Search

Reservoir formation in a river system changes a lotic environment to more lacustrine conditions, with impacts throughout the ecosystem. In this study, a river reach containing typical salmonid riffle/run habitat was flooded to create a large, deep pool from June to September in each of 3 years. We test the hypothesis that juvenile Atlantic salmon (Salmo salar) with their preference for run/riffle habitats will respond to the transformation to a lentic environment by moving into adjacent lotic environments. Movements of juvenile Atlantic salmon were monitored using a combination of biotelemetry (radio‐ and passive integrated transponder‐tagging) and electrofishing. Results showed that no tracked fish moved away from the created pool habitat. Mass‐specific growth rates showed the created pool habitat resulted in net growth of juveniles. The results confirm that fish may not immediately (i.e., at least for an approximate 2 months) respond to rapid, large‐scale habitat alterations by moving to find similar habitat conditions outside the altered habitat. This is most probably related to plasticity of behavior and habitat use, and no change in biological conditions to a point that would negatively impact fish growth and survival, for example food availability, competition, or predation. The results also support the hypothesis that the relative importance of physical habitat variables is not universal among streams and populations, therefore limiting the value of applying standard habitat suitability criteria and use. [ABSTRACT FROM AUTHOR]

The timing of flowering is central to plant life‐history as it initiates sexual reproduction, thus controlling plant interaction with pollinators and climate factors. A fundamental question is: what are the drivers of flowering time strategy in a species?We assembled mean flowering times for the indigenous dicotyledonous flora of New Zealand (n = 1303 species, including 177 tree species) and used phylogenetic models to determine how climate, plant traits, and evolutionary history (phylogeny) controlled interspecific variation in flowering times across an island flora.Across all species, on average, flowering was 19 days earlier in abiotically pollinated species relative to biotically pollinated species, 23 days earlier in woody species, relative to herbaceous species, 45 days earlier in species with fleshy‐fruits, relative to species with dry fruits and 31 days earlier in gender dimorphic species, relative to cosexual species. Species in warmer and drier climates flowered earlier than those growing under cool, moist climates.When all factors were considered together, the strongest influence on flowering time was sexual system: gender dimorphic species flowered earlier than cosexuals, even after accounting for other factors.Synthesis. We propose that these differences in flowering time arise because of sexual selection for early male flowering and sexual conflict between male and female individuals. As sexual selection and conflict may be stronger in gender dimorphic species than in cosexual species, our study suggests that plant sexual system is an important force structuring the phenology of plant communities, with potential consequences for ecological interactions and ecosystem processes. [ABSTRACT FROM AUTHOR]

This paper explores the co-occurring features of Attention Deficit Hyperactivity Disorder (ADHD) and Borderline Personality Disorder (BPD) and ADHD as a risk factor for the emergence of BPD. It emphasizes the importance of clinical treatment to improve resiliency and addresses co-occurring areas of vulnerability in individuals with ADHD and those with BPD, as well as in individuals with both disorders. Although the specific developmental pathways and mediating factors remain uncertain, many investigations have identified ADHD and emotion dysregulation in childhood as risk factors for developing personality disorders, particularly BPD, in late adolescence and early adulthood. The frequent co-occurrence of ADHD with BPD in adulthood contributes to worse outcomes and continuing problems with impulsivity and regulating emotional arousal among individuals with both disorders. While the comorbidity of ADHD and BPD poses a risk, it is essential to also consider what factors may help moderate the risks and contribute to resiliency. This review highlights the gaps in the literature about resilience by reviewing existing literature that points to treatment approaches, such as compassion-focused and mentalization-focused psychotherapy, that may mediate ADHD-related risks. Long-term treatment outcome studies of emotion regulation therapies with children are needed to ascertain their effectiveness in reducing the psychological adversity associated with experiencing ADHD in childhood and reducing the emergence of BPD in adolescents and adults. [ABSTRACT FROM AUTHOR]

This paper explores the potential for occupational therapists (OTs) to manage medicines and support patients in an in-patient psychiatric ward to effectively and safely self-administer their medication. Connelly House is an occupational therapy-led six-bed, open psychiatric rehabilitation in-patient ward supporting people transitioning from being in-patients to living in the community. Policy, process, governance and training needs are identified and discussed. Positive feedback was received from patients and staff involved with the service development, opening the door for OTs to manage medicines and support the self-administration of medication on other psychiatric rehabilitation in-patient wards using focused occupational interventions. [ABSTRACT FROM AUTHOR]

The establishment of pediatric hospital medicine (PHM) as a fellowship-trained subspecialty represents a major change in the practice landscape, particularly for combined internal medicine-pediatrics (med-peds) residents. The most recent literature on med-peds residents' career choices predates PHM fellowship and its impact has not been well studied. We aimed characterize med-peds residents' career plans and the factors influencing their choices. We distributed an electronic survey to the 1,505 resident members of the National Med-Peds Resident Association. In addition to sociodemographic data, participants reported their career plans, how well their residency prepared them for various aspects of practice, and their perceptions of PHM fellowship and its effect on their career choices. Among the 228 participants, the most planned careers were combined hospital medicine (36.8%, 84/228), combined subspecialty practice (32.5%, 74/228), and primary care (31.1%, 71/228). Residents felt well prepared for patient care and significantly more prepared for inpatient practice than for primary care. Participants rated the potential disadvantages of PHM fellowship as major deterrents and did not view the possible advantages as strong incentives. Among those who had considered a hospital medicine careers, 91.2% (186/203) were less likely to pursue PHM after its certification as a subspecialty. Med-peds residents have a wide range of career interests but fellowship has made them less likely to pursue PHM careers. These findings emphasize the importance of addressing the needs of med-peds trained providers as PHM certification pathways and fellowship curricula develop to avoid adverse effects on the workforce. [ABSTRACT FROM AUTHOR]

Beginning in 1920 and in keeping with Freud's sustained encouragement, the first two generations of European psychoanalysts initiated a progressive mental health movement by offering very low cost and free psychoanalytic services that were in harmony with Austrian social democratic and socialist political leaders' commitment to societal reforms in light of the economic and social inequities after the First World War. This synthesis of biographical and autobiographical accounts of early Freudian, Ego Psychology and Neo-Freudian theorists' contributions highlights their consideration of the effects of social injustice as central challenges to the development of psychological growth. [ABSTRACT FROM AUTHOR]

Biodiversity analyses across continental extents are important in providing comprehensive information on patterns and likely drivers of diversity. For vascular plants in Australia, community‐level diversity analyses have been restricted by the lack of a consistent plot‐based survey dataset across the continent. To overcome these challenges, we collated and harmonised plot‐based vegetation survey data from the major data sources across Australia and used them as the basis for modelling species richness (α‐diversity) and community compositional dissimilarity (β‐diversity), standardised to 400 m2, with the aim of mapping diversity patterns and identifying potential environmental drivers. The harmonised Australian vegetation plot (HAVPlot) dataset includes 219 552 plots, of which we used 115 083 to analyse plant diversity. Models of species richness and compositional dissimilarity both explained approximately one‐third of the variation in plant diversity across Australia (D2 = 33.0% and 32.7%, respectively). The strongest environmental predictors for both aspects of diversity were a combination of temperature and precipitation, with soil texture and topographic heterogeneity also important. The fine‐resolution (≈ 90 m) spatial predictions of species richness and compositional dissimilarity identify areas expected to be of particular importance for plant diversity, including south‐western Australia, rainforests of eastern Australia and the Australian Alps. Arid areas of central and western Australia are predicted to support assemblages that are less speciose or unique; however, these areas are most in need of additional survey data to fill the spatial, environmental and taxonomic gaps in the HAVPlot dataset. The harmonised data and model predictions presented here provide new insight into plant diversity patterns across Australia, enabling a wide variety of future research, such as exploring changes in species abundances, linking compositional patterns to functional traits or undertaking conservation assessments for selected components of the flora. [ABSTRACT FROM AUTHOR]

Questions: (1) What can be learned by extending a national classification into unsampled forest types? (2) Are both remotely sensed and environmental predictors needed to model and map associations? (3) For mapping, are LiDAR-generated canopy structure parameters or reflectance from spectral imagery more useful? (4) How can we assess uncertainty of a final map? Location: Warawara Forest, Northland, New Zealand. Methods: We sampled 205 vegetation plots and assigned them to an existing national classification using the fuzzy classification framework of noise clustering. Plots too distinct to be assigned were used to define new associations. We produced spatial models of each association using boosted regression trees. Predictors included 11 environmental, 11 canopy reflectance, and 17 canopy structure variables. We created a composite map by assigning each map pixel to the association with the highest occurrence probability. We evaluated uncertainty by examining locations where no class was predicted with probability above 0.2 and by creating a confusion map based on entropy. Results: Forty-five plots were assigned to six of 79 existing national associations and 147 plots were used to define two new forest associations. Three shrubland types are widespread nationally, whereas two young forest types are northern. Three mature forest types are narrowly distributed nationally, with the new "High-elevation hardwood forest" largely restricted to Warawara Forest. Three associations were mapped using remotely sensed predictors alone, whereas two also required environmental predictors. Overall, canopy reflectance predictors explained more deviance than canopy structure. Examining locations where no association was predicted well and where multiple associations were predicted equally showed areas mapped as younger forests to have greatest uncertainty. Conclusions: In answering our questions, we present a vegetation classification and map for Warawara Forest that provides a framework to guide the indigenous people's management responses to threats to valued communities and their species. [ABSTRACT FROM AUTHOR]

Atmospheric rivers (ARs) generate most of the economic losses associated with flooding in the western United States and are projected to increase in intensity with climate change. This is of concern as flood damages have been shown to increase exponentially with AR intensity. To assess how AR-related flood damages are likely to respond to climate change, we constructed county-level damage models for the western 11 conterminous states using 40 years of flood insurance data linked to characteristics of ARs at landfall. Damage functions were applied to 14 CMIP5 global climate models under the RCP4.5 "intermediate emissions" and RCP8.5 "high emissions" scenarios, under the assumption that spatial patterns of exposure, vulnerability, and flood protection remain constant at present day levels. The models predict that annual expected AR-related flood damages in the western United States could increase from $1 billion in the historical period to $2.3 billion in the 2090s under the RCP4.5 scenario or to $3.2 billion under the RCP8.5 scenario. County-level projections were developed to identify counties at greatest risk, allowing policymakers to target efforts to increase resilience to climate change. [ABSTRACT FROM AUTHOR]

Phylogenetic diversity analyses were used to interpret the timing and assembly of vegetation communities in temperate New Zealand. A data set comprising 1638 permanent vegetation plots provided plant-distributional data, and a plastid rbcL phylogenetic tree provided phylogenetic metrics. Mean crown age, standardized effect size of mean pairwise distance and standardized effect size of mean nearest taxon distance were analysed in relation to taxonomic groups (angiosperms, gymnosperms and pteridophytes), life form (woody angiosperms, non-woody angiosperms) and temperature and precipitation using generalized additive models. Angiosperms in South Island have a younger crown age than those in most North Island sites, and phylogenetic clustering is prevalent throughout. Angiosperms and pteridophytes from drier and cooler open-habitat communities in central and eastern South Island have younger crown ages and phylogenetic clustering compared to wetter and warmer closed-habitat communities of western South Island and North Island, with older crown ages and phylogenetic over-dispersion. Phylogenetic clustering is consistent with species-rich radiations that have diversified into newly available niches during the late Miocene to Plio-Pleistocene. Pteridophytes displayed less phylogenetic relatedness than angiosperms, reflecting their older crown ages. These findings are consistent with a view that northern New Zealand retained older lineages of subtropical origin during glaciations, whereas novel habitats in cool, dry climates in southern New Zealand facilitated more recent radiations. These results emphasize the strong legacy of history in the modern-day composition of plant communities. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to develop consensus for the surgical indications of anterior distal femur hemiepiphysiodesis in children with cerebral palsy using expert surgeon opinion through a modified Delphi technique. Methods: The panel used a 5-level Likert-type scale to record agreement or disagreement with 27 statements regarding anterior distal femur hemiepiphysiodesis. Consensus was defined as at least 80% of responses being in the highest or lowest 2 of the Likert-type ratings. General agreement was defined as 60%–79% falling into the highest or lowest 2 ratings. Results: For anterior distal femur hemiepiphysiodesis, 27 statements were surveyed: consensus or general agreement among the panelists was achieved for 22 of 27 statements (22/27, 82%) and 5 statements had no agreement (5/27, 18%). There was general consensus that anterior distal femur hemiepiphysiodesis is indicated for ambulatory children with cerebral palsy, with at least 2years growth remaining, and smaller (<30degrees) knee flexion contractures and for minimally ambulatory children to aid in standing/transfers. Consensus was achieved regarding the importance of close radiographic follow-up after screw insertion to identify or prevent secondary deformity. There was general agreement that percutaneous screws are preferred over anterior plates due to the pain and irritation associated with plates. Finally, it was agreed that anterior distal femur hemiepiphysiodesis was not indicated in the absence of a knee flexion contracture. Conclusion: Anterior distal femur hemiepiphysiodesis can be used to treat fixed knee flexion contractures in the setting of crouch gait, but other associated lever arm dysfunctions must be addressed by single-event multilevel surgery. [ABSTRACT FROM AUTHOR]

Purpose: There is marked variation in indications and techniques for hamstring surgery in children with cerebral palsy. There is particular uncertainty regarding the indications for hamstring transfer compared to traditional hamstring lengthening. The purpose of this study was for an international panel of experts to use the Delphi method to establish consensus indications for hamstring surgery in ambulatory children with cerebral palsy. Methods: The panel used a five-level Likert-type scale to record agreement or disagreement with statements regarding hamstring surgery, including surgical indications and techniques, post-operative care, and outcome measures. Consensus was defined as at least 80% of responses being in the highest or lowest two of the five Likert-type ratings. General agreement was defined as 60%–79% falling into the highest or lowest two ratings. There was no agreement if neither of these thresholds was reached. Results: The panel reached consensus or general agreement for 38 (84%) of 45 statements regarding hamstring surgery. The panel noted the importance of assessing pelvic tilt during gait when considering hamstring surgery, and also that lateral hamstring lengthening is rarely needed, particularly at the index surgery. They noted that repeat hamstring lengthening often has poor outcomes. The panel was divided regarding hamstring transfer surgery, with only half performing such surgery. Conclusion: The results of this study can help pediatric orthopedic surgeons optimize decision-making in their choice and practice of hamstring surgery for ambulatory children with cerebral palsy. This has the potential to reduce practice variation and significantly improve outcomes for ambulatory children with cerebral palsy. [ABSTRACT FROM AUTHOR]

Background: M5717 is the first plasmodium translation elongation factor 2 inhibitor to reach clinical development as an antimalarial. We aimed to characterise the safety, pharmacokinetics, and antimalarial activity of M5717 in healthy volunteers.Methods: This first-in-human study was a two-part, single-centre clinical trial done in Brisbane, QLD, Australia. Part one was a double-blind, randomised, placebo-controlled, single ascending dose study in which participants were enrolled into one of nine dose cohorts (50, 100, 200, 400, 600, 1000, 1250, 1800, or 2100 mg) and randomly assigned (3:1) to M5717 or placebo. A sentinel dosing strategy was used for each dose cohort whereby two participants (one assigned to M5717 and one assigned to placebo) were initially randomised and dosed. Randomisation schedules were generated electronically by independent, unblinded statisticians. Part two was an open-label, non-randomised volunteer infection study using the Plasmodium falciparum induced blood-stage malaria model in which participants were enrolled into three dose cohorts. Healthy men and women of non-childbearing potential aged 18-55 years were eligible for inclusion; individuals in the volunteer infection study were required to be malaria naive. Safety and tolerability (primary outcome of the single ascending dose study and secondary outcome of the volunteer infection study) were assessed by frequency and severity of adverse events. The pharmacokinetic profile of M5717 was also characterised (primary outcome of the volunteer infection study and secondary outcome of the single ascending dose study). Parasite clearance kinetics (primary outcome of the volunteer infection study) were assessed by the parasite reduction ratio and the corresponding parasite clearance half-life; the incidence of recrudescence up to day 28 was determined (secondary outcome of the volunteer infection study). Recrudescent parasites were tested for genetic mutations (exploratory outcome). The trial is registered with ClinicalTrials.gov (NCT03261401).Findings: Between Aug 28, 2017, and June 14, 2019, 221 individuals were assessed for eligibility, of whom 66 men were enrolled in the single ascending dose study (eight per cohort for 50-1800 mg cohorts, randomised three M5717 to one placebo, and two in the 2100 mg cohort, randomised one M5717 to one placebo) and 22 men were enrolled in the volunteer infection study (six in the 150 mg cohort and eight each in the 400 mg and 800 mg cohorts). No adverse event was serious; all M5717-related adverse events were mild or moderate in severity and transient, with increased frequency observed at doses above 1250 mg. In the single ascending dose study, treatment-related adverse events occurred in three of 17 individuals in the placebo group; no individual in the 50 mg, 100 mg, or 200 mg groups; one of six individuals in each of the 400 mg, 1000 mg, and 1250 mg groups; two of six individuals in the 600 mg group; and in all individuals in the 1800 mg and 2100 mg groups. In the volunteer infection study, M5717-related adverse events occurred in no participants in the 150 mg or 800 mg groups and in one of eight participants in the 400 mg group. Transient oral hypoesthesia (in three participants) and blurred vision (in four participants) were observed in the 1800 mg or 2100 mg groups and constituted an unknown risk; thus, further dosing was suspended after dosing of the two sentinel individuals in the 2100 mg cohort. Maximum blood concentrations occurred 1-7 h after dosing, and a long half-life was observed (146-193 h at doses ≥200 mg). Parasite clearance occurred in all participants and was biphasic, characterised by initial slow clearance lasting 35-55 h (half-life 231·1 h [95% CI 40·9 to not reached] for 150 mg, 60·4 h [38·6 to 138·6] for 400 mg, and 24·7 h [20·4 to 31·3] for 800 mg), followed by rapid clearance (half-life 3·5 h [3·1 to 4·0] for 150 mg, 3·9 h [3·3 to 4·8] for 400 mg, and 5·5 h [4·8 to 6·4] for 800 mg). Recrudescence occurred in three (50%) of six individuals dosed with 150 mg and two (25%) of eight individuals dosed with 400 mg. Genetic mutations associated with resistance were detected in four cases of parasite recrudescence (two individuals dosed with 150 mg and two dosed with 400 mg).Interpretation: The safety, pharmacokinetics, and antimalarial activity of M5717 support its development as a component of a single-dose antimalarial combination therapy or for malaria prophylaxis.Funding: Wellcome Trust and the healthcare business of Merck KGaA, Darmstadt, Germany. [ABSTRACT FROM AUTHOR]

