Towards Closing the Window on Strongly Interacting Dark Matter: Far-Reaching Constraints from Earth's Heat Flow

We point out a new and largely model-independent constraint on the dark matter scattering cross section with nucleons, applying when this quantity is larger than for typical weakly interacting dark matter candidates. When the dark matter capture rate in Earth is efficient, the rate of energy deposition by dark matter self-annihilation products would grossly exceed the measured heat flow of Earth. This improves the spin-independent cross section constraints by many orders of magnitude, and closes the window between astrophysical constraints (at very large cross sections) and underground detector constraints (at small cross sections). In the applicable mass range, from about 1 to about 10^{10} GeV, the scattering cross section of dark matter with nucleons is then bounded from above by the latter constraints, and hence must be truly weak, as usually assumed.Comment: 12 pages, 2 figures; minor updates to match published versio

ANALYSIS OF MULTIPLE CO-PLANAR SURFACE BREAKING FLAWS LOADED IN TENSION UNDER CLEAVAGE FAILURE CONDITIONS

ABSTRACT In procedures such as R6 and BS 7910 for assessing the structural integrity of structures, complex multiple flaws located in close proximity to each other are generally characterised as one, larger, single flaw. Recent studies have shown that the current characterisation rules may be non-conservative under some circumstances. Concurrent experimental and analytical programmes are being undertaken in order to further investigate this potential non-conservatism for situations where the possibility of cleavage failure has to be taken into account when assessing structures or components containing multiple flaws. The analytical work has involved inelastic finite element modelling in conjunction with numerical analysis based on the weakest link methodology for cleavage initiation to determine the probability of cleavage failure. This has allowed the probability of failure for the situation of multiple adjacent flaws to be compared with that for the single characterised flaw to determine whether the characterisation rules are conservative. Initial results from the cases studied so far indicate that

Low Self-Esteem and Impairments in Emotion Recognition Predict Behavioural Problems in Children

Research indicates that low self-esteem and impaired emotion recognition are risk factors for antisocial behaviour (ASB). Self-esteem and emotion recognition are essential for successful social interaction and previous research suggests that self-esteem and emotional intelligence are positively related. However, to our knowledge the relationship between these two risk factors for ASB has not been explored in children with behavioural problems. Thus, this study investigated self-esteem and emotion recognition, their relationship with one another and with behavioural problem severity. Participants were 8–11 year olds with behavioural problems (BP; n = 78) who were taking part in an early intervention program, and typically developing controls (TD; n = 54). Participants completed a self-esteem questionnaire and a computerised emotion recognition task. Teachers and parents rated children’s emotional and behavioural problems. BP participants had significantly lower self-esteem and exhibited an impairment in emotion recognition. Self-esteem and emotion recognition were positively related and inversely associated with behavioural problem severity and they predicted behaviour problems independently of one another. This is the first study to show that self-esteem and emotion recognition are related processes in children with behavioural problems and that both predict behavioural problems. This has important implications for the development of intervention strategies

Multicentre cohort study to define and validate pathological assessment of response to neoadjuvant therapy in oesophagogastric adenocarcinoma

BACKGROUND: This multicentre cohort study sought to define a robust pathological indicator of clinically meaningful response to neoadjuvant chemotherapy in oesophageal adenocarcinoma. METHODS: A questionnaire was distributed to 11 UK upper gastrointestinal cancer centres to determine the use of assessment of response to neoadjuvant chemotherapy. Records of consecutive patients undergoing oesophagogastric resection at seven centres between January 2000 and December 2013 were reviewed. Pathological response to neoadjuvant chemotherapy was assessed using the Mandard Tumour Regression Grade (TRG) and lymph node downstaging. RESULTS: TRG (8 of 11 centres) was the most widely used system to assess response to neoadjuvant chemotherapy, but there was discordance on how it was used in practice. Of 1392 patients, 1293 had TRG assessment; data were available for clinical and pathological nodal status (cN and pN) in 981 patients, and TRG, cN and pN in 885. There was a significant difference in survival between responders (TRG 1–2; median overall survival (OS) not reached) and non-responders (TRG 3–5; median OS 2·22 (95 per cent c.i. 1·94 to 2·51) years; P < 0·001); the hazard ratio was 2·46 (95 per cent c.i. 1·22 to 4·95; P = 0·012). Among local non-responders, the presence of lymph node downstaging was associated with significantly improved OS compared with that of patients without lymph node downstaging (median OS not reached versus 1·92 (1·68 to 2·16) years; P < 0·001). CONCLUSION: A clinically meaningful local response to neoadjuvant chemotherapy was restricted to the small minority of patients (14·8 per cent) with TRG 1–2. Among local non-responders, a subset of patients (21·3 per cent) derived benefit from neoadjuvant chemotherapy by lymph node downstaging and their survival mirrored that of local responders

Communicating employability: the role of communicative competence for Zimbabwean highly skilled migrants in the UK

Skilled migration is an increasingly important topic for both policy and research internationally. OECD governments in particular are wrestling with tensions between their desire to use skilled migration to be on the winning side in the ‘global war for talent’ and their pandering to and/or attempts to outflank rising xenophobia. One aspect that has received relatively little attention is skilled migration from the African Commonwealth to the UK, a situation in which skilled migrants have relatively high levels of linguistic capital in the language of the host country. We focus here on the case of Zimbabwe. In spite of its popular image as a failed state, Zimbabwe has an exceptionally strong educational tradition and high levels of literacy and fluency in English. Drawing on 20 in-depth interviews of Zimbabwean highly skilled migrants, we explore the specific ways in which the communicative competences of these migrants with high formal levels of English operate in complex ways to shape their employability strategies and outcomes. We offer two main findings: first, that a dichotomy exists between their high level formal linguistic competence and their ability to communicate in less formal interactions, which challenges their employability, at least when they first move to the UK; and second, that they also lack, at least initially, the competence to narrativise their employability in ways that are culturally appropriate in England. Thus, to realise the full potential of their high levels of human capital, they need to learn how to communicate competently in a very different social and occupational milieu. Some have achieved this, but others continue to struggle

Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance

Esophageal adenocarcinoma (EAC) has a poor outcome, and targeted therapy trials have thus far been disappointing owing to a lack of robust stratification methods. Whole-genome sequencing (WGS) analysis of 129 cases demonstrated that this is a heterogeneous cancer dominated by copy number alterations with frequent large-scale rearrangements. Co-amplification of receptor tyrosine kinases (RTKs) and/or downstream mitogenic activation is almost ubiquitous; thus tailored combination RTK inhibitor (RTKi) therapy might be required, as we demonstrate in vitro. However, mutational signatures showed three distinct molecular subtypes with potential therapeutic relevance, which we verified in an independent cohort (n = 87): (i) enrichment for BRCA signature with prevalent defects in the homologous recombination pathway; (ii) dominant T>G mutational pattern associated with a high mutational load and neoantigen burden; and (iii) C>A/T mutational pattern with evidence of an aging imprint. These subtypes could be ascertained using a clinically applicable sequencing strategy (low coverage) as a basis for therapy selection

Authentication and characterisation of a new oesophageal adenocarcinoma cell line: MFD-1.

New biological tools are required to understand the functional significance of genetic events revealed by whole genome sequencing (WGS) studies in oesophageal adenocarcinoma (OAC). The MFD-1 cell line was isolated from a 55-year-old male with OAC without recombinant-DNA transformation. Somatic genetic variations from MFD-1, tumour, normal oesophagus, and leucocytes were analysed with SNP6. WGS was performed in tumour and leucocytes. RNAseq was performed in MFD-1, and two classic OAC cell lines FLO1 and OE33. Transposase-accessible chromatin sequencing (ATAC-seq) was performed in MFD-1, OE33, and non-neoplastic HET1A cells. Functional studies were performed. MFD-1 had a high SNP genotype concordance with matched germline/tumour. Parental tumour and MFD-1 carried four somatically acquired mutations in three recurrent mutated genes in OAC: TP53, ABCB1 and SEMA5A, not present in FLO-1 or OE33. MFD-1 displayed high expression of epithelial and glandular markers and a unique fingerprint of open chromatin. MFD-1 was tumorigenic in SCID mouse and proliferative and invasive in 3D cultures. The clinical utility of whole genome sequencing projects will be delivered using accurate model systems to develop molecular-phenotype therapeutics. We have described the first such system to arise from the oesophageal International Cancer Genome Consortium project.Cancer Research UK, Medical Research CouncilThis is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/srep3241

Postoperative outcomes in oesophagectomy with trainee involvement

BACKGROUND: The complexity of oesophageal surgery and the significant risk of morbidity necessitates that oesophagectomy is predominantly performed by a consultant surgeon, or a senior trainee under their supervision. The aim of this study was to determine the impact of trainee involvement in oesophagectomy on postoperative outcomes in an international multicentre setting. METHODS: Data from the multicentre Oesophago-Gastric Anastomosis Study Group (OGAA) cohort study were analysed, which comprised prospectively collected data from patients undergoing oesophagectomy for oesophageal cancer between April 2018 and December 2018. Procedures were grouped by the level of trainee involvement, and univariable and multivariable analyses were performed to compare patient outcomes across groups. RESULTS: Of 2232 oesophagectomies from 137 centres in 41 countries, trainees were involved in 29.1 per cent of them (n = 650), performing only the abdominal phase in 230, only the chest and/or neck phases in 130, and all phases in 315 procedures. For procedures with a chest anastomosis, those with trainee involvement had similar 90-day mortality, complication and reoperation rates to consultant-performed oesophagectomies (P = 0.451, P = 0.318, and P = 0.382, respectively), while anastomotic leak rates were significantly lower in the trainee groups (P = 0.030). Procedures with a neck anastomosis had equivalent complication, anastomotic leak, and reoperation rates (P = 0.150, P = 0.430, and P = 0.632, respectively) in trainee-involved versus consultant-performed oesophagectomies, with significantly lower 90-day mortality in the trainee groups (P = 0.005). CONCLUSION: Trainee involvement was not found to be associated with significantly inferior postoperative outcomes for selected patients undergoing oesophagectomy. The results support continued supervised trainee involvement in oesophageal cancer surgery

Author Correction: The landscape of viral associations in human cancers

Correction to: Nature Genetics https://doi.org/10.1038/s41588-019-0558-9, published online 05 February 2020