Population modifiable risk factors associated with neonatal mortality in 35 sub-Saharan Africa countries: analysis of data from demographic and health surveys.

Background: Sub-Saharan Africa (SSA) has the highest burden of neonatal mortality in the world. Identifying the most critical modifiable risk factors is imperative for reducing neonatal mortality rates. This study is the first to calculate population-attributable fractions (PAFs) for modifiable risk factors of neonatal mortality in SSA. Methods: We analysed the most recent Demographic and Health Surveys data sets from 35 SSA countries conducted between 2010 and 2022. Generalized linear latent and mixed models were used to estimate odds ratios (ORs) along with 95% confidence intervals (CIs). PAFs adjusted for communality were calculated using ORs and prevalence estimates for key modifiable risk factors. Subregional analyses were conducted to examine variations in modifiable risk factors for neonatal mortality across Central, Eastern, Southern, and Western SSA regions. Findings: In this study, we included 255,891 live births in the five years before the survey. The highest PAFs of neonatal mortality among singleton children were attributed to delayed initiation of breastfeeding (>1 h after birth: PAF = 23.88%; 95% CI: 15.91, 24.86), uncleaned cooking fuel (PAF = 5.27%; 95% CI: 1.41, 8.73), mother's lacking formal education (PAF = 4.34%; 95% CI: 1.15, 6.31), mother's lacking tetanus vaccination (PAF = 3.54%; 95% CI: 1.55, 4.92), and infrequent antenatal care (ANC) visits (PAF = 2.45; 95% CI: 0.76, 3.63). Together, these five modifiable risk factors were associated with 39.49% (95% CI: 21.13, 48.44) of neonatal deaths among singleton children in SSA. Our subregional analyses revealed some variations in modifiable risk factors for neonatal mortality. Notably, delayed initiation of breastfeeding consistently contributed to the highest PAFs of neonatal mortality across all four regions of SSA: Central, Eastern, Southern, and Western SSA. Interpretation: The PAF estimates in the present study indicate that a considerable proportion of neonatal deaths in SSA are preventable. We identified five modifiable risk factors that accounted for approximately 40% of neonatal deaths in SSA. The findings have policy implications. Funding: None.

An updated technique to obtain explosive kinetics data on microsecond timescales.

There are few techniques available for chemists to obtain time-to-explosion data with known temperature inputs at the early stages of the design and synthesis of new explosives. In the 1960s, a technique was developed to rapidly heat milligram-quantities of confined explosives to ∼1000 K on microsecond timescales. Wenograd [Trans. Faraday Soc. 57, 1612 (1961)] loaded explosives inside stainless steel hypodermic needles, connected them to a fireset and rapidly discharged a capacitor through the steel. He obtained the temperature by measuring the needle resistance in a Wheatstone bridge arrangement and the time to explosion from a needle rupture. However, owing to the narrow-gauge needles used in the original research, the experiment was only possible with melt-castable explosives; it was never replicated, and modern diagnostics are now available with advances beyond the 1960s. Here, we report the development of the High Explosives Initiation Time (HEIT) test, which utilizes a 250 J pulsed power system to heat the needles. This work extends the Wenograd approach by using optical diagnostics, computational modeling, and advanced techniques to measure needle resistance and needle rupture. Preliminary rate information for pentaerythritol tetranitrate (PETN) will be presented.

CRISPR-based functional profiling of the Toxoplasma gondii genome during acute murine infection.

Examining host-pathogen interactions in animals can capture aspects of infection that are obscured in cell culture. Using CRISPR-based screens, we functionally profile the entire genome of the apicomplexan parasite Toxoplasma gondii during murine infection. Barcoded gRNAs enabled bottleneck detection and mapping of population structures within parasite lineages. Over 300 genes with previously unknown roles in infection were found to modulate parasite fitness in mice. Candidates span multiple axes of host-parasite interaction. Rhoptry Apical Surface Protein 1 was characterized as a mediator of host-cell tropism that facilitates repeated invasion attempts. GTP cyclohydrolase I was also required for fitness in mice and druggable through a repurposed compound, 2,4-diamino-6-hydroxypyrimidine. This compound synergized with pyrimethamine against T. gondii and malaria-causing Plasmodium falciparum parasites. This work represents a complete survey of an apicomplexan genome during infection of an animal host and points to novel interfaces of host-parasite interaction.

