Bristlebots and other friends. A progression of Epistemic insight workshops using small things to ask big questions

Small, handmade and inexpensive robots can help students across a range of ages unpack and explore big questions around the nature of life, curiosity and creativity. This is an introduction to a series of workshops where students learn how to frame and investigate different types of questions including big questions that bridge science, religion, computing and the wider humanities. The first workshop, aimed at upper KS2 looks at the ideas of what we mean by life and to be alive. The second workshop builds on this and asks, ‘can a robot have a sense of curiosity?’ What would a robot need to have a sense of curiosity, what do we need across a range of subject domains. The third workshop takes this further and helps KS3/4 students to ask questions about what it means to be creative, would a robot make a good friend and our we, ourselves, programmed by the society that we grow up in? The workshops are a part of wider activities delivered across primary, secondary, ITE and outreach activities by the LASAR team accompanied by research informing development of epistemic insight in children and young people and equipping them with curiosity, analytical and critical skills to understand current global problems and answer Big Questions

Cancer evolution: Darwin and beyond

Clinical and laboratory studies over recent decades have established branched evolution as a feature of cancer. However, while grounded in somatic selection, several lines of evidence suggest a Darwinian model alone is insufficient to fully explain cancer evolution. First, the role of macroevolutionary events in tumour initiation and progression contradicts Darwin's central thesis of gradualism. Whole-genome doubling, chromosomal chromoplexy and chromothripsis represent examples of single catastrophic events which can drive tumour evolution. Second, neutral evolution can play a role in some tumours, indicating that selection is not always driving evolution. Third, increasing appreciation of the role of the ageing soma has led to recent generalised theories of age-dependent carcinogenesis. Here, we review these concepts and others, which collectively argue for a model of cancer evolution which extends beyond Darwin. We also highlight clinical opportunities which can be grasped through targeting cancer vulnerabilities arising from non-Darwinian patterns of evolution

Diagnostic Validity of Patient-Reported History for Shoulder Pathology

Objective The purpose of this article is to determine whether patient-reported history items are predictive of shoulder pathology and have the potential for use in triaging patients with shoulder pathology to orthopaedic outpatient clinics. Setting It is set at two tertiary orthopaedic clinics. Patients All new patients reporting pain and/or disability of the shoulder joint were prospectively recruited. A total of 193 patients were enrolled, 15 of whom withdrew, leaving 178 patients composing the study sample. Design Patients completed a questionnaire on the history of their pathology, then the surgeon took a thorough history indicating the most likely diagnosis. The clinician then performed appropriate physical examination. Arthroscopy was the reference standard for those undergoing surgery and magnetic resonance imaging (MRI) with arthrogram for all others. We calculated the sensitivity, specificity, and likelihood ratios (LRs) of history items alone and in combination. We used the LRs to generate a clinical decision algorithm. Main Outcome Measures Diagnosis was determined through arthroscopy or MRI arthrogram. Reporting was standardized to ensure review of all structures. Results The physical examination and history agreed in 75% of cases. Of those that did not agree, the physical examination misdirected the diagnosis in 47% of our cases. In particular, history items were strong predictors of anterior and posterior instability and subscapularis tears and were combined in a tool to be utilized for screening patients. Conclusion The patient-reported history items were effective for diagnosing shoulder pathology and should be considered for use in a triaging instrument

Multi-Wavelength Variability of the Synchrotron Self-Compton Model for Blazar Emission

Motivated by recent reports of strongly correlated radio and X-ray variability in 3C279 (Grandi, etal 1995), we have computed the relative amplitudes of variations in the synchrotron flux at $\nu$ and the self-Compton X-ray flux at 1 keV ($R(\nu)$) for a homogeneous sphere of relativistic electrons orbiting in a tangled magnetic field. Relative to synchrotron self-Compton scattering without induced Compton scattering, stimulated scattering reduces the amplitude of $R(\nu)$ by as much as an order of magnitude when \tau_T \gtwid 1. When $\tau_T$ varies in a fixed magnetic field, $R_{\tau}$ increases monotonically from 0.01 at $\nu_o$, the self-absorption turnover frequency, to $0.5$ at $100 \nu_o$. The relative amplitudes of the correlated fluctuations in the radio-mm and X-ray fluxes from 3C279 are consistent with the synchrotron self-Compton model if $\tau_T$ varies in a fixed magnetic field and induced Compton scattering is the dominant source of radio opacity. The variation amplitudes are are too small to be produced by the passage of a shock through the synchrotron emission region unless the magnetic field is perpendicular to the shock front.Comment: 21 pages, 4 fig

Rare disruptive mutations in ciliary function genes contribute to testicular cancer susceptibility

