Improving strategic planning for nature: Panacea or pandora's box for the built and natural environment?

This paper assesses how strategic planning for nature can be improved for England's built and natural environment using mainstreaming and landscape-scale concepts. Whilst both concepts feature in academic literature, there has been limited attention on their role as catalytic agents for strategic planning. Addressing this gap, evidence is used from two stakeholder workshops involving 62 senior policy experts managing a range of operational and hypothetical strategic spatial planning challenges. The results reveal a significantly weakened strategic planning arena characterised by policy disintegration, short termism and uncertainty. Key findings highlight the fallacy of pursuing strategic planning for nature in isolation from wider policy integration fusing environmental, economic and social components from the outset. Current barriers to progress include institutional inertia, technocratic vocabularies and neoliberalist priorities exacerbated by a weak underlying theory. Conversely opportunities for mainstreaming processes may help knowledge generation and exchange within transdisciplinary partnerships, whilst landscape scale thinking can improve understanding of issues using natures inherent geometry transforming processes and outcomes. The paper recommends the adoption of strategic planning pathways using mainstreaming and landscape-scale approaches working in tandem. Whilst focused on the English context, our findings are transferable to other planning systems in the Global North, especially those championing neoliberal market led policies.

Pre-Younger Dryas megafaunal extirpation at Rancho La Brea linked to fire-driven state shift.

The cause, or causes, of the Pleistocene megafaunal extinctions have been difficult to establish, in part because poor spatiotemporal resolution in the fossil record hinders alignment of species disappearances with archeological and environmental data. We obtained 172 new radiocarbon dates on megafauna from Rancho La Brea in California spanning 15.6 to 10.0 thousand calendar years before present (ka). Seven species of extinct megafauna disappeared by 12.9 ka, before the onset of the Younger Dryas. Comparison with high-resolution regional datasets revealed that these disappearances coincided with an ecological state shift that followed aridification and vegetation changes during the Bølling-Allerød (14.69 to 12.89 ka). Time-series modeling implicates large-scale fires as the primary cause of the extirpations, and the catalyst of this state shift may have been mounting human impacts in a drying, warming, and increasingly fire-prone ecosystem.

Efficacy of partial spraying of SumiShield, Fludora Fusion and Actellic against wild populations of Anopheles gambiae s.l. in experimental huts in Tiassalé, Côte d'Ivoire.

From August 2020 to June 2021, we assessed the efficacy of SumiShield 50WG (clothianidin), Fludora Fusion 56.25WP-SB (mixture of clothianidin and deltamethrin) and Actellic 300CS (pirimiphos-methyl) in experimental huts when partially sprayed against wild, free-flying populations of Anopheles gambiae s.l. in Tiassalé, Côte d'Ivoire. A one-month baseline period of mosquito collections was conducted to determine mosquito density and resting behavior in unsprayed huts, after which two treatments of partial indoor residual spraying (IRS) were tested: spraying only the top half of walls + ceilings or only the bottom half of walls + ceilings. These were compared to fully sprayed applications using the three IRS insecticide formulations, during twenty nights per month of collection for nine consecutive months. Mortality was assessed at the time of collection, and after a 24 h holding period (Actellic) or up to 120 h (SumiShield and Fludora Fusion). Unsprayed huts were used as a negative control. The efficacy of each partially sprayed treatment of each insecticide was compared monthly to the fully sprayed huts over the study period with a non-inferiority margin set at 10%. The residual efficacy of each insecticide sprayed was also monitored. A total of 2197 Anopheles gambiae s.l. were collected during the baseline and 17,835 during the 9-month period after spraying. During baseline, 42.6% were collected on the bottom half versus 24.3% collected on the top half of the walls, and 33.1% on the ceilings. Over the nine-month post treatment period, 73.5% were collected on the bottom half of the wall, 11.6% collected on the top half and 14.8% on the ceilings. For Actellic, the mean mortality over the nine-month period was 88.5% [87.7, 89.3] for fully sprayed huts, 88.3% [85.1, 91.4] for bottom half + ceiling sprayed walls and 80.8% [74.5, 87.1] for the top half + ceiling sprayed huts. For Fludora Fusion an overall mean mortality of 85.6% [81.5, 89.7] was recorded for fully sprayed huts, 83.7% [82.9, 84.5] for bottom half + ceiling sprayed huts and 81.3% [79.6, 83.0] for the top half + ceiling sprayed huts. For SumiShield, the overall mean mortality was 86.7% [85.3, 88.1] for fully sprayed huts, 85.6% [85.4, 85.8] for the bottom half + ceiling sprayed huts and 76.9% [76.6, 77.3] for the top half + ceiling sprayed huts. For Fludora Fusion, both iterations of partial IRS were non-inferior to full spraying. However, for SumiShield and Actellic, this was true only for the huts with the bottom half + ceiling, reflecting the resting site preference of the local vectors. The results of this study suggest that partial spraying may be a way to reduce the cost of IRS without substantially compromising IRS efficacy.