Lineage through time plots (LTTs) are often used to explore past patterns of lineage diversification and community assembly. However, as they are based solely on extant species their ability to accurately depict past events can be questioned. Here, simulation models based on neutral processes are used to explore immigration and extinction scenarios to assist with interpretation of LTT plots generated from molecular clock age estimates for a nearly complete set of extant New Zealand vascular plant genera. With significant genus turnover, model simulations yield smooth exponential and linear semi-log LTT plots. Abrupt changes in extinction and immigration rates imposed in the scenarios caused only slight alterations of the curves. The vast majority of New Zealand vascular plant genera derive from trans-oceanic dispersal, and LTT plots generated from divergence dates and fossil data indicate consistently high turnover. Even major geological and climatic events leave minor signatures on LTT plots. Most notably, the maximum Oligocene Marine Transgression (27–22 Ma), when at least 85% of the current landmass was inundated, isn't clearly registered. By themselves, LTT plots shed little light on the biotic effects of climatic or geomorphic change in the remote past and need to be interpreted in the light of fossil and geological data. [ABSTRACT FROM AUTHOR]

Intracellular tau inclusions are a pathological hallmark of Alzheimer's disease, progressive supranuclear palsy, corticobasal degeneration and other sporadic neurodegenerative tauopathies. Recent in vitro and in vivo studies have shown that tau aggregates may spread to neighbouring cells and functionally connected brain regions, where they can seed further tau aggregation. This process is referred to as tau propagation. Here we describe an ex vivo system using organotypic hippocampal slice cultures (OHCs) which recapitulates aspects of this phenomenon. OHCs are explants of hippocampal tissue which may be maintained in culture for months. They maintain their synaptic connections and multicellular 3D architecture whilst also permitting direct control of the environment and direct access for various analysis types. We inoculated OHCs prepared from P301S mouse pups with brain homogenate from terminally ill P301S mice and then examined the slices for viability and the production and localization of insoluble phosphorylated tau. We show that following seeding, phosphorylated insoluble tau accumulate in a time and concentration dependent manner within OHCs. Furthermore, we show the ability of the conformation dependent anti-tau antibody, MC1, to compromise tau accrual in OHCs, thus showcasing the potential of this therapeutic approach and the utility of OHCs as an ex vivo model system for assessing such therapeutics. [ABSTRACT FROM AUTHOR]

Environmental variation is a crucial driver of ecological pattern, and spatial layers representing this variation are key to understanding and predicting important ecosystem distributions and processes. A national, standardised collection of different environmental gradients has the potential to support a variety of large-scale research questions, but to date these data sets have been limited and difficult to obtain. Here we describe the New Zealand Environmental Data Stack (NZEnvDS), a comprehensive set of 72 environmental layers quantifying spatial patterns of climate, soil, topography and terrain, as well as geographical distance at 100 m resolution, covering New Zealand's three main islands and surrounding inshore islands. NZEnvDS includes layers from the Land Environments of New Zealand (LENZ), additional layers generated for LENZ but never publicly released, and several additional layers generated more recently. We also include an analysis of correlation between variables. All final NZEnvDS layers, their original source layers, and the R-code used to generate them are available publicly for download at https://doi.org/10.7931/m6rm-vz40. [ABSTRACT FROM AUTHOR]

The global spread of invasive plant pathogens is increasing, putting natural forests and ecosystem services under threat. Spatial data can quantify range non‐overlap between invasive pathogens and their hosts to identify existing and potentially restorable refugia to enable 'escape' from the pathogen.In 2017, myrtle rust Austropuccinia psidii was detected in New Zealand. New Zealand has 27 native woody and liana species in the plant family susceptible to the disease (Myrtaceae), many of which are ecosystem dominants and economically important. Spatial methods were used to compare the current New Zealand distribution of myrtle rust with the modelled distributions of its potential native hosts. To guide management and set priorities for conservation of at‐risk species, areas of potential refugia where a Myrtaceae species is predicted to occur outside the pathogen range were identified under two myrtle rust distribution scenarios.Myrtle rust will thrive in New Zealand's warmer regions. Many native Myrtaceae are distributed within this area, but several species occur extensively outside the core range of the disease. Species distributed in cooler southern regions will be best placed to persist in refugia.Myrtaceae species with specific habitat requirements and narrow geographical ranges in warmer (northern) areas are likely to require ex situ or active in situ management. Even widely distributed species will benefit from the restoration of suitable habitat that supports multiple species outside the myrtle rust range.Synthesis and applications. Spatial data can be used to identify refugia and restoration opportunities, and thus inform landscape‐level management responses to invasive pathogens. This approach can guide decisions over where to implement in situ (e.g. fungicide spraying) versus ex situ (e.g. seed banking, botanic gardens) management efforts. [ABSTRACT FROM AUTHOR]

In contrast to the urban-centric framing of planetary urbanization, the concept of ‘planetary rural geographies’ emphasizes the ongoing importance and distinctiveness of pluriversal rural spaces and identities, including their continued centrality to the global economy. It also argues that rural spaces are especially defined by diverse relationships between the human and non-human that must be understood volumetrically, rather than through largely two-dimensional territorial imaginaries. These themes are developed and illustrated via consideration of contemporary rural geographies as spaces of crisis, spaces of conflict, and spaces of hope. The concept of planetary rural geographies could be enhanced by greater attention to key analytical commonalties among admittedly diverse rural geographies, particularly with respect to broader dynamics of capitalist development and climate change, an effort that could be supported via greater engagement between the literatures on specifically rural geographies, and those on rural populisms, climate adaptation and mitigation, and energy geographies. [ABSTRACT FROM AUTHOR]

Background MMV390048 is the first Plasmodium phosphatidylinositol 4-kinase inhibitor to reach clinical development as a new antimalarial. We aimed to characterize the safety, pharmacokinetics, and antimalarial activity of a tablet formulation of MMV390048. Methods A 2-part, phase 1 trial was conducted in healthy adults. Part 1 was a double-blind, randomized, placebo-controlled, single ascending dose study consisting of 3 cohorts (40, 80, 120 mg MMV390048). Part 2 was an open-label volunteer infection study using the Plasmodium falciparum induced blood-stage malaria model consisting of 2 cohorts (40 mg and 80 mg MMV390048). Results Twenty four subjects were enrolled in part 1 (n = 8 per cohort, randomized 3:1 MMV390048:placebo) and 15 subjects were enrolled in part 2 (40 mg [n = 7] and 80 mg [n = 8] cohorts). One subject was withdrawn from part 2 (80 mg cohort) before dosing and was not included in analyses. No serious or severe adverse events were attributed to MMV390048. The rate of parasite clearance was greater in subjects administered 80 mg compared to those administered 40 mg (clearance half-life 5.5 hours [95% confidence interval {CI}, 5.2–6.0 hours] vs 6.4 hours [95% CI, 6.0–6.9 hours]; P  = .005). Pharmacokinetic/pharmacodynamic modeling estimated a minimum inhibitory concentration of 83 ng/mL and a minimal parasiticidal concentration that would achieve 90% of the maximum effect of 238 ng/mL, and predicted that a single 120-mg dose would achieve an adequate clinical and parasitological response with 92% certainty. Conclusions The safety, pharmacokinetics, and pharmacodynamics of MMV390048 support its further development as a partner drug of a single-dose combination therapy for malaria. Clinical Trials Registration NCT02783820 (part 1); NCT02783833 (part 2). [ABSTRACT FROM AUTHOR]

Purpose Equinus is the most common deformity in cerebral palsy (CP) and gastrocsoleus lengthening (GSL) is the most commonly performed surgery to improve gait and function in ambulatory children with CP. Substantial variation exists in the indications for GSL and surgical technique. The purpose of this study was to review surgical anatomy and biomechanics of the gastrocsoleus and to utilize expert orthopaedic opinion through a Delphi technique to establish consensus for surgical indications for GSL in ambulatory children with CP. Methods A 17-member panel, of Fellowship-trained paediatric orthopaedic surgeons, each with at least 9 years of clinical post-training experience in the surgical management of children with CP, was established. Consensus for the surgical indications for GSL was achieved through a standardized, iterative Delphi process. Results Consensus was reached to support conservative Zone 1 surgery in diplegia and Zone 3 surgery (lengthening of the Achilles tendon) was contraindicated. Zone 2 or Zone 3 surgery reached general agreement as a choice in hemiplegia and under-correction was preferred to any degree of overcorrection. Agreement was reached that the optimum age for GSL surgery was 6 years to 10 years and should be avoided in children aged under 4 years. Physical examination measures with the child awake and under anaesthesia were important in decision making. Gait analysis was supported both for decision making and for assessing outcomes, in combination with patient reported outcomes (PROMS). Conclusions The results from this study may encourage informed practice evaluation, reduce practice variability, improve clinical outcomes and point to questions for further research. [ABSTRACT FROM AUTHOR]

Background: (+)-SJ000557733 (SJ733) is a novel, orally bioavailable inhibitor of Plasmodium falciparum ATP4. In this first-in-human and induced blood-stage malaria phase 1a/b trial, we investigated the safety, tolerability, pharmacokinetics, and antimalarial activity of SJ733 in humans.Methods: The phase 1a was a single-centre, dose-escalation, first-in-human study of SJ733 allowing modifications to dose increments and dose-cohort size on the basis of safety and pharmacokinetic results. The phase 1a took place at St Jude Children's Research Hospital and at the University of Tennessee Clinical Research Center (Memphis, TN, USA). Enrolment in more than one non-consecutive dose cohort was allowed with at least 14 days required between doses. Participants were fasted in seven dose cohorts and fed in one 600 mg dose cohort. Single ascending doses of SJ733 (75, 150, 300, 600, 900, or 1200 mg) were administered to participants, who were followed up for 14 days after SJ733 dosing. Phase 1a primary endpoints were safety, tolerability, and pharmacokinetics of SJ733, and identification of an SJ733 dose to test in the induced blood-stage malaria model. The phase 1b was a single-centre, open-label, volunteer infection study using the induced blood-stage malaria model in which fasted participants were intravenously infected with blood-stage P falciparum and subsequently treated with a single dose of SJ733. Phase 1b took place at Q-Pharm (Herston, QLD, Australia) and was initiated only after phase 1a showed that exposure exceeding the threshold minimum exposure could be safely achieved in humans. Participants were inoculated on day 0 with P falciparum-infected human erythrocytes (around 2800 parasites in the 150 mg dose cohort and around 2300 parasites in the 600 mg dose cohort), and parasitaemia was monitored before malaria inoculation, after inoculation, immediately before SJ733 dosing, and then post-dose. Participants were treated with SJ733 within 24 h of reaching 5000 parasites per mL or at a clinical score higher than 6. Phase 1b primary endpoints were calculation of a parasite reduction ratio (PRR48) and parasite clearance half-life, and safety and tolerability of SJ733 (incidence, severity, and drug-relatedness of adverse events). In both phases of the trial, SJ733 hydrochloride salt was formulated as a powder blend in capsules containing 75 mg or 300 mg for oral administration. Healthy men and women (of non-childbearing potential) aged 18-55 years were eligible for both studies. Both studies are registered with ClinicalTrials.gov (NCT02661373 for the phase 1a and NCT02867059 for the phase 1b).Findings: In the phase 1a, 23 healthy participants were enrolled and received one to three non-consecutive doses of SJ733 between March 14 and Dec 7, 2016. SJ733 was safe and well tolerated at all doses and in fasted and fed conditions. 119 adverse events were recorded: 54 (45%) were unrelated, 63 (53%) unlikely to be related, and two (2%) possibly related to SJ733. In the phase 1b, 17 malaria-naive, healthy participants were enrolled. Seven participants in the 150 mg dose cohort were inoculated and dosed with SJ733. Eight participants in the 600 mg dose cohort were inoculated, but two participants could not be dosed with SJ733. Two additional participants were subsequently inoculated and dosed with SJ733. SJ733 exposure increased proportional to the dose through to the 600 mg dose, then was saturable at higher doses. Fasted participants receiving 600 mg exceeded the target area under the concentration curve extrapolated to infinity (AUC0-∞) of 13 000 μg × h/L (median AUC0-∞ 24 283 [IQR 16 135-31 311] μg × h/L, median terminal half-life 17·4 h [IQR 16·1-24·0], and median timepoint at which peak plasma concentration is reached 1·0 h [0·6-1·3]), and this dose was tested in the phase 1b. All 15 participants dosed with SJ733 had at least one adverse event. Of the 172 adverse events recorded, 128 (74%) were mild. The only adverse event attributed to SJ733 was mild bilateral foot paraesthesia that lasted 3·75 h and resolved spontaneously. The most common adverse events were related to malaria. Based on parasite clearance half-life, the derived log10PRR48 and corresponding parasite clearance half-lives were 2·2 (95% CI 2·0-2·5) and 6·47 h (95% CI 5·88-7·18) for 150 mg, and 4·1 (3·7-4·4) and 3·56 h (3·29-3·88) for 600 mg.Interpretation: The favourable pharmacokinetic, tolerability, and safety profile of SJ733, and rapid antiparasitic effect support its development as a fast-acting component of combination antimalarial therapy.Funding: Global Health Innovative Technology Fund, Medicines for Malaria Venture, and the American Lebanese Syrian Associated Charities. [ABSTRACT FROM AUTHOR]

On January 22, 2010, the U.S. Environmental Protection Agency (EPA) established a new one-hour probabilistic National Ambient Air Quality Standard (NAAQS) for nitrogen dioxide (NO2) at 100 parts per billion (ppb) or approximately 188 micrograms per cubic meter (µg/m3). The 1-hr NO2 NAAQS is considerably more stringent than the longstanding annual standard of 53 ppb or approximately 100 µg/m3. AERMOD is the EPA recommended dispersion modeling tool for predicting impacts from emission sources, including compressor station reciprocating engines. Existing datasets were previously reviewed to evaluate and improve AERMOD 1-hr NO2 model performance. However, these datasets were not representative due to either an absence of accurate concurrent hourly emission inventories, being associated with larger electric generating units, shorter duration tracer studies, or were too site-specific (e.g., external influences such as terrain). To address this data gap, an intensive 13-month field data program was undertaken by Pipeline Research Council International (PRCI) to collect a comprehensive dataset including concurrent emissions, meteorological, and ambient ozone and nitrogen oxide measurements. This paper describes the Balko, OK natural gas compressor station host site and the design of the meteorological, ambient NOx and O3 monitors and continuous Parametric Emissions Monitoring System (PEMS). Two comparisons are made between the monitored data and AERMOD results. First, the measured onsite data (ambient air, meteorological, and emissions) were used as input to AERMOD to make comparisons between measured and modeled NOx and NO2. These comparisons showed that NOx was both over and under predicted, sometimes beyond a factor-of-two. The second comparison uses the typical permitting approach where onsite data are not available to contrast how conservative input assumptions for emissions, background O3, NO2, and offsite meteorology cause significant over predictions especially for this site where engines have a low annual utilization rate and operate infrequently throughout the year. Implications: This project resulted following the promulgation of the new 1-hr NO2 NAAQS and the challenges that natural gas pipeline compressor stations have in modeling intermittent emissions using AERMOD to demonstrate compliance with this standard. AERMOD was developed and validated with a primary focus on large sources with tall stacks, such as electric utility boilers. A recently collected dataset at a gas compressor station in Balko, Oklahoma shows that the use of permitted allowable emission values compared to actual hourly emission values causes over predictions using typical regulatory methods. Comparison of model results using actual hourly emission values to coincident ambient air monitoring values at the site shows that AERMOD over predicts near-field impacts due to simplifying assumptions including building downwash, plume dispersion, chemistry, and 1-hr invariant meteorological conditions. [ABSTRACT FROM AUTHOR]

Background: There is no study to date that has examined the association between history of abuse and adaptive functioning deficits in youth with co-occurring and psychotic disorders or mood disorders. Method: This study used a retrospective chart review of 98 youth under the age of 18 (Mean age = 16.06 years) with co-occurring intellectual impairment (Mean IQ = 63.9) and psychotic disorders, mood disorders, or other psychiatric disorders. Using multi-mediation models in the path analytic framework, this study examined the relationships between psychiatric diagnosis (based on DSM-IV criteria), cognitive functioning (Full Scale IQ Scores), adaptive functioning (Socialization, Communication, Motor Skills, Daily Living Skills), and the presence of the history of physical, sexual, and/or emotional abuse/neglect. Results: A very high incidence of all three forms of abuse was present in the study sample, with more than three-quarters of the youth having experienced at least one form of abuse and more than half having experienced two or the three forms of abuse. A history of sexual abuse was significantly and directly associated with an increased incidence of mood disorders. Mood disorders were the strongest predictors of adaptive functioning deficits. Youth with schizophrenia spectrum disorder scored significantly lower in communication skills than those with bipolar disorder. Conclusion: Results are discussed in terms of the need for treatment studies and further investigations of the relationship between childhood maltreatment and adaptive functioning in youth with intellectual impairment and psychiatric disorders. [ABSTRACT FROM AUTHOR]

Purpose Surgical procedures, such as medial hamstring lengthening (MHL) and femoral derotational osteotomy (FDO), can improve the gait of children with cerebral palsy (CP); however, substantial variation exists in the factors that influence the decision to perform surgery. The purpose of this study was to use expert surgeon opinion through a Delphi technique to establish consensus for indications in ambulatory children with CP. Methods A 15-member panel, all established experts with at least nine years' experience in the surgical management of children with CP, was created (mean of 20.81 years' experience). All panel members also had expertise of the use of movement analysis for the assessment of gait disorders in children with CP. The group initially focused on two of the most commonly performed procedures, MHL and FDO, in an attempt to gain consensus (> 80%). This was obtained through a standardized, iterative Delphi process. Results For MHL, a total of 59 questions were surveyed: 41 indication questions and 18 outcome questions, for which there was consensus on ten indication questions and seven outcomes. For FDO, a total of 55 questions were surveyed: 43 indication questions and 12 outcome questions, for which there was consensus on 29 indication questions and eight outcomes. Conclusion This study is the first to use an expert panel to identify best-practice indications for common surgical procedures of children with CP. The results from this study will allow for more informed evaluation of practice and form the basis for future improvement efforts to standardize surgical recommendations internationally. [ABSTRACT FROM AUTHOR]

Metabolic scaling theory (MST) is one of ecology's most high-profile general models and can be used to link size distributions and productivity in forest systems. Much of MST's foundation is based on size distributions following a power law function with a scaling exponent of −2, a property assumed to be consistent in steady-state ecosystems. We tested the theory's generality by comparing actual size distributions with those predicted using MST parameters assumed to be general. We then used environmental variables and functional traits to explain deviation from theoretical expectations. Finally, we compared values of relative productivity predicted using MST with a remote-sensed measure of productivity. We found that fire-prone heath communities deviated from MST-predicted size distributions, whereas fire-sensitive rainforests largely agreed with the theory. Scaling exponents ranged from −1.4 to −5.3. Deviation from the power law assumption was best explained by specific leaf area, which varies along fire frequency and moisture gradients. While MST may hold in low-disturbance systems, we show that it cannot be applied under many environmental contexts. The theory should remain general, but understanding the factors driving deviation from MST and subsequent refinements is required if it is to be applied robustly across larger scales. [ABSTRACT FROM AUTHOR]

Background Tafenoquine was recently approved for chemoprophylaxis of malaria. Its specific activity against liver and blood stages of Plasmodium species has been separately characterized in animals but not in humans. Methods In this randomized, double-blind, placebo-controlled study, 16 malaria-naive, glucose-6-phosphate dehydrogenase–normal participants aged 20–42 years received tafenoquine chemoprophylaxis prior to challenge with blood stage Plasmodium falciparum. Participants were randomly assigned to either tafenoquine (n = 12) or placebo (n = 4) and took blinded study medication (single 200-mg dose) on days 1, 2, 3, and 10, followed by intravenous inoculation with approximately 2800 P. falciparum parasitized erythrocytes on day 13. The primary endpoint was the number of participants requiring rescue treatment with artemether/lumefantrine due to the onset of parasitemia as determined by quantitative polymerase chain reaction. Results None of the 12 participants who received tafenoquine developed parasitemia, whereas all placebo participants developed parasitemia (P =.0005). Two cases of mild hemoglobin decrease and a single case of mild hyperbilirubinemia occurred in the tafenoquine group. Conclusions Tafenoquine chemoprophylaxis is safe and effective in preventing malaria in healthy nonimmune participants challenged with blood stage P. falciparum. Clinical Trials Registration Australian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12617000102370. [ABSTRACT FROM AUTHOR]

Recent years have seen the widespread rise of authoritarian leaders and populist politics around the world, a development of intense political concern. This special issue of the Annals explores the many and deep connections between this authoritarian and populist turn and environmental politics and governance, through a range of rich case studies that provide wide geographic, thematic, and theoretical coverage and perspectives. This introduction first summarizes major commonalities among many contemporary authoritarian and populist regimes and reviews debates regarding their relationships to neoliberalism, fascism, and more progressive forms of populism. It then reviews three major connections to environmental politics they all share as common contexts: roots in decades of neoliberal environmental governance, climate change and integrally related issues of energy development and agricultural change, and complex conflations of nation and nature. Next, it introduces the six sections in the special issue: (1) historical and comparative perspectives (two articles); (2) extractivism, populism, and authoritarianism (six articles); (3) the environment and its governance as a political proxy or arena for questions of security and citizenship (seven articles); (4) racialization and environmental politics (five articles); (5) politics of environmental science and knowledge (six articles); and (6) progressive alternatives (five articles). It concludes with the suggestion that environmental issues, movements, and politics can and must be central to resistance against authoritarian and reactionary populist politics and to visions of progressive alternatives to them. Key Words: authoritarianism, environmental governance, environmental politics, populism. [ABSTRACT FROM AUTHOR]

Understanding influences of environmental change on biodiversity requires consideration of more than just species richness. Here we present a novel framework for understanding possible changes in species' abundance structures within communities under climate change. We demonstrate this using comprehensive survey and environmental data from 1748 woody plant communities across southeast Queensland, Australia, to model rank‐abundance distributions (RADs) under current and future climates. Under current conditions, the models predicted RADs consistent with the region's dominant vegetation types. We demonstrate that under a business as usual climate scenario, total abundance and richness may decline in subtropical rainforest and shrubby heath, and increase in dry sclerophyll forests. Despite these opposing trends, we predicted evenness in the distribution of abundances between species to increase in all vegetation types. By assessing the information rich, multidimensional RAD, we show that climate‐driven changes to community abundance structures will likely vary depending on the current composition and environmental context. [ABSTRACT FROM AUTHOR]

