Equity in vaccine coverage in Uganda from 2000 to 2016: revealing the multifaceted nature of inequity.

BACKGROUND: This study analyses vaccine coverage and equity among children under five years of age in Uganda based on the 2016 Uganda Demographic and Health Survey (UDHS) dataset. Understanding equity in vaccine access and the determinants is crucial for the redress of emerging as well as persistent inequities. METHODS: Applied to the UDHS for 2000, 2006, 2011, and 2016, the Vaccine Economics Research for Sustainability and Equity (VERSE) Equity Toolkit provides a multivariate assessment of immunization coverage and equity by (1) ranking the sample population with a composite direct unfairness index, (2) generating quantitative measure of efficiency (coverage) and equity, and (3) decomposing inequity into its contributing factors. The direct unfairness ranking variable is the predicted vaccination coverage from a logistic model based upon fair and unfair sources of variation in vaccination coverage. Our fair source of variation is defined as the child's age - children too young to receive routine immunization are not expected to be vaccinated. Unfair sources of variation are the child's region of residence, and whether they live in an urban or rural area, the mother's education level, the household's socioeconomic status, the child's sex, and their insurance coverage status. For each unfair source of variation, we identify a "more privileged" situation. RESULTS: The coverage and equity of the Diphtheria-Pertussis-Tetanus vaccine, 3rd dose (DPT3) and the Measles-Containing Vaccine, 1st dose (MCV1) - two vaccines indicative of the health system's performance - improved significantly since 2000, from 49.7% to 76.8% and 67.8% to 82.7%, respectively, and there are fewer zero-dose children: from 8.4% to 2.2%. Improvements in retaining children in the program so that they complete the immunization schedule are more modest (from 38.1% to 40.8%). Progress in coverage was pro-poor, with concentration indices (wealth only) moving from 0.127 (DPT3) and 0.123 (MCV1) in 2000 to -0.042 and -0.029 in 2016. Gains in overall equity (composite) were more modest, albeit significant for most vaccines except for MCV1: concentration indices of 0.150 (DPT3) and 0.087 (MCV1) in 2000 and 0.054 and 0.055 in 2016. The influence of the region and settings (urban/rural) of residence significantly decreased since 2000. CONCLUSION: The past two decades have seen significant improvements in vaccine coverage and equity, thanks to the efforts to strengthen routine immunization and ongoing supplemental immunization activities such as the Family Health Days. While maintaining the regular provision of vaccines to all regions, efforts should be made to alleviate the impact of low maternal education and literacy on vaccination uptake.

Biomineralization of Uranium-Phosphates Fueled by Microbial Degradation of Isosaccharinic Acid (ISA).

Geological disposal is the globally preferred long-term solution for higher activity radioactive wastes (HAW) including intermediate level waste (ILW). In a cementitious disposal system, cellulosic waste items present in ILW may undergo alkaline hydrolysis, producing significant quantities of isosaccharinic acid (ISA), a chelating agent for radionuclides. Although microbial degradation of ISA has been demonstrated, its impact upon the fate of radionuclides in a geological disposal facility (GDF) is a topic of ongoing research. This study investigates the fate of U(VI) in pH-neutral, anoxic, microbial enrichment cultures, approaching conditions similar to the far field of a GDF, containing ISA as the sole carbon source, and elevated phosphate concentrations, incubated both (i) under fermentation and (ii) Fe(III)-reducing conditions. In the ISA-fermentation experiment, U(VI) was precipitated as insoluble U(VI)-phosphates, whereas under Fe(III)-reducing conditions, the majority of the uranium was precipitated as reduced U(IV)-phosphates, presumably formed via enzymatic reduction mediated by metal-reducing bacteria, including Geobacter species. Overall, this suggests the establishment of a microbially mediated "bio-barrier" extending into the far field geosphere surrounding a GDF is possible and this biobarrier has the potential to evolve in response to GDF evolution and can have a controlling impact on the fate of radionuclides.

Scene-Aware Audio Rendering via Deep Acoustic Analysis.