Multi-centre discriminating concentration determination of broflanilide and potential for cross-resistance to other public health insecticides in Anopheles vector populations.

Novel insecticides are urgently needed to control insecticide-resistant populations of Anopheles malaria vectors. Broflanilide acts as a non-competitive antagonist of the gamma-aminobutyric acid receptor and has shown prolonged effectiveness as an indoor residual spraying product (VECTRON T500) in experimental hut trials against pyrethroid-resistant vector populations. This multi-centre study expanded upon initial discriminating concentration testing of broflanilide, using six Anopheles insectary colonies (An. gambiae Kisumu KCMUCo, An. gambiae Kisumu NIMR, An. arabiensis KGB, An. arabiensis SENN, An. coluzzii N'Gousso and An. stephensi SK), representing major malaria vector species, to facilitate prospective susceptibility monitoring of this new insecticide; and investigated the potential for cross-resistance to broflanilide via the A296S mutation associated with dieldrin resistance (rdl). Across all vector species tested, the discriminating concentration for broflanilide ranged between LC99 × 2 = 1.126-54.00 µg/ml or LC95 × 3 = 0.7437-17.82 µg/ml. Lower concentrations of broflanilide were required to induce complete mortality of An. arabiensis SENN (dieldrin-resistant), compared to its susceptible counterpart, An. arabiensis KGB, and there was no association between the presence of the rdl mechanism of resistance and survival in broflanilide bioassays, demonstrating a lack of cross-resistance to broflanilide. Study findings provide a benchmark for broflanilide susceptibility monitoring as part of ongoing VECTRON T500 community trials in Tanzania and Benin.

Implementing OECD GLP principles for the evaluation of novel vector control tools: a case study with two novel LLINs, SafeNet® and SafeNet NF®.

BACKGROUND: To sustain high universal Long-Lasting Insecticidal Nets (LLINs) coverage, affordable nets that provide equivalent or better protection than standard LLINs, are required. Test facilities evaluating new LLINs require compliance to Good Laboratory Practice (GLP) standards to ensure the quality and integrity of test data. Following GLP principles allows for the reconstruction of activities during the conduct of a study and minimizes duplication of efficacy testing. This case study evaluated the efficacy of two LLINs: SafeNet NF® and SafeNet® LLIN. METHODS: The study was conducted according to GLP principles and followed World Health Organization guidelines for evaluating LLINs. The LLINs were assessed in experimental huts against wild, pyrethroid-resistant Anopheles arabiensis mosquitoes. Nets were either unwashed or washed 20 times and artificially holed to simulate a used torn net. Blood-feeding inhibition and mortality were compared with a positive control (Interceptor® LLIN) and an untreated net. RESULTS: Mosquito entry in the huts was reduced compared to negative control for the unwashed SafeNet NF, washed Safenet LLIN and the positive control arms. Similar exiting rates were found for all the treatment arms. Significant blood-feeding inhibition was only found for the positive control, both when washed and unwashed. All insecticide treatments induced significantly higher mortality compared to an untreated net. Compared to the positive control, the washed and unwashed SafeNet NF® resulted in similar mortality. For the SafeNet® LLINs the unwashed net had an equivalent performance, but the mortality for the washed net was significantly lower than the positive control. Internal audits of the study confirmed that all critical phases complied with Standard Operating Procedures (SOPs) and the study plan. The external audit confirmed that the study complied with GLP standards. CONCLUSIONS: SafeNet NF® and SafeNet® LLIN offered equivalent protection to the positive control (Interceptor® LLIN). However, further research is needed to investigate the durability, acceptability, and residual efficacy of these nets in the community. This study demonstrated that GLP-compliant evaluation of LLINs can be successfully conducted by African research institutions.

Enhancing the Quality of Spray Application in IRS: Evaluation of the Micron Track Sprayer.

Indoor residual spraying (IRS) has changed little since its introduction in the 1940s. Manual spraying is still prone to variation in insecticide dose. To improve the application of IRS in experimental hut trials, an automated track sprayer was developed, which regulates the speed of application and the distance of the nozzle from the wall, two key sources of variation. The automated track sprayer was compared to manual spraying, firstly using fluorescein solution in controlled indoor settings, and secondly in experimental huts in Tanzania using several IRS products. Manual spraying produced greater variation with both fluorescein and insecticide applications. Both manual and automated spray methods under-dosed the actual dose sprayed compared to the target dose. Overall, the track sprayer treats surfaces more consistently, offering a potential improvement over manual spraying for experimental hut evaluation of new IRS formulations.

Large-scale (Phase III) evaluation of broflanilide 50WP (VECTRON™ T500) for indoor residual spraying for malaria vector control in Northeast Tanzania: study protocol for a two-arm, non-inferiority, cluster-randomised community trial.

BACKGROUND: Indoor residual spraying (IRS) is a major method of malaria vector control across sub-Saharan Africa. Effective control is being undermined by the rapid spread of insecticide resistance. There is major investment in development of new insecticides for IRS that possess novel modes of action, long residual activity, low mammalian toxicity and minimal cross-resistance. VECTRON™ T500, a new IRS product containing the active ingredient broflanilide as a 50% wettable powder (WP), has been shown to be efficacious against pyrethroid susceptible and resistant vector species on mud and concrete substrates in experimental hut (Phase II) trials. METHODS: A two-arm non-inferiority cluster randomized controlled trial (Phase III) will be undertaken in Muheza District, Tanga Region, Tanzania. VECTRON™ T500 will be compared to the IRS product Fludora® Fusion (clothianidin 50% WP + deltamethrin 6.25% WP). The predominant malaria vectors in the study area are pyrethroid-resistant Anopheles gambiae s.s., An. arabiensis and An. funestus s.s. Sixteen village clusters will be pair-matched on baseline vector densities and allocated to reference and intervention arms. Consenting households in the intervention arm will be sprayed with VECTRON™ T500 and those in the reference arm will be sprayed with Fludora® Fusion. Each month, CDC light traps will collect mosquitoes to estimate changes in vector density, indoor biting, sporozoite and entomological inoculation rates (EIR). Susceptibility to IRS active ingredients will be assessed using World Health Organisation (WHO) bottle bioassays. Target site and metabolic resistance mechanisms will be characterised among Anopheles field populations from both trial arms. Residual efficacy of both IRS products will be monitored for 12 months post intervention. Questionnaire and focus group discussions will explore factors that influence adherence, adverse effects and benefits of IRS. DISCUSSION: This protocol describes a large-scale non-inferiority evaluation of a novel IRS product to reduce the density and EIR of pyrethroid-resistant Anopheles vectors. If VECTRON™ T500 proves non-inferior to Fludora® Fusion, it will be considered as an additional vector control product for malaria prevention and insecticide resistance management. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05150808, registered on 26 November 2021. Retrospectively registered.

Colonization and Authentication of the Pyrethroid-Resistant Anopheles gambiae s.s. Muleba-Kis Strain; an Important Test System for Laboratory Screening of New Insecticides.

BACKGROUND: The emergence and spread of insecticide resistance in malaria vectors to major classes of insecticides call for urgent innovation and application of insecticides with novel modes of action. When evaluating new insecticides for public health, potential candidates need to be screened against both susceptible and resistant mosquitoes to determine efficacy and to identify potential cross-resistance to insecticides currently used for mosquito control. The challenges and lessons learned from establishing, maintaining, and authenticating the pyrethroid-resistant An. gambiae s.s. Muleba-Kis strain at the KCMUCo-PAMVERC Test Facility are described in this paper. METHODS: Male mosquitoes from the F1 generation of wild-pyrethroid resistant mosquitoes were cross-bred with susceptible female An. gambiae s.s. Kisumu laboratory strain followed by larval selection using a pyrethroid insecticide solution. Periodic screening for phenotypic and genotypic resistance was done. WHO susceptibility tests and bottle bioassays were used to assess the phenotypic resistance, while Taqman™ assays were used to screen for known target-site resistance alleles (kdr and ace-1). Additionally, the strains were periodically assessed for quality control by monitoring adult weight and wing length. RESULTS: By out-crossing the wild mosquitoes with an established lab strain, a successful resistant insectary colony was established. Intermittent selection pressure using alphacypermethrin has maintained high kdr mutation (leucine-serine) frequencies in the selected colony. There was consistency in the wing length and weight measurements from the year 2016 to 2020, with the exception that one out of four years was significantly different. Mean annual wing length varied between 0.0142-0.0028 mm compared to values obtained in 2016, except in 2019 where it varied by 0.0901 mm. Weight only varied by approximately 0.001 g across four years, except in 2017 where it differed by 0.005 g. Routine phenotypic characterization on Muleba-Kis against pyrethroids using the WHO susceptibility test indicated high susceptibility when type I pyrethroids were used compared to type II pyrethroids. Dynamics on susceptibility status also depended on the lapse time when the selection was last done. CONCLUSIONS: This study described the procedure for introducing, colonizing, and maintaining a resistant An. gambiae s.s. strain in the laboratory with leucine to serine substitution kdr allele which reflects the features of the wild-resistant population in East Africa. Challenges in colonizing a wild-resistant mosquito strain were overcome by out-crossing between mosquito strains of desired traits followed by intermittent insecticide selection at the larval stage to select for the resistant phenotype.

Efficacy of indoor residual spraying with broflanilide (TENEBENAL), a novel meta-diamide insecticide, against pyrethroid-resistant anopheline vectors in northern Tanzania: An experimental hut trial.

Novel chemistry for vector control is urgently needed to counter insecticide resistance in mosquitoes. Here a new meta-diamide insecticide, broflanilide (TENEBENALTM), was evaluated in East African experimental huts in Moshi, northern Tanzania. Two consecutive experimental hut trials with broflanilide 50WP were conducted; the first evaluating the efficacy of three concentrations, 50 mg/m2, 100 mg/m2, and 200 mg/m2 using a prototype formulation, and the second trial evaluating an improved formulation. The IRS treatments were applied on both mud and concrete surfaces and efficacy was monitored over time. The mortality, blood-feeding inhibition and exiting behaviour of free-flying wild mosquitoes was compared between treatment arms. Additionally, cone assays with pyrethroid-susceptible and resistant mosquito strains were conducted in the huts to determine residual efficacy. The first trial showed a dosage-mortality response of the prototype formulation and 3-8 months of residual activity, with longer activity on concrete than mud. The second trial with an improved formulation showed prolonged residual efficacy of the 100 mg/m2 concentration to 5-6 months on mud, and mosquito mortality on the concrete surface ranged between 94-100% for the full duration of the trial. In both trials, results with free-flying, wild Anopheles arabiensis echoed the mortality trend shown in cone assays, with the highest dose inducing the highest mortality and the improved formulation showing increased mortality rates. No blood-feeding inhibition or insecticide-induced exiting effects were observed with broflanilide. Broflanilide 50WP was effective against both susceptible and pyrethroid-resistant mosquito strains, demonstrating an absence of cross resistance between broflanilide and pyrethroids. The improved formulation, which has now been branded VECTRONTM T500, resulted in a prolonged residual efficacy. These results indicate the potential of this insecticide as an addition to the arsenal of IRS products needed to maintain both control of malaria and resistance management of malaria-transmitting mosquitoes.

