MIRTO: an open-source robotic platform for education

This paper introduces the MIddlesex RoboTic platfOrm (MIRTO), an open-source platform that has been used for teaching First Year Computer Science students since the academic year 2013/2014, with the aim of providing a physical manifestation of Software Engineering concepts that are often delivered using only abstract or synthetic case studies. In this paper we provide a detailed description of the platform, whose hardware specifications and software libraries are all released open source; we describe a number of teaching usages of the platform, report students’ projects, and evaluate some of its aspects in terms of effectiveness, usability, and maintenance

Complexation of lanthanides, actinides and transition metal cations with a 6-(1,2,4-triazin-3-yl)-2,2’:6’,2’’-terpyridine ligand: implications for actinide(III) /lanthanide(III) partitioning

The quadridentate N-heterocyclic ligand 6-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzotriazin-3-yl)-2,2’:6’,2’’-terpyridine (CyMe4-hemi-BTBP) has been synthesized and its interactions with Am(III), U(VI), Ln(III) and some transition metal cations have been evaluated by X-ray crystallographic analysis, Am(III)/Eu(III) solvent extraction experiments, UV absorption spectrophotometry, NMR studies and ESI-MS. Structures of the 1:1 complexes with Eu(III), Ce(III) and the linear uranyl (UO22+) ion were obtained by X-ray crystallographic analysis, and showed similar coordination behavior to related BTBP complexes. In methanol, the stability constants of the Ln(III) complexes are slightly lower than those of the analogous quadridentate bis-triazine BTBP ligands, while the stability constant for the Yb(III) complex is higher. 1H NMR titrations and ESI-MS with lanthanide nitrates showed that the ligand forms only 1:1 complexes with Eu(III), Ce(III) and Yb(III), while both 1:1 and 1:2 complexes were formed with La(III) and Y(III) in acetonitrile. A mixture of isomeric chiral 2:2 helical complexes was formed with Cu(I), with a slight preference (1.4:1) for a single directional isomer. In contrast, a 1:1 complex was observed with the larger Ag(I) ion. The ligand was unable to extract Am(III) or Eu(III) from nitric acid solutions into 1-octanol, except in the presence of a synergist at low acidity. The results show that the presence of two outer 1,2,4-triazine rings is required for the efficient extraction and separation of An(III) from Ln(III) by quadridentate N-donor ligand

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Targeting Ergosterol Biosynthesis in <i>Leishmania donovani</i>: Essentiality of Sterol 14alpha-demethylase

<div><p><i>Leishmania</i> protozoan parasites (Trypanosomatidae family) are the causative agents of cutaneous, mucocutaneous and visceral leishmaniasis worldwide. While these diseases are associated with significant morbidity and mortality, there are few adequate treatments available. Sterol 14alpha-demethylase (CYP51) in the parasite sterol biosynthesis pathway has been the focus of considerable interest as a novel drug target in <i>Leishmania</i>. However, its essentiality in <i>Leishmania donovani</i> has yet to be determined. Here, we use a dual biological and pharmacological approach to demonstrate that CYP51 is indispensable in <i>L</i>. <i>donovani</i>. We show via a facilitated knockout approach that chromosomal <i>CYP51</i> genes can only be knocked out in the presence of episomal complementation and that this episome cannot be lost from the parasite even under negative selection. In addition, we treated wild-type <i>L</i>. <i>donovani</i> and CYP51-deficient strains with 4-aminopyridyl-based inhibitors designed specifically for <i>Trypanosoma cruzi</i> CYP51. While potency was lower than in <i>T</i>. <i>cruzi</i>, these inhibitors had increased efficacy in parasites lacking a <i>CYP51</i> allele compared to complemented parasites, indicating inhibition of parasite growth via a CYP51-specific mechanism and confirming essentiality of CYP51 in <i>L</i>. <i>donovani</i>. Overall, these results provide support for further development of CYP51 inhibitors for the treatment of visceral leishmaniasis.</p></div

Susceptibility of half knockout strains to CYP51 inhibitors (EC50, μM): compounds with decreased activity on HKO + CYP strains.

<p>Values ± standard error are shown. ^a p-values are for comparison between HKO+C and HKO+CYP.</p

Susceptibility of half knockout strains to CYP51 inhibitors (EC50, μM): compounds with no significant differences between HKO + C and HKO + CYP strains.

<p>Values ± standard error are shown. ^a p-values are for comparison between HKO+C and HKO+CYP.</p

Modulation of CYP51 levels in <i>L</i>. <i>donovani</i>.

<p><b>A</b>, Replacement of a <i>CYP51</i> allele by homologous recombination. Correct targeting of the knockout cassettes was verified by PCR using one primer within the knockout cassette and one upstream of <i>CYP51</i> (primers 7 and 8 (hygromycin), top or 7 and 9 (puromycin), bottom). <b>B</b>, qPCR quantification of chromosomal <i>CYP51</i> levels, normalized to SAT or to CBS and to wild-type levels. <b>C</b>, CYP51 protein levels in half knockout and complemented strains. CYP51 and GAPDH were detected by Western blot (top) and quantified by densitometry (bottom) <b>D</b>, <i>In vitro</i> infectivity of half knockout and complemented strains. THP1 macrophages were infected at a 10:1 parasite to macrophage ratio. Cells were fixed and stained with DAPI 24, 48 and 72 h post-infection, and macrophage infection levels were determined by automated high-throughput imaging and parasite detection. <b>E</b>, <i>In vivo</i> infectivity of half knockout and complemented strains. BALB/c mice were infected intravenously. Liver parasite burden (Leishman-Donovan Units, LDU) was determined 28 days post-infection by counting stained liver impressions. <b>F</b>, Sterol profiling by GC-MS.</p