We present a new method to capture the acoustic characteristics of real-world rooms using commodity devices, and use the captured characteristics to generate similar sounding sources with virtual models. Given the captured audio and an approximate geometric model of a real-world room, we present a novel learning-based method to estimate its acoustic material properties. Our approach is based on deep neural networks that estimate the reverberation time and equalization of the room from recorded audio. These estimates are used to compute material properties related to room reverberation using a novel material optimization objective. We use the estimated acoustic material characteristics for audio rendering using interactive geometric sound propagation and highlight the performance on many real-world scenarios. We also perform a user study to evaluate the perceptual similarity between the recorded sounds and our rendered audio.

Plutonium(IV) Sorption during Ferrihydrite Nanoparticle Formation.

Understanding interactions between iron (oxyhydr)oxide nanoparticles and plutonium is essential to underpin technology to treat radioactive effluents, in cleanup of land contaminated with radionuclides, and to ensure the safe disposal of radioactive wastes. These interactions include a range of adsorption, precipitation, and incorporation processes. Here, we explore the mechanisms of plutonium sequestration during ferrihydrite precipitation from an acidic solution. The initial 1 M HNO3 solution with Fe(III)(aq) and 242Pu(IV)(aq) underwent controlled hydrolysis via the addition of NaOH to pH 9. The majority of Fe(III)(aq) and Pu(IV)(aq) was removed from solution between pH 2 and 3 during ferrihydrite formation. Analysis of Pu-ferrihydrite by extended X-ray absorption fine structure (EXAFS) spectroscopy showed that Pu(IV) formed an inner-sphere tetradentate complex on the ferrihydrite surface, with minor amounts of PuO2 present. Best fits to the EXAFS data collected from Pu-ferrihydrite samples aged for 2 and 6 months showed no statistically significant change in the Pu(IV)-Fe oxyhydroxide surface complex despite the ferrihydrite undergoing extensive recrystallization to hematite. This suggests the Pu remains strongly sorbed to the iron (oxyhydr)oxide surface and could be retained over extended time periods.

The biogeochemical fate of nickel during microbial ISA degradation; implications for nuclear waste disposal.

Intermediate level radioactive waste (ILW) generally contains a heterogeneous range of organic and inorganic materials, of which some are encapsulated in cement. Of particular concern are cellulosic waste items, which will chemically degrade under the conditions predicted during waste disposal, forming significant quantities of isosaccharinic acid (ISA), a strongly chelating ligand. ISA therefore has the potential to increase the mobility of a wide range of radionuclides via complex formation, including Ni-63 and Ni-59. Although ISA is known to be metabolized by anaerobic microorganisms, the biodegradation of metal-ISA complexes remains unexplored. This study investigates the fate of a Ni-ISA complex in Fe(III)-reducing enrichment cultures at neutral pH, representative of a microbial community in the subsurface. After initial sorption of Ni onto Fe(III)oxyhydroxides, microbial ISA biodegradation resulted in >90% removal of the remaining Ni from solution when present at 0.1 mM, whereas higher concentrations of Ni proved toxic. The microbial consortium associated with ISA degradation was dominated by close relatives to Clostridia and Geobacter species. Nickel was preferentially immobilized with trace amounts of biogenic amorphous iron sulfides. This study highlights the potential for microbial activity to help remove chelating agents and radionuclides from the groundwater in the subsurface geosphere surrounding a geodisposal facility.

Microvascular Reconstruction of the Parotidectomy Defect.

Parotidectomy is a commonly performed procedure for both benign and malignant lesions. When a significant portion of the gland is resected and the lost tissue volume is not replaced, a disfiguring contour defect can result. This defect can be disfiguring and have a profound impact on quality of life. Large defects are best replaced with vascularized tissue to provide stable volume.

Evaluation of six synthetic surgical meshes implanted subcutaneously in a rat model.

