George Elson (ca. 1875-ca. 1950)

... We know little of Elson's childhood. His father, a Scot, worked for the Hudson's Bay Company and, as was often the custom of the country, married a Cree. George grew up nurtured by both cultures, yet in some respects caught between them, like so many children of mixed parentage. In his mid-twenties, having worked for a survey crew of the Grand Trunk Railroad, he found himself in Missanabie, Ontario, when fate struck. A journalist from New York by the name of Leonidas Hubbard, Jr., had written the Hudson's Bay post, seeking a reliable outdoorsman for an expedition to Labrador on behalf of Outing magazine. When two other candidates did not pan out, Elson was chosen. Hubbard proved to be friendly and generous - full of an almost boyish enthusiasm. But he had never travelled the bush for an extended period, nor had his companion, Dillon Wallace, a New York attorney. Elson felt at home in the woods, but could not help wondering about the expedition's outfit. It included two rifles and pistols, but no shotgun, which would make winging birds much more difficult. Nor was Hubbard able to purchase a gill net in Labrador, as he had hoped. On July 15, 1903, the trio set off down Grand Lake from Northwest River Post, seeking to ascend the Naskapi River into central Labrador and witness the autumn caribou hunt of the Naskapi Indians. Anxious to make up for lost time, Hubbard missed the Naskapi River and instead headed up the tiny Susan Brook, which soon dwindled into a rock-filled obstacle course. As conditions worsened, Elson saw the threat of starvation looming. ... For the next month the men retraced their steps in raw weather. Elson, with remarkable skill, bagged an occasional goose, but with no shotgun and no gill net, the expedition's plight was desperate. Finally Hubbard collapsed, unable to proceed. Making him as comfortable as possible in a tent, Wallace and Elson continued down Susan Brook on October 18; three days later they parted in the midst of the season's first blizzard, Wallace to return to Hubbard with some moldy flour they had retrieved (left behind earlier in the expedition), Elson to go for help on Grand Lake. For five days, he stumbled through snowdrifts, his trousers in tatters, his feet wrapped in scraps of blanket. ... Reaching a trapper's cabin, he sped rescuers upstream, but Hubbard was beyond help. He had died the day of the parting. Wallace was only barely alive - a hardly recognizable skeleton. Over that winter he and Elson recovered at Northwest River Post and returned home in May 1904. ... Devastated by the loss of her husband, Mina Hubbard turned from grief to anger. Why had her husband perished, when the other men had not? ... When Wallace, still loyal to the memory of his friend, announced he was returning to Labrador to finish Hubbard's work, Mina secretly organized an expedition of her own. ... Thus when Wallace headed north in June 1905, he was surprised to find a female rival determined to upstage him - with an able woodsman in charge of the task. Under Elson's leadership, Mina Hubbard completed her expedition nearly flawlessly. The party visited the Naskapi, witnessed the caribou migration, and arrived at George River Post in Ungava Bay on August 29. Wallace, who became lost pioneering an alternate route, did not arrive until mid-October. But the most poignant aspect of the tale was that Elson, struck by Mina Hubbard's kindness and spirited humor, seems to have fallen in love. ... Little has been uncovered of Elson's later years. He married relatively late, to a Cree woman. Working for Revillon Fur Company, he settled at Moose Factory. Only once, in 1936, did he see Mina Hubbard again, when she visited him in her sixties. ..

The emerging structure of the Extended Evolutionary Synthesis: where does Evo-Devo fit in?

The Extended Evolutionary Synthesis (EES) debate is gaining ground in contemporary evolutionary biology. In parallel, a number of philosophical standpoints have emerged in an attempt to clarify what exactly is represented by the EES. For Massimo Pigliucci, we are in the wake of the newest instantiation of a persisting Kuhnian paradigm; in contrast, Telmo Pievani has contended that the transition to an EES could be best represented as a progressive reformation of a prior Lakatosian scientific research program, with the extension of its Neo-Darwinian core and the addition of a brand-new protective belt of assumptions and auxiliary hypotheses. Here, we argue that those philosophical vantage points are not the only ways to interpret what current proposals to ‘extend’ the Modern Synthesis-derived ‘standard evolutionary theory’ (SET) entail in terms of theoretical change in evolutionary biology. We specifically propose the image of the emergent EES as a vast network of models and interweaved representations that, instantiated in diverse practices, are connected and related in multiple ways. Under that assumption, the EES could be articulated around a paraconsistent network of evolutionary theories (including some elements of the SET), as well as models, practices and representation systems of contemporary evolutionary biology, with edges and nodes that change their position and centrality as a consequence of the co-construction and stabilization of facts and historical discussions revolving around the epistemic goals of this area of the life sciences. We then critically examine the purported structure of the EES—published by Laland and collaborators in 2015—in light of our own network-based proposal. Finally, we consider which epistemic units of Evo-Devo are present or still missing from the EES, in preparation for further analyses of the topic of explanatory integration in this conceptual framework

Genome-Wide Identification of Calcium-Response Factor (CaRF) Binding Sites Predicts a Role in Regulation of Neuronal Signaling Pathways

