inbreedR: An R package for the analysis of inbreeding based on genetic markers

1. Heterozygosity fitness correlations (HFCs) have been used extensively to explore the impact of inbreeding on individual fitness. Initially, most studies used small panels of microsatellites, but more recently with the advent of next generation sequencing, large SNP datasets are becoming increasingly available and these provide greater power and precision to quantify the impact of inbreeding on fitness. 2. Despite the popularity of HFC studies, effect sizes tend to be rather small. One reason for this may be a low variation in inbreeding level across individuals. Using genetic markers, it is possible to measure variance in inbreeding through the strength of correlation in heterozygosity across marker loci, termed identity disequilibrium (ID). 3. ID can be quantified using the measure g2 which is also a central parameter in HFC theory that can be used within a wider framework to estimate the direct impact of inbreeding on both marker heterozygosity and fitness. However, no software exists to calculate g2 for large SNP datasets nor to implement this framework. 4. inbreedR is an R package that provides functions to calculate g2 based on microsatellite and SNP markers with associated p-values and confidence intervals. Within the framework of HFC theory, inbreedR also estimates the impact of inbreeding on marker heterozygosity and fitness. Moreover, we implemented easy-to-use simulations to explore the precision and magnitude of estimates based on different numbers of genetic markers. We hope this package will facilitate good practice in the analysis of HFCs and help to deepen our understanding of inbreeding effects in natural populations

Tips and tricks to avoid implant failure in proximal femur fractures treated with cephalomedullary nails: a review of the literature

Objective: To describe the surgical aspects potentially contributing to hardware failure of cephalomedullary nails. Data Sources: A search of the Embase, PubMed (MEDLINE), Web of Science, and the Cochrane library for reports of hardware failures after intramedullary fixation of proximal femur fractures. Issues of cut out and cut through phenomena related to technique were excluded. Expert opinion of 3 surgeons, each trained on several fixation systems at Level | trauma centers is reported. Data Extraction: Three authors extracted data using a predesigned form. Implant type, reported failure mechanism, and associated factors with implant failure were recorded as well as potential bias. Results: Of 2182 search results screened, 64 articles were deemed relevant for our research question and were included. The authors identified factors associated with implant failure: preoperative patient and fracture characteristics, intraoperative reduction, implant handling, and postoperative nonunion. Issues were identified as independent modifiable intraoperative risk factors: inadequate fracture reduction, varus position of femoral neck, direct damage of the cephalomedullary nail aperture by eccentric drilling related to guide sleeve handling, and implant design mechanism failures. Conclusions: Multiple factors associated with intraoperative handling can influence the healing of proximal femur fractures. Although many of these have been well described and are taught in fracture courses, surgeons should be aware of subtle intraoperative complications reported in the literature that can weaken implants and add to the likelihood of early failure

Buoyant Venus station mission feasibility study for 1972 and 1973 launch opportunities. Volume 3 - Configuration definition. Part 2 - Appendixes Final report

Buoyant Venus station mission study for 1972 - 1973 launch period - backup data including atmospheric models, heat shield requirements, etc

Miravirsen (SPC3649) can inhibit the biogenesis of miR-122

MicroRNAs (miRNAs) are short noncoding RNAs, which bind to messenger RNAs and regulate protein expression. The biosynthesis of miRNAs includes two precursors, a primary miRNA transcript (pri-miRNA) and a shorter pre-miRNA, both of which carry a common stem-loop bearing the mature miRNA. MiR-122 is a liver-specific miRNA with an important role in the life cycle of hepatitis C virus (HCV). It is the target of miravirsen (SPC3649), an antimiR drug candidate currently in clinical testing for treatment of HCV infections. Miravirsen is composed of locked nucleic acid (LNAs) ribonucleotides interspaced throughout a DNA phosphorothioate sequence complementary to mature miR-122. The LNA modifications endow the drug with high affinity for its target and provide resistance to nuclease degradation. While miravirsen is thought to work mainly by hybridizing to mature miR-122 and blocking its interaction with HCV RNA, its target sequence is also present in pri- and pre-miR-122. Using new in vitro and cellular assays specifically developed to discover ligands that suppress biogenesis of miR-122, we show that miravirsen binds to the stem-loop structure of pri- and pre-miR-122 with nanomolar affinity, and inhibits both Dicer- and Drosha-mediated processing of miR-122 precursors. This inhibition may contribute to the pharmacological activity of the drug in ma

Effects of housing, perches, genetics, and 25-hydroxycholecalciferol on keel bone deformities in laying hens

Several studies have shown a high prevalence of keel bone deformities in commercial laying hens. The aim of this project was to assess the effects of perch material, a vitamin D feed additive (25-hydroxyvitamin D3; HyD, DSM Nutritional Products, Basel, Switzerland), and genetics on keel bone pathology. The study consisted of 2 experiments. In the first experiment, 4,000 Lohmann Selected Leghorn hens were raised in aviary systems until 18 wk of age. Two factors were investigated: perch material (plastic or rubber-coated metal) and feed (with and without HyD). Afterward, the hens were moved to a layer house with 8 pens with 2 aviary systems. Daily feed consumption, egg production, mortality, and feather condition were evaluated. Every 6 wk, the keel bones of 10 randomly selected birds per pen were palpated and scored. In the second experiment, 2,000 Lohmann Brown (LB) hens and 2,000 Lohmann Brown parent stock (LBPS) hens were raised in a manner identical to the first experiment. During the laying period, the hens were kept in 24 identical floor pens but equipped with different perch material (plastic or rubber-coated metal). The same variables were investigated as in the first experiment. No keel bone deformities were found during the rearing period in either experiment. During the laying period, deformities gradually appeared and reached a prevalence of 35% in the first experiment and 43.8% in the second experiment at the age of 65 and 62 wk, respectively. In the first experiment, neither HyD nor the aviary system had any significant effect on the prevalence of keel bone deformities. In the second experiment, LBPS had significantly fewer moderate and severe deformities than LB, and rubber-coated metal perches were associated with a higher prevalence of keel bone deformities compared with plastic perches. The LBPS laid more but smaller eggs than the LB. Again, HyD did not affect the prevalence of keel bone deformities. However, the significant effect of breed affiliation strongly indicates a sizeable genetic component that may provide a basis for targeted selectio

A microfluidic technique for generating monodisperse submicron-sized drops

International audienceWe present a route for producing monodisperse micro and nanodrops that is based on a liquid-gas phase transition occurring within a microfluidic device. A gas which is soluble in water is mixed with an insoluble one and injected into an aqueous surfactant solution, using a microfluidic device that produces monodisperse bubbles. As the soluble gas diffuses out of the bubbles, they shrink and the remaining insoluble gas condenses into drops. Their radius can be tuned over a wide range by changing the initial gas mixing ratio