Provenance of Ordovician and Devonian sandstones from southern Peru and northern Bolivia - U-Pb and Lu-Hf isotope evidence of detrital zircons and its implications for the geodynamic evolution of the Western Gondwana margin (14° - 17° S)

In an attempt to trace the provenance of sedimentary detritus and to gain information on the crustal evolution of the Early Paleozoic western Gondwana margin (14°-17°S) we applied a combined in situ U-Pb and Lu-Hf LA-ICP-MS isotope analysis on detrital zircon from 12 Ordovician and Devonian sandstones in southern Peru and northern Bolivia. The sandstones are exposed in the Eastern Cordillera, the Altiplano and the Coastal Cordillera. The sedimentary basins are part of the Peru-Bolivia trough. Few intrusive and extrusive Early Paleozoic rocks indicate that the Ordovician basins developed in a back-arc position, with the arc on the Arequipa Massif in the west and the Amazonian craton in the east. This plate-tectonic setting appears to have changed into a passive margin in the Early Devonian. The U-Pb zircon age distribution of the Ordovician sandstones from the Eastern Cordillera has the most distinctive peak between 0.7 and 0.5 Ga (Brazilian interval). Contrastingly, the most prominent U-Pb zircon age peak of the Ordovician sandstones from the Altiplano is at 1.2-0.9 Ga (Grenvillian interval) with a smaller peak at 1.85-1.7 Ga. The Devonian sandstones from the same locality on the Altiplano contain zircons with a major age peak at 0.5-0.4 Ga (Famatinian interval). Smaller U-Pb age peaks can be connected to the Brazilian, Grenvillian and Transamazonian (2.2-1.8 Ga) intervals. Zircons of the Devonian sandstones from the Coastal Cordillera have a similar age distribution but the Grenvillian ages, in one case also the Transamazonian ages are significantly more pronounced than the Brazilian ages. Zircons formed during the Brazilian interval could have been derived from various eastern sources on the Amazonian craton, those with Grenvillian ages were derived either from the Sunsas belt to the east or from the Arequipa Massif to the west of the sedimentary basin. Zircons related to the Famatinan event most probably originated in the Arequipa Massif, the closest place where respective magmatic arc rocks were available. Thus, the Ordovician sandstones of the Eastern Cordillera and the Altiplano had an eastern source, while the Altiplano locality was fed from a very limited source area, probably the Sunsas belt. The Devonian siliciclastic strata instead were mainly influenced by the Arequipa Massif. Minor influences of eastern sources are documented by the presence of Brazilian zircon ages. The in situ Lu-Hf isotope signature provides information about crustal recycling. Together with the U-Pb zircon ages, crustal evolution paths can be reconstructed. εHf(t) values of the analysed zircons spread between –20 and +12. Zircons with a very juvenile signatures (less than 5 εHf-units below the respective depleted mantle composition) we detected only in the interval between 1.5 and 0.9 Ga. Hence, of the Brazilian and Famatinian events we only find zircons derived from an evolved crust. A striking feature is the common Hf model ages (c.1.5-1.2 Ga) of zircons formed during the Grenvillian, Brazilian and Famatinian orogenies. This indicates that Famatinian-aged crystalline rocks of the Arequipa Massif and the Brazilianaged crystalline rocks of the Amazonian craton have a similar crustal origin

Sedimentological analysis of the Ordovician and Devonian basins in southern Peru and northern Bolivia

We present data from a study of the evolution of the Early Paleozoic Peru-Bolivia Trough, its facies development and the provenance of sediments deposited during Ordovician and Devonian time. We measured and sampled sections in the Ordovician successions in the Cordillera Oriental of southern Peru (Ollantaytambo, Verónica, San José, Sandia and Calapuja Formations) and northern Bolivia (Coroico, Amutara and Cancañiri Formations), and in the Upper Silurian to Devonian Lampa Formation on the Altiplano, and the Devonian Cabanillas Group on the Altiplano and the Peruvian Coastal Cordillera (Arequipa Massif). Our data contribute to a better understanding of the plate tectonic evolution of the Western Gondwana margin during early Paleozoic times

