Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials

Background: After breast-conserving surgery, radiotherapy reduces recurrence and breast cancer death, but it may do so more for some groups of women than for others. We describe the absolute magnitude of these reductions according to various prognostic and other patient characteristics, and relate the absolute reduction in 15-year risk of breast cancer death to the absolute reduction in 10-year recurrence risk.
Methods: We undertook a meta-analysis of individual patient data for 10?801 women in 17 randomised trials of radiotherapy versus no radiotherapy after breast-conserving surgery, 8337 of whom had pathologically confirmed node-negative (pN0) or node-positive (pN+) disease.
Findings: Overall, radiotherapy reduced the 10-year risk of any (ie, locoregional or distant) first recurrence from 35·0% to 19·3% (absolute reduction 15·7%, 95% CI 13·7–17·7, 2p<0·00001) and reduced the 15-year risk of breast cancer death from 25·2% to 21·4% (absolute reduction 3·8%, 1·6–6·0, 2p=0·00005). In women with pN0 disease (n=7287), radiotherapy reduced these risks from 31·0% to 15·6% (absolute recurrence reduction 15·4%, 13·2–17·6, 2p<0·00001) and from 20·5% to 17·2% (absolute mortality reduction 3·3%, 0·8–5·8, 2p=0·005), respectively. In these women with pN0 disease, the absolute recurrence reduction varied according to age, grade, oestrogen-receptor status, tamoxifen use, and extent of surgery, and these characteristics were used to predict large (=20%), intermediate (10–19%), or lower (<10%) absolute reductions in the 10-year recurrence risk. Absolute reductions in 15-year risk of breast cancer death in these three prediction categories were 7·8% (95% CI 3·1–12·5), 1·1% (–2·0 to 4·2), and 0·1% (–7·5 to 7·7) respectively (trend in absolute mortality reduction 2p=0·03). In the few women with pN+ disease (n=1050), radiotherapy reduced the 10-year recurrence risk from 63·7% to 42·5% (absolute reduction 21·2%, 95% CI 14·5–27·9, 2p<0·00001) and the 15-year risk of breast cancer death from 51·3% to 42·8% (absolute reduction 8·5%, 1·8–15·2, 2p=0·01). Overall, about one breast cancer death was avoided by year 15 for every four recurrences avoided by year 10, and the mortality reduction did not differ significantly from this overall relationship in any of the three prediction categories for pN0 disease or for pN+ disease.
Interpretation: After breast-conserving surgery, radiotherapy to the conserved breast halves the rate at which the disease recurs and reduces the breast cancer death rate by about a sixth. These proportional benefits vary little between different groups of women. By contrast, the absolute benefits from radiotherapy vary substantially according to the characteristics of the patient and they can be predicted at the time when treatment decisions need to be made.
Funding: Cancer Research UK, British Heart Foundation, and UK Medical Research Council.

Mejoramiento del sistema de recursos humanos en cuatro localidades de santa fe de Bogotá

en el presente estudio se ha analizado el recurso humano de cuatro localidades de Santa Fe de Bogotá, con el fin de crear un sistema que mejore los procesos de contratación, capacitación, remuneración y motivación de las personas.

Impacto de las cirugías múltiples, en un solo tiempo quirúrgico, sobre el patrón de marcha en niños con parálisis cerebral

Introducción: La Parálisis Cerebral (PC) es la enfermedad neurológica más incapacitante en niños, su historia natural tiende al deterioro motor y funcional. Con este estudio se busca establecer sí las cirugías múltiples de miembros inferiores, en un tiempo quirúrgico, mantienen el nivel motor y funcional. Material y Método: Estudio analítico de cohortes. Se compara un grupo de pacientes sometidos a cirugías múltiples contra un grupo de pacientes no operados, en el Instituto de Ortopedia Infantil Roosevelt. Se evaluaron los pacientes con dos Laboratorios para el Análisis del Movimiento (LAM) y se midieron los desenlaces mediante el cambio en la puntuación del perfil de marcha (GPS) y el nivel funcional motor grueso (GMFCS). Resultados: 109 pacientes cumplieron con los criterios de selección, 67 pacientes fueron sometidos a cirugía y 42 pacientes no. Los pacientes operados mejoraron el GPS promedio (diferencia -1,94; p=0,002) comparado con los pacientes no operados (diferencia 1,74; p=0,001), indicando una mejoría significativa de la cinemática de la marcha. En un modelo de regresión logística predictivo, el paciente que es operado tiene una probabilidad del 78% de mantener su patrón de marcha, mientras que sí no se opera su probabilidad disminuye al 37%. El nivel funcional motor GMFCS no mostró cambios significativos entre los grupos. Discusión: Las cirugías múltiples de miembros inferiores mantienen de manera significativa el patrón de marcha en pacientes con PC. Se destaca el seguimiento de los pacientes mediante el LAM y se sugiere el uso del GPS para valorar resultados en este tipo de pacientes.

