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.

An anatomical investigation of the cervicothoracic ganglion

Anatomical variability within the autonomic nervous system has long been accepted. This study evaluated the anatomical variability of the cervicothoracic ganglion (CTG) according to its form and, in addition, provided precise measurements between the CTG and the anterior tubercle of the transverse process of the sixth cervical vertebra (C6TP), the first costovertebral articulation, and the vertebral artery. Forty-two adult cadavers were dissected, 22 male and 20 females. Five main forms of CTG were documented; spindle (31.9%), dumbbell (23.2%), truncated (21.7%), perforated (14.5%), and inverted-L (8.7%). The means for length, width, and thickness of the CTG were 18.5 mm, 8.2 mm, and 4.5 mm, respectively. The dimensions were found to be slightly larger in the males than females and on the left sides as compared to the right. The mean shortest distance between the CTGs and the vertebral artery was found to be 2.8 mm, whilst the mean shortest distances to C6TP was 25.7 mm and to the first costovertebral articulation was 1.7 mm. There is great variability in the morphology of the CTG with five common forms consistently seen. The relation to the vertebral artery may influence the form of the ganglion. Two previously undocumented forms are recorded; the truncated which describes the important juxtaposition of the CTG and the vertebral artery and the perforated which describes the piercing of the ganglion itself by the artery. The findings are considered to be of clinical importance to anesthetists, surgeons, neurosurgeons, and anatomists.

[Integration process and organ-related fantasies in patients undergoing organ transplantation]

This review deals with an important aspect of organ transplantation, namely the process of psychic organ integration and organ-related fantasies. The body schema and body self are two important concepts in the integration of a transplanted organ. Different models and theories on organ integration are presented and will be discussed. There is evidence that beside the emotional impact and the influence on well-being, organ integration depends closely on psychic processes involving in the incorporation of the transplanted organ and the respective organ-related fantasies. Therefore, these organ fantasies - whether unconscious or conscious - may play an important role in the future development of the instinctive and highly individual relation the patients elaborate with the new organ. Beside the concern with the new organ, a bereavement to the lost old and sick organ may also influence the patients thoughts. Moreover, the good resolving of all these issues evokes the "good practice" patients develop towards the new situation. This will bring up issues as compliance, infections, rejection episodes and - most important - also organ survival.

Cognitive functioning, behavior, and quality of life after stroke in childhood

Rationale: To provide a better understanding of cognitive functioning, motor outcome, behavior and quality of life after childhood stroke and to study the relationship between variables expected to influence rehabilitation and outcome (age at stroke, time elapsed since stroke, lateralization, location and size of lesion). Methods: Children who suffered from stroke between birth and their eighteenth year of life underwent an assessment consisting of cognitive tests (WISC-III, WAIS-R, K-ABC, TAP, Rey-Figure, German Version of the CVLT) and questionnaires (Conner's Scales, KIDSCREEN). Results: Twenty-one patients after stroke in childhood (15 males, mean 11;11 years, SD 4;3, range 6;10-21;2) participated in the study. Mean Intelligence Quotients (IQ) were situated within the normal range (mean Full Scale IQ 96.5, range IQ 79-129). However, significantly more patients showed deficits in various cognitive domains than expected from a healthy population (Performance IQ p = .000; Digit Span p = .000, Arithmetic's p = .007, Divided Attention p = .028, Alertness p = .002). Verbal IQ was significantly better than Performance IQ in 13 of 17 patients, independent of the hemispheric side of lesion. Symptoms of ADHD occurred more often in the patients' sample than in a healthy population (learning difficulties/inattention p = .000; impulsivity/hyperactivity p = .006; psychosomatics p = .006). Certain aspects of quality of life were reduced (autonomy p = .003; parents' relation p = .003; social acceptance p = .037). Three patients had a right-sided hemiparesis, mean values of motor functions of the other patients were slightly impaired (sequential finger movements p = .000, hand alternation p = .001, foot tapping p = .043). In patients without hemiparesis, there was no relation between the lateralization of lesion and motor outcome. Lesion that occurred in the midst of childhood (5-10 years) led to better cognitive outcome than lesion in the very early (0-5 years) or late childhood (10-18 years). Other variables such as presence of seizure, elapsed time since stroke and size of lesion had a small to no impact on prognosis. Conclusion: Moderate cognitive and motor deficits, behavioral problems, and impairment in some aspects of quality of life frequently remain after stroke in childhood. Visuospatial functions are more often reduced than verbal functions, independent of the hemispheric side of lesion. This indicates a functional superiority of verbal skills compared to visuospatial skills in the process of recovery after brain injury. Compared to the cognitive outcome following stroke in adults, cognitive sequelae after childhood stroke do indicate neither the lateralization nor the location of the lesion focus. Age at stroke seems to be the only determining factor influencing cognitive outcome.