A newly identified secreted larval antigen elicits basophil-dependent protective immunity against N. brasiliensis infection

Hookworms infect more that 400 million people and cause significant socio-economic burden on endemic countries. The lack of efficient vaccines and the emergence of anthelminthic drug resistance are of major concern. Free-living hookworm larvae infect their hosts via the skin and live as adult worms in the small intestine where they feed on host tissue and blood. Excretory/secretory (E/S) products, released by helminths as they migrate through their host, are thought to play a key role in facilitating infection and successful establishment of parasitism. However, E/S products can also elicit protective immune responses that might be harnessed for vaccine development. By performing Western blots with serum of Nippostrongylus brasiliensis (Nb) infected mice as a model for human hookworm infection, we identified a largely overlapping set of IgG1- and IgE-reactive antigens in E/S from infective L3 stage larvae. Mass spectrometry analysis led to the identification of a new protein family with 6 paralogues in the Nb genome which we termed Nb-LSA1 for “Nippostrongylus brasiliensis larval secreted protein 1”. The recombinantly expressed 17 kDa family member Nb-LSA1a was recognized by antibodies in the serum of Nb immune mice. Immunization of mice with Nb-LSA1a in alum elicited a strong IgG1 response but no detectable antigen-specific IgE. Most importantly, immunized mice were largely protected against a challenge Nb infection. This effect was dependent on the presence of basophils and occurred before the parasites reached the intestine. Therefore, basophils appear to play a critical role for rapid control of infection with L3 stage larvae in mice immunized with a single secreted larval protein. A better understanding of basophil-mediated protective immunity and identification of potent larval antigens of human hookworms could help to develop promising vaccination strategies

Contribution of smoking and air pollution exposure in urban areas to social differences in respiratory health

<p>Abstract</p> <p>Background</p> <p>Socio-economic status, smoking, and exposure to increased levels of environmental air pollution are associated with adverse effects on respiratory health. We assessed the contribution of occupational exposures, smoking and outdoor air pollution as competing factors for the association between socio-economic status and respiratory health indicators in a cohort of women from the Ruhr area aged 55 at the time of investigation between 1985 and 1990.</p> <p>Methods</p> <p>Data of 1251 women with spirometry and complete questionnaire information about respiratory diseases, smoking and potential confounders were used in the analyses. Exposure to large-scale air pollution was assessed with data from monitoring stations. Exposure to small-scale air pollution was assessed as traffic-related exposure by distance to the nearest major road. Socio-economic status was defined by educational level. Multiple regression models were used to estimate the contribution of occupational exposures, smoking and outdoor air pollution to social differences in respiratory health.</p> <p>Results</p> <p>Women with less than 10 years of school education in comparison to more than 10 years of school education were more often occupationally exposed (16.4% vs. 10.1%), smoked more often (20.3% vs. 13.9%), and lived more often close to major roads (26.0% vs. 22.9%). Long-term exposure to increased levels of PM₁₀was significantly associated with lower school education. Women with low school education were more likely to suffer from respiratory symptoms and had reduced lung function. In the multivariate analysis the associations between education and respiratory health attenuated after adjusting for occupational exposure, smoking and outdoor air pollution. The crude odds ratio for the association between the lung function indicator FEV₁less than 80% of predicted value and educational level (<10 years vs. >10 years of school education) was 1.83 (95% CI: 1.22–2.74). This changed to 1.56 (95% CI: 1.03–2.37) after adjusting for occupational exposure, smoking and outdoor air pollution.</p> <p>Conclusion</p> <p>We found an association between socio-economic status and respiratory health. This can partly be explained by living conditions indicated by occupational exposure, smoking behaviour and ambient air pollution. A relevant part of the social differences in respiratory health, however, remained unexplained.</p

