Raman-free, noble-gas-filled PCF source for ultrafast, very bright twin-beam squeezed vacuum

We report a novel source of twin beams based on modulational instability in high-pressure argon-filled hollow-core kagom\'e-style photonic-crystal fibre. The source is Raman-free and manifests strong photon-number correlations for femtosecond pulses of squeezed vacuum with a record brightness of ~2500 photons per mode. The ultra-broadband (~50 THz) twin beams are frequency tunable and contain one spatial and less than 5 frequency modes

Economic evaluation alongside pragmatic randomised trials: developing a standard operating procedure for clinical trials units

<p>Abstract</p> <p>Background</p> <p>There is wide recognition that pragmatic randomised trials are the best vehicle for economic evaluation. This is because trials provide the best chance of ensuring internal validity, not least through the rigorous prospective collection of patient-specific data. Furthermore the marginal cost of collecting economic data alongside clinical data is typically modest. UK Clinical Research Collaboration (UKCRC) does not require a standard operating procedure (SOP) for economic evaluation as a prerequisite for trial unit registration. We judge that such a SOP facilitates the integration of health economics into trials.</p> <p>Methods</p> <p>A collaboration between health economists and trialists at Bangor University led to the development of a SOP for economic evaluation alongside pragmatic trials, in addition to the twenty SOPs required by UKCRC for registration, which include randomisation, data management and statistical analysis.</p> <p>Results</p> <p>Our recent telephone survey suggests that no other UKCRC-registered trials unit currently has an economic SOP.</p> <p>Conclusion</p> <p>We argue that UKCRC should require, from all Trials Units undertaking economic evaluation and seeking registration or re-registration, a SOP for economic evaluation as one of their portfolio of supporting SOPs.</p

Impact of generic alendronate cost on the cost-effectiveness of osteoporosis screening and treatment

Introduction: Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women. Methods: Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorptiometry (DXA), and alendronate treatment for individuals with osteoporosis; with a comparator of "no screening" and treatment only after fracture occurrence. We evaluated annual alendronate costs of $20 through$800; outcome measures included fractures; nursing home admission; medication adverse events; death; costs; quality-adjusted life-years (QALYs); and incremental cost-effectiveness ratios (ICERs) in 2010 U.S. dollars per QALY gained. A lifetime time horizon was used, and direct costs were included. Base-case and sensitivity analyses were performed. Results: Base-case analysis results showed that at annual alendronate costs of $200 or less, osteoporosis screening followed by treatment was cost-saving, resulting in lower total costs than no screening as well as more QALYs (10.6 additional quality-adjusted life-days). When assuming alendronate costs of$400 through $800, screening and treatment resulted in greater lifetime costs than no screening but was highly cost-effective, with ICERs ranging from$714 per QALY gained through $13,902 per QALY gained. Probabilistic sensitivity analyses revealed that the cost-effectiveness of osteoporosis screening followed by alendronate treatment was robust to joint input parameter estimate variation at a willingness-to-pay threshold of$50,000/QALY at all alendronate costs evaluated. Conclusions: Osteoporosis screening followed by alendronate treatment is effective and highly cost-effective for postmenopausal women across a range of alendronate costs, and may be cost-saving at annual alendronate costs of $200 or less. © 2012 Nayak et al

Ethnicity, voter alignment and political party affiliation - an African case: Zambia

Conventional wisdom holds that ethnicity provides the social cleavage for voting behav-iour and party affiliation in Africa. Because this is usually inferred from aggregate data of national election results, it might prove to be an ecological fallacy. The evidence based on individual data from an opinion survey in Zambia suggests that ethnicity matters for voter alignment and even more so for party affiliation, but it is certainly not the only factor. The analysis also points to a number of qualifications which are partly methodology-related. One is that the degree of ethnic voting can differ from one ethno-political group to the other depending on various degrees of ethnic mobilisation. Another is that if smaller eth-nic groups or subgroups do not identify with one particular party, it is difficult to find a significant statistical correlation between party affiliation and ethnicity - but that does not prove that they do not affiliate along ethnic lines.Wahlverhalten und Mitgliedschaft in politischen Parteien Afrikas ist nur wenig untersucht worden. Gewöhnlich wird argumentiert, dass Ethnizität als soziale Konfliktlinie das Wahlverhalten und die Parteienmitgliedschaft strukturiert. Da dieses Argument auf hoch aggregierten Wahldaten beruht, kann hier ein ökologischer Fehlschuss vorliegen. Die vorliegende Analyse beruht deshalb auf individuellen Umfragedaten aus Sambia. Das Ergebnis ist, dass Ethnizität tatsächlich eine Rolle für das Wahlverhalten und die Parteienmitgliedschaft spielt, aber keineswegs den einzigen Erklärungsfaktor darstellt. Die Analyse offenbart zudem eine Reihe von Einschränkungen und Qualifizierungen, die teilweise methodischer Natur sind. Eine ist, dass ethnisches Wahlverhalten und Parteienmitgliedschaft von einer ethnischen Gruppe zur anderen unterschiedlich ist, dass, wenn sich kleinere ethnische Gruppen oder Untergruppen mit keiner Partei identifizieren, es schwierig wird, statistisch signifikante Korrelationen zu finden - was indessen noch nicht beweist, dass Ethnizität keine Rolle spielt

Correction: Folate Augmentation of Treatment – Evaluation for Depression (FolATED): protocol of a randomised controlled trial

This correction reports changes in our protocol since its publication. These include changes to authorship and acknowledgements, together with improvements to study design and procedures, and correction of an internal inconsistency. The improvements relate to the exclusion criteria, assessments carried out at screening, and mode of data collection

A transient homotypic interaction model for the influenza A virus NS1 protein effector domain

Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal 'tail'. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed 'helix-closed' and 'helix-open') in virus-infected cells. 'Helix-closed' conformations appear to enhance dsRNA binding, and 'helix-open' conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins