Search

Recent studies have shown that during the typical resting‐state, echo planar imaging (EPI) time series obtained from the eye orbit area correlate with brain regions associated with oculomotor control and lower‐level visual cortex. Here, we asked whether congenitally blind (CB) shows similar patterns, suggesting a hard‐wired constraint on connectivity. We find that orbital EPI signals in CB do correlate with activity in the motor cortex, but less so with activity in the visual cortex. However, the temporal patterns of this eye movement‐related signal differed strongly between CB and sighted controls. Furthermore, in CB, a few participants showed uncoordinated orbital EPI signals between the two eyes, each correlated with activity in different brain networks. Our findings suggest a retained circuitry between motor cortex and eye movements in blind, but also a moderate reorganization due to the absence of visual input, and the inability of CB to control their eye movements or sense their positions. [ABSTRACT FROM AUTHOR]

An analysis of Conservative and Labour Party candidate selections reveals persistent gender disparities, with the Conservative Party nominating a significantly higher proportion of men. While various factors, such as local connections and harassment, abuse and intimidation (HAI) are cited as explanations, they fail to address systemic issues within the Conservative Party's recruitment processes and organisational culture. This article argues that the focus should shift from individual women to party structures and practices that perpetuate gender inequality. Drawing on previous research and empirical evidence, it calls for institutional reforms including the implementation of quotas and greater transparency in candidate selection. Finally, it calls for a gender‐sensitive audit of party culture to address underlying barriers to women's participation in politics. [ABSTRACT FROM AUTHOR]

Ceftazidime‐avibactam is a novel cephalosporin/B‐lactamase inhibitor developed in the context of increasing resistance. This case reports the pharmacokinetics of ceftazidime‐avibactam in a critically ill child under continuous renal replacement (CRRT) therapy for fluid overload. The patient was a 6‐month‐old female with sepsis due to bloodstream infection to Stenotrophomonas maltophilia following stem cell transplantation for severe combined immunodeficiency. CRRT was started on Day 2. Concentrations have been monitored using liquid chromatography–tandem mass spectrometry. Treatment was given every 8 h with a 2 h infusion of 30–7,5 mg/kg and did not reach pharmacokinetic/pharmacodynamic targets. Total clearance was respectively 1.7 and 3.02 L/h, with CRRT clearance respectively 28.8%–60% for ceftazidime and 14%–33% for avibactam. Those clearances are higher than reported in adult literature leading to a risk of treatment failure and emerging resistance. This supports the benefit of monitoring antimicrobial therapy under CRRT and the necessity to assess higher dosing or continuous infusion of ceftazidime‐avibactam. [ABSTRACT FROM AUTHOR]

Design, design management and design thinking as drivers of innovation and as means to enhance organizational performance are only now, however slowly, being taken seriously by private sector service providers and manufacturing industries, the public sector, and third sector organizations. Like everything else, the field of design changes to keep pace with the world around us. Learn about a unique tool that facilitates an examination of an organization's vision and mission in relation to the powers of design. [ABSTRACT FROM AUTHOR]

Quinones are electrochemical probes which are used for a large range of applications including bioenergetics. One electrochemical feature of quinones is their possible slow electron transfer kinetics. In this article we compared several quinones towards electron transfer kinetics and the ability of anodic pretreatment to increase electron transfer rate constant. Rotating disk electrode and chronoamperometry measurements were used to revisit their electrochemical behavior. Additionally, the number of electrons exchanged as a function of the characteristic time was used as a proxy to investigate kinetic limitations. A model was suggested to rationalize our results. Beyond a classification of quinones regarding the kinetic and thermodynamic ability of the hydroquinone form to be re‐oxidized, some intrinsic physicochemical properties were identified from our model (such as a time dependency of the exchanged number of electrons) to characterize such important redox mediators. [ABSTRACT FROM AUTHOR]

Glyphosate (GS) specifically inhibits the 5‐enolpyruvyl‐shikimate‐3‐phosphate (EPSP) synthase that converts phosphoenolpyruvate (PEP) and shikimate‐3‐phosphate to EPSP in the shikimate pathway of bacteria and other organisms. The inhibition of the EPSP synthase depletes the cell of the EPSP‐derived aromatic amino acids as well as of folate and quinones. A variety of mechanisms (e.g., EPSP synthase modification) has been described that confer GS resistance to bacteria. Here, we show that the Burkholderia anthina strain DSM 16086 quickly evolves GS resistance by the acquisition of mutations in the ppsR gene. ppsR codes for the pyruvate/ortho‐Pi dikinase PpsR that physically interacts and regulates the activity of the PEP synthetase PpsA. The mutational inactivation of ppsR causes an increase in the cellular PEP concentration, thereby abolishing the inhibition of the EPSP synthase by GS that competes with PEP for binding to the enzyme. Since the overexpression of the Escherichia coli ppsA gene in Bacillus subtilis and E. coli did not increase GS resistance in these organisms, the mutational inactivation of the ppsR gene resulting in PpsA overactivity is a GS resistance mechanism that is probably unique to B. anthina. [ABSTRACT FROM AUTHOR]

Geysers fascinate scientists and visitors for several centuries. However, many driving mechanisms such as heat transfer in the conduit and in the subsurface remain poorly understood. We document for the first time transient temperature variations inside the active Strokkur's and nearby quasi‐dormant Great Geysir's conduits, Iceland. While recording temperature inside the conduit, we visually monitored Strokkur's activity at the vent with a high‐speed camera, providing a high temporal resolution of the eruptions. Our results reveal heat transfer from a bubble trap to and through the conduit. We propose a model for the eruptive cycle of Strokkur that includes vapor slug rise, eruption, and conduit refill. Each water jet of an eruption is marked by an initial pulse of liquid water and vapor, emitted at a velocity between 5 and 28 m/s and generally followed by a second pulse less than a second later. The timing of eruptions coincides with temperature maxima in the conduit. After the eruption, the conduit is refilled by water falling back in the pool and drained from neighboring groundwater‐saturated geological units. This results in a temperature drop, the amplitude of which increases with depth while its period is reduced. This reflects faster heat transfer in the deeper than shallower part of the conduit. The amplitude of temperature drop following an eruption also increases with the eruption order, implying larger heat release by higher‐order eruptions. Temperature in the conduit subsequently increases until the next eruption, starting then a new cycle. Plain Language Summary: Geysers are hot springs that erupt intermittently. Although they have been studied for several centuries, many aspects such as heat transfer in the conduit and subsurface remains poorly understood. We recorded the temperature evolution inside the active Strokkur and quasi‐dormant Great Geysir geysers, located 100 m apart, in the Haukadalur hydrothermal field (Iceland). Comparing the timing of eruptions, visually monitored at Strokkur with its temperature records allowed us to characterize the thermal cycle associated with eruptions. Each eruption is marked by a temperature drop and subsequent rise inside the conduit to which we refer as the cooling and warming phases, respectively. We characterize the duration of these phases and the associated temperature variations, which revealed a faster heat transfer in the deeper than shallower part of the conduit and larger heat release by higher‐order eruption. A high‐speed camera revealed the eruption of a water jet in details. Each jet is marked by a first pulse of liquid water and vapor, emitted at a velocity between 5 and 28 m/s, which is generally followed by a second pulse, less than a second later. We propose a new and complementary model for vapor rise, eruption and, conduit refill of Strokkur. Key Points: In situ temperature evolution from an active geyser reveals heat transfer from a bubble trap to the conduitTransient measurement reveals the conduit dynamics during the geyser's eruptive cycleDetails of water jet eruptions captured by high‐speed camera [ABSTRACT FROM AUTHOR]

A 78-year-old woman presented to the emergency department with mild headaches and a sudden onset of blurred vision. Computerized tomography scan and magnetic resonance imaging showed what was described at first as a meningioma invading and occluding the torcular Herophili, the posterior third of the superior sagittal sinus and the proximal part of the right transverse sinus. Gross total resection of the tumor was performed without reconstructing dural sinuses. The patient was discharged home without new neurological deficit. Histopathology was in favor of a hemangiopericytoma Grade II World Health Organization (WHO). Total body positron emission tomography [18F]fluorodeoxyglucose found no secondary location. Radiotherapy was planned post-operatively. [ABSTRACT FROM AUTHOR]

Another patient had an interruption of the treatment with blinatumomab because of hyperammonemia on the second cycle, but this patient had a portocaval shunt. Only one other patient had blast after treatment with blinatumomab, but this patient did not have myelogram before treatment with blinatumomab and had a prolonged interruption of treatment. Only one patient had >5% medullary blasts, 15 patients (65%) had negative MRD and 7 (30%) patients had detectable MRD. [Extracted from the article]

Since the release of the ICH E9(R1) (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Addendum on Estimands and Sensitivity Analysis in Clinical Trials to the Guideline on Statistical Principles for Clinical Trials) document in 2019, the estimand framework has become a fundamental part of clinical trial protocols. In parallel, complex innovative designs have gained increased popularity in drug development, in particular in early development phases or in difficult experimental situations. While the estimand framework is relevant to any study in which a treatment effect is estimated, experience is lacking as regards its application to these designs. In a basket trial for example, should a different estimand be specified for each subpopulation of interest, defined, for example, by cancer site? Or can a single estimand focusing on the general population (defined, for example, by the positivity to a certain biomarker) be used? In the case of platform trials, should a different estimand be proposed for each drug investigated? In this work we discuss possible ways of implementing the estimand framework for different types of complex innovative designs. We consider trials that allow adding or selecting experimental treatment arms, modifying the control arm or the standard of care, and selecting or pooling populations. We also address the potentially data‐driven, adaptive selection of estimands in an ongoing trial and disentangle certain statistical issues that pertain to estimation rather than to estimands, such as the borrowing of nonconcurrent information. We hope this discussion will facilitate the implementation of the estimand framework and its description in the study protocol when the objectives of the trial require complex innovative designs. [ABSTRACT FROM AUTHOR]

