Preoperative CYFRA 21-1 and CEA as Prognostic Factors in Patients with Stage I Non-Small Cell Lung Cancer

Objective: To validate the prognostic value of preoperative levels of CYFRA 21-1, CEA and the corresponding tumor marker index (TMI) in patients with stage I non-small cell lung cancer (NSCLC). Methods: Two hundred forty stage I NSCLC patients (80 in pT1 and 160 in pT2; 100 squamous cell carcinomas, 91 adenocarcinomas, 32 large-cell carcinomas, 17 with other histologies; 171 males and 69 females) who had complete resection (R0) between 1986 and 2004 were included in the analysis. CYFRA 21-1 and CEA were measured using the Elecsys system (Roche) and AxSym-System (Abbott), respectively. Univariate analysis was performed using the Kaplan-Meier method to identify potential associations between survival and age, gender, CYFRA 21-1, CEA and TMI. Results: Overall 3- and 5-year survival rates were 74 and 64%, respectively. Male gender (p = 0.0009) and age 1 70 years (p = 0.0041) were associated with a worse prognosis; there were no differences between pT1 and pT2 nor between histological subtypes. Three- year survival was 72% for CYFRA 21-1 levels > 3.3 ng/ml versus 75% for levels 6.7 ng/ ml versus 75% for CEA 70 years were associated with a worse outcome, but elevated levels of CEA and CYFRA 21-1, and TMI risk were not. Copyright (C) 2008 S. Karger AG, Basel

Radiation-induced second malignancies after involved-node radiotherapy with deep-inspiration breath-hold technique for early stage Hodgkin Lymphoma: a dosimetric study

BACKGROUND: To estimate the risk of radiation induced second cancers after radiotherapy using deep-inspiration breath-hold (DI) technique with three-dimensional conformal (3DCRT) and volumetric arc therapy (VMAT) for patients with Hodgkin’s lymphoma (HL). METHODS: Early-stage HL with mediastinal and supraclavicular involvement was studied using an Alderson phantom. A whole body CT was performed and all tissues were delineated. The clinical target volumes and planning target volumes (PTV) were determined according to the German Hodgkin study group guidelines. Free-breathing (FB) technique and DI technique were simulated by different safety margins for the PTV definition. In both cases, 30 Gy in 15 fractions was prescribed. Second cancer risk was estimated for various tissues with a second cancer model including fractionation. RESULTS: When compared with FB-3DCRT, estimated relative life time attributable risk (LAR) of cancer induction after DI-3DCRT was 0.86, 0.76, 0.94 and 0.92 for breast, lung, esophagus and stomach, respectively. With DI-VMAT, the corresponding values were 2.05, 1.29, 1.01, 0.93, respectively. For breast cancer, the LAR observed with DI-VMAT was not substantially distinguishable from the LAR computed for mantle RT with an administered dose of 40 Gy. CONCLUSIONS: This study suggests that DI may reduce the LAR of secondary cancers of all OARs and may be a valuable technique when using 3DCRT. Conversely, VMAT may increase substantially the LAR and should be cautiously implemented in clinical practice

Sonoelastography of the Common Flexor Tendon of the Elbow with Histologic Agreement: A Cadaveric Study.

Purpose To determine the correlation of the results of conventional B-mode ultrasonography (US) and compression sonoelastography with histologic results in common flexor tendons of the elbow in human cadavers. Materials and Methods Twenty-five common flexor tendons were evaluated in 16 fresh, unembalmed cadavers of 11 women with a median age of 85 years (range, 71-101 years) and five men with a median age of 78 years (range, 70-88 years). Informed consent was provided according to the last will of the donors. B-mode US results were classified as grade 1, normal tendon with homogeneous fibrillar pattern; grade 2, tendon thickening or hypoechoic areas and/or calcifications in less than 30% of the tendon; or grade 3, hypoechoic areas and/or calcifications greater than 30% of the tendon. Sonoelastographic results were grade 1, blue (hardest) to green (hard); grade 2, yellow (soft); and grade 3, red (softest). The intraclass correlation coefficient was calculated to determine agreement with histologic findings for each B-mode US, sonoelastographic, and combined B-mode US and sonoelastographic examination. Histologic results were grade 1, normal, with parallel fibrillar pattern; grade 2, mild tendinopathy, with cellular infiltration, angiogenesis, or fatty vacuoles; or grade 3, severe tendinopathy, with loss of parallel collagen structure and necrosis. Results Histologic alterations were detected in 44% (11 of 25) of biopsy specimens. Intraclass correlation with histologic results was 0.57 for B-mode US, 0.68 for sonoelastography, and 0.84 for the combination of the two approaches. Conclusion The addition of sonoelastography to B-mode US provided statistically significant improvement in correlation with histologic results compared with the use of B-mode US alone (P \u3c .02). (©) RSNA, 2016 Online supplemental material is available for this article

