Common origin of the gelsolin gene variant in 62 Finnish AGel amyloidosis families

Finnish gelsolin amyloidosis (AGel amyloidosis) is an autosomal dominantly inherited systemic disorder with ophthalmologic, neurologic and dermatologic symptoms. Only the gelsolin (GSN) c.640G>A variant has been found in the Finnish patients thus far. The purpose of this study was to examine whether the Finnish patients have a common ancestor or whether multiple mutation events have occurred at c.640G, which is a known mutational hot spot. A total of 79 Finnish AGel amyloidosis families including 707 patients were first discovered by means of patient interviews, genealogic studies and civil and parish registers. From each family 1-2 index patients were chosen. Blood samples were available from 71 index patients representing 64 families. After quality control, SNP array genotype data were available from 68 patients from 62 nuclear families. All the index patients had the same c.640G>A variant (rs121909715). Genotyping was performed using the Illumina CoreExome SNP array. The homozygosity haplotype method was used to analyse shared haplotypes. Haplotype analysis identified a shared haplotype, common to all studied patients. This shared haplotype included 17 markers and was 361 kb in length (GRCh37 coordinates 9:124003326–124364349) and this level of haplotype sharing was found to occur highly unlikely by chance. This GSN haplotype ranked as the largest shared haplotype in the 68 patients in a genome-wide analysis of haplotype block lengths. These results provide strong evidence that although there is a known mutational hot spot at GSN c.640G, all of the studied 62 Finnish AGel amyloidosis families are genetically linked to a common ancestor.Peer reviewe

STARD 2015: An Updated List of Essential Items for Reporting Diagnostic Accuracy Studies.

Incomplete reporting has been identified as a major source of avoidable waste in biomedical research. Essential information is often not provided in study reports, impeding the identification, critical appraisal, and replication of studies. To improve the quality of reporting of diagnostic accuracy studies, the Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement was developed. Here we present STARD 2015, an updated list of 30 essential items that should be included in every report of a diagnostic accuracy study. This update incorporates recent evidence about sources of bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD. As such, STARD 2015 may help to improve completeness and transparency in reporting of diagnostic accuracy studies

A multi-disciplinary perspective on emergent and future innovations in peer review [version 2; referees: 2 approved]

Peer review of research articles is a core part of our scholarly communication system. In spite of its importance, the status and purpose of peer review is often contested. What is its role in our modern digital research and communications infrastructure? Does it perform to the high standards with which it is generally regarded? Studies of peer review have shown that it is prone to bias and abuse in numerous dimensions, frequently unreliable, and can fail to detect even fraudulent research. With the advent of web technologies, we are now witnessing a phase of innovation and experimentation in our approaches to peer review. These developments prompted us to examine emerging models of peer review from a range of disciplines and venues, and to ask how they might address some of the issues with our current systems of peer review. We examine the functionality of a range of social Web platforms, and compare these with the traits underlying a viable peer review system: quality control, quantified performance metrics as engagement incentives, and certification and reputation. Ideally, any new systems will demonstrate that they out-perform and reduce the biases of existing models as much as possible. We conclude that there is considerable scope for new peer review initiatives to be developed, each with their own potential issues and advantages. We also propose a novel hybrid platform model that could, at least partially, resolve many of the socio-technical issues associated with peer review, and potentially disrupt the entire scholarly communication system. Success for any such development relies on reaching a critical threshold of research community engagement with both the process and the platform, and therefore cannot be achieved without a significant change of incentives in research environments

A multi-disciplinary perspective on emergent and future innovations in peer review