Geysers are among the most fascinating geological features on Earth. Yet, little is still known about their hydrogeological structure at depth. To shed light on the spatial relationships between the vertical conduits and the aquifers feeding them, we conducted a 3D geoelectrical campaign in the Haukadalur hydrothermal field, Iceland. We deployed 24 Iris Fullwavers across the hydrothermal field and inverted resistivity and chargeability measurements. Additionally, we measured temperature variations inside Strokkur and Great Geysir geysers showing temperature fluctuations pointing out the oscillatory behavior that characterizes the geysering cycle of the geysers. By combining a semi‐quantitative temperature distribution of the thermal springs across the hydrothermal field with the inversion of the geoelectrical data, we highlight the control that extensional tectonics have on the distribution of fluids across the hydrothermal field. We also point out the occurrence of a common deep groundwater reservoir feeding the hydrothermal centers. Induced polarization data show that the geysers are fed by sub‐vertical water‐filled fracture zones. The geysers are found at the margins of highly resistive regions where we speculate boiling groundwater and vapor is found. Our proposed model suggests that local waters feeding the main groundwater reservoir downwell from the nearby region and then convect upwards, phase transitioning into vapor at about 200 m depth. From here, fluids flow toward the surface through pipes cutting a highly pressurized and hot system. This study shows to the best of our knowledge the first full 3D tomographic image of a hydrothermal field hosting geysers. Plain Language Summary: Geysers are erupting jets of boiling waters. Despite being one of the most fascinating geological processes on Earth, little is still known about their plumbing system at depth. To investigate the 3D geological structure of the Haukadalur hydrothermal field in Iceland, we injected electrical current into the ground and recorded the voltage across the hydrothermal field caused by such an injection. The measured voltage is proportional to the resistive structure of the hydrothermal field where the roots of the Strokkur and Great Geysir geysers are located. We also lowered thermometers into the geyser's conduits to measure temperature variations during geysering cycles. Our multidisciplinary study has shown the occurrence of a fault system along which the hydrothermal fluids are focused. We believe that the shallow hydrothermal springs are fed by a common reservoir at depth but we could not infer whether the two main geysers share the same reservoir. To the best of our knowledge our study shows the first 3D image of the structure of a geyser field. Key Points: 3D resistive structure of the geyser‐hosting Haukadalur hydrothermal fieldVapor‐saturated boiling reservoirs feeding geysers and hydrothermal pondsFluid flow controlled by local tectonics [ABSTRACT FROM AUTHOR]

Summary: Hepatic dysfunction (HD) is common in patients with haematological malignancies. Hepatic haemophagocytosis (HH) was detected in >50% of liver biopsies taken when HD remained unresolved after standard examination. We aimed to explore the contribution of liver biopsy in patients with both haematological malignancies and HD, describe the population of patients with HH, assess the prognostic impact of HH, and investigate haemophagocytic syndrome diagnostic score (HScore) utility in patients with HH. Between 2016 and 2019, 116 consecutive liver biopsies (76 transjugular, 40 percutaneous) were taken in 110 patients with haematological malignancy and HD (hyperbilirubinaemia, elevated transaminases, and/or cholestasis) and without a clear diagnosis. Liver biopsies were safe and diagnostically efficient. Predominant diagnoses included: HH (56%), graft‐versus‐host disease (55%), associated infections (24%), sinusoidal obstruction syndrome (15%), and tumoral infiltration (8%). Of patients, 35% were critically ill and 74% were allogeneic haematopoietic stem cell transplantation recipients, while 1‐year overall survival (OS) was 35% with HH versus 58% without HH (p = 0.026). The 1‐year OS was 24% with a HScore of ≥169 versus 50% with a HScore of <169 (p = 0.019). Liver biopsies are feasible in and contribute significantly to haematology patients with HD. HH occurred frequently and was associated with a poor prognosis. Combined with liver biopsy, the HScore may be helpful in refining haemophagocytic syndrome diagnosis. [ABSTRACT FROM AUTHOR]

It is well documented that early sensory loss typically alters brain morphology in the areas associated with the lost sense. However, much less is known about the impact of early sensory loss on the remainder of the sensory regions. Therefore, we investigated whether congenitally blind (CB) individuals show brain alterations in the olfactory system by comparing cortical morphology and olfactory bulb (OB) volume between 16 congenitally blind individuals and 16 sighted matched controls. Our results showed that not only CB blind individuals exhibited smaller OB but also alterations of cortical density in some higher olfactory processing centres, but unchanged cortical thickness. Our current findings suggest that a lifelong absence of visual input leads to morphological alterations in olfactory processing areas. [ABSTRACT FROM AUTHOR]