The long-term efficacy and mechanical integrity of implanted materials is largely determined by early host response. Therefore, implanting materials with well-characterized tissue responses provides the greatest chance of 'one-hit' surgical successes, without repeated interventions to replace, repair or remove non-compliant biomaterials. Six synthetic meshes were implanted subcutaneously in a rat model to deduce and quantify modulations in host response, based on material fabrication variables. The materials consisted of knitting variations of polypropylene (PP), polyethyleneterephthalate (PET) and polyglycolic acid (PGA) yarns and were implanted for 2, 5, 7, 14 and 28 days before fixation and both semi- and fully quantitative histopathology. In a subcutaneous niche, material weight did not influence foreign body response. PET stimulated earlier inflammation than PP and PGA, which normalized over 28 days. Multifilament meshes recruited foreign body giant cells, which were largely absent from monofilaments. Using CD68, PGA was demonstrated to be the greatest leukocyte-activating polymer at a number of the time points analysed. This research therefore highlights that underlying polymer composition may be more over-arching in deciding the inflammatory properties of surgical meshes, based on increased macrophagic responses to PGA vs alternative base polymers of comparable weights and porosities. Copyright © 2013 John Wiley & Sons, Ltd.

Microbial degradation of isosaccharinic acid at high pH.

Intermediate-level radioactive waste (ILW), which dominates the radioactive waste inventory in the United Kingdom on a volumetric basis, is proposed to be disposed of via a multibarrier deep geological disposal facility (GDF). ILW is a heterogeneous wasteform that contains substantial amounts of cellulosic material encased in concrete. Upon resaturation of the facility with groundwater, alkali conditions will dominate and will lead to the chemical degradation of cellulose, producing a substantial amount of organic co-contaminants, particularly isosaccharinic acid (ISA). ISA can form soluble complexes with radionuclides, thereby mobilising them and posing a potential threat to the surrounding environment or 'far field'. Alkaliphilic microorganisms sampled from a legacy lime working site, which is an analogue for an ILW-GDF, were able to degrade ISA and couple this degradation to the reduction of electron acceptors that will dominate as the GDF progresses from an aerobic 'open phase' through nitrate- and Fe(III)-reducing conditions post closure. Furthermore, pyrosequencing analyses showed that bacterial diversity declined as the reduction potential of the electron acceptor decreased and that more specialised organisms dominated under anaerobic conditions. These results imply that the microbial attenuation of ISA and comparable organic complexants, initially present or formed in situ, may play a role in reducing the mobility of radionuclides from an ILW-GDF, facilitating the reduction of undue pessimism in the long-term performance assessment of such facilities.

Systemic inflammatory cytokine analysis to monitor biomaterial augmented tissue healing.

PURPOSE: Hernias can be repaired by reinforcement of damaged fascia using biomaterials to provide stabilisation. Repair materials are usually porous, through which cells infiltrate, proliferate and secrete ECM. Their efficacy relies on good tissue integration and resolution of host defence mechanisms. Therefore, understanding the dynamics by which biomaterials interact with tissue will provide knowledge to advance prosthesis design. Furthermore, determining host response in real time would provide significant advantage both clinically and scientifically over the current terminal process of histology. METHODS: 3 materials comprising synthetic and composite (synthetic materials hybridised with a resorbable biologic component) meshes were implanted into a rat full-thickness abdominal wall excision model. Their efficacy was evaluated using histopathology whilst also monitoring systemic concentrations of cytokines associated with inflammation and wound healing to predict material outcome over 12 weeks. RESULTS: The noncomposite material (polyester) and Material B (polypropylene mesh with oligocaprone film and polydioxanone glue) stimulated the largest degree of adhesion from the 3 materials tested, although after 28 days adhesions were stronger to Material B. Histologically, all 3 materials integrated well with abdominal musculature and infiltrated completely with cells. CONCLUSIONS: Analysis of systemic inflammation biomarkers confirmed inflammation elicited by surgeries and meshes irrespective of their composition. However, at an early postoperative endpoint (i.e., 1 week), some biomarkers, namely, IL-18 and RANTES, appeared to discriminate the noncomposite mesh from the composite materials, although in this study all materials successfully repaired the defects without recurrence or external indicators of postoperative chronic pain.

Behaviour and mobility of U and Ra in sediments near an abandoned uranium mine, Cornwall, UK.

