Immune checkpoint inhibitors in renal cell carcinoma

The immune system has long been known to play a critical role in the body's defence against cancer, and there have been multiple attempts to harness it for therapeutic gain. Renal cancer was, historically, one of a small number of tumour types where immune manipulation had been shown to be effective. The current generation of immune checkpoint inhibitors are rapidly entering into routine clinical practice in the management of a number of tumour types, including renal cancer, where one drug, nivolumab, an anti-programmed death-1 (PD-1) monoclonal antibody (mAb), is licensed for patients who have progressed on prior systemic treatment. Ongoing trials aim to maximize the benefits that can be gained from this new class of drug by exploring optimal timing in the natural course of the disease as well as combinations with other checkpoint inhibitors and drugs from different classes

Understanding the Heavy Tailed Dynamics in Human Behavior

The recent availability of electronic datasets containing large volumes of communication data has made it possible to study human behavior on a larger scale than ever before. From this, it has been discovered that across a diverse range of data sets, the inter-event times between consecutive communication events obey heavy tailed power law dynamics. Explaining this has proved controversial, and two distinct hypotheses have emerged. The first holds that these power laws are fundamental, and arise from the mechanisms such as priority queuing that humans use to schedule tasks. The second holds that they are a statistical artifact which only occur in aggregated data when features such as circadian rhythms and burstiness are ignored. We use a large social media data set to test these hypotheses, and find that although models that incorporate circadian rhythms and burstiness do explain part of the observed heavy tails, there is residual unexplained heavy tail behavior which suggests a more fundamental cause. Based on this, we develop a new quantitative model of human behavior which improves on existing approaches, and gives insight into the mechanisms underlying human interactions.Comment: 9 pages in Physical Review E, 201

Human sensitivity to gearshift loads

This paper describes an investigation of the ability of humans to distinguish different levels of gearlever load. A test rig with a forward-backward moving gearshift lever was constructed using the typical interior dimensions of European B segment automobiles. The rig used a system of weights and pulleys to provide a load which could be varied in steps of 1%. Four reference loads were chosen which were considered representative of automotive gearshift operation: 0.5, 1.0, 2.0 and 5.0 kg. Twenty subjects took part in the study. Using a variation on the psychophysical method of limits, the subjects were asked to respond whether a test load was heavier or lighter than a reference load. The Weber Fraction was found to decrease monotonically from a value of 0.036 for the 0.5 kg reference load to a value of 0.029 at the 5.0 kg reference load. The average value across all reference loads was 0.032. Measurements of the gearshift force made by means of a knob containing a load cell suggested that the variation in the measured Weber Fraction might be attributable to the time behaviour of the force exchanged between the human subject and the control surface

Measuring the electrical impedance of mouse brain tissue

We report on an experimental method to measure conductivity of cortical tissue. We use a pair of 5mm diameter Ag/AgCl electrodes in a Perspex sandwich device that can be brought to a distance of 400 microns apart. The apparatus is brought to uniform temperature before use. Electrical impedance of a sample is measured across the frequency range 20 Hz-2.0 MHz with an Agilent 4980A four-point impedance monitor in a shielded room. The equipment has been used to measure the conductivity of mature mouse brain cortex in vitro. Slices 400 microns in thickness are prepared on a vibratome. Slices are bathed in artificial cerebrospinal fluid (ACSF) to keep them alive. Slices are removed from the ACSF and sections of cortical tissue approximately 2 mm times 2 mm are cut with a razor blade. The sections are photographed through a calibrated microscope to allow identification of their cross-sectional areas. Excess ACSF is removed from the sample and the sections places between the electrodes. The impedance is measured across the frequency range and electrical conductivity calculated. Results show two regions of dispersion. A low frequency region is evident below approximately 10 kHz, and a high frequency dispersion above this. Results at the higher frequencies show a good fit to the Cole-Cole model of impedance of biological tissue; this model consists of resistive and non-linear capacitive elements. Physically, these elements are likely to arise due to membrane polarization and migration of ions both intra- and extra-cellularly.http://www.iupab2014.org/assets/IUPAB/NewFolder/iupab-abstracts.pd

Multi-Scale Entropy Analysis as a Method for Time-Series Analysis of Climate Data

Evidence is mounting that the temporal dynamics of the climate system are changing at the same time as the average global temperature is increasing due to multiple climate forcings. A large number of extreme weather events such as prolonged cold spells, heatwaves, droughts and floods have been recorded around the world in the past 10 years. Such changes in the temporal scaling behaviour of climate time-series data can be difficult to detect. While there are easy and direct ways of analysing climate data by calculating the means and variances for different levels of temporal aggregation, these methods can miss more subtle changes in their dynamics. This paper describes multi-scale entropy (MSE) analysis as a tool to study climate time-series data and to identify temporal scales of variability and their change over time in climate time-series. MSE estimates the sample entropy of the time-series after coarse-graining at different temporal scales. An application of MSE to Central European, variance-adjusted, mean monthly air temperature anomalies (CRUTEM4v) is provided. The results show that the temporal scales of the current climate (1960–2014) are different from the long-term average (1850–1960). For temporal scale factors longer than 12 months, the sample entropy increased markedly compared to the long-term record. Such an increase can be explained by systems theory with greater complexity in the regional temperature data. From 1961 the patterns of monthly air temperatures are less regular at time-scales greater than 12 months than in the earlier time period. This finding suggests that, at these inter-annual time scales, the temperature variability has become less predictable than in the past. It is possible that climate system feedbacks are expressed in altered temporal scales of the European temperature time-series data. A comparison with the variance and Shannon entropy shows that MSE analysis can provide additional information on the statistical properties of climate time-series data that can go undetected using traditional method