Cell-selective proteomics reveal novel effectors secreted by an obligate intracellular bacterial pathogen.

Pathogenic bacteria secrete protein effectors to hijack host machinery and remodel their infectious niche. Rickettsia spp. are obligate intracellular bacteria that can cause life-threatening disease, but their absolute dependence on the host cell has impeded discovery of rickettsial effectors and their host targets. We implemented bioorthogonal non-canonical amino acid tagging (BONCAT) during R. parkeri infection to selectively label, isolate, and identify effectors delivered into the host cell. As the first use of BONCAT in an obligate intracellular bacterium, our screen more than doubles the number of experimentally validated effectors for the genus. The seven novel secreted rickettsial factors (Srfs) we identified include Rickettsia-specific proteins of unknown function that localize to the host cytoplasm, mitochondria, and ER. We further show that one such effector, SrfD, interacts with the host Sec61 translocon. Altogether, our work uncovers a diverse set of previously uncharacterized rickettsial effectors and lays the foundation for a deeper exploration of the host-pathogen interface.

Multiple, simultaneous, independent gradients for a versatile multidimensional liquid chromatography. Part II: Application 3 - Scouting optimization strategies for separation of monoclonal antibodies by dual simultaneous independent gradients of pH & salt on a weak cation exchange stationary phase.

In previous publications we have described the pISep dual simultaneous, independent gradients (DSIGs) liquid chromatography (LC) for uncoupling gradients of non-buffering solute (NaCl, urea or acetonitrile) from externally generated pH gradients. In DSIGs the shape and slope of the [salute] gradient does not depend on the shape and slope of the pH gradient. The technique allows in a single run true simultaneous two dimensional LC separation of complex protein mixtures on various stationary phases including anion, cation exchangers (AEX, CEX), reversed phase (RP), mixed mode and mixed bed. Using a humanized IgG1 (HIgG1) monoclonal antibody (MAb) and a variety of pH & [NaCl] DSIGs, we show that most of MAb isoforms can be successfully separated from each other. These experimental observations are supported by an initial theoretical argument presented here predicting an overall improvement of all MAb isoforms separation by DSIGs of pH & [NaCl]. Theoretical calculations predict that, in general, there exists an optimal non-zero isocratic salt concentration in a pH gradient separation that will resolve isoforms close in binding energy, but a wide range of salt concentrations will be required for acceptable resolution of all isoforms. Theory also predicts better separation of weaker rather than stronger binding isoforms. Experimentally, we have found that no one set of DSIGs LC conditions could optimally baseline resolve all identifiable MAb isoforms in a single run of reasonable duration. The versatility and simplicity of the pH & [NaCl] pISep DSIGs LC allows fast, automated scouting of protein separations over any range of pH from 2.4 to 10.8 and [NaCl] from 0 to 1 M without changing the chemistry of the buffering system. Due to the universal applicability of the pISep buffering system in IEX LC, the researcher is given a powerful tool to easily develop pH & [NaCl] DSIGs protocols that vary mobile phase compositions to achieve high resolution separations of targeted proteins.

Conformational disorder in the crystal structure of methyl 2-acetamido-2-deoxy-ß-D-glucopyranosyl-(1→4)-2-acetamido-2-deoxy-ß-D-glucopyranoside (methyl ß-chitobioside) methanol monosolvate.

