Rewilding – departures in conservation policy and practice? An evaluation of developments in Britain

Rewilding has been hailed as ‘radical’ and ‘agenda-setting’ in the challenge it poses to mainstream conservation. This paper questions whether that is still the case, or if rewilding is now being mainstreamed and with what consequences? Our analysis focuses upon developments in Britain, up until 2018, discussing what changes have become manifest and the barriers and restraints that have been observed. As such, we evaluate the extent to which rewilding – in practice - departs from longstanding conservation sensibilities. Discussion is structured around three key questions— Who is now involved in rewilding across Britain? What they are seeking to do, in terms of how nature is conceptualised and managed (or not)? In what ways do their objectives involve people and human-centred aspirations? Our findings reveal three key differences from current conservation approaches. First, rewilding is associated with a proliferation of new actors, new mechanisms of finance and new spaces of conservation interest. Second, rewilding as an approach exhibits clear novelty in its stated aim to be nature-led and, despite challenges, attempts to work through ongoing negotiation and experimentation. Finally, rewilding is currently being advocated and pursued as an agenda for people and nature, which moves beyond earlier nature conservation paradigms of protecting nature from human influence. However, it remains to be seen whether rewilding advocates can realise their ambitions to popularise and create peopled wild spaces across Britain's landscapes

A powerful intervention: general practitioners' use of sickness certification in depression

<b>Background</b> Depression is frequently cited as the reason for sickness absence, and it is estimated that sickness certificates are issued in one third of consultations for depression. Previous research has considered GP views of sickness certification but not specifically in relation to depression. This study aimed to explore GPs views of sickness certification in relation to depression.<p></p> <b>Methods</b> A purposive sample of GP practices across Scotland was selected to reflect variations in levels of incapacity claimants and antidepressant prescribing. Qualitative interviews were carried out between 2008 and 2009.<p></p> <b>Results</b> A total of 30 GPs were interviewed. A number of common themes emerged including the perceived importance of GP advocacy on behalf of their patients, the tensions between stakeholders involved in the sickness certification system, the need to respond flexibly to patients who present with depression and the therapeutic nature of time away from work as well as the benefits of work. GPs reported that most patients with depression returned to work after a short period of absence and that it was often difficult to predict which patients would struggle to return to work.<p></p> <b>Conclusions</b> GPs reported that dealing with sickness certification and depression presents distinct challenges. Sickness certificates are often viewed as powerful interventions, the effectiveness of time away from work for those with depression should be subject to robust enquiry

Quasichemical Models of Multicomponent Nonlinear Diffusion

Diffusion preserves the positivity of concentrations, therefore, multicomponent diffusion should be nonlinear if there exist non-diagonal terms. The vast variety of nonlinear multicomponent diffusion equations should be ordered and special tools are needed to provide the systematic construction of the nonlinear diffusion equations for multicomponent mixtures with significant interaction between components. We develop an approach to nonlinear multicomponent diffusion based on the idea of the reaction mechanism borrowed from chemical kinetics. Chemical kinetics gave rise to very seminal tools for the modeling of processes. This is the stoichiometric algebra supplemented by the simple kinetic law. The results of this invention are now applied in many areas of science, from particle physics to sociology. In our work we extend the area of applications onto nonlinear multicomponent diffusion. We demonstrate, how the mechanism based approach to multicomponent diffusion can be included into the general thermodynamic framework, and prove the corresponding dissipation inequalities. To satisfy thermodynamic restrictions, the kinetic law of an elementary process cannot have an arbitrary form. For the general kinetic law (the generalized Mass Action Law), additional conditions are proved. The cell--jump formalism gives an intuitively clear representation of the elementary transport processes and, at the same time, produces kinetic finite elements, a tool for numerical simulation.Comment: 81 pages, Bibliography 118 references, a review paper (v4: the final published version

Constructing therapeutic support and negotiating competing agendas: A discourse analysis of vocational advice provided to individuals who are absent from work due to ill-health

Work participation is known to benefit people’s overall health and wellbeing, but accessing vocational support during periods of sickness absence to facilitate return-to-work can be challenging for many people. In this study, we explored how vocational advice was delivered by trained vocational support workers (VSWs) to people who had been signed-off from work by their General Practitioner (GP), as part of a feasibility study testing a vocational advice intervention. We investigated the discursive and interactional strategies employed by VSWs and people absent from work, to pursue their joint and respective goals. Theme-oriented discourse analysis was carried out on eight VSW consultations. These consultations were shown to be complex interactions, during which VSWs utilised a range of strategies to provide therapeutic support in discussions about work. These included; signalling empathy with the person’s perspective; positively evaluating their personal qualities and prior actions; reflecting individuals’ views back to them to show they had been heard and understood; fostering a collaborative approach to action-planning; and attempting to reassure individuals about their return-to-work concerns. Some individuals were reluctant to engage in return-to-work planning, resulting in back-and-forth interactional negotiations between theirs and the VSW’s individual goals and agendas. This led to VSWs putting in considerable interactional ‘work’ to subtly shift the discussion towards return-to-work planning. The discursive strategies we have identified have implications for training health professionals to facilitate work-orientated conversations with their patients, and will also inform training provided to VSWs ahead of a randomised controlled trial. </jats:p

