Defining disease modification in myelofibrosis in the era of targeted therapy

The development of targeted therapies for the treatment of myelofibrosis highlights a unique issue in a field that has historically relied on symptom relief, rather than survival benefit or modification of disease course, as key response criteria. There is, therefore, a need to understand what constitutes disease modification of myelofibrosis to advance appropriate drug development and therapeutic pathways. Here, the authors discuss recent clinical trial data of agents in development and dissect the potential for novel end points to act as disease modifying parameters. Using the rationale garnered from latest clinical and scientific evidence, the authors propose a definition of disease modification in myelofibrosis. With improved overall survival a critical outcome, alongside the normalization of hematopoiesis and improvement in bone marrow fibrosis, there will be an increasing need for surrogate measures of survival for use in the early stages of trials. As such, the design of future clinical trials will require re-evaluation and updating to incorporate informative parameters and end points with standardized definitions and methodologies

The role of mentorship in protege performance

The role of mentorship on protege performance is a matter of importance to academic, business, and governmental organizations. While the benefits of mentorship for proteges, mentors and their organizations are apparent, the extent to which proteges mimic their mentors' career choices and acquire their mentorship skills is unclear. Here, we investigate one aspect of mentor emulation by studying mentorship fecundity---the number of proteges a mentor trains---with data from the Mathematics Genealogy Project, which tracks the mentorship record of thousands of mathematicians over several centuries. We demonstrate that fecundity among academic mathematicians is correlated with other measures of academic success. We also find that the average fecundity of mentors remains stable over 60 years of recorded mentorship. We further uncover three significant correlations in mentorship fecundity. First, mentors with small mentorship fecundity train proteges that go on to have a 37% larger than expected mentorship fecundity. Second, in the first third of their career, mentors with large fecundity train proteges that go on to have a 29% larger than expected fecundity. Finally, in the last third of their career, mentors with large fecundity train proteges that go on to have a 31% smaller than expected fecundity.Comment: 23 pages double-spaced, 4 figure

Use of domesticated pigs by Mesolithic hunter-gatherers in northwestern Europe

Acknowledgements We thank the Archaeological State Museum Schleswig-Holstein, the Archaeological State Offices of Brandenburg, Lower Saxony and Saxony and the following individuals who provided sample material: Betty Arndt, Jo¨rg Ewersen, Frederick Feulner, Susanne Hanik, Ru¨diger Krause, Jochen Reinhard, Uwe Reuter, Karl-Heinz Ro¨hrig, Maguerita Scha¨fer, Jo¨rg Schibler, Reinhold Schoon, Regina Smolnik, Thomas Terberger and Ingrid Ulbricht. We are grateful to Ulrich Schmo¨lcke, Michael Forster, Peter Forster and Aikaterini Glykou for their support and comments on the manuscript. We also thank many institutions and individuals that provided sample material and access to collections, especially the curators of the Museum fu¨r Naturkunde, Berlin; Muse´um National d0 Histoire Naturelle, Paris; Smithsonian Institution, National Museum of Natural History, Washington D.C.; Zoologische Staatssammlung, Mu¨nchen; Museum fu¨r Haustierkunde, Halle; the American Museum of Natural History, New-York. This work was funded by the Graduate School ‘Human Development in Landscapes’ at Kiel University (CAU) and supported by NERC project Grant NE/F003382/1. Radiocarbon dating was carried out at the Leibniz Laboratory, CAU. This work is licensed under a Creative Commons AttributionNonCommercial-NoDerivs 3.0 Unported License.Peer reviewedPublisher PD

Exploring the impact of mentoring functions on job satisfaction and organizational commitment of new staff nurses

<p>Abstract</p> <p>Background</p> <p>Although previous studies proved that the implementation of mentoring program is beneficial for enhancing the nursing skills and attitudes, few researchers devoted to exploring the impact of mentoring functions on job satisfaction and organizational commitment of new nurses. In this research we aimed at examining the effects of mentoring functions on the job satisfaction and organizational commitment of new nurses in Taiwan's hospitals.</p> <p>Methods</p> <p>We employed self-administered questionnaires to collect research data and select new nurses from three regional hospitals as samples in Taiwan. In all, 306 nurse samples were obtained. We adopted a multiple regression analysis to test the impact of the mentoring functions.</p> <p>Results</p> <p>Results revealed that career development and role modeling functions have positive effects on the job satisfaction and organizational commitment of new nurses; however, the psychosocial support function was incapable of providing adequate explanation for these work outcomes.</p> <p>Conclusion</p> <p>It is suggested in this study that nurse managers should improve the career development and role modeling functions of mentoring in order to enhance the job satisfaction and organizational commitment of new nurses.</p

