Avalanche in Adhesion at Metal Interfaces

Simulations have shown that as two metal surfaces approach each other, the surface layers can avalanche together when the rigid interfacial spacing falls below a critical distance. This is accompanied by a discontinuous decrease in the adhesive energy. Here we present an examination of this phenomenon for the body centered cubic (BCC) metals Fe and W using the Equivalent Crystal Theory. In order to identify the circumstances under which avalanche might be inhibited, the effect of loss of registry between the two surfaces is investigated in detail. The avalanche is inhibited when the two surfaces are sufficiently far out of registry and when only a few layers near the surface are allowed to relax. As the relaxing slabs get thicker a sharp avalanche reappears. However, as the loss of registry increases the energy released in the avalanche decreases

A service evaluation of FIT and anaemia for risk stratification in the two week wait pathway for colorectal cancer

Introduction: New national guidance on urgent referral for investigation for Colorectal Cancer (CRC) included faecal occult blood testing in 2015. We evaluated faecal immunochemical testing (FIT) and anaemia as risk stratification tools in symptomatic patients suspected of having CRC.Methods: Postal FIT was incorporated into the CRC two week wait (2WW) pathway for all patients without rectal bleeding in 2016. Patients were investigated in the 2WW pathway as normal and outcomes of investigations were prospectively recorded. Anaemia was defined as haemoglobin less than 120g/L in women and less than 130g/L in men.Results: FIT kits were sent to 1106 patients with an 80.9% return rate; 810 patients completed investigation with 40 CRCs diagnosed (4.9%). Median FIT results were significantly higher in patients who were anaemic (median 4.8 iqr 0.8-34.1 versus 1.2 iqr 0-6.4, Mann-Whitney p less than 0.001).Some 538 (60.4%) had a result of less than 4 µgHb/gFaeces (limit of detectability) and 621 (69.7%) a result less than 10 µgHb/gFaeces. Sixty per cent of CRCs had a FIT reading of >150 µgHb/gFaeces. Five CRCs diagnosed in patients with a FIT4 µgHb/gFaeces had 97.5% sensitivity and 64.5% specificity for CRC diagnosis. A FIT result of >4 µgHb/gFaeces and/or anaemia had a 100% sensitivity and 45.3% specificity for CRC diagnosis.Conclusion: FIT is most useful at the extremes of detectability; strongly positive readings predict high rates of CRC and other significant pathology, whilst very low readings in the absence of anaemia or palpable rectal mass identify a group with very low risk. High return rates for FIT within this 2WW pathway indicate its acceptability

Dynamics of Transformation from Segregation to Mixed Wealth Cities

We model the dynamics of the Schelling model for agents described simply by a continuously distributed variable - wealth. Agents move to neighborhoods where their wealth is not lesser than that of some proportion of their neighbors, the threshold level. As in the case of the classic Schelling model where segregation obtains between two races, we find here that wealth-based segregation occurs and persists. However, introducing uncertainty into the decision to move - that is, with some probability, if agents are allowed to move even though the threshold level condition is contravened - we find that even for small proportions of such disallowed moves, the dynamics no longer yield segregation but instead sharply transition into a persistent mixed wealth distribution. We investigate the nature of this sharp transformation between segregated and mixed states, and find that it is because of a non-linear relationship between allowed moves and disallowed moves. For small increases in disallowed moves, there is a rapid corresponding increase in allowed moves, but this tapers off as the fraction of disallowed moves increase further and finally settles at a stable value, remaining invariant to any further increase in disallowed moves. It is the overall effect of the dynamics in the initial region (with small numbers of disallowed moves) that shifts the system away from a state of segregation rapidly to a mixed wealth state. The contravention of the tolerance condition could be interpreted as public policy interventions like minimal levels of social housing or housing benefit transfers to poorer households. Our finding therefore suggests that it might require only very limited levels of such public intervention - just sufficient to enable a small fraction of disallowed moves, because the dynamics generated by such moves could spur the transformation from a segregated to mixed equilibrium.Comment: 12 pages, 7 figure

Role of RNA interference (RNAi) in dengue virus replication and identification of NS4B as an RNAi suppressor

RNA interference (RNAi) is an important antiviral defense response in plants and invertebrates; however, evidences for its contribution to mammalian antiviral defense are few. In the present study, we demonstrate the anti-dengue virus role of RNAi in mammalian cells. Dengue virus infection of Huh 7 cells decreased the mRNA levels of host RNAi factors, namely, Dicer, Drosha, Ago1, and Ago2, and in corollary, silencing of these genes in virus-infected cells enhanced dengue virus replication. In addition, we observed downregulation of many known human microRNAs (miRNAs) in response to viral infection. Using reversion-of-silencing assays, we further showed that NS4B of all four dengue virus serotypes is a potent RNAi suppressor. We generated a series of deletion mutants and demonstrated that NS4B mediates RNAi suppression via its middle and C-terminal domains, namely, transmembrane domain 3 (TMD3) and TMD5. Importantly, the NS4B N-terminal region, including the signal sequence 2K, which has been implicated in interferon (IFN)-antagonistic properties, was not involved in mediating RNAi suppressor activity. Site-directed mutagenesis of conserved residues revealed that a Phe-to-Ala (F112A) mutation in the TMD3 region resulted in a significant reduction of the RNAi suppression activity. The green fluorescent protein (GFP)-small interfering RNA (siRNA) biogenesis of the GFP-silenced line was considerably reduced by wild-type NS4B, while the F112A mutant abrogated this reduction. These results were further confirmed by in vitro dicer assays. Together, our results suggest the involvement of miRNA/RNAi pathways in dengue virus establishment and that dengue virus NS4B protein plays an important role in the modulation of the host RNAi/miRNA pathway to favor dengue virus replication

