Sustainable reductions in African malaria transmission require innovative tools for mosquito control. One proposal involves the use of low-threshold gene drive in Anopheles vector species, where a ...'causal pathway' would be initiated by (i) the release of a gene drive system in target mosquito vector species, leading to (ii) its transmission to subsequent generations, (iii) its increase in frequency and spread in target mosquito populations, (iv) its simultaneous propagation of a linked genetic trait aimed at reducing vectorial capacity for Plasmodium, and (v) reduced vectorial capacity for parasites in target mosquito populations as the gene drive system reaches fixation in target mosquito populations, causing (vi) decreased malaria incidence and prevalence. Here the scope, objectives, trial design elements, and approaches to monitoring for initial field releases of such gene dive systems are considered, informed by the successful implementation of field trials of biological control agents, as well as other vector control tools, including insecticides, Wolbachia, larvicides, and attractive-toxic sugar bait systems. Specific research questions to be addressed in initial gene drive field trials are identified, and adaptive trial design is explored as a potentially constructive and flexible approach to facilitate testing of the causal pathway. A fundamental question for decision-makers for the first field trials will be whether there should be a selective focus on earlier points of the pathway, such as genetic efficacy via measurement of the increase in frequency and spread of the gene drive system in target populations, or on wider interrogation of the entire pathway including entomological and epidemiological efficacy. How and when epidemiological efficacy will eventually be assessed will be an essential consideration before decisions on any field trial protocols are finalized and implemented, regardless of whether initial field trials focus exclusively on the measurement of genetic efficacy, or on broader aspects of the causal pathway. Statistical and modelling tools are currently under active development and will inform such decisions on initial trial design, locations, and endpoints. Collectively, the considerations here advance the realization of developer ambitions for the first field trials of low-threshold gene drive for malaria vector control within the next 5 years.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This paper describes the design, construction, and initial operation of SLD's upgraded vertex detector which comprises 96 two-dimensional charge-coupled devices (CCDs) with a total of 307 Mpixel. ...Each pixel functions as an independent particle detecting element, providing space point measurements of charged particle tracks with a typical precision of 4 μm in each co-ordinate. The CCDs are arranged in three concentric cylinders just outside the beam-pipe which surrounds the e
+e
− collision point of the SLAC Linear Collider (SLC). The detector is a powerful tool for distinguishing displaced vertex tracks, produced by decay in flight of heavy flavour hadrons or tau leptons, from tracks produced at the primary event vertex. The requirements for this detector include a very low mass structure (to minimize multiple scattering) both for mechanical support and to provide signal paths for the CCDs; operation at low temperature with a high degree of mechanical stability; and high speed CCD readout, signal processing, and data sparsification. The lessons learned in achieving these goals should be useful for the construction of large arrays of CCDs or active pixel devices in the future in a number of areas of science and technology.
Every year, malaria kills approximately 405,000 people in Sub-Saharan Africa, most of them children under the age of five years. In many countries, progress in malaria control has been threatened by ...the rapid spread of resistance to antimalarial drugs and insecticides. Novel genetic mosquito control approaches could play an important role in future integrated malaria control strategies. In July 2019, the Target Malaria consortium proceeded with the first release of hemizygous genetically-modified (GM) sterile and non-transgenic sibling males of the malaria mosquito Anopheles coluzzii in Burkina Faso. This study aimed to determine the potential fitness cost associated to the transgene and gather important information related to the dynamic of transgene-carrying mosquitoes, crucial for next development steps. Bayesian estimations confirmed that GM males had lower survival and were less mobile than their wild type (WT) siblings. The estimated male population size in Bana village, at the time of the release was 28,000 - 37,000. These results provide unique information about the fitness and behaviour of released GM males that will inform future releases of more effective strains of the A. gambiae complex.