Genomic diversity and differentiation of a managed island wild boar population

The evolution of island populations in natural systems is driven by local adaptation and genetic drift. However, evolutionary pathways may be altered by humans in several ways. The wild boar (WB) (Sus scrofa) is an iconic game species occurring in several islands, where it has been strongly managed since prehistoric times. We examined genomic diversity at 49 803 single-nucleotide polymorphisms in 99 Sardinian WBs and compared them with 196 wild specimens from mainland Europe and 105 domestic pigs (DP; 11 breeds). High levels of genetic variation were observed in Sardinia (80.9% of the total number of polymorphisms), which can be only in part associated to recent genetic introgression. Both Principal Component Analysis and Bayesian clustering approach revealed that the Sardinian WB population is highly differentiated from the other European populations (F ST =0.126-0.138), and from DP (F ST =0.169). Such evidences were mostly unaffected by an uneven sample size, although clustering results in reference populations changed when the number of individuals was standardized. Runs of homozygosity (ROHs) pattern and distribution in Sardinian WB are consistent with a past expansion following a bottleneck (small ROHs) and recent population substructuring (highly homozygous individuals). The observed effect of a non-random selection of Sardinian individuals on diversity, F ST and ROH estimates, stressed the importance of sampling design in the study of structured or introgressed populations. Our results support the heterogeneity and distinctiveness of the Sardinian population and prompt further investigations on its origins and conservation status.</p

Clobetasol promotes neuromuscular plasticity in mice after motoneuronal loss via sonic hedgehog signaling, immunomodulation and metabolic rebalancing

Motoneuronal loss is the main feature of amyotrophic lateral sclerosis, although pathogenesis is extremely complex involving both neural and muscle cells. In order to translationally engage the sonic hedgehog pathway, which is a promising target for neural regeneration, recent studies have reported on the neuroprotective effects of clobetasol, an FDA-approved glucocorticoid, able to activate this pathway via smoothened. Herein we sought to examine functional, cellular, and metabolic effects of clobetasol in a neurotoxic mouse model of spinal motoneuronal loss. We found that clobetasol reduces muscle denervation and motor impairments in part by restoring sonic hedgehog signaling and supporting spinal plasticity. These effects were coupled with reduced pro-inflammatory microglia and reactive astrogliosis, reduced muscle atrophy, and support of mitochondrial integrity and metabolism. Our results suggest that clobetasol stimulates a series of compensatory processes and therefore represents a translational approach for intractable denervating and neurodegenerative disorders

Исследование оптических спектров химически модифицированного поливинилиденфторида

The present study aims to extend insights of surf zone turbulence dynamics to wave groups. In a large-scale wave flume, bichromatic wave groups were produced with 31.5 s group period, 4.2 s mean wave period, and a 0.58 m maximum wave height near the paddle. This condition resulted in plunging-type wave breaking over a fixed, gravel-bed, barred profile. Optic, acoustic and electromagnetic instruments were used to measure the flow and the spatial and temporal distributions of turbulent kinetic energy (TKE). The measurements showed that turbulence in the shoaling region is primarily bed-generated and decays almost fully within one wave cycle, leading to TKE variations at the short wave frequency. The wave breaking-generated turbulence, in contrast, decays over multiple wave cycles, leading to a gradual increase and decay of TKE during a wave group cycle. In the wave breaking region, TKE dynamics are driven by the production and subsequent downward transport of turbulence under the successive breaking waves in the group. Consequently, the maximum near-bed TKE in the breaking region can lag the highest breaking wave by up to 2.5 wave cycles. The net cross-shore transport of TKE is in the shoaling region primarily driven by short-wave velocities and is shoreward-directed; in the wave breaking region, the TKE transport is seaward-directed by the undertow and the long-wave velocities. Downward transport of TKE is driven by the vertical component of the time-averaged flow. The cross-shore and vertical diffusive transport rates are small relative to the advective transport rates

The present state of research into industrial clusters and districts. Content analysis of material published 1997-2006

[EN] The aim of this work is to help gain a better understanding of the research conducted on territorial agglomerations of firms at a multidisciplinary level. To this end, an analysis was performed of the contents of the most significant scientific literature on economics, management, planning and development, urban studies and geography published over the period 1997-2006. From the results, a database of 142 papers from 43 journals was then elaborated. An analysis of these works reveals the level of development of the main lines of research in this field and, consequently, makes it possible to detect the topics that require greater attention and that can be the object of future research for researchers and academics. The main conclusions include the growing number of studies conducted on the subject in recent years, as well as a greater predominance of empirical research over conceptual work, and the existence of a significant change in the topics or lines of research throughout the period under study. © 2012 Copyright Taylor and Francis Group, LLC.This research was financed by the Spanish Ministry of Education and Science, National R&D & Innovation Plan 2007–2010, under the project entitled “El Distrito Industrial: el impacto del Capital Social sobre la Gestio´n de la Cadena de Suministro” (The Industrial District: the impact of Social Capital on the management of the Supply Chain) (SEJ2007- 62876/ECON).Martinez-Fernandez, M.; Capó Vicedo, J.; Vallet-Bellmunt, T. (2012). The present state of research into industrial clusters and districts. Content analysis of material published 1997-2006. European Planning Studies. 20(2):281-304. doi:10.1080/09654313.2012.650906S28130420