Developing laboratory capacity for Good Laboratory Practice certification: lessons from a Tanzanian insecticide testing facility.

Background: With increasing insecticide resistance in malaria-endemic countries there is an urgent need for safe and effective novel vector control products. To improve the capacity of facilities that test insecticides in sub-Saharan Africa, a programme is supporting seven facilities towards Good Laboratory Practice (GLP) certification, the globally recognized standard for quality management system (QMS) for the conduct of non-clinical and environmental studies. The World Health Organization (WHO) GLP Handbook provides guidance on a stepwise approach to implement a GLP compliant QMS. This study assesses auditor GLP checklists and timings outlined in the WHO GLP Handbook in the real-life context of a Tanzanian insecticide-testing facility, evaluating their implementation in this context. Methods and Principle Findings: We conducted document review and semi-structured interviews with staff at all levels of the test facility to explore factors that influenced progress towards GLP certification. We found that while auditor GLP checklists underemphasised computer systems, they were otherwise broadly applicable. Factors that delayed time to completion of GLP certification included the need for extensive infrastructure improvements, the availability of regional expertise related to GLP, the capacity of national and regional external systems and services to meet GLP compliance requirements, and training development required for Standard Operating Procedure implementation. Conclusion: The standards required for full GLP compliance are rigorous, with an expected completion timeline to implementation of 24 months. This study shows that in low and middle-income countries this timeline may be unrealistic due to challenges related to infrastructure development and lack of regional capacity and expertise. We recommend a comprehensive gap analysis when starting a project, including these areas which are beyond those recommended by the WHO GLP Handbook. These challenges can be successfully overcome and the experience in Tanzania provides key lessons for other facilities seeking GLP certification or the development of similar QMS.

Stability Series for the Complexation of Six Key Siderophore Functional Groups with Uranyl Using Density Functional Theory.

Determining stability constants of uranyl complexes with the principal functional groups in siderophores and identifying stability series is of great importance to predict which siderophore classes preferentially bind to UVI and, hence, impact uranium speciation in the environment. It also helps to develop resins for scavenging UVI from aqueous solutions. Here, we apply a recently developed computational approach to calculate log ß values for a set of geochemically relevant uranium organometallic complexes using Density Functional Theory (DFT). We determined the stability series for catecholate, hydroxamate, α-hydroxycarboxylate, α-aminocarboxylate, hydroxy-phenyloxazolonate, and α-hydroxyimidazole with the uranyl cation. In this work, the stability constants (log ß110) of α-hydroxyimidazolate and hydroxy-phenyloxazolonate are calculated for the first time. Our approach employed the B3LYP density functional approximation, aug-cc-pVDZ basis set for ligand atoms, MDF60 ECP for UVI, and the IEFPCM solvation model. DFT calculated log ß110 were corrected using a previously established fitting equation. We find that the siderophore functional groups stability decreases in the order: α-hydroxycarboxylate bound via the α-hydroxy and carboxylate groups (log ß110 = 17.08), α-hydroxyimidazolate (log ß110 = 16.55), catecholate (log ß110 = 16.43), hydroxamate (log ß110 = 9.00), hydroxy-phenyloxazolonate (log ß110 = 8.43), α-hydroxycarboxylate bound via the carboxylate group (log ß110 = 7.51) and α-aminocarboxylate (log ß110 = 4.73). We confirm that the stability for the binding mode of the functional groups decrease in the order: bidentate, monodentate via ligand O atoms, and monodentate via ligand N atoms. The stability series strongly suggests that α-hydroxyimidazolate is an important functional group that needs to be included when assessing uranyl mobility and removal from aqueous solutions.