Phenotypic screening identifies a trisubstituted imidazo[1,2-a]pyridine series that induces differentiation in multiple AML cell lines

Acute myeloid leukaemia (AML) is an aggressive type of leukaemia with low rates of long-term survival. While the current standard of care is based on cytotoxic chemotherapy, a promising emerging approach is differentiation therapy. However, most current differentiating agents target specific mutations and are effective only in certain patient subtypes. To identify agents which may be effective in wider population cohorts, we performed a phenotypic screen with the myeloid marker CD11b and identified a compound series that was able to differentiate AML cell lines in vitro regardless of their mutation status. Structure-activity relationship studies revealed that replacing the formamide and catechol methyl ether groups with sulfonamide and indazole respectively improved the in vitro metabolic profile of the series while maintaining the differentiation profile in multiple cell lines. This optimisation exercise enabled progression of a lead compound to in vivo efficacy testing. Our work supports the promise of phenotypic screening to identify novel small molecules that induce differentiation in a wide range of AML subtypes

Structural Requirements for Dihydrobenzoxazepinone Anthelmintics:Actions against Medically Important and Model Parasites: Trichuris muris, Brugia malayi, Heligmosomoides polygyrus, and Schistosoma mansoni

Nine hundred million people are infected with the soil-transmitted helminths Ascaris lumbricoides (roundworm), hookworm, and Trichuris trichiura (whipworm). However, low single-dose cure rates of the benzimidazole drugs, the mainstay of preventative chemotherapy for whipworm, together with parasite drug resistance, mean that current approaches may not be able to eliminate morbidity from trichuriasis. We are seeking to develop new anthelmintic drugs specifically with activity against whipworm as a priority and previously identified a hit series of dihydrobenzoxazepinone (DHB) compounds that block motility of ex vivo Trichuris muris. Here, we report a systematic investigation of the structure–activity relationship of the anthelmintic activity of DHB compounds. We synthesized 47 analogues, which allowed us to define features of the molecules essential for anthelmintic action as well as broadening the chemotype by identification of dihydrobenzoquinolinones (DBQs) with anthelmintic activity. We investigated the activity of these compounds against other parasitic nematodes, identifying DHB compounds with activity against Brugia malayi and Heligmosomoides polygyrus. We also demonstrated activity of DHB compounds against the trematode Schistosoma mansoni, a parasite that causes schistosomiasis. These results demonstrate the potential of DHB and DBQ compounds for further development as broad-spectrum anthelmintics

Chemical Instability and Promiscuity of Arylmethylidenepyrazolinone-Based MDMX Inhibitors.

Targeting the protein-protein interaction between p53 and MDM2/MDMX (MDM4) represents an attractive anticancer strategy for the treatment of p53-competent tumors. Several selective and potent MDM2 inhibitors have been developed and entered the clinic; however, the repertoire of MDMX antagonists is still limited. The arylmethylidenepyrazolinone SJ-172550 has been reported as a selective MDMX antagonist; yet, uncertainties about its mechanism of action have raised doubts about its use as a chemical probe. Here, we show that, in addition to its unclear mode of action, SJ-172550 is unstable in aqueous buffers, giving rise to side products of unknown biological activity. Using an SJ-172550-derived affinity probe, we observed promiscuous binding to cellular proteins whereas cellular thermal shift assays did not reveal a stabilizing effect on MDMX. Overall, our results raise further questions about the interpretation of data using SJ-172550 and related compounds to investigate cellular phenotypes

Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials

Participation as Post-Fordist Politics: Demos, New Labour, and Science Policy

In recent years, British science policy has seen a significant shift ‘from deficit to dialogue’ in conceptualizing the relationship between science and the public. Academics in the interdisciplinary field of Science and Technology Studies (STS) have been influential as advocates of the new public engagement agenda. However, this participatory agenda has deeper roots in the political ideology of the Third Way. A framing of participation as a politics suited to post-Fordist conditions was put forward in the magazine Marxism Today in the late 1980s, developed in the Demos thinktank in the 1990s, and influenced policy of the New Labour government. The encouragement of public participation and deliberation in relation to science and technology has been part of a broader implementation of participatory mechanisms under New Labour. This participatory program has been explicitly oriented toward producing forms of social consciousness and activity seen as essential to a viable knowledge economy and consumer society. STS arguments for public engagement in science have gained influence insofar as they have intersected with the Third Way politics of post-Fordism

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13