The way in which research-based knowledge is used, interpreted and communicated by different actors can influence the dynamics of conservation conflicts. The conflict that occurs between grouse ...shooting interests and the conservation of birds of prey in Scotland is notoriously complex, involving multiple actors at multiple levels, and shaped by the values and world views of these actors. This paper explores how research-based knowledge is used in the debate by six key organisations, and looks to understand the drivers that may influence knowledge use and interpretation in this, and other, cases of conservation conflict.
Research was used to both legitimise and reinforce certain world views, and to support associated political actions that would cause these to become reality. Actors offered divergent interpretations of the same piece of research, emphasising different findings and outcomes. Research-based knowledge was thus employed by actors to support or counter the ‘status quo’, and challenge other claims that clashed with their own values. Although the intention of such knowledge use is unclear, the selective reconstruction of research by actors could stem from, and reiterate, divergent value systems. This may pose significant challenges to conflict mitigation efforts; whilst some may look to research-based knowledge as the bringer of truth, its interpretation by different actors may exacerbate existing rifts between stakeholders; promoting polarisation of views. Mitigation strategies should be sensitive to this, and aim to improve the inclusiveness and transparency of the knowledge transfer process.
•Research-based knowledge has an important role in conservation conflicts.•Analysis showed evidence of conceptual and strategic knowledge use.•Research was used to legitimise or challenge the ‘status quo’.•Interpretation of research-based knowledge could reflect and reinforce different value systems.•Knowledge use can promote polarisation of views between stakeholder groups.
•We analysed the discourses of six high-profile organisations with conflicting interests.•Organisations offered diverging interpretations of central issues.•Discursive strategies were employed to ...gain ‘dominance’ in the debate.•Discourses were dismissive of the motives and actions of other actors.•Discursive contestation at this level could widen barriers between stakeholders and damage conflict mitigation efforts.
Conflict is currently one of the greatest challenges facing wildlife conservation. Whilst conflicts may first appear to concern wildlife, they are often embedded within wider debates surrounding land use, land ownership, and the governance of natural resources. Disputes over the impacts or management of a species therefore become symbols for conflicts that are fundamentally between the divergent interests and values of the people involved. NGOs representing the interests of local stakeholders can become actors within the conflict, often utilising publicly available platforms such as websites and social media in an attempt to influence over others and gain a dominant foothold in the debate.
Here, we examined discourses of organisations in relation to a contentious and high-profile case of conflict in Scotland, that occurs between interests of raptor conservation and grouse moor management. News articles sourced from the websites of six organisations – identified as key voices in the debate – were subjected to discourse analysis. 36 storylines were drawn from common phrases and statements within the text. Storylines demonstrated a clear divide in the discourse; organisations differed not only in their portrayal of central issues, but also in their representation of other actors. Discourses were strategic; organisations interpreted the situation in ways that either supported their own interests and agendas, or damaged the image of opposing parties. We argue that discursive contestation at this level could be damaging to mitigation efforts – widening barriers between stakeholders and risking already fragile relationships. This in turn reduces the likelihood of consensus and impacts on successful decision-making and policy implementation. We conclude that conflict managers should be aware of the contestation between high-profile actors, and the ramifications this may have for conflict mitigation processes. An understanding of what constitutes these discourses should therefore be used as a foundation to improve dialogue and collaborative management.
Median survival of patients with brain metastases from nonsmall cell lung cancer (NSCLC) is poor and more effective treatments are urgently needed. We have evaluated the efficacy of erlotinib in this ...setting and its association with activating mutations in the epidermal growth factor receptor (EGFR) gene. We retrospectively identified patients with NSCLC and brain metastases treated with erlotinib. EGFR mutations in exons 19 and 21 were analysed by direct sequencing. Efficacy and tolerability were compared according to EGFR mutational status. 69 NSCLC patients with brain metastases were identified, 17 of whom harboured EGFR mutations. Objective response rate in patients with EGFR mutations was 82.4%; no responses were observed in unselected patients (p<0.001). Median (95% CI) time to progression within the brain for patients harbouring EGFR mutations was 11.7 (7.9-15.5) months, compared to 5.8 (5.2-6.4) months for control patients whose EGFR mutational status had not been assessed (p<0.05). Overall survival was 12.9 (6.2-19.7) months and 3.1 (2.5-3.9) months (p<0.001), respectively. The toxicity of erlotinib was as expected and no differences between cohorts were observed. Erlotinib is active in brain metastases from NSCLC; this clinical benefit is related to the presence of activating mutations in exons 19 or 21 of the EGFR gene.
