Working memory capacity and surgical performance whilst exposed to mild hypoxic hypoxaemia (3000m)

INTRODUCTION: Medical Emergency Response Team (MERT) helicopters fly at altitudes of 3,000m in Afghanistan (9,843ft). Civilian hospitals and disaster-relief surgical teams may have to operate at such altitudes or even higher. Mild hypoxia has been seen to affect the performance of novel tasks at flight levels as low as 5,000ft. Aeromedical teams frequently work in unpressurised environments; it is important to understand the implications of this mild hypoxia and investigate whether supplementary oxygen systems are required for some or all of the team members. METHODS: Ten UK orthopaedic surgeons were recruited and in a double blind randomised experimental protocol, were acutely exposed for 45 minutes to normobaric hypoxia (fraction of inspired oxygen (FiO2) ~14.1% - equivalent to 3000m/10,000ft) or normobaric normoxia (sea-level). Basic physiological parameters were recorded. Subjects completed validated tests of verbal working memory capacity (VWMC) and also applied an orthopaedic external fixator (Hoffmann® 3, Stryker UK) to a plastic tibia under test conditions. RESULTS: Significant hypoxia was induced with the reduction of FiO2 to ~14.1% (SpO2 87% vs. 98%). No effect of hypoxia on VWMC was observed. The pin-divergence score (a measure of frame asymmetry) was significantly greater in hypoxic conditions (4.6mm) compared to sea level (3.0mm), there was no significant difference in the penetrance depth (16.9 vs. 17.2mm). One frame would have failed early. DISCUSSION: We believe that surgery at an altitude of 3000m when unacclimated individuals are acutely exposed to atmospheric hypoxia for 45 minutes, can likely take place without supplemental oxygen use but further work is required

HAWKS: Evolving Challenging Benchmark Sets for Cluster Analysis

Comprehensive benchmarking of clustering algorithms is rendered difficult by two key factors: (i) the elusiveness of a unique mathematical definition of this unsupervised learning approach and (ii) dependencies between the generating models or clustering criteria adopted by some clustering algorithms and indices for internal cluster validation. Consequently, there is no consensus regarding the best practice for rigorous benchmarking, and whether this is possible at all outside the context of a given application. Here, we argue that synthetic datasets must continue to play an important role in the evaluation of clustering algorithms, but that this necessitates constructing benchmarks that appropriately cover the diverse set of properties that impact clustering algorithm performance. Through our framework, HAWKS, we demonstrate the important role evolutionary algorithms play to support flexible generation of such benchmarks, allowing simple modification and extension. We illustrate two possible uses of our framework: (i) the evolution of benchmark data consistent with a set of hand-derived properties and (ii) the generation of datasets that tease out performance differences between a given pair of algorithms. Our work has implications for the design of clustering benchmarks that sufficiently challenge a broad range of algorithms, and for furthering insight into the strengths and weaknesses of specific approaches

Cumulative mutagenesis of the basic residues in the 201-218 region of insulin-like growth factor (IGF)-binding protein-5 results in progressive loss of both IGF-I binding and inhibition of IGF-I biological action

We have reported previously that mutation of two conserved nonbasic amino acids (G203 and Q209) within the highly basic 201–218 region in the C-terminal domain of IGF-binding protein-5 (IGFBP-5) decreases binding to IGFs. This study reveals that cumulative mutagenesis of the 10 basic residues in this region, to create the C-Term series of mutants, ultimately results in a 15-fold decrease in the affinity for IGF-I and a major loss in heparin binding. We examined the ability of mutants to inhibit IGF-mediated survival of MCF-7 cells and were able to demonstrate that this depended not only upon the affinity for IGF-I, but also the kinetics of this interaction, because IGFBP-5 mutants with similar affinity constants (KD) values, but with different association (Ka) and dissociation (Kd) rate values, had markedly different inhibitory properties. In contrast, the affinity for IGF-I provided no predictive value in terms of the ability of these mutants to enhance IGF action when bound to the substratum. Instead, these C-Term mutants appeared to enhance the actions of IGF-I by a combination of increased dissociation of IGF-IGFBP complexes from the substratum, together with dissociation of IGF-I from IGFBP-5 bound to the substratum. These effects of the IGFBPs were dependent upon binding to IGF-I, because a non-IGF binding mutant (N-Term) was unable to inhibit or enhance the actions of IGF-I. These results emphasize the importance of the kinetics of association/dissociation in determining the enhancing or inhibiting effects of IGFBP-5 and demonstrate the ability to generate an IGFBP-5 mutant with exclusively IGF-enhancing activity

Birth outcomes by type of attendance at antenatal education: An observational study

Background: Antenatal education aims to prepare expectant parents for pregnancy, birth, and parenthood. Studies have reported antenatal education teaching breathing and relaxation methods for pain relief, termed psychoprophylaxis, is associated with reduction in caesarean section rates compared with general birth and parenting classes. Given the rising rates of caesarean section, we aimed to determine whether there was a difference in mode of birth in women based on the type of antenatal education attended. Materials and methods: A cross-sectional antenatal survey of nulliparous women ≥28 weeks gestation with a singleton pregnancy was conducted in two maternity hospitals in Sydney, Australia in 2018. Women were asked what type of antenatal education they attended and sent a follow-up survey post-birth. Hospital birth data were also obtained. Education was classified into four groups: psychoprophylaxis, birth and parenting, other, or none. Results: Five hundred and five women with birth data were included. A higher proportion of women who attended psychoprophylaxis education had a vaginal birth (instrumental/spontaneous) (79%) compared with women who attended birth and parenting, other or no education (69%, 67%, 60%, respectively P = 0.045). After adjusting for maternal characteristics, birth and hospital factors, the association was attenuated (odds ratio 2.03; 95% CI 0.93–4.43). Conclusions: Women who attended psychoprophylaxis couple-based education had a trend toward higher rates of vaginal birth. Randomised trials comparing different types of antenatal education are required to determine whether psychoprophylaxis education can reduce caesarean section rates and improve other birth outcomes

pySuStaIn: A Python implementation of the Subtype and Stage Inference algorithm

Progressive disorders are highly heterogeneous. Symptom-based clinical classification of these disorders may not reflect the underlying pathobiology. Data-driven subtyping and staging of patients has the potential to disentangle the complex spatiotemporal patterns of disease progression. Tools that enable this are in high demand from clinical and treatment-development communities. Here we describe the pySuStaIn software package, a Python-based implementation of the Subtype and Stage Inference (SuStaIn) algorithm. SuStaIn unravels the complexity of heterogeneous diseases by inferring multiple disease progression patterns (subtypes) and individual severity (stages) from cross-sectional data. The primary aims of pySuStaIn are to enable widespread application and translation of SuStaIn via an accessible Python package that supports simple extension and generalization to novel modeling situations within a single, consistent architecture

Core excitations across the neutron shell gap in ²⁰⁷Tl

The single closed-neutron-shell, one proton-hole nucleus 207Tl was populated in deep-inelastic collisions of a 208Pb beam with a 208Pb target. The yrast and near-yrast level scheme has been established up to high excitation energy, comprising an octupol

Sensitive SERS nanotags for use with 1550 nm (retina-safe) laser excitation

Chalcogenopyrylium nanotags demonstrate an unprecedented SERS performance with a retina safe, 1550 nm laser excitation. These unique nanotags consisting of chalcogenopyrylium dyes and 100 nm gold nanoparticles produce exceptional SERS signals with picomolar detection limits obtained at this extremely red-shifted and eye-safe laser excitation