The History of International Development Aid

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Engineering Civil Society

Papers originally presented at a conference and workshop

Encoding of low-quality DNA profiles as genotype probability matrices for improved profile comparisons, relatedness evaluation and database searches

Many DNA profiles recovered from crime scene samples are of a quality that does not allow them to be searched against, nor entered into, databases. We propose a method for the comparison of profiles arising from two DNA samples, one or both of which can have multiple donors and be affected by low DNA template or degraded DNA. We compute likelihood ratios to evaluate the hypothesis that the two samples have a common DNA donor, and hypotheses specifying the relatedness of two donors. Our method uses a probability distribution for the genotype of the donor of interest in each sample. This distribution can be obtained from a statistical model, or we can exploit the ability of trained human experts to assess genotype probabilities, thus extracting much information that would be discarded by standard interpretation rules. Our method is compatible with established methods in simple settings, but is more widely applicable and can make better use of information than many current methods for the analysis of mixed-source, low-template DNA profiles. It can accommodate uncertainty arising from relatedness instead of or in addition to uncertainty arising from noisy genotyping. We describe a computer program GPMDNA, available under an open source license, to calculate LRs using the method presented in this paper

Fast-dissolving core-shell composite microparticles of quercetin fabricated using a coaxial electrospray process

This study reports on novel fast-dissolving core-shell composite microparticles of quercetin fabricated using coaxial electrospraying. A PVC-coated concentric spinneret was developed to conduct the electrospray process. A series of analyses were undertaken to characterize the resultant particles in terms of their morphology, the physical form of their components, and their functional performance. Scanning and transmission electron microscopies revealed that the microparticles had spherical morphologies with clear core-shell structure visible. Differential scanning calorimetry and X-ray diffraction verified that the quercetin active ingredient in the core and sucralose and sodium dodecyl sulfate (SDS) excipients in the shell existed in the amorphous state. This is believed to be a result of second-order interactions between the components; these could be observed by Fourier transform infrared spectroscopy. In vitro dissolution and permeation studies showed that the microparticles rapidly released the incorporated quercetin within one minute, and had permeation rates across the sublingual mucosa around 10 times faster than raw quercetin

Electrosprayed Janus Particles for Combined Photo-Chemotherapy

This work is a proof of concept study establishing the potential of electrosprayed Janus particles for combined photodynamic therapy-chemotherapy. Sub-micron-sized particles of polyvinylpyrrolidone containing either an anti-cancer drug (carmofur) or a photosensitiser (rose bengal; RB), and Janus particles containing both in separate compartments were prepared. The functional components were present in the amorphous form in all the particles, and infrared spectroscopy indicated that intermolecular interactions formed between the different species. In vitro drug release studies showed that both carmofur and RB were released at approximately the same rate, with dissolution complete after around 250 min. Cytotoxicity studies were undertaken on model human dermal fibroblasts (HDF) and lung cancer (A549) cells, and the influence of light on cell death explored. Formulations containing carmofur as the sole active ingredient were highly toxic to both cell lines, with or without a light treatment. The RB formulations were non-toxic to HDF when no light was applied, and with photo-treatment caused large amounts of cell death for both A549 and HDF cells. The Janus formulation containing both RB and carmofur was non-toxic to HDF without light, and only slightly toxic with the photo-treatment. In contrast, it was hugely toxic to A549 cells when light was applied. The Janus particles are thus highly selective for cancer cells, and it is hence proposed that such electrosprayed particles containing both a chemotherapeutic agent and photosensitiser have great potential in combined chemotherapy/photodynamic therapy

In the face of threat: neural and endocrine correlates of impaired facial emotion recognition in cocaine dependence.

The ability to recognize facial expressions of emotion in others is a cornerstone of human interaction. Selective impairments in the recognition of facial expressions of fear have frequently been reported in chronic cocaine users, but the nature of these impairments remains poorly understood. We used the multivariate method of partial least squares and structural magnetic resonance imaging to identify gray matter brain networks that underlie facial affect processing in both cocaine-dependent (n = 29) and healthy male volunteers (n = 29). We hypothesized that disruptions in neuroendocrine function in cocaine-dependent individuals would explain their impairments in fear recognition by modulating the relationship with the underlying gray matter networks. We found that cocaine-dependent individuals not only exhibited significant impairments in the recognition of fear, but also for facial expressions of anger. Although recognition accuracy of threatening expressions co-varied in all participants with distinctive gray matter networks implicated in fear and anger processing, in cocaine users it was less well predicted by these networks than in controls. The weaker brain-behavior relationships for threat processing were also mediated by distinctly different factors. Fear recognition impairments were influenced by variations in intelligence levels, whereas anger recognition impairments were associated with comorbid opiate dependence and related reduction in testosterone levels. We also observed an inverse relationship between testosterone levels and the duration of crack and opiate use. Our data provide novel insight into the neurobiological basis of abnormal threat processing in cocaine dependence, which may shed light on new opportunities facilitating the psychosocial integration of these patients.This work was funded by a research grant from the Medical Research Council (G0701497) and supported by the infrastructure of the Behavioural and Clinical Neuroscience Institute (which is supported by a joint award from the Medical Research Council and the Wellcome Trust). This study was jointly sponsored by the Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge. KD Ersche, CC Hagan, and PS Jones are supported by the Medical Research Council, and DG Smith by the Cambridge Overseas Trust.This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/tp.2015.5

