Artemether resistance in vitro is linked to mutations in PfATP6 that also interact with mutations in PfMDR1 in travellers returning with Plasmodium falciparum infections.

BACKGROUND: Monitoring resistance phenotypes for Plasmodium falciparum, using in vitro growth assays, and relating findings to parasite genotype has proved particularly challenging for the study of resistance to artemisinins. METHODS: Plasmodium falciparum isolates cultured from 28 returning travellers diagnosed with malaria were assessed for sensitivity to artemisinin, artemether, dihydroartemisinin and artesunate and findings related to mutations in pfatp6 and pfmdr1. RESULTS: Resistance to artemether in vitro was significantly associated with a pfatp6 haplotype encoding two amino acid substitutions (pfatp6 A623E and S769N; (mean IC50 (95% CI) values of 8.2 (5.7 - 10.7) for A623/S769 versus 623E/769 N 13.5 (9.8 - 17.3) nM with a mean increase of 65%; p = 0.012). Increased copy number of pfmdr1 was not itself associated with increased IC50 values for artemether, but when interactions between the pfatp6 haplotype and increased copy number of pfmdr1 were examined together, a highly significant association was noted with IC50 values for artemether (mean IC50 (95% CI) values of 8.7 (5.9 - 11.6) versus 16.3 (10.7 - 21.8) nM with a mean increase of 87%; p = 0.0068). Previously described SNPs in pfmdr1 are also associated with differences in sensitivity to some artemisinins. CONCLUSIONS: These findings were further explored in molecular modelling experiments that suggest mutations in pfatp6 are unlikely to affect differential binding of artemisinins at their proposed site, whereas there may be differences in such binding associated with mutations in pfmdr1. Implications for a hypothesis that artemisinin resistance may be exacerbated by interactions between PfATP6 and PfMDR1 and for epidemiological studies to monitor emerging resistance are discussed

Melatonin attenuates pulmonary hypertension in chronically hypoxic rats

published_or_final_versio

Simulation-Based Safety Training for Plant Maintenance in Virtual Reality

This paper presents a 3-D simulation model for safety training in an interactive and fully immersive virtual environment (IVE). The training comprises application of serious games (SGs) designed for filter replacements on a gas-powered plant (GPP) engine model by participants based on plant maintenance health and safety environment (HSE) regulations. Although maintenance work on GPP constitutes significantly in the share of hazards in the industry, there is however, scanty research related to simulation-based training for safety. Research nonetheless indicates the success of this technology in other industrial fields. For this reason, this study explored the possibility for training in safe work practices during maintenance in a gamified virtual environment. The Unreal real-time 3D game engine software was employed for creating virtual objects in the simulation. In total, 38 participants individually undertook the training in the virtual realm and provided feedback on a 5-point Likert scale. Questions pursuant to the assessment included the efficacy of acquired safety knowledge and skills, proximity of the simulation-based training to reality, and the interests and preference of SGs-IVE towards safety training. Results demonstrates participant’s perception of the prospects and learning outcome of SGs-IVE towards safety training: A factor that promotes greater cognitive learning for mindful safety practices.© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2021. This is a post-peer-review, pre-copyedit version of an article published in Advances in Simulation and Digital Human Modeling: Proceedings of the AHFE 2020 Virtual Conferences on Human Factors and Simulation, and Digital Human Modeling and Applied Optimization, July 16-20, 2020, USA. The final authenticated version is available online at: http://dx.doi.org/10.1007/978-3-030-51064-0_22fi=vertaisarvioitu|en=peerReviewed

Optimal leverage from non-ergodicity

In modern portfolio theory, the balancing of expected returns on investments against uncertainties in those returns is aided by the use of utility functions. The Kelly criterion offers another approach, rooted in information theory, that always implies logarithmic utility. The two approaches seem incompatible, too loosely or too tightly constraining investors' risk preferences, from their respective perspectives. The conflict can be understood on the basis that the multiplicative models used in both approaches are non-ergodic which leads to ensemble-average returns differing from time-average returns in single realizations. The classic treatments, from the very beginning of probability theory, use ensemble-averages, whereas the Kelly-result is obtained by considering time-averages. Maximizing the time-average growth rates for an investment defines an optimal leverage, whereas growth rates derived from ensemble-average returns depend linearly on leverage. The latter measure can thus incentivize investors to maximize leverage, which is detrimental to time-average growth and overall market stability. The Sharpe ratio is insensitive to leverage. Its relation to optimal leverage is discussed. A better understanding of the significance of time-irreversibility and non-ergodicity and the resulting bounds on leverage may help policy makers in reshaping financial risk controls.Comment: 17 pages, 3 figures. Updated figures and extended discussion of ergodicit

