A response to “Likelihood ratio as weight of evidence: a closer look” by Lund and Iyer

Recently, Lund and Iyer (L&I) raised an argument regarding the use of likelihood ratios in court. In our view, their argument is based on a lack of understanding of the paradigm. L&I argue that the decision maker should not accept the expert’s likelihood ratio without further consideration. This is agreed by all parties. In normal practice, there is often considerable and proper exploration in court of the basis for any probabilistic statement. We conclude that L&I argue against a practice that does not exist and which no one advocates. Further we conclude that the most informative summary of evidential weight is the likelihood ratio. We state that this is the summary that should be presented to a court in every scientific assessment of evidential weight with supporting information about how it was constructed and on what it was based

Knowledge, attitudes and practices (KAP) towards rabies and free-roaming dogs (FRD) in Shirsuphal village in western India: A community based cross-sectional study

The lack of awareness about dog-bite related rabies in the rural population of developing countries, including India, is a major impediment to controlling the incidence of disease in humans. A survey of 127 rural residents was undertaken in Shirsuphal village in western India using a structured questionnaire to assess the influence of demographic and pet/livestock owning characteristics on the knowledge, attitudes and practices of the respondents towards rabies and free roaming dogs (FRD). Multivariable logistic regression models were constructed and the knowledge of the rural residents of Shirsuphal village was found to be significantly influenced by family size (OR 2.1, 95%CI 1.0–4.6, p = 0.04) and poultry ownership (OR 2.3, 95%CI 1.1–4.9, p = 0.03), while their attitudes towards FRD was significantly influenced by age of the respondents (OR 2.6, 95% CI 1.2–5.8) and ownership of cattle/ buffalo (OR 2.2, 95% CI 1.1–5.5). Although the knowledge score about rabies was high, a comprehensive understanding of the disease was lacking. Concerted efforts to widen the knowledge about rabies and promote healthier practices towards FRD are recommended

Knowledge, attitudes and practices towards dog-bite related rabies in para-medical staff at rural primary health centres in Baramati, western India

The lack of awareness regarding rabies amongst rural primary care health staff and their adverse practices towards the management of dog-bite wounds is a major contributor to the high incidence of rabies infection and subsequent human mortality in India. A Knowledge, Attitudes and Practices survey was carried out involving 54 nursing and non-nursing staff working in 18 rural Primary Health centres and sub-centres around Baramati town of Pune district in Western India. Multivariable logistic regression models were constructed to assess factors that influenced knowledge of rabies and practices towards management of dog-bite related wounds. The more experienced and better-educated workers were found to have a good awareness of rabies (OR 3.4, 95%CI 1.0–12.1) and good practices towards dog-bite wound management (OR 5.6, 95%CI 1.2–27.0). Surprisingly, non-nursing staff were significantly more knowledgeable about rabies (OR 3.5, 95%CI 1.0–12.3), but their practices towards dog-bite wound management were inadequate (OR 0.18, 95%CI 0.04–0.8) compared to the nursing staff. It is recommended that a mandatory training module for primary care health staff be developed and implemented to improve their knowledge regarding rabies and management of dog-bite wounds to reduce the incidence of human rabies in rural India

Knowledge, attitudes and practices towards dog-bite related rabies in para-medical staff at rural primary health centres in Baramati, western India

The lack of awareness regarding rabies amongst rural primary care health staff and their adverse practices towards the management of dog-bite wounds is a major contributor to the high incidence of rabies infection and subsequent human mortality in India. A Knowledge, Attitudes and Practices survey was carried out involving 54 nursing and non-nursing staff working in 18 rural Primary Health centres and sub-centres around Baramati town of Pune district in Western India. Multivariable logistic regression models were constructed to assess factors that influenced knowledge of rabies and practices towards management of dog-bite related wounds. The more experienced and better-educated workers were found to have a good awareness of rabies (OR 3.4, 95%CI 1.0–12.1) and good practices towards dog-bite wound management (OR 5.6, 95%CI 1.2–27.0). Surprisingly, non-nursing staff were significantly more knowledgeable about rabies (OR 3.5, 95%CI 1.0–12.3), but their practices towards dog-bite wound management were inadequate (OR 0.18, 95%CI 0.04–0.8) compared to the nursing staff. It is recommended that a mandatory training module for primary care health staff be developed and implemented to improve their knowledge regarding rabies and management of dog-bite wounds to reduce the incidence of human rabies in rural India

Search for gravitational wave bursts in LIGO's third science run

We report on a search for gravitational wave bursts in data from the three LIGO interferometric detectors during their third science run. The search targets subsecond bursts in the frequency range 100-1100 Hz for which no waveform model is assumed, and has a sensitivity in terms of the root-sum-square (rss) strain amplitude of hrss ~ 10^{-20} / sqrt(Hz). No gravitational wave signals were detected in the 8 days of analyzed data.Comment: 12 pages, 6 figures. Amaldi-6 conference proceedings to be published in Classical and Quantum Gravit

Searching for a Stochastic Background of Gravitational Waves with LIGO

The Laser Interferometer Gravitational-wave Observatory (LIGO) has performed the fourth science run, S4, with significantly improved interferometer sensitivities with respect to previous runs. Using data acquired during this science run, we place a limit on the amplitude of a stochastic background of gravitational waves. For a frequency independent spectrum, the new limit is $\Omega_{\rm GW} < 6.5 \times 10^{-5}$. This is currently the most sensitive result in the frequency range 51-150 Hz, with a factor of 13 improvement over the previous LIGO result. We discuss complementarity of the new result with other constraints on a stochastic background of gravitational waves, and we investigate implications of the new result for different models of this background.Comment: 37 pages, 16 figure

Quantum state preparation and macroscopic entanglement in gravitational-wave detectors

Long-baseline laser-interferometer gravitational-wave detectors are operating at a factor of 10 (in amplitude) above the standard quantum limit (SQL) within a broad frequency band. Such a low classical noise budget has already allowed the creation of a controlled 2.7 kg macroscopic oscillator with an effective eigenfrequency of 150 Hz and an occupation number of 200. This result, along with the prospect for further improvements, heralds the new possibility of experimentally probing macroscopic quantum mechanics (MQM) - quantum mechanical behavior of objects in the realm of everyday experience - using gravitational-wave detectors. In this paper, we provide the mathematical foundation for the first step of a MQM experiment: the preparation of a macroscopic test mass into a nearly minimum-Heisenberg-limited Gaussian quantum state, which is possible if the interferometer's classical noise beats the SQL in a broad frequency band. Our formalism, based on Wiener filtering, allows a straightforward conversion from the classical noise budget of a laser interferometer, in terms of noise spectra, into the strategy for quantum state preparation, and the quality of the prepared state. Using this formalism, we consider how Gaussian entanglement can be built among two macroscopic test masses, and the performance of the planned Advanced LIGO interferometers in quantum-state preparation

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Age-related clonal haematopoiesis is associated with increased epigenetic age

Age-related clonal haemopoiesis (ARCH) in healthy individuals was initially observed through an increased skewing in X-chromosome inactivation [1]. More recently, several groups reported that ARCH is driven by somatic mutations [2], with the most prevalent ARCH mutations being in the DNMT3A and TET2 genes, previously described as drivers of myeloid malignancies. ARCH is associated with an increased risk for haematological cancers [2]. ARCH also confers an increased risk for non-haematological diseases, such as cardiovascular disease, atherosclerosis, and chronic ischemic heart failure, for which age is a main risk factor 3, 4. Whether ARCH is linked to accelerated ageing has remained unexplored. The most accurate and commonly used tools to measure age acceleration are epigenetic clocks: they are based on age-related methylation differences at specific CpG sites [5]. Deviations from chronological age towards an increased epigenetic age have been associated with increased risk of earlier mortality and age-related morbidities 5, 6. Here we present evidence of accelerated epigenetic age in individuals with ARCH