Planned surgery in the COVID-19 pandemic: a prospective cohort study from Nottingham

PurposeGlobally planned surgical procedures have been deferred during the current COVID-19 pandemic. The study aimed to report the outcomes of planned urgent and cancer cases during the current pandemic using a multi-disciplinary prioritisation group.MethodsA prospective cohort study of patients having urgent or cancer surgery at a NHS Trust from 1st March to 30th April 2020 who had been prioritised by a multi-disciplinary COVID Surgery group. Rates of post-operative PCR positive and suspected COVID-19 infections within 30 days, 30-day mortality and any death related to COVID-19 are reported.ResultsOverall 597 patients underwent surgery with a median age of 65 years (interquartile range (IQR) 54–74 years). Of these, 86.1% (514/597) had a current cancer diagnosis. During the period, 60.8% (363/597) of patients had surgery at the NHS Trust whilst 39.2% (234/597) had surgery at Independent Sector hospitals. The incidence of COVID-19 in the East Midlands was 193.7 per 100,000 population during the study period. In the 30 days following surgery, 1.3% (8/597) of patients tested positive for COVID-19 with all cases at the NHS site. Overall 30-day mortality was 0.7% (4/597). Following a PCR positive COVID-19 diagnosis, mortality was 25.0% (2/8). Including both PCR positive and suspected cases, 3.0% (18/597) developed COVID-19 infection with 1.3% at the independent site compared to 4.1% at the NHS Trust (p=0.047).ConclusionsRates of COVID-19 infection in the post-operative period were low especially in the Independent Sector site. Mortality following a post-operative diagnosis of COVID-19 was high

Towards transnational feminist queer methodologies

This article introduces the possibilities of transnational feminist queer research as seeking to conceptualise the transnational as a methodology composed of a series of flows that can augment feminist and queer research. Transnational feminist queer methodologies can contest long-standing configurations of power between researcher and researched, subject and object, academics and activists across places, typically those which are embedded in the hierarchies of the Global North/Global South. Beginning with charting our roots in, and routes through, the diverse arenas of transnational, feminist, participatory and queer methodologies, the article uses a transcribed and edited conversation between members of the Liveable Lives research team in Kolkata and Brighton, to start an exploration of transnational feminist queer methodologies. Understanding the difficult, yet constructive moments of collaborative work and dialogue, we argue for engagements with the multiplicities of ‘many-many' lives that recognise local specificities, and the complexities of lives within transnational research, avoiding creating a currency of comparison between places. We seek to work toward methodologies that take seriously the politics of place, namely by creating research that answers the same question in different places, using methods that are created in context and may not be ‘comparable'. Using a dialogue across the boundaries of activism/academia, as well as across geographical locations, the article contends that there are potentials, as well as challenges, in thinking ourselves through transnational research praxis. This seeks complexities and spatial nuances within as well as between places

GP access to FIT increases the proportion of colorectal cancers detected on urgent pathways in symptomatic patients in Nottingham

ObjectiveService evaluation of GP access to Faecal Immunochemical Test (FIT) for colorectal cancer (CRC) detection in Nottinghamshire and use of FIT for “rule out”, “rule in” and “first test selection”.DesignRetrospective audit of FIT results, CRC outcomes and resource utilisation before and after introduction of FIT in Primary Care in November 2017. Data from the new pathway up to December 2018 was compared with previous experience.ResultsBetween November 2017 and December 2018, 6747 GP FIT test requests yielded 5733 FIT results, of which 4082 (71.2%) were [less than]4.0 μg Hb/g faeces, 579 (10.1%) were 4.0–9.9 μg Hb/g faeces, 836 (14.6%) were 10.0–149.9 μg Hb/g faeces, and 236 (4.1%) were ≥150.0 μg Hb/g faeces. The proportion of “rule out” results [less than]4.0 μg Hb/g faeces was significantly higher than in the Getting FIT cohort (71.2% vs 60.4%, Chi squared 42.8, p [less than] 0.0001) and the proportion of “rule in” results ≥150.0 μg Hb/g faeces was significantly lower (4.1% vs 8.1%, Chi squared 27.3,P [less than] 0.0001).There was a 33% rise in urgent referrals across Nottingham overall during the evaluation period. 2 CRC diagnoses were made in 4082 patients who had FIT[less than]4.0 μg Hb/g faeces. 58.4% of new CRC diagnoses associated with a positive FIT were early stage cancers (Stage I and II). The proportion of all CRC diagnoses that follow an urgent referral s rose after introduction of FIT.ConclusionsFIT allows GP's to select a more appropriate cohort for urgent investigation without a large number of missed diagnoses. FIT appears to promise a “stage migration” effect which may ultimately improve CRC outcomes