Three-dimensional laparoscopy: is it as good as it looks?- a review of the literature

published_or_final_versio

Problematic attention processing and fear learning in adolescent anxiety: Testing a combined cognitive and learning processes model

Newton Fund (managed by the UK Medical Research Council) (HB, VK, SN, JL) and the India Department of Biotechnology (RP

Hong Kong Chinese school children with elevated urine melamine levels: A prospective follow up study

<p>Abstract</p> <p>Background</p> <p>In 2008, the outbreak of kidney stones in children fed by melamine-tainted milk products in Mainland China has caused major public concern of food safety. We identified Hong Kong school children with elevated urine melamine level from a community-based school survey in 2007-08 and reviewed their clinical status in 2009.</p> <p>Methods</p> <p>In 2007-08, 2119 school children participated in a primary and secondary school survey in Hong Kong using a cluster sampling method. Urine aliquots from 502 subjects were assayed for melamine level. High urine melamine level was defined as urine melamine/creatinine ratio >7.1 μg/mmol. Subjects with high urine melamine level were invited for clinical evaluation in 2009 including urinalysis and ultrasound imaging of the urinary system.</p> <p>Results</p> <p>The age range of this subcohort was 6 - 20 years with 67% girls (335 female and 167 male subjects). The spot urine melamine/creatinine ratio of the 502 urine aliquots ranged from undetectable to 1467 μg/mmol (median 0.8 μg/mmol). Of these, 213 subjects had undetectable level (42%). We invited 47 (9%) subjects with high urine melamine level for re-evaluation and one subject declined. The median duration of follow-up was 23.5 months (interquartile range: 19.8 - 30.6 months). None of the 46 subjects (28% boys, mean age 13.9 ± 2.9 years) had any abnormality detected on ultrasound study of the urinary system. All subjects had stable renal function with a median urine albumin-creatinine ratio of 0.70 mg/mmol (interquartile range: 0.00 - 2.55 mg/mmol).</p> <p>Conclusions</p> <p>Hong Kong Chinese school children with high urine melamine levels appeared to have benign clinical course in the short term although a long term follow-up study is advisable in those with persistently high urine melamine level.</p

Association between the mood stabilizing treatment of bipolar disorder and risk of suicide attempts: A self-controlled case series study

Bipolar disorder (BPD) is associated with high rates of suicide attempts but the anti-suicidal effect of mood stabilizing agents remains unclear. This study aimed to examine the association between mood stabilizing agents (lithium, valproate, lamotrigine, carbamazepine or antipsychotics) and risk of suicide attempts in patients with BPD using self-controlled case series study design. Among 14,087 patients with BPD who received mood stabilizing agents from 2001 to 2020 in Hong Kong, 1316 patients had at least one suicide attempts during the observation period. An increased risk of suicide attempts was observed 14 days before treatment initiation compared to non-exposed period. Following treatment initiation, an increased risk with smaller magnitude was found with the use of mood stabilizing agents. A lower risk was observed with lithium and antiepileptics while the risk remained attenuated with decreasing magnitude with antipsychotics. During 30-day post-treatment period, the risk was elevated. Therefore, this study suggests that use of mood stabilizing agents is not causally associated with an increased risk of suicide attempts. Indeed, there are potential protective effects of lithium and antiepileptics against suicide attempts. Assiduous monitoring of symptoms relapse and warning signs of suicide should be part of the management plan and discussed between clinicians, caregivers and patients

Analysis of Transaction Logs from National Museums Liverpool

The websites of Cultural Heritage institutions attract the full range of users, from professionals to novices, for a variety of tasks. However, many institutions are reporting high bounce rates and therefore seeking ways to better engage users. The analysis of transaction logs can provide insights into users’ searching and navigational behaviours and support engagement strategies. In this paper we present the results from a transaction log analysis of web server logs representing user-system interactions from the seven websites of National Museums Liverpool (NML). In addition, we undertake an exploratory cluster analysis of users to identify potential user groups that emerge from the data. We compare this with previous studies of NML website users