The 21 cm Signature of Cosmic String Wakes

We discuss the signature of a cosmic string wake in 21cm redshift surveys. Since 21cm surveys probe higher redshifts than optical large-scale structure surveys, the signatures of cosmic strings are more manifest in 21cm maps than they are in optical galaxy surveys. We find that, provided the tension of the cosmic string exceeds a critical value (which depends on both the redshift when the string wake is created and the redshift of observation), a cosmic string wake will generate an emission signal with a brightness temperature which approaches a limiting value which at a redshift of $z + 1 = 30$ is close to 400 mK in the limit of large string tension. The signal will have a specific signature in position space: the excess 21cm radiation will be confined to a wedge-shaped region whose tip corresponds to the position of the string, whose planar dimensions are set by the planar dimensions of the string wake, and whose thickness (in redshift direction) depends on the string tension. For wakes created at $z_i + 1 = 10^3$, then at a redshift of $z + 1 = 30$ the critical value of the string tension $\mu$ is $G \mu = 6 \times 10^{-7}$, and it decreases linearly with redshift (for wakes created at the time of equal matter and radiation, the critical value is a factor of two lower at the same redshift). For smaller tensions, cosmic strings lead to an observable absorption signal with the same wedge geometry.Comment: 11 pages, 4 figures; a couple of comments added in the discussion sectio

Development of Lentiviral Vectors Pseudotyped With Influenza B Hemagglutinins: Application in Vaccine Immunogenicity, mAb Potency, and Sero-Surveillance Studies.

Influenza B viruses (IBV) cause respiratory disease epidemics in humans and are therefore components of seasonal influenza vaccines. Serological methods are employed to evaluate vaccine immunogenicity prior to licensure. However, classical methods to assess influenza vaccine immunogenicity such as the hemagglutination inhibition assay (HI) and the serial radial hemolysis assay (SRH), have been proven to have many limitations. As such, there is a need to develop innovative methods that can improve on these traditional assays and provide advantages such as ease of production and access, safety, reproducibility, and specificity. It has been previously demonstrated that the use of replication-defective viruses, such as lentiviral vectors pseudotyped with influenza A hemagglutinins in microneutralization assays (pMN) is a safe and sensitive alternative to study antibody responses elicited by natural influenza infection or vaccination. Consequently, we have produced Influenza B hemagglutinin-pseudotypes (IBV PV) using plasmid-directed transfection. To activate influenza B hemagglutinin, we have explored the use of proteases in increasing PV titers via their co-transfection during pseudotype virus production. When tested for their ability to transduce target cells, the influenza B pseudotypes produced exhibit tropism for different cell lines. The pseudotypes were evaluated as alternatives to live virus in microneutralization assays using reference sera standards, mouse and human sera collected during vaccine immunogenicity studies, surveillance sera from seals, and monoclonal antibodies (mAbs) against IBV. The influenza B pseudotype pMN was found to effectively detect neutralizing and cross-reactive responses in all assays and shows promise as an effective and versatile tool in influenza research

Unknowable bodies, unthinkable sexualities: lesbian and transgender legal invisibility in the Toronto women's bathhouse raid

Although litigation involving sexual orientation and gender identity discrimination claims has generated considerable public attention in recent years, lesbian and transgender bodies and sexualities still remain largely invisible in Anglo-American courts. While such invisibility is generally attributed to social norms that fail to recognize lesbian and transgender experiences, the capacity to 'not see' or 'not know' queer bodies and sexualities also involves wilful acts of ignorance. Drawing from R. v Hornick (2002) a Canadian case involving the police raid of a women's bathhouse, this article explores how lesbian and transgender bodies and sexualities are actively rendered invisible via legal knowledge practices, norms and rationalities. It argues that limited knowledge and limited thinking not only regulate the borders of visibility and belonging, but play an active part in shaping identities, governing conduct and producing subjectivity

