Anticancer drug clustering in lung cancer based on gene expression profiles and sensitivity database

BACKGROUND: The effect of current therapies in improving the survival of lung cancer patients remains far from satisfactory. It is consequently desirable to find more appropriate therapeutic opportunities based on informed insights. A molecular pharmacological analysis was undertaken to design an improved chemotherapeutic strategy for advanced lung cancer. METHODS: We related the cytotoxic activity of each of commonly used anti-cancer agents (docetaxel, paclitaxel, gemcitabine, vinorelbine, 5-FU, SN38, cisplatin (CDDP), and carboplatin (CBDCA)) to corresponding expression pattern in each of the cell lines using a modified NCI program. RESULTS: We performed gene expression analysis in lung cancer cell lines using cDNA filter and high-density oligonucleotide arrays. We also examined the sensitivity of these cell lines to these drugs via MTT assay. To obtain our reproducible gene-drug sensitivity correlation data, we separately analyzed two sets of lung cancer cell lines, namely 10 and 19. In our gene-drug correlation analyses, gemcitabine consistently belonged to an isolated cluster in a reproducible fashion. On the other hand, docetaxel, paclitaxel, 5-FU, SN-38, CBDCA and CDDP were gathered together into one large cluster. CONCLUSION: These results suggest that chemotherapy regimens including gemcitabine should be evaluated in second-line chemotherapy in cases where the first-line chemotherapy did not include this drug. Gene expression-drug sensitivity correlations, as provided by the NCI program, may yield improved therapeutic options for treatment of specific tumor types

World Atlas of Desertification - Introductory Brochure

The brochure introduces the concept of the World Atlas of Desertification which relies on converging evidence of combined human-environment processes pointing out that land degradation cannot be modeled satisfactorily at global scales.The introductory brochure provides a short overview of the main land degradation issues, through illustration of a number key global datasets and some case study examples that reflect the global patterns and pathways to solutions. The brochure start with highlighting the human dominance that drives global environmental changes. The consequences of feeding a growing population include agriculture expansion and intensification, illustrated by maps and data on irrigation and nutrient use. Aridity and drought are important phenomena aggravating the already present human pressures on the environment. Other pressure patterns playing at global scale are illustrated with examples from China, India, S. America and the Sahel, along with a forward view on solutions.JRC.H.5-Land Resources Managemen

Realist review of just transition

The Independent Evaluation Unit of the Green Climate Fund and the International Labour Organisation are jointly undertaking a rigorous and precise global evidence review of interventions that could be regarded as aiming at outcomes consistent with a just transition in non-Annex I countries, specifically in the energy, agriculture, and infrastructure sectors and in ecosystem services. This approach paper describes this research in detail and sets out the realist approach to reviewing just transition. It identifies the need for a just transition, the paucity of evidence in non-Annex I countries and hence the case for this GCF–IEU / ILO evidence review. It also introduces the four systems to examine: energy, agriculture/food, infrastructure and ecosystem services. It also details the review's scope and objectives and explains the methods to be applied, including the search strategy, data screening, data extraction and management, data synthesis, and learning and uptake of findings

How active are women who play bingo: a cross-sectional study from the Well!Bingo project

BackgroundThe benefits of physical activity are well established, yet large numbers of people are not sufficiently active to gain health benefits. Certain population groups are less physically active than others, including older women from areas of high economic deprivation. The Well!Bingo project was established with the aim of engaging such women in the development of a health promotion intervention in a bingo club. This paper reports on the assessment of health status, physical activity and sedentary behaviour of women attending a bingo club in central Scotland, UK as part of the Well!Bingo project.MethodsWomen attending the bingo club were invited to provide information on demographic characteristics, and self-reported physical activity and sedentary behaviour via a self-complete questionnaire as part of a cross-sectional study (n = 151). A sub-sample (n = 29) wore an accelerometer for an average of 5.7 ± 1.4 days. Differences between younger (under 60 years) and older adults (60 years and over) were assessed using a chi-square test for categorical data and the independent samples t-test was used to assess continuous data (p < 0.05).ResultsThe mean age was 56.5 ± 17.7 years, with 57% living in areas of high deprivation (Scottish Index of Multiple Deprivation quintile one and two). Sixty-three percent of women (n = 87) reported they were meeting physical activity guidelines. However, objective accelerometer data showed that, on average, only 18.1 ± 17.3 min a day were spent in moderate to vigorous physical activity. Most accelerometer wear time was spent sedentary (9.6 ± 1.7 h). For both self-report and accelerometer data, older women were significantly less active and more sedentary than younger women. On average, older women spent 1.8 h more than younger women in sedentary activities per day, and took part in 21 min less moderate to vigorous physical activity (9.4 mins per day).ConclusionThe findings of this study suggest that bingo clubs are settings that attract women from areas of high deprivation and older women in bingo clubs in particular would benefit from interventions to target their physical activity and sedentary behaviour. Bingo clubs may therefore be potential intervention settings in which to influence these behaviours

Heterogeneity in outcomes of treated HIV-positive patients in Europe and North America: relation with patient and cohort characteristics