Photophysics of azobenzene constrained in a UiO metal‐organic framework: effects of pressure, solvation and dynamic disorder

Photophysical studies of chromophoric linkers in metal–organic frameworks (MOFs) are undertaken commonly in the context of sensing applications, in search of readily observable changes of optical properties in response to external stimuli. The advantages of the MOF construct as a platform for investigating fundamental photophysical behaviour have been somewhat overlooked. The linker framework offers a unique environment in which the chromophore is geometrically constrained and its structure can be determined crystallographically, but it exists in spatial isolation, unperturbed by inter‐chromophore interactions. Furthermore, high‐pressure studies enable the photophysical consequences of controlled, incremental changes in local environment or conformation to be observed and correlated with structural data. This approach is demonstrated in the present study of the trans‐azobenzene chromophore, constrained in the form of the 4,4’‐azobenzenedicarboxylate (abdc) linker, in a UiO topology framework. Previously unobserved effects of pressure‐induced solvation and conformational distortion on the lowest energy, nπ* transition are reported, and interpreted the light of crystallographic data. It was found that trans‐azobenzene remains non‐fluorescent (with a quantum yield less than 10(−4)) despite the prevention of trans‐cis isomerization by the constraining MOF structure. We propose that efficient non‐radiative decay is mediated by the local, pedal‐like twisting of the azo group that is evident as dynamic disorder in the crystal structure

Is God really good to the upright? Theological educators exploring Psalm 73 through the Jungian lenses of sensing, intuition, feeling and thinking

Psalm 73 is a challenging Psalm in which the Psalmist draws on rich imagery to juxtapose doctrine and experience, and to juxtapose the goodness of God with divine retribution. Drawing on data provided by 15 theological educators within the Anglican Diocese of Cyprus and the Gulf, this study tests the thesis that the imagery of Psalm 73 will be perceived differently by sensing types and by intuitive types, and that the issue ‘Is God really good to the upright?’ will be judged differently by feeling types and by thinking types. The findings from this study are consistent with the broader hermeneutical theory that the psychological type profile of the reader, in terms of perceiving preference and judging preference, plays a formative part in shaping the interpretation of biblical material

Making sexual and reproductive healthcare environments safe and supportive for disclosure of sexual violence:interview findings from patients and healthcare professionals using a realist approach

Objectives: Most people who have experienced sexual violence (SV) will disclose the event(s) to someone. Key recipients of disclosure are those working in healthcare. Telling someone in healthcare about experiences of SV can be an important step in accessing necessary medical care and being signposted to other services. While recognising healthcare settings are a key place for people to seek support, evidence is lacking about how best to create a safe environment for disclosure to take place, how services can make changes to better facilitate this experience and what changes matter most.Design: This study used a realist approach to identify mechanisms that facilitate safe and supported disclosure. Data were generated through three focus groups with Sexual and Reproductive Health Services healthcare professionals in the UK, and one-to-one interviews with survivors of SV who attended healthcare settings (n=18).Results: The analysis found that service users needed to feel empowered and recognised as appropriate candidates for care in the material used to promote sexual healthcare services after SV. This promotional material needs to address rape myths, stereotypes and silence surrounding SV, to ensure that all individuals and especially those from diverse groups are empowered to access care. Three fundamental mechanisms for safe and supported disclosure were identified: being listened to, being validated and having choice. Trauma-informed care was identified as being essential for implementing these mechanisms. Healthcare professionals who were confident and competent regarding enquiry about SV and response to disclosures of SV were key.Conclusions: The development of services that are conducive to the disclosure of SV is needed to provide better support for those who have experienced SV and are ready to seek support. Use of appropriate promotional material, specific staff training and a trauma-informed approach are key elements to improve services.<br/

Making sexual and reproductive healthcare environments safe and supportive for disclosure of sexual violence:interview findings from patients and healthcare professionals using a realist approach

Objectives: Most people who have experienced sexual violence (SV) will disclose the event(s) to someone. Key recipients of disclosure are those working in healthcare. Telling someone in healthcare about experiences of SV can be an important step in accessing necessary medical care and being signposted to other services. While recognising healthcare settings are a key place for people to seek support, evidence is lacking about how best to create a safe environment for disclosure to take place, how services can make changes to better facilitate this experience and what changes matter most.Design: This study used a realist approach to identify mechanisms that facilitate safe and supported disclosure. Data were generated through three focus groups with Sexual and Reproductive Health Services healthcare professionals in the UK, and one-to-one interviews with survivors of SV who attended healthcare settings (n=18).Results: The analysis found that service users needed to feel empowered and recognised as appropriate candidates for care in the material used to promote sexual healthcare services after SV. This promotional material needs to address rape myths, stereotypes and silence surrounding SV, to ensure that all individuals and especially those from diverse groups are empowered to access care. Three fundamental mechanisms for safe and supported disclosure were identified: being listened to, being validated and having choice. Trauma-informed care was identified as being essential for implementing these mechanisms. Healthcare professionals who were confident and competent regarding enquiry about SV and response to disclosures of SV were key.Conclusions: The development of services that are conducive to the disclosure of SV is needed to provide better support for those who have experienced SV and are ready to seek support. Use of appropriate promotional material, specific staff training and a trauma-informed approach are key elements to improve services.<br/