In this work, four different new fluorescent false neurotransmitters (FFN) probes were synthesized to contribute to the rationale of the FFN design. Their electroactive and spectroscopic properties were investigated. Hence, the optimal excitation and emission wavelengths (from 344 to 393 nm and 423 to 474 nm, respectively) make these probes adapted to fluorescence microscopy. Moreover, their electroactivity were demonstrated to occur at relatively low oxidation potentials for three of them (FFN132, FFN145 and FFN122: 0.26, 0.25 and 0.30 V vs. Ag/AgCl, respectively) and at 0.74 V vs. Ag/AgCl for FFN21 on carbon fiber electrodes. However, epifluorescence observations evidenced that the new designed FFN with the best spectroscopic and electrochemical properties (FFN122) did unfortunately not accumulate into secretory vesicles of model BON N13 cells. It thus confirms that FFN42 is currently the best "bioelectrofluorescent" compromise. This is why total internal fluorescence reflection microscopy measurements were then studied with the model FFN42 and BON N13 cells. Beyond the choice of the appropriate FFN, other analytical requirements are needed. As a consequence, the features of the transparent and conducting indium tin oxide (ITO) microdevice for coupled amperometry‐fluorescent measurements were investigated and optimized in terms of effects on the electrochemical performances and reusability. These results pave the way for future coupled investigations of exocytosis with the FFN‐ITO device association. [ABSTRACT FROM AUTHOR]

Summary: Roundup® is the brand name for herbicide solutions containing glyphosate, which specifically inhibits the 5‐enolpyruvyl‐shikimate‐3‐phosphate (EPSP) synthase of the shikimate pathway. The inhibition of the EPSP synthase causes plant death because EPSP is required for biosynthesis of aromatic amino acids. Glyphosate also inhibits the growth of archaea, bacteria, Apicomplexa, algae and fungi possessing an EPSP synthase. Here, we have characterized two glyphosate‐resistant bacteria from a Roundup solution. Taxonomic classification revealed that the isolates 1CH1 and 2CH1 are Burkholderia anthina and Burkholderia cenocepacia strains respectively. Both isolates cannot utilize glyphosate as a source of phosphorus and synthesize glyphosate‐sensitive EPSP synthase variants. Burkholderia. anthina 1CH1 and B. cenocepacia 2CH1 tolerate high levels of glyphosate because the herbicide is not taken up by the bacteria. Previously, it has been observed that the exposure of soil bacteria to herbicides like glyphosate promotes the development of antibiotic resistances. Antibiotic sensitivity testing revealed that the only the B. cenocepacia 2CH1 isolate showed increased resistance to a variety of antibiotics. Thus, the adaptation of B. anthina 1CH1 and B. cenocepacia 2CH1 to glyphosate did not generally increase the antibiotic resistance of both bacteria. However, our study confirms the genomic adaptability of bacteria belonging to the genus Burkholderia. [ABSTRACT FROM AUTHOR]

This article explores the role gender plays in the harassment, abuse and intimidation (HAI) of parliamentary candidates in the UK at election time. Using data from the Representative Audit of Britain surveys (2015–2019) this article takes an intersectional approach to investigate whether trends identified in 2017 suggesting that women candidates reported more incidences of HAI and were more likely to be concerned for their personal safety as a result than men, remain apparent in the subsequent election. Results suggest that HAI is getting worse for candidates in general, and the gender gap is widening. About three in every four women experienced some levels of fear while campaigning. [ABSTRACT FROM AUTHOR]

This short review is aimed at emphasizing the most prominent recent works devoted to the fluorescence modulation of organic fluorescent or fluorogenic molecules by electrochemistry. This still expanding research field not only addresses the smart uses of known molecules or the design of new ones, but also investigates the development of instrumentation providing time‐ and space‐resolved information at the molecular level. Important considerations including fluorescent/fluorogenic probes, reversible/irreversible fluorescence switch, direct/indirect fluorescence modulation, or environment properties are especially scrutinized in recent works dealing with bioanalysis perspectives. [ABSTRACT FROM AUTHOR]

For the development of coronavirus disease 2019 (COVID‐19) drugs during the ongoing pandemic, speed is of essence whereas quality of evidence is of paramount importance. Although thousands of COVID‐19 trials were rapidly started, many are unlikely to provide robust statistical evidence and meet regulatory standards (e.g., because of lack of randomization or insufficient power). This has led to an inefficient use of time and resources. With more coordination, the sheer number of patients in these trials might have generated convincing data for several investigational treatments. Collaborative platform trials, comparing several drugs to a shared control arm, are an attractive solution. Those trials can utilize a variety of adaptive design features in order to accelerate the finding of life‐saving treatments. In this paper, we discuss several possible designs, illustrate them via simulations, and also discuss challenges, such as the heterogeneity of the target population, time‐varying standard of care, and the potentially high number of false hypothesis rejections in phase II and phase III trials. We provide corresponding regulatory perspectives on approval and reimbursement, and note that the optimal design of a platform trial will differ with our societal objective and by stakeholder. Hasty approvals may delay the development of better alternatives, whereas searching relentlessly for the single most efficacious treatment may indirectly diminish the number of lives saved as time is lost. We point out the need for incentivizing developers to participate in collaborative evidence‐generation initiatives when a positive return on investment is not met. [ABSTRACT FROM AUTHOR]

