Modelling the suppression of a malaria vector using a CRISPR-Cas9 gene drive to reduce female fertility.

BACKGROUND: Gene drives based on CRISPR-Cas9 technology are increasingly being considered as tools for reducing the capacity of mosquito populations to transmit malaria, and one of the most promising options is driving endonuclease genes that reduce the fertility of female mosquitoes. In particular, there is much interest in constructs that target the conserved mosquito doublesex (dsx) gene such that the emergence of functional drive-resistant alleles is unlikely. Proof of principle that these constructs can lead to substantial population suppression has been obtained in population cages, and they are being evaluated for use in sub-Saharan Africa. Here, we use simulation modelling to understand the factors affecting the spread of this type of gene drive over a one million-square kilometre area of West Africa containing substantial environmental and social heterogeneity. RESULTS: We found that a driving endonuclease gene targeting female fertility could lead to substantial reductions in malaria vector populations on a regional scale. The exact level of suppression is influenced by additional fitness costs of the transgene such as the somatic expression of Cas9, and its deposition in sperm or eggs leading to damage to the zygote. In the absence of these costs, or of emergent drive-resistant alleles that restore female fertility, population suppression across the study area is predicted to stabilise at ~ 95% 4 years after releases commence. Small additional fitness costs do not greatly affect levels of suppression, though if the fertility of females whose offspring transmit the construct drops by more than ~ 40%, then population suppression is much less efficient. We show the suppression potential of a drive allele with high fitness costs can be enhanced by engineering it also to express male bias in the progeny of transgenic males. Irrespective of the strength of the drive allele, the spatial model predicts somewhat less suppression than equivalent non-spatial models, in particular in highly seasonal regions where dry season stochasticity reduces drive efficiency. We explored the robustness of these results to uncertainties in mosquito ecology, in particular their method of surviving the dry season and their dispersal rates. CONCLUSIONS: The modelling presented here indicates that considerable suppression of vector populations can be achieved within a few years of using a female sterility gene drive, though the impact is likely to be heterogeneous in space and time

Microwave pulse compression using a helically corrugated waveguide

There has been a drive in recent years to produce ultrahigh power short microwave pulses for a range of applications. These high-power pulses can be produced by microwave pulse compression. Sweep-frequency based microwave pulse compression using smooth bore hollow waveguides is one technique of passive pulse compression, however, at very high powers, this method has some limitation due to its operation close to cutoff. A special helical corrugation of a circular waveguide ensures an eigenwave with strongly frequency dependent group velocity far from cutoff, which makes the helically corrugated waveguide attractive for use as a passive pulse compressor for very high-power amplifiers and oscillators. The results of proof-of-principle experiments and calculations of the wave dispersion using a particle in cell particle-in-cell (PIC) code are presented. In the experiments, a 70-ns 1-kW pulse from a conventional traveling-wave tube (TWT) was compressed in a 2-m-long helical waveguide. The compressed pulse had a peak power of 10.9 kW and duration of 3 ns. In order to find the optimum pulse compression ratio, the waveguide's dispersion characteristics must be well known. The dispersion of the helix was calculated using the PIC code Magic and verified using an experimental technique. Future work detailing plans to produce short ultrahigh power gigawatt (GW) pulses will be discussed

Surgical management of mediastinal liposarcoma extending from hypopharynx to carina: Case report

We describe the complete resection of a giant, well-differentiated mediastinal liposarcoma extending retropharynx to envelop the aortic arch, trachea and esophagus following preoperative radiotherapy

Grouping of tooth surfaces by susceptibility to caries: a study in 5–16 year-old children

BACKGROUND: The decline in caries has slowed and this may be indicative of variation in the susceptibility of differing teeth to caries. This study tests the hypothesis that in children, there are groups of tooth sites that exhibit differences in caries susceptibility. METHODS: Probit analysis of caries data collected from a 4-year longitudinal study of 20,000 schoolchildren aged between 5 and 16 years in 10 differing locations in the United States. RESULTS: The development of dental caries within the mouth followed a fixed hierarchy indicating that tooth surfaces show variation in caries susceptibility. Certain teeth and tooth sites have similar susceptibilities and can be grouped, the sizes of the groups vary. The most susceptible group consists of six tooth surfaces: the buccal pits and occlusal fissured surfaces of the first molar teeth. The second group consisted of 12 sites on the second molar and premolar teeth. The group formed by the least susceptible sites included the largest number of tooth surfaces and consists of the majority of the lower anterior teeth and canines. CONCLUSION: Variation in the caries susceptibility of tooth surfaces exists. Surfaces can be grouped according to caries susceptibility. An effect that reduces the cariogenic challenge of one of the sites within a group is likely to affect all the other sites within the particular group

Chest Wall Resection for Adult Soft Tissue Sarcomas and Chondrosarcomas: Analysis of Prognostic Factors

Background: Wide resection with tumor-free margins is necessary in soft-tissue sarcomas to minimize local recurrence and to contribute to long-term survival. Information about treatment outcome and prognostic factors of adult sarcoma requiring chest wall resection (CWR) is limited. Methods: Sixty consecutive patients were retrospectively studied for overall survival (OS), local recurrence-free survival (LRFS), and disease-free survival (DFS). Twenty-one prognostic factors regarding survival were analyzed by univariate analysis using the Kaplan-Meier method and the log-rank test. Results: With a median survival of 2.5 years, the OS was 46% (33%) at 5 (10) years. The LRFS was 64% at 5 and 10 years, and the DFS was 30% and 25% at 5 and 10 years. At the end of the study period, 26 patients (43%) were alive, of which 20 patients (33%) had no evidence of disease and 40 patients (67%) had no chest wall recurrence. In the group of 9 patients with a radiation-induced soft-tissue sarcoma, the median survival was 8 months. Favorable outcome in univariate analysis in OS and LRFS applied for the low-grade sarcoma, bone invasion, and sternal resection. For OS only, age below 60 years and no radiotherapy were significant factors contributing to an improved survival. CWR was considered radical (R0) at the pathological examination in 43 patients. There were 52 patients with an uneventful recovery. There was one postoperative death. Conclusions: CWR for soft-tissue sarcoma is a safe surgical procedure with low morbidity and a mortality rate of less than 1%. With proper patient selection acceptable survival can be reached in a large group of patients. Care must be given to patients with radiation-induced soft-tissue sarcoma who have a significantly worse prognosis

Paternal mtDNA and Maleness Are Co-Inherited but Not Causally Linked in Mytilid Mussels

BACKGROUND: In marine mussels of the genus Mytilus there are two mitochondrial genomes. One is transmitted through the female parent, which is the normal transmission route in animals, and the other is transmitted through the male parent which is an unusual phenomenon. In males the germ cell line is dominated by the paternal mitochondrial genome and the somatic cell line by the maternal. Research to date has not allowed a clear answer to the question of whether inheritance of the paternal genome is causally related to maleness. METHODOLOGY/PRINCIPAL FINDINGS: Here we present results from hybrid crosses, from triploid mussels and from observations of sperm mitochondria in fertilized eggs which clearly show that maleness and presence of the paternal mitochondrial genome can be decoupled. These same results show that the female mussel has exclusive control of whether her progeny will inherit the mitochondrial genome of the male parent. CONCLUSIONS/SIGNIFICANCE: These findings are important in our efforts to understand the mechanistic basis of this unusual mode of mitochondrial DNA inheritance that is common among bivalves

Barriers to the acceptance of electronic medical records by physicians from systematic review to taxonomy and interventions

<p>Abstract</p> <p>Background</p> <p>The main objective of this research is to identify, categorize, and analyze barriers perceived by physicians to the adoption of Electronic Medical Records (EMRs) in order to provide implementers with beneficial intervention options.</p> <p>Methods</p> <p>A systematic literature review, based on research papers from 1998 to 2009, concerning barriers to the acceptance of EMRs by physicians was conducted. Four databases, "Science", "EBSCO", "PubMed" and "The Cochrane Library", were used in the literature search. Studies were included in the analysis if they reported on physicians' perceived barriers to implementing and using electronic medical records. Electronic medical records are defined as computerized medical information systems that collect, store and display patient information.</p> <p>Results</p> <p>The study includes twenty-two articles that have considered barriers to EMR as perceived by physicians. Eight main categories of barriers, including a total of 31 sub-categories, were identified. These eight categories are: A) Financial, B) Technical, C) Time, D) Psychological, E) Social, F) Legal, G) Organizational, and H) Change Process. All these categories are interrelated with each other. In particular, Categories G (Organizational) and H (Change Process) seem to be mediating factors on other barriers. By adopting a change management perspective, we develop some barrier-related interventions that could overcome the identified barriers.</p> <p>Conclusions</p> <p>Despite the positive effects of EMR usage in medical practices, the adoption rate of such systems is still low and meets resistance from physicians. This systematic review reveals that physicians may face a range of barriers when they approach EMR implementation. We conclude that the process of EMR implementation should be treated as a change project, and led by implementers or change managers, in medical practices. The quality of change management plays an important role in the success of EMR implementation. The barriers and suggested interventions highlighted in this study are intended to act as a reference for implementers of Electronic Medical Records. A careful diagnosis of the specific situation is required before relevant interventions can be determined.</p

Spatial quantum noise interferometry in expanding ultracold atom clouds

In a pioneering experiment, Hanbury Brown and Twiss (HBT) demonstrated that noise correlations could be used to probe the properties of a (bosonic) particle source through quantum statistics; the effect relies on quantum interference between possible detection paths for two indistinguishable particles. HBT correlations -- together with their fermionic counterparts -- find numerous applications, ranging from quantum optics to nuclear and elementary particle physics. Spatial HBT interferometry has been suggested as a means to probe hidden order in strongly correlated phases of ultracold atoms. Here we report such a measurement on the Mott insulator phase of a rubidium Bose gas as it is released from an optical lattice trap. We show that strong periodic quantum correlations exist between density fluctuations in the expanding atom cloud. These spatial correlations reflect the underlying ordering in the lattice, and find a natural interpretation in terms of a multiple-wave HBT interference effect. The method should provide a useful tool for identifying complex quantum phases of ultracold bosonic and fermionic atoms