Methyl 2-acetamido-2-deoxy-ß-D-glucopyranosyl-(1→4)-2-acetamido-2-deoxy-ß-D-glucopyranoside (methyl ß-chitobioside), (IV), crystallizes from aqueous methanol at room temperature to give a structure (C17H30N2O22·CH3OH) containing conformational disorder in the exocyclic hydroxymethyl group of one of its ßGlcNAc residues. As observed in other X-ray structures of disaccharides containing ß-(1→4) O-glycosidic linkages, inter-residue hydrogen bonding between O3H of the ßGlcNAc bearing the OCH3 aglycone and O5 of the adjacent ßGlcNAc is observed based on the 2.79 Šinternuclear distance between the O atoms. The structure of (IV) was compared to that determined previously for 2-acetamido-2-deoxy-ß-D-glucopyranosyl-(1→4)-2-acetamido-2-deoxy-ß-D-glucopyranose (ß-chitobiose), (III). The O-glycosidic linkage torsion angles, phi (φ) and psi (ψ), in (III) and (IV) differ by 6-8°. The N-acetyl side chain conformation in (III) and (IV) shows some context dependence, with the C1-C2-N-Ccar torsion angle 10-15° smaller for the ßGlcNAc residue involved in the internal O-glycosidic linkage. In (IV), conformational disorder is observed in the exocyclic hydroxymethyl (-CH2OH) group in the ßGlcNAc residue bearing the OCH3 aglycone, and a fitting of the electron density indicates an approximate 50:50 distribution of the gauche-gauche (gg) and gauche-trans (gt) conformers in the lattice. Similar behavior is not observed in (III), presumably due to the different packing structure in the vicinity of the -CH2OH substituent that affects its ability to hydrogen bond to proximal donors/acceptors. Unlike (IV), a re-examination of the previously reported electron density of (III) revealed conformational disorder in the N-acetyl side chain attached to the reducing-end ßGlcNAc residue caused by rotation about the C2-N bond.

Circadian regulation of locomotion, respiration, and arousability in adult blacklegged ticks (Ixodes scapularis).

The blacklegged tick, Ixodes scapularis, is an ectoparasitic arachnid and vector for infectious diseases, including Lyme borreliosis. Here, we investigate the diurnal activity and respiration of wild-caught and lab-reared adult ticks with long-term video recording, multi-animal tracking and high-resolution respirometry. We find male and female ticks are in a more active, more arousable state during circadian night. We find respiration is augmented by light, with dark onset triggering more frequent bouts of discontinuous gas exchange and a higher overall volume of CO2 respired. Observed inactivity during the day meets the criteria of sleep: homeostatic in nature, rapidly reversible, a characteristic pose, and reduced arousal threshold. Our findings indicate that blacklegged ticks are in a distinct, heightened state of activity and arousability during night and in dark, suggesting this period may carry higher risk for tick bites and subsequent contraction of tick-borne diseases.

Mausolates: Large-Cavity Chelates with Potential as Delivery Vehicles in Nuclear Medicine.

A new type of diborate clathrochelate (cage) ligand featuring nine inwardly pointing nitrogen donors that form a large, rigid cavity, termed a mausolate, is presented. The cavity size and high denticity make this an attractive delivery vehicle for large radionuclides in nuclear medicine. Metal mausolate complexes are stable to air and water (neutral pH) and display extremely high thermal stability (>400 °C). Lanthanide uptake by the mausolate ligand occurs rapidly in solution at room temperature and once complexed, the lanthanide ions are not displaced by a 250-fold excess of a competitive lanthanide salt over more than one week.

Mechanistic study of the atomic layer deposition of cobalt: a combined mass spectrometric and computational approach.