A tool kit for rapid cloning and expression of recombinant antibodies

Over the last four decades, molecular cloning has evolved tremendously. Efficient products allowing assembly of multiple DNA fragments have become available. However, cost-effective tools for engineering antibodies of different specificities, isotypes and species are still needed for many research and clinical applications in academia. Here, we report a method for one-step assembly of antibody heavy- and light-chain DNAs into a single mammalian expression vector, starting from DNAs encoding the desired variable and constant regions, which allows antibodies of different isotypes and specificity to be rapidly generated. As a proof of principle we have cloned, expressed and characterized functional recombinant tumor-associated antigen-specific chimeric IgE/κ and IgG(1)/κ, as well as recombinant grass pollen allergen Phl p 7 specific fully human IgE/λ and IgG(4)/λ antibodies. This method utilizing the antibody expression vectors, available at Addgene, has many applications, including the potential to support simultaneous processing of antibody panels, to facilitate mechanistic studies of antigen-antibody interactions and to conduct early evaluations of antibody functions

Who participates in web-assisted tobacco interventions? The quit-primo and national dental practice-based research network hi-quit studies

INTRODUCTION: Smoking is the most preventable cause of death. Although effective, Web-assisted tobacco interventions are underutilized and recruitment is challenging. Understanding who participates in Web-assisted tobacco interventions may help in improving recruitment. OBJECTIVES: To understand characteristics of smokers participating in a Web-assisted tobacco intervention (Decide2Quit.org). METHODS: In addition to the typical Google advertisements, we expanded Decide2Quit.org recruitment to include referrals from medical and dental providers. We assessed how the expanded recruitment of smokers changed the users\u27 characteristics, including comparison with a population-based sample of smokers from the national Behavioral Risk Factors Surveillance Survey (BRFSS). Using a negative binomial regression, we compared demographic and smoking characteristics by recruitment source, in particular readiness to quit and association with subsequent Decide2Quit.org use. RESULTS: The Decide2Quit.org cohort included 605 smokers; the 2010 BRFSS dataset included 69,992. Compared to BRFSS smokers, a higher proportion of Decide2Quit.org smokers were female (65.2% vs 45.7%, P=.001), over age 35 (80.8% vs 67.0%, P=.001), and had some college or were college graduates (65.7% vs 45.9%, P=.001). Demographic and smoking characteristics varied by recruitment; for example, a lower proportion of medical- (22.1%) and dental-referred (18.9%) smokers had set a quit date or had already quit than Google smokers (40.1%, P CONCLUSIONS: Recruitment from clinical practices complimented Google recruitment attracting smokers less motivated to quit and less experienced with Web-assisted tobacco interventions. TRIAL REGISTRATION: Clinicaltrials.gov NCT00797628; http://clinicaltrials.gov/ct2/show/NCT00797628 (Archived by WebCite at http://www.webcitation.org/6F3tqz0b3)

Damage patterns at the head-stem taper junction helps understand the mechanisms of material loss

Background: Material loss at the taper junction of metal-on-metal total hip replacements (MOM THRs) has been implicated in their early failure. The mechanisms of material loss are not fully understood; analysis of the patterns of damage at the taper can help us better understand why material loss occurs at this junction. Methods: We mapped the patterns of material loss in a series of 155 MOM-THRs received at our centre by scanning the taper surface using a roundness-measuring machine. We examined these material loss maps to develop a five-tier classification system based on visual differences between different patterns. We correlated these patterns to surgical, implant and patient factors known to be important for head-stem taper damage. Results: We found that 63 implants had ‘minimal damage’ at the taper (material loss <1mm3 ) and the remaining 92 implants could be categorised by four distinct patterns of taper material loss. We found that (1) head diameter and (2) time to revision were key significant variables separating the groups. Conclusion: These material loss maps allow us to suggest different mechanisms that dominate the cause of the material loss in each pattern: (a) corrosion, (b) mechanically assisted corrosion or (c) intra-operative damage or poor size tolerances leading to toggling of trunnion in taper

A live RSV vaccine with engineered thermostability is immunogenic in cotton rats despite high attenuation

Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization and there remains no pediatric vaccine. RSV live-attenuated vaccines (LAVs) have a history of safe testing in infants; however, achieving an effective balance of attenuation and immunogenicity has proven challenging. Here we seek to engineer an RSV LAV with enhanced immunogenicity. Genetic mapping identifies strain line 19 fusion (F) protein residues that correlate with pre-fusion antigen maintenance by ELISA and thermal stability of infectivity in live RSV. We generate a LAV candidate named OE4 which expresses line 19F and is attenuated by codon-deoptimization of non-structural (NS1 and NS2) genes, deletion of the small hydrophobic (SH) gene, codon-deoptimization of the attachment (G) gene and ablation of the secreted form of G. OE4 (RSV-A2-dNS1-dNS2-ΔSH-dGm-Gsnull-line19F) exhibits elevated pre-fusion antigen levels, thermal stability, immunogenicity, and efficacy despite heavy attenuation in the upper and lower airways of cotton rats

