Governing with nature: a European perspective on putting rewilding principles into practice.

Academic interest in rewilding is moving from commentary to discussion on future research agendas. The quality of rewilding research design will be enhanced if it is informed by knowledge of the rewilding practice. Here, we describe the conceptual origins and six case study examples of a mode of rewilding that emerged in the Dutch Delta and is being promoted and supported by Rewilding Europe, an umbrella organization established in 2011. The case experiences presented help position this version of rewilding in relation to the US 3C's version and point towards a rewilding action philosophy characterized by pragmatic realism and pioneer projects around which multiactor networks interested in policy innovation and change form. We argue that scaling-up the models of rewilding presented is constrained by institutional cultures and will require innovations in conservation finance and business models. Nonetheless, we suggest that the expanding European Rewilding Network and associated facilities, such as the European Wildlife Bank, represent a valuable asset for natural science research, aimed at exploring the ecological impacts of grazing and the relationship between role of restored herbivore guilds and biotical expansion, and for social science research investigating concepts such as non-human agency and autonomy. Lastly, we ask applied scientists to view rewilding as an uncertain and unfolding conservation approach and to refrain from seeking to specify it as a management approach supporting the delivery of pre-determined targets and/or ideals. This is because such actions may constrain the transformative potential of rewilding practice.This article is part of the theme issue 'Trophic rewilding: consequences for ecosystems under global change'.

Use of population approach non-linear mixed effects models in the evaluation of biosimilarity of monoclonal antibodies.

PURPOSE: Population pharmacokinetic analyses (PPK) have been used to establish bioequivalence for small molecules and some biologicals. We investigated whether PPK could also be useful in biosimilarity testing for monoclonal antibodies (MAbs). METHODS: Data from a biosimilarity trial with two trastuzumab products were used to build population pharmacokinetic models. First, a combined model was developed and similarity between test and reference product was evaluated by performing a covariate analysis with trastuzumab drug product (test or reference) on all model parameters. Next, two separate models were developed, one for each drug product. The model structure and parameters were compared and evaluated for differences. RESULTS: Drug product could not be identified as statistically significant covariate on any parameter in the combined model, and the addition of drug product as covariate did not improve the model fit. A similar structural model described both the test and reference data best. Only minor differences were found between the estimated parameters from these separate models. CONCLUSIONS: PPK can also be used to support a biosimilarity claim for a MAb. However, in contrast to the standard non-compartmental analysis, there is less experience with a PPK approach. Here, we describe two methods of how PPK can be incorporated in biosimilarity testing for complex therapeutics.

Characteristics of biter and victim piglets apparent before a tail-biting outbreak.

Little is known about the characteristics of biters and victims before the appearance of a tail-biting outbreak in groups of pigs. This study aimed to characterise biters and victims (according to gender and performance) and to quantify their behavioural development during the 6 days preceding the tail-biting outbreak. The hypotheses tested were: (a) biters are more often female, are the lighter pigs in the group, are more restless and perform more aggressive behaviour; and (b) victims are more often male, heavier and less active. Using video recordings we carried out a detailed study of 14 pens with a tail-biting outbreak among the weaned piglets. All piglets were individually marked and we observed the behaviour of biters, victims and control piglets (piglet types). In every pen, each piglet type was observed every other day from 6 days before (D-6) to the day of the first visible tail damage (i.e. day of tail biting outbreak; D0). While the number of male biters (6 of the 14 biters) and male victims (11 of the 14 victims) was not significantly different (P = 0.13), this numerical contrast was considerable. The start weight of victims was significantly (P = 0.03) higher (8.6 kg) than those of biters (7.5 kg) and control piglets (8.0 kg). Biters tended (P = 0.08) to spend longer sitting/kneeling (3.1 min/h) than controls (1.7 min/h), but no differences were seen in the time spent lying or standing. Victims tended (P = 0.07) to change posture more often (restlessness) than controls and chased penmates more (P = 0.04) than biters. Victims also performed more (P = 0.04) aggressive behaviour than biters and controls. In contrast, biters tended (P = 0.08) to be chased by penmates more often and tended (P = 0.06) to receive more aggressive behaviour than controls. Furthermore, biters spent longer manipulating the enrichment device (P = 0.01) and the posterior/tail (P = 0.02) of their penmates than controls and tended (P = 0.06) to perform more tail bites than victims. Victims received more posterior/tail manipulation (P = 0.02) and tail bites (P = 0.04) than controls. It was also noticed that, independent of piglet type, restlessness (P = 0.03) increased and the frequency of performed tail bites tended (P = 0.08) to increase in the 6 days preceding a tail-biting outbreak. These findings may contribute to the early identification of biters or victims and support the development of strategies to minimise the occurrence of tail biting.

