The war on cancer: have we won the battle but lost the war?
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ABSTRACT:
SUBMITTER: Brennan R
PROVIDER: S-EPMC2945373 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The neural mechanism underlying preparation for tasks that vary in difficulty has not been explored. This functional magnetic resonance imaging study manipulated task difficulty by varying the working memory (WM) load of the n-back task. Each n-back task block was preceded by a preparation period involving a screen that indicated the level of difficulty of the upcoming task. Consistent with previous work, activation in some brain regions depended on WM load in the task. These regions were used as regions of interest for the univariate and multivariate (classification) analyses of preparation periods. The findings were that the patterns of brain activation during task preparation contain information about the upcoming task difficulty. (1) A support vector machine classifier was able to decode the n-back task difficulty from the patterns of brain activation during task preparation. Those individuals whose activation patterns for anticipated 1- versus 2- versus 3-back conditions were classified with higher accuracy showed better behavioral performance on the task, suggesting that task performance depends on task preparation. (2) Left inferior frontal gyrus, intraparietal sulcus, and anterior cingulate cortex parametrically decreased activation as anticipated task difficulty increased. Taken together, these results suggest dynamic involvement of the WM network not only during WM task performance, but also during task preparation.
| S-EPMC4318533 | biostudies-literature
Project description:This paper discusses the process of retrieval and updating legacy data to allow on-line discovery and delivery. There are many pitfalls of institutional and non-institutional ecological data conservation over the long term. Interruptions to custodianship, old media, lost knowledge and the continuous evolution of species names makes resurrection of old data challenging. We caution against technological arrogance and emphasise the importance of international standards. We use a case study of a compiled set of continent-wide vegetation survey data for which, although the analyses had been published, the raw data had not. In the original study, publications containing plot data collected from the 1880s onwards had been collected, interpreted, digitised and integrated for the classification of vegetation and analysis of its conservation status across Australia. These compiled data are an extremely valuable national collection that demanded publishing in open, readily accessible online repositories, such as the Terrestrial Ecosystem Research Network (http://www.tern.org.au) and the Atlas of Living Australia (ALA: http://www.ala.org.au), the Australian node of the Global Biodiversity Information Facility (GBIF: http://www.gbif.org). It is hoped that the lessons learnt from this project may trigger a sober review of the value of endangered data, the cost of retrieval and the importance of suitable and timely archiving through the vicissitudes of technological change, so the initial unique collection investment enables multiple re-use in perpetuity.
| S-EPMC6235994 | biostudies-literature
Project description:Contemporary accounts of battles are often incomplete or even erroneous because they reflect the-often biased-viewpoints of the authors. Battlefield archaeology faces the task of compiling an historical analysis of a battle and of gathering all the available facts. Besides cultural historical evidence and artefacts, the human remains of those who have fallen in battle also provide invaluable information. In studying mass graves from a military context, the injury types and patterns are significant. They allow us to reconstruct the circumstances surrounding the soldiers' deaths and provide information on the hostilities that occurred on the battlefield. One such mass grave was discovered in 2011 at Lützen, Saxony-Anhalt (Germany). Based on its geographical location and on the results obtained from archaeological examinations carried out in the area, the grave could be dated to the Thirty Years War (1618-1648). Further archaeological research confirmed that the dead had been soldiers from the Battle of Lützen (1632). The mass grave was block-lifted and then comprehensively examined at the State Museum of Prehistory in Halle (Saale). As well as osteological examinations to determine age, sex, height, state of health, i.e. diseases or injuries, imaging methods were also employed and histological and isotopic analyses carried out. The focus of this study was on the injuries sustained by the soldiers both prior to and during the battle. The results revealed that the 47 deceased had been between the ages of 15 and 50 when they died. Numerous healed injuries showed that the men had often been involved in violent encounters. Approximately three in every four soldiers had injuries that could have been fatal. Wounds inflicted by handguns, particularly to the skull, were predominant. The integrative analysis of the archaeological and anthropological data allowed us to conclude that the majority had been killed during a cavalry attack.
| S-EPMC5439951 | biostudies-literature
Project description:Background: Suicide is an important public health problem in the African continent whose economic burden remains largely unknown. This study estimated the monetary value of human lives lost due to suicide in the African continent in 2017. Methods: The human capital approach was applied to monetarily value the years of life lost due to premature mortality from suicide deaths (SD) among 54 African countries. A 3% discount rate was used to convert future losses into their present values. The sensitivity of monetary value of human lives lost to changes in discount rate and average life expectancy was tested. Results: The 75,505 human lives lost from suicide had a grand total monetary value of International Dollars (Int$) 6,989,963,325; and an average present value of Int$ 92,576 per SD. About 31.1% of the total monetary value of SD was borne by high-income and upper-middle-income countries (Group 1); 54.4% by lower-middle-income countries (Group 2); and 14.5% by low-income countries (Group 3). The average monetary value per human life lost from SD was Int$ 234,244 for Group 1, Int$ 109,545 for Group 2 and Int$ 32,223 for Group 3. Conclusions: Evidence shows that suicide imposes a substantive economic burden on African economies. The evidence reinforces the case for increased investments to ensure universal coverage of promotive, preventive, curative and rehabilitative mental health services.