In 2011 the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP) started a joint project to establish guidelines on biomarker testing in patients with advanced ...non-small-cell lung cancer (NSCLC) based on current evidence. As this field is constantly evolving, these guidelines have been updated, previously in 2012 and 2015 and now in 2019. Current evidence suggests that the mandatory tests to conduct in all patients with advanced NSCLC are for
EGFR
and
BRAF
mutations,
ALK
and
ROS1
rearrangements and PD-L1 expression. The growing need to study other emerging biomarkers has promoted the routine use of massive sequencing (next-generation sequencing, NGS). The coordination of every professional involved and the prioritisation of the most suitable tests and technologies for each case remains a challenge.
Efforts to manage conservation conflicts are typically focused on reconciling disputes between opposing stakeholders over conservation objectives. However, this is an oversimplification of conflict ...dynamics, driven by the difficulties of understanding and addressing deeper-rooted issues. In this study, an ethnographic approach using a combination of informal discussions, participant observation, and in-depth interviews was used to examine local stakeholder narratives around a conservation conflict over grouse shooting and raptor conservation. Analysis highlighted three main narratives - cooperation, resistance, and despondence, that served as a basis for individuals to justify their responses to conflict: to work toward collaboration, act antagonistically, or avoid. Our analysis suggests that the current status quo in conflict management serves to reinforce antagonistic positions. We recommend a more nuanced approach to understanding stakeholder decision-making that goes beyond superficial disputes to recognize diversity within stakeholder groups, access hidden voices, and encompass the wider socio-political context.
Background
In Mexico, 80% women with cervical cancer are diagnosed at locally advanced stages and are treated with concomitant chemoradiotherapy. The treatment modality and catabolic state confer a ...nutritional risk. The present study aimed to thoroughly evaluate the nutritional status and change in body composition of locally advanced cervical cancer (LACC) patients throughout treatment.
Methods
An observational prospective study, carried out at the Mexican National Cancer Institute, included 55 LACC patients. Nutritional status was evaluated before, during and after treatment, using anthropometric, dietary and biochemical measurements. Body composition was analysed using computed tomography images obtained at the time of diagnosis and approximately 4 months after treatment completion. Clinical outcomes were associated with changes in body composition.
Results
At the time of diagnosis, no patients were clinically malnourished, although 33.3% presented sarcopenia and most were overweight; by the end of treatment, 69% became clinically malnourished and 58% were sarcopenic. Average weight loss was 7.4 kg (P = 0.001). Adequacy of energy intake was reduced to 54%, obtained predominantly from carbohydrates. By the week 9, 62.8% patients became anemic and 34.5% had low albumin levels. Body composition analysis revealed that patients lost both, muscle and adipose tissues, although 27% patients were muscle depleted by the end of treatment. Patients who lost ≥10% skeletal muscle presented a higher tumour recurrence (hazard ratio = 2.957, P = 0.006) and a tendency towards diminished overall survival (hazard ratio = 2.572, not significant).
Conclusions
The nutritional status of cervical cancer patients deteriorates during treatment with concomitant chemoradiotherapy and, most importantly, muscle loss impacts the clinical outcome of patients.
Most organs consist of networks of interconnected tubes that serve as conduits to transport fluid and cells and act as physiological barriers between compartments. Biological tubes are assembled ...through very diverse developmental processes that generate structures of different shapes and sizes. Nevertheless, all biological tubes invariably possess one single lumen. The mechanisms responsible for single lumen specification are not known. Here we show that zebrafish mutants for the MODY5 and familial GCKD gene tcf2 (also known as vhnf1) fail to specify a single lumen in their gut tube and instead develop multiple lumens. We show that Tcf2 controls single lumen formation by regulating claudin15 and Na+/K+-ATPase expression. Our in vivo and in vitro results indicate that Claudin15 functions in paracellular ion transport to specify single lumen formation. This work shows that single lumen formation is genetically controlled and appears to be driven by the accumulation of fluid.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Approximately 30% of tumor biopsies from patients with advanced-stage lung adenocarcinomas yield insufficient tissue for successful molecular subtyping. We have analyzed the clinical utility of ...next-generation sequencing (NGS) of cell-free circulating tumor DNA (ctDNA) in patients with inadequate tumor samples for tissue genotyping.