Sediment samples were collected from the vicinity of the abandoned South Terras uranium mine in south-west UK and analysed for uranium and (226)Ra to explore their geochemical dispersion. The radioactivity concentrations in the sediment samples were measured using alpha spectrometry for uranium, and gamma spectrometry for radium. Sequential chemical extraction was applied to selected sediments in order to investigate the speciation of the radionuclides and their association with stable elements. The activity ratio of the uranium isotopes was used to explore the mobility of uranium, and scanning electron microscopy (SEM) and electron microprobe analysis (EMPA) were used to characterise the sediments. The radiochemical results identified two locations with enhanced radioactivity, so two samples from these locations were further investigated. The geochemical distribution of the radionuclides in these two samples varies within the five operationally-defined fractions. In one sample, the majority of the uranium was released from the 'carbonate' fraction, followed by the organic fractions. Similarly, in the second sample, the uranium was mainly resealed from the carbonate fraction, although a considerable percentage associated with the resistant fraction. The fractionation trend of radium noticed to show some similarities to that of barium, as expected from the similarity in their chemistries. Geochemical distributions of the stable elements, such as Mn, Ti and As, were different in the enhanced radioactivity samples. The activity ratio of (234)U/(238)U shows different trends in the two sediments, signifying the impact of organic matter and/or the exchange between water and sediment. SEM and EMPA analysis identified uranium-bearing phases in association with potassium, calcium, iron, manganese and arsenic.

Characterisation and comparison of the host response of 6 tissue-based surgical implants in a subcutaneous in vivo rat model.

BACKGROUND: Hernia repair often involves fascial augmentation using biologic prostheses. Small processing changes during preparation modulate host tissue response, which influence material efficacy and longevity. In this pilot study, a rat model was used to determine the specific influence of tissue origin, decellularisation treatment and 1,6-hexamethylene diisocyanate (HMDI) cross-linking. METHODS: Materials (1 cm2) were implanted subcutaneously into 6-week-old Wistar rats (4 materials per animal, n=6/material per time point) for 2, 5, 7, 14 and 28 days. Histologic processing was carried out after resin infiltration, observing classical histopathology and pathologic indexing. Materials comprised 6 tissue-based grafts covering both experimental and commercial porcine decellularised dermal and small intestinal submucosal materials. RESULTS: Subcutaneous delivery of biologics demonstrated material-specific inflammatory/host responses. Controlled variations of the PermacolTM manufacturing process showed sodium dodecyl sulfate (SDS) was the most proinflammatory decellularisation reagent, and HMDI cross-linking had no effect on host response. All materials remained recoverable after 28 days, although SurgisisTM had partially resorbed. CONCLUSION: Differences in host responses exist between biologic implants for hernia repair in this rat model. It is postulated that these modifications are induced during processing and may have an effect on the clinical outcome of hernia repair.

Porcine dermis implants in soft-tissue reconstruction: current status.

Soft-tissue reconstruction for a variety of surgical conditions, such as abdominal wall hernia or pelvic organ prolapse, remains a challenge. There are numerous meshes available that may be simply categorized as either synthetic or biologic. Within biologic meshes, porcine dermal meshes have come to dominate the market. This review examines the current evidence for their use and the limitations of knowledge. Although there is increasing evidence to support their safety, long-term follow-up studies that support their efficacy are lacking. Numerous clinical trials that remain ongoing may help elucidate their precise role in soft-tissue reconstruction.

Dispersion of U-series natural radionuclides in stream sediments from Edale, UK.

The spatial distribution of (238)U-series radionuclides, specifically 238U, 234U, 230Th and 226Ra, has been determined in stream sediments from Edale, Derbyshire, United Kingdom, to explore the behaviour of U-series radionuclides during weathering. For uranium and thorium, two different extraction methods were used, total dissolution with HNO3/HF in a microwave and leaching with aqua regia. This was followed by radiochemical separation using extraction chromatography, then alpha spectrometry measurement. The total radium contents in the sediments were measured using gamma spectrometry, while the leached fraction was measured in the same way as for uranium and thorium. The total sediment content of uranium and thorium ranges from ∼10 up to ∼200 Bq kg(-1), while the radium specific activity lies between ∼15 and 180 Bq kg(-1). In the aqua regia extractions, the uranium and thorium contents are in the range of ∼5 to ∼100 Bq kg(-1), while the radium specific activities are similar to those measured by total dissolution. All the radionuclides show no correlation with organic matter content. The activity ratios 234U/238U, 230Th/238U and 226Ra/238U were used to determine the degree of radioactive disequilibrium. The data show disequilibrium in most of the sediments, with activity ratios of 234U/238U, 230Th/238U and 226Ra/238U>1, inconsistent with evolution through straightforward weathering processes. Multivariate cluster analysis based on five variables, the specific activities of 238U, 234U, 230Th, 226Ra and loss on ignition, was employed to group the data and identify five distinct clusters. There seems to be a link between high radionuclide concentrations and proximity to landslips.

The in vivo evaluation of tissue-based biomaterials in a rat full-thickness abdominal wall defect model.

Hernias are defects in which an anatomical fascia is breached resulting in ectopic positioning of an organ into an orifice which routinely does not contain it. Intervention often involves repositioning translocated organs and repair of damaged fascia using exogenous grafts. Despite hernia prevalence, repairs can still fail due to postoperative complications, such as chronic pain and decreased mobility. This study compared repair capacities and characterized the foreign body response elicited by a number of hernia repair grafts to deduce their bulk inflammatory properties while also concluding the point in their fabrication when these are inferred. Materials derived from human dermis (Alloderm(®) ), porcine dermis (Permacol™, patch A, patch D and Strattice(®) ), porcine small-intestinal submucosa (Surgisis™) and a synthetic (multifilament Surgipro™) were implanted into a rat full-thickness abdominal wall excision model, incubated for up to 2 years and characterized histopathologically. Surgisis™ resorbed the fastest of the materials tested (1-3 months) resulting in a mechanically stable parietal peritoneum. Decellularization using sodium dodecyl sulfate (patch A) stimulated a large early inflammatory response which ultimately may have contributed to increased resorption of porcine dermal matrix however the remaining materials typically persisted throughout the 2-year incubation. Cross-linking porcine dermis using 1,6-hexamethylene disocyanate (vs. an identical noncross-linked counterpart) showed no difference in cell recruitment or material integration over 2 years. Typically Strattice(®) and Alloderm(®) recruited larger early populations of cells than Permacol™; however, over extended periods of time in vivo this response normalized.

Hydrogels for tissue engineering and regenerative medicine.

Injectable hydrogels have become an incredibly prolific area of research in the field of tissue engineering and regenerative medicine, because of their high water content, mechanical similarity to natural tissues, and ease of surgical implantation, hydrogels are at the forefront of biomedical scaffold and drug carrier design. The aim of this review is to concisely summarise current state-of-the-art in natural and synthetic hydrogels with respect to their synthesis and fabrication, comparing and contrasting the many chemistries available for biomedical hydrogel generation using both biologic and synthetic base materials. We then discuss these hydrogels in the specific instance of several pertinent areas of TERM which have been specifically selected to demonstrate how this versatile class of materials can be modified to augment damage and disease of a seemingly limitless array of adult tissues.

Impact of cell purification technique of autologous human adult stem cells on inflammatory reaction.

Adult stem cells have shown fantastic regenerative potential as the cellular components of biomaterial mediated tissue engineering. Realising the biomedical potential of human adult stem cells (hASCs) however will require delivery in an ultra- purified format, without competing cells which may mediate inflammation, fibrosis or tumorigenesis. Purifying ASCs involves exhuming cells from primary tissue using immunoaffinity; which isolates pure populations with the complication of retained immunoglobulin (Ig); the clinical impact of which is currently not known. One of the negative outcomes of retained surface Ig is exacerbation of inflammation by leucocyte Fc receptor (FcR) activation, with consequences ranging from inflammatory cytokine and ROS release to chronic inflammation. The balance of ROS within a tissue will impact the efficacy of a stem cell therapy as ROS play an important role in stem cell self renewal and differentiation. In this study we utilised a chemiluminescent monitoring technique based on a ROS excitable photoprotein Pholasin, to quantify leucocyte ROS production in response to xenogeneic and recombinant human Ig of varying class and isotype with applications in stem cell selection. We were able to demonstrate inter-class differences in leucocyte ROS response to Ig which also varied between donors. This study highlighted the potential for utilising this technique for personalisation of autologous ASC therapies. This would allow clinicians to perform a rapid pre-operative screen to maximise the probability for success of an ASC intervention based on cell isolation using an Ig most appropriate for a specific patient.

