Oral vinorelbine and cisplatin with concomitant radiotherapy in stage III non-small cell lung cancer (NSCLC): A feasibility study

Background: Concurrent chemoradiotherapy has improved survival in inoperable stage III non-small cell lung cancer (NSCLC). This phase I trial was performed in order to establish a dose recommendation for oral vinorelbine in combination with cisplatin and simultaneous radiotherapy. Patients and Methods: Previously untreated patients with stage IIIB NSCLC received concurrent chemoradiotherapy with 66 Gy and 2 cycles of cisplatin and oral vinorelbine which was administered at 3 different levels (40, 50 and 60 mg/m(2)). This was to be followed by 2 cycles of cisplatin/vinorelbine oral consolidation chemotherapy. The study goal was to determine the maximal recommended dose of oral vinorelbine during concurrent treatment. Results: 11 stage IIIB patients were entered into the study. The median radiotherapy dose was 66 Gy. Grade 3-4 toxicity included neutropenia, esophagitis, gastritis and febrile neutropenia. The dose-limiting toxicity for concurrent chemoradiotherapy was esophagitis. 9 patients received consolidation chemotherapy, with neutropenia and anemia/thrombocytopenia grade 3 being the only toxicities. The overall response was 73%. Conclusion: Oral vinorelbine 50 mg/m(2) (days 1, 8, 15 over 4 weeks) in combination with cisplatin 20 mg/m2 (days 1-4) is the recommended dose in combination with radiotherapy (66 Gy) and will be used for concurrent chemoradiotherapy in a forthcoming phase III trial testing the efficacy of consolidation chemotherapy in patients not progressing after chemoradiotherapy

Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia.

Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = -0.71 to -1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = -0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10-6, 1.7 × 10-9, 3.5 × 10-12 and 1.0 × 10-4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes

Psychological morbidity as a moderator of intention to quit smoking : a study of smokers and former smokers

Objective: To analyze psychological morbidity as a moderator of the relationship between smoking representations and quality of life in smokers and former smokers, as well as to determine which psychological variables discriminate between smokers with and without the intention to quit smoking. Methods: This was a quantitative, correlational cross-sectional study involving a convenience sample of 224 smokers and 169 former smokers. Results: In smokers and former smokers, psychological morbidity had a moderating effect on the relationship between mental/physical quality of life and smoking representations (cognitive representations, emotional representations, and comprehensibility). Smokers with the intention to quit smoking more often presented with low comprehensibility, threatening emotional representations, behavioral beliefs, and perceived behavioral control, as well as with normative/control beliefs, than did those without the intention to quit. Conclusions: The results of this study underscore the importance of the moderating effect exerted by psychological morbidity, as well as that of sociocognitive variables, among smokers who have the intention to quit smoking.ResumoObjetivo: Analisar a morbidade psicológica como um moderador na relação entre as representações do tabaco e a qualidade de vida em fumantes e ex-fumantes, assim como conhecer as variáveis psicológicas que discriminam os fumantes com e sem intenção para deixar de fumar. Métodos: Estudo quantitativo, correlacional e transversal com uma amostra de conveniência constituída por 224 fumantes e 169 ex-fumantes. Resultados: Verificou-se um efeito moderador da morbidade psicológica na relação entre a qualidade de vida (física e mental) e as representações do tabaco (representações cognitivas e emocionais e compreensão) nos fumantes e nos ex-fumantes. Os fumantes com intenção para deixar de fumar apresentavam menor compreensão, representações emocionais mais ameaçadoras, mais crenças de comportamento, maior controle comportamental percebido e mais crenças normativas/controle do que aqueles sem essa intenção. Conclusões: Os resultados deste estudo enfatizam a importância da morbidade psicológica como moderadora, bem como das variáveis sociocognitivas, junto dos fumantes que querem deixar de fumar

Kinetics of the hydrogen abstraction ·C2H5 + alkane → C2H6 + alkyl reaction class: an application of the reaction class transition state theory