Among all the chemical and biotechnological strategies implemented to extract energy from oxygenic photosynthesis, several concern the use of intact photosynthetic organisms (algae, cyanobacteria...). This means rerouting (fully or partially) the electron flow from the photosynthetic chain to an outer collecting electrode thus generating a photocurrent. While diverting photosynthetic electrons from living biological systems is an encouraging approach, this strategy is limited by the need to use an electron shuttle. Redox mediators that are able to interact with an embedded photosynthetic chain are rather scarce. In this respect, exogenous quinones are the most frequently used. Unfortunately, some of them also act as poisoning agents within relatively long timeframes. It thus raises the question of the best quinone. In this work, we use a previously reported electrochemical device to analyze the performance of different quinones. Photocurrents (maximum photocurrent, stability) were measured from suspensions of Chlamydomonas reinhardtii algae/quinones by chronoamperometry and compared to parameters like quinone redox potentials or cytotoxic concentration. From these results, several quinones were synthesized and analyzed in order to find the best compromise between bioelectricity production and toxicity. [ABSTRACT FROM AUTHOR]

The coronavirus, named SARS‐CoV‐2, is the cause of COVID‐19. This virus spreads readily from person to person and predominantly to and from the respiratory route and through droplets. There are many different interventions that can be and are used to decrease successfully the risk and spread of COVID‐19. Most of the principles underpinning these interventions relate to isolation and social distancing. These will need to be continued, at least in part, until safe and very effective vaccines become widely available and are delivered extensively and successfully globally. This new norm is isolation, plus social and physical distancing, and this new norm will likely be with us for some time to come. It will also be with us in any future pandemics, whether caused by bacteria or viruses, but especially when the causative pathogen spreads predominantly through the respiratory route. However, lockdowns and restrictions also cause many adverse but unintended economic, social and health consequences. Therefore, what is put into place needs to be proportionate to levels of risk of disease as well as spread, and which will vary in different localities and with time. [ABSTRACT FROM AUTHOR]

Switzerland promotes the energy transition by supporting the development of geothermal energy. We built a 3D basin‐scale fluid flow model of the Geneva Basin, France‐Switzerland, using the open‐source Matlab Reservoir Simulation Toolbox (MRST). The model is calibrated on available well and active seismic data. The goal of the numerical study is to investigate temperature and pressure distribution at the depth that could be used to identify large‐scale positive thermal anomalies. Previous and ongoing projects have assessed the geothermal potential of the region using static conductive models interpolated from bottom hole temperatures. However, a consistent basin‐scale fluid flow model of the Geneva Basin is still lacking. We perform 14 numerical models, articulated into three complementary studies to investigate how thermal properties, petrophysical parameters, and tectonic features affect fluid flow. We constrain our simulations by implementing a progressive degree of geological and petrophysical realism to study the physical processes driving fluid flow in the Geneva basin. We propose based on the simulation results a conceptual model showing that fluid flow is driven by the down‐welling of meteoric waters that cool down rocks at the edge of the Geneva Basin. In turn, this temperature drop promotes the up‐welling of warmer fluids in the center of the basin where we suggest that exploration for geothermal resources should focus. Finally, the approach presented in this study could be used for the first assessment of geothermal resources in other sedimentary basins. Key Points: We performed 14 basin‐scale simulations to investigate how thermal and petrophysical properties and tectonic features affect fluid flowWe propose a conceptual model showing that fluid flow is driven by gravitational flow following preferential fault pathwaysWe propose an integrated methodology in Matlab Reservoir Simulation Toolbox that could be used for the assessment of geothermal resources in sedimentary basins [ABSTRACT FROM AUTHOR]

To achieve economies of scope, most motor carriers combine long‐term contracts with shippers and brokers with periodic spot assignments found on electronic marketplaces (EMs). While previous research has addressed how carriers adopt an EM, we know little about factors that influence carriers to adopt multiple EMs. Given the rise of the platform economy of the trucking industry, we chose to address this gap and generate mid‐range theory on adopting multiple EMs in a logistics context. To do this, we applied grounded theory and conducted 23 interviews with motor carriers and EM experts in North America and Europe until we reached theoretical saturation. Our findings reveal that many motor carriers adopt a portfolio of different EMs, and that their awareness of platforms, expected and realized benefits, attitude, and vigilance determine how they configure their EM portfolios. The implication for existing theory is that, while previous studies depicted EM adoption from a single‐system perspective, we found that it is actually a continuous selection process that follows a portfolio perspective. Our paper also has implications for practice in that it illuminates the rationales behind EM portfolio development and identifies actionable factors that can help managers configure stronger portfolios. [ABSTRACT FROM AUTHOR]

