CTCF is a haploinsufficient tumour suppressor gene with diverse normal functions in genome structure and gene regulation. However the mechanism by which CTCF haploinsufficiency contributes to cancer development is not well understood. CTCF is frequently mutated in endometrial cancer. Here we show that most CTCF mutations effectively result in CTCF haploinsufficiency through nonsense mediated decay of mutant transcripts, or loss-of-function missense mutation. Conversely, we identified a recurrent CTCF mutation K365T, which alters a DNA binding residue, and acts as a gain-of-function mutation enhancing cell survival. CTCF genetic deletion occurs predominantly in poor prognosis serous subtype tumours, and this genetic deletion is associated with poor overall survival. In addition, we have shown that CTCF haploinsufficiency also occurs in poor prognosis endometrial clear cell carcinomas and has some association with endometrial cancer relapse and metastasis. Using shRNA targeting CTCF to recapitulate CTCF haploinsufficiency, we have identified a novel role for CTCF in the regulation of cellular polarity of endometrial glandular epithelium. Overall, we have identified two novel pro-tumorigenic roles (promoting cell survival and altering cell polarity) for genetic alterations of CTCF in endometrial cancer.

This article questions the utility of the term ‘radicalization’ as a focus for counter‐terrorism response in the UK. It argues that the lack of clarity as to who the radicalized are has helped to facilitate a ‘Prevent’ strand of counterterrorism strategy that has confusingly oscillated between tackling violent extremism, in particular, to promoting community cohesion and ‘shared values’ more broadly. The article suggests that the focus of counterterrorism strategy should be on countering terrorism and not on the broader remit implied by wider conceptions of radical‐ization. This is not to diminish the importance of contextual or ‘root cause’ factors behind terrorism, but, if it is terrorism that is to be understood and countered, then such factors should be viewed within the terrorism‐counterterrorism discourse and not a radicalization‐counter‐radicalization one. The article goes on to consider the characterization of those presenting a terrorist threat to the UK as being ‘vulnerable’ to violent extremism. While it argues that the notion of vulnerable individuals and communities also lends itself to a wider ‘Prevent’ remit, it cautions that the impetus towards viewing terrorism as the product of vulnerability should not deflect us from what has generally been agreed in terrorism studies—that terrorism involves the perpetration of rational and calculated acts of violence.

BackgroundLate stage diagnosis of oesophageal and gastric cancer is common, which limits treatment options and contributes to poor survival.AimTo explore patients' understanding, experience and presentation of symptoms before a diagnosis of oesophageal or gastric cancer.Design & settingBetween May 2016 and October 2017, all patients newly diagnosed with oesophageal or gastric cancer were identified at weekly multidisciplinary team meetings at two large hospitals in England. A total of 321 patients were invited to participate in a survey and secondary care medical record review; 127 (40%) participants responded (102 patients had oesophageal cancer and 25 had gastric cancer). Of these, 26 participated in an additional face-to-face interview.MethodSurvey and medical record data were analysed descriptively. Interviews were analysed using thematic analysis, informed by the Model of Pathways to Treatment.ResultsParticipants experienced multiple symptoms before diagnosis. The most common symptom associated with oesophageal cancer was dysphagia (n = 66, 65%); for gastric cancer, fatigue or tiredness (n = 20, 80%) was the most common symptom. Understanding of heartburn, reflux and indigestion, and associated symptoms differed between participants and often contrasted with clinical perspectives. Bodily changes attributed to personal and/or lifestyle factors were self-managed, with presentation to primary care prompted when symptoms persisted, worsened, or impacted daily life, or were notably severe or unusual. Participants rarely presented all symptoms at the initial consultation.ConclusionThe patient interval may be lengthened by misinterpretation of key terms, such as heartburn, or misattribution or non-recognition of important bodily changes. Clearly defined symptom awareness messages may encourage earlier help-seeking, while eliciting symptom experience and meanings in primary care consultations could prompt earlier referral and diagnosis.

In an Australian population, HE4 and ROMA are useful in the diagnosis of epithelial ovarian cancer.

This article argues that there has been an increasing convergence of the discourses of terrorism, radicalization and, more lately, extremism in the UK and that this has caused counterterrorism to lose its focus. This is particularly evident in the counterterrorism emphasis on non‐violent but extremist ideology that is said to be ‘conducive’ to terrorism. Yet, terrorism is ineluctably about violence or the threat of violence; hence, if a non‐violent ideology is in and of itself culpable for terrorism in some way then it ceases to be non‐violent. The article argues that there should be a clearer distinction made between (non‐violent) extremism of thought and extremism of method because it is surely violence and the threat of violence (integral to terrorism) that should be the focus of counterterrorism. The concern is that counterterrorism has gone beyond its remit of countering terrorism and has ventured into the broader realm of tackling ideological threats to the state.