Interactive effects of age and respiratory virus on severe lower respiratory infection.

We investigated risk factors for severe acute lower respiratory infections (ALRI) among hospitalised children 8 months were at greater risk from influenza-associated ICU admissions and long hospital stay. Children with ADV had increased LOS across all ages. In the first 2 years of life, the effects of different viruses on ALRI severity varies with age. Our findings help to identify specific ages that would most benefit from virus-specific interventions such as vaccines and antivirals.

Experimental Bayesian Quantum Phase Estimation on a Silicon Photonic Chip.

Quantum phase estimation is a fundamental subroutine in many quantum algorithms, including Shor's factorization algorithm and quantum simulation. However, so far results have cast doubt on its practicability for near-term, nonfault tolerant, quantum devices. Here we report experimental results demonstrating that this intuition need not be true. We implement a recently proposed adaptive Bayesian approach to quantum phase estimation and use it to simulate molecular energies on a silicon quantum photonic device. The approach is verified to be well suited for prethreshold quantum processors by investigating its superior robustness to noise and decoherence compared to the iterative phase estimation algorithm. This shows a promising route to unlock the power of quantum phase estimation much sooner than previously believed.

Chip-based quantum key distribution.

Improvement in secure transmission of information is an urgent need for governments, corporations and individuals. Quantum key distribution (QKD) promises security based on the laws of physics and has rapidly grown from proof-of-concept to robust demonstrations and deployment of commercial systems. Despite these advances, QKD has not been widely adopted, and large-scale deployment will likely require chip-based devices for improved performance, miniaturization and enhanced functionality. Here we report low error rate, GHz clocked QKD operation of an indium phosphide transmitter chip and a silicon oxynitride receiver chip-monolithically integrated devices using components and manufacturing processes from the telecommunications industry. We use the reconfigurability of these devices to demonstrate three prominent QKD protocols-BB84, Coherent One Way and Differential Phase Shift-with performance comparable to state-of-the-art. These devices, when combined with integrated single photon detectors, pave the way for successfully integrating QKD into future telecommunications networks.

60 dB high-extinction auto-configured Mach-Zehnder interferometer.

Imperfections in integrated photonics manufacturing have a detrimental effect on the maximal achievable visibility in interferometric architectures. These limits have profound implications for further technological developments in photonics and in particular for quantum photonic technologies. Active optimization approaches, together with reconfigurable photonics, have been proposed as a solution to overcome this. In this Letter, we demonstrate an ultrahigh (>60 dB) extinction ratio in a silicon photonic device consisting of cascaded Mach-Zehnder interferometers, in which additional interferometers function as variable beamsplitters. The imperfections of fabricated beamsplitters are compensated using an automated progressive optimization algorithm with no requirement for pre-calibration. This work shows the possibility of integrating and accurately controlling linear-optical components for large-scale quantum information processing and other applications.

Incidence and viral aetiologies of acute respiratory illnesses (ARIs) in the United States: a population-based study.

We conducted prospective, community-wide surveillance for acute respiratory illnesses (ARIs) in Rochester, NY and Marshfield, WI during a 3-month period in winter 2011. We estimated the incidence of ARIs in each community, tested for viruses, and determined the proportion of ARIs associated with healthcare visits. We used a rolling cross-sectional design to sample participants, conducted telephone interviews to assess ARI symptoms (defined as a current illness with feverishness or cough within the past 7 days), collected nasal/throat swabs to identify viruses, and extracted healthcare utilization from outpatient/inpatient records. Of 6492 individuals, 321 reported an ARI within 7 days (4·9% total, 5·7% in Rochester, 4·4% in Marshfield); swabs were collected from 208 subjects. The cumulative ARI incidence for the entire 3-month period was 52% in Rochester [95% confidence interval (CI) 42-63] and 35% in Marshfield (95% CI 28-42). A specific virus was identified in 39% of specimens: human coronavirus (13% of samples), rhinovirus (12%), RSV (7%), influenza virus (4%), human metapneumovirus (4%), and adenovirus (1%). Only 39/200 (20%) had a healthcare visit (2/9 individuals with influenza). ARI incidence was ~5% per week during winter.

Effectiveness of seasonal influenza vaccine in preventing influenza primary care visits and hospitalisation in Auckland, New Zealand in 2015: interim estimates.

Preliminary results for influenza vaccine effectiveness (VE) against acute respiratory illness with circulating laboratory-confirmed influenza viruses in New Zealand from 27 April to 26 September 2015, using a case test-negative design were 36% (95% confidence interval (CI): 11-54) for general practice encounters and 50% (95% CI: 20-68) for hospitalisations. VE against hospitalised influenza A(H3N2) illnesses was moderate at 53% (95% CI: 6-76) but improved compared with previous seasons.