Three-dimensional rendering of trabecular bone microarchitecture using a probabilistic approach.

In the past, researchers have attempted to model trabecular bone using computational techniques. However, only a few of these models are visually similar, but not representative of the microstructural characteristics of real trabecular bones. In this study, we hypothesized that probabilistic modeling approaches could be used to generate representative digital models that capture the microstructural features of real trabecular bones. To test this hypothesis, we proposed a novel mathematical framework to build the digital models and compared the digital models to real bone specimens. First, an initial three-dimensional cellular structure was generated using Voronoi tessellation, with the faces and edges of the Voronoi cells considered as a pool of potential trabecular plates and rods, respectively. Then, inverse Monte Carlo simulations were performed to select, delete, or reassign plates and rods until the underlying size, orientation, and spatial distributions of the plates and rods converged to the target distributions obtained from real trabecular bone microstructures. Next, digital graphics techniques were used to define the thickness of trabecular plates and the diameter of trabecular rods, followed by writing the model into a Standard Tessellation Language file and then smoothing the model surfaces for a more natural appearance. To verify the efficacy of the digital model in capturing the microstructural features of real trabecular bones, forty-six digital models with a large variation in microstructural features were generated based on the target distributions obtained from trabecular bone specimens of twelve human cadaveric femurs. Then, the histomorphological parameters of the digital models were compared with those of the real trabecular bone specimens. The results indicate that the digital models are capable of capturing major microstructural features of the trabecular bone samples, thus proving the hypothesis that the proposed probabilistic modeling approach could render real trabecular bone microstructures.

Ripple effects of research capacity strengthening: a study of the effects of a project to support test facilities in three African countries towards Good Laboratory Practice certification.

Background: Strengthening capacity for public health research is essential to the generation of high-quality, reliable scientific data. This study focuses on a research capacity strengthening project supporting seven test facilities in Africa conducting studies on mosquito vector control products towards Good Laboratory Practice (GLP) certification. It captures the primary effects of the project on each facility's research capacity, the secondary effects at the individual and institutional level, and the ripple effects that extend beyond the research system. The relationships between effects at different levels are identified and compared to an existing framework for the evaluation of research capacity strengthening initiatives. Methods: To capture the views of individuals engaged in the project at all levels within each facility, a maximum-variation purposive sampling strategy was used. This allowed triangulation between different data sources. Semi-structured interviews were conducted with individuals in three facilities and a combination of email and remote video-call interviews were conducted with individuals at two further facilities. Results: We found that, despite a focus of the GLP certification project at the institutional level, the project had effects also at individual (including enhanced motivation, furtherment of careers) and national/international levels (including development of regional expertise). In addition, we detected ripple effects of the project which extended beyond the research system. Conclusion: This study shows that research capacity strengthening interventions that are focussed on institutional level goals require actions also at individual and national/international levels. The effects of engagement at all three levels can be amplified by collaborative actions at the national/international level. These findings show that research capacity strengthening projects must develop plans that address and evaluate impact at all three levels. Capturing the ripple effects of investment in research capacity strengthening should also be planned for from the beginning of projects to support further engagement of all stakeholders.

Correction to: Monitoring changes in malaria epidemiology and effectiveness of interventions in Ethiopia and Uganda: Beyond Garki Project baseline survey.

Please be advised that one of the author names is incorrectly spelled in the published article: 'Irene Kyomuhagi' should be 'Irene Kyomuhangi'.

Movement and habitat selection of the western spadefoot (Spea hammondii) in southern California.

