Interplay of Magnetic Interactions and Active Movements in the Formation of Magnetosome Chains

Magnetotactic bacteria assemble chains of magnetosomes, organelles that contain magnetic nano-crystals. A number of genetic factors involved in the controlled biomineralization of these crystals and the assembly of magnetosome chains have been identified in recent years, but how the specific biological regulation is coordinated with general physical processes such as diffusion and magnetic interactions remains unresolved. Here, these questions are addressed by simulations of different scenarios for magnetosome chain formation, in which various physical processes and interactions are either switched on or off. The simulation results indicate that purely physical processes of magnetosome diffusion, guided by their magnetic interactions, are not sufficient for the robust chain formation observed experimentally and suggest that biologically encoded active movements of magnetosomes may be required. Not surprisingly, the chain pattern is most resembling experimental results when both magnetic interactions and active movement are coordinated. We estimate that the force such active transport has to generate is compatible with forces generated by the polymerization or depolymerization of cytoskeletal filaments. The simulations suggest that the pleiotropic phenotypes of mamK deletion strains may be due to a defect in active motility of magnetosomes and that crystal formation in magneteosome vesicles is coupled to the activation of their active motility in M. gryphiswaldense, but not in M. magneticum

The inclusion of Slovak Roma pupils in secondary school: contexts of language policy and planning

The arrival of large numbers of Slovak Roma to Sheffield over a relatively short period has inserted two new languages (Slovak and Romani) into an already diverse, multilingual school environment. Schools face challenges in welcoming the new migrant children, inducting and integrating them and facilitating access to the English school curriculum. This paper draws on longitudinal ethnolinguistic research in one secondary school in Sheffield that has experienced this migration and language situation and responded in a variety of ways. Utilizing an analytical framework based upon “language-in-education planning” (LEP, [Kaplan & Baldauf, 1997, Language planning. From practice to theory. Clevedon: Multilingual Matters]) and “micro language planning” (MLP, [Liddicoat & Taylor-Leech, 2014, Micro language planning for multilingual education: Agency in local contexts. Current Issues in Language Planning, 15(3), 237–244]), the various emergent practices are examined. Findings show that the school is engaging in various “unplanned” practices to surmount the language and pedagogical issues, thus highlighting the role of MLP as a necessary part of more macro LEP processes

A systematic review of the clinical effectiveness of 64-slice or higher computed tomography angiography as an alternative to invasive coronary angiography in the investigation of suspected coronary artery disease

<p>Abstract</p> <p>Background</p> <p>This systematic review summarized recent evidence pertaining to the clinical effectiveness of 64-slice or higher computed tomography angiography (CTA) in patients with suspected coronary artery disease (CAD). If CTA proves to be a successful diagnostic performance measure, it could prevent the use of invasive diagnostic procedures in some patients. This would provide multiple health and cost benefits, particularly for under resourced areas where invasive coronary angiography is not always available.</p> <p>Methods</p> <p>A systematic method of literature searching and selection was employed with searches limited to December 2006 to March 2009. Included studies were quality assessed using National Health and Medical Research Council (NHMRC) diagnostic levels of evidence and a modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Individual and pooled diagnostic performance measures were calculated using standard meta-analytic techniques at the patient, vessel and segment level. A positive result was defined as greater than or equal to 50% stenosis.</p> <p>Results</p> <p>Twenty-eight studies were included in the systematic review examining 3,674 patients. The primary meta-analysis at the patient-level indicated a sensitivity of 98.2% and specificity of 81.6%. The median (range) positive predictive value (PPV) was 90.5% (76%-100%) and negative predictive value (NPV) 99.0% (83%-100%). In all vessels, the pooled sensitivity was 94.9%, specificity 89.5%, and median (range) PPV 75.0% (53%-95%) and NPV 99.0% (93%-100%). At the individual artery level, overall diagnostic accuracy appeared to be slightly higher in the left main coronary artery and slightly lower in the left anterior descending and circumflex artery. In all segments, the sensitivity was 91.3%, specificity 94.0% and median (range) PPV 69.0% (44%-86%) and NPV 99.0% (98%-100%).</p> <p>Conclusions</p> <p>The high sensitivity indicates that CTA can effectively identify the majority of patients with significant coronary artery stenosis. The high NPV at the patient, vessel and segment level establishes CTA as an effective non-invasive alternative to invasive coronary angiography (ICA) for the exclusion of stenosis.</p

Opportunities and Challenges in Using Learning Analytics in Learning Design

Educational institutions are designing, creating and evaluating courses to optimize learning outcomes for highly diverse student populations. Yet, most of the delivery is still monitored retrospectively with summative evaluation forms. Therefore, improvements to the course design are only implemented at the very end of a course, thus missing to benefit the current cohort. Teachers find it difficult to interpret and plan interventions just-in-time. In this context, Learning Analytics (LA) data streams gathered from ‘authentic’ student learning activities, may provide new opportunities to receive valuable information on the students' learning behaviors and could be utilised to adjust the learning design already "on the fly" during runtime. We presume that Learning Analytics applied within Learning Design (LD) and presented in a learning dashboard provide opportunities that can lead to more personalized learning experiences, if implemented thoughtfully. In this paper, we describe opportunities and challenges for using LA in LD. We identify three key opportunities for using LA in LD: (O1) using on demand indicators for evidence based decisions on learning design; (O2) intervening during the run-time of a course; and, (O3) increasing student learning outcomes and satisfaction. In order to benefit from these opportunities, several challenges have to be overcome. We mapped the identified opportunities and challenges in a conceptual model that considers the interaction of LA in LD.SURF Foundation & NRO under the REFLECTOR project grant

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study

Background Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours.Methods In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186.Findings Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78 center dot 6%] female patients and 4922 [21 center dot 4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1 center dot 4 [IQR 0 center dot 6-3 center dot 4]) compared with the prepandemic phase (2 center dot 0 [0 center dot 9-3 center dot 7]; p&lt;0 center dot 0001) and pandemic decrease phase (2 center dot 3 [1 center dot 0-5 center dot 0]; p&lt;0 center dot 0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69 center dot 0%] of 3704 vs 1515 [71 center dot 5%] of 2119; OR 1 center dot 1 [95% CI 1 center dot 0-1 center dot 3]; p=0 center dot 042), lymph node metastases (343 [9 center dot 3%] vs 264 [12 center dot 5%]; OR 1 center dot 4 [1 center dot 2-1 center dot 7]; p=0 center dot 0001), and tumours at high risk of structural disease recurrence (203 [5 center dot 7%] of 3584 vs 155 [7 center dot 7%] of 2006; OR 1 center dot 4 [1 center dot 1-1 center dot 7]; p=0 center dot 0039).Interpretation Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation.Funding None.Copyright (c) 2023 Published by Elsevier Ltd. All rights reserved

Templated and self-limiting calcite formation directed by coccolith organic macromolecules

The formation of intricately shaped crystalline minerals by organisms is orchestrated by specialized biomacromolecules. The macromolecules associated with coccoliths, nanometer-sized calcite crystal arrays produced by marine microalgae, can form a distinct calcium-rich phase via macromolecular recognition. Here, we show that this calcium-rich phase can be mineralized into a thin film of single-crystalline calcite by the balanced addition of carbonate ions. Such crystallization process provides a strategy to direct crystalline products via local interactions between soluble macromolecules and compatible templates