Designing a broad-spectrum integrative approach for cancer prevention and treatment

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notablesuccesses in some cancers; however, significant problems remain with this approach. Many targetedtherapies are highly toxic, costs are extremely high, and most patients experience relapse after a fewdisease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistantimmortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are notreliant upon the same mechanisms as those which have been targeted). To address these limitations, aninternational task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspectsof relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a widerange of high-priority targets (74 in total) that could be modified to improve patient outcomes. For thesetargets, corresponding low-toxicity therapeutic approaches were then suggested, many of which werephytochemicals. Proposed actions on each target and all of the approaches were further reviewed forknown effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixedevidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of therelationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. Thisnovel approach has potential to be relatively inexpensive, it should help us address stages and types ofcancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for futureresearch is offered

On thermodynamically consistent Stefan problems with variable surface energy

A thermodynamically consistent two-phase Stefan problem with temperature-dependent surface tension and with or without kinetic undercooling is studied. It is shown that these problems generate local semiflows in well-defined state manifolds. If a solution does not exhibit singularities, it is proved that it exists globally in time and converges towards an equilibrium of the problem. In addition, stability and instability of equilibria is studied. In particular, it is shown that multiple spheres of the same radius are unstable if surface heat capacity is small; however, if kinetic undercooling is absent, they are stable if surface heat capacity is sufficiently large.Comment: To appear in Arch. Ration. Mech. Anal. The final publication is available at Springer via http://dx.doi.org/10.1007/s00205-015-0938-y. arXiv admin note: substantial text overlap with arXiv:1101.376

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements

Sugarcane root length density and distribution from root intersection counting on a trench-profile

Root length density (RLD) is a critical feature in determining crops potential to uptake water and nutrients, but it is difficult to be measured. No standard method is currently available for assessing RLD in the soil. In this study, an in situ method used for other crops for studying root length density and distribution was tested for sugarcane (Saccharum spp.). This method involved root intersection counting (RIC) on a Rhodic Eutrudox profile using grids with 0.05 x 0.05 m and modeling RLD from RIC. The results were compared to a conventional soil core-sampled method (COR) (volume 0.00043 m³). At four dates of the cropping season in three tillage treatments (plowing soil, minimum tillage and direct planting), with eight soil depths divided in 0.1 m soil layer (between 0-0.6 and 1.6-1.8 m) and three horizontal distances from the row (0-0.23, 0.23-0.46 and 0.46-0.69 m), COR and RIC methods presented similar RLD results. A positive relationship between COR and RIC was found (R² = 0.76). The RLD profiles considering the average of the three row distances per depth obtained using COR and RIC (mean of four dates and 12 replications) were close and did not differ at each depth of 0.1 m within a total depth of 0.6 m. Total RLD between 0 and 0.6 m was 7.300 and 7.100 m m-2 for COR and RIC respectively. For time consumption, the RIC method was tenfold less time-consuming than COR and RIC can be carried out in the field with no need to remove soil samples. The RLD distribution in depth and row distance (2-D variability) by RIC can be assessed in relation to the soil properties in the same soil profiles. The RIC method was suitable for studying these 2-D (depth and row distance in the soil profile) relationships between soil, tillage and root distribution in the field.A densidade de comprimento de raízes (DCR) é uma característica importante para determinar o potencial de absorção de água e nutrientes das plantas, mas é difícil de ser medida. Nenhum método padrão está atualmente disponível para avaliar a DCR no solo. Neste estudo, um método in situ usado em outras culturas para estudo da densidade de comprimento e distribuições das raízes foi testado para a cana-de-açúcar (Saccharum spp.). O método envolveu contagem de intersecções de raízes (CIR) no perfil de um Latossolo Vermelho eutroférrico, usando grade com quadrículas de 0.05 x 0.05 m, modelizando a DCR a partir da CIR. Os resultados foram comparados com o método do trado cilíndrico (TRA) (volume de 0.00043 m-3). Em quatro épocas durante o ciclo em três manejos do solo (plantio convencional, cultivo mínimo e plantio direto), em oito profundidades divididas a cada 0.1 m (entre 0 - 0.6 e 1.6 - 1.8 m) e três distâncias horizontais em relação à linha de plantio (0 - 0.23, 0.23 - 0.46 e 0.46 - 0.69 m), os métodos TRA e CIR apresentaram resultados de DCR similares. Encontrou-se positiva entre TRA e CIR (R² = 0,76). As DCRs nos perfis, considerando as médias das três distâncias da linha por profundidade, obtida utilizando-se de TRA e CIR (média de quatro datas e 12 repetições), foram próximas e não diferiram a cada 0.1 m de profundidade até 0.6 m de profundidade. A DCR total entre 0 e 0.6 m foi de 7.300 e 7.100 m m-2 para TRA e CIR, respectivamente. Para o tempo de realização, o método CIR foi 10 vezes mais rápido do que TRA e o método CIR pode ser realizado no campo, sem necessidade de remover amostras de solo. A distribuição da DCR em profundidade e distância da linha (variabilidade 2D) pelo método CIR pode ser avaliada em relação às propriedades do solo nos mesmos perfis do solo. O método CIR foi apropriado para estudos dessas relações 2D (profundidade e distância da linha no perfil do solo) entre solo, manejo e distribuição de raízes no campo

Responses of wood anatomy and carbon isotope composition of Quercus pubescens saplings subjected to two consecutive years of summer drought

International audienceTo withstand and to recover from severe summer drought is crucial for trees, as dry periods are predicted to occur more frequently over the coming decades.* In order to better understand growth-related tree responses to drought, wood formation, vessel characteristics and stable carbon isotope composition (δ13C) in tree rings of Quercus pubescens saplings imposed to two consecutive summer droughts were compared with regularly watered control trees.* In both years, photosynthetic activity was strongly inhibited during the drought periods of five to seven weeks but quickly restored after re-watering, reinitiating wood formation. Stress caused more than a 20% reduction in ring width, a 0.5‰ increase in latewood δ13C and changes in vessels characteristics in both the current year latewood and the next year earlywood. The latewood displayed up to 90% increased hydraulic conductivity than control trees, likely to compensate for a cavitation-induced reduction of water transport.* The earlywood after the first drought year was characterized by more but smaller vessels suggesting the attempt of restoring conductivity while minimizing the risk of hydraulic failure. However, after the second year, the reduction of hydraulic conductivity and the increased δ13C values indicate a structural adjustment towards a reduced growth induced by exhaustion of carbon reserves

Patient-reported outcome measures for hip-related pain: A review of the available evidence and a consensus statement from the International Hip-related Pain Research Network, Zurich 2018

Hip-related pain is a well-recognised complaint among active young and middle-aged active adults. People experiencing hip-related disorders commonly report pain and reduced functional capacity, including difficulties in executing activities of daily living. Patient-reported outcome measures (PROMs) are essential to accurately examine and compare the effects of different treatments on disability in those with hip pain. In November 2018, 38 researchers and clinicians working in the field of hip-related pain met in Zurich, Switzerland for the first International Hip-related Pain Research Network meeting. Prior to the meeting, evidence summaries were developed relating to four prioritised themes. This paper discusses the available evidence and consensus process from which recommendations were made regarding the appropriate use of PROMs to assess disability in young and middle-aged active adults with hip-related pain. Our process to gain consensus had five steps: (1) systematic review of systematic reviews; (2) preliminary discussion within the working group; (3) update of the more recent high-quality systematic review and examination of the psychometric properties of PROMs according to established guidelines; (4) formulation of the recommendations considering the limitations of the PROMs derived from the examination of their quality; and (5