Background HIV cohort collaborations, which pool data from diverse patient cohorts, have provided key insights into outcomes of antiretroviral therapy (ART). However, the extent of, and reasons for, between-cohort heterogeneity in rates of AIDS and mortality are unclear. Methods We obtained data on adult HIV-positive patients who started ART from 1998 without a previous AIDS diagnosis from 17 cohorts in North America and Europe. Patients were followed up from 1 month to 2 years after starting ART. We examined between-cohort heterogeneity in crude and adjusted (age, sex, HIV transmission risk, year, CD4 count and HIV-1 RNA at start of ART) rates of AIDS and mortality using random-effects meta-analysis and meta-regression. Results During 61 520 person-years, 754/38 706 (1.9%) patients died and 1890 (4.9%) progressed to AIDS. Between-cohort variance in mortality rates was reduced from 0.84 to 0.24 (0.73 to 0.28 for AIDS rates) after adjustment for patient characteristics. Adjusted mortality rates were inversely associated with cohorts' estimated completeness of death ascertainment [excellent: 96-100%, good: 90-95%, average: 75-89%; mortality rate ratio 0.66 (95% confidence interval 0.46-0.94) per category]. Mortality rate ratios comparing Europe with North America were 0.42 (0.31-0.57) before and 0.47 (0.30-0.73) after adjusting for completeness of ascertainment. Conclusions Heterogeneity between settings in outcomes of HIV treatment has implications for collaborative analyses, policy and clinical care. Estimated mortality rates may require adjustment for completeness of ascertainment. Higher mortality rate in North American, compared with European, cohorts was not fully explained by completeness of ascertainment and may be because of the inclusion of more socially marginalized patients with higher mortality ris

Accessing and engaging women from socio-economically disadvantaged areas: a participatory approach to the design of a public health intervention for delivery in a Bingo club

Background Our aim was to use participatory methods to investigate the feasibility and acceptability of using Bingo clubs for the design and delivery of an evidence-based physical activity and/or healthy eating intervention to socio-economically disadvantaged women. This paper describes the participatory process that has resulted in a physical activity intervention for women aged >55years, ready for pilot-testing in a Bingo club setting. Methods Studies using different quantitative and qualitative approaches were conducted among customers and staff of a Bingo club in a city of 85,000 inhabitants in central Scotland. These were designed to take the views of different stakeholders into account, with a view to enhancing uptake, engagement and effectiveness with any proposed intervention. Results Sixteen relevant studies were identified in a literature review that generated ideas for intervention components. A questionnaire completed by 151 women in the Bingo club showed that almost half (47%) aged >55years were not meeting physical activity guidelines; evidence backed up by accelerometer data from 29 women. Discussions in six focus groups attended by 27 club members revealed different but overlapping motivations for attending the Bingo club (social benefits) and playing Bingo (cognitive benefits). There was some scepticism as to whether the Bingo club was an appropriate setting for an intervention, and a dietary intervention was not favoured. It was clear that any planned intervention needed to utilise the social motivation and habitual nature of attendance at the Bingo club, without taking women away from Bingo games. These results were taken forward to a 5-h long participative workshop with 27 stakeholders (including 19 Bingo players). Intervention design (form and content) was then finalised during two round table research team meetings. Conclusions It was possible to access and engage with women living in areas of socio-economic disadvantage through a Bingo club setting. A physical activity intervention for women >55years is realistic for recruitment, will address the needs of potential recipients in the Bingo club, appears to be feasible and acceptable to club members and staff, and has been designed with their input. A pilot study is underway, investigating recruitment, retention and feasibility of delivery

Global assessment of sand and dust storms

The specific objectives of the assessment are to: 1) Synthesise and highlight the environmental and socio-economic causes and impacts of SDS, as well as available technical measures for their mitigation, at the local, regional and global levels; 2) Show how the mitigation of SDS can yield multiple sustainable development benefits; 3) Synthesize information on current policy responses for mitigating SDS and 4) Present options for an improved strategy for mitigating SDS at the local, regional and global levels, building on existing institutions and agreements

Anti-Nogo-A Immunotherapy Does Not Alter Hippocampal Neurogenesis after Stroke in Adult Rats

Ischemic stroke is a leading cause of adult disability, including cognitive impairment. Our laboratory has previously shown that treatment with function-blocking antibodies against the neurite growth inhibitory protein Nogo-A promotes functional recovery after stroke in adult and aged rats, including enhancing spatial memory performance, for which the hippocampus is critically important. Since spatial memory has been linked to hippocampal neurogenesis, we investigated whether anti-Nogo-A treatment increases hippocampal neurogenesis after stroke. Adult rats were subject to permanent middle cerebral artery occlusion followed 1 week later by 2 weeks of antibody treatment. Cellular proliferation in the dentate gyrus was quantified at the end of treatment, and the number of newborn neurons was determined at 8 weeks post-stroke. Treatment with both anti-Nogo-A and control antibodies stimulated the accumulation of new microglia/macrophages in the dentate granule cell layer, but neither treatment increased cellular proliferation or the number of newborn neurons above stroke-only levels. These results suggest that anti-Nogo-A immunotherapy does not increase post-stroke hippocampal neurogenesis

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant