Innovation in smallholder farming in Africa: recent advances and recommendations: Proceedings of the International Workshop on Agricultural Innovation Systems in Africa (AISA)

In the wake of a series of recent international events and initiatives focusing on understanding and fostering innovation1, there is growing awareness and interest in applying and making sense of the Agricultural Innovation Systems (AIS) concepts and perspectives and what they offer for understanding and supporting innovation systems, processes and networks. This has particular relevance for African agriculture as it faces several challenges, such as increasing and intensifying food production in a sustainable way and nourishing its fast-growing population, adapting to the consequences of climate change, and finding its rightful place in an increasingly global and complex international scene. Several initiatives and programmes seeking answers to these questions jointly organised a series of events during a Week on Agricultural Innovation in Africa (WAIA) held in Nairobi, Kenya, on 25–31 May 2013, of which the international workshop on Agricultural Innovation Systems in Africa (AISA) on 29–31 May was a major part. Another key event during this week, was the Eastern African Farmer Innovation Fair (EAFIF) held on 28–29 May, which was linked to AISA

A study in high-risk, maximally pretreated patients to determine the potential use of PCSK9 inhibitors at various thresholds of total and LDL cholesterol levels

PURPOSE OF THE STUDY: Statins and ezetimibe reduce low-density lipoprotein cholesterol (LDL-c) and cardiovascular disease (CVD) risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors lower LDL-c by 50%-70% and might be useful in refractory patients. The National Institute for Health and Care Excellence (NICE) technology appraisal guidance (TAG) recommends use of these drugs in secondary prevention and familial hypercholesterolaemia (FH) at differing LDL-c thresholds. We have estimated the proportion of patients in whom this third-line drug might be useful. STUDY DESIGN: We used data from a lipid-lowering audit programme to study 72 with FH and/or CVD of 271 patients referred over 12 months who failed to achieve target total cholesterol (TC) and LDL-c levels. All 72 patients were treated with ezetimibe, and 69 cases also received statins. We used LDL-c thresholds 1.5-5.5 mmol/L to estimate how many of these refractory patients could benefit from PCSK9 inhibitors. RESULTS: In 72 patients, TC and LDL-c targets were not met by 64 and 53 patients, respectively. We judged using the NICE TAG that only one patient (1.4% ezetimibe requiring and 0.4% total referrals) required a PCSK9 inhibitor. CONCLUSIONS: We determined that the proportion of patients eligible for a PCSK9 inhibitor at various TC and LDL-c levels is modest. This may reflect the use of all available statins in UK lipid clinics often at non-daily frequency. We suggest that cost-effective use of PCSK9 inhibitors requires prescribing being restricted to clinicians working in specialised lipid clinics

tRNAs Promote Nuclear Import of HIV-1 Intracellular Reverse Transcription Complexes

Infection of non-dividing cells is a biological property of HIV-1 crucial for virus transmission and AIDS pathogenesis. This property depends on nuclear import of the intracellular reverse transcription and pre-integration complexes (RTCs/PICs). To identify cellular factors involved in nuclear import of HIV-1 RTCs, cytosolic extracts were fractionated by chromatography and import activity examined by the nuclear import assay. A near-homogeneous fraction was obtained, which was active in inducing nuclear import of purified and labeled RTCs. The active fraction contained tRNAs, mostly with defective 3′ CCA ends. Such tRNAs promoted HIV-1 RTC nuclear import when synthesized in vitro. Active tRNAs were incorporated into and recovered from virus particles. Mutational analyses indicated that the anticodon loop mediated binding to the viral complex whereas the T-arm may interact with cellular factors involved in nuclear import. These tRNA species efficiently accumulated into the nucleus on their own in a energy- and temperature-dependent way. An HIV-1 mutant containing MLV gag did not incorporate tRNA species capable of inducing HIV-1 RTC nuclear import and failed to infect cell cycle–arrested cells. Here we provide evidence that at least some tRNA species can be imported into the nucleus of human cells and promote HIV-1 nuclear import