This paper presents an application of the reaction class transition state theory (RC-TST) to predict thermal rate constants for hydrogen abstraction reactions at alkane by the C2H5 radical on-the-fly. The linear energy relationship (LER), developed for acyclic alkanes, was also proven to hold for cyclic alkanes. We have derived all RCTST parameters from rate constants of 19 representative reactions, coupling with LER and the barrier height grouping (BHG) approach. Both the RC-TST/LER, where only reaction energy is needed, and the RC-TST/BHG, where no other information is needed, can predict rate constants for any reaction in this reaction class with satisfactory accuracy for combustion modeling. Our analysis indicates that less than 50% systematic errors on the average exist in the predicted rate constants using either the RC-TST/LER or RC-TST/BHG method, while in comparison with explicit rate calculations, the differences are within a factor of 2 on the average. The results also show that the RC-TST method is not sensitive to the choice of density functional theory used

Land Law, Property Ideologies and the British-Irish relationship

English and Irish land law are deeply influenced by the historical context of the British-Irish relationship, yet property scholarship comparing the two jurisdictions is surprisingly rare. The current Brexit negotiations provide a timely reminder of the strategic importance of property and trade relations between the two countries; and of their related-but-different legal cultures. In this article we examine how the property cultures of England and Ireland were shaped by the politics and practices of land tenure, by competing economic and property ideologies, and by the influence of both on national identity and statehood in both jurisdictions. The article reveals the role of local contexts and events in shaping land reform, and demonstrates the fertile potential of the comparative frame to contextualise each jurisdiction’s doctrines and practices. As domestic land law systems are drawn together in the context of emerging EU jurisdiction over areas like mortgage credit, each jurisdiction’s underpinning ideological commitments have important implications for the ease – or not – of attempts to harmonize member state practices. We explain the alignments and divergences between domestic underpinnings of Irish and English law, and reflect on the implications of our findings for contemporary property problems in the context of evolving economic and political relationships between the UK and Ireland

A scoping review of the implications of adult obesity in the delivery and acceptance of dental care.

Background Due to the increasing prevalence of obesity within the general population it is presumed that the prevalence of overweight and obese adults accessing dental services will also increase. For this reason dentists need to be aware of implications of managing such patients.Methods A scoping review was carried out. Both Medline via OVID and Scopus databases were searched along with grey literature databases and the websites of key organizations. Inclusion and exclusion criteria were established. The data were collected on a purpose-made data collection form and analysed descriptively.Results The review identified 28 relevant published articles and two relevant items of grey literature. Following review of this literature three themes relating to adult obesity in the delivery and acceptance of dental care emerged; clinical, service delivery and patient implications. The majority of the papers focused on the clinical implications.Conclusion On the topic of adult obesity and dental care, the majority of published and grey literature focuses on the clinical implications. Further research is needed on both the patients' perspectives of being overweight or obese and the delivery and acceptance of dental care and the service delivery implications

Genetic variability of hepatitis C virus before and after combined therapy of interferon plus ribavirin

We present an analysis of the selective forces acting on two hepatitis C virus genome regions previously postulated to be involved in the viral response to combined antiviral therapy. One includes the three hypervariable regions in the envelope E2 glycoprotein, and the other encompasses the PKR binding domain and the V3 domain in the NS5A region. We used a cohort of 22 non-responder patients to combined therapy (interferon alpha-2a plus ribavirin) for which samples were obtained before initiation of therapy and after 6 or/and 12 months of treatment. A range of 25-100 clones per patient, genome region and time sample were sequenced. These were used to detect general patterns of adaptation, to identify particular adaptation mechanisms and to analyze the patterns of evolutionary change in both genome regions. These analyses failed to detect a common adaptive mechanism for the lack of response to antiviral treatment in these patients. On the contrary, a wide range of situations were observed, from patients showing no positively selected sites to others with many, and with completely different topologies in the reconstructed phylogenetic trees. Altogether, these results suggest that viral strategies to evade selection pressure from the immune system and antiviral therapies do not result from a single mechanism and they are likely based on a range of different alternatives, in which several different changes, or their combination, along the HCV genome confer viruses the ability to overcome strong selective [email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected]