Cobaltcarbonyl-tert-butylacetylene (CCTBA) is a conventional precursor for the selective atomic layer deposition of Co onto silicon surfaces. However, a limited understanding of the deposition mechanism of such cobalt precursors curbs rational improvements on their design for increased efficiency and tuneable selectivity. The impact of using a less reactive internal alkyne instead of a terminal alkyne was investigated using experimental and computational methods. Using electrospray-ionization mass spectrometry, the formation of CCTBA analogs and their gas phase decomposition pathways were studied. Decomposition experiments show very similar decomposition pathways between the two complexes. The internal alkyne dissociates from the Co complex at slightly lower energies than the terminal alkyne, suggesting that an internal alkynyl ligand may be more suited to low temperature ALD. In addition, transition state calculations using the nudged elastic band method confirm an increased reaction barrier between the internal alkyne and the Si-H surface bonds on Si(111). These results suggests that using a less reactive internal alkyne will result in fewer embedded carbon impurities during deposition onto Si wafers. DFT calculations using the PBE functional and periodic boundary conditions also predict increased surface binding with the metal centers of the internal alkynyl complex.

Metal-cation-induced shifts in thiolate redox and reduced sulfur speciation.

Sulfur-containing anions (e.g. thiolates, polysulfides) readily exchange in solution, making control over their solution speciation and distribution challenging. Here, we demonstrate that different redox-inactive alkali, alkaline earth, and transition metals (Li+, Na+, K+, Mg2+, Ca2+, Zn2+, and Cd2+) shift the equilibria of sulfur catenation or sulfur reduction/oxidation between thiolate, polysulfanide, and polysulfide anions in acetonitrile solution. The thermodynamic factors that govern these equilibria are examined by identification of intermediate metal thiolate and metal polysulfide species using a combination of NMR spectroscopy, electronic absorption spectroscopy, and mass spectrometry. Electrochemical measurements demonstrate that the metal cation of the electrolyte modulates both sulfur reduction and thiolate oxidation potentials. DFT calculations suggest that the changes in equilibria are driven by stronger covalent interactions between polysulfide anions and more highly charged cations.

The unanti-cipated oxidation of a tertiary amine in a tetra-cyclic glyoxal-cyclam condensate yielding zinc(II) coordinated to a sterically hindered amine oxide.

The complex, tri-chlorido-(1,4,11-tri-aza-8-azonia-tetra-cyclo-[6.6.2.04,16.011,15]hexa-decane 1-oxide-κO)zinc(II) monohydrate, [ZnCl3(C12H23N4O)]·H2O, (I), has monoclinic symmetry (space group P21/n) at 120 K. The zinc(II) center adopts a slightly distorted tetra-hedral coordination geometry and is coordinated by three chlorine atoms and the oxygen atom of the oxidized tertiary amine of the tetra-cycle. The amine nitro-gen atom, inside the ligand cleft, is protonated and forms a hydrogen bond to the oxygen of the amine oxide. Additional hydrogen-bonding inter-actions involve the protonated amine, the water solvate oxygen atom, and one of the chloro ligands.

Stroke Prevention in Blunt Cerebrovascular Injury: Role of Aspirin 81 mg.

BACKGROUND: The stroke rate in blunt cerebrovascular injury (BCVI) varies from 25% without treatment to less than 8% with antithrombotic therapy. There is no consensus on the optimal management to prevent stroke BCVI. We investigated the efficacy and safety of oral Aspirin (ASA) 81 mg to prevent BCVI-related stroke compared to historically reported stroke rates with ASA 325 mg and heparin. METHODS: A single-center retrospective study included adult trauma patients who received oral ASA 81 mg for BCVI management between 2013 and 2022. Medical records were reviewed for demographic and injury characteristics, imaging findings, treatment-related complications, and outcomes. RESULTS: Eighty-four patients treated with ASA 81 mg for BCVI were identified. The mean age was 41.50 years, and 61.9% were male. The mean Injury Severity Score and Glasgow Coma Scale were 19.82 and 12.12, respectively. A total of 101 vessel injuries were identified, including vertebral artery injuries in 56.4% and carotid artery injuries in 44.6%. Traumatic brain injury was found in 42.9%, and 16.7% of patients had a solid organ injur. Biffl grade I (52.4%) injury was the most common, followed by grade II (37.6%) and grade III (4.9%). ASA 81 mg was started in the first 24 hours in 67.9% of patients, including 20 patients with traumatic brain injury and 8 with solid organ injuries. BCVI-related stroke occurred in 3 (3.5%) patients with Biffl grade II (n = 2) and III (n = 1). ASA-related complications were not identified in any patient. The mean length of stay in the hospital was 10.94 days, and 8 patients died during hospitalization due to complications of polytrauma. Follow-up with computed tomography angiography was performed in 8 (9.5%) patients, which showed improvement in 5 and a stable lesion in 3 at a mean time of 58 days after discharge. CONCLUSIONS: In the absence of clear guidelines regarding appropriate medication, BCVI management should be individualized case-by-case through a multidisciplinary approach. ASA 81 mg is a viable option for BCVI-related stroke prevention compared to the reported stroke rates (2%-8%) with commonly used antithrombotics like heparin and ASA 325 mg. Future prospective studies are needed to provide insight into the safety and efficacy of the current commonly used agent in managing BCVI.

