Culture-adapted Plasmodium falciparum isolates from UK travellers: in vitro drug sensitivity, clonality and drug resistance markers.

BACKGROUND: The screening of lead compounds against in vitro parasite cultures is an essential step in the development of novel anti-malarial drugs, but currently relies on laboratory parasite lines established in vitro during the last century. This study sought to establish in continuous culture a series of recent Plasmodium falciparum isolates to represent the current parasite populations in Africa, all of which are now exposed to artemisinin combination therapy. METHODS: Pre-treatment P. falciparum isolates were obtained in EDTA, and placed into continuous culture after sampling of DNA. One post-treatment blood sample was also collected for each donor to monitor parasite clonality during clearance in vivo. IC₅₀ estimates were obtained for 11 anti-malarial compounds for each established parasite line, clonal multiplicity measured in vivo and in vitro, and polymorphic sites implicated in parasite sensitivity to drugs were investigated at the pfmdr1, pfcrt, pfdhfr, pfdhps and pfap2mu loci before and after treatment, and in the cultured lines. RESULTS: Plasmodium falciparum isolates from seven malaria patients with recent travel to three West African and two East African countries were successfully established in long-term culture. One of these, HL1211, was from a patient with recrudescent parasitaemia 14 days after a full course of artemether-lumefantrine. All established culture lines were shown to be polyclonal, reflecting the in vivo isolates from which they were derived, and at least two lines reliably produce gametocytes in vitro. Two lines displayed high chloroquine IC₅₀ estimates, and carried the CVIET haplotype at codons 72-76, whereas the remaining five lines carried the CVMNK haplotype and were sensitive in vitro. All were sensitive to the endoperoxides dihydroartemisinin and OZ277, but IC₅₀ estimates for lumefantrine varied, with the least sensitive parasites carrying pfmdr1 alleles encoding Asn at codon 86. CONCLUSIONS: This study describes the establishment in continuous culture, in vitro drug sensitivity testing and molecular characterization of a series of multiclonal P. falciparum isolates taken directly from UK malaria patients following recent travel to various malaria-endemic countries in Africa. These "HL" isolates are available as an open resource for studies of drug response, antigenic diversity and other aspects of parasite biology

Undergraduate student experience in dental service delivery in rural South Australia: An analysis of costs and benefits

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: Rural experience for dental students can provide valuable clinical education, change attitudes to rural practice, and make a valuable contribution to clinical service provision. The aim of this paper is to assess the costs and benefits of service delivery by students through rural training programmes. Methods: Groups of two students worked in the public dental clinics in adjacent rural centres where there had been long-term difficulties in recruiting staff. The costs and benefits of the programme were assessed by the impact on waiting lists, the total cost per patient of a course of care and by the marginal cost of adding service provision by students to existing arrangements. Results: The total costs of emergency and complete treatment provided by students were greater than the costs of treatment provided by public-sector dentists but less than the costs of private providers treating public patients. However, the value of services were greater when care was provided by students or private providers and the marginal cost of students providing services was 50-70 per cent of the cost of care provided by public dentists. Conclusion: This assessment suggests that the service benefits achieved compliment the primary objective of influencing the attitude of students to rural practice.L Richards, B Symon, D Burrow, A Chartier, G Misan and D Wilkinso

Implications of non-feasible transformations among icosahedral hh orbitals

The symmetric group $S_6$ that permutes the six five-fold axes of an icosahedron is introduced to go beyond the simple rotations that constitute the icosahedral group $I$. Owing to the correspondence $h\leftrightarrow d$, the calculation of the Coulomb energies for the icosahedral configurations $h^N$ based on the sequence $O(5) \supset S_6 \supset S_5 \supset I$ can be brought to bear on Racah's classic theory for the atomic d shell based on $SO(5) \supset SO_L(3) \supset I$. Among the elements of $S_6$ is the kaleidoscope operator ${\cal K}$ that rotates the weight space of SO(5) by $\pi/2$. Its use explains some puzzling degeneracies in d^3 involving the spectroscopic terms ^2P, ^2F, ^2G and ^2H.Comment: Tentatively scheduled to appear in Physical Preview Letters Apr 5, 99. Revtex, 1 ps figur

Relationships between farmer psychological profiles and farm business performance amongst smallholder beef and poultry farmers in South Africa

Beef cattle and poultry are critically important livestock for improving household food security and alleviating poverty amongst smallholder farmers in South Africa. In this paper, our goal is to examine the relationships between farmer psychological profiles and farm business performance of commercially oriented beef cattle and poultry smallholder farmers in South Africa. We employ a multipronged interdisciplinary approach to test the theory of planned behaviour and its relationship to farm business performance. First, a behavioural science-informed survey instrument was employed to collect data from randomly selected farmer participants in two major beef and poultry projects undertaken by the authors. Second, a latent profile analysis was used to identify the psychological profiles of those farmers. Third, traditional and estimated indicators of farm business performance were obtained using descriptive and econometric-based approaches, including logistic regression and stochastic frontier analyses. The estimated farm business performance indicators were correlated with the psychological profiles of farmers. Results from the latent profile analysis showed three distinct profiles of beef and poultry farmers clearly differentiated by their ability to control and succeed in their farm business enterprises; criteria included attitude, openness to ideas, personality, perceived capabilities, self-efficacy, time orientation, and farm- and personal-related concerns. Profile 1 (‘Fatalists’) scored themselves negatively on their ability to control and succeed in their business enterprises. The majority of farmers were generally neutral about their ability to control and succeed in their businesses (Profile 2, ‘Traditionalists’), while a relatively small group of farmers were confident of their ability to succeed (Profile 3, ‘Entrepreneurs’). We found evidence of significant differences in farm business performance amongst the different profiles of farmers. As far as we can determine, this is the only study to have assessed farm business performance based on a differentiation of farmers’ psychological profiles. Our results provide a framework to further investigate whether particular types of on-farm interventions and training methods can be customised for different segments of farmers based on their preferred learning styles

Assessing the utility of acoustic communication for wireless sensors deployed beneath ice sheets

The environments underneath ice sheets are of high scientific interest. Wireless sensors offer the prospect of sustained, distributed remote sensing in the subglacial environment. Typically, wireless sensor networks use radio-frequency (RF) electromagnetic communications, but these are highly attenuated in wet environments. In such environments, acoustic communications may be more power-efficient. Here we review the literature on acoustic and RF attenuation through ice and other relevant media, and present the results of new experiments on acoustic attenuation in glacial ice. Link budgets for communications from a range of subglacial environments show that acoustic communications are a viable strategy for transmission through water and ice where RF is too highly attenuated to be detected. Acoustic communication at 30 kHz is predicted to be possible through 1 km of glacial ice, using a 1 W transmitter. Such a strategy may be appropriate for shallow ice-stream environments around the Antarctic and Greenland ice sheet margins

Novel wireless sensors for in situ measurement of sub-ice hydrologic systems

Wireless sensors have the potential to provide significant insight into in situ physical and biogeochemical processes in sub-ice hydrologic systems. However, the nature of the glacial environment means that sensor deployment and data return is challenging. We describe two bespoke sensor platforms, electronic tracers or ‘ETracers’, and ‘cryoegg’, for untethered, wireless data collection from glacial hydrologic systems, including subglacial channels. Both employ radio frequencies for data transmission, are designed to endure harsh environmental conditions and can withstand low temperatures, high pressure, turbulence and abrasion. We discuss the design, optimization and field testing of the ETracers and cryoegg, culminating in test deployments beneath the Greenland ice sheet. The small, low-cost ETracers were able to travel through subglacial drainage channels, from where they returned water pressure measurements through 100m of ice, and could measure water depth in crevasses. The larger cryoegg was able to return multi-parameter data from moulins through 500m of wet ice to receivers up to 2km away, and from 12m depth in a proglacial lake to a receiver on the shore. The tests demonstrate that the cryoegg and ETracers are low-power, versatile, robust wireless sensor platforms suitable for glacial environments, which may be used with portable, low-cost receiving equipment

Cryoegg: development and field trials of a wireless subglacial probe for deep, fast-moving ice

nnovative technological solutions are required to access and observe subglacial hydrological systems beneath glaciers and ice sheets. Wireless sensing systems can be used to collect and return data without the risk of losing data from cable breakage, which is a major obstacle when studying fast flowing glaciers and other high-strain environments. However, the performance of wireless sensors in deep and fast-moving ice has yet to be evaluated formally. We report experimental results from Cryoegg: a spherical probe that can be deployed along an ice borehole and either remain fixed in place or potentially travel through the subglacial hydrological system. The probe makes measurements in-situ and sends them back to the surface via a wireless link. Cryoegg uses very high frequency (VHF) radio to transmit data through up to 1.3 km of cold ice to a surface receiving array. It measures temperature, pressure and electrical conductivity, returning all data in real time. This transmission uses Wireless M-Bus on 169 MHz; we present a simple “radio link budget” model for its performance in cold ice and confirm its validity experimentally. Power is supplied by an internal battery with sufficient capacity for two measurements per day for up to a year, although higher reporting rates are available at the expense of battery life. Field trials were conducted in 2019 at two locations in Greenland (the EastGRIP borehole and the RESPONDER project site on Sermeq Kujalleq/Store Glacier) and on the Rhone Glacier in Switzerland. Our results from the field demonstrate Cryoegg’s utility in studying englacial channels and moulins, including estimating moulin discharge through salt dilution gauging with the instrument deployed deep within the moulin. Future iterations of the radio system will allow Cryoegg to transmit through up to 2.5 km of ice

Effectiveness of en masse versus two-step retraction:a systematic review and meta-analysis

Abstract Background This review aims to compare the effectiveness of en masse and two-step retraction methods during orthodontic space closure regarding anchorage preservation and anterior segment retraction and to assess their effect on the duration of treatment and root resorption. Methods An electronic search for potentially eligible randomized controlled trials and prospective controlled trials was performed in five electronic databases up to July 2017. The process of study selection, data extraction, and quality assessment was performed by two reviewers independently. A narrative review is presented in addition to a quantitative synthesis of the pooled results where possible. The Cochrane risk of bias tool and the Newcastle-Ottawa Scale were used for the methodological quality assessment of the included studies. Results Eight studies were included in the qualitative synthesis in this review. Four studies were included in the quantitative synthesis. En masse/miniscrew combination showed a statistically significant standard mean difference regarding anchorage preservation − 2.55 mm (95% CI − 2.99 to − 2.11) and the amount of upper incisor retraction − 0.38 mm (95% CI − 0.70 to − 0.06) when compared to a two-step/conventional anchorage combination. Qualitative synthesis suggested that en masse retraction requires less time than two-step retraction with no difference in the amount of root resorption. Conclusions Both en masse and two-step retraction methods are effective during the space closure phase. The en masse/miniscrew combination is superior to the two-step/conventional anchorage combination with regard to anchorage preservation and amount of retraction. Limited evidence suggests that anchorage reinforcement with a headgear produces similar results with both retraction methods. Limited evidence also suggests that en masse retraction may require less time and that no significant differences exist in the amount of root resorption between the two methods