The unprecedented speed of delivery of SARS-CoV-2 pandemic vaccines has redefined the limits for all vaccine development. Beyond the aspirational 100-day timeline for tomorrow's hypothetical pandemic vaccines, there is a sense of optimism that development of other high priority vaccines can be accelerated. Early in the COVID-19 pandemic, an intense and polarised academic and public discourse arose concerning the role of human challenge trials for vaccine development. A case was made for human challenge trials as a powerful tool to establish early proof-of-concept of vaccine efficacy in humans, inform vaccine down selection, and address crucial knowledge gaps regarding transmission, pathogenesis, and immune protection. We review the track record of human challenge trials contributing to the development of vaccines for 19 different pathogens and discuss relevant limitations, barriers, and pitfalls. This Review also highlights opportunities for efforts to broaden the scope and boost the effects of human challenge trials, to accelerate all vaccine development. [ABSTRACT FROM AUTHOR]

In this paper, we argue that energy should be seen as a critical aspect of changing historical regimes in the social production of space. We suggest the common definition of energy as the 'capacity to do work' ignores key aspects of the space required for energy in the first place (particularly the concept of power density). Articulating the basic spatial concept of power density with a historical-geographical materialist understanding of energy regimes, we argue that industrial capitalism is defined by an intensive vertical reliance upon subterranean stocks of energy that require relatively little surface land to harness. Previous modes of production were characterised by a more 'horizontal' reliance upon extensive territory (e.g. forests) to meet fuel needs. While attentive to the spatialities of overall energy complexes, we focus in particular on how the spatialities of energy sources affect the production of space in major and distinctive ways. Drawing from environmental and economic history, we argue the use of fossil fuels ushered in a 'subterranean energy regime' that not only relied on underground stocks of energy, but substantially relieved the societal demand for land-based and spatially extensive sources of fuel (i.e. wood and other organic sources). The use of subterranean fuel (first coal) not only powered machines, but revolutionised 'heat-process' industries like iron smelting that dramatically expanded the steel and other metal industries; thus, transforming the built environment. We then consider the spatial and land-use implications of a transition away from this subterranean regime to renewable energy sources (solar and wind). A return to the surface for energy would not be biological as in pre-industrial times, but industrial in the sense that these systems require industrial production. Moreover, the spatially extensive nature of such energy technologies should raise important political questions about existing land-use patterns and livelihoods, particularly in rural areas. [ABSTRACT FROM AUTHOR]

The ecological prominence of diatoms in the ocean environment largely results from their superior competitive ability for dissolved nitrate (NO3  −). To investigate the cellular and genetic basis of diatom NO3  − assimilation, we generated a knockout in the nitrate reductase gene (NR -KO) of the model pennate diatom Phaeodactylum tricornutum. In NR -KO cells, N-assimilation was abolished although NO3  − transport remained intact. Unassimilated NO3  − accumulated in NR -KO cells, resulting in swelling and associated changes in biochemical composition and physiology. Elevated expression of genes encoding putative vacuolar NO3  − chloride channel transporters plus electron micrographs indicating enlarged vacuoles suggested vacuolar storage of NO3  −. Triacylglycerol concentrations in the NR -KO cells increased immediately following the addition of NO3  −, and these increases coincided with elevated gene expression of key triacylglycerol biosynthesis components. Simultaneously, induction of transcripts encoding proteins involved in thylakoid membrane lipid recycling suggested more abrupt repartitioning of carbon resources in NR -KO cells compared with the wild type. Conversely, ribosomal structure and photosystem genes were immediately deactivated in NR -KO cells following NO3  − addition, followed within hours by deactivation of genes encoding enzymes for chlorophyll biosynthesis and carbon fixation and metabolism. N-assimilation pathway genes respond uniquely, apparently induced simultaneously by both NO3  − replete and deplete conditions. [ABSTRACT FROM AUTHOR]

Computed tomography revealed transverse colonic intussusception with a hepatic flexure lipoma acting as the lead point (Fig. Intestinal intussusception: etiology, diagnosis, and treatment. [Extracted from the article]

Background: DSM265 is a novel antimalarial that inhibits plasmodial dihydroorotate dehydrogenase, an enzyme essential for pyrimidine biosynthesis. We investigated the safety, tolerability, and pharmacokinetics of DSM265, and tested its antimalarial activity.Methods: Healthy participants aged 18-55 years were enrolled in a two-part study: part 1, a single ascending dose (25-1200 mg), double-blind, randomised, placebo-controlled study, and part 2, an open-label, randomised, active-comparator controlled study, in which participants were inoculated with Plasmodium falciparum induced blood-stage malaria (IBSM) and treated with DSM265 (150 mg) or mefloquine (10 mg/kg). Primary endpoints were DSM265 safety, tolerability, and pharmacokinetics. Randomisation lists were created using a validated, automated system. Both parts were registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12613000522718 (part 1) and number ACTRN12613000527763 (part 2).Findings: In part 1, 73 participants were enrolled between April 12, 2013, and July 14, 2015 (DSM265, n=55; placebo, n=18). In part 2, nine participants were enrolled between Sept 30 and Nov 25, 2013 (150 mg DSM265, n=7; 10 mg/kg mefloquine, n=2). In part 1, 117 adverse events were reported; no drug-related serious or severe events were reported. The most common drug-related adverse event was headache. The mean DSM265 peak plasma concentration (Cmax) ranged between 1310 ng/mL and 34 800 ng/mL and was reached in a median time (tmax) between 1·5 h and 4 h, with a mean elimination half-life between 86 h and 118 h. In part 2, the log10 parasite reduction ratio at 48 h in the DSM265 (150 mg) group was 1·55 (95% CI 1·42-1·67) and in the mefloquine (10 mg/kg) group was 2·34 (2·17-2·52), corresponding to a parasite clearance half-life of 9·4 h (8·7-10·2) and 6·2 h (5·7-6·7), respectively. The median minimum inhibitory concentration of DSM265 in blood was estimated as 1040 ng/mL (range 552-1500), resulting in a predicted single efficacious dose of 340 mg. Parasite clearance was significantly faster in participants who received mefloquine than in participants who received DSM265 (p<0·0001).Interpretation: The good safety profile, long elimination half-life, and antimalarial effect of DSM265 supports its development as a partner drug in a single-dose antimalarial combination treatment.Funding: Wellcome Trust, UK Department for International Development, Global Health Innovative Technology Fund, Bill & Melinda Gates Foundation. [ABSTRACT FROM AUTHOR]

Statins constitute a class of medications commonly used in the treatment of elevated cholesterol. However, in experimental studies, statins also have other non-cholesterol-mediated mechanisms of action, which may have neuroprotective effects. The aim of this study was to determine whether administration of atorvastatin for 7 days post-injury would improve neurological recovery in patients with mild traumatic brain injury (mTBI). The hypothesis was that atorvastatin administration would reduce post-concussion symptoms and also that atorvastatin administration for 1 week post-injury would be safe. One hundred forty patients with mTBI were planned to be enrolled and randomly assigned to receive atorvastatin 1 mg/kg (up to 80 mg/kg) per day or placebo for 7 days starting within 24 h of injury. Assessments of post-concussion syndrome, post-traumatic stress and depressive symptoms, cognition, memory, verbal fluency, functional, and work status were performed at baseline, 1 week, and 1 and 3 months. The result on the Rivermead Post-Concussion Symptoms Questionnaire at 3 months was the primary outcome. Enrollment in the trial was stopped early because of difficulty in recruiting sufficient numbers of subjects. Fifty-two patients with mTBI were enrolled; 28 patients received atorvastatin and 24 received placebo. The median Rivermead score was 2 for the atorvastatin group, compared to 3.5 for the placebo group, at 3 months post-injury (χ2(1) = 0.0976; p = 0.7547). The change in the Rivermead score between baseline and 3 months was also analyzed. The median decrease in score was 4 for the atorvastatin group and 10.5 for the placebo group (χ2(1) = 0.8750; p = 0.3496). No serious adverse events occurred, and there was no significant difference in the incidence of adverse events in the two treatment groups. Atorvastatin administration for 7 days post-injury was safe, but there were no significant differences in neurological recovery post-mTBI with atorvastatin. [ABSTRACT FROM AUTHOR]