Agricultural activity, urban development and habitat alteration have caused the disappearance of the western spadefoot (Spea hammondii) from 80% of its geographic range in southern California. Despite the western spadefoot's continuing decline, little research has been conducted on its natural history. The home range of adult spadefoots is unknown, and their use of upland habitat is poorly understood. Both factors are important for the long-term conservation of the species because adult spadefoots spend the majority of their lives away from breeding pools in self-excavated burrows. Between January 2012 and January 2013, we surgically implanted radio transmitters in 15 spadefoots at two locations and recorded their movements and habitat use. The mean distance moved between burrow locations was 18 m (SD ± 24.1 m, range1-204 m). The mean distance of burrows from the breeding pools was 40 m (SD ± 37.42 m, range 1-262 m). Rain was a significant predictor of spadefoot movement, with more rain predicting higher probability of movement and larger distances moved. At remote sensing scale (1 m) spadefoots selected grassland habitat for their burrow locations. At the microsite scale (< 1 m) spadefoots strongly selected duff over grass or shrub cover. Spadefoots burrowed in friable, sandy/loam soil with significantly less clay than random pseudoabsence points. This research enhances our understanding of a little-studied species and will contribute to the development of effective management plans for the western spadefoot.

Reduced mosquito survival in metal-roof houses may contribute to a decline in malaria transmission in sub-Saharan Africa.

In The Gambia, metal-roof houses were hotter during the day than thatched-roof houses. After 24 h, the mortality of Anopheles gambiae, the principal African malaria vector, was 38% higher in metal-roof houses than thatched ones. During the day, mosquitoes in metal-roof houses moved from the hot roof to cooler places near the floor, where the temperature was still high, reaching 35 °C. In laboratory studies, at 35 °C few mosquitoes survived 10 days, the minimum period required for malaria parasite development. Analysis of epidemiological data showed there was less malaria and lower vector survival rates in Gambian villages with a higher proportion of metal roofs. Our findings are consistent with the hypothesis that the indoor climate of metal-roof houses, with higher temperatures and lower humidity, reduces survivorship of indoor-resting mosquitoes and may have contributed to the observed reduction in malaria burden in parts of sub-Saharan Africa.

Computational Tools for Calculating log ß Values of Geochemically Relevant Uranium Organometallic Complexes.

Uranium (UVI) interacts with organic ligands, subsequently controlling its aqueous chemistry. It is therefore imperative to assess the binding ability of natural organic molecules. We evidence that density functional theory (DFT) can be used as a practical protocol for predicting the stability of UVI organic ligand complexes, allowing for the development of a relative stability series for organic complexes with limited experimental data. Solvation methods and DFT settings were benchmarked to suggest a suitable off-the-shelf solution. The results indicate that the IEFPCM solvation method should be employed. A mixed solvation approach improves the accuracy of the calculated stability constant (log ß); however, the calculated log ß are approximately five times more favorable than experimental data. Different basis sets, functionals, and effective core potentials were tested to check that there were no major changes in molecular geometries and Δr G. The recommended method employed is the B3LYP functional, aug-cc-pVDZ basis set for ligands, MDF60 ECP and basis set for UVI, and the IEFPCM solvation model. Using the fitting approach employed in the literature with these updated DFT settings allows fitting of 1:1 UVI complexes with root-mean-square deviation of 1.38 log ß units. Fitting multiple bound carboxylate ligands indicates a second, separate fitting for 1:2 and 1:3 complexes.

Commonality in the microarchitecture of trabecular bone: A preliminary study.

Understanding the relationship between the microstructure and mechanical function of trabecular bone is critical for prediction and prevention of bone fragility fractures. However, a detailed understanding of the structural design of trabecular microarchitecture is still missing. This study hypothesized that there exists a commonality in the underlying probabilistic distributions of microstructural features of trabecular bones, whereas the microstructural differences among individuals are primarily describe by a set of scalar parameters. To test the hypothesis, twenty-three trabecular bone specimens were obtained from two anatomic locations (i.e., femoral neck and vertebral body) and a diverse group of seventeen donors of different age and sex. The number, size, spatial location, and orientation of individual plates and rods in the trabecular bone specimens were determined via volumetric decomposition of 3D µCT images using the Individual Trabecula Segmentation (ITS) technique. Then, m/n bootstrap Kolmogorov-Smirnov tests were performed to compare the normalized distributions of size, orientation, and spatial arrangement of trabecular plates and rods in the specimens. The results showed that 100% of the twenty-three normalized distributions of each microstructural feature were statistically equivalent irrespective of individual differences among the bone specimens, except the distributions of rod spatial arrangement (<100%). On the other hand, nonparametric Mann-Whitney U tests showed that a set of scalar parameters (i.e., the number, average size, and average nearest neighbor distance of trabecular plates and rods) were statistically different among the individual specimens (p<0.05). Due to the commonality of the underlying distributions, the individual differences in the trabecular microstructure among the specimens seemed to be reflected primarily by changes in the scalar parameters. The above results strongly support the hypothesis of this study and may shed more light on understanding the natural design of trabecular bone microstructures.