We conducted the study in a multi-institutional prospective cohort of clinically unselected patients with advanced-stage lung adenocarcinomas with insufficient tissue for EGFR, ALK or ROS1 genotyping across 12 Spanish institutions (n = 93). ctDNA NGS was carried out by Guardant Health (Guardant360, Redwood City, CA), using a hybrid-capture-based 73-gene panel. Variants were deemed actionable if they were part of the OncoKB precision oncology knowledge database and classified in four levels of actionability based on their clinical or preclinical evidence for drug response.
Eighty-three out of 93 patients (89%) had detectable levels of ctDNA. Potentially actionable level 1–4 genomic alterations were detected in 53 cases (57%), of which 13 (14%) had level 1–2A alterations (Food and Drug Administration-approved and standard-care biomarkers according to lung cancer guidelines). Frequencies of each genomic alteration in ctDNA were consistent with those observed in unselected pulmonary adenocarcinomas. The majority of the patients (62%), particularly those with actionable alterations (87%), had more than one pathogenic variant in ctDNA. The median turnaround time to genomic results was 13 days. Twelve patients (13%) received genotype-matched therapies based on ctDNA results, deriving the expected clinical benefit. Patients with co-occurring pathogenic alterations had a significantly shorter median overall survival as compared with patients without co-occurring pathogenic alteration (multivariate hazard ratio = 5.35, P = 0.01).
Digital NGS of ctDNA in lung cancers with insufficient tumor samples for tissue sequencing detects actionable variants that frequently co-occur with other potentially clinically relevant genomic alterations, allowing timely initiation of genotype-matched therapies.
Despite the concurrence of histidine and cysteine in the active sites of proteins associated with Zn
2+
, Cd
2+
and Hg
2+
, coordination studies of these metal ions with chelating ligands containing ...a combination of aromatic amine and alkylthiolate (N
A
x
S
y
−
) donors have been rare. The potentially tetradentate ligand 2-bis(2-pyridinylmethyl)aminoethanethiol (
LH
) and chloride salts were used to prepare new complexes of Cd
2+
and Hg
2+
for comparison with the known Zn
2+
complex. Solution NMR studies revealed concentration-dependent equilibria between aggregate forms of the new complexes in CD
3
CN. Trends in homonuclear and heteronuclear coupling provided additional insight regarding solution equilibria. ESI-MS from acetonitrile solutions supported differences in preferred aggregation states consistent with the solution NMR studies.
Group 12 complexes incorporating chelating mixed aromatic amine-alkylthiolate ligands have rarely been investigated; metal ion dependent differences in solid, solution, and gas phase aggregation are reported.
Small-cell lung cancer (SCLC) accounts for 15% of lung cancers. Only one-third of patients are diagnosed at limited stage. The median survival remains to be around 15–20 months without significative ...changes in the strategies of treatment for many years. In stage I and IIA, the standard treatment is the surgery followed by adjuvant therapy with platinum–etoposide. In stage IIB–IIIC, the recommended treatment is early concurrent chemotherapy with platinum–etoposide plus thoracic radiotherapy followed by prophylactic cranial irradiation in patients without progression. However, in the extensive stage, significant advances have been observed adding immunotherapy to platinum–etoposide chemotherapy to obtain a significant increase in overall survival, constituting the new recommended standard of care. In the second-line treatment, topotecan remains as the standard treatment. Reinduction with platinum–etoposide is the recommended regimen in patients with sensitive relapse (≥ 3 months) and new drugs such as lurbinectedin and immunotherapy are new treatment options. New biomarkers and new clinical trials designed according to the new classification of SCLC subtypes defined by distinct gene expression profiles are necessary.
PDF