Climate change is expected to increase the frequency of above-normal atmospheric water deficits contemporaneous with periods of high temperatures. Here we explore alterations in physiology and gene expression in leaves of Coffea canephora Pierre ex A. Froehner caused by a sharp drop in relative humidity (RH) at three different temperatures. Both stomatal conductance (gs) and CO2 assimilation (A) measurements showed that gs and A values fell quickly at all temperatures after the transfer to low RH. However, leaf relative water content measurements indicated that leaves nonetheless experienced substantial water losses, implying that stomatal closure and/or resupply of water was not fast enough to stop excessive evaporative losses. At 27 and 35 °C, upper leaves showed significant decreases in Fv/Fm compared with lower leaves, suggesting a stronger impact on photosystem II for upper leaves, while at 42 °C, both upper and lower leaves were equally affected. Quantitative gene expression analysis of transcription factors associated with conventional dehydration stress, and genes involved with abscisic acid signalling, such as CcNCED3, indicated temperature-dependent, transcriptional changes during the Humidity Shock ('HuS') treatments. No expression was seen at 27 °C for the heat-shock gene CcHSP90-7, but it was strongly induced during the 42 °C 'HuS' treatment. Consistent with a proposal that important cellular damage occurred during the 42 °C 'HuS' treatment, two genes implicated in senescence were induced by this treatment. Overall, the data show that C. canephora plants subjected to a sharp drop in RH exhibit major, temperature-dependent alterations in leaf physiology and important changes in the expression of genes associated with abiotic stress and senescence. The results presented suggest that more detailed studies on the combined effects of low RH and high temperature are warranted. [ABSTRACT FROM AUTHOR]

Despite established differences in cognitive functioning of adults with mood disorder-related psychosis and those with non-affective psychotic disorders, there is limited evidence of the impact of psychotic symptoms on the cognitive functioning of children and adolescents with mood disorders. This study investigates IQ, working memory, and processing speed scores in 80 child and adolescent inpatients discharged from an intermediate care state psychiatric hospital, using a retrospective chart review. Associations between diagnosis based on DSM-IV criteria (7 with Major Depression- MDD; 43 with Bipolar Disorders-BD, and 30 with Mood Disorders Not Otherwise Specified-NOS), presence of current psychotic features, and cognitive functioning (WISC-IV IQ, Coding, Symbol Search, and Digit Span) were investigated using Multivariate Analyses of Variance. No differences were found in cognitive functioning between patients with MDD and BD, or between those with severe Mood Disorders (MDD or BD) and those with NOS, when controlling for age, gender, and presence of psychotic features. However, patients with severe mood disorders and psychotic features showed lower IQs and greater working memory deficits than those without psychotic features or NOS. Results are discussed in terms of treatment planning for children and adolescents at risk for developing psychotic symptoms and severe mood disorders. [ABSTRACT FROM AUTHOR]

Aims Accurate field quantification of stem counts is time consuming and laborious, especially in ecosystems containing many small individuals where counts are immense. There are many large, long-term data sets worldwide that include various measures of woody plant abundance, such as crown cover, that are faster and easier to measure than true counts of individuals. Quantifying the number of individuals allows in-depth research into various topics including functional ecology, carbon accounting, conservation and metabolic theory. Here we test the accuracy of predicting the abundance of individual woody plants from cover and forest structure measures, and explore the implications of refined abundance measures for understanding the rarity of woody plant species across southeast Queensland. Location Southeast Queensland ( SEQ), Australia. Methods To supplement an existing data set of 1251 sites with measured crown covers for woody plants in various strata, we sampled stem counts in an additional 30 sites, forming a calibration data set. We ensured that these 30 sites covered the environmental variation in the study area. Generalized additive mixed effects models were used to predict stem counts for all woody plants in the original data set from their crown cover and forest structure values and a site-level variable accounting for water balance. We used these refined abundance data to investigate relationships between local and regional abundance for different size classes. Results Stem densities increased with crown cover in a non-linear fashion; slowing once crown cover reached ca. 5% for shrubs and ca. 50% for trees, depending on their maximum potential height. Using the predicted stem count data, we found that shrubs were more locally abundant than trees, but less regionally abundant. Larger trees (>20 m maximum potential height) showed a negative relationship between local and regional abundance; there was no significant relationship between other size classes. Conclusions Our study demonstrates how crown cover can be converted to stem counts using a calibration data set and flexible mixed-effects models. This enables further ecological analysis at a fraction of the investment required to re-survey. Analyses of abundances revealed that tree species are less locally abundant than smaller woody species, likely due to space filling constraints, but more regionally abundant. [ABSTRACT FROM AUTHOR]

Background: Ferroquine (SSR97193) is a candidate anti-malarial currently undergoing clinical trials for malaria. To better understand its pharmacokinetic (PK) and pharmacodynamic (PD) parameters the compound was tested in the experimentally induced blood stage malaria infection model in volunteers. Methods: Male and non-pregnant female aged 18-50 years were screened for this phase II, controlled, single-centre clinical trial. Subjects were inoculated with ~1800 viable Plasmodium falciparum 3D7A-infected human erythrocytes, and treated with a single-dose of 800 mg ferroquine. Blood samples were taken at defined time-points to measure PK and PD parameters. The blood concentration of ferroquine and its active metabolite, SSR97213, were measured on dry blood spot samples by ultra-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS). Parasitaemia and emergence of gametocytes were monitored by quantitative PCR. Safety was determined by recording adverse events and monitoring clinical laboratory assessments during the course of the study. Results: Eight subjects were enrolled into the study, inoculated with infected erythrocytes and treated with 800 mg ferroquine. Ferroquine was rapidly absorbed with maximal exposure after 4-8 and 4-12 h exposure for SSR97213. Non-compartmental PK analysis resulted in estimates for half-lives of 10.9 and 23.8 days for ferroquine and SSR97213, respectively. Parasite clearance as reported by parasite reduction ratio was 162.9 (95 % CI 141-188) corresponding to a parasite clearance half-life of 6.5 h (95 % CI: 6.4-6.7 h). PK/PD modelling resulted in a predicted minimal parasiticidal concentration of 20 ng/mL, and the single dosing tested in this study was predicted to maintain an exposure above this threshold for 454 h (37.8 days). Although ferroquine was overall well tolerated, transient elevated transaminase levels were observed in three subjects. Paracetamol was the only concomitant treatment among the two out of these three subjects that may have played a role in the elevated transaminases levels. No clinically significant ECG abnormalities were observed. Conclusions: The parameters and PK/PD model derived from this study pave the way to the further rational development of ferroquine as an anti-malarial partner drug. The safety of ferroquine has to be further explored in controlled human trials. [ABSTRACT FROM AUTHOR]

Objectives: OZ439, or artefenomel, is an investigational synthetic ozonide antimalarial with similar potency, but a significantly improved pharmacokinetic profile, compared with artemisinins. We wished to measure key pharmacokinetic and pharmacodynamic parameters and the pharmacokinetic/pharmacodynamic relationship of artefenomel in humans to guide the drug's further development as combination therapy in patients.Patients and Methods: We tested artefenomel in the human induced blood-stage malaria (IBSM) model. Plasmodium infection was monitored by quantitative PCR (qPCR) and upon reaching 1000 parasites/mL single doses of 100, 200 and 500 mg of artefenomel were administered orally with evaluation of drug exposure and parasitaemia until rescue treatment after 16 days or earlier, if required.Results: A single 100 mg dose had only a transient effect, while the 200 mg dose resulted in a significant reduction in parasitaemia before early recrudescence. At the highest (500 mg) dose, initial clearance of parasites below the limit of detection of qPCR was observed, with a 48 h parasite reduction ratio (PRR48) >10 000 and a parasite clearance half-life of 3.6 h (95% CI 3.4-3.8 h). However, at this dose, recrudescence was seen in four of eight subjects 6-10 days after treatment. Pharmacokinetic/pharmacodynamic modelling predicted an MIC of 4.1 ng/mL.Conclusions: These results confirm the antimalarial potential of artefenomel for use in a single-exposure combination therapy. The observations from this study support and will assist further clinical development of artefenomel. [ABSTRACT FROM AUTHOR]

The obliteration of intra-thoracic dead space following tumor or empyema extirpation is imperative to successful long-term outcomes. We sought to describe the technique of using a pedicled latissmus dorsi muscle flap for obliteration of a large 14 × 6cm intrathoracic dead space following pleural decortication of chronic empyema, without thoracotomy or rib spreading via video-assisted thoracoscopic surgery (VATS). Specific attention is directed to the technical details of the flap harvest and inset in relation to the modifications required to inset the flap without a thoracotomy or rib spreading. The patient's history, presenting symptoms, pre-operative imaging, intraoperative details, and post-operative course are delineated with a focus on the length of stay, post-operative pain, and morbidity. The length of stay was 2 days with minimal pain on post-operative day one managed with oral nacrotic; long term post-operative X-ray revealed obliterated dead space and the patient experienced no complications. Inset of pedicled latissmus muscle flaps via VATS technique without thoracotomy or rib spreading seems a safe and effective technique that can offer short hospitalization with minimal pain morbidity. Level of Evidence: Level V, therapeutic study [ABSTRACT FROM AUTHOR]