Heilungs- oder Geistergeschichten? Post/koloniale Erinnerungen im belgischen AfricaMuseum

In Belgien findet eine kritische Aufarbeitung der Kolonialgeschichte nur sehr zögerlich statt. Erst anlässlich der Renovierung des AfricaMuseums (Tervuren bei Brüssel) kam Bewegung in die Debatte: sie gab den Anstoß zu einer Neukonzeptualisierung der Daueraustellung, mit der das Museum versucht, den kolonialen Blick auf Afrika durch eine Darstellung der Vielfalt, Schönheit und Resilienz afrikanischer Kultur und Natur zu ersetzen. Eine zentrale Komponente dieser versuchten Selbst-Dekolonisierung des Museums ist die künstlerische Intervention des Bildhauers Aimè Mpane (‚Congo Nouveau Souffle‘). Diese Ouvertüre analysiert mit den Instrumenten postkolonialer Traumatheorie die Erinnerungspolitiken, die an ‚Congo Nouveau Souffle‘ Haftung finden, und zeigt auf, dass postkoloniale Geschichtsschreibung nicht nur dekolonisierende, sondern auch rekolonisierende Effekte haben kann. Zentral bleibt daher die Frage, welcher postkoloniale Erinnerungsdiskurs am effektivsten zu einer Dekolonisierung europäisch-afrikanischer Beziehungen führt.Public and political discourses in Belgium are slow and hesitant to tackle the country’s colonial history. Only once the AfricaMuseum in Tervuren near Brussels started a multi-year renovation process, public debates around Belgium’s postcolonial memory started to increase. The museum itself aimed to decolonize its permanent exhibition, shifting from a colonial representation of Africa to a portrayal of the beauty and resilience of African culture and nature. Aimé Mpane’s statue ‘Congo Nouveau Souffle’, that replaced a bust of King Leopold II in the museum’s former entrance hall, plays a central role in the new (post)colonial narrative of the AfricaMuseum. This short article analyzes the post/colonial narratives that this statue gives rise to through the lens of postcolonial trauma theory and argues that postcolonial historiography can have both, decolonizing or recolonizing effect. The central question, therefore, is: Which postcolonial memory politics can best effect a decolonization of European-African relations

Exorcising Grice’s ghost : an empirical approach to studying intentional communication in animals

Language’s intentional nature has been highlighted as a crucial feature distinguishing it from other communication systems. Specifically, language is often thought to depend on highly structured intentional action and mutual mindreading by a communicator and recipient. Whilst similar abilities in animals can shed light on the evolution of intentionality, they remain challenging to detect unambiguously. We revisit animal intentional communication and suggest that progress in identifying analogous capacities has been complicated by (i) the assumption that intentional (that is, voluntary) production of communicative acts requires mental-state attribution, and (ii) variation in approaches investigating communication across sensory modalities. To move forward, we argue that a framework fusing research across modalities and species is required. We structure intentional communication into a series of requirements, each of which can be operationalised, investigated empirically, and must be met for purposive, intentionally communicative acts to be demonstrated. Our unified approach helps elucidate the distribution of animal intentional communication and subsequently serves to clarify what is meant by attributions of intentional communication in animals and humans

Dissenting Church: Exploring the Theological Power of Conflict and Disagreement

This book challenges the prevailing notion of stability, cohesiveness, and uniformity within Christian communities, inviting readers to view contestation and disagreement as integral to theological reflection and church identity. While the volume focuses predominantly on the Roman Catholic Church as a case study, various chapters broaden the exploration across other Christian and non-Christian traditions. Beginning with the philosophical and theological foundations of conflict, contestation, and community, the book subsequently focuses on four main conflict fields: liturgy, canon law, gender, and sexuality, as well as race and postcolonial critical theory. The book finishes with a constructive proposal on how to think theologically about identity and antagonisms, as well as how to construct an ecclesiology of dissent. Contributors employ diverse methodological perspectives to offer constructive theological reflections, enhancing both understanding and practice of theology in the context of polarised public debates. This is an open access book

Deterring discrimination with data

Discrimination on grounds of race, sex, and handicap persists in many local school districts in spite of nearly twenty years of sustained attention from federal policymakers. Because litigation proceeds slowly and expensively, and because administrative attacks on discrimination have been stymied by political controversy, additional policy strategies merit careful consideration. We studied the operation of one such strategy in nine local districts: the mandatory collection of data concerning civil rights matters in schools. Data collection and reporting shaped local compliance with civil rights laws in four ways: by threatening local officials with future penalties, by providing political ammunition to constituencies that care about civil rights, by allowing local districts to learn about their own performance, and by framing school practices in ways that heighten awareness about equity. In this policy setting, data collection has advantages and disadvantages that complement those of other enforcement strategies. In this and other policy settings, data collection has power to elicit compliance even in the absence of conventional enforcement.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45444/1/11077_2004_Article_BF00229728.pd