Qubit entanglement between ring-resonator photon-pair sources on a silicon chip.

Entanglement--one of the most delicate phenomena in nature--is an essential resource for quantum information applications. Scalable photonic quantum devices must generate and control qubit entanglement on-chip, where quantum information is naturally encoded in photon path. Here we report a silicon photonic chip that uses resonant-enhanced photon-pair sources, spectral demultiplexers and reconfigurable optics to generate a path-entangled two-qubit state and analyse its entanglement. We show that ring-resonator-based spontaneous four-wave mixing photon-pair sources can be made highly indistinguishable and that their spectral correlations are small. We use on-chip frequency demultiplexers and reconfigurable optics to perform both quantum state tomography and the strict Bell-CHSH test, both of which confirm a high level of on-chip entanglement. This work demonstrates the integration of high-performance components that will be essential for building quantum devices and systems to harness photonic entanglement on the large scale.

Interim estimates of the effectiveness of seasonal trivalent inactivated influenza vaccine in preventing influenza hospitalisations and primary care visits in Auckland, New Zealand, in 2014.

We present preliminary results of influenza vaccine effectiveness (VE) in New Zealand using a case test-negative design for 28 April to 31 August 2014. VE adjusted for age and time of admission among all ages against severe acute respiratory illness hospital presentation due to laboratory-confirmed influenza was 54% (95% CI: 19 to 74) and specifically against A(H1N1)pdm09 was 65% (95% CI:33 to 81). For influenza-confirmed primary care visits, VE was 67% (95% CI: 48 to 79) overall and 73% (95% CI: 50 to 85) against A(H1N1)pdm09.

Reference-frame-independent quantum-key-distribution server with a telecom tether for an on-chip client.

We demonstrate a client-server quantum key distribution (QKD) scheme. Large resources such as laser and detectors are situated at the server side, which is accessible via telecom fiber to a client requiring only an on-chip polarization rotator, which may be integrated into a handheld device. The detrimental effects of unstable fiber birefringence are overcome by employing the reference-frame-independent QKD protocol for polarization qubits in polarization maintaining fiber, where standard QKD protocols fail, as we show for comparison. This opens the way for quantum enhanced secure communications between companies and members of the general public equipped with handheld mobile devices, via telecom-fiber tethering.

Kilovoltage energy imaging with a radiotherapy linac with a continuously variable energy range.

PURPOSE: In this paper, the effect on image quality of significantly reducing the primary electron energy of a radiotherapy accelerator is investigated using a novel waveguide test piece. The waveguide contains a novel variable coupling device (rotovane), allowing for a wide continuously variable energy range of between 1.4 and 9 MeV suitable for both imaging and therapy. METHOD: Imaging at linac accelerating potentials close to 1 MV was investigated experimentally and via Monte Carlo simulations. An imaging beam line was designed, and planar and cone beam computed tomography images were obtained to enable qualitative and quantitative comparisons with kilovoltage and megavoltage imaging systems. The imaging beam had an electron energy of 1.4 MeV, which was incident on a water cooled electron window consisting of stainless steel, a 5 mm carbon electron absorber and 2.5 mm aluminium filtration. Images were acquired with an amorphous silicon detector sensitive to diagnostic x-ray energies. RESULTS: The x-ray beam had an average energy of 220 keV and half value layer of 5.9 mm of copper. Cone beam CT images with the same contrast to noise ratio as a gantry mounted kilovoltage imaging system were obtained with doses as low as 2 cGy. This dose is equivalent to a single 6 MV portal image. While 12 times higher than a 100 kVp CBCT system (Elekta XVI), this dose is 140 times lower than a 6 MV cone beam imaging system and 6 times lower than previously published LowZ imaging beams operating at higher (4-5 MeV) energies. CONCLUSIONS: The novel coupling device provides for a wide range of electron energies that are suitable for kilovoltage quality imaging and therapy. The imaging system provides high contrast images from the therapy portal at low dose, approaching that of gantry mounted kilovoltage x-ray systems. Additionally, the system provides low dose imaging directly from the therapy portal, potentially allowing for target tracking during radiotherapy treatment. There is the scope with such a tuneable system for further energy reduction and subsequent improvement in image quality.

Comparative study of a low-Z cone-beam computed tomography system.

Computed tomography images have been acquired using an experimental (low atomic number (Z) insert) megavoltage cone-beam imaging system. These images have been compared with standard megavoltage and kilovoltage imaging systems. The experimental system requires a simple modification to the 4 MeV electron beam from an Elekta Precise linac. Low-energy photons are produced in the standard medium-Z electron window and a low-Z carbon electron absorber located after the window. The carbon electron absorber produces photons as well as ensuring that all remaining electrons from the source are removed. A detector sensitive to diagnostic x-ray energies is also employed. Quantitative assessment of cone-beam computed tomography (CBCT) contrast shows that the low-Z imaging system is an order of magnitude or more superior to a standard 6 MV imaging system. CBCT data with the same contrast-to-noise ratio as a kilovoltage imaging system (0.15 cGy) can be obtained in doses of 11 and 244 cGy for the experimental and standard 6 MV systems, respectively. Whilst these doses are high for everyday imaging, qualitative images indicate that kilovoltage like images suitable for patient positioning can be acquired in radiation doses of 1-8 cGy with the experimental low-Z system.

