Should patients with abnormal liver function tests in primary care be tested for chronic viral hepatitis: cost minimisation analysis based on a comprehensively tested cohort

Background Liver function tests (LFTs) are ordered in large numbers in primary care, and the Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS) study was set up to assess their usefulness in patients with no pre-existing or self-evident liver disease. All patients were tested for chronic viral hepatitis thereby providing an opportunity to compare various strategies for detection of this serious treatable disease. Methods This study uses data from the BALLETS cohort to compare various testing strategies for viral hepatitis in patients who had received an abnormal LFT result. The aim was to inform a strategy for identification of patients with chronic viral hepatitis. We used a cost-minimisation analysis to define a base case and then calculated the incremental cost per case detected to inform a strategy that could guide testing for chronic viral hepatitis. Results Of the 1,236 study patients with an abnormal LFT, 13 had chronic viral hepatitis (nine hepatitis B and four hepatitis C). The strategy advocated by the current guidelines (repeating the LFT with a view to testing for specific disease if it remained abnormal) was less efficient (more expensive per case detected) than a simple policy of testing all patients for viral hepatitis without repeating LFTs. A more selective strategy of viral testing all patients for viral hepatitis if they were born in countries where viral hepatitis was prevalent provided high efficiency with little loss of sensitivity. A notably high alanine aminotransferase (ALT) level (greater than twice the upper limit of normal) on the initial ALT test had high predictive value, but was insensitive, missing half the cases of viral infection. Conclusions Based on this analysis and on widely accepted clinical principles, a "fast and frugal" heuristic was produced to guide general practitioners with respect to diagnosing cases of viral hepatitis in asymptomatic patients with abnormal LFTs. It recommends testing all patients where a clear clinical indication of infection is present (e.g. evidence of intravenous drug use), followed by testing all patients who originated from countries where viral hepatitis is prevalent, and finally testing those who have a notably raised ALT level (more than twice the upper limit of normal). Patients not picked up by this efficient algorithm had a risk of chronic viral hepatitis that is lower than the general population

A New Era in the Quest for Dark Matter

There is a growing sense of `crisis' in the dark matter community, due to the absence of evidence for the most popular candidates such as weakly interacting massive particles, axions, and sterile neutrinos, despite the enormous effort that has gone into searching for these particles. Here, we discuss what we have learned about the nature of dark matter from past experiments, and the implications for planned dark matter searches in the next decade. We argue that diversifying the experimental effort, incorporating astronomical surveys and gravitational wave observations, is our best hope to make progress on the dark matter problem.Comment: Published in Nature, online on 04 Oct 2018. 13 pages, 1 figur

The Be Our Ally Beat Smoking (BOABS) study, a randomised controlled trial of an intensive smoking cessation intervention in a remote aboriginal Australian health care setting

Background: Australian Aboriginal and Torres Strait Islander peoples (Indigenous Australians) smoke at much higher rates than non-Indigenous people and smoking is an important contributor to increased disease, hospital admissions and deaths in Indigenous Australian populations. Smoking cessation programs in Australia have not had the same impact on Indigenous smokers as on non-Indigenous smokers. This paper describes the outcome of a study that aimed to test the efficacy of a locally-tailored, intensive, multidimensional smoking cessation program. Methods: A randomised controlled trial of Aboriginal researcher delivered tailored smoking cessation counselling during face-to-face visits, aiming for weekly for the first four weeks, monthly to six months and two monthly to12 months. The control (“usual care”) group received routine care relating to smoking cessation at their local primary health care service. Data collection occurred at enrolment, six and 12 months. The primary outcome was self-reported smoking cessation with urinary cotinine confirmation at final follow-up (median 13 (interquartile range 12–15) months after enrolment).Results: Participants in the intervention (n = 55) and usual care (n = 108) groups were similar in baseline characteristics, except the intervention group was slightly older. At final follow-up the smoking cessation rate for participants assigned to the intervention group (n = 6; 11%), while not statistically significant, was double that of usual care (n = 5; 5%; p = 0.131). A meta-analysis of these findings and a similarly underpowered but comparable study of pregnant Indigenous Australian women showed that Indigenous Australian participants assigned to the intervention groups were 2.4 times (95% CI, 1.01-5.5) as likely to quit as participants assigned to usual care. Conclusions: Culturally appropriate, multi-dimensional Indigenous quit smoking programs can be successfully implemented in remote primary health care. Intensive one-on-one interventions with substantial involvement from Aboriginal and Torres Strait Islander workers are likely to be effective in these settings. Trial registration: Australian New Zealand Clinical Trials Registry (ACTRN12608000604303)

Effect of intraperitoneally administered recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF) on the cytotoxic potential of murine peritoneal cells

We studied the effect of recombinant murine granulocyte–macrophage colony-stimulating factor(rmGM-CSF) on the cytotoxic potential of murine peritoneal cells. Mice received rmGM-CSF intraperitoneally using different dosages and injection schemes. At different time points after the last injection, mice were sacrificed, peritoneal cells isolated and their tumour cytotoxicity was determined by a cytotoxicity assay using syngeneic [methyl-3H]thymidine-labelled colon carcinoma cells. Also, the cytotoxic response to a subsequent in vitro stimulation with lipopolysaccharide was determined. Upon daily injection of 6000–54 000 U rmGM-CSF over a 6-day period, the number of peritoneal cells increased over ten fold with the highest rmGM-CSF dose. Increases in cell numbers was mainly due to increases in macrophage numbers. Upon injection of three doses of 3000 U rmGM-CSF per day for 3 consecutive days, the number of macrophages remained elevated for minimally 6 days. Although the peritoneal cells from rmGM-CSF-treated mice were not activated to a tumoricidal state, they could be activated to high levels of cytotoxicity with an additional in vitro stimulation of lipopolysaccharide. Resident cells isolated from control mice could be activated only to low levels of tumour cytotoxicity with lipopolysaccharide. Tumour cytotoxicity strongly correlated with nitric oxide secretion. When inhibiting nitric oxide synthase, tumour cell lysis decreased. Thus, the expanded peritoneal cell population induced by multiple injections of rmGM-CSF has a strong tumour cytotoxic potential and might provide a favourable condition for immunotherapeutic treatment of peritoneal neoplasms. © 1999 Cancer Research Campaig

Constitutive Type VI Secretion System Expression Gives Vibrio cholerae Intra- and Interspecific Competitive Advantages

The type VI secretion system (T6SS) mediates protein translocation across the cell membrane of Gram-negative bacteria, including Vibrio cholerae – the causative agent of cholera. All V. cholerae strains examined to date harbor gene clusters encoding a T6SS. Structural similarity and sequence homology between components of the T6SS and the T4 bacteriophage cell-puncturing device suggest that the T6SS functions as a contractile molecular syringe to inject effector molecules into prokaryotic and eukaryotic target cells. Regulation of the T6SS is critical. A subset of V. cholerae strains, including the clinical O37 serogroup strain V52, express T6SS constitutively. In contrast, pandemic strains impose tight control that can be genetically disrupted: mutations in the quorum sensing gene luxO and the newly described regulator gene tsrA lead to constitutive T6SS expression in the El Tor strain C6706. In this report, we examined environmental V. cholerae isolates from the Rio Grande with regard to T6SS regulation. Rough V. cholerae lacking O-antigen carried a nonsense mutation in the gene encoding the global T6SS regulator VasH and did not display virulent behavior towards Escherichia coli and other environmental bacteria. In contrast, smooth V. cholerae strains engaged constitutively in type VI-mediated secretion and displayed virulence towards prokaryotes (E. coli and other environmental bacteria) and a eukaryote (the social amoeba Dictyostelium discoideum). Furthermore, smooth V. cholerae strains were able to outcompete each other in a T6SS-dependent manner. The work presented here suggests that constitutive T6SS expression provides V. cholerae with an advantage in intraspecific and interspecific competition.Canadian Institutes of Health Research (Operating Grant MOP-84473)Alberta Heritage Foundation for Medical Research (Alberta Innovates-Health Solutions, Endowment Fund)National Institutes of Health (U.S.) (grant MD001091-01)National Institutes of Health (U.S.) (grant GM068855-02)Olegario V. Rana FellowshipAlberta Heritage Foundation for Medical Research (Alberta Innovates-Health Solutions Graduate Studentships

Treatment of synthetic textile wastewater containing dye mixtures with microcosms

The aim was to assess the ability of microcosms (laboratory-scale shallow ponds) as a post polishing stage for the remediation of artificial textile wastewater comprising two commercial dyes (basic red 46 (BR46) and reactive blue 198 (RB198)) as a mixture. The objectives were to evaluate the impact of Lemna minor L. (common duckweed) on the water quality outflows; the elimination of dye mixtures, organic matter, and nutrients; and the impact of synthetic textile wastewater comprising dye mixtures on the L. minor plant growth. Three mixtures were prepared providing a total dye concentration of 10 mg/l. Findings showed that the planted simulated ponds possess a significant (p < 0.05) potential for improving the outflow characteristics and eliminate dyes, ammonium-nitrogen (NH4-N), and nitrate-nitrogen (NO3-N) in all mixtures compared with the corresponding unplanted ponds. The removal of mixed dyes in planted ponds was mainly due to phyto-transformation and adsorption of BR46 with complete aromatic amine mineralisation. For ponds containing 2 mg/l of RB198 and 8 mg/l of BR46, removals were around 53%, which was significantly higher than those for other mixtures: 5 mg/l of RB198 and 5 mg/l of BR46 and 8 mg/l of RB198 and 2 mg/l of BR46 achieved only 41 and 26% removals, respectively. Dye mixtures stopped the growth of L. minor, and the presence of artificial wastewater reduced their development

The protocol for the Be Our Ally Beat Smoking (BOABS) study, a randomised controlled trial of an intensive smoking cessation intervention in a remote Aboriginal Australian health care setting

Background: Australian Aboriginal peoples and Torres Strait Islanders (Indigenous Australians) smoke at much higher rates than non-Indigenous people and smoking is an important contributor to increased disease, hospital admissions and deaths in Indigenous Australian populations. Smoking cessation programs in Australia have not had the same impact on Indigenous smokers as on non-Indigenous smokers. This paper describes the protocol for a study that aims to test the efficacy of a locally-tailored, intensive, multidimensional smoking cessation program.\ud \ud Methods/Design: This study is a parallel, randomised, controlled trial. Participants are Aboriginal and Torres Strait Islander smokers aged 16 years and over, who are randomly allocated to a 'control' or 'intervention' group in a 2:1 ratio. Those assigned to the 'intervention' group receive smoking cessation counselling at face-to-face visits, weekly for the first four weeks, monthly to six months and two monthly to 12 months. They are also encouraged to attend a monthly smoking cessation support group. The 'control' group receive 'usual care' (i.e. they do not receive the smoking cessation program). Aboriginal researchers deliver the intervention, the goal of which is to help Aboriginal peoples and Torres Strait Islanders quit smoking. Data collection occurs at baseline (when they enrol) and at six and 12 months after enrolling. The primary outcome is self-reported smoking cessation with urinary cotinine confirmation at 12 months.\ud \ud Discussion: Stopping smoking has been described as the single most important individual change Aboriginal and Torres Strait Islander smokers could make to improve their health. Smoking cessation programs are a major priority in Aboriginal and Torres Strait Islander health and evidence for effective approaches is essential for policy development and resourcing. A range of strategies have been used to encourage Aboriginal peoples and Torres Strait Islanders to quit smoking however there have been few good quality studies that show what approaches work best. More evidence of strategies that could work more widely in Indigenous primary health care settings is needed if effective policy is to be developed and implemented. Our project will make an important contribution in this area.\ud \ud Trial Registration: Australian New Zealand Clinical Trials Registry (ACTRN12608000604303

Multipurpose silicon photonics signal processor core

[EN] Integrated photonics changes the scaling laws of information and communication systems offering architectural choices that combine photonics with electronics to optimize performance, power, footprint, and cost. Application-specific photonic integrated circuits, where particular circuits/chips are designed to optimally perform particular functionalities, require a considerable number of design and fabrication iterations leading to long development times. A different approach inspired by electronic Field Programmable Gate Arrays is the programmable photonic processor, where a common hardware implemented by a two-dimensional photonic waveguide mesh realizes different functionalities through programming. Here, we report the demonstration of such reconfigurable waveguide mesh in silicon. We demonstrate over 20 different functionalities with a simple seven hexagonal cell structure, which can be applied to different fields including communications, chemical and biomedical sensing, signal processing, multiprocessor networks, and quantum information systems. Our work is an important step toward this paradigm.J.C. acknowledges funding from the ERC Advanced Grant ERC-ADG-2016-741415 UMWP-Chip, I.G. acknowledges the funding through the Spanish MINECO Ramon y Cajal program. D.P. acknowledges financial support from the UPV through the FPI predoctoral funding scheme. D.J.T. acknowledges funding from the Royal Society for his University Research Fellowship.Pérez-López, D.; Gasulla Mestre, I.; Crudgington, L.; Thomson, DJ.; Khokhar, AZ.; Li, K.; Cao, W.... (2017). Multipurpose silicon photonics signal processor core. Nature Communications. 8(1925):1-9. https://doi.org/10.1038/s41467-017-00714-1S1981925Doerr, C. R. & Okamoto, K. Advances in silica planar lightwave circuits. J. Lightw. Technol. 24, 4763–4789 (2006).Coldren, L. A. et al. High performance InP-based photonic ICs—A tutorial. J. Lightw. Technol 29, 554–570 (2011).Soref, R. The past, present, and future of silicon photonics. IEEE J. Sel. Top. Quantum Electron. 12, 1678–1687 (2006).Bogaerts, W. Design challenges in silicon photonics. IEEE J. Sel. Top. Quantum Electron. 20, 8202008 (2014).Bogaerts, W. et al. Nanophotonic waveguides in silicon-on-insulator fabricated with CMOS technology. J. Lightw. Technol. 23, 401–412 (2005).Smit, M. K. et al. An introduction to InP-based generic integration technology. Semicond. Sci. Technol. 29, 083001 (2014).Leinse, A. et al. TriPleX waveguide platform: low-loss technology over a wide wavelength range. Proc. SPIE 8767, 87670E (2013).Kish, F. et al. From visible light-emitting diodes to large-scale III–V photonic integrated circuits. Proc. IEEE 101, 2255–2270 (2013).Heck, M. J. R. et al. Hybrid silicon photonic integrated circuit technology. IEEE J. Sel. Top. Quantum Electron. 19, 6100117 (2013).Sacher, W. et al. Multilayer silicon nitride-on-silicon integrated photonic platforms and devices. J. Lightw. Technol. 33, 901–910 (2015).Asghari, M. Silicon photonics: A low cost integration platform for datacom and telecom applications. In OFC/NFOEC 2008 – 2008 Conference on Optical Fiber Communication/National Fiber Optic Engineers Conference 1–10 (San Diego, USA, 2008).Melati, D. et al. Integrated all-optical MIMO demultiplexer for mode- and wavelength-division-multiplexed transmission. Opt. Lett. 42, 342–345 (2017).Waterhouse, R. & Novak, D. Realizing 5G: microwave photonics for 5G mobile wireless systems. IEEE Microw. Mag. 16, 84–92 (2015).Marpaung, D. et al. Integrated microwave photonics. Laser Photon. Rev. 7, 506–538 (2013).Iezekiel, S., Burla, M., Klamkin, J., Marpaung, D. & Capmany, J. RF engineering meets optoelectronics: Progress in integrated microwave photonics. IEEE Microw. Mag. 16, 28–45 (2015).Technology focus on microwave photonics. Nat. Photon. 5, 723 (2011).Ghelfi, P. et al. A fully photonics-based coherent radar system. Nature 507, 341–345 (2014).Heideman, R. G. TriPleX™-based integrated optical ring resonators for lab-ona-chip-and environmental detection. IEEE J. Sel. Top. Quantum Electron. 18, 1583–1596 (2012).Estevez, M. C., Alvarez, M. & Lechuga, L. Integrated optical devices for lab-on-a-chip biosensing applications. Laser Photon. Rev. 6, 463–487 (2012).Almeida, V. R., Barrios, C. A., Panepucci, R. & Lipson, M. All-optical control of light on a silicon chip. Nature 431, 1081–1084 (2004).Norberg, E. J., Guzzon, R. S., Parker, J. S., Johansson, L. A. & Coldren, L. A. Programmable photonic microwave filters monolithically integrated in InP/InGaAsP. J. Lightw. Technol. 29, 1611–1619 (2011).Wang, J. et al. Reconfigurable radio-frequency arbitrary waveforms synthesized in a silicon photonic chip. Nat. Commun. 6, 5957 (2015).Hill, M. T. et al. A fast low power optical memory based on coupled micro-ring lasers. Nature 432, 206–209 (2004).Slavík, R. et al. Photonic temporal integrator for all-optical computing. Opt. Express 16, 18202–18214 (2008).Sun, C. et al. A monolithically-integrated chip-to-chip optical link in bulk CMOS. IEEE J. Solid-State Circ. 50, 828–844 (2015).Sun, C. et al. Single-chip microprocessor that communicates directly using light. Nature 528, 534–538 (2015).Assefa, S. et al. in Optical Fibre Communication Conference OMM6, https://www.osapublishing.org/abstract.cfm?uri=OFC-2011-OMM6 (Optical Society of America, 2011).Peruzzo, A. et al. Multimode quantum interference of photons in multiport integrated devices. Nat. Commun. 2, 224 (2011).Bonneau, D. et al. Quantum interference and manipulation of entanglement in silicon wire waveguide quantum circuits. N. J. Phys. 14, 045003 (2012).Metcalf, B. J. et al. Multiphoton quantum interference in a multiport integrated photonic device. Nat. Commun. 4, 1356 (2013).Muñoz, P. et al. in 16th International Conference on Transparent Optical Networks (ICTON), 1–4 (Graz, 2014).Ribeiro, A. et al. Demonstration of a 4×4-port universal linear circuit. Optica 3, 1348–1357 (2016).Liu, W. et al. A fully reconfigurable photonic integrated signal processor. Nat. Photon 10, 190–195 (2016).Graydon, O. Birth of the programmable optical chip. Nat. Photon 10, 1 (2016).Pérez, D., Gasulla, I. & Capmany, J. Software-defined reconfigurable microwave photonics processor. Opt. Express 23, 14640–14654 (2015).Miller, D. A. B. Self-configuring universal linear optical component. Photon. Res. 1, 1–15 (2013).Miller, D. A. B. Self-aligning universal beam coupler. Opt. Express 21, 6360–6370 (2013).Clements, W. R. et al. Optimal design for universal multiport interferometers. Optica 3, 1460–1465 (2016).Zhuang, L., Roeloffzen, C. G. H., Hoekman, M., Boller, K.-J. & Lowery, A. J. Programmable photonic signal processor chip for radiofrequency applications. Optica 2, 854–859 (2015).Capmany, J., Gasulla, I. & Pérez, D. Microwave photonics: The programmable processor. Nat. Photon. 10, 6–8 (2016).Pérez, D., Gasulla., Capmany, J. & Soref, R. A. Reconfigurable lattice mesh designs for programmable photonic processors. Opt. Express 24, 12093–12106 (2016).Madsen, C. K. & Zhao, J. H. Optical Filter Design and Analysis: A Signal Processing Approach. 1st edn. (Wiley, 1999).Jinguji, K. Synthesis of coherent two-port lattice-form optical delay-line circuit. J. Lightw. Technol. 13, 73–82 (1995).Jinguji, K. Synthesis of coherent two-port Optical delay-line circuit with ring waveguides. J. Lightw. Technol. 14, 1882–1898 (1996).Madsen, C. K. General IIR optical filter design for WDM applications using all-pass filters. J. Lightw. Technol. 18, 860–868 (2000).Burla, M. et al. On-chip CMOS compatible reconfigurable optical delay line with separate carrier tuning for microwave photonic signal processing. Opt. Express 19, 21475–21484 (2011).Yariv, A. et al. Coupled resonator optical waveguides: a proposal and analysis. Opt. Lett. 24, 711–713 (1999).Hebner, J. E. et al. Distributed and localized feedback in microresonator sequences for linear and nonlinear optics. J. Opt. Soc. Am. B. 21, 1665–1673 (2004).Fandiño, J. S. et al. A monolithic integrated photonic microwave filter. Nat. Photon. 11, 124–129 (2017).Miller, D. A. B. All linear optical devices are mode converters. Opt. Express 20, 23985–23993 (2012).Reck, M. et al. Experimental realization of any discrete unitary operator. Phys. Rev. Lett. 73, 58–61 (1994).Carolan, J. et al. Universal linear optics. Science 349, 711 (2015).Nielsen, M. A. & Chuang, I. L. Quantum Computation and Quantum Information. 1st edn. (Cambridge University Press, 2001).Miller, D. A. B. Perfect optics with imperfect components. Optica 2, 747–750 (2015).Grillanda, S. et al. Non-invasive monitoring and control in silicon photonics using CMOS integrated electronics. Optica 1, 129–136 (2014)

Secondary prevention of heart disease – knowledge among cardiologists and Ω-3 (Omega-3) fatty acid prescribing behaviors in Karachi, Pakistan

<p>Abstract</p> <p>Background</p> <p>The use of omega-3 fatty acids is a currently proven strategy for secondary prevention of heart disease. The prescription practices for this important nutraceutical is not currently known. It is imperative to assess the knowledge of cardiologists regarding the benefits of omega-3 fatty acids and to determine the frequency of its prescription. The aim of the study was to determine the practices and associations of dietary fish prescribing among cardiologists of Karachi and to assess their knowledge of fish oil supplementation and attitudes toward dietary practices.</p> <p>Methods</p> <p>A cross sectional survey was conducted during the period of January to March, 2008. A self report questionnaire was employed. All practicing cardiologists of Karachi were included in the study. Multiple logistic regression analysis was performed to determine the independent factors associated with high fish prescribers.</p> <p>Results</p> <p>The sample comprised of a total of 163 cardiologists practicing in Karachi, Pakistan. Most (73.6%) of the cardiologists fell in the age range of 28 – 45 years and were male (90.8%). High fish prescribers only comprised 36.2% of the respondents. After adjusting for age and gender, multivariate analysis revealed that only the variable of knowledge about fish oil's role in reducing sudden cardiac death was independently associated with high fish prescribers OR = 6.38 [95% CI 2.58–15.78].</p> <p>Conclusion</p> <p>The level of knowledge about the benefits of omega-3 fatty acids is high and the cardiologists harbor a favorable attitude towards dispensing dietary fish advice. However, the prescription practices are less than optimal and not concordant with recommendations of organisations such as the American Heart Association and National Heart Foundation of Australia. The knowledge of prevention of sudden cardiac death in CVD patients has been identified as an important predictor of high fish prescription. This particular life-saving property of omega-3 fatty acids should be the focus of any implemented educational strategy targeted to improve secondary CVD prevention via omega-3 fatty acid supplementation.</p