Assessment of Global Ocean Biogeochemistry Models for Ocean Carbon Sink Estimates in RECCAP2 and Recommendations for Future Studies

The ocean is a major carbon sink and takes up 25%–30% of the anthropogenically emitted CO2. A state-of-the-art method to quantify this sink are global ocean biogeochemistry models (GOBMs), but their simulated CO2 uptake differs between models and is systematically lower than estimates based on statistical methods using surface ocean pCO2 and interior ocean measurements. Here, we provide an in-depth evaluation of ocean carbon sink estimates from 1980 to 2018 from a GOBM ensemble. As sources of inter-model differences and ensemble-mean biases our study identifies (a) the model setup, such as the length of the spin-up, the starting date of the simulation, and carbon fluxes from rivers and into sediments, (b) the simulated ocean circulation, such as Atlantic Meridional Overturning Circulation and Southern Ocean mode and intermediate water formation, and (c) the simulated oceanic buffer capacity. Our analysis suggests that a late starting date and biases in the ocean circulation cause a too low anthropogenic CO2 uptake across the GOBM ensemble. Surface ocean biogeochemistry biases might also cause simulated anthropogenic fluxes to be too low, but the current setup prevents a robust assessment. For simulations of the ocean carbon sink, we recommend in the short-term to (a) start simulations at a common date before the industrialization and the associated atmospheric CO2 increase, (b) conduct a sufficiently long spin-up such that the GOBMs reach steady-state, and (c) provide key metrics for circulation, biogeochemistry, and the land-ocean interface. In the long-term, we recommend improving the representation of these metrics in the GOBMs

Cyclophilin inhibitors restrict Middle East respiratory syndrome coronavirus via interferon-λ in vitro and in mice

While severe coronavirus infections, including Middle East respiratory syndrome coronavirus (MERS-CoV), cause lung injury with high mortality rates, protective treatment strategies are not approved for clinical use. We elucidated the molecular mechanisms by which the cyclophilin inhibitors cyclosporin A (CsA) and alisporivir (ALV) restrict MERS-CoV to validate their suitability as readily available therapy in MERS-CoV infection. Calu-3 cells and primary human alveolar epithelial cells (hAECs) were infected with MERS-CoV and treated with CsA or ALV or inhibitors targeting cyclophilin inhibitor-regulated molecules including calcineurin, nuclear factor of activated T-cells (NFATs) or mitogen-activated protein kinases. Novel CsA-induced pathways were identified by RNA sequencing and manipulated by gene knockdown or neutralising antibodies. Viral replication was quantified by quantitative real-time PCR and 50% tissue culture infective dose. Data were validated in a murine MERS-CoV infection model. Both CsA and ALV reduced MERS-CoV titres and viral RNA replication in Calu-3 cells and hAECs, improving epithelial integrity. While neither calcineurin nor NFAT inhibition reduced MERS-CoV propagation, blockade of c-Jun N-terminal kinase diminished infectious viral particle release but not RNA accumulation. Importantly, CsA induced interferon regulatory factor 1 (IRF1), a pronounced type III interferon (IFNλ) response and expression of antiviral genes. Downregulation of IRF1 or IFNλ increased MERS-CoV propagation in the presence of CsA. Importantly, oral application of CsA reduced MERS-CoV replication in vivo, correlating with elevated lung IFNλ levels and improved outcome. We provide evidence that cyclophilin inhibitors efficiently decrease MERS-CoV replication in vitro and in vivo via upregulation of inflammatory antiviral cell responses, in particular IFNλ. CsA might therefore represent a promising candidate for treating MERS-CoV infection

The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with potential resistance to existing drugs emphasizes the need for new therapeutic modalities with broad variant activity. Here we show that ensovibep, a trispecific DARPin (designed ankyrin repeat protein) clinical candidate, can engage the three units of the spike protein trimer of SARS-CoV-2 and inhibit ACE2 binding with high potency, as revealed by cryo-electron microscopy analysis. The cooperative binding together with the complementarity of the three DARPin modules enable ensovibep to inhibit frequent SARS-CoV-2 variants, including Omicron sublineages BA.1 and BA.2. In Roborovski dwarf hamsters infected with SARS-CoV-2, ensovibep reduced fatality similarly to a standard-of-care monoclonal antibody (mAb) cocktail. When used as a single agent in viral passaging experiments in vitro, ensovibep reduced the emergence of escape mutations in a similar fashion to the same mAb cocktail. These results support further clinical evaluation of ensovibep as a broad variant alternative to existing targeted therapies for Coronavirus Disease 2019 (COVID-19)