| 1. |
-
- 2019
-
Tidskriftsartikel (refereegranskat)
|
|
| 2. |
- Fresard, Laure, et al.
(författare)
-
Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
-
Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
-
Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
|
|
| 3. |
- Furness, James, et al.
(författare)
-
Acute Injuries in Recreational and Competitive Surfers : Incidence, Severity, Location, Type, and Mechanism
- 2015
-
Ingår i: American Journal of Sports Medicine. - : Sage Publications. - 0363-5465 .- 1552-3365. ; 43:5, s. 1246-1254
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:There are an estimated 37 million surfers worldwide, with 2.5 million recreational surfers in Australia. The recreational activity and sport of surfing has grown dramatically since the 1960s, but scientific research has been poorly mirrored in comparison with most other mainstream sports.PURPOSE:To identify the incidence, severity, location, type, and mechanism of acute injuries in recreational and competitive surfers over a 12-month period.STUDY DESIGN:Descriptive epidemiology study.METHODS:An online survey using an open-source survey application was utilized. The survey consisted of 2 primary sections: Section 1 included demographic information and participation levels (age, height, weight, hours surfed, competitive level); section 2 incorporated injury type, mechanism, severity, and injury management.RESULTS:A total of 1348 participants (91.3% males; 43.1% competitive surfers) were included in data analysis. A total of 512 acute injuries were classified as major, providing an incidence proportion of 0.38 (CI, 0.35-0.41) acute injuries per year. The incidence rate was calculated to be 1.79 (CI, 1.67-1.92) major injuries per 1000 hours of surfing. The shoulder, ankle, and head/face regions had the highest frequencies of acute injury, representing 16.4%, 14.6%, and 13.3%, respectively. Injuries were predominantly of muscular, joint, and skin origin, representing 30.3%, 27.7%, and 18.9%, respectively. Skin injuries were primarily a result of direct trauma, while joint and muscular injuries were mainly a result of maneuvers performed and repetitive actions. Key risk factors that increased the incidence of sustaining an acute injury included competitive status, hours surfed (>6.5 hours/week), and the ability to perform aerial maneuvers. The incidence proportion for surfers completing aerial maneuvers was calculated to be 0.48 (CI, 0.39-0.58) major injuries per year, this being the highest incidence proportion irrespective of competitive status.CONCLUSION:This is the largest surfing-specific survey that included both recreational and competitive surfers conducted in Australia to date. The shoulder, ankle, head, and face were identified as the key regions where acute injuries occur in surfers. This research may aid in reducing the occurrence of injury through musculoskeletal screening in these key injury-prone regions and through the use of sport-specific strength training and conditioning.
|
|
| 4. |
- Furness, James, et al.
(författare)
-
Retrospective analysis of chronic injuries in recreational and competitive surfers : injury, location, type and mechanism
- 2014
-
Ingår i: International Journal of Aquatic Research and Education. - : Human Kinetics. - 1932-9997 .- 1932-9253. ; 8:3, s. 277-287
-
Tidskriftsartikel (refereegranskat)abstract
- Only two studies have reported on chronic musculoskeletal surfing injuries. They found over half of the injuries were non-musculoskeletal, but did not consider mechanisms of injury. This study identified the location, type, and mechanisms of chronic injury in Australian recreational and competitive surfers using a cross-sectional retrospective observational design. A total of 1,348 participants (91.3% males, 43.1% competitive surfers) reported 1,068 chronic injuries, 883 of which were classified as major. Lower back (23.2%), shoulder (22.4%), and knee (12.1%) regions had the most chronic injuries. Competitive surfers had significantly (p < .05) more lower back, ankle/foot, and head/face injuries than recreational surfers. Injuries were mostly musculoskeletal with only 7.8% being of non-musculoskeletal origin. Prolonged paddling was the highest frequency (21.1%) for mechanism of injury followed by turning maneuvers (14.8%). The study results contribute to the limited research on chronic surfing injuries.
|
|
| 5. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
|
|