Getting our ducks in a row:The need for data utility comparisons of healthcare systems data for clinical trials

BACKGROUND: Better use of healthcare systems data, collected as part of interactions between patients and the healthcare system, could transform planning and conduct of randomised controlled trials. Multiple challenges to widespread use include whether healthcare systems data captures sufficiently well the data traditionally captured on case report forms. "Data Utility Comparison Studies" (DUCkS) assess the utility of healthcare systems data for RCTs by comparison to data collected by the trial. Despite their importance, there are few published UK examples of DUCkS.METHODS-AND-RESULTS: Building from ongoing and selected recent examples of UK-led DUCkS in the literature, we set out experience-based considerations for the conduct of future DUCkS. Developed through informal iterative discussions in many forums, considerations are offered for planning, protocol development, data, analysis and reporting, with comparisons at "patient-level" or "trial-level", depending on the item of interest and trial status.DISCUSSION: DUCkS could be a valuable tool in assessing where healthcare systems data can be used for trials and in which trial teams can play a leading role. There is a pressing need for trials to be more efficient in their delivery and research waste must be reduced. Trials have been making inconsistent use of healthcare systems data, not least because of an absence of evidence of utility. DUCkS can also help to identify challenges in using healthcare systems data, such as linkage (access and timing) and data quality. We encourage trial teams to incorporate and report DUCkS in trials and funders and data providers to support them.</p

Getting our ducks in a row: The need for data utility comparisons of healthcare systems data for clinical trials

Background: Better use of healthcare systems data, collected as part of interactions between patients and the healthcare system, could transform planning and conduct of randomised controlled trials. Multiple challenges to widespread use include whether healthcare systems data captures sufficiently well the data traditionally captured on case report forms. “Data Utility Comparison Studies” (DUCkS) assess the utility of healthcare systems data for RCTs by comparison to data collected by the trial. Despite their importance, there are few published UK examples of DUCkS. // Methods-and-Results: Building from ongoing and selected recent examples of UK-led DUCkS in the literature, we set out experience-based considerations for the conduct of future DUCkS. Developed through informal iterative discussions in many forums, considerations are offered for planning, protocol development, data, analysis and reporting, with comparisons at “patient-level” or “trial-level”, depending on the item of interest and trial status. // Discussion: DUCkS could be a valuable tool in assessing where healthcare systems data can be used for trials and in which trial teams can play a leading role. There is a pressing need for trials to be more efficient in their delivery and research waste must be reduced. Trials have been making inconsistent use of healthcare systems data, not least because of an absence of evidence of utility. DUCkS can also help to identify challenges in using healthcare systems data, such as linkage (access and timing) and data quality. We encourage trial teams to incorporate and report DUCkS in trials and funders and data providers to support them

Getting our ducks in a row:The need for data utility comparisons of healthcare systems data for clinical trials

BACKGROUND: Better use of healthcare systems data, collected as part of interactions between patients and the healthcare system, could transform planning and conduct of randomised controlled trials. Multiple challenges to widespread use include whether healthcare systems data captures sufficiently well the data traditionally captured on case report forms. "Data Utility Comparison Studies" (DUCkS) assess the utility of healthcare systems data for RCTs by comparison to data collected by the trial. Despite their importance, there are few published UK examples of DUCkS.METHODS-AND-RESULTS: Building from ongoing and selected recent examples of UK-led DUCkS in the literature, we set out experience-based considerations for the conduct of future DUCkS. Developed through informal iterative discussions in many forums, considerations are offered for planning, protocol development, data, analysis and reporting, with comparisons at "patient-level" or "trial-level", depending on the item of interest and trial status.DISCUSSION: DUCkS could be a valuable tool in assessing where healthcare systems data can be used for trials and in which trial teams can play a leading role. There is a pressing need for trials to be more efficient in their delivery and research waste must be reduced. Trials have been making inconsistent use of healthcare systems data, not least because of an absence of evidence of utility. DUCkS can also help to identify challenges in using healthcare systems data, such as linkage (access and timing) and data quality. We encourage trial teams to incorporate and report DUCkS in trials and funders and data providers to support them.</p