[Cochlear implantation, new prosthetic alternative in the management of the profoundly deaf child]. / L'implant cochléaire, nouvelle alternative prothétique dans la prise en charge de l'enfant sourd profond.

Cochlear implants are new medical devices. In contrast to acoustic hearing aids which work by amplification, cochlear implants directly stimulate the hearing neurons via electrode implanted in the cochlear tympanic ramp. They are indicated in case of profound hearing deficiency or in cases of bilateral cophosis, congenital or acquired. Implanted early, they allow deaf children to improve their speech comprehension and their verbal expression considerably, thereby favouring social integration. A concurrent system of support including the use of visual-manual means of communication nevertheless remains vital for the first years. The frequency and duration of such support varies according to the individual.

Effects of P(SAG12)-IPT gene expression on development and senescence in transgenic lettuce.

An ipt gene under control of the senescence-specific SAG12 promoter from Arabidopsis (P(SAG12)-IPT) significantly delayed developmental and postharvest leaf senescence in mature heads of transgenic lettuce (Lactuca sativa L. cv Evola) homozygous for the transgene. Apart from retardation of leaf senescence, mature, 60-d-old plants exhibited normal morphology with no significant differences in head diameter or fresh weight of leaves and roots. Induction of senescence by nitrogen starvation rapidly reduced total nitrogen, nitrate, and growth of transgenic and azygous (control) plants, but chlorophyll was retained in the lower (outer) leaves of transgenic plants. Harvested P(SAG12)-IPT heads also retained chlorophyll in their lower leaves. During later development (bolting and preflowering) of transgenic plants, the decrease in chlorophyll, total protein, and Rubisco content in leaves was abolished, resulting in a uniform distribution of these components throughout the plants. Homozygous P(SAG12)-IPT lettuce plants showed a slight delay in bolting (4-6 d), a severe delay in flowering (4-8 weeks), and premature senescence of their upper leaves. These changes correlated with significantly elevated concentrations of cytokinin and hexoses in the upper leaves of transgenic plants during later stages of development, implicating a relationship between cytokinin and hexose concentrations in senescence.

Increased stable inheritance of herbicide resistance in transgenic lettuce carrying a petE promoter-bar gene compared with a CaMV 35S-bar gene.

Inheritance of resistance to herbicide (300 mg/l glufosinate ammonium) up to the third (T3) seed generation was compared in two populations of transgenic lettuce (Lactuca sativa L. cv 'Evola') harbouring a T-DNA containing the bar gene, linked to either the Cauliflower Mosaic Virus (CaMV) 35S promoter, or a -784-bp plastocyanin promoter from pea (petE). Only 2.5% (4/163) of CaMV 35S-bar plants, selected by their kanamycin resistance(T0 generation), transmitted herbicide resistance at high frequency to their T3 seed generation compared with 97% (29/30) for kanamycin resistant petE-bar plants. In the case of 35S-bar transformants, only 16% (341/2,150) of the first seed generation (T1) plants, 22% (426/1,935) T2 plants and 11% (1,235/10,949) T3 plants were herbicide-resistant. In contrast, 63% (190/300) T1 plants, 83% (2,370/2,845) T2 plants and 99% (122/123) T3 petE-bar transformed plants were resistant to glufosinate ammonium. The T-DNAs carrying the petE-bar and CaMV 35S-bar genes also contained a CaMV 35S-neomycin phosphotransferase (nptII) gene. ELISA showed that NPTII protein was absent in 29% (45/156) of the herbicide-resistant T2 plants from 8/19 herbicide-resistant petE-bar lines. This indicated specific inactivation of the CaMV 35S promoter on the same T-DNA locus as an active petE promoter. The choice of promoter and T-DNA construct are crucial for long-term expression of transgenes in lettuce.