Calcium-Response Factor (CaRF) was first identified as a transcription factor based on its affinity for a neuronal-selective calcium-response element (CaRE1) in the gene encoding Brain-Derived Neurotrophic Factor (BDNF). However, because CaRF shares no homology with other transcription factors, its properties and gene targets have remained unknown. Here we show that the DNA binding domain of CaRF has been highly conserved across evolution and that CaRF binds DNA directly in a sequence-specific manner in the absence of other eukaryotic cofactors. Using a binding site selection screen we identify a high-affinity consensus CaRF response element (cCaRE) that shares significant homology with the CaRE1 element of Bdnf. In a genome-wide chromatin immunoprecipitation analysis (ChIP-Seq), we identified 176 sites of CaRF-specific binding (peaks) in neuronal genomic DNA. 128 of these peaks are within 10kB of an annotated gene, and 60 are within 1kB of an annotated transcriptional start site. At least 138 of the CaRF peaks contain a common 10-bp motif with strong statistical similarity to the cCaRE, and we provide evidence predicting that CaRF can bind independently to at least 64.5% of these motifs in vitro. Analysis of this set of putative CaRF targets suggests the enrichment of genes that regulate intracellular signaling cascades. Finally we demonstrate that expression of a subset of these target genes is altered in the cortex of Carf knockout (KO) mice. Together these data strongly support the characterization of CaRF as a unique transcription factor and provide the first insight into the program of CaRF-regulated transcription in neurons

Cediranib combined with carboplatin and paclitaxel in patients with metastatic or recurrent cervical cancer (CIRCCa): a randomised, double-blind, placebo-controlled phase 2 trial

Background: Patients treated with standard chemotherapy for metastatic or relapsed cervical cancer respond poorly to conventional chemotherapy (response achieved in 20–30% of patients) with an overall survival of less than 1 year. High tumour angiogenesis and high concentrations of intratumoural VEGF are adverse prognostic features. Cediranib is a potent tyrosine kinase inhibitor of VEGFR1, 2, and 3. In this trial, we aimed to assess the effect of the addition of cediranib to carboplatin and paclitaxel chemotherapy in patients with metastatic or recurrent cervical cancer. Methods: In this randomised, double-blind, placebo-controlled phase 2 trial, which was done in 17 UK cancer treatment centres, patients aged 18 years or older initially diagnosed with metastatic carcinoma or who subsequently developed metastatic disease or local pelvic recurrence after radical treatment that was not amenable to exenterative surgery were recruited. Eligible patients received carboplatin AUC of 5 plus paclitaxel 175 mg/m2 by infusion every 3 weeks for a maximum of six cycles and were randomised centrally (1:1) through a minimisation approach to receive cediranib 20 mg or placebo orally once daily until disease progression. The stratification factors were disease site, disease-free survival after primary therapy or primary stage IVb disease, number of lines of previous treatment, Eastern Cooperative Oncology Group performance status, and investigational site. All patients, investigators, and trial personnel were masked to study drug allocation. The primary endpoint was progression-free survival. Efficacy analysis was by intention to treat, and the safety analysis included all patients who received at least one dose of study drug. This trial is registered with the ISCRTN registry, number ISRCTN23516549, and has been completed. Findings: Between Aug 19, 2010, and July 27, 2012, 69 patients were enrolled and randomly assigned to cediranib (n=34) or placebo (n=35). After a median follow-up of 24·2 months (IQR 21·9–29·5), progression-free survival was longer in the cediranib group (median 8·1 months [80% CI 7·4–8·8]) than in the placebo group (6·7 months [6·2–7·2]), with a hazard ratio (HR) of 0·58 (80% CI 0·40–0·85; one-sided p=0·032). Grade 3 or worse adverse events that occurred in the concurrent chemotherapy and trial drug period in more than 10% of patients were diarrhoea (five [16%] of 32 patients in the cediranib group vs one [3%] of 35 patients in the placebo group), fatigue (four [13%] vs two [6%]), leucopenia (five [16%] vs three [9%]), neutropenia (10 [31%] vs four [11%]), and febrile neutropenia (five [16%] vs none). The incidence of grade 2–3 hypertension was higher in the cediranib group than in the control group (11 [34%] vs four [11%]). Serious adverse events occurred in 18 patients in the placebo group and 19 patients in the cediranib group. Interpretation: Cediranib has significant efficacy when added to carboplatin and paclitaxel in the treatment of metastatic or recurrent cervical cancer. This finding was accompanied by an increase in toxic effects (mainly diarrhoea, hypertension, and febrile neutropenia)

Developing Behavior Change Interventions

Peer reviewe

Changing Behavior : A Theory- and Evidence-Based Approach

Social problems in many domains, including health, education, social relationships, and the workplace, have their origins in human behavior. The documented links between behavior and social problems have sparked interest in governments and organizations to develop effective interventions to promote behavior change. The Handbook of Behavior Change provides comprehensive coverage of contemporary theory, research, and practice on behavior change. The handbook incorporates theory- and evidence-based approaches to behavior change with chapters from leading theorists, researchers, and practitioners from multiple disciplines, including psychology, sociology, behavioral science, economics, and implementation science. Chapters are organized into three parts: (1) Theory and Behavior Change; (2) Methods and Processes of Behavior Change: Intervention Development, Application, and Translation; and (3) Behavior Change Interventions: Practical Guides to Behavior Change. This chapter provides an overview of the theory- and evidence-based approaches of the handbook, introduces the content of the handbook, and provides suggestions on how the handbook may be used by different readers. The handbook aims to provide all interested in behavior change, including researchers and students, practitioners, and policy makers, with up-to-date knowledge on behavior change and guidance on how to develop effective interventions to change behavior in different populations and contexts.Peer reviewe