The Role of Artefacts in the Process of Replication

This paper investigates the role of artefacts for the replication or routines in organizations. Drawing on data of a large franchise organization in the UK, we show that actors' engagement with a portfolio of different primary (e.g. software, tools) and secondary (e.g. manuals) artefacts that are part of the business format, gives rise to five artefact enabled practices of replication (activity scoping, time patterning, practical enquiry, use in practice and contextual enquiry). Importantly, these practices of replication enable three different types of franchisee agency (iterational, practical evaluative and projective agency) that support but partly also challenge replication in terms of the similarity of organizational routines across units. Our findings have several theoretical contributions for the growing literature on replication as well as materiality and artefacts in organizations.

Cellular hyper-excitability caused by mutations that alter the activation process of voltage-gated sodium channels.

Voltage-gated sodium channels (Nav) are widely expressed as macro-molecular complexes in both excitable and non-excitable tissues. In excitable tissues, the upstroke of the action potential is the result of the passage of a large and rapid influx of sodium ions through these channels. NaV dysfunction has been associated with an increasingly wide range of neurological, muscular and cardiac disorders. The purpose of this review is to summarize the recently identified sodium channel mutations that are linked to hyper-excitability phenotypes and associated with the alteration of the activation process of voltage gated sodium channels. Indeed, several clinical manifestations that demonstrate an alteration of tissue excitability were recently shown to be strongly associated with the presence of mutations that affect the activation process of the Nav. These emerging genotype-phenotype correlations have expanded the clinical spectrum of sodium channelopathies to include disorders which feature a hyper-excitability phenotype that may or may not be associated with a cardiomyopathy. The p.I141V mutation in SCN4A and SCN5A, as well as its homologous p.I136V mutation in SCN9A, are interesting examples of mutations that have been linked to inherited hyperexcitability myotonia, exercise-induced polymorphic ventricular arrhythmias and erythromelalgia, respectively. Regardless of which sodium channel isoform is investigated, the substitution of the isoleucine to valine in the locus 141 induces similar modifications in the biophysical properties of the Nav by shifting the voltage-dependence of steady state activation toward more negative potentials.

The Arduous Process of Climate Change Negotiations: How Science Can Facilitate the Desired Outcome

Effective interaction between climate science and policy is important for moving climate negotiations forward to reach an ambitious global climate change deal. Lack of progress in the United Nations Framework Convention on Climate Change (UNFCCC) negotiations during recent years is a good reason for taking a closer look at the process of climate science–policy interaction to identify and eliminate existing shortcomings hindering climate policymaking. This paper examines the current state of climate science–policy interaction and suggests ways to integrate scientific input into the UNFCCC process more effectively. Suggestions relate to improvement in institutional structures, processes and procedures of the UNFCCC and the Intergovernmental Panel on Climate Change (IPCC), quality of scientific input, credibility of scientific message and public awareness of climate change.

Mechanical and radiological assessment of the influence of rhTGFbeta-3 on bone regeneration in a segmental defect in the ovine tibia: pilot study

Limitations in the use of autologous bone graft, which is the gold standard therapy in bone defect healing, drive the search for alternative treatments. In this study the influence of rhTGFbeta-3 on mechanical and radiological parameters of a healing bone defect in the sheep tibia was assessed. In the sheep, an 18-mm long osteoperiosteal defect in the tibia was treated by rhTGFbeta-3 seeded on a poly(L/DL-lactide) carrier (n = 4). In a second group (n = 4), the defect was treated by the carrier only, in a third group (n = 4) by autologous cancellous bone graft, and in a fourth group (n = 2) the defect remained blank. The healing process of the defect was assessed by weekly in vivo stiffness measurements and radiology as well as by quantitative computed tomographic assessment of bone mineral density (BMD) every 4 weeks. The duration of the experiment was 12 weeks under loading conditions. In the bone graft group, a marginally significant higher increase in stiffness was observed than in the PLA/rhTGFbeta-3 group (p = 0.06) and a significantly higher increase than in the PLA-only group (p = 0.03). The radiographic as well as the computed tomographic evaluation yielded significant differences between the groups (p = 0.03), indicating the bone graft treatment (bone/per area, 83%; BMD, 0.57 g/cm(3)) performing better than the PLA/rhTGFbeta-3 (38%; 0.23 g/cm(3)) and the PLA-only treatment (2.5%; 0.09 g/cm(3)), respectively. Regarding the mechanical and radiological parameters assessed in this study, we conclude that rhTGFbeta-3 has a promoting effect on bone regeneration. However, under the conditions of this study, this effect does not reach the potential of autologous cancellous bone graft transplantation.

