An advance notification letter increases participation in colorectal cancer screening

© 2007 Royal Society of MedicineObjectives: To determine the impact of novel invitation strategies on population participation in faecal immunochemical test (FIT)-based colorectal cancer (CRC) screening. Setting A community screening programme in Adelaide, South Australia. Methods: In total, 2400 people aged 50–74 years were randomly allocated to one of four CRC screening invitation strategies: (a) Control: standard invitation-to-screen letter explaining risk of CRC and the concept, value and method of screening; (b) Risk: invitation with additional messages related to CRC risk; (c) Advocacy: invitation with additional messages related to advocacy for screening from previous screening programme participants and (d) Advance Notification: first, a letter introducing Control letter messages followed by the standard invitation-to-screen. Invitations included an FIT kit. Programme participation rates were determined for each strategy relative to control. Associations between participation and sociodemographic variables were explored. Results: At 12 weeks after invitation, participation was: Control: 237/600 (39.5%); Risk: 242/600 (40.3%); Advocacy: 216/600 (36.0%) and Advance Notification: 290/600 (48.3%). Participation was significantly greater than Control only in the Advance Notification group (Relative risk [RR] 1.23, 95% confidence interval [CI] 1.06–1.43). This effect was apparent as early as two weeks from date of offer; Advance Notification: 151/600 (25.2%) versus Control: 109/600 (18.2%, RR 1.38, 95% CI 1.11–1.73). Conclusions: Advance notification significantly increased screening participation. The effect may be due to a population shift in readiness to undertake screening, and is consistent with the Transtheoretical Model of behaviour change. Risk or lay advocacy strategies did not improve screening participation. Organized screening programmes should consider using advance notification letters to improve programme participation.S R Cole, A Smith, CWilson, D Turnbull, A Esterman and G P Youn

Exact diagonalization of the S=1/2 Heisenberg antiferromagnet on finite bcc lattices to estimate properties on the infinite lattice

Here we generate finite bipartite body-centred cubic lattices up to 32 vertices. We have studied the spin one half Heisenberg antiferromagnet by diagonalizing its Hamiltonian on each of the finite lattices and hence computing its ground state properties. By extrapolation of these data we obtain estimates of the T = 0 properties on the infinite bcc lattice. Our estimate of the T = 0 energy agrees to five parts in ten thousand with third order spin wave and series expansion method estimates, while our estimate of the staggered magnetization agrees with the spin wave estimate to within a quarter of one percent.Comment: 16 pages, LaTeX, 1 ps figure, to appear in J.Phys.

Proof of the Hyperplane Zeros Conjecture of Lagarias and Wang

We prove that a real analytic subset of a torus group that is contained in its image under an expanding endomorphism is a finite union of translates of closed subgroups. This confirms the hyperplane zeros conjecture of Lagarias and Wang for real analytic varieties. Our proof uses real analytic geometry, topological dynamics and Fourier analysis.Comment: 25 page

Distribution and Molecular Evolution of Bacillus anthracis Genotypes in Namibia

The recent development of genetic markers for Bacillus anthracis has made it possible to monitor the spread and distribution of this pathogen during and between anthrax outbreaks. In Namibia, anthrax outbreaks occur annually in the Etosha National Park (ENP) and on private game and livestock farms. We genotyped 384 B. anthracis isolates collected between 1983–2010 to identify the possible epidemiological correlations of anthrax outbreaks within and outside the ENP and to analyze genetic relationships between isolates from domestic and wild animals. The isolates came from 20 animal species and from the environment and were genotyped using a 31-marker multi-locus-VNTR-analysis (MLVA) and, in part, by twelve single nucleotide polymorphism (SNP) markers and four single nucleotide repeat (SNR) markers. A total of 37 genotypes (GT) were identified by MLVA, belonging to four SNP-groups. All GTs belonged to the A-branch in the cluster- and SNP-analyses. Thirteen GTs were found only outside the ENP, 18 only within the ENP and 6 both inside and outside. Genetic distances between isolates increased with increasing time between isolations. However, genetic distance between isolates at the beginning and end of the study period was relatively small, indicating that while the majority of GTs were only found sporadically, three genetically close GTs, accounting for more than four fifths of all the ENP isolates, appeared dominant throughout the study period. Genetic distances among isolates were significantly greater for isolates from different host species, but this effect was small, suggesting that while species-specific ecological factors may affect exposure processes, transmission cycles in different host species are still highly interrelated. The MLVA data were further used to establish a model of the probable evolution of GTs within the endemic region of the ENP. SNR-analysis was helpful in correlating an isolate with its source but did not elucidate epidemiological relationships

Hadroproduction of the Chi1 and Chi2 States of Charmonium in 800 GeV/c Proton-Silicon Interactions

The cross sections for the hadroproduction of the Chi1 and Chi2 states of charmonium in proton-silicon collisions at sqrt{s}=38.8 GeV have been measured in Fermilab fixed target Experiment 771. The Chi states were observed via their radiative decay to J/psi+gamma, where the photon converted to e+e- in the material of the spectrometer. The measured values for the Chi1 and Chi2 cross sections for x_F>0 are 263+-69(stat)+-32(syst) and 498+-143(stat)+-67(syst) nb per nucleon respectively. The resulting sigma(Chi1}/sigma(Chi2) ratio of 0.53+-0.20(stat)+-0.07(syst), although somewhat larger than most theoretical expectations, can be accomodated by the latest theoretical estimates.Comment: 4 pages, 4 figure

Communicating antimicrobial resistance and stewardship in the national press: lessons from sepsis awareness campaigns

No abstract available

LEO to GEO (and Beyond) Transfers Using High Power Solar Electric Propulsion (HP-SEP)

Rideshare, or Multi-Payload launch configurations, are becoming more and more commonplace but access to space is only one part of the overall mission needs. The ability for payloads to achieve their target orbits or destinations can still be difficult and potentially not feasible with on-board propulsion limitations. The High Power Solar Electric Propulsion (HP-SEP) Orbital Maneuvering Vehicle (OMV) provides transfer capabilities for both large and small payload in excess of what is possible with chemical propulsion. Leveraging existing secondary payload adapter technology like the ESPA provides a platform to support Multi-Payload launch and missions. When coupled with HP-SEP, meaning greater than 30 kW system power, very large delta-V maneuvers can be accomplished. The HP-SEP OMV concept is designed to perform a Low Earth Orbit to Geosynchronous Orbit (LEO-GEO) transfer of up to six payloads each with 300kg mass. The OMV has enough capability to perform this 6 kms maneuver and have residual capacity to extend an additional transfer from GEO to Lunar orbit. This high deltaV capability is achieved using state of the art 12.5kW Hall Effect Thrusters (HET) coupled with high power roll up solar arrays. The HP-SEP OMV also provides a demonstration platform for other SEP technologies such as advanced Power Processing Units (PPU), Xenon Feed Systems (XFS), and other HET technologies. The HP-SEP OMV platform can be leveraged for other missions as well such as interplanetary science missions and applications for resilient space architectures

Mitochondrial changes within axons in multiple sclerosis

Multiple sclerosis is the most common cause of non-traumatic neurological impairment in young adults. An energy deficient state has been implicated in the degeneration of axons, the pathological correlate of disease progression, in multiple sclerosis. Mitochondria are the most efficient producers of energy and play an important role in calcium homeostasis. We analysed the density and function of mitochondria using immunohistochemistry and histochemistry, respectively, in chronic active and inactive lesions in progressive multiple sclerosis. As shown before in acute pattern III and Balo’s lesions, the mitochondrial respiratory chain complex IV activity is reduced despite the presence of mitochondria in demyelinated axons with amyloid precursor protein accumulation, which are predominantly located at the active edge of chronic active lesions. Furthermore, the strong non-phosphorylated neurofilament (SMI32) reactivity was associated with a significant reduction in complex IV activity and mitochondria within demyelinated axons. The complex IV defect associated with axonal injury may be mediated by soluble products of innate immunity, as suggested by an inverse correlation between complex IV activity and macrophage/microglial density in chronic lesions. However, in inactive areas of chronic multiple sclerosis lesions the mitochondrial respiratory chain complex IV activity and mitochondrial mass, judged by porin immunoreactivity, are increased within approximately half of large (>2.5 μm diameter) chronically demyelinated axons compared with large myelinated axons in the brain and spinal cord. The axon-specific mitochondrial docking protein (syntaphilin) and phosphorylated neurofilament-H were increased in chronic lesions. The lack of complex IV activity in a proportion of Na+/K+ ATPase α-1 positive demyelinated axons supports axonal dysfunction as a contributor to neurological impairment and disease progression. Furthermore, in vitro studies show that inhibition of complex IV augments glutamate-mediated axonal injury (amyloid precursor protein and SMI32 reactivity). Our findings have important implications for both axonal degeneration and dysfunction during the progressive stage of multiple sclerosis