A low Z linac and flat panel imager: comparison with the conventional imaging approach.

Experimental and Monte Carlo simulations were conducted for an Elekta Ltd Precise Treatment System linac fitted with a low Z insert of sufficient thickness to remove all primary electrons. A variety of amorphous silicon based panels employing different scintillators were modelled to determine their response to a variety of x-ray spectra and produce an optimized portal imaging system. This study has shown that in a low Z configuration the vast majority of x-rays are produced in the nickel electron window, and with a combination of a carbon insert and caesium iodide based XVI-panel, significant improvement in the object contrast was achieved. For thin, head and neck-type geometries, contrast is 4.62 times greater for 1.6 cm bone in 5.8 cm water than the standard 6 MV/iViewGT system. For thicker, pelvis-type geometries contrast increases by a factor of 1.3 for 1.6 cm of bone in 25.8 cm water. To obtain images with the same signal-to-noise ratio as the 6 MV/iViewGT system, dose reductions of a factor of 15 and 4.2 are possible for 5.8 cm and 25.8 cm phantoms respectively. This design has the advantage of being easily implemented on a standard linac and provides a portal image directly from the therapy beam aperture.

Decoupling initial electron beam parameters for Monte Carlo photon beam modelling by removing beam-modifying filters from the beam path.

A new method is presented to decouple the parameters of the incident e(-) beam hitting the target of the linear accelerator, which consists essentially in optimizing the agreement between measurements and calculations when the difference filter, which is an additional filter inserted in the linac head to obtain uniform lateral dose-profile curves for the high energy photon beam, and flattening filter are removed from the beam path. This leads to lateral dose-profile curves, which depend only on the mean energy of the incident electron beam, since the effect of the radial intensity distribution of the incident e- beam is negligible when both filters are absent. The location of the primary collimator and the thickness and density of the target are not considered as adjustable parameters, since a satisfactory working Monte Carlo model is obtained for the low energy photon beam (6 MV) of the linac using the same target and primary collimator. This method was applied to conclude that the mean energy of the incident e- beam for the high energy photon beam (18 MV) of our Elekta SLi Plus linac is equal to 14.9 MeV. After optimizing the mean energy, the modelling of the filters, in accordance with the information provided by the manufacturer, can be verified by positioning only one filter in the linac head while the other is removed. It is also demonstrated that the parameter setting for Bremsstrahlung angular sampling in BEAMnrc ('Simple' using the leading term of the Koch and Motz equation or 'KM' using the full equation) leads to different dose-profile curves for the same incident electron energy for the studied 18 MV beam. It is therefore important to perform the calculations in 'KM' mode. Note that both filters are not physically removed from the linac head. All filters remain present in the linac head and are only rotated out of the beam. This makes the described method applicable for practical usage since no recommissioning process is required.

Hepatic stellate cells: role in microcirculation and pathophysiology of portal hypertension.

Accumulating evidence suggests that stellate cells are involved in the regulation of the liver microcirculation and portal hypertension. Activated hepatic stellate cells have the necessary machinery to contract or relax in response to a number of vasoactive substances. Because stellate cells play a role in both fibrosis and portal hypertension, they are currently regarded as therapeutic targets to prevent and treat the complications of chronic liver disease.

Activation of ATP-ubiquitin-dependent proteolysis in skeletal muscle in vivo and murine myoblasts in vitro by a proteolysis-inducing factor (PIF).

Loss of skeletal muscle is a major factor in the poor survival of patients with cancer cachexia. This study examines the mechanism of catabolism of skeletal muscle by a tumour product, proteolysis-inducing factor (PIF). Intravenous administration of PIF to normal mice produced a rapid decrease in body weight (1.55 +/- 0.12 g in 24 h) that was accompanied by increased mRNA levels for ubiquitin, the Mr 14 000 ubiquitin carrier-protein, E2, and the C9 proteasome subunit in gastrocnemius muscle. There was also increased protein levels of the 20S proteasome core and 19S regulatory subunit, detectable by immunoblotting, suggesting activation of the ATP-ubiquitin-dependent proteolytic pathway. An increased protein catabolism was also seen in C(2)C(12)myoblasts within 24 h of PIF addition with a bell-shaped dose-response curve and a maximal effect at 2-4 nM. The enhanced protein degradation was attenuated by anti-PIF antibody and by the proteasome inhibitors MG115 and lactacystin. Glycerol gradient analysis of proteasomes from PIF-treated cells showed an elevation in chymotrypsin-like activity, while Western analysis showed a dose-related increase in expression of MSSI, an ATPase that is a regulatory subunit of the proteasome, with a dose-response curve similar to that for protein degradation. These results confirm that PIF acts directly to stimulate the proteasome pathway in muscle cells and may play a pivotal role in protein catabolism in cancer cachexia.