The passenger pigeon (Ectopistes migratorius) was an iconic species in eastern North America that was one of the most numerous birds in the world at the time of European colonization. Passenger pigeons went extinct in 1914 due to excessive hunting. Current research aims to de‐extinct the passenger pigeon and someday release the species into its historic range. To determine under which conditions a passenger pigeon colony could survive a reintroduction into a natural habitat, we developed an agent‐based model to simulate the population dynamics of the passenger pigeon in a number of present‐day forest environments. The model incorporates the following stochastic processes: resource distribution, reproduction, and natural death. Bioenergetics, forest composition, and other ecological values were obtained from literature. Our simulation results suggest that passenger pigeons could survive a reintroduction into a modern natural environment, but their survival can be optimized with certain release dates, sex ratios, and forest composition. Recommendations for Resource Managers Genome engineering advancements suggest that the de‐extinction of passenger pigeons is feasible; however, the ability for passenger pigeons to live in the modern forest composition of their old habitat remains unexplored. Our model suggests the following regarding reintroduction strategies: A successful reintroduction of passenger pigeons is plausible, but sensitive to the strategy selected. Moderate deviations from optimal reintroduction strategies can greatly diminish the probability of a successful reintroduction.The optimal successful reintroduction strategy has an equal number of male and female passenger pigeons released in a dense oak‐hickory forest at the peak of the forest's masting cycle.Beyond persistence, the population growth of passenger pigeons within 10 years is at best, limited. Efforts to monitor and protect passenger pigeons during the transient phase of their reintroduction is critical. [ABSTRACT FROM AUTHOR]

Amelogenesis imperfecta (AI) represents rare tooth anomalies that affect the quality and/or quantity of the enamel. Clinical phenotypes display a wide spectrum, ranging from mild color changes to severe structural alterations with daily pain. However, all affect the quality of life because of mechanical, psychological, esthetic, and/or social repercussions. Several gene mutations have been linked to AI as a nonsyndromic (isolated) phenotype or a wider syndrome. This case report aimed to present a family with dental structure anomalies followed up in the dental department of the Louis Mourier Hospital (APHP, France) for their extremely poor dental condition. The proband and his mother were clinically diagnosed with AI, and genetic analysis revealed an already described variant in DLX3. Then, the family was further examined for tricho-dento-osseous syndrome. This report illustrates the challenge of diagnosing dental structure anomalies, specifically AI, in adults and highlights the need for an accurate and accessible molecular diagnosis for those anomalies to discriminate between isolated and syndromic pathologies. [ABSTRACT FROM AUTHOR]

Management science professors who teach large classes often assess students with multiple‐choice questions (MCQs) because it is efficient. However, traditional MCQ formats are ill‐fitted for constructive feedback. We propose the reward for omission with confidence in knowledge (ROCK) format as an original formative assessment technique to help guide feedback associated with MCQs in an introductory undergraduate management science course. Our study contributes to theory by empirically showing that students can self‐assess their state of knowledge, signal it to the professor, and use proper answering options. In practice, ROCK is an easily implementable MCQ format that allows professors to gain information on student learning based on answers selected. ROCK identifies lack of knowledge or misinformation at both individual and collective levels thus providing opportunities for better feedback in class and during office hours. Limitations of the application of ROCK are also discussed. [ABSTRACT FROM AUTHOR]

Master protocols have received a growing interest during the last years. By assigning patients to specific substudies, they aim at targeting and accelerating clinical development. Given their complexity, basket, umbrella, and platform designs have raised challenging regulatory and statistical questions, especially the control of multiplicity in confirmatory trials. In basket trials, regulatory assessment of the benefit/risk in pooled populations and choice of the treatment indication is challenging. We provide here our perspectives on these topics. In master protocols, as long as the statistical hypotheses tested between the different substudies are independent, no supplementary adjustment for multiplicity over the different substudies should be required. Moreover, sharing a control arm within an umbrella or a platform trial investigating different drugs would not require a correction for the type I error rate, whereas the chance of multiple false positive regulatory decisions should be recognized. In basket trials, pooling across substudies requires a rationale supporting the intended indication and should be preplanned. Assessment of the benefit/risk in pooled target populations can be complicated by differences in design or in efficacy/safety signals between the substudies. While trials governed by a master protocol can offer logistic and financial advantages, more experience is needed to gain a deeper insight into this novel framework. [ABSTRACT FROM AUTHOR]

The use of political violence to attain political goals has long been a source of concern. Once thought to be exclusive to countries with high levels of general violence, recent evidence suggests that harassment and intimidation of political elites in the UK is more widespread than previously thought. Using data from the 2017 general election candidate survey, we find that four in every ten candidates experienced at least one type of harassment. Evidence suggests that women and young candidates are more likely to suffer from harassment and intimidation. We conclude by formulating an agenda for future research, focussing, in particular, on the perception of harassment and the effect of harassment on political careers. [ABSTRACT FROM AUTHOR]

