3D printing and high tibial osteotomy

High tibial osteotomy (HTO) is a relatively conservative surgical option in the management of medial knee pain. Thus far, the outcomes have been variable, and apparently worse than the arthroplasty alternatives when judged using conventional metrics, owing in large part to uncer - tainty around the extent of the correction planned and achieved. This review paper introduces the concept of detailed 3D planning of the procedure, and describes the 3D printing technology that enables the plan to be performed. The different ways that the osteotomy can be undertaken, and the varying guide designs that enable accurate regis - tration are discussed and described. The system accuracy is reported. In keeping with other assistive technologies, 3D printing enables the surgeon to achieve a preoperative plan with a degree of accuracy that is not possible using conventional instruments. With the advent of low dose CT, it has been possible to confirm that the procedure has been under - taken accurately too. HTO is the ‘ultimate’ personal intervention: the amount of correction needed for optimal offloading is not yet com - pletely understood. For the athletic person with early medial joint line over - load who still runs and enjoys life, HTO using 3D printing is an attractive option. The clinical effectiveness remains unproven

An on-line solid phase extraction procedure for the routine quantification of urinary methylmalonic acid by liquid chromatography-tandem mass spectrometry

Background: The goal of this study was to develop and to validate an improved isotope-dilution-liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of methylmalonic acid (MMA) in urine. Methods: A previously described sample preparation protocol requires two solvent extraction steps, including evaporation. The first extraction is to extract the analyte from the sample, and second occurs following derivatization of the extract. In the method described here, the second evaporation step was substituted by on-line solid phase extraction employing column-switching and a permanent co-polymer based extraction cartridge. A standard validation protocol was applied to investigate the performance of the method. Results: The method was found to be linear in the clinically relevant range of concentrations (6-100 mu mol/L). Total coefficients of variation were below 10% and inaccuracy was <10% for quality control samples at three concentrations. Conclusions: By omitting one evaporation step, the semi-automated method described in this article enables for more convenient work-flow in the quantification of urinary MMA compared to the previous protocol. This is of relevance for MMA measurement in the routine clinical laboratory setting. Validation demonstrated acceptable analytical performance. Clin Chem Lab Med 2010;48:1647-50

Are Girls the Fairer Sex in India? Revisiting Intra-Household Allocation of Education Expenditure

Using a Hurdle model, the paper finds that although significant progress in gender equality in education was achieved during 1993–2005, pro-male gender bias still exists in the within-household allocation of educational expenditure. This bias occurs primarily through differential spending on sons and daughters in the primary and middle school age groups, but through the decision to enroll sons and not daughters in the secondary school age group. Bias is substantially greater in rural than urban areas. An important mechanism through which households spend less on girls is by sending sons to private schools and daughters to the fee-free government schools

Assessing teacher quality in India

Using administrative data from linked private schools from one Indian district that matches 8319 pupils to their subject specific teachers at the senior secondary level, we estimate the importance of individual teachers for student outcomes in the high-stake senior secondary exam (at the end of twelfth-grade) controlling for prior achievement at the secondary level (at the end of tenth-grade). In addition to controlling for prior achievement, we exploit the fact that students took exams in multiple subjects during their senior secondary exam to control for pupil fixed effects. We find a considerable variability in teacher effectiveness over a two year course—a one standard deviation improvement in teacher quality adds 0.366 standard deviation points in students score. Furthermore, consistent with studies in the US, we find that although teacher quality matters, the observed characteristics explain little of the variability in teacher quality

Fluid flow and mixing in a novel intermittently rotating bioreactor for CAR-T cell therapy manufacturing

This work explores the mixing and fluid dynamics in a novel bioreactor currently used for the automated manufacturing of CAR-T cell therapy, which offers a single-dose cure for several forms of advanced blood cancer. The cylindrical bioreactor has a low aspect ratio and a free surface. Agitation is achieved by intermittent rotation of the entire vessel around its central axis. No engineering characterisation has been conducted to date for this system in a bioprocessing context. The study examines the fluid dynamics problems of spin-up from rest and spin-down to rest. Novel Particle Image Velocimetry and Planar Laser-Induced Fluorescence data is presented alongside reflective flakes results, shedding light on the different transient flow regions inside the intermittently rotating bioreactor, and determining the timescales of macro- and micromixing. The results presented can be used to design a custom rotation pattern of the bioreactor for improved mixing performance during the cell expansion step

Decreased gene expression from T7 promoters may be due to impaired production of active T7 RNA polymerase

BACKGROUND: Protein expression vectors that utilize the bacteriophage T7 polymerase/promoter system are capable of very high levels of protein production. Frequently, however, expression from these vectors does not reliably achieve optimal levels of protein production. Strategies have been proposed previously that successfully maintain high expression levels, however we sought to determine the cause of induction failure. RESULTS: We demonstrated that decreases in protein overproduction levels are not due to significant plasmid loss nor to mutations arising on the plasmid, but instead largely are attributable to chromosomal mutations that diminish the level of functional T7 RNA polymerase, resulting in decreased expression from the plasmid. Isolation of plasmid DNA from non-expressing strains and reintroduction of the plasmid into a T7 RNA polymerase-producing strain such as BL21(λDE3) reproducibly restored high level protein production. CONCLUSIONS: Our results suggest that a major contributing factor to decreased expression levels in T7 based systems is chromosomal mutation resulting in loss of functional T7 RNA polymerase. Consistent with this hypothesis, we found that optimal protein overproduction was obtained reproducibly from T7 promoters using freshly transformed cells that had not been subjected to outgrowth during which mutations could accumulate

Delay-induced rebounds in CO_{2} emissions and critical time-scales to meet global warming targets

While climate science debates are focused on the attainment of peak anthropogenic CO2 emissions and policy tools to reduce peak temperatures, the human‐energy‐climate system can hold “rebound” surprises beyond this peak. Following the second industrial revolution, global per capita CO_{2} emissions (c_{c}) experienced a punctuated growth of about 100% every 60 years, mainly attributable to technological development and its global spread. A model of the human‐energy‐climate system capable of reproducing past punctuated dynamics shows that rebounds in global CO_{2} emissions emerge due to delays intrinsic to the diffusion of innovations. Such intrinsic delays in the adoption and spread of low‐carbon emitting technologies, together with projected population growth, upset the warming target set by the Paris Agreement. To avoid rebounds and their negative climate effects, model calculations show that the diffusion of climate‐friendly technologies must occur with lags one‐order of magnitude shorter (i.e., ∼6 years) than the characteristic timescale of past punctuated growth in c_{c}. Radically new strategies to globally implement the technological advances at unprecedented rates are needed if the current emission goals are to be achieved

Chaos and Elliptical Galaxies

Recent results on chaos in triaxial galaxy models are reviewed. Central mass concentrations like those observed in early-type galaxies -- either stellar cusps, or massive black holes -- render most of the box orbits in a triaxial potential stochastic. Typical Liapunov times are 3-5 crossing times, and ensembles of stochastic orbits undergo mixing on time scales that are roughly an order of magnitude longer. The replacement of the regular orbits by stochastic orbits reduces the freedom to construct self-consistent equilibria, and strong triaxiality can be ruled out for galaxies with sufficiently high central mass concentrations.Comment: uuencoded gziped PostScript, 12 pages including figure

On the k-Boundedness for Existential Rules

The chase is a fundamental tool for existential rules. Several chase variants are known, which differ on how they handle redundancies possibly caused by the introduction of nulls. Given a chase variant, the halting problem takes as input a set of existential rules and asks if this set of rules ensures the termination of the chase for any factbase. It is well-known that this problem is undecidable for all known chase variants. The related problem of boundedness asks if a given set of existential rules is bounded, i.e., whether there is a predefined upper bound on the number of (breadth-first) steps of the chase, independently from any factbase. This problem is already undecidable in the specific case of datalog rules. However, knowing that a set of rules is bounded for some chase variant does not help much in practice if the bound is unknown. Hence, in this paper, we investigate the decidability of the k-boundedness problem, which asks whether a given set of rules is bounded by an integer k. We prove that k-boundedness is decidable for three chase variants, namely the oblivious, semi-oblivious and restricted chase.Comment: 20 pages, revised version of the paper published at RuleML+RR 201

Fragment-based lead discovery on G-protein-coupled receptors

Introduction: G-protein-coupled receptors (GPCRs) form one of the largest groups of potential targets for novel medications. Low druggability of many GPCR targets and inefficient sampling of chemical space in high-throughput screening expertise however often hinder discovery of drug discovery leads for GPCRs. Fragment-based drug discovery is an alternative approach to the conventional strategy and has proven its efficiency on several enzyme targets. Based on developments in biophysical screening techniques, receptor stabilization and in vitro assays, virtual and experimental fragment screening and fragment-based lead discovery recently became applicable for GPCR targets. Areas covered: This article provides a review of the biophysical as well as biological detection techniques suitable to study GPCRs together with their applications to screen fragment libraries and identify fragment-size ligands of cell surface receptors. The article presents several recent examples including both virtual and experimental protocols for fragment hit discovery and early hit to lead progress. Expert opinion: With the recent progress in biophysical detection techniques, the advantages of fragment-based drug discovery could be exploited for GPCR targets. Structural information on GPCRs will be more abundantly available for early stages of drug discovery projects, providing information on the binding process and efficiently supporting the progression of fragment hit to lead. In silico approaches in combination with biological assays can be used to address structurally challenging GPCRs and confirm biological relevance of interaction early in the drug discovery project