The Influence of high pressure on the bending rigidity of model membranes

Curvature is a fundamental lipid membrane property that influences many membrane-mediated biological processes and dynamic soft materials. One of the key parameters that determines the energetics of curvature change is the membrane bending rigidity. Understanding the intrinsic effect of pressure on membrane bending is critical to understanding the adaptation and structural behavior of biomembranes in deep-sea organisms as well as soft material processing. However, it has not previously been possible to measure the influence of high hydrostatic pressure on membrane bending energetics, and this bottleneck has primarily been due to a lack of technology platforms for performing such measurements. We have developed a new high-pressure microscopy cell which, combined with vesicle fluctuation analysis, has allowed us to make the first measurements of membrane bending rigidity as a function of pressure. Our results show a significant increase in bending rigidity at pressures up to 40 MPa. Above 40 MPa, the membrane mechanics become more complex. Corresponding small and wide-angle X-ray diffraction shows an increase in density and thickness of the bilayer with increasing pressure which correlates with the micromechanical measurements. These results are consistent with recent theoretical predictions of the bending rigidity as a function of hydrocarbon chain density. This technology has the potential to transform our quantitative understanding of the role of pressure in soft material processing, the structural behavior of biomembranes, and the adaptation mechanisms employed by deep-sea organisms

Sorting It Out: A Community Mediation Training Program at a Therapeutic Prison

A pilot study was conducted to assess the feasibility and effect of a community mediation program (‘Sorting It Out’) in a therapeutic prison (the Compulsory Drug Treatment Correctional Centre, or CDTCC). The program is unique as both staff and inmates were trained together. Also, in contrast to traditional dispute resolution, which is invoked after conflict has progressed, the program, which is based on therapeutic jurisprudence principles, trains participants in mediation to constructively address issues at the point of identification, prior to escalation. Measured outcomes included pre- and post-program questionnaires incorporating a social climate scale (EssenCES©), qualitative interviews and researcher observations. The participation rate was high, with all participants recommending the program. The outcomes included an enduring improvement in social climate and improvement in the CDTCC operation. Staff reported increased feelings of safety and support, and inmates reported increased understanding of staff and their roles. A large majority reported benefits to themselves and the community, including adoption of attitudes and behaviours learned in the program, improvement in staff–inmate interaction and a positive effect on staff work

Photoluminescence upconversion at GaAs/InGaP2 interfaces driven by a sequential two-photon absorption mechanism

This paper reports on the results of an investigation into the nature of photoluminescence upconversion at GaAs/InGaP2 interfaces. Using a dual-beam excitation experiment, we demonstrate that the upconversion in our sample proceeds via a sequential two-photon optical absorption mechanism. Measurements of photoluminescence and upconversion photoluminescence revealed evidence of the spatial localization of carriers in the InGaP2 material, arising from partial ordering of the InGaP2. We also observed the excitation of a two-dimensional electron gas at the GaAs/InGaP2 heterojunction that manifests as a high-energy shoulder in the GaAs photoluminescence spectrum. Furthermore, the results of upconversion photoluminescence excitation spectroscopy demonstrate that the photon energy onset of upconversion luminescence coincides with the energy of the two-dimensional electron gas at the GaAs/InGaP2 interface, suggesting that charge accumulation at the interface can play a crucial role in the upconversion process

Diagnostic accuracy of perinatal post-mortem ultrasound (PMUS): a systematic review

OBJECTIVE Ultrasound is ubiquitous in live paediatric imaging; however, its usage in post-mortem setting is less established. This systematic review aims to evaluate the diagnostic accuracy of paediatric post-mortem ultrasound (PMUS). DESIGN MEDLINE, Embase and Cochrane Library databases were queried for studies published between 1998 and 2018 assessing PMUS diagnostic accuracy rates in children<18 years old, using autopsy as reference standard. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies 2. A bivariate random-effects model was used to obtain combined mean estimates of sensitivity and specificity for different body systems. RESULTS Four studies were included, all relating to ultrasound for perinatal deaths. The mean diagnostic sensitivity and specificity for neurological abnormalities were 84.3% (95% CI: 70.8% to 92.2%) and 96.7% (95% CI: 86.5% to 99.3%); for cardiothoracic abnormalities 52.1% (95% CI: 27.6% to 75.5%,) and 96.6% (95% CI: 86.8% to 99.2%); and for abdominal abnormalities 78.4% (95% CI: 61.0% to 89.4%) and 97.3% (95% CI: 88.9% to 99.4%). Combining all body systems, the mean sensitivity and specificity were 73.3% (95% CI: 59.9% to 83.5%) and 96.6% (95% CI: 92.6% to 98.4%). CONCLUSIONS PMUS demonstrates a reasonable diagnostic accuracy, particularly for abdominal and neurological abnormalities, although cardiac anomalies were less readily identified. TRIAL REGISTRATION NUMBER CRD42018106968

