Microbiological quality and metal levels in wells and boreholes water in some peri-urban communities in Kumasi, Ghana

Many communities in Kumasi, Ghana, are increasingly dependent on boreholes and hand dug wells. The aim of this study was to examine the drinking water suitability of 6 wells and 3 boreholes in periurban communities in Kumasi, between December 2003 and January 2005. Total coliforms, faecal coliforms and enterococci were enumerated using the standard most probable number method and membrane filtration methods. The heavy metals in the water samples were determined using the atomic absorption spectrometry method. Overall, significantly higher bacterial counts were recorded during the wet (rainy) season compared to the dry (harmattan) season. Faecal coliforms counts (FCC) in 3 borehole samples ranged between 3 x 101 and 3.5 x 107 per 100 ml (geometric means 1.82, 1.75 and 2.8 x 104) while mean numbers of enterococci were 103-105 times lower. The range and geometric means of FCC was similar in samples from wells but levels of enterococci were 8 times higher than in boreholes. Manganese and iron levels were well within the WHO standards for all 9 sites but lead levels except for one site (Boadi) were all higher than the WHO standard. A brief sanitation survey at each site suggested that wells and boreholes were frequently cited near latrines, refuse tips and other social amenities, and in the vicinity of domestic or grazing animals. In Kumasi, the water from shallow wells and boreholes, upon which the local communities depend is of poor quality. The data are being used to advise the local government. An integrated approach is required to minimise faecal pollution of wells and boreholes within peri-urban communities.Key words: Boreholes, enterococci, faecal coliforms, peri-urban communities, total coliforms, wells

Modeling of Community- and Hospital-acquired Methicillin-resistant Staphylococcus Aureus Transmission in Hospital Settings

In this paper we developed both deterministicand stochastic models of community- and hospital-acquired methicillin-resistant staphylococcus aureus transmission (MRSA) to quantify their interactions in a hospital settings. The disease-free equilibrium of the model is locally-asymptotically stable whenever the associated reproduction number is less than unity. The disease persists in the community whenever the reproduction number is greater than unity. Although our stochastic model evolves on an unbounded state space, we show it is positive recurrent. The result obtained from the sensitivity analysis using the deterministic model indicates that the dominant parameters are the hand washing compliance rate, the health-care workers decolonization rate, environmental contamination rate, the admission rates into the hospital, isolation rate of patients with CA-MRSA and isolation rate of patients with HA-MRSA, the transmission probabilities of CA- and HA-MRSA  per contact with health-care workers and transmission probability of health-care workers  per contact with patients. Numerical simulations of the deterministic model obtained from using the dominate parameters as combination of control strategies such as low-, moderate and high-effectiveness control strategies show that disease prevalence among the hospital patients and the bacterial in the hospital environment can be controlled by moderate- and high-effectiveness control strategies. However, for health-care workers the disease prevalence can only be effectively controlled by the high-effectiveness control strategy

DNA damage response inhibitors enhance tumour treating fields (TTFields) potency in glioma stem-like cells

Background High-grade gliomas are primary brain cancers with unacceptably low and persistent survival rates of 10–16 months for WHO grade 4 gliomas over the last 40 years, despite surgical resection and DNA-damaging chemo-radiotherapy. More recently, tumour-treating fields therapy (TTFields) has demonstrated modest survival benefit and been clinically approved in several countries. TTFields is thought to mediate anti-cancer activity by primarily disrupting mitosis. However, recent data suggest that TTFields may also attenuate DNA damage repair and replication fork dynamics, providing a potential platform for therapeutic combinations incorporating standard-of-care treatments and targeted DNA damage response inhibitors (DDRi). Methods We have used patient-derived, typically resistant, glioma stem-like cells (GSCs) in combination with the previously validated preclinical Inovitro™ TTFields system together with a number of therapeutic DDRi. Results We show that TTFields robustly activates PARP- and ATR-mediated DNA repair (including PARylation and CHK1 phosphorylation, respectively), whilst combining TTFields with PARP1 or ATR inhibitor treatment leads to significantly reduced clonogenic survival. The potency of each of these strategies is further enhanced by radiation treatment, leading to increased amounts of DNA damage with profound delay in DNA damage resolution. Conclusion To our knowledge, our findings represent the first report of TTFields applied with clinically approved or in-trial DDRi in GSC models and provides a basis for translational studies toward multimodal DDRi/TTFields-based therapeutic strategies for patients with these currently incurable tumours

Androgen regulation of axon growth and neurite extension in motoneurons

Androgens act on the CNS to affect motor function through interaction with a widespread distribution of intracellular androgen receptors (AR). This review highlights our work on androgens and process outgrowth in motoneurons, both in vitro and in vivo. The actions of androgens on motoneurons involve the generation of novel neuronal interactions that are mediated by the induction of androgen-dependent neurite or axonal outgrowth. Here, we summarize the experimental evidence for the androgenic regulation of the extension and regeneration of motoneuron neurites in vitro using cultured immortalized motoneurons, and axons in vivo using the hamster facial nerve crush paradigm. We place particular emphasis on the relevance of these effects to SBMA and peripheral nerve injurie

Unary Pushdown Automata and Straight-Line Programs

We consider decision problems for deterministic pushdown automata over a unary alphabet (udpda, for short). Udpda are a simple computation model that accept exactly the unary regular languages, but can be exponentially more succinct than finite-state automata. We complete the complexity landscape for udpda by showing that emptiness (and thus universality) is P-hard, equivalence and compressed membership problems are P-complete, and inclusion is coNP-complete. Our upper bounds are based on a translation theorem between udpda and straight-line programs over the binary alphabet (SLPs). We show that the characteristic sequence of any udpda can be represented as a pair of SLPs---one for the prefix, one for the lasso---that have size linear in the size of the udpda and can be computed in polynomial time. Hence, decision problems on udpda are reduced to decision problems on SLPs. Conversely, any SLP can be converted in logarithmic space into a udpda, and this forms the basis for our lower bound proofs. We show coNP-hardness of the ordered matching problem for SLPs, from which we derive coNP-hardness for inclusion. In addition, we complete the complexity landscape for unary nondeterministic pushdown automata by showing that the universality problem is $\Pi_2 \mathrm P$-hard, using a new class of integer expressions. Our techniques have applications beyond udpda. We show that our results imply $\Pi_2 \mathrm P$-completeness for a natural fragment of Presburger arithmetic and coNP lower bounds for compressed matching problems with one-character wildcards

Entrained metal aerosol emissions from air-fired biomass and coal combustion for carbon capture applications

Biomass energy with CO₂ capture could achieve net negative emissions, vital for meeting carbon budgets and emission targets. However, biomass often has significant quantities of light metals/inorganics that cause issues for boiler operation and downstream processes; including deposition, corrosion, and solvent degradation. This study investigated the pilot-scale combustion of a typical biomass used for power generation (white wood) and assessed the variations in metal aerosol release compared to bituminous coal. Using inductively coupled plasma optical emission spectrometry, it was found that K aerosol levels were significantly greater for biomass than coal, on average 6.5 times, with peaks up to 10 times higher; deposition could thus be more problematic, although Na emissions were only 20% of those for coal. Transition metals were notably less prevalent in the biomass flue gas; with Fe and V release in particular much lower (3⁻4% of those for coal). Solvent degradation may therefore be less severe for biomass-generated flue gases. Furthermore, aerosol emissions of toxic/heavy metals (As/Cd/Hg) were absent from biomass combustion, with As/Cd also not detected in the coal flue gas. Negligible Cr aerosol concentrations were found for both. Overall, except for K, metal aerosol release from biomass combustion was considerably reduced compared to coal

Background model systematics for the Fermi GeV excess

The possible gamma-ray excess in the inner Galaxy and the Galactic center (GC) suggested by Fermi-LAT observations has triggered a large number of studies. It has been interpreted as a variety of different phenomena such as a signal from WIMP dark matter annihilation, gamma-ray emission from a population of millisecond pulsars, or emission from cosmic rays injected in a sequence of burst-like events or continuously at the GC. We present the first comprehensive study of model systematics coming from the Galactic diffuse emission in the inner part of our Galaxy and their impact on the inferred properties of the excess emission at Galactic latitudes $2^\circ<|b|<20^\circ$ and 300 MeV to 500 GeV. We study both theoretical and empirical model systematics, which we deduce from a large range of Galactic diffuse emission models and a principal component analysis of residuals in numerous test regions along the Galactic plane. We show that the hypothesis of an extended spherical excess emission with a uniform energy spectrum is compatible with the Fermi-LAT data in our region of interest at $95\%$ CL. Assuming that this excess is the extended counterpart of the one seen in the inner few degrees of the Galaxy, we derive a lower limit of $10.0^\circ$ ($95\%$ CL) on its extension away from the GC. We show that, in light of the large correlated uncertainties that affect the subtraction of the Galactic diffuse emission in the relevant regions, the energy spectrum of the excess is equally compatible with both a simple broken power-law of break energy $2.1\pm0.2$ GeV, and with spectra predicted by the self-annihilation of dark matter, implying in the case of $\bar{b}b$ final states a dark matter mass of $49^{+6.4}_{-5.4}$ GeV.Comment: 65 pages, 28 figures, 7 table

Ex-vivo drug screening of surgically resected glioma stem cells to replace murine avatars and provide personalise cancer therapy for glioblastoma patients