Hookworm burden reductions in BALB/c mice vaccinated with recombinant Ancylostoma secreted proteins (ASPs) from Ancylostoma duodenale, Ancylostoma caninum and Necator americanus.

Vaccination of mice with alum-precipitated recombinant Ancylostoma secreted protein-1 from the canine hookworm Ancylostoma caninum (Ac-ASP-1) results in protection against A. caninum larval challenge. Vaccine protection is manifested by host reductions in hookworm burden compared to control mice. The goal of this study was to determine whether ASP antigens cloned and expressed from different hookworm species will cross protect against A. caninum larval challenge. Cross-species protection against A. caninum challenge infections was observed with immunizations using recombinant ASP-1 from the human hookworms Ancylostoma duodenale and Necator americanus. However, the degree of protection was proportional to the extent of amino acid sequence homology between the ASP immunogen used for vaccination and the Ac-ASP-1 produced by the challenge larval strain. Vaccine protection was noted to decrease significantly as amino acid sequence homologies diverged 10% or more. It was also determined that Ac-ASP-2, a molecule cloned from A. caninum having 55% amino acid sequence homology to the C-terminus of Ac-ASP-1, did not elicit vaccine protection. These observations were partly reflected in the titer of antibodies that recognize Ac-ASP-1. The studies reported here will help to design immunogenic peptide vaccines based on the sequence divergence of hookworm ASPs.

The role of phosphatidic acid in platelet-derived growth factor-induced proliferation of rat hepatic stellate cells.

Platelet-derived growth factor (PDGF) is the most potent mitogen for hepatic stellate cells (HSCs) in vitro. The aim of this study was to investigate the role of the lipid-derived second messenger phosphatidic acid (PA) in mediating this effect and, in particular, to determine its interaction with the extracellular signal-regulated kinase (ERK) cascade. HSCs were isolated from rat livers. PA production was determined by lipid extraction and thin-layer chromatography (TLC) after prelabeling cells with [(3)H]myristate. ERK activity was measured by an in vitro kinase assay after immunoprecipitation. Mitogenic concentrations of PDGF, but not those of the relatively less potent mitogen, transforming growth factor alpha (TGF-alpha), stimulated the sustained production of PA from HSCs. Exogenous PA stimulated HSC proliferation and a sustained increase in ERK activity, and proliferation was completely blocked by the inhibition of ERK activation with PD98059. The stimulation of ERK by PDGF was of a similar magnitude but more sustained than that caused by TGF-alpha. These results suggest that the potent mitogenic effect of PDGF in HSCs may be caused, in part, by the generation of PA and subsequently by a more sustained activation of ERK than occurs with less potent mitogens that do not induce the production of this lipid second messenger.

Stimulation of myofibrillar protein degradation and expression of mRNA encoding the ubiquitin-proteasome system in C(2)C(12) myotubes by dexamethasone: effect of the proteasome inhibitor MG-132.

Addition of the synthetic glucocorticoid, dexamethasone (Dex) to serum-deprived C(2)C(12) myotubes elicited time- and concentration-dependent changes in N(tau)-methylhistidine (3-MH), a marker of myofibrillar protein degradation. Within 24 h, 100 nM Dex significantly decreased the cell content of 3-MH and increased release into the medium. Both of these responses had increased in magnitude by 48 h and then declined toward basal values by 72 h. The increase in the release of 3-MH closely paralleled its loss from the cell protein. Furthermore, Dex also decreased the 3-MH:total cell protein ratio, suggesting that myofibrillar proteins were being preferentially degraded. Incubation of myotubes with the peptide aldehyde, MG-132, an inhibitor of proteolysis by the (ATP)-ubiquitin (Ub)-dependent proteasome, prevented both the basal release of 3-MH (>95%) and the increased release of 3-MH into the medium in response to Dex (>95%). Northern hybridization studies demonstrated that Dex also elicited similar time- and concentration-dependent increases in the expression of mRNA encoding two components (14 kDa E(2) Ub-conjugating enzyme and Ub) of the ATP-Ub-dependent pathway. The data demonstrate that Dex stimulates preferential hydrolysis of myofibrillar proteins in C(2)C(12) myotubes and suggests that the ATP-Ub-dependent pathway is involved in this response.