Linking adaptation science to action to build food secure Pacific Island communities

Climate change is a major threat to food security in Pacific Island countries, with declines in food production and increasing variability in food supplies already evident across the region. Such impacts have already led to observed consequences for human health, safety and economic prosperity. Enhancing the adaptive capacity of Pacific Island communities is one way to reduce vulnerability and is underpinned by the extent to which people can access, understand and use new knowledge to inform their decision-making processes. However, effective engagement of Pacific Island communities in climate adaption remains variable and is an ongoing and significant challenge. Here, we use a qualitative research approach to identify the impediments to engaging Pacific Island communities in the adaptations needed to safeguard food security. The main barriers include cultural differences between western science and cultural knowledge, a lack of trust among local communities and external scientists, inappropriate governance structures, and a lack of political and technical support. We identify the importance of adaptation science, local social networks, key actors (i.e., influential and trusted individuals), and relevant forms of knowledge exchange as being critical to overcoming these barriers. We also identify the importance of co-ordination with existing on-ground activities to effectively leverage, as opposed to duplicating, capacity

How to use the HOME Core Outcome Set for atopic dermatitis trials - a users' guide

The Harmonizing Outcome Measures for Eczema (HOME) initiative has agreed upon the core outcome set for use in atopic dermatitis (AD) clinical trials, but additional guidance is needed to maximise uptake of the core set. This article provides answers to some of the commonly asked questions about using the HOME core outcome set. It also provides data to aid interpretation of trial results and to support sample size calculations for future trials. By encouraging adoption of the core outcome set and facilitating consistent reporting of outcome data, we hope that results of eczema trials will be more comprehensive and readily combined in meta-analyses and patient care will be improved

Estimating rodent losses to stored rice as a means to assess efficacy of rodent management

Context: Post-harvest losses by rodents have traditionally been calculated by estimates of consumption determined in the laboratory. Methods for assessing storage losses by rodents under smallholder conditions will help farmers and policy makers understand the impact rodents may have on food security, nutrition and health. Stored product loss assessment methods could also be used to monitor the effects of rodent control in villages. Aims: The present study examined a method to measure the amount of rice eaten by rodents in household granaries. The effects of trapping and better hygiene around granaries to reduce rodent populations were investigated using the post-harvest monitoring method to determine whether the program was successful in lowering rodent numbers sufficiently to reduce post-harvest losses. Methods: Baskets with known quantities of rice were placed within household granaries and monitored periodically for moisture content, weight loss, faecal contamination and percentage of rodent-damaged grains. Using an empirical treatment–control study, rodent management was performed at the community level through daily trapping in two Bangladesh villages and in Myanmar at the granary storehouse level. Post-harvest losses were monitored in granaries in villages with rodent management and in similar granaries in villages where there was no management. Key results: Estimates of household losses in the absence of rodent control were 2.5% in Bangladesh and 17% in Myanmar. These losses were reduced when rodent control was implemented, down to 0.5% in Bangladesh and 5% in Myanmar. Conclusions: The impact of rodents on smallholder storage can be accurately assessed in the field under realistic conditions. Intensive daily trapping at the community level together with improved hygiene practices can successfully reduce rodent numbers, and this can significantly reduce stored grain losses and rodent contamination and damage levels. Implications: In addition to the threat of rodent pests during crop production, rodents are a major threat to food security after harvest and have, as of yet, unquantified impacts on household nutrition and health through potential transmission of gastroenteric diseases and zoonoses to householders and domestic livestock. Trapping and environmental management are affordable and effective tools to reduce rodent impacts on stored grain within communities and are viable alternatives to rodenticides

Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma

BACKGROUND: We wished to evaluate the clinical response following ATP-Tumor Chemosensitivity Assay (ATP-TCA) directed salvage chemotherapy in a series of UK patients with advanced ovarian cancer. The results are compared with that of a similar assay used in a different country in terms of evaluability and clinical endpoints. METHODS: From November 1998 to November 2001, 46 patients with pre-treated, advanced ovarian cancer were given a total of 56 courses of chemotherapy based on in-vitro ATP-TCA responses obtained from fresh tumor samples or ascites. Forty-four patients were evaluable for results. Of these, 18 patients had clinically platinum resistant disease (relapse < 6 months after first course of chemotherapy). There was evidence of cisplatin resistance in 31 patients from their first ATP-TCA. Response to treatment was assessed by radiology, clinical assessment and tumor marker level (CA 125). RESULTS: The overall response rate was 59% (33/56) per course of chemotherapy, including 12 complete responses, 21 partial responses, 6 with stable disease, and 15 with progressive disease. Two patients were not evaluable for response having received just one cycle of chemotherapy: if these were excluded the response rate is 61%. Fifteen patients are still alive. Median progression free survival (PFS) was 6.6 months per course of chemotherapy; median overall survival (OAS) for each patient following the start of TCA-directed therapy was 10.4 months (95% confidence interval 7.9-12.8 months). CONCLUSION: The results show similar response rates to previous studies using ATP-TCA directed therapy in recurrent ovarian cancer. The assay shows high evaluability and this study adds weight to the reproducibility of results from different centre

Models of Neocortical Layer 5b Pyramidal Cells Capturing a Wide Range of Dendritic and Perisomatic Active Properties