With diminishing returns and high clinical failure rates from traditional preclinical and animal-based drug discovery strategies, more emphasis is being placed on alternative drug discovery platforms. Ex vivo approaches represent a departure from both more traditional preclinical animal-based models and clinical-based strategies and aim to address intra-tumoural and inter-patient variability at an earlier stage of drug discovery. Additionally, these approaches could also offer precise treatment stratification for patients within a week of tumour resection in order to direct tailored therapy. One tumour group that could significantly benefit from such ex vivo approaches are high-grade gliomas, which exhibit extensive heterogeneity, cellular plasticity and therapy-resistant glioma stem cell (GSC) niches. Historic use of murine-based preclinical models for these tumours has largely failed to generate new therapies, resulting in relatively stagnant and unacceptable survival rates of around 12-15 months post-diagnosis over the last 50 years. The near universal use of DNA damaging chemoradiotherapy after surgical resection within standard-of-care (SoC) therapy regimens provides an opportunity to improve current treatments if we can identify efficient drug combinations in preclinical models that better reflect the complex inter-/intra-tumour heterogeneity, GSC plasticity and inherent DNA damage resistance mechanisms. We have therefore developed and optimised a high-throughput ex vivo drug screening platform; GliExP, which maintains GSC populations using immediately dissociated fresh surgical tissue. As a proof-of-concept for GliExP, we have optimised SoC therapy responses and screened 30+ small molecule therapeutics and preclinical compounds against tumours from 18 different patients, including multi-region spatial heterogeneity sampling from several individual tumours. Our data therefore provides a strong basis to build upon GliExP to incorporate combination-based oncology therapeutics in tandem with SoC therapies as an important preclinical alternative to murine models (reduction and replacement) to triage experimental therapeutics for clinical translation and deliver rapid identification of effective treatment strategies for individual gliomas

Fitting the integrated Spectral Energy Distributions of Galaxies

Fitting the spectral energy distributions (SEDs) of galaxies is an almost universally used technique that has matured significantly in the last decade. Model predictions and fitting procedures have improved significantly over this time, attempting to keep up with the vastly increased volume and quality of available data. We review here the field of SED fitting, describing the modelling of ultraviolet to infrared galaxy SEDs, the creation of multiwavelength data sets, and the methods used to fit model SEDs to observed galaxy data sets. We touch upon the achievements and challenges in the major ingredients of SED fitting, with a special emphasis on describing the interplay between the quality of the available data, the quality of the available models, and the best fitting technique to use in order to obtain a realistic measurement as well as realistic uncertainties. We conclude that SED fitting can be used effectively to derive a range of physical properties of galaxies, such as redshift, stellar masses, star formation rates, dust masses, and metallicities, with care taken not to over-interpret the available data. Yet there still exist many issues such as estimating the age of the oldest stars in a galaxy, finer details ofdust properties and dust-star geometry, and the influences of poorly understood, luminous stellar types and phases. The challenge for the coming years will be to improve both the models and the observational data sets to resolve these uncertainties. The present review will be made available on an interactive, moderated web page (sedfitting.org), where the community can access and change the text. The intention is to expand the text and keep it up to date over the coming years.Comment: 54 pages, 26 figures, Accepted for publication in Astrophysics & Space Scienc

Confocal endomicroscopy of neuromuscular junctions stained with physiologically inert protein fragments of tetanus toxin

Live imaging of neuromuscular junctions (NMJs) in situ has been constrained by the suitability of ligands for inert vital staining of motor nerve terminals. Here, we constructed several truncated derivatives of the tetanus toxin C-fragment (TetC) fused with Emerald Fluorescent Protein (emGFP). Four constructs, namely full length emGFP-TetC (emGFP-865:TetC) or truncations comprising amino acids 1066–1315 (emGFP-1066:TetC), 1093–1315 (emGFP-1093:TetC) and 1109–1315 (emGFP-1109:TetC), produced selective, high-contrast staining of motor nerve terminals in rodent or human muscle explants. Isometric tension and intracellular recordings of endplate potentials from mouse muscles indicated that neither full-length nor truncated emGFP-TetC constructs significantly impaired NMJ function or transmission. Motor nerve terminals stained with emGFP-TetC constructs were readily visualised in situ or in isolated preparations using fibre-optic confocal endomicroscopy (CEM). emGFP-TetC derivatives and CEM also visualised regenerated NMJs. Dual-waveband CEM imaging of preparations co-stained with fluorescent emGFP-TetC constructs and Alexa647-α-bungarotoxin resolved innervated from denervated NMJs in axotomized WldS mouse muscle and degenerating NMJs in transgenic SOD1G93A mouse muscle. Our findings highlight the region of the TetC fragment required for selective binding and visualisation of motor nerve terminals and show that fluorescent derivatives of TetC are suitable for in situ morphological and physiological characterisation of healthy, injured and diseased NMJs