Breaking records in the evolutionary race

We explore some aspects of the relationship between biological evolution processes and the mathematical theory of records. For Eigen's quasispecies model with an uncorrelated fitness landscape, we show that the evolutionary trajectories traced out by a population initially localized at a randomly chosen point in sequence space can be described in close analogy to record dynamics, with two complications. First, the increasing number of genotypes that become available with increasing distance from the starting point implies that fitness records are more frequent than for the standard case of independent, identically distributed random variables. Second, fitness records can be bypassed, which strongly reduces the number of genotypes that take part in an evolutionary trajectory. For exponential and Gaussian fitness distributions, this number scales with sequence length $N$ as $\sqrt{N}$, and it is of order unity for distributions with a power law tail. This is in strong contrast to the number of records, which is of order $N$ for any fitness distribution.Comment: Proceedings of 8th ICCMSP/Marrakech, to be published in Physica

Advancing the Right to Health: The Vital Role of Law

Effective laws and an enabling legal environment are essential to a healthy society. Most public health challenges – from infectious and non-communicable diseases to injuries, from mental illness to universal health coverage – have a legal component. At global, national and local levels, law is a powerful tool for advancing the right to health. This tool is, however, often underutilized. This report aims to raise awareness about the role that public health laws can play in advancing the right to health and in creating the conditions for all people to live healthy lives. The report provides guidance about issues and requirements to be addressed during the process of developing or reforming public health laws, with case studies drawn from countries around the world to illustrate effective practices and critical features of effective public health legislation. Advancing the right to health: the vital role of law is the result of a collaboration between the World Health Organisation, the International Development Law Organisation (IDLO), the O’Neill Institute for National and Global Health Law, Washington D.C., USA, and Sydney Law School, University of Sydney. The Project Directors were: Professor Lawrence O. Gostin, Linda D. and Timothy J. O’Neill Professor of Global Health Law and University Professor, Georgetown University; Faculty Director, O’Neill Institute for National and Global Health Law, Georgetown University; Mr David Patterson, Senior Legal Expert – Health; Department of Research & Learning, International Development Law Organization; Professor Roger Magnusson, Professor of Health Law & Governance, Sydney Law School, University of Sydney; Mr Oscar Cabrera, Executive Director, O’Neill Institute for National and Global Health Law, Georgetown University Law Center; Ms Helena Nygren-Krug (2011–2013), Senior Advisor, Human Rights & Law, UNAIDS. The content and structure of the report reflect the consensus reached at the second of two international consultations in public health law that preceded the preparation of the report, hosted by WHO and IDLO in Cairo, Egypt, 26-28 April 2010. Part 1 introduces the human right to health and its role in guiding and evaluating law reform efforts, including efforts to achieve the goal of universal health coverage. Part 2 discusses the process of public health law reform. The law reform process refers to the practical steps involved in advancing the political goal of law reform, and the kinds of issues and obstacles that may be encountered along the way. Part 2 identifies some of the actors who may initiate or lead the public health law reform process, discusses principles of good governance during that process, and ways of building a consensus around the need for public health law reform. Part 3 turns from the process of reforming public health laws to the substance or content of those laws. It identifies a number of core areas of public health practice where regulation is essential in order to ensure that governments (at different levels) discharge their basic public health functions. Traditionally, these core areas of public health practice have included: the provision of clean water and sanitation, monitoring and surveillance of public health threats, the management of communicable diseases, and emergency powers. Building on these core public health functions, Part 3 goes on to consider a range of other public health priorities where law has a critical role to play. These priorities include tobacco control, access to essential medicines, the migration of health care workers, nutrition, maternal, reproductive and child health, and the role of law in advancing universal access to quality health services for all members of the population. The report includes many examples that illustrate the ways in which different countries have used law to protect the health of their populations in ways that are consistent with their human rights obligations. Countries vary widely in terms of their constitutional structure, size, history and political culture. For these reasons, the examples given are not intended to be prescriptive, but to provide useful comparisons for countries involved in the process of legislative review

Determinants of organised sports participation patterns during the transition from childhood to adolescence in Germany: results of a nationwide cohort study

Abstract Background Organised sports (OS) participation is an important health behaviour but it seems to decline from childhood to adolescence. The aim of this study was to investigate OS participation patterns from childhood to adolescence and potential determinants for those patterns. Methods Data from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) cohort study with a 6 year follow-up period were used (KiGGS0: 2003-06, KiGGS1: 2009-12). Participants aged 6–10 years at KiGGS0, who were aged 12–16 at KiGGS1, were included (n = 3790). The outcome variable was ‘OS participation’ between KiGGS0 and KiGGS1 with the categories ‘maintenance’ (reference), ‘dropout’, ‘commencement’ and ‘nonparticipation’. Relative risk ratios (RRRs) were calculated using multinomial logistic regression to identify potential predictors for OS patterns. Socio-demographic, family-related, health-related, behavioural and environmental factors were considered as independent variables. Results 48.5 % maintained OS, 20.5 % dropped out, 12.3 % commenced OS between KiGGS0 and KiGGS1 and 18.7 % did not participate at both times. The RRRs for dropout rather than maintenance were 0.6 (95 % Cl 0.5–0.7) for boys versus girls, 1.5 (1.3–1.9) for the age group 8–10 versus 6–7 years, 0.7 (0.5–0.9) for high versus intermediate parental education, 1.4 (1.1–1.8) for low versus middle household income, 1.4 (1.0–1.8) for below-average versus average motor fitness. The RRRs for commencement rather than maintenance were 0.6 (0.5–0.8) for boys versus girls, 0.6 (0.5–0.8) for the age group 8–10 versus 6–7 years, 1.5 (1.1–2.1) for low versus intermediate parental education, 1.5 (1.1–2.0) for low versus middle household income, 0.7 (0.5–1.0) for no single-parent versus single parent family, 1.8 (1.3–2.5) for below-average and 0.6 (0.4–0.8) for above-average versus average motor fitness, and 1.4 (1.1–1.9) for high versus middle screen-based media use. The RRRs for abstinence rather than maintenance were 0.6 (0.4–0.7) for boys versus girls, 1.5 (1.1–2.0) for low versus intermediate parental education, 2.2 (1.7–2.8) for low and 0.6 (0.5–0.8) for high versus middle household income, 1.6 (1.2–2.1) for psychopathological problems versus no problems, 1.7 (1.3–2.2) for below-average and 0.4 (0.3–0.6) for above-average versus average motor fitness, and 1.6 (1.0–2.6) for rural versus metropolitan residential area. Conclusions OS participation rates among all children living in Germany need to be improved. More tailored offerings are needed which consider the preferences and interests of adolescents as well as a cooperation between public health actors to reduce barriers to OS

Optimizing Chronic Pain Management: Self-Care utilization among Veterans with Post-Traumatic Stress Disorder

Purpose: To implement a chronic pain management regimen that utilizes a self-care approach, integrating all dimensions of the biopsychosocial model to optimally treat the complex needs of younger Veterans with comorbid PTSD and chronic pain. The project aims to provide more insight and knowledge on safer chronic pain management among Veterans, reflected by improvement in patient’s pain level, quality of life, and depression scale. Design: The project was implemented at the ASPIRE Center, a domiciliary residential rehabilitation treatment program for Veterans who suffer from PTSD and traumatic brain injury. The 5A’s behavior change model was utilized during clinic visits and during follow-up phone calls. During each month’s clinic visit the provider and the Veteran discussed self-care modalities they thought would work best for them. Subsequent telephone follow-ups assessed the efficacy of the treatment and identified any barriers to treatment. Results: The intervention gained modest improvements in pain level and quality of life, and a negative effect in depression symptoms. Results were affected by high drop-out rates as a result of irregular or unplanned discharges caused by multiple confounding factors. When surveyed post hoc, 97% of the participants felt the collaborative effort was beneficial. Clinical Implications: Self-care utilization can provide a safe and effective way to manage chronic pain among Veterans with PTSD. This can be implemented in primary care and any site where effective chronic pain management is indicated. Overall, certain aspects of self-care interventions were effective in managing chronic pain

Differential Extinction and the Contrasting Structure of Polar Marine Faunas

Background: The low taxonomic diversity of polar marine faunas today reflects both the failure of clades to colonize or diversify in high latitudes and regional extinctions of once-present clades. However, simple models of polar evolution are made difficult by the strikingly different faunal compositions and community structures of the two poles.Methodology/Principal Findings: A comparison of early Cenozoic Arctic and Antarctic bivalve faunas with modern ones, within the framework of a molecular phylogeny, shows that while Arctic losses were randomly distributed across the tree, Antarctic losses were significantly concentrated in more derived families, resulting in communities dominated by basal lineages. Potential mechanisms for the phylogenetic structure to Antarctic extinctions include continental isolation, changes in primary productivity leading to turnover of both predators and prey, and the effect of glaciation on shelf habitats.Conclusions/Significance: These results show that phylogenetic consequences of past extinctions can vary substantially among regions and thus shape regional faunal structures, even when due to similar drivers, here global cooling, and provide the first phylogenetic support for the “retrograde” hypothesis of Antarctic faunal evolution.</p

