How to Research the Changing Outlines of African Livelihoods

This paper examines how to research the changing outlines of African livelihoods in the present era of globalisation. After an analysis of the historical and theoretical  context in which the modern livelihood approach developed, two trends in modern livelihood studies are discussed, i.e. its increased holistic features and the  surmounting of its micro-orientation. Subsequently, the most pressing issues in livelihood research are reviewed: decomposition of households, and the increased diversification and increased multi-locality of livelihoods under globalisation. The next section focuses on two major theoretical and methodological challenges facing the livelihood approach at present. First, with respect to the problem of access, we will demonstrate that the livelihood approach can become more powerful analytically by improving its theoretical depth through incorporating valuable elements of sovereignty and power. Second, there is the access to livelihood opportunities in relation to decision-making. In this context, we review various relevant concepts, such as livelihood strategies and styles, in order to operationalise the improved theoretical depth. We then propose livelihood trajectories as an appropriate  methodology for examining pathways of African livelihoods. In doing so, the paper also suggests an agenda for future research on African livelihoods. Cet article examine les aspects changeants des systèmes de survie africains dans le contexte actuel de la mondialisation. Après une analyse du contexte historique et théorique au sein duquel l’approche moderne aux systèmes de survie a été   développée, nous débattons de deux tendances existant au niveau les études sur les moyens de survie, notamment l’aspect holistique grandissant caractérisant ces études et le dépassement de sa micro-orientation. Des questions d’actualité dans le domaine de la recherche en systèmes de survie sont ensuite évoquées : la décomposition des foyers, et la diversification accrûe ainsi que le caractère de plus en plus multi-local des moyens de survie dans le contexte de la mondialisation. La partie suivante porte sur deux principaux défis théoriques et méthodologiques auxquels est actuellement confrontée l’approche aux systèmes de survie. Tout d’abord, en ce qui concerne le problème de l’accès, nous démontrons que l’approche aux systèmes de survie peut avoir un contenu analytique plus percutant, en améliorant sa profondeur théorique à travers l’intégration des éléments de  souveraineté et de pouvoir. Deuxièmement, il existe la question de l’accès aux opportunités donnant accès aux moyens de survie, en relation au processus de prise de décision. Dans ce contexte, nous passons en revue divers concepts, tels que les stratégies et styles de survie, afin de rendre opérationnelle cette  amélioration de la teneur théorique. Ensuite, nous proposons des trajectoires de survie, comme méthodologie adaptée permettant d’examiner les voies de survie en Afrique. Cet article propose par la même, un agenda pour la recherche future en matière de systèmes de survie africains

Adult cortical plasticity depends on an early postnatal critical period

Development of the cerebral cortex is influenced by sensory experience during distinct phases of postnatal development known as critical periods. Disruption of experience during a critical period produces neurons that lack specificity for particular stimulus features, such as location in the somatosensory system. Synaptic plasticity is the agent by which sensory experience affects cortical development. Here, we describe, in mice, a developmental critical period that affects plasticity itself. Transient neonatal disruption of signaling via the C-terminal domain of "disrupted in schizophrenia 1" (DISC1)-a molecule implicated in psychiatric disorders-resulted in a lack of long-term potentiation (LTP) (persistent strengthening of synapses) and experience-dependent potentiation in adulthood. Long-term depression (LTD) (selective weakening of specific sets of synapses) and reversal of LTD were present, although impaired, in adolescence and absent in adulthood. These changes may form the basis for the cognitive deficits associated with mutations in DISC1 and the delayed onset of a range of psychiatric symptoms in late adolescence

Poverty is Bad: Ways forward in livelihood research

In this paper, we take the view that the essence of poverty is the fact that one or several basic conditions for generating a living are not being met. The conditions considered most vital for making a living are to a certain extent context specific and subject to (cultural and social) interpretation and evaluation

Dual-component structural plasticity mediated by αCaMKII autophosphorylation on basal dendrites of cortical layer 2/3 neurones

Sensory cortex exhibits receptive field plasticity throughout life in response to changes in sensory experience and offers the experimental possibility of aligning functional changes in receptive field properties with underpinning structural changes in synapses. We looked at the effects on structural plasticity of two different patterns of whisker deprivation in male and female mice: chessboard deprivation, which causes functional plasticity; and all deprived, which does not. Using 2-photon microscopy and chronic imaging through a cranial window over the barrel cortex, we found that layer 2/3 neurones exhibit robust structural plasticity, but only in response to whisker deprivation patterns that cause functional plasticity. Chessboard pattern deprivation caused dual-component plasticity in layer 2/3 by (1) increasing production of new spines that subsequently persisted for weeks and (2) enlarging spine head sizes in the preexisting stable spine population. Structural plasticity occurred on basal dendrites, but not apical dendrites. Both components of plasticity were absent in αCaMKII-T286A mutants that lack LTP and experience-dependent potentiation in barrel cortex, implying that αCaMKII autophosphorylation is not only important for stabilization and enlargement of spines, but also for new spine production. These studies therefore reveal the relationship between spared whisker potentiation in layer 2/3 neurones and the form and mechanisms of structural plasticity processes that underlie them

Radiotherapy for Ledderhose disease:Results of the LedRad-study, a prospective multicentre randomised double-blind phase 3 trial

Background and purpose: Radiotherapy is considered a treatment option for Ledderhose disease. However, its benefits have never been confirmed in a randomised controlled trial. Therefore, the LedRad-study was conducted. Materials and methods: The LedRad-study is a prospective multicentre randomised double-blind phase three trial. Patients were randomised to sham-radiotherapy (placebo) or radiotherapy. The primary endpoint was pain reduction at 12 months after treatment, measured with the Numeric Rating Scale (NRS). Secondary endpoints were pain reduction at 6 and 18 months after treatment, quality of life (QoL), walking abilities and toxicity.Results: A total of 84 patients were enrolled. At 12 and 18 months, patients in the radiotherapy group had a lower mean pain score compared to patients in the sham-radiotherapy group (2.5 versus 3.6 (p = 0.03) and 2.1 versus 3.4 (p = 0.008), respectively). Pain relief at 12 months was 74% in the radiotherapy group and 56% in the sham-radiotherapy group (p = 0.002). Multilevel testing for QoL scores showed higher QoL scores in the radiotherapy group compared to the sham-radiotherapy group (p &lt; 0.001). Moreover, patients in the radiotherapy group had a higher mean walking speed and step rate with barefoot speed walking (p = 0.02). Erythema, skin dryness, burning sensations and increased pain were the most frequently reported side effects. These side effects were generally graded as mild (95%) and the majority (87%) were resolved at 18 months follow-up.Conclusion: Radiotherapy for symptomatic Ledderhose disease is an effective treatment resulting in a significant pain reduction, improvement of QoL scores and bare feet walking abilities, in comparison to sham-radiotherapy.</p

Concurrent Detection of Circulating Minor Histocompatibility Antigen-Specific CD8+ T Cells in SCT Recipients by Combinatorial Encoding MHC Multimers

Allogeneic stem cell transplantation (SCT) is a potentially curative treatment for patients with hematologic malignancies. Its therapeutic effect is largely dependent on recognition of minor histocompatibility antigens (MiHA) by donor-derived CD8+ T cells. Therefore, monitoring of multiple MiHA-specific CD8+ T cell responses may prove to be valuable for evaluating the efficacy of allogeneic SCT. In this study, we investigated the use of the combinatorial encoding MHC multimer technique to simultaneously detect MiHA-specific CD8+ T cells in peripheral blood of SCT recipients. Feasibility of this approach was demonstrated by applying dual-color encoding MHC multimers for a set of 10 known MiHA. Interestingly, single staining using a fluorochrome- and Qdot-based five-color combination showed comparable results to dual-color staining for most MiHA-specific CD8+ T cell responses. In addition, we determined the potential value of combinatorial encoding MHC multimers in MiHA identification. Therefore, a set of 75 candidate MiHA peptides was predicted from polymorphic genes with a hematopoietic expression profile and further selected for high and intermediate binding affinity for HLA-A2. Screening of a large cohort of SCT recipients resulted in the detection of dual-color encoded CD8+ T cells following MHC multimer-based T cell enrichment and short ex vivo expansion. Interestingly, candidate MiHA-specific CD8+ T cell responses for LAG3 and TLR10 derived polymorphic peptides could be confirmed by genotyping of the respective SNPs. These findings demonstrate the potency of the combinatorial MHC multimer approach in the monitoring of CD8+ T cell responses to known and potential MiHA in limited amounts of peripheral blood from allogeneic SCT recipients

Phenobarbital, midazolam pharmacokinetics, effectiveness, and drug-drug interaction in asphyxiated neonates undergoing therapeutic hypothermia

Background: Phenobarbital and midazolam are commonly used drugs in (near-)term neonates treated with therapeutic hypothermia for hypoxic-ischaemic encephalopathy, for sedation, and/or as anti-epileptic drug. Phenobarbital is an inducer of cytochrome P450 (CYP) 3A, while midazolam is a CYP3A substrate. Therefore, co-treatment with phenobarbital might impact midazolam clearance. Objectives: To assess pharmacokinetics and clinical anti-epileptic effectiveness of phenobarbital and midazolam in asphyxiated neonates and to develop dosing guidelines. Methods: Data were collected in the prospective multicentre PharmaCool study. In the present study, neonates treated with therapeutic hypothermia and receiving midazolam and/or phenobarbital were included. Plasma concentrations of phenobarbital and midazolam including its metabolites were determined in blood samples drawn on days 2–5 after birth. Pharmacokinetic analyses were performed using non-linear mixed effects modelling; clinical effectiveness was defined as no use of additional anti-epileptic drugs. Results: Data were available from 113 (phenobarbital) and 118 (midazolam) neonates; 68 were treated with both medications. Only clearance of 1-hydroxy midazolam was influenced by hypothermia. Phenobarbital co-administration increased midazolam clearance by a factor 2.3 (95% CI 1.9–2.9, p < 0.05). Anticonvulsant effectiveness was 65.5% for phenobarbital and 37.1% for add-on midazolam. Conclusions: Therapeutic hypothermia does not influence clearance of phenobarbital or midazolam in (near-)term neonates with hypoxic-ischaemic encephalopathy. A phenobarbital dose of 30 mg/kg is advised to reach therapeutic concentrations. Phenobarbital co-administration significantly increased midazolam clearance. Should phenobarbital be substituted by non-CYP3A inducers as first-line anticonvulsant, a 50% lower midazolam maintenance dose might be appropriate to avoid excessive exposure during the first days after birth. © 2019 The Author(s) Published by S. Karger AG, Base

Evaluation of a system-specific function to describe the pharmacokinetics of benzylpenicillin in term neonates undergoing moderate hypothermia

The pharmacokinetic (PK) properties of intravenous (i.v.) benzylpenicillin in term neonates undergoing moderate hypothermia after perinatal asphyxia were evaluated, as they have been unknown until now. A system-specific modeling approach was applied, in which our recently developed covariate model describing developmental and temperature-induced changes in amoxicillin clearance (CL) in the same patient study population was incorporated into a population PK model of benzylpenicillin with a priori birthweight (BW)-based allometric scaling. Pediatric population covariate models describing the developmental changes in drug elimination may constitute system-specific information and may therefore be incorporated into PK models of drugs cleared through the same pathway. The performance of this system-specific model was compared to that of a reference model. Furthermore, Monte-Carlo simulations were performed to evaluate the optimal dose. The systemspecific model performed as well as the reference model. Significant correlations were found between CL and postnatal age (PNA), gestational age (GA), body temperature (TEMP), urine output (UO; system-specific model), and multiorgan failure (reference model). For a typical patient with a GA of 40 weeks, BW of 3, 000 g, PNA of 2 days (TEMP, 33.5°C), and normal UO (2 ml/kg/h), benzylpenicillin CL was 0.48 liter/h (interindividual variability [IIV] of 49%) and the volume of distribution of the central compartment was 0.62 liter/kg (IIV of 53%) in the system-specific model. Based on simulations, we advise a benzylpenicillin i.v. dose regimen of 75, 000 IU/kg/day every 8 h (q8h), 150, 000 IU/kg/day q8h, and 200, 000 IU/kg/day q6h for patients with GAs of 36 to 37 weeks, 38 to 41 weeks, and ≥42 weeks, respectively. Thesystem-specific model may be used for other drugs cleared through the same pathway accelerating model development

Gendered discourses in coaching high-performance sport

One of the most important sources of knowledge coaches draw on to inform their practice is their experience of being coached themselves. These experiences are gendered. To date, however, relatively little research is available that indicates how coaches do gender in their discursive coaching practices. We used a Foucauldian lens to explore discourses drawn on by 12 international elite rowing coaches to legitimate their ‘regimes of truth’ in their thinking about elite women rowers. Although they professed to treat everyone the same regardless of gender, they drew on discourses that constituted their women athletes as inferior to various implicit male norms. We suggest that coaches are reproducing the discourses about gender into which they were disciplined during their athletic careers and regard these as ‘regimes of truth’ in their own coaching practice. We discuss the implications of these findings with regard to the perpetuation of the gendering of coaching and conclude that the normalization of men and the gendered hierarchy in sport remains largely unchallenged