Transformation of local medicinal knowledge in the Andean Highlands: Case studies from Peru and Bolivia

In the Andean highlands, indigenous environmental knowledge is currently undergoing major changes as a result of various external and internal factors. As in other parts of the world, an overall process of erosion of local knowledge can be observed. In response to this trend, some initiatives that adopt a biocultural approach aim at actively strengthening local identities and revalorizing indigenous environmental knowledge and practices, assuming that such practices can contribute to more sustainable management of biodiversity. However, these initiatives usually lack a sound research basis, as few studies have focused on the dynamics of indigenous environmental knowledge in the Andes and on its links with biodiversity management. Against this background, the general objective of this research project was to contribute to the understanding of the dynamics of indigenous environmental knowledge in the Andean highlands of Peru and Bolivia by investigating how local medicinal knowledge is socially differentiated within rural communities, how it is transformed, and which external and internal factors influence these transformation processes. The project adopted an actor-oriented perspective and emphasized the concept of knowledge dialogue by analyzing the integration of traditional and formal medicinal systems within family therapeutic strategies. It also aimed at grasping some of the links between the dynamics of medicinal knowledge and the types of land use systems and biodiversity management. Research was conducted in two case study areas of the Andes, both Quechua-speaking and situated in comparable agro-ecological production belts - Pitumarca District, Department of Cusco (Southern Peruvian Highlands) and the Tunari National Park, Department of Cochabamba (Bolivian inner-Andean valleys). In each case study area, the land use systems and strategies of 18 families from two rural communities, their environmental knowledge related to medicine and to the local therapeutic flora, and an appreciation of the dynamics of this knowledge were assessed. Data were collected through a combination of disciplinary and participatory action-research methods. It was mostly analyzed using qualitative methods, though some quantitative ethnobotanical methods were also used. In both case studies, traditional medicine still constitutes the preferred option for the families interviewed, independently of their age, education level, economic status, religion, or migration status. Surprisingly and contrary to general assertions among local NGOs and researchers, results show that there is a revival of Andean medicine within the younger generation, who have greater knowledge of medicinal plants than the previous one, value this knowledge as an important element of their way of life and relationship with “Mother Earth” (Pachamama), and, at least in the Bolivian case, prefer to consult the traditional healer rather than go to the health post. Migration to the urban centres and the Amazon lowlands, commonly thought to be an important factor of local medicinal knowledge loss, only affects people’s knowledge in the case of families who migrate over half of the year or permanently. Migration does not influence the knowledge of medicinal plants or the therapeutic strategies of families who migrate temporarily for shorter periods of time. Finally, economic status influences neither the status of people’s medicinal knowledge, nor families’ therapeutic strategies, even though the financial factor is often mentioned by practitioners and local people as the main reason for not using the formal health system. The influence of the formal health system on traditional medicinal knowledge varies in each case study area. In the Bolivian case, where it was only introduced in the 1990s and access to it is still very limited, the main impact was to give local communities access to contraceptive methods and to vaccination. In the Peruvian case, the formal system had a much greater impact on families’ health practices, due to local and national policies that, for instance, practically prohibit some traditional practices such as home birth. But in both cases, biomedicine is not considered capable of responding to cultural illnesses such as “fear” (susto), “bad air” (malviento), or “anger” (colerina). As a consequence, Andean farmers integrate the traditional medicinal system and the formal one within their multiple therapeutic strategies, reflecting an inter-ontological dialogue between different conceptions of health and illness. These findings reflect a more general trend in the Andes, where indigenous communities are currently actively revalorizing their knowledge and taking up traditional practices, thus strengthening their indigenous collective identities in a process of cultural resistance.