IMPORTANCE: Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19. Uncertainty exists ...regarding the effectiveness and safety of these noninvasive respiratory strategies. OBJECTIVE: To determine whether either CPAP or HFNO, compared with conventional oxygen therapy, improves clinical outcomes in hospitalized patients with COVID-19–related acute hypoxemic respiratory failure. DESIGN, SETTING, AND PARTICIPANTS: A parallel group, adaptive, randomized clinical trial of 1273 hospitalized adults with COVID-19–related acute hypoxemic respiratory failure. The trial was conducted between April 6, 2020, and May 3, 2021, across 48 acute care hospitals in the UK and Jersey. Final follow-up occurred on June 20, 2021. INTERVENTIONS: Adult patients were randomized to receive CPAP (n = 380), HFNO (n = 418), or conventional oxygen therapy (n = 475). MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of tracheal intubation or mortality within 30 days. RESULTS: The trial was stopped prematurely due to declining COVID-19 case numbers in the UK and the end of the funded recruitment period. Of the 1273 randomized patients (mean age, 57.4 95% CI, 56.7 to 58.1 years; 66% male; 65% White race), primary outcome data were available for 1260. Crossover between interventions occurred in 17.1% of participants (15.3% in the CPAP group, 11.5% in the HFNO group, and 23.6% in the conventional oxygen therapy group). The requirement for tracheal intubation or mortality within 30 days was significantly lower with CPAP (36.3%; 137 of 377 participants) vs conventional oxygen therapy (44.4%; 158 of 356 participants) (absolute difference, −8% 95% CI, −15% to −1%, P = .03), but was not significantly different with HFNO (44.3%; 184 of 415 participants) vs conventional oxygen therapy (45.1%; 166 of 368 participants) (absolute difference, −1% 95% CI, −8% to 6%, P = .83). Adverse events occurred in 34.2% (130/380) of participants in the CPAP group, 20.6% (86/418) in the HFNO group, and 13.9% (66/475) in the conventional oxygen therapy group. CONCLUSIONS AND RELEVANCE: Among patients with acute hypoxemic respiratory failure due to COVID-19, an initial strategy of CPAP significantly reduced the risk of tracheal intubation or mortality compared with conventional oxygen therapy, but there was no significant difference between an initial strategy of HFNO compared with conventional oxygen therapy. The study may have been underpowered for the comparison of HFNO vs conventional oxygen therapy, and early study termination and crossover among the groups should be considered when interpreting the findings. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN16912075
Genetic control of Aedes mosquitoes Alphey, Luke; McKemey, Andrew; Nimmo, Derric ...
Pathogens and global health,
06/2013, Letnik:
107, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Aedes mosquitoes include important vector species such as Aedes aegypti, the major vector of dengue. Genetic control methods are being developed for several of these species, stimulated by an urgent ...need owing to the poor effectiveness of current methods combined with an increase in chemical pesticide resistance. In this review we discuss the various genetic strategies that have been proposed, their present status, and future prospects. We focus particularly on those methods that are already being tested in the field, including RIDL and Wolbachia-based approaches.
An array of 116 p-channel radiation-sensitive MOSFET transistors (RadFETs) has been commissioned for the BaBar experiment at the PEP-II accelerator at the Stanford Linear Accelerator Center (SLAC). ...The aim of this system is to map the integrated dose absorbed by different regions of the calorimeter during the course of the experiment. This paper reports the design, characterization and installation of the sensors and briefly describes the readout system designed by co-workers. The response at low doses and the temperature coefficient for 130
RadFETs has been determined. At a “read” current of 160
μA an average shift in voltage of 51±4
mV was measured at an integrated dose of 30
rad with a temperature coefficient of 2.3±0.3
mV/°C. Calibration for high doses is also described. The system provides a novel method for real-time measurements of the spatial distribution of ionizing radiation dose within a large particle physics experiment.
The effects of
60
Co
γ-irradiation on six
Φ2.54×2.54
cm
2 CsI(Tl) crystals, grown by the Kyropoulos technique, have been studied. The scintillation light output and radiation-induced optical ...absorption spectra of these crystals have been measured over a wide range of γ-ray doses. A high-Tl concentration always reduces radiation-tolerance and scintillation light output. A group of six distinct absorption bands in the 350–600
nm region, referred to as the sextet band, and one infrared band peaked at 840
nm were observed in all samples following γ-irradiation. Arguments are made that the 840
nm band and the sextet band induced by γ-irradiation are the F
A and L bands, respectively.
We present a measurement of time-dependent CP-violating asymmetries in fully reconstructed $B^0->D^{(*)\pm}\pi^\mp$ decays in a data sample of approximately 88 million $Y(4S)\to B\bar{B}$ decays ...collected with the BaBar detector at the PEP-II asymmetric-energy B factory at SLAC. We interpret the results in terms of the angles of the Cabibbo-Kobayashi-Maskawa unitarity triangle, and find $|sin(2\beta+\gamma)|>0.69$ at 68% confidence level. We exclude the hypothesis of no CP-violation ($sin(2\beta+\gamma) = 0$) at 83% confidence level.
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