Insecticide resistance patterns in Uganda and the effect of indoor residual spraying with bendiocarb on kdr L1014S frequencies in Anopheles gambiae s.s.

BACKGROUND: Resistance of malaria vectors to pyrethroid insecticides has been attributed to selection pressure from long-lasting insecticidal nets (LLINs), indoor residual spraying (IRS), and the use of chemicals in agriculture. The use of different classes of insecticides in combination or by rotation has been recommended for resistance management. The aim of this study was to understand the role of IRS with a carbamate insecticide in management of pyrethroid resistance. METHODS: Anopheles mosquitoes were collected from multiple sites in nine districts of Uganda (up to five sites per district). Three districts had been sprayed with bendiocarb. Phenotypic resistance was determined using standard susceptibility tests. Molecular assays were used to determine the frequency of resistance mutations. The kdr L1014S homozygote frequency in Anopheles gambiae s.s. was used as the outcome measure to test the effects of various factors using a logistic regression model. Bendiocarb coverage, annual rainfall, altitude, mosquito collection method, LLIN use, LLINs distributed in the previous 5 years, household use of agricultural pesticides, and malaria prevalence in children 2-9 years old were entered as explanatory variables. RESULTS: Tests with pyrethroid insecticides showed resistance and suspected resistance levels in all districts except Apac (a sprayed district). Bendiocarb resistance was not detected in sprayed sites, but was confirmed in one unsprayed site (Soroti). Anopheles gambiae s.s. collected from areas sprayed with bendiocarb had significantly less kdr homozygosity than those collected from unsprayed areas. Mosquitoes collected indoors as adults had significantly higher frequency of kdr homozygotes than mosquitoes collected as larvae, possibly indicating selective sampling of resistant adults, presumably due to exposure to insecticides inside houses that would disproportionately affect susceptible mosquitoes. The effect of LLIN use on kdr homozygosity was significantly modified by annual rainfall. In areas receiving high rainfall, LLIN use was associated with increased kdr homozygosity and this association weakened as rainfall decreased, indicating more frequency of exposure to pyrethroids in relatively wet areas with high vector density. CONCLUSION: This study suggests that using a carbamate insecticide for IRS in areas with high levels of pyrethroid resistance may reduce kdr frequencies in An. gambiae s.s.

Evidence for coseismic subsidence events in a southern California coastal saltmarsh.

Paleoenvironmental records from a southern California coastal saltmarsh reveal evidence for repeated late Holocene coseismic subsidence events. Field analysis of sediment gouge cores established discrete lithostratigraphic units extend across the wetland. Detailed sediment analyses reveal abrupt changes in lithology, percent total organic matter, grain size, and magnetic susceptibility. Microfossil analyses indicate that predominantly freshwater deposits bury relic intertidal deposits at three distinct depths. Radiocarbon dating indicates that the three burial events occurred in the last 2000 calendar years. Two of the three events are contemporaneous with large-magnitude paleoearthquakes along the Newport-Inglewood/Rose Canyon fault system. From these data, we infer that during large magnitude earthquakes a step-over along the fault zone results in the vertical displacement of an approximately 5-km2 area that is consistent with the footprint of an estuary identified in pre-development maps. These findings provide insight on the evolution of the saltmarsh, coseismic deformation and earthquake recurrence in a wide area of southern California, and sensitive habitat already threatened by eustatic sea level rise.