Next-Generation 3,3'-AlkoxyBTPs as Complexants for Minor Actinide Separation from Lanthanides: A Comprehensive Separations, Spectroscopic, and DFT Study.

Progress toward the closure of the nuclear fuel cycle can be achieved if satisfactory separation strategies for the chemoselective speciation of the trivalent actinides from the lanthanides are realized in a nonproliferative manner. Since Kolarik's initial report on the utility of bis-1,2,4-triazinyl-2,6-pyridines (BTPs) in 1999, a perfect complexant-based, liquid-liquid separation system has yet to be realized. In this report, a comprehensive performance assessment for the separation of 241Am3+ from 154Eu3+ as a model system for spent nuclear fuel using hydrocarbon-actuated alkoxy-BTP complexants is described. These newly discovered complexants realize gains that contemporary aryl-substituted BTPs have yet to achieve, specifically: long-term stability in highly concentrated nitric acid solutions relevant to the low pH of unprocessed spent nuclear fuel, high DAm over DEu in the economical, nonpolar diluent Exxal-8, and the demonstrated capacity to complete the separation cycle with high efficiency by depositing the chelated An3+ to the aqueous layer via decomplexation of the metal-ligand complex. These soft-N-donor BTPs are hypothesized to function as bipolar complexants, effectively traversing the organic/aqueous interface for effective chelation and bound metal/ligand complex solubility. Complexant design, separation assays, spectroscopic analysis, single-crystal X-ray crystallographic data, and DFT calculations are reported.

Population modifiable risk factors associated with under-5 acute respiratory tract infections and diarrhoea in 25 countries in sub-Saharan Africa (2014-2021): an analysis of data from demographic and health surveys.

Background: Identifying the critical modifiable risk factors for acute respiratory tract infections (ARIs) and diarrhoea is crucial to reduce the burden of disease and mortality among children under 5 years of age in sub-Saharan Africa (SSA) and ultimately achieving the Sustainable Development Goals (SDGs). We investigated the modifiable risk factors of ARI and diarrhoea among children under five using nationally representative surveys. Methods: We used the most recent demographic and health survey (DHS) data (2014-2021) from 25 SSA countries, encompassing a total of 253,167 children. Countries were selected based on the availability of recent datasets (e.g., DHS-VII or DHS-VIII) that represent the current socioeconomic situations. Generalised linear latent mixed models were used to compute odds ratios (ORs). Population attributable fractions (PAFs) were calculated using adjusted ORs and prevalence estimates for key modifiable risk factors among ARI and diarrhoeal cases. Findings: This study involved 253,167 children, with a mean age of 28.7 (±17.3) months, and 50.5% were male. The highest PAFs for ARI were attributed to unclean cooking fuel (PAF = 15.7%; 95% CI: 8.1, 23.1), poor maternal education (PAF = 13.4%; 95% CI: 8.7, 18.5), delayed initiation of breastfeeding (PAF = 12.4%; 95% CI: 9.0, 15.3), and poor toilets (PAF = 8.5%; 95% CI: 4.7, 11.9). These four modifiable risk factors contributed to 41.5% (95% CI: 27.2, 52.9) of ARI cases in SSA. The largest PAFs of diarrhoea were observed for unclean cooking fuel (PAF = 17.3%; 95% CI: 13.5, 22.3), delayed initiation of breastfeeding (PAF = 9.2%; 95% CI: 7.5, 10.5), household poverty (PAF = 7.0%; 95% CI: 5.0, 9.1) and poor maternal education (PAF = 5.6%; 95% CI: 2.9, 8.8). These four modifiable risk factors contributed to 34.0% (95% CI: 26.2, 42.3) of cases of diarrhoea in SSA. Interpretation: This cross-sectional study identified four modifiable risk factors for ARI and diarrhoea that should be a priority for policymakers in SSA. Enhancing home-based care and leveraging female community health workers is crucial for accelerating the reduction in under-5 mortality linked to ARI and diarrhoea in SSA. Funding: None.