This thematic issue stems from a session organized in Quebec in 2018 for the joint meeting of the International Geographical Union (IGU) and the Canadian Association of Geographers (CAG) Annual Congress in Quebec City. Hence counter-mapping practices are definitely a powerful means for Indigenous peoples to reclaim spatial capital. They demonstrate that digital online mapping effectively empowers Indigenous peoples: first, because they allow better control of the way their knowledge and territorialities are represented; and second, because digital and online mapping better convey storytelling, a privileged way of building knowledge among Indigenous peoples, for example by linking place-names with audio or video and hence limiting the decontextualization of oral knowledge. [Extracted from the article]

The 3‐O‐desacyl‐4'‐monophosphoryl lipid A (MPL) activates immunity through Toll‐like receptor 4 (TLR4) signaling. The Adjuvant System AS01 contains MPL and is used in the candidate malaria vaccine and the licensed zoster vaccine. Recent studies reported that AS01 adjuvant activity depends on a transient inflammation at the site of vaccination, but the role of stromal or structural cells in the adjuvant effect is unknown. We investigated this question in mouse models by assessing the role of TLR4 on hematopoietic versus resident structural cells during immunization with AS01‐adjuvanted vaccines. We first established that TLR4‐deficient animals had a reduced immune response to an AS01‐adjuvanted vaccine. Using bone marrow chimera, we consistently found that Tlr4 expression in radio‐sensitive cells, i.e., hematopoietic cells, was required for an optimal adjuvant effect on antibody and T‐cell responses. At day 1 after injection, the pro‐inflammatory reaction at the site of injection was strongly dependent on TLR4 signaling in hematopoietic cells. Similarly, activation of dendritic cells in muscle‐draining lymph nodes was strictly associated with the radio‐sensitive cells expressing Tlr4. Altogether, these data suggest that MPL‐mediated TLR4‐signaling in hematopoietic cells is critical in the mode of action of AS01. [ABSTRACT FROM AUTHOR]

A dual electrofluorescent probe (FFN42) belonging to the fluorescent false neurotransmitter family was rationally designed for investigating cell secretion. This probe, which comprises a coumarin core with one amino and two hydroxy groups, is very promising due to its electroactive and fluorescent properties. The optimal excitation and emission wavelengths (380 nm and 470 nm respectively) make this probe adapted for use in fluorescence microscopy. FFN42 has a quantum yield of 0.18, a molar absorption coefficient of 12000 M−1cm−1 and pKa values of 5.4 and 6.7 for the hydroxy groups. The electroactivity of FFN42 was evidenced on carbon fiber and ITO electrodes at relatively low oxidation potentials (0.24 V and 0.45 V vs Ag/AgCl respectively). Epifluorescence observations showed that FFN42 accumulated into secretory vesicles of PC12 and N13 cells. Toxicity tests further revealed that FFN42 had no lethal effect on these cells. Amperometric data obtained on carbon fiber electrodes proved that the probe is released by N13 cells. [ABSTRACT FROM AUTHOR]

Coupling between tectonics and surface processes is usually ill‐quantified as other factors such as climate and lithology affect the later. We provide catchment‐wide 10Be denudation rates of the Mand catchment in the Zagros Fold Belt (Iran) to infer correlations between these rates and ongoing tectonic shortening in the region. Denudation rates are generally low (~0.05–0.1 mm/a) but increase to ~1 mm/a near the Halikan anticline, where changes in precipitation, lithology or hillslope gradient are insignificant. The denudation rates upstream and downstream of the Halikan anticline are consistent with the GPS convergence rates in these areas. The sharp increase in denudation rates over the Halikan anticline denotes its growth as previously detected from terrace incision. It also reveals small wavelength coupling between crustal deformation and erosion. Denudation rates are therefore a useful and sensitive tool that helps constraining non‐brittle active tectonics such as folding of a sedimentary cover. [ABSTRACT FROM AUTHOR]

