Trends in the incidence of pulmonary nodules in chest computed tomography:10-year results from two Dutch hospitals

Objective: To study trends in the incidence of reported pulmonary nodules and stage I lung cancer in chest CT. Methods: We analyzed the trends in the incidence of detected pulmonary nodules and stage I lung cancer in chest CT scans in the period between 2008 and 2019. Imaging metadata and radiology reports from all chest CT studies were collected from two large Dutch hospitals. A natural language processing algorithm was developed to identify studies with any reported pulmonary nodule. Results: Between 2008 and 2019, a total of 74,803 patients underwent 166,688 chest CT examinations at both hospitals combined. During this period, the annual number of chest CT scans increased from 9955 scans in 6845 patients in 2008 to 20,476 scans in 13,286 patients in 2019. The proportion of patients in whom nodules (old or new) were reported increased from 38% (2595/6845) in 2008 to 50% (6654/13,286) in 2019. The proportion of patients in whom significant new nodules (≥ 5 mm) were reported increased from 9% (608/6954) in 2010 to 17% (1660/9883) in 2017. The number of patients with new nodules and corresponding stage I lung cancer diagnosis tripled and their proportion doubled, from 0.4% (26/6954) in 2010 to 0.8% (78/9883) in 2017. Conclusion: The identification of incidental pulmonary nodules in chest CT has steadily increased over the past decade and has been accompanied by more stage I lung cancer diagnoses. Clinical relevance statement: These findings stress the importance of identifying and efficiently managing incidental pulmonary nodules in routine clinical practice. Key Points: • The number of patients who underwent chest CT examinations substantially increased over the past decade, as did the number of patients in whom pulmonary nodules were identified. • The increased use of chest CT and more frequently identified pulmonary nodules were associated with more stage I lung cancer diagnoses.</p

An Investigation Comparing the Efficacy of Topical Ocular Application of Tacrolimus and Cyclosporine in Dogs

The purpose of this paper was to determine the efficacy and safety of topical tacrolimus, compared to cyclosporine, for treating keratoconjunctivitis sicca (KCS) in dogs. This study was a two-phase, randomized, controlled, masked clinical trial. Phase 1 evaluated ophthalmic 0.03% tacrolimus in normal dogs. Ocular examinations were performed daily. Phase 2 evaluated the efficacy of tacrolimus in treating KCS. Half the dogs received 2% cyclosporine A; the others received 0.03% tacrolimus, both diluted in olive oil. Four ophthalmic examinations were done over 12 weeks. There was no significant difference between groups in phase I. In phase 2, there was no significant difference in Schirmer tear test I (STT) results between the two groups, and both groups had a significant increase in STT over time. Both drugs were effective in increasing the STT in dogs naïve to lacrimostimulants. Tacrolimus was effective in increasing the STT in 4 dogs currently nonresponsive to cyclosporine

External sources of clean technology: evidence from the clean development mechanism

New technology is fundamental to sustainable development. However, inventors from industrialized countries often refuse technology transfer because they worry about reverse-engineering. When can clean technology transfer succeed? We develop a formal model of the political economy of North–South technology transfer. According to the model, technology transfer is possible if (1) the technology in focus has limited global commercial potential or (2) the host developing country does not have the capacity to absorb new technologies for commercial use. If both conditions fail, inventors from industrialized countries worry about the adverse competitiveness effects of reverse-engineering, so technology transfer fails. Data analysis of technology transfer in 4,894 projects implemented under the Kyoto Protocol’s Clean Development Mechanism during the 2004–2010 period provides evidence in support of the model

Development of a specific fluorescent phage endolysin for in situ detection of Clostridium species associated with cheese spoilage

Late blowing defect (LBD) is a major cause of spoilage in cheeses, caused by the growth of Clostridium spp. in the cheese matrix. We investigated the application of CTP1L, a bacteriophage endolysin active against Clostridium tyrobutyricum, and its enzymatically active and cell wall-binding domains (EAD and CBD) attached to green fluorescent protein (GFP) to detect dairy-related Clostridium species by fluorescence microscopy. GFP-CTP1L and GFP-CBD demonstrated specificity for Clostridium spp. by labelling 15 and 17 of 20 Clostridium strains, respectively, but neither bound to other members of the cheese microbiota. However, GFP-EAD did not label any Clostridium strain tested. Unexpectedly, GFP-CTP1L and GFP-CBD were also able to bind to clostridial spores. In addition, GFP-CBD allowed us to visualize the vegetative cells of C. tyrobutyricum directly in the matrix of a LBD cheese. Site-directed mutants of GFP-CTP1L and GFP-CBD were made to examine the amino acids involved in binding and oligomer formation. Oligomerization was not essential for binding, but specific mutations in the CBD which affected oligomer formation also affected binding and lytic activity. We conclude that GFP-CTP1L and GFP-CBD could be good biomarkers for rapid detection of Clostridium spores in milk, so measures can be taken for the prevention of LBD in cheese, and also provide effective tools to study the development of Clostridium populations during cheese ripening

Demand, supply, and restraint: Determinants of domestic water conflict and cooperation

This article focuses on one of the most likely empirical manifestations of the "environment-conflict" claim by examining how demand for and supply of water may lead to domestic water conflict. It also studies what factors may reduce the risk of conflict and, hence, induce cooperation. To this end, the article advances several theory-based arguments about the determinants of water conflict and cooperation, and then analyzes time-series cross-section data for 35 Mediterranean, Middle Eastern, and Sahel countries between 1997 and 2009. The empirical results show that demand-side drivers, such as population pressure, agricultural productivity, and economic development are likely to have a stronger impact on water conflict risk than supply-side factors, represented by climate variability. The analysis also reveals that violent water conflicts are extremely rare, and that factors conducive to restraint, such as stable political conditions, may stimulate cooperation. Overall, these results suggest that the joint analysis of demand, supply, and restraint improves our ability to account for domestic water-related conflict and cooperation

Modeling preference and willingness to pay for drought tolerance (DT) in maize in rural Zimbabwe

Maize plays a leading role in the food security of millions in southern Africa, yet it is highly vulnerable to the moisture stress brought about by the erratic rainfall patterns that characterize weather systems in the area. Developing and making drought-tolerant maize varieties available to farmers in the region has thus long been a key goal on the regional development agenda. Farm-level adoption of these varieties, however, depends on local perceptions of the value they add, along with willingness to pay (WTP) for it. Focusing on Zimbabwe, this research aimed at estimating the implicit prices farmers are willing to pay for drought tolerance in maize compared to other preferred traits. Using a choice experiment framework, we generated 12,600 observations from a random sample of 1,400 households in communal areas within 14 districts of Zimbabwe. Taste parameters and heterogeneities were estimated using the generalized multinomial logit model (G-MNL). The results reveal drought tolerance, grain yield, covered cob tip, cob size, and semi-flint texture to be the most preferred traits by farm households in Zimbabwe. The WTP estimates show that farmers are willing to pay a premium for drought tolerance equal to 2.56, 7, 3.2, and 5 times higher than for an additional ton of yield per acre, bigger cob size, larger grain size, and covered cob tip, respectively. We suggest designing and implementing innovative ways of promoting DT maize along with awareness-raising activities to enhance contextual understandings of drought and drought risk to speed adoption of new DT maize varieties by risk-prone farming communities. Given the high level of rural literacy and the high rate of adoption of improved maize, trait-based promotion and marketing of varieties constitutes the right strategy

Tissue-engineered dermo-epidermal skin analogs exhibit de novo formation of a near natural neurovascular link 10 weeks after transplantation