Peer review of research articles is a core part of our scholarly communication system. In spite of its importance, the status and purpose of peer review is often contested. What is its role in our modern digital research and communications infrastructure? Does it perform to the high standards with which it is generally regarded? Studies of peer review have shown that it is prone to bias and abuse in numerous dimensions, frequently unreliable, and can fail to detect even fraudulent research. With the advent of web technologies, we are now witnessing a phase of innovation and experimentation in our approaches to peer review. These developments prompted us to examine emerging models of peer review from a range of disciplines and venues, and to ask how they might address some of the issues with our current systems of peer review. We examine the functionality of a range of social Web platforms, and compare these with the traits underlying a viable peer review system: quality control, quantified performance metrics as engagement incentives, and certification and reputation. Ideally, any new systems will demonstrate that they out-perform and reduce the biases of existing models as much as possible. We conclude that there is considerable scope for new peer review initiatives to be developed, each with their own potential issues and advantages. We also propose a novel hybrid platform model that could, at least partially, resolve many of the socio-technical issues associated with peer review, and potentially disrupt the entire scholarly communication system. Success for any such development relies on reaching a critical threshold of research community engagement with both the process and the platform, and therefore cannot be achieved without a significant change of incentives in research environments

Computational analysis of interference phenomena on the lexical level

Because of the celebration of the thirty-three years of the Faculty of Education, we have decided to gather data, memories and reflections on an academic-administrative instance that has contributed so much to the internal constitution of the Surcolombiana University as to the region where it develops. It is clear that these notes do not aspire to be a historical treaty; his pretension is rather to contribute punctual references of each one of the moments that the Faculty has lived.Con ocasión de la celebración de los treinta y tres años de la Facultad de Educación, hemos decidido reunir datos, recuerdos y reflexiones sobre una instancia académica-administrativa que tanto le ha aportado a la constitución interna de la Universidad Surcolombiana como a la región en donde se desarrolla. Es claro que estos apuntes no aspiran a ser un tratado histórico; su pretensión es más bien aportar referencias puntuales de cada uno de los momentos que ha vivido la Facultad

[Clinical reasoning and decision making in practice. A man with pneumonia and ill smelling watery sputum: the truth revealed after 80 years]

A 24-year-old man was admitted to hospital with pneumonia. On admission he was seen to have an asymmetrical build. During treatment of the lung infiltrate his clinical condition deteriorated. On the third day he coughed up great quantities of fluid which had a urine-like smell. The concentration of creatinine in this fluid was the same as in urine. On X-ray of the thorax, a massive accumulation of pleural fluid was seen. Shortly after aspiration of 1000 ml of pleural fluid the patient died. At autopsy, an ectopic kidney was found in the left thoracic cavity. The pneumonia had caused an abscess that had broken into the pelvis of this ectopic kidney causing the loss of urine into the pleural cavity (urothorax) and 'uroptysis'. On the basis of anatomical and embryological aspects it is debatable if this case was genuine. It is in fact a duplication of a case report published in this journal in 1923 the reliability of which was never clarified. Biographical information from Professor A. Querido (1901-1983) which has since become available indicates that the case was faked by mischievous medical students preparing for their examinations. They had never imagined that the editors might actually accept it for publication. The case report of 1923 has now been retracted

Synthesis, enzymatic stability and base-pairing properties of oligothymidylates containing thymidine dimers with different N-substituted guanidine linkages

Reaction of 5'-amino-5'-deoxythymidine 1 with different SS-dimethyl-N-substituted dithiocarbonimidates 2a-j afforded the N-substituted isothioureas 3a-j which, on further reaction with 3'-amino-3'-deoxythymidine 4 in the presence of AgNO3, led to thymidine dimers 5a-j with different N-substituted guanidine linkages. The dimer with a thiourea linkage (compound 9) was also prepared. Dimers 5a-h were incorporated at different positions in oligothymidylates by using phosphoramidite chemistry. Attempts to incorporate compounds 5i,j and 9 led to complex mixtures. 3'-Protected oligonucleotides showed somewhat higher stability to snake venom phosphodiesterase. Melting experiments revealed that the N-methylsulfonyl-substituted guanidine linkage best mimics the natural phosphodiester bridge. The fluorescence properties of oligonucleotides with dimer 5f were studied in view of its potential use as a non-radioactive label for DNA.status: publishe

The risk of early occurrence and recurrence of hepatocellular carcinoma in hepatitis C infected patients treated with direct acting antivirals with and without pegylated interferon

status: publishe