The thick-tufted layer 5b pyramidal cell extends its dendritic tree to all six layers of the mammalian neocortex and serves as a major building block for the cortical column. L5b pyramidal cells have been the subject of extensive experimental and modeling studies, yet conductance-based models of these cells that faithfully reproduce both their perisomatic Na+-spiking behavior as well as key dendritic active properties, including Ca2+ spikes and back-propagating action potentials, are still lacking. Based on a large body of experimental recordings from both the soma and dendrites of L5b pyramidal cells in adult rats, we characterized key features of the somatic and dendritic firing and quantified their statistics. We used these features to constrain the density of a set of ion channels over the soma and dendritic surface via multi-objective optimization with an evolutionary algorithm, thus generating a set of detailed conductance-based models that faithfully replicate the back-propagating action potential activated Ca2+ spike firing and the perisomatic firing response to current steps, as well as the experimental variability of the properties. Furthermore, we show a useful way to analyze model parameters with our sets of models, which enabled us to identify some of the mechanisms responsible for the dynamic properties of L5b pyramidal cells as well as mechanisms that are sensitive to morphological changes. This automated framework can be used to develop a database of faithful models for other neuron types. The models we present provide several experimentally-testable predictions and can serve as a powerful tool for theoretical investigations of the contribution of single-cell dynamics to network activity and its computational capabilities

Tyrosine Phosphorylation of Tau by the Src Family Kinases Lck and Fyn

<p>Abstract</p> <p>Background</p> <p>Tau protein is the principal component of the neurofibrillary tangles found in Alzheimer's disease, where it is hyperphosphorylated on serine and threonine residues, and recently phosphotyrosine has been demonstrated. The Src-family kinase Fyn has been linked circumstantially to the pathology of Alzheimer's disease, and shown to phosphorylate Tyr18. Recently another Src-family kinase, Lck, has been identified as a genetic risk factor for this disease.</p> <p>Results</p> <p>In this study we show that Lck is a tau kinase. <it>In vitro</it>, comparison of Lck and Fyn showed that while both kinases phosphorylated Tyr18 preferentially, Lck phosphorylated other tyrosines somewhat better than Fyn. In co-transfected COS-7 cells, mutating any one of the five tyrosines in tau to phenylalanine reduced the apparent level of tau tyrosine phosphorylation to 25-40% of that given by wild-type tau. Consistent with this, tau mutants with only one remaining tyrosine gave poor phosphorylation; however, Tyr18 was phosphorylated better than the others.</p> <p>Conclusions</p> <p>Fyn and Lck have subtle differences in their properties as tau kinases, and the phosphorylation of tau is one mechanism by which the genetic risk associated with Lck might be expressed pathogenically.</p

The role of ongoing dendritic oscillations in single-neuron dynamics

The dendritic tree contributes significantly to the elementary computations a neuron performs while converting its synaptic inputs into action potential output. Traditionally, these computations have been characterized as temporally local, near-instantaneous mappings from the current input of the cell to its current output, brought about by somatic summation of dendritic contributions that are generated in spatially localized functional compartments. However, recent evidence about the presence of oscillations in dendrites suggests a qualitatively different mode of operation: the instantaneous phase of such oscillations can depend on a long history of inputs, and under appropriate conditions, even dendritic oscillators that are remote may interact through synchronization. Here, we develop a mathematical framework to analyze the interactions of local dendritic oscillations, and the way these interactions influence single cell computations. Combining weakly coupled oscillator methods with cable theoretic arguments, we derive phase-locking states for multiple oscillating dendritic compartments. We characterize how the phase-locking properties depend on key parameters of the oscillating dendrite: the electrotonic properties of the (active) dendritic segment, and the intrinsic properties of the dendritic oscillators. As a direct consequence, we show how input to the dendrites can modulate phase-locking behavior and hence global dendritic coherence. In turn, dendritic coherence is able to gate the integration and propagation of synaptic signals to the soma, ultimately leading to an effective control of somatic spike generation. Our results suggest that dendritic oscillations enable the dendritic tree to operate on more global temporal and spatial scales than previously thought

Characterization of Voltage-Gated Ca2+ Conductances in Layer 5 Neocortical Pyramidal Neurons from Rats

Neuronal voltage-gated Ca2+ channels are involved in electrical signalling and in converting these signals into cytoplasmic calcium changes. One important function of voltage-gated Ca2+ channels is generating regenerative dendritic Ca2+ spikes. However, the Ca2+ dependent mechanisms used to create these spikes are only partially understood. To start investigating this mechanism, we set out to kinetically and pharmacologically identify the sub-types of somatic voltage-gated Ca2+ channels in pyramidal neurons from layer 5 of rat somatosensory cortex, using the nucleated configuration of the patch-clamp technique. The activation kinetics of the total Ba2+ current revealed conductance activation only at medium and high voltages suggesting that T-type calcium channels were not present in the patches. Steady-state inactivation protocols in combination with pharmacology revealed the expression of R-type channels. Furthermore, pharmacological experiments identified 5 voltage-gated Ca2+ channel sub-types – L-, N-, R- and P/Q-type. Finally, the activation of the Ca2+ conductances was examined using physiologically derived voltage-clamp protocols including a calcium spike protocol and a mock back-propagating action potential (mBPAP) protocol. These experiments enable us to suggest the possible contribution of the five Ca2+ channel sub-types to Ca2+ current flow during activation under physiological conditions