Testicular germ cell tumour (TGCT) is the most common cancer in young men. Here we sought to identify risk factors for TGCT by performing whole-exome sequencing on 328 TGCT cases from 153 families, 634 sporadic TGCT cases and 1,644 controls. We search for genes that are recurrently affected by rare variants (minor allele frequency <0.01) with potentially damaging effects and evidence of segregation in families. A total of 8.7% of TGCT families carry rare disruptive mutations in the cilia-microtubule genes (CMG) as compared with 0.5% of controls (P=2.1 × 10¯⁸). The most significantly mutated CMG is DNAAF1 with biallelic inactivation and loss of DNAAF1 expression shown in tumours from carriers. DNAAF1 mutation as a cause of TGCT is supported by a dnaaf1hu²⁵⁵h(+/−) zebrafish model, which has a 94% risk of TGCT. Our data implicate cilia-microtubule inactivation as a cause of TGCT and provide evidence for CMGs as cancer susceptibility genes

The Impact of Migration on the Welfare of Households Left Behind in Rural Ghana: A Quasi-Experimental Impact Evaluation

Using panel data collected in 2015 and 2018, this paper employs econometric techniques to evaluate the impact of migration on the welfare of households left behind in rural Ghana. We find that poverty is an important driver of migration. Households with lower baseline food and nonfood consumption are more likely to have a member migrating over the three-year period of the study. Specifically, households with migrants had a lower level of consumption at baseline compared to non-migrant households. Using both propensity score matching (PSM) and difference-in-differences (DID) estimation approaches to explore migration’s welfare impact, we find no significant differences between treated and control households once initial baseline differences in consumption are accounted for. Our results suggest that migration has helped to bridge the gap in welfare between disadvantaged (low consumption) and advantaged (higher consumption) households in rural Ghana.DFI

XMM-Newton observation of the long-period polar V1309 Ori: The case for pure blobby accretion

Using XMM-Newton we have obtained the first X-ray observation covering a complete orbit of the longest period polar, V1309 Ori. The X-ray light curve is dominated by a short, bright phase interval with EPIC pn count rates reaching up to 15 cts/sec per 30 sec resolution bin. The bright phase emission is well described by a single blackbody component with kT_bb = (45 +- 3) eV. The absence of a bremsstrahlung component at photon energies above 1 keV yields a flux ratio F_bb/F_br > 6700. This represents the most extreme case of a soft X-ray excess yet observed in an AM Herculis star. The bright, soft X-ray emission is subdivided into a series of individual flare events supporting the hypothesis that the soft X-ray excess in V1309 is caused by accretion of dense blobs. In addition to the bright phase emission, a faint, hard X-ray component is visible throughout the binary orbit with an almost constant count rate of 0.01 cts/sec. Spectral modelling indicates that this emission originates from a complex multi-temperature plasma. At least three components of an optically thin plasma with temperatures kT= 0.065, 0.7, and 2.9 keV are required to fit the observed flux distribution. The faint phase emission is occulted during the optical eclipse. Eclipse ingress lasts about 15--20 min and is substantially prolonged beyond nominal ingress of the white dwarf. This and the comparatively low plasma temperature provide strong evidence that the faint-phase emission is not thermal bremsstrahlung from a post-shock accretion column above the white dwarf. A large fraction of the softer faint-phase emission could be explained by scattering of photons from the blackbody component in the infalling material above the accretion region. The remaining hard X-ray flux could be produced in the coupling region, so far unseen in other polars.Comment: 10 pages, 5 figures, A&A publishe

Tracking Cancer Evolution through the Disease Course.

During cancer evolution, constituent tumor cells compete under dynamic selection pressures. Phenotypic variation can be observed as intratumor heterogeneity, which is propagated by genome instability leading to mutations, somatic copy-number alterations, and epigenomic changes. TRACERx was set up in 2014 to observe the relationship between intratumor heterogeneity and patient outcome. By integrating multiregion sequencing of primary tumors with longitudinal sampling of a prospectively recruited patient cohort, cancer evolution can be tracked from early- to late-stage disease and through therapy. Here we review some of the key features of the studies and look to the future of the field. SIGNIFICANCE: Cancers evolve and adapt to environmental challenges such as immune surveillance and treatment pressures. The TRACERx studies track cancer evolution in a clinical setting, through primary disease to recurrence. Through multiregion and longitudinal sampling, evolutionary processes have been detailed in the tumor and the immune microenvironment in non-small cell lung cancer and clear-cell renal cell carcinoma. TRACERx has revealed the potential therapeutic utility of targeting clonal neoantigens and ctDNA detection in the adjuvant setting as a minimal residual disease detection tool primed for translation into clinical trials