MAST: Phylogenetic Inference with Mixtures Across Sites and Trees.

Hundreds or thousands of loci are now routinely used in modern phylogenomic studies. Concatenation approaches to tree inference assume that there is a single topology for the entire dataset, but different loci may have different evolutionary histories due to incomplete lineage sorting, introgression, and/or horizontal gene transfer; even single loci may not be treelike due to recombination. To overcome this shortcoming, we introduce an implementation of a multi-tree mixture model that we call MAST. This model extends a prior implementation by Boussau et al. (2009) by allowing users to estimate the weight of each of a set of pre-specified bifurcating trees in a single alignment. The MAST model allows each tree to have its own weight, topology, branch lengths, substitution model, nucleotide or amino acid frequencies, and model of rate heterogeneity across sites. We implemented the MAST model in a maximum-likelihood framework in the popular phylogenetic software, IQ-TREE. Simulations show that we can accurately recover the true model parameters, including branch lengths and tree weights for a given set of tree topologies, under a wide range of biologically realistic scenarios. We also show that we can use standard statistical inference approaches to reject a single-tree model when data are simulated under multiple trees (and vice versa). We applied the MAST model to multiple primate datasets and found that it can recover the signal of incomplete lineage sorting in the Great Apes, as well as the asymmetry in minor trees caused by introgression among several macaque species. When applied to a dataset of four Platyrrhine species for which standard concatenated maximum likelihood and gene tree approaches disagree, we observe that MAST gives the highest weight (i.e. the largest proportion of sites) to the tree also supported by gene tree approaches. These results suggest that the MAST model is able to analyse a concatenated alignment using maximum likelihood, while avoiding some of the biases that come with assuming there is only a single tree. We discuss how the MAST model can be extended in the future.

Perceptions and barriers about mental health services among Pacific Islanders: An interpretative phenomenological analysis.

Every year, millions of Americans do not receive needed mental health (MH) services. Although Pacific Islanders (PI) have a high need for MH services, this group has the lowest rate of MH care help seeking. This is especially concerning as the rate of suicide has been increasing within the PI community. This study explored how Pacific Islanders think about MH supports, including their attitudes toward and perceptions of barriers to receiving MH services. An interpretative phenomenological analysis focus group study was conducted with cross-generational Pacific Islanders residing in one western state. The findings include (a) PI perceptions that MH help seeking results in family burdensomeness, stigma, and shame; (b) negotiating PI social customs and beliefs related to MH help seeking, care, and support; and (c) PI mistrust of institutional resources. These themes seemed to interact with each other and create perpetuate barriers which prevent help-seeking behaviors. Clinical and research implications will be provided. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Efficacy and clinical potential of phage therapy in treating methicillin-resistant Staphylococcus aureus (MRSA) infections: A review.

