unen o separan los rasgos identificables se han seleccionado dos ejemplos: el Buscapies (son jarocho) y el Seis Numerao (joropo llanero). Ambos comparten el mismo patrón acordal y son ejemplo de consanguinidad rítmica con acentuaciones específicas. En este sentido, se presentará un análisis musical comparativo de las formas mencionadas, partiendo de la metodología de Simha Ahrom Buscando aproximaciones que se perfilen en los aspectos musicales principalmente

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk

We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.Swedish Research Council et al.Manuscrip

Partnerships in a Global Mental Health Research Programme-the Example of PRIME.

Collaborative research partnerships are necessary to answer key questions in global mental health, to share expertise, access funding and influence policy. However, partnerships between low- and middle-income countries (LMIC) and high-income countries have often been inequitable with the provision of technical knowledge flowing unilaterally from high to lower income countries. We present the experience of the Programme for Improving Mental Health Care (PRIME), a LMIC-led partnership which provides research evidence for the development, implementation and scaling up of integrated district mental healthcare plans in Ethiopia, India, Nepal, South Africa and Uganda. We use Tuckman's first four stages of forming, storming, norming and performing to reflect on the history, formation and challenges of the PRIME Consortium. We show how this resulted in successful partnerships in relation to management, research, research uptake and capacity building and reflect on the key lessons for future partnerships

Recurrent Coding Sequence Variation Explains only A Small Fraction of the Genetic Architecture of Colorectal Cancer

Whilst common genetic variation in many non-coding genomic regulatory regions are known to impart risk of colorectal cancer (CRC), much of the heritability of CRC remains unexplained. To examine the role of recurrent coding sequence variation in CRC aetiology, we genotyped 12,638 CRCs cases and 29,045 controls from six European populations. Single-variant analysis identified a coding variant (rs3184504) in SH2B3 (12q24) associated with CRC risk (OR = 1.08, P = 3.9 × 10-7), and novel damaging coding variants in 3 genes previously tagged by GWAS efforts; rs16888728 (8q24) in UTP23 (OR = 1.15, P = 1.4 × 10-7); rs6580742 and rs12303082 (12q13) in FAM186A (OR = 1.11, P = 1.2 × 10-

Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer.

Excessive exposure to estrogen is a well-established risk factor for endometrial cancer (EC), particularly for cancers of endometrioid histology. The physiological function of estrogen is primarily mediated by estrogen receptor alpha, encoded by ESR1. Consequently, several studies have investigated whether variation at the ESR1 locus is associated with risk of EC, with conflicting results. We performed comprehensive fine-mapping analyses of 3633 genotyped and imputed single nucleotide polymorphisms (SNPs) in 6607 EC cases and 37 925 controls. There was evidence of an EC risk signal located at a potential alternative promoter of the ESR1 gene (lead SNP rs79575945, P=1.86×10(-5)), which was stronger for cancers of endometrioid subtype (P=3.76×10(-6)). Bioinformatic analysis suggests that this risk signal is in a functionally important region targeting ESR1, and eQTL analysis found that rs79575945 was associated with expression of SYNE1, a neighbouring gene. In summary, we have identified a single EC risk signal located at ESR1, at study-wide significance. Given SNPs located at this locus have been associated with risk for breast cancer, also a hormonally driven cancer, this study adds weight to the rationale for performing informed candidate fine-scale genetic studies across cancer types.This work was supported by the National Health and Medical Research Council of Australia (ID#1031333 to A B Spurdle, DF, A M Dunning, ID#39435 to ANECS, ID#552402, QIMR Controls); National Health and Medical Research Council of Australia Fellowship Scheme (to A B Spurdle); Principal Research Fellow of Cancer Research UK (to D F Easton); Joseph Mitchell Trust (to A M Dunning); Oxford Comprehensive Biomedical Research Centre (to I Tomlinson); The European Community's Seventh Framework Programme (grant agreement number 22175 (HEALTH-F2-2009-223175) (COGS); Cancer Research UK (C1287/A10118 to COGS and BCAC, C1287/A10710, C12292/A11174, C1281/A12014 to COGS and BCAC, C5047/A15007, C5047/A10692, C8197/A16565, C490/A10124 to SEARCH, CORGI - NSECG, to I Tomlinson); National Institutes of Health (CA128978, R01 CA122443 to MECS and MAY, P30 CA15083 to MECS, P50 CA136393 to MECS and MAY, CAHRES); Post-Cancer GWAS Initiative (1U19 CA148537, 1U19 CA148065, 1U19 CA148112 – the GAME-ON initiative); Department of Defence (W81XWH-10-1-0341); Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer; Komen Foundation for the Cure; The Breast Cancer Research Foundation; Ovarian Cancer Research Fund (to COGS); Cancer Council Queensland (ID#4196615 to ANECS); Council Cancer Tasmania (ID#403031, #ID457636 to ANECS); Medical Research Council (G0000934 to the British 1958 Birth Cohort); Wellcome Trust (068545/Z/02, 085475 to the British 1958 Birth Cohort); Wellcome Trust Human Genetics Grant (090532/Z/09/Z to NSECG); European Union (EU FP7 CHIBCHA to NSECG); The University of Newcastle (to QIMR Controls, to NECS); Gladys M Brawn Senior Research Fellowship (QIMR Controls); The Vincent Fairfax Family Foundation (QIMR Controls); Hunter Medical Research Institute (HCS, NECS); Hunter Area Pathology Service (HCS); ELAN fund of the University of Erlangen (BECS); Verelst Foundation for endometrial cancer (LES); Fred C and Katherine B Anderson Foundation (to MECS, to MAY); Mayo Foundation (to MECS, to MAY); Ovarian Cancer Research Fund with support of the Smith family, in memory of Kathryn Sladek Smith (MECS, PPD/RPCI.07 to OCAC); Helse Vest Grant (MoMaTEC); University of Bergen (MoMaTEC); Melzer Foundation (MoMaTEC); The Norwegian Cancer Society – Harald Andersens legat (MoMaTEC); The Research Council of Norway (MoMaTEC); Haukeland University of Hospital (MoMaTEC); NBN Children's Cancer Research Group (NECS); Ms Jennie Thomas (NECS); regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet (20110222, 20110483, 20110141 and DF 07015 all to RENDOCAS, to KARBAC); The Swedish Labor Market Insurance (100069 to RENDOCAS); The Swedish Cancer Society (11 0439 to RENDOCAS); Agency for Science, Technology and Research of Singapore (CAHRES); Susan G Komen Breast Cancer Foundation (CAHRES); UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge (OCAC); Baden-Württemberg state Ministry of Science, Research and Arts (ESTHER); Federal Ministry of Family Affairs, Senior Citizens, Women and Youth (ESTHER); Federal Ministry of Education and Research (BMBF) Germany (01KW9975/5 to GENICA, 01KW9976/8 to GENICA, 01KW9977/0 to GENICA, 01KW0114 to GENICA, to ESTHER); Robert Bosch Foundation (GENICA); Deutsches Krebsforschungszentrum – DKFZ (GENICA); Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum, IPA (GENICA); Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus (GENICA); Deutsche Krebshilfe e.V. (70-2892-BR I to MARIE); Hamburg Cancer Society (MARIE); German Cancer Research Center (MARIE); Breast Cancer Research Foundation (MCBCS); David F. and Margaret T. Grohne Family Foundation (MCBCS); Ting Tsung and Wei Fong Chao Foundation (MCBCS); VicHealth (MCCS); Cancer Council Victoria (MCCS); Breakthrough Breast Cancer (UKBGS); Institute of Cancer Research (UKBGS); and NHS funding to the NIHR Biomedical Research Centre (UKBGS/ICR).This is the final version of the article. It first appeared from the Society for Endocrinology via http://dx.doi.org/10.1530/ERC-15-031