Starvation Resistance is Associated with Developmentally Specified Changes in Sleep, Feeding and Metabolic Rate

Food shortage represents a primary challenge to survival, and animals have adapted diverse developmental, physiological and behavioral strategies to survive when food becomes unavailable. Starvation resistance is strongly influenced by ecological and evolutionary history, yet the genetic basis for the evolution of starvation resistance remains poorly understood. The fruit fly Drosophila melanogaster provides a powerful model for leveraging experimental evolution to investigate traits associated with starvation resistance. While control populations only live a few days without food, selection for starvation resistance results in populations that can survive weeks. We have previously shown that selection for starvation resistance results in increased sleep and reduced feeding in adult flies. Here, we investigate the ontogeny of starvation resistance-associated behavioral and metabolic phenotypes in these experimentally selected flies. We found that selection for starvation resistance resulted in delayed development and a reduction in metabolic rate in larvae that persisted into adulthood, suggesting that these traits may allow for the accumulation of energy stores and an increase in body size within these selected populations. In addition, we found that larval sleep was largely unaffected by starvation selection and that feeding increased during the late larval stages, suggesting that experimental evolution for starvation resistance produces developmentally specified changes in behavioral regulation. Together, these findings reveal a critical role for development in the evolution of starvation resistance and indicate that selection can selectively influence behavior during defined developmental time points

Lancet

BACKGROUND: In 2015, the second cycle of the CONCORD programme established global surveillance of cancer survival as a metric of the effectiveness of health systems and to inform global policy on cancer control. CONCORD-3 updates the worldwide surveillance of cancer survival to 2014. METHODS: CONCORD-3 includes individual records for 37.5 million patients diagnosed with cancer during the 15-year period 2000-14. Data were provided by 322 population-based cancer registries in 71 countries and territories, 47 of which provided data with 100% population coverage. The study includes 18 cancers or groups of cancers: oesophagus, stomach, colon, rectum, liver, pancreas, lung, breast (women), cervix, ovary, prostate, and melanoma of the skin in adults, and brain tumours, leukaemias, and lymphomas in both adults and children. Standardised quality control procedures were applied; errors were rectified by the registry concerned. We estimated 5-year net survival. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: For most cancers, 5-year net survival remains among the highest in the world in the USA and Canada, in Australia and New Zealand, and in Finland, Iceland, Norway, and Sweden. For many cancers, Denmark is closing the survival gap with the other Nordic countries. Survival trends are generally increasing, even for some of the more lethal cancers: in some countries, survival has increased by up to 5% for cancers of the liver, pancreas, and lung. For women diagnosed during 2010-14, 5-year survival for breast cancer is now 89.5% in Australia and 90.2% in the USA, but international differences remain very wide, with levels as low as 66.1% in India. For gastrointestinal cancers, the highest levels of 5-year survival are seen in southeast Asia: in South Korea for cancers of the stomach (68.9%), colon (71.8%), and rectum (71.1%); in Japan for oesophageal cancer (36.0%); and in Taiwan for liver cancer (27.9%). By contrast, in the same world region, survival is generally lower than elsewhere for melanoma of the skin (59.9% in South Korea, 52.1% in Taiwan, and 49.6% in China), and for both lymphoid malignancies (52.5%, 50.5%, and 38.3%) and myeloid malignancies (45.9%, 33.4%, and 24.8%). For children diagnosed during 2010-14, 5-year survival for acute lymphoblastic leukaemia ranged from 49.8% in Ecuador to 95.2% in Finland. 5-year survival from brain tumours in children is higher than for adults but the global range is very wide (from 28.9% in Brazil to nearly 80% in Sweden and Denmark). INTERPRETATION: The CONCORD programme enables timely comparisons of the overall effectiveness of health systems in providing care for 18 cancers that collectively represent 75% of all cancers diagnosed worldwide every year. It contributes to the evidence base for global policy on cancer control. Since 2017, the Organisation for Economic Co-operation and Development has used findings from the CONCORD programme as the official benchmark of cancer survival, among their indicators of the quality of health care in 48 countries worldwide. Governments must recognise population-based cancer registries as key policy tools that can be used to evaluate both the impact of cancer prevention strategies and the effectiveness of health systems for all patients diagnosed with cancer. FUNDING: American Cancer Society; Centers for Disease Control and Prevention; Swiss Re; Swiss Cancer Research foundation; Swiss Cancer League; Institut National du Cancer; La Ligue Contre le Cancer; Rossy Family Foundation; US National Cancer Institute; and the Susan G Komen Foundation

Global survival trends for brain tumors, by histology: analysis of individual records for 556,237 adults diagnosed in 59 countries during 2000–2014 (CONCORD-3)

Background: Survival is a key metric of the effectiveness of a health system in managing cancer. We set out to provide a comprehensive examination of worldwide variation and trends in survival from brain tumors in adults, by histology. Methods: We analyzed individual data for adults (15–99 years) diagnosed with a brain tumor (ICD-O-3 topography code C71) during 2000–2014, regardless of tumor behavior. Data underwent a 3-phase quality control as part of CONCORD-3. We estimated net survival for 11 histology groups, using the unbiased nonparametric Pohar Perme estimator. Results: The study included 556,237 adults. In 2010–2014, the global range in age-standardized 5-year net survival for the most common sub-types was broad: in the range 20%–38% for diffuse and anaplastic astrocytoma, from 4% to 17% for glioblastoma, and between 32% and 69% for oligodendroglioma. For patients with glioblastoma, the largest gains in survival occurred between 2000–2004 and 2005–2009. These improvements were more noticeable among adults diagnosed aged 40–70 years than among younger adults. Conclusions: To the best of our knowledge, this study provides the largest account to date of global trends in population-based survival for brain tumors by histology in adults. We have highlighted remarkable gains in 5-year survival from glioblastoma since 2005, providing large-scale empirical evidence on the uptake of chemoradiation at population level. Worldwide, survival improvements have been extensive, but some countries still lag behind. Our findings may help clinicians involved in national and international tumor pathway boards to promote initiatives aimed at more extensive implementation of clinical guidelines

Preliminary Efficacy of Online Traumatic Brain Injury Professional Development for Educators: An Exploratory Randomized Clinical Trial

Objective: To examine the efficacy of an online traumatic brain injury (TBI) professional development intervention, In the Classroom After Concussion: Best Practices for Student Success. Design: A randomized controlled trial with a sample of 100 general educators, who were randomly assigned to the In the Classroom Web site (treatment group) or the LEARNet Web site (control group). Participants completed the pretest, accessed the In the Classroom or LEARNet site and the posttest and completed follow-up assessments 60 days after posttest. Measures: (1) Knowledge of effective strategies for working with students with TBI; (2) knowledge application; (3) self-efficacy in handling situations presented in text and video scenarios, and (4) a standardized self-efficacy measure. Results: On the posttest assessment, In the Classroom educators showed significantly greater gains in knowledge (P \u3c .0001, d = 1.36 [large effect]), TBI knowledge application (P = .0261, d = 0.46), and general self-efficacy (P = .0106, d = 0.39) than the LEARNet controls. In the Classroom educators maintained significant gains in knowledge (P = .001, d = 0.82) and general self-efficacy (P = .018, d = 0.38) but not in TBI knowledge application (P = .921, d = 0.02). Conclusion: Given the prevalence of TBI, it is important to develop evidence-based, cost-effective approaches to knowledge transfer and exchange in TBI professional development. In the Classroom is one such approach

Management of Return to School Following Brain Injury: An Evaluation Model

Traumatic brain injury (TBI) affects children’s ability to succeed at school. Few educators have the necessary training and knowledge needed to adequately monitor and treat students with a TBI, despite schools regularly serving as the long-term service provider. In this article, we describe a return to school model used in Oregon that implements best practices indicated by the extant literature, as well as our research protocol for evaluating this model. We discuss project aims and our planned procedures, including the measures used, our quasi-experimental design using matched controls, statistical power, and impact analyses. This project will provide the evidential base for implementation of a return to school model at scale. Highlights: Traumatic brain injury can significantly affect educational and social functioning. Schools provide long-term services to children with traumatic brain injuries. A research protocol is described for evaluating a return-to-school model. Propensity scores are used within a matched comparison group design

Enhanced Sleep Is an Evolutionarily Adaptive Response to Starvation Stress in <i>Drosophila</i>

<div><p>Animals maximize fitness by modulating sleep and foraging strategies in response to changes in nutrient availability. Wild populations of the fruit fly, <i>Drosophila melanogaster</i>, display highly variable levels of starvation and desiccation resistance that differ in accordance with geographic location, nutrient availability, and evolutionary history. Further, flies potently modulate sleep in response to changes in food availability, and selection for starvation resistance enhances sleep, revealing strong genetic relationships between sleep and nutrient availability. To determine the genetic and evolutionary relationship between sleep and nutrient deprivation, we assessed sleep in flies selected for desiccation or starvation resistance. While starvation resistant flies have higher levels of triglycerides, desiccation resistant flies have enhanced glycogen stores, indicative of distinct physiological adaptations to food or water scarcity. Strikingly, selection for starvation resistance, but not desiccation resistance, leads to increased sleep, indicating that enhanced sleep is not a generalized consequence of higher energy stores. Thermotolerance is not altered in starvation or desiccation resistant flies, providing further evidence for context-specific adaptation to environmental stressors. F₂ hybrid flies were generated by crossing starvation selected flies with desiccation selected flies, and the relationship between nutrient deprivation and sleep was examined. Hybrids exhibit a positive correlation between starvation resistance and sleep, while no interaction was detected between desiccation resistance and sleep, revealing that prolonged sleep provides an adaptive response to starvation stress. Therefore, these findings demonstrate context-specific evolution of enhanced sleep in response to chronic food deprivation, and provide a model for understanding the evolutionary relationship between sleep and nutrient availability.</p></div

Selection for DR does not alter sleep.

<p>A) Sleep profiles depicting hourly sleep reveal that sleep in SR_c flies is increased during both day and night compared to the DR_c flies and respective controls (N = 64 for all groups). B) The total sleep duration over 24hrs on food is significantly longer in SR_c flies than in F_SRc flies. No differences are observed between DR_c flies and F_DRc flies (SR_c group: P<0.001; DR_c lines: P>0.05; See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131275#pone.0131275.s004" target="_blank">S1 Table</a>). C) Beam crossings per waking minute are reduced in DR_c and SR_c flies compared to respective controls (SR_c group: P<0.001; DR_c lines: P<0.001; See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131275#pone.0131275.s004" target="_blank">S1 Table</a>).</p

Distinct resistance to nutrient deprivation in SR and DR flies.

<p>Survival of flies placed in activity monitors under starvation conditions. A) Flies from the SR_c lines survived longer than F_SRc controls, whereas DR lines do not differ from F_DRc controls (SR lines: P < 0.001 in all groups; DR lines: P>0.05). B) DR_c flies survive longer than F_DRc controls under desiccation conditions. SR_c flies were also resistant to desiccation compared to F_SRc controls (DR_c line: P<0.001; SR_c line: P<0.001, See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131275#pone.0131275.s004" target="_blank">S1 Table</a>.) C) SR_c flies did not live as long as F_SRc controls, and no difference in longevity was observed in DR_c flies and controls, under thermal stress conditions (SR lines: P = 0.01; DR lines P>0.05; See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131275#pone.0131275.s004" target="_blank">S1 Table</a>).</p

SR and DR selection increases body size and alters metabolic profile.

<p>A) Schematic of selection processes for SR and DR flies. Adult outbred flies were placed under desiccation or starvation conditions until ~15% of the flies survived. The flies were then moved to food. This process was repeated over >80 generations. The F_DR controls were placed on agar during desiccation selection to account for food deprivation in DR selected flies. There were three replicated SR populations (designated SR_a, SR_b and SR_c) and three fed control populations (F_SRa, F_SRb and F_SRc). For DR experiments there were three replicated groups (designated DR_a, DR_b and DR_c) and three fed control populations (F_DRa, F_DRb and F_DRc). B) Flies from the C Group. SR_c and DR_c flies are visibly larger than F_SRc and F_DRc controls. C) Triglyceride levels are elevated in the SR_c flies compared to F_SRc controls. No differences are observed between DR_c flies and F_DRc controls (P<0.001; See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131275#pone.0131275.s004" target="_blank">S1 Table</a>). D) Glycogen levels were greater in DR_c flies than in F_DRc controls. No differences were present between SR_c flies and F_SRc controls (P<0.001; See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131275#pone.0131275.s004" target="_blank">S1 Table</a>). E) Free glucose levels did not differ between SR_c or DR_c flies and their respective controls (P>0.05; See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131275#pone.0131275.s004" target="_blank">S1 Table</a>).</p