No difference in strength and clinical outcome between early and late repair after Achilles tendon rupture

PURPOSE: This retrospective study aimed to determine the patient-reported and functional outcome of patients with delayed presentation, who had received no treatment until 14 days following injury of Achilles tendon rupture repaired with minimally invasive surgery and were compared with a group of sex- and age-matched patients presenting acutely. Based on the outcomes following delayed presentation reported in the literature, it was hypothesized that outcomes would be inferior for self-reported outcome, tendon elongation, heel-rise performance, ability to return to play, and complication rates than for acutely managed patients. METHODS: Repair was performed through an incision large enough to permit mobilisation of the tendon ends, core suture repair consisting of a modified Bunnell suture proximally and a Kessler suture distally and circumferential running suture augmentation. RESULTS: Nine patients presented 21.8 (14.9) days (range 14-42 days) after rupture. The rate of delayed presentation was estimated to be 1 in 10. At 12 months following repair, patients with delayed treatment had median (range) ATRS score of 90 (69-99) compared with 94 (75-100) in patients treated acutely presenting 0.66 (1.7) (0-5) days. There were no significant differences between groups: ATRA [mean (SD) delayed: - 6.9° (5.5), acute: - 6° (4.7)], heel-rise height index [delayed: 79% (20), acute: 74% (14)], or heel-rise repetition index [delayed: 77% (20), acute: 71% (20)]. In the delayed presentation group, two patients had wound infection and one iatrogenic sural nerve injury. CONCLUSIONS: Patients presenting more than 2 weeks after Achilles tendon rupture may be successfully treated with minimally invasive repair. LEVEL OF EVIDENCE: III

Age and tightness of repair are predictors of heel-rise height after Achilles tendon rupture

Background: Achilles tendon rupture leads to weakness of ankle plantarflexion. Treatment of Achilles tendon rupture should aim to restore function while minimizing weakness and complications of management. Purpose: To determine the influence of factors (age, sex, body mass index [BMI], weight, time from injury to operative repair, and tightness of repair) in the initial surgical management of patients after an acute Achilles tendon rupture on 12-month functional outcome assessment after percutaneous and minimally invasive repair. Study Design: Cohort study; Level of evidence, 3. Methods: From May 2012 to January 2018, patients sustaining an Achilles tendon rupture receiving operative repair were prospectively evaluated. Tightness of repair was quantified using the intraoperative Achilles tendon resting angle (ATRA). Heel-rise height index (HRHI) was used as the primary 12-month outcome variable. Secondary outcome measures included Achilles tendon total rupture score (ATRS) and Tegner score. Stepwise multiple regression was used to create a model to predict 12-month HRHI. Results: A total of 122 patients met the inclusion criteria for data analysis (mean ± SD age, 44.1 ± 10.8 years; 78% male; mean ± SD BMI, 28.1 ± 4.3 kg/m Conclusion: Age was found to be the strongest predictor of outcome after Achilles tendon rupture. The most important modifiable risk factor was the tightness of repair. It is recommended that repair be performed as tight as possible to optimize heel-rise height 1 year after Achilles tendon rupture and possibly to reduce tendon elongation

Targeted analysis of four breeds narrows equine Multiple Congenital Ocular Anomalies locus to 208 kilobases

The syndrome Multiple Congenital Ocular Anomalies (MCOA) is the collective name ascribed to heritable congenital eye defects in horses. Individuals homozygous for the disease allele (MCOA phenotype) have a wide range of eye anomalies, while heterozygous horses (Cyst phenotype) predominantly have cysts that originate from the temporal ciliary body, iris, and/or peripheral retina. MCOA syndrome is highly prevalent in the Rocky Mountain Horse but the disease is not limited to this breed. Affected horses most often have a Silver coat color; however, a pleiotropic link between these phenotypes is yet to be proven. Locating and possibly isolating these traits would provide invaluable knowledge to scientists and breeders. This would favor maintenance of a desirable coat color while addressing the health concerns of the affected breeds, and would also provide insight into the genetic basis of the disease. Identical-by-descent mapping was used to narrow the previous 4.6-Mb region to a 264-kb interval for the MCOA locus. One haplotype common to four breeds showed complete association to the disease (Cyst phenotype, n = 246; MCOA phenotype, n = 83). Candidate genes from the interval, SMARCC2 and IKZF4, were screened for polymorphisms and genotyped, and segregation analysis allowed the MCOA syndrome region to be shortened to 208 kb. This interval also harbors PMEL17, the gene causative for Silver coat color. However, by shortening the MCOA locus by a factor of 20, 176 other genes have been unlinked from the disease and only 15 genes remain

A Novel Unstable Duplication Upstream of HAS2 Predisposes to a Breed-Defining Skin Phenotype and a Periodic Fever Syndrome in Chinese Shar-Pei Dogs

Hereditary periodic fever syndromes are characterized by recurrent episodes of fever and inflammation with no known pathogenic or autoimmune cause. In humans, several genes have been implicated in this group of diseases, but the majority of cases remain unexplained. A similar periodic fever syndrome is relatively frequent in the Chinese Shar-Pei breed of dogs. In the western world, Shar-Pei have been strongly selected for a distinctive thick and heavily folded skin. In this study, a mutation affecting both these traits was identified. Using genome-wide SNP analysis of Shar-Pei and other breeds, the strongest signal of a breed-specific selective sweep was located on chromosome 13. The same region also harbored the strongest genome-wide association (GWA) signal for susceptibility to the periodic fever syndrome (praw = 2.3×10−6, pgenome = 0.01). Dense targeted resequencing revealed two partially overlapping duplications, 14.3 Kb and 16.1 Kb in size, unique to Shar-Pei and upstream of the Hyaluronic Acid Synthase 2 (HAS2) gene. HAS2 encodes the rate-limiting enzyme synthesizing hyaluronan (HA), a major component of the skin. HA is up-regulated and accumulates in the thickened skin of Shar-Pei. A high copy number of the 16.1 Kb duplication was associated with an increased expression of HAS2 as well as the periodic fever syndrome (p<0.0001). When fragmented, HA can act as a trigger of the innate immune system and stimulate sterile fever and inflammation. The strong selection for the skin phenotype therefore appears to enrich for a pleiotropic mutation predisposing these dogs to a periodic fever syndrome. The identification of HA as a major risk factor for this canine disease raises the potential of this glycosaminoglycan as a risk factor for human periodic fevers and as an important driver of chronic inflammation

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification

Kvinnorollen och mansrollen i opera – då och nu

För att ligga i framkant vid operautbildningen på Högskolan för scen och musik (HSM) behöver vi kontinuerligt komplettera synen på vår musikdramatiska interpretationsmetod och lösa upp genrehierarkier, inte minst för att kunna möta och vinna den nya generationens publik, ”de icke redan frälsta”. Ovanstående KU-projekt Lucia möter Pajazzo är en fristående fortsättning på de två konstnärliga KU-projekten En kvinnas många röster, 2008 samt En kvinnas möten, 2009. Dessa tre KU-projekt har med progression och fördjupning behandlat specifika frågeställningar i utvalda operascener med syfte att: - utveckla en genreöverskridande/genrelös sångteknik för att främja ett fungerande musikdramatiskt skådespeleri med texten i fokus - belysa könsmaktsordningen samt kvinnorollens och mansrollens försvar av det egna perspektivet samt problematisera offer- och förövarrollen I detta tredje KU-projekt prövar och fördjupar jag de frågeställningar, som genomsyrat samtliga KU-projekt genom att arbeta med en större blandad ensemble och interpretera scener från den mer konservativa operalitteraturen. Dessa ”pärlor” ur 1800-talets operaverk är ofta musikaliskt excellenta men gällande könsroller och klass är de oftast berättarmässigt konservativa. Den genreöverskridande eller genrelösa sångmetod, som kontinuerligt utvecklats i de tre forskningsprojekten, ger den sceniske sångaren redskap och möjligheter att låta rösten direkt spegla de känslor som text och musik förmedlar. Detta leder till ett mer trovärdigt och mångdimensionellt musikdramatiskt skådespeleri. Till min hjälp i alla tre projekten har jag haft sångcoachen Marianne Khoso, lektor på HSM. Jag har under årens lopp utarbetat ett antal övningar, som stöttar denna ”genreöverskridande” metod. Marianne Khoso har i sin tur utarbetat en grundsångteknik, som hon kallar ”genrelös”. Vi brinner båda för att försöka få ”operavärlden” att våga förändra en konservativ tradition av alltför kontrollerad och ibland rentav endimensionell operasång med ett överdrivet vibrato, som gärna uppkommer i ett alltför starkt sångbeteende. Denna ”genrelösa” teknik grundar sig i alla de samlade och fungerande tekniker, som sångarna lagrat i sin kropps minnesbank. Sångarnas erfarenheter av olika tekniker, från jazz, visa, belting, modern opera och klassisk opera samt deras mod att inte ge efter för en traditionell och ”överkontrollerad operateknik” har här gett ett slående resultat. Vi har i detta projekt prövat våra frågeställningar i några klassiska operascener, där rollkaraktärer från olika århundraden går i klinch med varandra. Vi har mött Molly Cutpurse, en rollfigur inspirerad av en autentisk kvinna från det tidiga 1600-talets England. Hon har klätt ut sig till man för att få bättre förutsättningar för sitt leverne. Hon försörjer sig som entreprenör, musiker, hälare, hallick mm. Molly har gestaltats av Katarina A Karlsson (doktorand vid HSM). Över denna tidsvandring i operans värld har La Finta Pazza, (den falska galna), sångerska från 1600-talets Venedig, svävat . Denna roll har katalyserat rollernas känslor, mannens såväl som kvinnans, bland annat genom att ge dem möjlighet att låta förståndet och själen fly in i ”vansinnets räddande bubbla”, just som livets våndor blir som svårast att hantera. La Finta Pazza har gestaltats av Elisabeth Belgrano (doktorand vid HSM). Även om de flesta kvinnliga roller på 1600-talet spelades av män, så fanns under renässansen någon slags grogrund till att i opera- och teaterkonsten försöka försvara ett kvinnligt perspektiv. Hoppet om att erkänna kvinnan som en fullvärdig varelse på scenen och i livet kom dock på skam under 1800-talet. Man kan nog efter vårt arbete våga dra slutsatsen att 1800-talet inte blev en bra utveckling för operaberättandet, varken när det gäller jämställdhet eller när det gäller sångligt uttryck. Formen/operamallen blev dogmatisk, ja rent av ”fundamentalistisk” på båda dessa punkter. Därför är det extra viktigt att inte ge efter för denna förlegade syn utan försöka finna ett sätt att interpretera dessa operaskatter på ett för dagens generation relevant sätt. I detta projekt har processen utvecklats i en komplett miljö. Det har inneburit scenkonstnärliga studentmöten från grundutbildningsnivå till doktorandnivå. Två doktorander, en student från operaprogrammets masterutbildning, fem studenter från operaprogrammets kandidatutbildning årskurs 2 samt fyra musikerstudenter har mötts och samarbetat i utvalda klassiska operascener. De medverkande studenterna har med olika bakgrunder, olika nivåer och förutsättningar, under min ledning utvecklat ett samstämmigt musikdramatiskt uttryck, alltså försökt komma överens om en gemensam syn på berättandet, läsarten, i våra utvalda operascener. De två doktoranderna som burit med sig sina frågeställningar från sitt avhandlingsarbete rakt in i vårt projekt har utmanat och berikat allas vårt arbete med nya perspektiv när det gäller vår gemensamma process i arbetet