Many have argued that the burning of fossil fuels is an essential component of the socionatural metabolism of capitalism as we know it, and that the anthropogenic climate change it is causing may finally bring about capitalism’s end. In this paper, I explore the potential for, instead, a societal shift towards renewable energy sources as the dominant components of global energy supplies to provide a socioecological ‘fix’ to current forms of crisis. In so doing, I develop a notion of an integrated socioecological fix that combines the central elements of Harvey’s ‘spatial fix’ and of neoliberal environmental ‘fixes’ that maintain accumulation by enrolling new elements of nonhuman nature into circuits of capital. I argue, first, that the capital intensiveness and spatial extensiveness of any such transition could provide a global-scale, if temporary, socioecological fix to capitalist crisis tendencies; and, second, that the creation of global scale geographies of renewable energy production, distribution, and consumption would necessarily involve powerful new rounds of investment in, and claims on, rural areas. These impacts would likely fall disproportionately on rural areas, where land values are lowest and existing users often have less power and fewer formal land rights. [ABSTRACT FROM AUTHOR]

Currently, the majority of diagnoses of malaria rely on a combination of the patient's clinical presentation and the visualization of parasites on a stained blood film. Breath offers an attractive alternative to blood as the basis for simple, noninvasive diagnosis of infectious diseases. In this study, breath samples were collected from individuals during controlled malaria to determine whether specific malaria-associated volatiles could be detected in breath. We identified 9 compounds whose concentrations varied significantly over the course of malaria: carbon dioxide, isoprene, acetone, benzene, cyclohexanone, and 4 thioethers. The latter group, consisting of allyl methyl sulfide, 1-methylthio-propane, (Z)-1-methylthio-1-propene, and (E)-1-methylthio-1-propene, had not previously been associated with any disease or condition. Before the availability of antimalarial drug treatment, there was evidence of concurrent 48-hour cyclical changes in the levels of both thioethers and parasitemia. When thioether concentrations were subjected to a phase shift of 24 hours, a direct correlation between the parasitemia and volatile levels was revealed. Volatile levels declined monotonically approximately 6.5 hours after initial drug treatment, correlating with clearance of parasitemia. No thioethers were detected in in vitro cultures of Plasmodium falciparum. The metabolic origin of the thioethers is not known, but results suggest that interplay between host and parasite metabolic pathways is involved in the production of these thioethers. [ABSTRACT FROM AUTHOR]

Loas, Dimassi, Monestes, and Yon (2013 ) studied a version of the Cognitive Slippage Scale and the Schizotypal Ambivalence Scale in support of the view that thought disorder and withdrawal are highly correlated with schizotypy, a central concept in investigations of the vulnerability for schizophrenia. As a brief comment on Loas, et al ., I will draw attention to the need for expanding studies of schizotypal traits and the possibility of using these scales with adolescents and young adults who are developing personality disorders as well as with individuals who have experienced prodromal phases of psychosis. Investigations of the Cognitive Slippage Scale and the Schizotypal Ambivalence Scale might be enhanced by conducting studies with individuals at different points on the psychosis continuum, including those who have developed schizophrenia and other psychotic disorders, as well as with their first-degree relatives. [ABSTRACT FROM AUTHOR]

There is a market demand for nonfat fermented goats' milk products. A nonfat goats' milk yogurt containing probiotics ( Lactobacillus acidophilus, and Bifidobacterium spp.) was developed using heat-treated whey protein concentrate (HWPC) as a fat replacer and pectin as a thickening agent. Yogurts containing untreated whey protein concentrate (WPC) and pectin, and the one with only pectin were also prepared. Skim cows' milk yogurt with pectin was also made as a control. The yogurts were analyzed for chemical composition, water holding capacity (syneresis), microstructure, changes in pH and viscosity, mold, yeast and coliform counts, and probiotic survivability during storage at 4 °C for 10 wk. The results showed that the nonfat goats' milk yogurt made with 1.2% HWPC (WPC solution heated at 85 °C for 30 min at pH 8.5) and 0.35% pectin had significantly higher viscosity ( P < 0.01) than any of the other yogurts and lower syneresis than the goats' yogurt with only pectin ( P < 0.01). Viscosity and pH of all the yogurt samples did not change much throughout storage. Bifidobacterium spp. remained stable and was above 106CFU g-1 during the 10-wk storage. However, the population of Lactobacillus acidophilus dropped to below 106CFU g-1 after 2 wk of storage. Microstructure analysis of the nonfat goats' milk yogurt by scanning electron microscopy revealed that HWPC interacted with casein micelles to form a relatively compact network in the yogurt gel. The results indicated that HWPC could be used as a fat replacer for improving the consistency of nonfat goats' milk yogurt and other similar products. [ABSTRACT FROM AUTHOR]

This article is concerned with the environmental dimensions of rescaling. Specifically, it explores debates around centralization and decentralization, introduces a key distinction between rescaling to jurisdictional spaces and ecosystem spaces, and suggests three future research trajectories: (1) analytical clarification of the differences between rescaling to natural versus jurisdictional scales; (2) examination of rescaling in light of its attendant process of creating new objects of governance; and (3) investigation of rescaling processes through a temporal lens, with the suggestion that rescaled environmental governance may be the site of some of the first and last manifestations of neoliberal governance reforms. [ABSTRACT FROM AUTHOR]

Major depression and bipolar disorder in children and adolescents are diagnosed with criteria that are similar to those which are used with adults. Developmental differences occur in the symptom trajectories of both disorders which are highly heterogeneous and stem from poorly understood interactions of multidimensional risk factors. Mood disorder-related psychotic symptoms in children and adolescents frequently reflect severe patterns of illness and require comprehensive assessment and sustained, multimodal treatment approaches. [ABSTRACT FROM PUBLISHER]

Background. Major impediments to development of vaccines and drugs for Plasmodium vivax malaria are the inability to culture this species and the extreme difficulty in undertaking clinical research by experimental infection.Methods. A parasite bank was collected from a 49-year-old woman with P. vivax infection, characterized, and used in an experimental infection study.Results. The donor made a full recovery from malaria after collection of a parasite bank, which tested negative for agents screened for in blood donations. DNA sequence analysis of the isolate indicated that it was clonal. Two subjects inoculated with the isolate became polymerase chain reaction positive on days 8 and 9, with onset of symptoms and positive blood smears on day 14, when they were treated with artemether-lumefantrine, with rapid clinical and parasitologic response. Transcripts of the parasite gene pvs25 that is expressed in gametocytes, the life cycle stage infectious to mosquitoes, were first detected on days 11 and 12.Conclusions. This experimental system results in in vivo parasite growth, probably infectious to mosquitoes. It offers the opportunity to undertake studies previously impossible in P. vivax that will facilitate a better understanding of the pathology of vivax malaria and development of antimalarial drugs and vaccines.Trial Registration. ANZCTR: 12612001096842. [ABSTRACT FROM AUTHOR]

Ecological studies of pairwise interactions are constrained by the methods available for rapid species identification of the interacting organisms. The resolution of data required to characterize species interaction networks at multiple spatio-temporal scales can be intensive, and therefore laborious and costly to collect. We explore the utility of high-resolution DNA melt-curve analysis ( HRM) as a rapid species identification method. An approach was developed to identify organisms at the pairwise interaction level, with particular application to cryptic species interactions that are traditionally difficult to study. Here, we selected a challenging application; to identify the presence/absence of pathogenic fungi ( Sporothrix inflata, Ophiostoma nigrocarpum and Ophiostoma galeiforme) transported by bark beetle vectors ( Hylastes ater and Hylurgus ligniperda). The technique was able to distinguish between different species of DNA within a single, pooled sample. In test applications, HRM was effective in the mass screening and identification of pathogenic fungal species carried by many individual bark beetle vectors ( n = 455 beetles screened) across large geographic scales. For two of the fungal species, there was no difference in the frequency of association with either of their vectors, but for the third fungal species there was a shift in vector-pathogen associations across locations. This technique allows rapid, mass screening and characterization of species interactions at a fraction of the time and cost of traditional methods. It is anticipated that this method can be readily applied to explore other cryptic species interactions, or other studies requiring rapid generation of large data sets and/or high-throughput efficiency. [ABSTRACT FROM AUTHOR]