Boost and hypofractionation in DCIS

Zwischen Juni 2007 und Juni 2014 wurden 1608 Patientinnen in die Studie aufgenommen. Von den Patientinnen wurden 503 bezüglich Boost und Fraktionierung randomisiert, 581 wurden randomisiert für den Boost bei Vorauswahl für konventionelle Fraktionierung und 524 randomisiert bei Vorauswahl für Hypofraktionierung. Es zeigte sich ein signifikanter Vorteil durch den Boost im Hinblick auf die lokale Tumorkontrolle: Die Lokalrezidivrate in der Brust nach 5 Jahren betrug 7,3 % ohne Boost vs. 2,9 % mit Boost (HR 0,47, p = 0,00031). Insgesamt war der Effekt des Boosts also besser als erwartet (HR 0,47, die statistische Planung ging ja von 0,56 aus). Die verbesserte lokale Kontrolle war verbunden mit einem verbesserten krankheitsfreien Überleben nach 5 Jahren (89,6 % ohne Boost vs. 93,7 % mit Boost, HR 0,63, p = 0,004). Erwartungsgemäß bestand kein Effekt auf das Überleben (5-J-Überleben 98,2 % ohne Boost vs. 99,0 % mit Boost, HR 0,81, p = n. s.). In multivariater Analyse war der Boost der wichtigste Prognosefaktor für ein intramammäres Rezidiv; der einzige weitere Risikofaktor war die Tumorgröße. Schlussfolgerungen Die Autoren folgern, dass erstens ein Boost auch beim DCIS die lokale Kontrolle optimiert und dass zweitens Hypofraktionierung auch beim DCIS sinnvoll ist

Enzalutamide vs active surveillance in patients with low-risk prostate cancer

Hintergrund Für Patienten mit Low-risk-Prostatakarzinom gelten aktive Überwachung, Strahlentherapie und Prostatektomie als anerkannte Therapieoptionen. Eine alleinige medikamentöse antihormonelle Therapie ist primär nicht indiziert und wird in der S3-Leitlinie nur empfohlen, wenn entweder Therapiebedarf besteht und die Standardtherapieverfahren nicht möglich sind oder wenn eine kurative Therapie abgelehnt wird. In der Leitlinie wird explizit gefordert, Patienten über den palliativen Charakter dieser Option sowie die mit einer hormonablativen Therapie verbundenen unerwünschten Wirkungen und die uneinheitliche Datenlage bezüglich eines Überlebensvorteils aufzuklären. In den einschlägigen Metaanalysen gibt es nämlich keinen Überlebensvorteil durch eine primäre antihormonelle Therapie bei Patienten mit Low-risk-Prostatakarzinom, sondern nur bei Vorliegen erheblicher Risikofaktoren, insbesondere T3–4, PSA > 50 μg/l und PSA-Verdopplungszeit unter einem Jahr. In den vor etwa 20 Jahren durchgeführten Studien mit Bicalutamid wurde der Studienteil für Patienten mit aktiver Überwachung vorzeitig geschlossen. Auch in neoadjuvanten Konzepten wurden keine relevanten Effekte erzielt

Evolutionary trajectories in rugged fitness landscapes

We consider the evolutionary trajectories traced out by an infinite population undergoing mutation-selection dynamics in static, uncorrelated random fitness landscapes. Starting from the population that consists of a single genotype, the most populated genotype \textit{jumps} from a local fitness maximum to another and eventually reaches the global maximum. We use a strong selection limit, which reduces the dynamics beyond the first time step to the competition between independent mutant subpopulations, to study the dynamics of this model and of a simpler one-dimensional model which ignores the geometry of the sequence space. We find that the fit genotypes that appear along a trajectory are a subset of suitably defined fitness \textit{records}, and exploit several results from the record theory for non-identically distributed random variables. The genotypes that contribute to the trajectory are those records that are not \textit{bypassed} by superior records arising further away from the initial population. Several conjectures concerning the statistics of bypassing are extracted from numerical simulations. In particular, for the one-dimensional model, we propose a simple relation between the bypassing probability and the dynamic exponent which describes the scaling of the typical evolution time with genome size. The latter can be determined exactly in terms of the extremal properties of the fitness distribution.Comment: Figures in color; minor revisions in tex

Application of Foreland Basin Detrital-Zircon Geochronology to the Reconstruction of the Southern and Central Appalachian Orogen

We report the U-Pb age distribution of detrital zircons collected from central and southern Appalachian foreland basin strata, which record changes of sediment provenance in response to the different phases of the Appalachian orogeny. Taconic clastic wedges have predominantly ca. 1080–1180 and ca. 1300–1500 Ma zircons, whereas Acadian clastic wedges contain abundant Paleozoic zircons and minor populations of 550–700 and 1900–2200 Ma zircons consistent with a Gondwanan affinity. Alleghanian clastic wedges contain large populations of ca. 980–1080 Ma and ca. 2700 Ma and older Archean zircons and fewer Paleozoic zircons than occur in the Acadian clastic wedges. The abundance of Paleozoic detrital zircons in Acadian clastic wedges indicates that the Acadian hinterland consisted of recycled material and Taconic-aged plutons, which provided significant detritus to the Acadian foreland basin. The appearance of Pan-African/Brasiliano- and Eburnean/Trans-Amazonian-aged zircons in Acadian clastic wedges suggests a Devonian accretion of the Carolina terrane. In contrast, the relative decrease in abundance of Paleozoic detrital zircons coupled with an increase of Archean and Grenville zircons in Alleghanian clastic wedges indicates the development of an orogenic hinterland consisting of deformed passive margin strata and Grenville basement. The younging-upward age progression in Grenville province sources revealed in Taconic through Alleghanian successions suggest a reverse unroofing sequence that indicates at least two cycles of Grenville zircon recycling