Nanofibers Fabricated Using Triaxial Electrospinning as Zero Order Drug Delivery Systems

A new strategy for creating functional trilayer nanofibers through triaxial electrospinning is demonstrated. Ethyl cellulose (EC) was used as the filament-forming matrix in the outer, middle, and inner working solutions and was combined with varied contents of the model active ingredient ketoprofen (KET) in the three fluids. Triaxial electrospinning was successfully carried out to generate medicated nanofibers. The resultant nanofibers had diameters of 0.74 ± 0.06 μm, linear morphologies, smooth surfaces, and clear trilayer nanostructures. The KET concentration in each layer gradually increased from the outer to the inner layer. In vitro dissolution tests demonstrated that the nanofibers could provide linear release of KET over 20 h. The protocol reported in this study thus provides a facile approach to creating functional nanofibers with sophisticated structural features

Development and validation of a novel bioassay to determine glucocorticoid sensitivity

BACKGROUND: Glucocorticoids (GCs) remain the first line treatment for almost all non-infectious inflammatory diseases, ranging from acute asthma to rheumatoid arthritis. However, across all conditions, patients have a variable response to GCs with approximately 30% being non-responders. This group of GC resistant patients is typically exposed to high-dose GCs and their side-effects before more appropriate immunotherapy is instituted. Hence, there is a pressing clinical need for a predictive biomarker of GC responsiveness. The availability of such a tool would also enable patient stratification for the conduct of smart clinical trials in GC resistance. Lymphocyte GC sensitivity has been shown to be closely associated with clinical GC sensitivity in a number of inflammatory diseases. However, the method for determining in vitro GC response is not standardized and requires the use of specialist equipment, including a radioisotope to quantify cellular proliferation, making it challenging to translate into clinical practice. RESULTS: Here we describe the optimization and validation of a novel non-radioactive in vitro bioassay based on measuring cellular proliferation by incorporation of bromodeoxyuridine (BrdU), termed the BrdU incorporation in lymphocyte steroid sensitivity assay (BLISS). In comparison to the current gold standard lymphocyte GC sensitivity assay in 101 healthy control samples, BLISS has an area under receiver operating characteristic of 0.82 and a sensitivity of 83% for correctly identifying GC resistant subjects. CONCLUSIONS: The performance of the novel BLISS bioassay makes it a strong candidate biomarker for clinical application. It now requires validation in a prospective patient cohort. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40364-016-0079-y) contains supplementary material, which is available to authorized users

Hydroxy double salts loaded with bioactive ions: Synthesis, intercalation mechanisms, and functional performance

The intercalation of the anions of diclofenac (Dic), naproxen (Nap), and valproic acid (Val) into three hydroxy double salts (HDSs) has been explored in this work. Experiments were performed with [Co1.2Zn3.8(OH)8](NO3)2·2H2O (CoZn-NO3), [Ni2Zn3(OH)8](NO3)2·2H2O (NiZn-NO3) and [Zn5(OH)8](NO3)2·2H2O (Zn-NO3). It proved possible to intercalate diclofenac and naproxen into all three HDSs. In contrast, Val could be intercalated into CoZn-NO3 but when it was reacted with Zn-NO3 the HDS structure was destroyed, and the product comprised ZnO. Successful intercalation was verified by X-ray diffraction, IR spectroscopy, and elemental microanalysis. Molecular dynamics simulations showed the Dic and Nap ions to arrange themselves in an “X” shape in the interlayer space, forming a bilayer. Val was found to adopt a position with its aliphatic groups parallel to the HDS layer, again in a bilayer. In situ time resolved X-ray diffraction experiments revealed that intercalation of Dic and Nap into CoZn-NO3 and Zn-NO3 is mechanistically complex, with a number of intermediate phases observed. In contrast, the intercalation of all three guests into NiZn-NO3 and of Val into CoZn-NO3 are simple one step reactions proceeding directly from the starting material to the product. The HDS-drug composites were found to have sustained release profiles

Multifunctional fabrics finished using electrosprayed hybrid Janus particles containing nanocatalysts

There is great market demand for fabrics equipped with multiple functionalities. However, most methods to impart these properties to a pristine fabric are complicated, time-consuming, and expensive. In this work, Janus particles with one side comprising TiO2 nanoparticles (NPs)-PVDF (poly (vinylidene fluoride)) and the other an epoxy resin (TPE) were deposited on a fabric surface. The aim was to endow the fabric with the superhydrophobic, UV resistance, and antimicrobial properties. The Janus particles were firmly attached to the fabrics through the adhesion effects of the epoxy resin. Characterization by XRD, SEM, EDX, and FTIR verified the successful finishing of the fabric with TPE particles. The ultraviolet protection factor increased from 7.86 for the pristine fabric to 733 after finishing. The finished fabric also exhibited superhydrophobic properties, with a water contact angle of 152°. Further, the coating of the fabric did not hamper its gas permeability. Potent antibacterial properties against E. coli were observed owing to the antibacterial properties of TiO2 under pre-irradiation by UV light. The protocols reported here provide a new platform for the nano-finishing of fabrics, allowing new functions to be imparted without compromising