Long-Range Conformational Changes in Monoclonal Antibodies Revealed Using FPOP-LC-MS/MS

Differences in conformational dynamics between two full-length monoclonal antibodies have been probed in detail using Fast Photochemical Oxidation of Proteins (FPOP) followed by proteolysis and LC-ESI-MS/MS analyses. FPOP uses hydroxyl radical labelling to probe the surface-accessible regions of proteins and has the advantage that the resulting covalent modifications are irreversible, thus permitting optimal down-stream analysis. Despite the two monoclonal antibodies (mAbs) differing by only three amino acids in the heavy chain complementarity determining regions (CDRs), one mAb, MEDI1912-WFL, has been shown to undergo reversible self-association at high concentrations and exhibited poor pharmacokinetic properties in vivo, properties which are markedly improved in the variant, MEDI1912-STT. Identifying the differences in oxidative labelling between the two antibodies at residue level revealed long-range effects which provide a key insight into their conformational differences. Specifically, the amino acid mutations in the CDR region of the heavy chain resulted in significantly different labelling patterns at the interfaces of the CL–CH1 and CH1–CH2 domains, with the non-aggregating variant undergoing up to four times more labelling in this region than the aggregation prone variant, thus suggesting a change in the structure and orientation of the CL – CH1 interface. The wealth of FPOP and LC-MS data obtained enabled the study of the LC elution properties of FPOP-oxidised peptides. Some oxidised amino acids, specifically histidine and lysine, were noted to have unique effects on the retention time of the peptide, offering the promise of using such an analysis as an aid to MS/MS in assigning oxidation sites

Comparative study of intradermal smear microscopy in the diagnosis of malaria in symptomatic pregnant women

A comparative study of intradermal smear in the diagnosis of malaria in symptomatic pregnant women.Venous blood served as the control.Fifty consecutive symptomatic pregnant women were recruited. Thick films of both venous and intradermal blood were examined. Questionnaires were used to determine patients' preference for the two techniques. Tests of statistical significance were done with Fisher exact and Yates correlationcoefficient at 95% confidence interval. Sensitivity, specificity and accuracy rates were used to assess the validity of intradermal smear.Intradermal smear more frequently diagnosed malaria parasitaemia than peripheral venous blood (66% vs 56%). This was statistically significant (P value: 0.0065). The sensitivity of intradermal smear was 85.7% while the positive predictive value was 77.4%. The accuracy rate was 76.7%. The technique of intradermal blood collection was preferred by28%of women.Intradermal smear is useful in malaria diagnosis in pregnancy and may be an additional evaluation tool for persistent fever in pregnancy

Applying the natural capital approach to decision making for the marine environment

The aspirations for natural capital and ecosystem service approaches to support environmental decision-making have not been fully realised in terms of their actual application in policy and management contexts. Application of the natural capital approach requires a range of methods, which as yet have not been fully tested in the context of decision making for the marine environment. It is unlikely that existing methodologies, which were developed for terrestrial systems and are based on land cover assessment approaches, will ever be feasible in the marine context at the national scale. Land cover approaches are also fundamentally insufficient for the marine environment because they do not take account of the water column, the significant interconnections between spatially disparate components, or the highly dynamic nature of the marine ecosystem, for example the high spatial mobility of many species. Data gaps have been a significant impediment to progress, so alternative methods that use proxies for quality information as well as the opportunities for remote sensing should be explored further. Greater effort to develop methodologies specifically for the marine environment is required, which should be interdisciplinary and cross-sectoral, coherent across policy areas, and applicable across a range of contexts