Decompressive craniectomy plus best medical treatment versus best medical treatment alone for spontaneous severe deep supratentorial intracerebral haemorrhage:a randomised controlled clinical trial

BACKGROUND: It is unknown whether decompressive craniectomy improves clinical outcome for people with spontaneous severe deep intracerebral haemorrhage. The SWITCH trial aimed to assess whether decompressive craniectomy plus best medical treatment in these patients improves outcome at 6 months compared to best medical treatment alone.METHODS: In this multicentre, randomised, open-label, assessor-blinded trial conducted in 42 stroke centres in Austria, Belgium, Finland, France, Germany, the Netherlands, Spain, Sweden, and Switzerland, adults (18-75 years) with a severe intracerebral haemorrhage involving the basal ganglia or thalamus were randomly assigned to receive either decompressive craniectomy plus best medical treatment or best medical treatment alone. The primary outcome was a score of 5-6 on the modified Rankin Scale (mRS) at 180 days, analysed in the intention-to-treat population. This trial is registered with ClincalTrials.gov, NCT02258919, and is completed.FINDINGS: SWITCH had to be stopped early due to lack of funding. Between Oct 6, 2014, and April 4, 2023, 201 individuals were randomly assigned and 197 gave delayed informed consent (96 decompressive craniectomy plus best medical treatment, 101 best medical treatment). 63 (32%) were women and 134 (68%) men, the median age was 61 years (IQR 51-68), and the median haematoma volume 57 mL (IQR 44-74). 42 (44%) of 95 participants assigned to decompressive craniectomy plus best medical treatment and 55 (58%) assigned to best medical treatment alone had an mRS of 5-6 at 180 days (adjusted risk ratio [aRR] 0·77, 95% CI 0·59 to 1·01, adjusted risk difference [aRD] -13%, 95% CI -26 to 0, p=0·057). In the per-protocol analysis, 36 (47%) of 77 participants in the decompressive craniectomy plus best medical treatment group and 44 (60%) of 73 in the best medical treatment alone group had an mRS of 5-6 (aRR 0·76, 95% CI 0·58 to 1·00, aRD -15%, 95% CI -28 to 0). Severe adverse events occurred in 42 (41%) of 103 participants receiving decompressive craniectomy plus best medical treatment and 41 (44%) of 94 receiving best medical treatment.INTERPRETATION: SWITCH provides weak evidence that decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep intracerebral haemorrhage. The results do not apply to intracerebral haemorrhage in other locations, and survival is associated with severe disability in both groups.FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Inselspital Stiftung, and Boehringer Ingelheim.</p

Decompressive craniectomy plus best medical treatment versus best medical treatment alone for spontaneous severe deep supratentorial intracerebral haemorrhage: a randomised controlled clinical trial

Background It is unknown whether decompressive craniectomy improves clinical outcome for people with spontaneous severe deep intracerebral haemorrhage. The SWITCH trial aimed to assess whether decompressive craniectomy plus best medical treatment in these patients improves outcome at 6 months compared to best medical treatment alone. Methods In this multicentre, randomised, open-label, assessor-blinded trial conducted in 42 stroke centres in Austria, Belgium, Finland, France, Germany, the Netherlands, Spain, Sweden, and Switzerland, adults (18–75 years) with a severe intracerebral haemorrhage involving the basal ganglia or thalamus were randomly assigned to receive either decompressive craniectomy plus best medical treatment or best medical treatment alone. The primary outcome was a score of 5–6 on the modified Rankin Scale (mRS) at 180 days, analysed in the intention-to-treat population. This trial is registered with ClincalTrials.gov , NCT02258919 , and is completed. Findings SWITCH had to be stopped early due to lack of funding. Between Oct 6, 2014, and April 4, 2023, 201 individuals were randomly assigned and 197 gave delayed informed consent (96 decompressive craniectomy plus best medical treatment, 101 best medical treatment). 63 (32%) were women and 134 (68%) men, the median age was 61 years (IQR 51–68), and the median haematoma volume 57 mL (IQR 44–74). 42 (44%) of 95 participants assigned to decompressive craniectomy plus best medical treatment and 55 (58%) assigned to best medical treatment alone had an mRS of 5–6 at 180 days (adjusted risk ratio [aRR] 0·77, 95% CI 0·59 to 1·01, adjusted risk difference [aRD] −13%, 95% CI −26 to 0, p=0·057). In the per-protocol analysis, 36 (47%) of 77 participants in the decompressive craniectomy plus best medical treatment group and 44 (60%) of 73 in the best medical treatment alone group had an mRS of 5–6 (aRR 0·76, 95% CI 0·58 to 1·00, aRD −15%, 95% CI −28 to 0). Severe adverse events occurred in 42 (41%) of 103 participants receiving decompressive craniectomy plus best medical treatment and 41 (44%) of 94 receiving best medical treatment. Interpretation SWITCH provides weak evidence that decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep intracerebral haemorrhage. The results do not apply to intracerebral haemorrhage in other locations, and survival is associated with severe disability in both groups. Funding Swiss National Science Foundation, Swiss Heart Foundation, Inselspital Stiftung, and Boehringer Ingelheim

Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

Chronic obstructive pulmonary disease (COPD) and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking and exert a considerable societal burden. People suffering from COPD are at higher risk of developing lung cancer than those without, and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower postoperative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we provide a detailed overview of possible underlying factors that link COPD and lung cancer, and current therapeutic advances from both human and preclinical animal models that can effectively mitigate this unholy relationship

Discourse and Regulation Failures: The Ambivalent Influence of NGOs on Political Organizations

In the last decades, NGOs have become an important participant in the work of political organizations (e.g., national authorities, the EU or the UN). This development brings many opportunities and also some challenges, including discourse failure which is one of the topics discussed in this paper. We present a case study that illustrates the interdependence of discourse failure and regulations failure. We conclude that discourse failure is frequently not merely an accidental by-product, but rather, a non-intended consequence of deliberate NGOs’ campaigns. We make particular note of probable discourse failure when campaigns attempt to deal with complex issues in an environment rife with wide-spread prejudices and where the NGO’s work is transparent. In this situation, regulation failure may be consequent upon discourse failure. We present collectively binding commitments for NGOs and binding services enforced by political organizations to prevent discourse failure. In conclusion, we argue that the field of political economy can benefit from this challenging environment if it systematically researches the interdependencies between discourses and regulations.In den letzten Jahrzehnten kamen NGOs als wichtige Akteure im politischen Regelsetzungsprozess hinzu (z. B. in der EU, der UN und auch auf den nationalen Ebenen). Aus dieser Entwicklung ergeben sich für die Zivilgesellschaft vielfältige Chancen, allerdings auch einige Herausforderungen. Zu den Herausforderungen zählt unter anderem Diskursversagen, woraus häufig Regulierungsversagen resultiert. Der Beitrag präsentiert eine Fallstudie, die das Zusammenspiel aus Diskurs- und Regulierungsversagen aufzeigt. Das Beispiel illustriert, dass Diskursversagen nicht nur ein zufälliger Nebeneffekt von öffentlichen Diskursen ist, sondern eine nicht-intendierte Folge zielgerichteter Kampagnen von NGOs sein kann. Insbesondere Kampagnen, die sich mit komplexen Themen auseinandersetzen, über die es in der Öffentlichkeit weitverbreitete Vorurteile gibt, neigen zu Diskursversagen. Durch transparente Kampagnen seitens der NGOs wird dies sogar begünstigt. Zur Überwindung dieser Defizite stellt der Beitrag verschiedene Bindungsmechanismen für NGOs und Bindungsservices durch Behörden und Politik vor. Abschließend zeigt der Beitrag auf, dass die Politische Ökonomik davon profitieren kann, wenn sie systematisch das Zusammenspiel zwischen Diskurs und Regulierung erforscht