Staphylococcus aureus infections have already presented a substantial public health challenge, encompassing different clinical manifestations, ranging from bacteremia to sepsis and multi-organ failures. Among these infections, methicillin-resistant S. aureus (MRSA) is particularly alarming due to its well-documented resistance to multiple classes of antibiotics, contributing significantly to global mortality rates. Consequently, the urgent need for effective treatment options has prompted a growing interest in exploring phage therapy as a potential non-antibiotic treatment against MRSA infections. Phages represent a class of highly specific bacterial viruses known for their ability to infect certain bacterial strains. This review paper explores the clinical potential of phages as a treatment for MRSA infections due to their low toxicity and auto-dosing capabilities. The paper also discusses the synergistic effect of phage-antibiotic combination (PAC) and the promising results from in vitro and animal model studies, which could lead to extensive human clinical trials. However, clinicians need to establish and adhere to standard protocols governing phage administration and implementation. Prominent clinical trials are needed to develop and advance phage therapy as a non-antibiotic therapy intervention, meeting regulatory guidelines, logistical requirements, and ethical considerations, potentially revolutionizing the treatment of MRSA infections.

Equipping for risk: Lessons learnt from the UK shale-gas experience on assessing environmental risks for the future geoenergy use of the deep subsurface.

findings are presented from an investigation to improve understanding of the environmental risks associated with developing an unconventional-hydrocarbons industry in the UK. The EQUIPT4RISK project, funded by UK Research Councils, focused on investigations around Preston New Road (PNR), Fylde, Lancashire, and Kirby Misperton Site A (KMA), North Yorkshire, where operator licences to explore for shale gas by hydraulic fracturing (HF) were issued in 2016, although exploration only took place at PNR. EQUIPT4RISK considered atmospheric (greenhouse gases, air quality), water (groundwater quality) and solid-earth (seismicity) compartments to characterise and model local conditions and environmental responses to HF activities. Risk assessment was based on the source-pathway-receptor approach. Baseline monitoring of air around the two sites characterised the variability with meteorological conditions, and isotopic signatures were able to discriminate biogenic methane (cattle) from thermogenic (natural-gas) sources. Monitoring of a post-HF nitrogen-lift (well-cleaning) operation at PNR detected the release of atmospheric emissions of methane (4.2 ± 1.4 t CH4). Groundwater monitoring around KMA identified high baseline methane concentrations and detected ethane and propane at some locations. Dissolved methane was inferred from stable-isotopic evidence as overwhelmingly of biogenic origin. Groundwater-quality monitoring around PNR found no evidence of HF-induced impacts. Two approaches for modelling induced seismicity and associated seismic risk were developed using observations of seismicity and operational parameters from PNR in 2018 and 2019. Novel methodologies developed for monitoring include use of machine learning to identify fugitive atmospheric methane, Bayesian statistics to assess changes to groundwater quality, a seismicity forecasting model seeded by the HF-fluid injection rate and high-resolution monitoring of soil-gas methane. The project developed a risk-assessment framework, aligned with ISO 31000 risk-management principles, to assess the theoretical combined and cumulative environmental risks from operations over time. This demonstrated the spatial and temporal evolution of risk profiles: seismic and atmospheric impacts from the shale-gas operations are modelled to be localised and short-lived, while risk to groundwater quality is longer-term.

Schistosome Transgenesis: The Long Road to Success.

As research on parasitic helminths has entered the post-genomic era, research efforts have turned to deciphering the function of genes in the public databases of genome sequences. It is hoped that, by understanding the role of parasite genes in maintaining their parasitic lifestyle, critical insights can be gained to develop new intervention and control strategies. Methods to manipulate and transform parasitic worms are now developed to a point where it has become possible to gain a comprehensive understanding of the molecular mechanisms underlying host-parasite interplay, and here, we summarise and discuss the advances that have been made in schistosome transgenesis over the past 25 years. The ability to genetically manipulate schistosomes holds promise in finding new ways to control schistosomiasis, which ultimately may lead to the eradication of this debilitating disease.