Maintaining high vaccination coverage is key to successful rabies control, but mass dog vaccination can be challenging and population turnover erodes coverage. Declines in rabies incidence following ...successive island-wide vaccination campaigns in Bali suggest that prospects for controlling and ultimately eliminating rabies are good. Rabies, however, has continued to circulate at low levels. In the push to eliminate rabies from Bali, high coverage needs to be maintained across all areas of the island. We carried out door-to-door (DTD) questionnaire surveys (
= 10,352 dog-owning households) and photographic mark-recapture surveys (536 line transects, 2,597 observations of free-roaming dogs) in 2011-2012 to estimate dog population sizes and assess rabies vaccination coverage and dog demographic characteristics in Bali, Indonesia. The median number of dogs per subvillage unit (
) was 43 (range 0-307) for owned dogs estimated from the DTD survey and 17 (range 0-83) for unconfined dogs (including both owned and unowned) from transects. Vaccination coverage of owned dogs was significantly higher in adults (91.4%) compared to juveniles (<1 year, 43.9%), likely due to insufficient targeting of pups and from puppies born subsequent to vaccination campaigns. Juveniles had a 10-70 times greater risk of not being vaccinated in urban, suburban, and rural areas combined odds ratios (ORs): 9.9-71.1, 95% CI: 8.6-96.0. Free-roaming owned dogs were also 2-3 times more likely to be not vaccinated compared to those confined (combined Ors: 1.9-3.6, 95% CI: 1.4-5.4), with more dogs being confined in urban (71.2%) than in suburban (16.1%) and rural areas (8.0%). Vaccination coverage estimates from transects were also much lower (30.9%) than household surveys (83.6%), possibly due to loss of collars used to identify the vaccination status of free-roaming dogs, but these unconfined dogs may also include dogs that were unowned or more difficult to vaccinate. Overall, coverage levels were high in the owned dog population, but for future campaigns in Bali to have the highest chance of eliminating rabies, concerted effort should be made to vaccinate free-roaming dogs particularly in suburban and rural areas, with advertising to ensure that owners vaccinate pups. Long-lasting, cheap, and quick methods are needed to mark vaccinated animals and reassure communities of the reach of vaccination campaigns.
Argus is an experimental antenna array system designed to demonstrate all-sky monitoring for transient signals in the frequency range 1200-1700 MHz. It currently consists of 22 broadband spiral ...antennas (expandable to 32) which are individually instrumented, digitized, and analyzed in an attempt to detect and localize both broadband and narrowband astronomical transients. In this paper, we describe the design of the instrument. Notable features include a novel array data aggregation architecture, a detection algorithm which does not require accurate calibration or detailed knowledge of the array manifold, and very low per-element cost of about US1 k/element. A sensitivity of at least 6.6times10 -22 Wm -2 Hz -1 = 66 kJy (zenith at 1700 MHz for a 209 ms observation with 60 kHz bandwidth) is achieved for the system as implemented. Performance is demonstrated in an experiment in which the Sun is detected, localized, and tracked as it moves across the sky. Other experiments confirming the functionality of Argus as an all-sky surveillance system are summarized.
Corruption of C-band microwave brightness observations by radio-frequency interference (RFI) has been reported in recent data from orbiting radiometers; methods for mitigating these effects are of ...great importance for the design of future spaceborne microwave radiometers. One approach that has been suggested involves the use of multiple subchannels at C-band as opposed to a single channel; the use of multiple subchannels allows RFI to be detected and mitigated by analyzing relationships among subchannel brightnesses. While this approach has been utilized in previous airborne measurements, demonstrations of the RFI mitigation performance achieved have been difficult to obtain. To address this issue, an enhanced airborne system for observing radio-frequency interference effects on C-band microwave radiometers was developed, and is described in this paper. The system includes a traditional microwave radiometer with four C-band subchannels, so that RFI removal is possible using a subchannel mitigation algorithm. In addition, the system includes a digital receiver with the capability of providing high temporal and spectral resolution observations of interference. This high-resolution data allows improved understanding of RFI sources to be obtained, and also allows analysis of subchannel mitigation algorithm performance. Observations using the system in a test flight near Wallops Island, VA are described. Results show the four subchannel approach generally to be effective in mitigating the observed RFI sources, although examples are also illustrated using the digital receiver data to demonstrate failure of this approach. While studies of the digital receiver data alone could be performed to demonstrate further improvements in RFI mitigation, issues with this initial dataset limit the extent of such studies. Nevertheless, the results obtained still demonstrate qualitatively the improved RFI mitigation that can be achieved in brightness observations through the use of digital receivers
Silicon deficiency in animals leads to bone defects. This element may therefore play an important role in bone metabolism. Silicon is absorbed from the diet as orthosilicic acid and concentrations in ...plasma are 5–20 μM. The
in vitro effects of orthosilicic acid (0–50 μM) on collagen type 1 synthesis was investigated using the human osteosarcoma cell line (MG-63), primary osteoblast-like cells derived from human bone marrow stromal cells, and an immortalized human early osteoblastic cell line (HCC1). Collagen type 1 mRNA expression and prolyl hydroxylase activity were also determined in the MG-63 cells. Alkaline phosphatase and osteocalcin (osteoblastic differentiation) were assessed both at the protein and the mRNA level in MG-63 cells treated with orthosilicic acid. Collagen type 1 synthesis increased in all treated cells at orthosilicic acid concentrations of 10 and 20 μM, although the effects were more marked in the clonal cell lines (MG-63, HCCl 1.75- and 1.8-fold, respectively,
P < 0.001, compared to 1.45-fold in the primary cell lines). Treatment at 50 μM resulted in a smaller increase in collagen type 1 synthesis (MG-63 1.45-fold,
P = 0.004). The effect of orthosilicic acid was abolished in the presence of prolyl hydroxylase inhibitors. No change in collagen type 1 mRNA level was seen in treated MG-63 cells. Alkaline phosphatase activity and osteocalcin were significantly increased (1.5, 1.2-fold at concentrations of 10 and 20 μM, respectively,
P < 0.05). Gene expression of alkaline phosphatase and osteocalcin also increased significantly following treatment. In conclusion, orthosilicic acid at physiological concentrations stimulates collagen type 1 synthesis in human osteoblast-like cells and enhances osteoblastic differentiation.
Chronic nonbacterial osteomyelitis (CNO) is a rare autoinflammatory bone disorder primarily affecting children and adolescents. It can lead to chronic pain, bony deformities and fractures. The ...pathophysiology of CNO is incompletely understood. Scientific evidence suggests dysregulated expression of pro- and anti-inflammatory cytokines to be centrally involved. Currently, treatment is largely based on retrospective observational studies and expert opinion. Treatment usually includes nonsteroidal anti-inflammatory drugs and/or glucocorticoids, followed by a range of drugs in unresponsive cases. While randomised clinical trials are lacking, retrospective and prospective non-controlled studies suggest effectiveness of TNF inhibitors and bisphosphonates. The objective of the Bayesian consensus meeting was to quantify prior expert opinion.
Twelve international CNO experts were randomly chosen to be invited to a Bayesian prior elicitation meeting.
Results showed that a typical new patient treated with pamidronate would have an 84% chance of improvement in their pain score relative to baseline at 26 weeks and an 83% chance on adalimumab. Experts thought there was a 50% chance that a new typical patient would record a pain score of 28mm (pamidronate) to 30mm (adalimumab) or better at 26 weeks. There was a modest trend in prior opinion to indicate an advantage of pamidronate vs adalimumab, with a 68% prior chance that pamidronate is superior to adalimumab by some margin. However, it is clear that there is considerable uncertainty about the precise relative merits of the two treatments.
The rarity of CNO leads to challenges in conducting randomised controlled trials with sufficient power to provide a definitive outcome. We address this using a Bayesian design, and here describe the process and outcome of the elicitation exercise to establish expert prior opinion. This opinion will be tested in the planned prospective CNO study. The process for establishing expert consensus opinion in CNO will be helpful for developing studies in other rare paediatric diseases.
A central question in the assessment of benefit/harm of new treatments is: how does the average outcome on the new treatment (the factual) compare to the average outcome had patients received no ...treatment or a different treatment known to be effective (the counterfactual)? Randomized controlled trials (RCTs) are the standard for comparing the factual with the counterfactual. Recent developments necessitate and enable a new way of determining the counterfactual for some new medicines. For select situations, we propose a new framework for evidence generation, which we call “threshold‐crossing.” This framework leverages the wealth of information that is becoming available from completed RCTs and from real world data sources. Relying on formalized procedures, information gleaned from these data is used to estimate the counterfactual, enabling efficacy assessment of new drugs. We propose future (research) activities to enable “threshold‐crossing” for carefully selected products and indications in which RCTs are not feasible.
The WHO Global Agenda on Influenza calls for measuring the progress of national influenza vaccination programs. In response, the Macroepidemiology of Influenza Vaccination (MIV) Study Group has ...gathered information on influenza vaccination in 56 countries. During the period 1997–2003, influenza vaccine distribution increased considerably in almost all countries. In 2003, the countries with the highest levels of vaccination (doses distributed/1000 population) were Canada (344), the Republic of Korea (311), the United States (286) and Japan (230). Most countries recommended influenza vaccination for elderly persons and those with high-risk medical conditions, including immunocompromise. Fewer countries provided public reimbursement for vaccination through national or social health insurance. Higher levels of vaccination were not closely related to higher levels of economic development, but in many instances public reimbursement for vaccination seemed to be associated with greater vaccine use. From 1994 to 2003, the global use of influenza vaccines increased more than two-fold. In 2003, the 56 MIV Study Group countries accounted for approximately 95% of the 292 million doses of influenza vaccine distributed worldwide, and 62% of these doses were distributed within nine vaccine-producing countries in North America, Western Europe, Japan and Australia. However, influenza vaccination was increasing rapidly in many non vaccine-producing countries, and this change has important implications for pandemic vaccination.
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