Adjudication-related processes are underreported and lack standardization in clinical trials of venous thromboembolism: a systematic review

OBJECTIVES Although the use of an adjudication committee (AC) for outcomes is recommended in randomized controlled trials, there are limited data on the process of adjudication. We therefore aimed to assess whether the reporting of the adjudication process in venous thromboembolism (VTE) trials meets existing quality standards and which characteristics of trials influence the use of an AC. STUDY DESIGN AND SETTING We systematically searched MEDLINE and the Cochrane Library from January 1, 2003, to June 1, 2012, for randomized controlled trials on VTE. We abstracted information about characteristics and quality of trials and reporting of adjudication processes. We used stepwise backward logistic regression model to identify trial characteristics independently associated with the use of an AC. RESULTS We included 161 trials. Of these, 68.9% (111 of 161) reported the use of an AC. Overall, 99.1% (110 of 111) of trials with an AC used independent or blinded ACs, 14.4% (16 of 111) reported how the adjudication decision was reached within the AC, and 4.5% (5 of 111) reported on whether the reliability of adjudication was assessed. In multivariate analyses, multicenter trials [odds ratio (OR), 8.6; 95% confidence interval (CI): 2.7, 27.8], use of a data safety-monitoring board (OR, 3.7; 95% CI: 1.2, 11.6), and VTE as the primary outcome (OR, 5.7; 95% CI: 1.7, 19.4) were associated with the use of an AC. Trials without random allocation concealment (OR, 0.3; 95% CI: 0.1, 0.8) and open-label trials (OR, 0.3; 95% CI: 0.1, 1.0) were less likely to report an AC. CONCLUSION Recommended processes of adjudication are underreported and lack standardization in VTE-related clinical trials. The use of an AC varies substantially by trial characteristics.

Genomics and the origin of species

Speciation is a fundamental evolutionary process, the knowledge of which is crucial for understanding the origins of biodiversity. Genomic approaches are an increasingly important aspect of this research field. We review current understanding of genome-wide effects of accumulating reproductive isolation and of genomic properties that influence the process of speciation. Building on this work, we identify emergent trends and gaps in our understanding, propose new approaches to more fully integrate genomics into speciation research, translate speciation theory into hypotheses that are testable using genomic tools and provide an integrative definition of the field of speciation genomics

Observations of the northern seasonal polar cap on Mars II: HiRISE photometric analysis of evolution of northern polar dunes in spring

We present an overview of our analyses of HiRISE observations of spring evolution of selected dune areas of the north polar erg. The north polar erg is covered annually by seasonal volatile ice layer, a mixture of CO2 and H2O with mineral dust contamination. In spring, this layer sublimes creating visually enigmatic phenomena, e.g. dark and bright fan-shaped deposits, dark–bright–dark bandings, dark down-slope streaks, and seasonal polygonal cracks. Similar phenomena in southern polar areas are believed to be related to the specific process of solid-state greenhouse effect. In the north, it is currently unclear if the solid-state greenhouse effect is able to explain all the observed phenomena especially because the increased influence of H2O on the time scales of this process has not yet been quantified. HiRISE observations of our selected locations show that the ground exhibits a temporal behaviour similar to the one observed in the southern polar areas: a brightening phase starting close to the spring equinox with a subsequent darkening towards summer solstice. The resolution of HiRISE enabled us to study dunes and substrate individually and even distinguish between different developments on windward and slip face sides of single dunes. Differences in the seasonal evolution between steep slip faces and flatter substrate and windward sides of dunes have been identified and compared to CRISM data of CO2 and H2O distributions on dunes. We also observe small scale dark blotches that appear in early observations and tend to sustain a low reflectivity throughout the spring. These blotches can be regarded as the analogue of dark fan deposits in southern polar areas, leading us to the conclusion that both martian polar areas follow similar spring evolutions.