Recommendations for laboratory workflow that better support centralised amalgamation of genomic variant data: findings from CanVIG-UK national molecular laboratory survey.

BACKGROUND: National and international amalgamation of genomic data offers opportunity for research and audit, including analyses enabling improved classification of variants of uncertain significance. Review of individual-level data from National Health Service (NHS) testing of cancer susceptibility genes (2002-2023) submitted to the National Disease Registration Service revealed heterogeneity across participating laboratories regarding (1) the structure, quality and completeness of submitted data, and (2) the ease with which that data could be assembled locally for submission. METHODS: In May 2023, we undertook a closed online survey of 51 clinical scientists who provided consensus responses representing all 17 of 17 NHS molecular genetic laboratories in England and Wales which undertake NHS diagnostic analyses of cancer susceptibility genes. The survey included 18 questions relating to 'next-generation sequencing workflow' (11), 'variant classification' (3) and 'phenotypical context' (4). RESULTS: Widely differing processes were reported for transfer of variant data into their local LIMS (Laboratory Information Management System), for the formatting in which the variants are stored in the LIMS and which classes of variants are retained in the local LIMS. Differing local provisions and workflow for variant classifications were also reported, including the resources provided and the mechanisms by which classifications are stored. CONCLUSION: The survey responses illustrate heterogeneous laboratory workflow for preparation of genomic variant data from local LIMS for centralised submission. Workflow is often labour-intensive and inefficient, involving multiple manual steps which introduce opportunities for error. These survey findings and adoption of the concomitant recommendations may support improvement in laboratory dataflows, better facilitating submission of data for central amalgamation

Importance of competing risks in the analysis of anti-epileptic drug failure

BACKGROUND: Retention time (time to treatment failure) is a commonly used outcome in antiepileptic drug (AED) studies. METHODS: Two datasets are used to demonstrate the issues in a competing risks analysis of AEDs. First, data collection and follow-up considerations are discussed with reference to information from 15 monotherapy trials. Recommendations for improved data collection and cumulative incidence analysis are then illustrated using the SANAD trial dataset. The results are compared to the more common approach using standard survival analysis methods. RESULTS: A non-significant difference in overall treatment failure time between gabapentin and topiramate (logrank test statistic = 0.01, 1 degree of freedom, p-value = 0.91) masked highly significant differences in opposite directions with gabapentin resulting in fewer withdrawals due to side effects (Gray's test statistic = 11.60, 1 degree of freedom, p = 0.0007) but more due to poor seizure control (Gray's test statistic = 14.47, 1 degree of freedom, p-value = 0.0001). The significant difference in overall treatment failure time between lamotrigine and carbamazepine (logrank test statistic = 5.6, 1 degree of freedom, p-value = 0.018) was due entirely to a significant benefit of lamotrigine in terms of side effects (Gray's test statistic = 10.27, 1 degree of freedom, p = 0.001). CONCLUSION: Treatment failure time can be measured reliably but care is needed to collect sufficient information on reasons for drug withdrawal to allow a competing risks analysis. Important differences between the profiles of AEDs may be missed unless appropriate statistical methods are used to fully investigate treatment failure time. Cumulative incidence analysis allows comparison of the probability of failure between two AEDs and is likely to be a more powerful approach than logrank analysis for most comparisons of standard and new anti-epileptic drugs