The influence of measles vaccination on the incidence of otosclerosis in Germany

The pathologic process of otosclerosis is characterized by an inflammatory lytic phase followed by an abnormal bone remodeling at very specific sites of predilection. There is a clear genetic predisposition with about half of all cases occurring in families with more than one affected member. Females are affected more frequently than males with an approximate 2:1 ratio. N, H, and F measles proteins as well as measles virus RNA have been demonstrated in osteoblasts, chondroblasts, and macrophages of the inflammatory phase of the disease. These observations merely show an association between measles viruses and otosclerosis. In the present study, we tried to prove that there is a causal relationship: voluntary measles vaccination has been available in Germany since 1974. In the absence of official data, we reconstructed the rate of vaccination coverage between 1974 and 2004 using information from the Robert Koch Institute (RKI, Berlin) and from the literature. From the German Federal Office of Statistics, we received the data of 64,112 patients who had been hospitalized between 1993 and 2004 and in whom otosclerosis (ICD-9: 387; ICD-10: H80) had been confirmed. We calculated the effect of measles vaccination on the incidence of hospital treatments for otosclerosis in the period from 1993 to 2004 in Germany. For this purpose, we divided the female and male otosclerosis patients treated as inpatients each year in the observation period into two age groups: those up to 25 years, who had in most cases been vaccinated (designated below as "vaccinated patients") and those over 25 years who mostly could not have been vaccinated (designated below as "unvaccinated patients"). We calculated the incidence of otosclerosis requiring inpatient treatment for the two age groups in each year in the period of observation. For external validation of the study results, the same analysis was carried out in all patients who received inpatient treatment for otitis media in the same period. Between 1993 and 2004 the incidence of hospital treatments for otosclerosis decreased to a significantly greater extent in the vaccinated patients than in the unvaccinated patients. The decline is much greater in men than in women. A comparable effect cannot be demonstrated in patients with otitis media. The results indicate that measles vaccination in Germany has resulted in a significant reduction in the number of hospital treatments for otosclerosis in the vaccinated age groups. We conclude that there is a causal relationship between measles viruses and the development of otosclerosis.

Pattern and process: competition causes regular spacing of individuals within plant populations

1 We used simulated and experimental plant populations to analyse mortality-driven pattern formation under size-dependent competition. Larger plants had an advantage under size-asymmetric but not under symmetric competition. Initial patterns were random or clumped. 2 The simulations were individual-based and spatially explicit. Size-dependent competition was modelled with different rules to partition overlapping zones of influence. 3 The experiment used genotypes of Arabidopsis thaliana with different morphological plasticity and hence size-dependent competition. Compared with wild types, transgenic individuals over-expressed phytochrome A and had decreased plasticity because of disabled phytochrome-mediated shade avoidance. Therefore, competition among transgenics was more asymmetric compared with wild-types. 4 Density-dependent mortality under symmetric competition did not substantially change the initial spatial pattern. Conversely, simulations under asymmetric competition and experimental patterns of transgenic over-expressors showed patterns of survivors that deviated substantially from random mortality independent of initial patterns. 5 Small-scale initial patterns of wild types were regular rather than random or clumped. We hypothesize that this small-scale regularity may be explained by early shade avoidance of seedlings in their cotyledon stage. 6 Our experimental results support predictions from an individual-based simulation model and support the conclusion that regular spatial patterns of surviving individuals should be interpreted as evidence for strong, asymmetric competitive interactions and subsequent density-dependent mortality.