The type and frequency of interactions that occur between staff and children outside in Early Years Foundation Stage settings during a fixed playtime period when there are tricycles available

This study reports on an investigation into adult and child interactions observed in the outdoor play environment in four Local Authority early years foundation stage settings in England. In this instance the common two features across the settings were the presence of tricycles and a timetabled outdoor play period. In total, across the four schools, there were 204 children. The study aimed to gain an understanding of the nature of the dialogues between staff and children, that is, the types of exchange that occurred when either the child approached an adult or the adult approached a child. The most frequent type of utterance was also analysed. The study concludes that adults in these settings spoke more than children and the greatest type of utterance was that of the adult about domestic matters. When the child initiated the conversation there were more extended child utterances than domestic utterances. This may suggest that children wish to be involved in conversations of depth and meaning and that staff need to become aware of how to develop this conversational language with children

The properties of the first galaxies in the BlueTides simulation

We employ the very large cosmological hydrodynamical simulation BlueTides to investigate the predicted properties of the galaxy population during the epoch of reionization (z > 8). BlueTides has a resolution and volume ((400/h ≈ 577)3 cMpc3) providing a population of galaxies that is well matched to depth and area of current observational surveys targeting the high-redshift Universe. At z = 8, BlueTides includes almost 160 000 galaxies with stellar masses >108 M⊙. The population of galaxies predicted by BlueTides closely matches observational constraints on both the galaxy stellar mass function and far-UV (150 nm) luminosity function. Galaxies in BlueTides are characterized by rapidly increasing star formation histories. Specific star formation rates decrease with redshift though remain largely insensitive to stellar mass. As a result of the enhanced surface density of metals, more massive galaxies are predicted to have higher dust attenuation resulting in a significant steepening of the observed far-UV luminosity function at high luminosities. The contribution of active supermassive black holes (SMBHs) to the UV luminosities of galaxies with stellar masses 109–10 M⊙ is around 3 per cent on average. Approximately 25 per cent of galaxies with M∗ ≈ 1010 M⊙ are predicted to have active SMBHs that contribute >10 per cent of the total UV luminosity

Intrinsic excitability changes induced by acute treatment of hippocampal CA1 pyramidal neurons with exogenous amyloid β peptide

Accumulation of Aβ peptides in the human brain is a canonical pathological hallmark of Alzheimer’s disease (AD). Recent work in Aβ-overexpressing transgenic mice indicates that elevated brain Aβlevels can be associated with aberrant epileptiform activity. In line with this, such mice can also exhibit altered intrinsic excitability (IE) of cortical and hippocampal neurons: these observations may relate to the increased prevalence of seizures in AD patients. In this study we examined what changes in IE are produced in hippocampal CA1 pyramidal cells following 2-5 hours treatment with an oligomeric preparation of synthetic human Aβ1-42 peptide. Whole cell current clamp recordings were compared between Aβ-(500 nM) and vehicle-(DMSO 0.05%) treated hippocampal slices obtained from mice. The soluble Aβtreatment did not produce alterations in sub-threshold intrinsic properties including membrane potential, input resistance and hyperpolarization activated “sag”. Similarly, no changes were noted in the firing profile evoked by 500 ms square current supra-threshold stimuli. However, Aβ 500 nM treatment resulted in the hyperpolarization of the action potential (AP) threshold. In addition, treatment with Aβ at 500 nM depressed the after-hyperpolarization (AHP) that followed both a 1 single AP or 50Hz trains of between 5 and 25 APs. These data suggest that acute exposure to soluble Aβ oligomers affects IE properties of CA1 pyramidal neurons differently from outcomes seen in transgenic models of amyloidopathy. However, in both chronic and acute models the IE changes are towards hyper-excitability, reinforcing the idea that amyloidopathy and increased incidence in seizures might be causally related in AD patients

Skunk River Review Fall 1997, Vol 9

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