| S-EPMC7348721 | biostudies-literature
Project description:At the beginning of the COVID-19 pandemic, governments around the world employed militaristic metaphors to draw attention to the dangers of the virus. But, do militaristic metaphors truly affect individuals' perceived threat of the COVID-19 virus and increase their support for corresponding restrictive policies? This study assessed the effects of fictitious newspaper articles that described COVID-19 policies using similarly negatively valenced metaphors but with differing militaristic connotations (e.g., "war" vs. "struggle"). Overall, data from three framing experiments (N = 1114) in Germany and the United States indicate limited evidence on the effectiveness of the tested militaristic metaphors. In the U.S. context, the non-militaristic concept of struggle was consistently more strongly associated with the desired outcomes than militaristic metaphors were. In Studies 2 and 3, we also tested whether reporting using a narrative or straightforward facts had additional influence on the framing effect. A congruency effect of the use of a narrative and of warfare metaphors was found in the German sample, but not in that of the United States. Results of post-experimental norming studies (N = 437) in both countries revealed that the metaphor of war is associated with people ascribing greater responsibility to their governments, whereas the concept of struggle triggers a sense of individual responsibility. These results are discussed in terms of the usefulness and appropriateness of militaristic metaphors in the context of a pandemic.
| S-EPMC8652818 | biostudies-literature
Project description:The Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial represents the first completed prospective, biopsy-mandated, biomarker-based, adaptively randomized study in 255 pretreated lung cancer patients. Following an initial equal randomization period, chemorefractory non-small cell lung cancer (NSCLC) patients were adaptively randomized to erlotinib, vandetanib, erlotinib plus bexarotene, or sorafenib, based on relevant molecular biomarkers analyzed in fresh core needle biopsy specimens. Overall results include a 46% 8-week disease control rate (primary end point), confirm prespecified hypotheses, and show an impressive benefit from sorafenib among mutant-KRAS patients. BATTLE establishes the feasibility of a new paradigm for a personalized approach to lung cancer clinical trials.The BATTLE study is the first completed prospective, adaptively randomized study in heavily pretreated NSCLC patients that mandated tumor profiling with "real-time" biopsies, taking a substantial step toward realizing personalized lung cancer therapy by integrating real-time molecular laboratory findings in delineating specific patient populations for individualized treatment.
| S-EPMC4211116 | biostudies-literature
Project description:Recent discussion on invasive species has invigorated the debate on strategies to manage these species. Lantana camara L., a shrub native to the American tropics, has become one of the worst weeds in recorded history. In Australia, India and South Africa, Lantana has become very widespread occupying millions of hectares of land. Here, we examine historical records to reconstruct invasion and management of Lantana over two centuries and ask: Can we fight the spread of invasive species or do we need to develop strategies for their adaptive management? We carried out extensive research of historical records constituting over 75% of records on invasion and management of this species in the three countries. The records indicate that governments in Australia, India and South Africa have taken aggressive measures to eradicate Lantana over the last two centuries, but these efforts have been largely unsuccessful. We found that despite control measures, the invasion trajectory of Lantana has continued upwards and that post-war land-use change might have been a possible trigger for this spread. A large majority of studies on invasive species address timescales of less than one year; and even fewer address timescales of >10 years. An understanding of species invasions over long time-scales is of paramount importance. While archival records may give only a partial picture of the spread and management of invasive species, in the absence of any other long-term dataset on the ecology of Lantana, our study provides an important insight into its invasion, spread and management over two centuries and across three continents. While the established paradigm is to expend available resources on attempting to eradicate invasive species, our findings suggest that in the future, conservationists will need to develop strategies for their adaptive management rather than fighting a losing battle.
| S-EPMC3293794 | biostudies-literature
Project description:Aneuploidy, an irregular number of chromosomes in cells, is a hallmark feature of cancer. Aneuploidy results from chromosomal instability (CIN) and occurs in almost 90% of all tumours. While many cancers display an ongoing CIN phenotype, cells can also be aneuploid without displaying CIN. CIN drives tumour evolution as ongoing chromosomal missegregation will yield a progeny of cells with variable aneuploid karyotypes. The resulting aneuploidy is initially toxic to cells because it leads to proteotoxic and metabolic stress, cell cycle arrest, cell death, immune cell activation and further genomic instability. In order to overcome these aneuploidy-imposed stresses and adopt a malignant fate, aneuploid cancer cells must develop aneuploidy-tolerating mechanisms to cope with CIN. Aneuploidy-coping mechanisms can thus be considered as promising therapeutic targets. However, before such therapies can make it into the clinic, we first need to better understand the molecular mechanisms that are activated upon aneuploidization and the coping mechanisms that are selected for in aneuploid cancer cells. In this review, we discuss the key biological responses to aneuploidization, some of the recently uncovered aneuploidy-coping mechanisms and some strategies to exploit these in cancer therapy.
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Project description:Breast cancer is the most prevalent malignancy in women and the second most common cause of cancer-related death worldwide. Despite major innovations in early detection and advanced therapeutics, up to 30% of women with node-negative breast cancer and 70% of women with node-positive breast cancer will develop recurrence. The recognition that breast tumors are infiltrated by a complex array of immune cells that influence their development, progression, and metastasis, as well as their responsiveness to systemic therapies has sparked major interest in the development of immunotherapies. In fact, not only the native host immune system can be altered to promote potent antitumor response, but also its components can be manipulated to generate effective therapeutic strategies. We present here a review of the major approaches to immunotherapy in breast cancers, both successes and failures, as well as new therapies on the horizon.
| S-EPMC5810622 | biostudies-literature