Increased understanding of the underlying pathophysiology has highlighted the heterogeneity of asthma and identified that most children with asthma have type 2 inflammation with elevated biomarkers, ...such as blood eosinophils and/or FeNO. Although in the past most of these children may have been categorized as having allergic asthma, identifying the type 2 inflammatory phenotype provides a mechanism to explain both allergic and non-allergic triggers in pediatric patients with asthma. Most children achieve control with low to medium doses of inhaled corticosteroids. However, in a small but significant proportion of children, asthma remains uncontrolled despite maximum conventional treatment, with an increased risk of severe exacerbations. In this review, we focus on the role of type 2 inflammation and allergic processes in children with asthma, together with evidence of the efficacy of available treatment options for those who experience severe symptoms.
Introduction
Point‐of‐care (POC) early infant diagnosis (EID) testing has been shown to dramatically decrease turnaround times from sample collection to caregiver result receipt and time to ART ...initiation for HIV‐positive infants compared to centralized laboratory testing. As governments in sub‐Saharan Africa implement POC EID technologies, we report on the feasibility and effectiveness of POC EID testing and the impact of same‐day result delivery on rapid ART initiation within national programmes across six countries.
Methods
This pre‐/post‐evaluation compared centralized laboratory‐based (pre) with POC (post) EID testing in 52 facilities across Cameroon, Democratic Republic of Congo, Ethiopia, Kenya, Senegal and Zimbabwe between April 2017 and October 2019 (country‐dependent). Data were collected retrospectively from routine records at health facilities for all infants tested under two years of age. Hazard ratios and 95% confidence intervals were calculated to compare time‐to‐event outcomes, visualized with Kaplan–Meier curves, and the Somers’ D test was used to compare continuous outcomes.
Results
Data were collected for 2892 EID tests conducted on centralized laboratory‐based platforms and 4610 EID tests on POC devices with 127 (4%) and 192 (4%) HIV‐positive infants identified, respectively. POC EID significantly reduced the time from sample collection to caregiver result receipt (POC median: 0 days, IQR: 0 to 0 vs. centralized: 35 days, IQR: 26 to 56) and time from sample collection to ART initiation for HIV‐positive infants (POC median: 1 day, IQR: 0 to 7 vs. centralized: 39 days, IQR: 26 to 57). With POC testing, 72% of infants received results on the same day as sample collection; HIV‐positive infants with a same‐day diagnosis had six times the rate of ART initiation compared to those diagnosed one or more days after sample collection (HR: 6.39; 95% CI: 3.44 to 11.85).
Conclusions
Same‐day diagnosis and treatment initiation for infants is possible with POC EID within routine government‐led and ‐supported public sector healthcare facilities in resource‐limited settings. Given that POC EID allows for rapid ART initiation, aligning to the World Health Organization’s recommendation of ART initiation within seven days, its use in public sector programmes has the potential to reduce overall mortality for infants with HIV through early treatment initiation.
Introduction
In many low‐ and middle‐income countries, HIV viral load (VL) testing occurs at centralized laboratories and time‐to‐result‐delivery is lengthy, preventing timely monitoring of HIV ...treatment adherence. Near point‐of‐care (POC) devices, which are placed within health facility laboratories rather than clinics themselves (i.e. “true” POC), can offer VL in conjunction with centralized laboratories to expedite clinical decision making and improve outcomes, especially for patients at high risk of treatment failure. We assessed impacts of near‐POC VL testing on result receipt and clinical action in public sector programmes in Cameroon, Democratic Republic of Congo, Kenya, Malawi, Senegal, Tanzania and Zimbabwe.
Methods
Routine health data were collected retrospectively after introducing near‐POC VL testing at 57 public sector health facilities (2017 to 2019, country‐dependent). Where possible, key indicators were compared to data from patients receiving centralized laboratory testing using hazard ratios and the Somers’ D test.
Results
Data were collected from 6795 tests conducted on near‐POC and 17614 tests on centralized laboratory‐based platforms. Thirty‐one percent (2062/6694) of near‐POC tests were conducted for high‐risk populations: pregnant and breastfeeding women, children and those with suspected failure. Compared to conventional testing, near‐POC improved the median time from sample collection to return of results to patient six vs. sixty‐eight days, effect size: −32.2%; 95% CI: −41.0% to −23.4% and to clinical action for individuals with an elevated HIV VL three vs. fourty‐nine days, effect size: −35.4%; 95% CI: −46.0% to −24.8%. Near‐POC VL results were two times more likely to be returned to the patient within 90 days compared to centralized tests 50% (1781/3594) vs. 27% (4172/15271); aHR: 2.22, 95% CI: 2.05 to 2.39. Thirty‐seven percent (340/925) of patients with an elevated near‐POC HIV VL result had documented clinical follow‐up actions within 30 days compared to 7% (167/2276) for centralized testing.
Conclusions
Near‐POC VL testing enabled rapid test result delivery for high‐risk populations and led to significant improvements in the timeliness of patient result receipt compared to centralized testing. While there was some improvement in time‐to‐clinical action with near‐POC VL testing, major gaps remained. Strengthening of systems supporting the utilization of results for patient management are needed to truly capitalize on the benefits of decentralized testing.
A pressure-tunable ensemble of two capillary separation columns is combined with time-of-flight mass spectral detection for the high-speed characterization and analysis of volatile organic compounds. ...The detector can record up to 500 complete mass spectra per second and can obtain spectral deconvolution and thus characterization of severely overlapping and unknown chromatographic peaks. The tunable capillary column ensemble consists of the series combination of a nonpolar 5% phenyl poly(dimethylsiloxane) column and a polar poly(ethylene glycol) column. Adjustment of the pressure at the column junction point is achieved by the use of an electronic pressure controller. Changes in the junction pressure result in changes in the relative contribution that each of the columns makes to overall retention. This causes changes in the retention patterns, which can be used to enhance the utility of the TOFMS detector. The use of high spectral acquisition rates allows for the deconvolution of very closely spaced peaks. Adjustment of the column junction pressure often allows for the control of peak separation for critical component pairs. Since severely overlapping chromatographic peaks can be tolerated in many cases, the time axis of the chromatogram can be compressed, thus obtaining very fast GC/MS characterization of unknown mixtures. Tunable columns are very useful for facilitating time compression since significant control of relative peak positions can be achieved.
A tandem-column ensemble consisting of two capillary columns with different stationary-phase chemistries and computer-controlled carrier-gas pressure at the column junction point is used to change ...the ensemble selectivity on-the-fly during a separation. When the pressure at the column junction point is changed, differential changes occur in the carrier gas velocities in the two columns. This changes the relative contribution that each column makes to the ensemble selectivity. This programmable selectivity control is applied to the problem of high-speed, isothermal GC analysis of volatile organic compound (VOC) mixtures. For the ensemble configuration described here, the pressure control system provides over 200 computer-selected junction-point pressures in 0.1 psi steps. Repeatability typically is ±0.01 psi. This provides for very stable retention patterns. The relatively large dead volume in the controller is managed by the use of a pneumatic vent line. The vent line restriction is set to give pressure set-point transition times of 0.3−3 s. A model is developed to aid in the selection of the pressure program (pressure vs time profile) that will result in a rapid separation of the target compounds. The model results in plots of the position of component bands in the column ensemble vs time. These sample-band trajectory plots show discontinuous changes in slope (migration velocity) at pressure set-point change times and when each component band migrates across the column junction. The model provides quantitative information on elution peak positions. The model is used to predict the effects of changes in the selectivity program on retention patterns.
The Rocky Mountain Red Fox (Vulpes vulpes macroura), once common in the Blue Mountains ecoregion of northeastern Oregon, was considered rare in eastern Oregon by the 1930s and thought to be ...extirpated by the 1960s, when putatively new Red Fox populations began to appear. Although the new foxes were long presumed to be nonnative (originating from fur-farms or deliberate release), they were often phenotypically similar to native Red Foxes, suggesting the alternative possibility that they arose from range expansions, either by small numbers of remnant native foxes at higher elevations or by Rocky Mountain Red Foxes to the east. In this study, we used mitochondrial DNA to investigate the origins of extant Red Fox populations in northeastern Oregon. Our findings show that both native and nonnative sources contributed to the Red Fox populations currently occupying this region. In particular, Red Foxes in montane habitats of their former range in northeastern Oregon reflect predominantly native ancestry, whereas those in more lowland habitats outside the boundaries of their former range represent a mix of native and nonnative ancestry. Recognizing the existence of foxes with native ancestry in northeastern Oregon may shape management decisions regarding this species, especially in respect to control versus conservation.
Recent advances in column heating technology have made possible very fast linear temperature programming for high-speed gas chromatography. A fused-silica capillary column is contained in a tubular ...metal jacket, which is resistively heated by a precision power supply. With very rapid column heating, the rate of peak-capacity production is significantly enhanced, but the total peak capacity and the boiling-point resolution (minimum boiling-point difference required for the separation of two nonpolar compounds on a nonpolar column) are reduced relative to more conventional heating rates used with convection-oven instruments. As temperature-programming rates increase, elution temperatures also increase with the result that retention may become insignificant prior to elution. This results in inefficient utilization of the downstream end of the column and causes a loss in the rate of peak-capacity production. The rate of peak-capacity production is increased by the use of shorter columns and higher carrier gas velocities. With high programming rates (100−600 °C/min), column lengths of 6−12 m and average linear carrier gas velocities in the 100−150 cm/s range are satisfactory. In this study, the rate of peak-capacity production, the total peak capacity, and the boiling point resolution are determined for C10−C28 n-alkanes using 6−18 m long columns, 50−200 cm/s average carrier gas velocities, and 60−600 °C/min programming rates. It was found that with a 6-meter-long, 0.25-mm i.d. column programmed at a rate of 600 °C/min, a maximum peak-capacity production rate of 6.1 peaks/s was obtained. A total peak capacity of about 75 peaks was produced in a 37-s long separation spanning a boiling-point range from n-C10 (174 °C) to n-C28 (432 °C).
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