Evaluation of a novel non-destructive catch and release technology for harvesting autologous adult stem cells.

BACKGROUND: Cell based therapies are required now to meet the critical care needs of paediatrics and healthy ageing in an increasingly long-lived human population. Repair of compromised tissue by supporting autologous regeneration is a life changing objective uniting the fields of medical science and engineering. Adipose stem cells (adSCs) are a compelling candidate for use in cell based medicine due to their plasticity and residence in numerous tissues. Adipose found in all animals contains a relatively high concentration of stem cells and is easily isolated by a minimally invasive clinical intervention; such as liposuction. METHODS: This study utilised primary rat adipose to validate a novel strategy for selecting adult stem cells. Experiments explored the use of large, very dense cell-specific antibody loaded isolation beads (diameter 5x-10x greater than target cells) which overcome the problem of endocytosis and have proved to be very effective in cell isolation from minimally processed primary tissue. The technique also benefited from pH mediated release, which enabled elution of captured cells using a simple pH shift. RESULTS: Large beads successfully captured and released adSCs from rat adipose, which were characterised using a combination of microscopy, flow cytometry and PCR. The resultant purified cell population retains minimal capture artefact facilitating autologous reperfusion or application in in vitro models. CONCLUSION: Although evidenced here for adSCs, this approach provides a technological advance at a platform level; whereby it can be applied to isolate any cell population for which there is a characterised surface antigen.

The use of acoustic force capture to ultra-purify lymphocyte subpopulations from human adult whole blood.

Pre-analytical enrichment of cell populations prior to therapeutic delivery is of paramount interest throughout the fields of regenerative medicine and clinical interventional therapies. Enrichment of a cell population typically involves two aspects: (a) the increase in concentration of particular subpopulation of the total cell fraction by means of removal of other cells of no interest to the particular interrogation; and (b) improvement of resolution of signal by removal of 'noise' mostly arising from cellular debris in the treated sample. In this research, leukocyte populations were obtained from erythrocyte-depleted primary whole blood from human adults and subjected to flow through acoustic fields within the ultrasound range to remove cellular debris. It was possible to demonstrate aggregation and holding of leukocytes by using ultrasound within the frequency range 11.448-11.483 MHz, which facilitated removal of cellular debris by washing under continuous perfusion. The T-lymphocyte population were phenotypically characterized using CD4/CD8 (T(h)/T(c)) immunocytochemistry by flow cytometry and demonstrated a significant decrease in 'false-positive' events during cellular analysis, due to the efficient eradication of non-specifically reactive cells and tissue debris from the cell populations of interest. Therefore, it was possible to conclude that flow through an ultrasonic acoustic system was capable of providing a non-destructive method for the hyper-purification of primary derived cell populations, with potential exploitations throughout the fields of cellular research, medical diagnostics and clinical therapies.

Reactive oxygen species (ROS)--a family of fate deciding molecules pivotal in constructive inflammation and wound healing.

Wound healing requires a fine balance between the positive and deleterious effects of reactive oxygen species (ROS); a group of extremely potent molecules, rate limiting in successful tissue regeneration. A balanced ROS response will debride and disinfect a tissue and stimulate healthy tissue turnover; suppressed ROS will result in infection and an elevation in ROS will destroy otherwise healthy stromal tissue. Understanding and anticipating the ROS niche within a tissue will greatly enhance the potential to exogenously augment and manipulate healing. Tissue engineering solutions to augment successful healing and remodelling of wounded or diseased tissue rely on a controlled balance between the constructive and destructive capacity of the leukocyte secretome, including ROS. This review comprehensively considers leukocyte derived ROS in tissue repair with particular interest in surgical intervention with inclusion of a biomaterial. The article considers ROS fundamental chemistry, formation, stimulation and clearance before applying this to discuss the implications of ROS in healing tissue with and without a biomaterial. We also systematically discuss ROS in leukocyte signalling and compare and contrast experimental means of measuring ROS.