Parasite fate and involvement of infected cells in the induction of CD4+ and CD8+ T cell responses to Toxoplasma gondii

During infection with the intracellular parasite Toxoplasma gondii, the presentation of parasite-derived antigens to CD4+ and CD8+ T cells is essential for long-term resistance to this pathogen. Fundamental questions remain regarding the roles of phagocytosis and active invasion in the events that lead to the processing and presentation of parasite antigens. To understand the most proximal events in this process, an attenuated non-replicating strain of T. gondii (the cpsII strain) was combined with a cytometry-based approach to distinguish active invasion from phagocytic uptake. In vivo studies revealed that T. gondii disproportionately infected dendritic cells and macrophages, and that infected dendritic cells and macrophages displayed an activated phenotype characterized by enhanced levels of CD86 compared to cells that had phagocytosed the parasite, thus suggesting a role for these cells in priming naïve T cells. Indeed, dendritic cells were required for optimal CD4+ and CD8+ T cell responses, and the phagocytosis of heat-killed or invasion-blocked parasites was not sufficient to induce T cell responses. Rather, the selective transfer of cpsII-infected dendritic cells or macrophages (but not those that had phagocytosed the parasite) to naïve mice potently induced CD4+ and CD8+ T cell responses, and conferred protection against challenge with virulent T. gondii. Collectively, these results point toward a critical role for actively infected host cells in initiating T. gondii-specific CD4+ and CD8+ T cell responses

Advances in rapid compression machine studies of low- and intermediate-temperature autoignition phenomena

© 2017 Elsevier Ltd Rapid compression machines (RCMs) are widely used to acquire experimental insights into fuel autoignition and pollutant formation chemistry, especially at conditions relevant to current and future combustion technologies. RCM studies emphasize important experimental regimes, characterized by low- to intermediate-temperatures (600–1200 K) and moderate to high pressures (5–80 bar). At these conditions, which are directly relevant to modern combustion schemes including low temperature combustion (LTC) for internal combustion engines and dry low emissions (DLE) for gas turbine engines, combustion chemistry exhibits complex and experimentally challenging behaviors such as the chemistry attributed to cool flame behavior and the negative temperature coefficient regime. Challenges for studying this regime include that experimental observations can be more sensitive to coupled physical-chemical processes leading to phenomena such as mixed deflagrative/autoignitive combustion. Experimental strategies which leverage the strengths of RCMs have been developed in recent years to make RCMs particularly well suited for elucidating LTC and DLE chemistry, as well as convolved physical-chemical processes. Specifically, this work presents a review of experimental and computational efforts applying RCMs to study autoignition phenomena, and the insights gained through these efforts. A brief history of RCM development is presented towards the steady imp rovement in design, characterization, instrumentation and data analysis. Novel experimental approaches and measurement techniques, coordinated with computational methods are described which have expanded the utility of RCMs beyond empirical studies of explosion limits to increasingly detailed understanding of autoignition chemistry and the role of physical-chemical interactions. Fundamental insight into the autoignition chemistry of specific fuels is described, demonstrating the extent of knowledge of low-temperature chemistry derived from RCM studies, from simple hydrocarbons to multi-component blends and full-boiling range fuels. Emerging needs and further opportunities are suggested, including investigations of under-explored fuels and the implementation of increasingly higher fidelity diagnostics

Wound dressings for a proteolytic-rich environment

Wound dressings have experienced continuous and significant changes over the years based on the knowledge of the biochemical events associated with chronic wounds. The development goes from natural materials used to just cover and conceal the wound to interactive materials that can facilitate the healing process, addressing specific issues in non-healing wounds. These new types of dressings often relate with the proteolytic wound environment and the bacteria load to enhance the healing. Recently, the wound dressing research is focusing on the replacement of synthetic polymers by natural protein materials to delivery bioactive agents to the wounds. This article provides an overview on the novel protein-based wound dressings such as silk fibroin keratin and elastin. The improved properties of these dressings, like the release of antibiotics and growth factors, are discussed. The different types of wounds and the effective parameters of healing process will be reviewed