PURPOSE: Human autologous tissue-engineered skin grafts are a promising way to cover skin defects. Clearly, it is mandatory to study essential biological dynamics after transplantation, including reinnervation. Previously, we have already shown that human tissue-engineered skin analogs are reinnervated by host nerve fibers as early as 8 weeks after transplantation. In this study, we tested the hypothesis that there is a de novo formation of a "classical" neurovascular link in tissue-engineered and then transplanted skin substitutes. METHODS: Keratinocytes, melanocytes, and fibroblasts were isolated from human skin biopsies. After expansion in culture, keratinocytes and melanocytes were seeded on dermal fibroblast-containing collagen type I hydrogels. These human tissue-engineered dermo-epidermal skin analogs were transplanted onto full-thickness skin wounds on the back of immuno-incompetent rats. Grafts were analyzed after 3 and 10 weeks. Histological sections were examined with regard to the ingrowth pattern of myelinated and unmyelinated nerve fibers into the skin analogs using markers such as PGP9.5, NF-200, and NF-160. Blood vessels were identified with CD31, lymphatic vessels with Lyve1. In particular, we focused on alignment patterns between nerve fibers and either blood and/or lymphatic vessels with regard to neurovascular link formation. RESULTS: 3 weeks after transplantation, blood vessels, but no nerve fibers or lymphatic vessels could be observed. 10 weeks after transplantation, we could detect an ingrowth of myelinated and unmyelinated nerve fibers into the skin analogs. Nerve fibers were found in close proximity to CD31-positive blood vessels, but not alongside Lyve1-positive lymphatic vessels. CONCLUSION: These data suggest that host-derived innervation of tissue-engineered dermo-epidermal skin analogs is initiated by and guided alongside blood vessels present early post-transplantation. This observation is consistent with the concept of a cross talk between neurovascular structures, known as the neurovascular link

Worldwide comparison of survival from childhood leukaemia for 1995–2009, by subtype, age, and sex (CONCORD-2): a population-based study of individual data for 89 828 children from 198 registries in 53 countries

Background Global inequalities in access to health care are reflected in differences in cancer survival. The CONCORD programme was designed to assess worldwide differences and trends in population-based cancer survival. In this population-based study, we aimed to estimate survival inequalities globally for several subtypes of childhood leukaemia. Methods Cancer registries participating in CONCORD were asked to submit tumour registrations for all children aged 0-14 years who were diagnosed with leukaemia between Jan 1, 1995, and Dec 31, 2009, and followed up until Dec 31, 2009. Haematological malignancies were defined by morphology codes in the International Classification of Diseases for Oncology, third revision. We excluded data from registries from which the data were judged to be less reliable, or included only lymphomas, and data from countries in which data for fewer than ten children were available for analysis. We also excluded records because of a missing date of birth, diagnosis, or last known vital status. We estimated 5-year net survival (ie, the probability of surviving at least 5 years after diagnosis, after controlling for deaths from other causes [background mortality]) for children by calendar period of diagnosis (1995-99, 2000-04, and 2005-09), sex, and age at diagnosis (< 1, 1-4, 5-9, and 10-14 years, inclusive) using appropriate life tables. We estimated age-standardised net survival for international comparison of survival trends for precursor-cell acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Findings We analysed data from 89 828 children from 198 registries in 53 countries. During 1995-99, 5-year agestandardised net survival for all lymphoid leukaemias combined ranged from 10.6% (95% CI 3.1-18.2) in the Chinese registries to 86.8% (81.6-92.0) in Austria. International differences in 5-year survival for childhood leukaemia were still large as recently as 2005-09, when age-standardised survival for lymphoid leukaemias ranged from 52.4% (95% CI 42.8-61.9) in Cali, Colombia, to 91.6% (89.5-93.6) in the German registries, and for AML ranged from 33.3% (18.9-47.7) in Bulgaria to 78.2% (72.0-84.3) in German registries. Survival from precursor-cell ALL was very close to that of all lymphoid leukaemias combined, with similar variation. In most countries, survival from AML improved more than survival from ALL between 2000-04 and 2005-09. Survival for each type of leukaemia varied markedly with age: survival was highest for children aged 1-4 and 5-9 years, and lowest for infants (younger than 1 year). There was no systematic difference in survival between boys and girls. Interpretation Global inequalities in survival from childhood leukaemia have narrowed with time but remain very wide for both ALL and AML. These results provide useful information for health policy makers on the effectiveness of health-care systems and for cancer policy makers to reduce inequalities in childhood survival