Evaluación de intervención de alertas para riesgo cardiovascular por diclofenaco en afiliados al régimen contributivo 2014 -2015

El objetivo fue evaluar la intervención de las alertas en la prescripción de diclofenaco. Estudio observacional, comparativo, post intervención, de un antes después, en pacientes con prescripción de diclofenaco. Se evaluó la intervención de las alertas restrictivas antes y después de su implementación en los pacientes prescritos con diclofenaco y que tenían asociado un diagnóstico de riesgo cardiovascular según CIE 10 o eran mayores de 65 años. Un total de 315.135 transacciones con prescripción de diclofenaco, en 49.355 pacientes promedio mes. El 94,8% (298.674) de las transacciones fueron prescritas por médicos generales.

The drop goes plop : a first look at the water cycle.

Mamá y su bebé gaviota siguen el viaje épico de una gota de agua desde la formación de las nubes hasta la caída de la gota. Proporciona una primera introducción al ciclo del agua y se acompaña de distintas actividades para realizar en clase y que ayudan a los niños a comprenderlo. Por su tamaño, es idóneo para debates en grupo y lectura compartida. Al final hay un pequeño glosario.

Evolutionary dynamics of Staphylococcus aureus during progression from carriage to disease

Whole-genome sequencing offers new insights into the evolution of bacterial pathogens and the etiology of bacterial disease. Staph- ylococcus aureus is a major cause of bacteria-associated mortality and invasive disease and is carried asymptomatically by 27% of adults. Eighty percent of bacteremias match the carried strain. How- ever, the role of evolutionary change in the pathogen during the progression from carriage to disease is incompletely understood. Here we use high-throughput genome sequencing to discover the genetic changes that accompany the transition from nasal carriage to fatal bloodstream infection in an individual colonized with meth- icillin-sensitive S. aureus. We found a single, cohesive population exhibiting a repertoire of 30 single-nucleotide polymorphisms and four insertion/deletion variants. Mutations accumulated at a steady rate over a 13-mo period, except for a cluster of mutations preceding the transition to disease. Although bloodstream bacteria differed by just eight mutations from the original nasally carried bacteria, half of those mutations caused truncation of proteins, including a prema- ture stop codon in an AraC-family transcriptional regulator that has been implicated in pathogenicity. Comparison with evolution in two asymptomatic carriers supported the conclusion that clusters of pro- tein-truncating mutations are highly unusual. Our results demon- strate that bacterial diversity in vivo is limited but nonetheless detectable by whole-genome sequencing, enabling the study of evolutionary dynamics within the host. Regulatory or structural changes that occur during carriage may be functionally important for pathogenesis; therefore identifying those changes is a crucial step in understanding the biological causes of invasive bacterial disease.

Within-host evolution of Staphylococcus aureus during asymptomatic carriage

Background Staphylococcus aureus is a major cause of healthcare associated mortality, but like many important bacterial pathogens, it is a common constituent of the normal human body flora. Around a third of healthy adults are carriers. Recent evidence suggests that evolution of S. aureus during nasal carriage may be associated with progression to invasive disease. However, a more detailed understanding of within-host evolution under natural conditions is required to appreciate the evolutionary and mechanistic reasons why commensal bacteria such as S. aureus cause disease. Therefore we examined in detail the evolutionary dynamics of normal, asymptomatic carriage. Sequencing a total of 131 genomes across 13 singly colonized hosts using the Illumina platform, we investigated diversity, selection, population dynamics and transmission during the short-term evolution of S. aureus. Principal Findings We characterized the processes by which the raw material for evolution is generated: micro-mutation (point mutation and small insertions/deletions), macro-mutation (large insertions/deletions) and the loss or acquisition of mobile elements (plasmids and bacteriophages). Through an analysis of synonymous, non-synonymous and intergenic mutations we discovered a fitness landscape dominated by purifying selection, with rare examples of adaptive change in genes encoding surface-anchored proteins and an enterotoxin. We found evidence for dramatic, hundred-fold fluctuations in the size of the within-host population over time, which we related to the cycle of colonization and clearance. Using a newly-developed population genetics approach to detect recent transmission among hosts, we revealed evidence for recent transmission between some of our subjects, including a husband and wife both carrying populations of methicillin-resistant S. aureus (MRSA). Significance This investigation begins to paint a picture of the within-host evolution of an important bacterial pathogen during its prevailing natural state, asymptomatic carriage. These results also have wider significance as a benchmark for future systematic studies of evolution during invasive S. aureus disease.

Mobile elements drive recombination hotspots in the core genome of Staphylococcus aureus

Horizontal gene transfer is an important driver of bacterial evolution, but genetic exchange in the core genome of clonal species, including the major pathogen Staphylococcus aureus, is incompletely understood. Here we reveal widespread homologous recombination in S. aureus at the species level, in contrast to its near-complete absence between closely related strains. We discover a patchwork of hotspots and coldspots at fine scales falling against a backdrop of broad-scale trends in rate variation. Over megabases, homoplasy rates fluctuate 1.9-fold, peaking towards the origin-of-replication. Over kilobases, we find core recombination hotspots of up to 2.5-fold enrichment situated near fault lines in the genome associated with mobile elements. The strongest hotspots include regions flanking conjugative transposon ICE6013, the staphylococcal cassette chromosome (SCC) and genomic island νSaα. Mobile element-driven core genome transfer represents an opportunity for adaptation and challenges our understanding of the recombination landscape in predominantly clonal pathogens, with important implications for genotype–phenotype mapping.

Peak residential electricity demand and social practices: Deriving flexibility and greenhouse gas intensities from time use and locational data

Peak residential electricity demand takes place when people conduct simultaneous activities at specific times of the day. Social practices generate patterns of demand and can help understand why, where, with whom and when energy services are used at peak time. The aim of this work is to make use of recent UK time use and locational data to better understand: (i) how a set of component indices on synchronisation, variation, sharing and mobility indicate flexibility to shift demand; and (ii) the links between people’s activities and peaks in greenhouse gases’ intensities. The analysis is based on a recent UK time use dataset, providing 1 minute interval data from GPS devices and 10 minute data from diaries and questionnaires for 175 data days comprising 153 respondents. Findings show how greenhouse gases’ intensities and flexibility to shift activities vary throughout the day. Morning peaks are characterised by high levels of synchronisation, shared activities and occupancy, with low variation of activities. Evening peaks feature low synchronisation, and high spatial mobility variation of activities. From a network operator perspective, the results indicate that periods with lower flexibility may be prone to more significant local network loads due to the synchronization of electricity-demanding activities.

A glimpse of the ERM proteins

In all eukaryotes, the plasma membrane is critically important as it maintains the architectural integrity of the cell. Proper anchorage and interaction between the plasma membrane and the cytoskeleton is critical for normal cellular processes. The ERM (ezrin-radixin-moesin) proteins are a class of highly homologous proteins involved in linking the plasma membrane to the cortical actin cytoskeleton. This review takes a succinct look at the biology of the ERM proteins including their structure and function. Current reports on their regulation that leads to activation and deactivation was examined before taking a look at the different interacting partners. Finally, emerging roles of each of the ERM family members in cancer was highlighted.

The Probe, Issue 204 - September 1999

USFWS to Explore Canada Goose Management Strategies -- from a press release issued Aug. 3 by the US. Fish & Wildlife Service, written by Chris Tollefson. Anti-Trapping Measure Passes House Oregon Legislature Moves To Ensure Safety Of Its Citizens Against Cougars Acord Promoted Away From Wildlife Services New State Director US DA/APHIS in Mississippi is Kristina Godwin BOOk R e v i e w : "Living With Wildlife: How to Enjoy, Cope With, and Protect North America's Wild Creatures Around Your Home and Theirs," The California Center for Wildlife, with Diana Landau and Shelley Stump. San Francisco: A Sierra Club Book. 1994. 340 pp. + index $15.00. French Shepherds Protest Predators Rabbit Calicivirus Kills 65% of Rabbit Population Abstracts from the 2nd International Wildlife Management Congress, Hungary Crop Damage by Wildlife in Northern Ghana – O. I. Aalangdon* and A.S. Langyintuo, *Dept. of Renewable Natural Resources, University for Development Studies, Tamale Northern Region, Ghana Large Predators in Slovenia On the Way from Near Extermination to Overprotection and Back: Is Conservation Management of Large Predators in Cultural Landscapes Possible At All? -- M. Adamic, Chair of Wildlife Ecology, Biotechnical Faculty, University of Ljubljana, Slovenia Human-wolf Conflicts in the East Baltic: Past, Present, and Future -- Z. Andersone*, L. Balciauskas, and H. Valdmann., *Kemeri National Park, KemeriJurmala, Latvia Gray Wolf Restoration in the Northwestern United States -- E.E. Bangs*, J.A. Fontaine, D.W. Smith, C. Mack, and C. C. Niemeyer, *U.S. Fish & Wildlife Service, Helena, MT The Impact of Changing U.S. Demographics on the Future of Deer Hunting -- R. D. Brown, Wildlife & Fisheries Sciences, Texas A&M University, College Station, TX Management of Overabundant Marcropods in Nature Reserves: 6 Case Studies from Southeastern Australia -- G. Coulson, Dept. of Zoology,University of Melbourne,Parkville, Victoria, Australia

The ring vaccination trial: a novel cluster randomised controlled trial design to evaluate vaccine efficacy and effectiveness during outbreaks, with special reference to Ebola

A World Health Organization expert meeting on Ebola vaccines proposed urgent safety and efficacy studies in response to the outbreak in West Africa. One approach to communicable disease control is ring vaccination of individuals at high risk of infection due to their social or geographical connection to a known case. This paper describes the protocol for a novel cluster randomised controlled trial design which uses ring vaccination.In the Ebola ça suffit ring vaccination trial, rings are randomised 1:1 to (a) immediate vaccination of eligible adults with single dose vaccination or (b) vaccination delayed by 21 days. Vaccine efficacy against disease is assessed in participants over equivalent periods from the day of randomisation. Secondary objectives include vaccine effectiveness at the level of the ring, and incidence of serious adverse events.Ring vaccination trials are adaptive, can be run until disease elimination, allow interim analysis, and can go dormant during inter-epidemic periods.