Existing momentum budgets over coral reefs have predominantly focused on cross‐reef dynamics, lacking analysis of alongshore processes. To complement existing cross‐reef research and enhance our understanding of forcing variability at the semidiurnal period, this study examines the σ–coordinate, depth‐averaged alongshore momentum budget over a fore‐reef as a function of tidal phase. The observations were gathered over a 3‐week timespan, between the 12‐ and 20‐m isobaths of a Hawaiian fringing reef system, focusing on two moorings on the 12‐m isobath, where median drag coefficients estimated from log fits are CD=0.0080[−0.002,+0.004] and CD=0.0023[−0.0006,+0.0009]. Analysis at one location shows that the unsteadiness, barotropic pressure gradient, and bottom drag are equally important, and their combination is sufficient to close the momentum budget. However, bottom drag is less important at the second mooring; the difference between unsteadiness and pressure gradient suggests that advective acceleration plays a significant role. Plain Language Summary: Coral reefs are important, productive ocean ecosystems that are highly influenced by hydrodynamic forcing. Although a lot of research has been done to understand what forces drive the flow across tropical reefs (from offshore to onshore), less is known about the forces that drive flow parallel to the shoreline (alongshore). Here we study the physical dynamics over a coral reef in Hawai'i and determine that two primary forces drive the alongshore flow acceleration. One of the dominant forces is the drag exerted by the bottom reef, since coral are rougher than typical sandy coastal beds. The other dominant force is the pressure gradient, associated with the difference in sea level set up by the tide. The tidal cycle and the resulting flow response has important implications for the reef environment, with relevance for reef biology and, eventually, for ecosystem management policies. Key Points: A tidal alongshore momentum budget is estimated over a tropical fringing coral reef systemUnsteadiness, barotropic pressure gradient, and bottom drag play a dominant role on the fore‐reefAdvective acceleration can be of similar magnitude and necessary for budget closure [ABSTRACT FROM AUTHOR]

Along with the reduction in human papillomavirus (HPV) infection and cervical abnormalities as a result of the successful HPV vaccination program, Australia is adopting a new screening strategy. This involves a new paradigm moving from cervical cytological screening to molecular nucleic acid technology (NAT), using HPV DNA assays as primary screening methodology for cervical cancer prevention. These assays must strike a balance between sufficient clinical sensitivity to detect or predict high‐grade cervical intraepithelial lesions, the precursor to cervical cancer, without being too sensitive and detecting transient infection not destined for disease. Ensuring the highest quality HPV NAT is thus a priority in order to reduce the possibility of falsely negative screens and manage the risk associated with false positive HPV NAT test results. How to do this needs informed discussion and on‐going refinement of the screening algorithm. This is of relevance as more countries move to more sensitive HPV NAT tests for secondary prevention of cervical cancer and as more HPV assays become available. [ABSTRACT FROM AUTHOR]

In drug development, comparability of dissolution profiles of 2 different formulations is usually assessed using the similarity factor f2 . In practice, the drug dissolution profiles are deemed similar if the f2 exceeds 50, which occurs when a 10% maximum difference in the mean percentage of the dissolved drug at each time point between test and reference formulation is obtained. According to the Guideline on the Investigation of Bioequivalence (CPMP/EWP/QWP/1401/98 Rev. 1/ Corr **) use of the f2 is however restricted by a set of validity conditions. If some of these conditions are not satisfied, the f2 is not considered suitable, and alternative statistical methods are needed. In this article, we propose an inferential framework based on the maximum deviation between curves to test the comparability of drug dissolution profiles. The new methodology is applicable regardless whether the validity criteria of the f2 are met or not. Contrary to the f2 , this approach also integrates the variability of the measurements over time and not only their average. To benchmark our method, we performed simulations informed by 3 real case studies provided by the European Medicines Agency and extracted from dossiers submitted to the Centralised Procedure for Marketing Authorisation Application. In the scenarios of the simulation study, the new method controlled its type I error rate when the maximum deviation was greater than the similarity acceptance limit of 10%. The power exceeded 80% for small values of the maximum deviation, while the test was more conservative for intermediate ones. Our results were also very robust to sampling variations. Based on these positive findings, we encourage applicants to consider the new maximum deviation-based method as a valid alternative to the f2 , especially when the validity criteria of the latter are not met. [ABSTRACT FROM AUTHOR]

Outcrops in the southeastern Democratic Republic of the Congo (DRC) are recognized as some of the largest copper-cobalt orebodies in the world. They support a unique vegetation with nearly 600 metallophytes that include rare and endemic species. Mineral exploitation has increased considerably in the region since the 1900s, affecting both environmental and public health. Phytostabilisation of polluted areas represents an opportunity to decrease the bioavailability of heavy metals in the highly polluted soils that result from ore extraction. Such a technique has been successfully implemented near Lubumbashi with the grass Microchloa altera. However, long-term maintenance requires a good understanding of interspecific relationships, such as competition and facilitation. This study tested the establishment success of four herbaceous species from the Katangan Copperbelt by assessing the potential role of Microchloa altera as a nurse species. Two annual and two perennial species were sown in an experiment designed to study the influence of soil amendment and vegetation cover on seedling emergence, growth, and survival. These variables were monitored during the vegetation growing season as well as resprouting success for perennials. Microchloa altera showed a distinct effect on the emergence and survival of annual and perennial species and negatively affected the growth of individuals belonging to both groups of species. [ABSTRACT FROM AUTHOR]

Summary: To investigate the factors determining the clonal composition of Escherichia coli in poultry meat samples, 306 samples were collected from 16 shops, representing three supermarket chains and an independent butchery located in each of the four town centers of Canberra, Australia, during the summer, autumn and winter. A total of 3415 E. coli isolates were recovered and assigned to a phylogenetic group using the Clermont quadruplex PCR method, fingerprinted using repetitive element palindromic (REP) PCR and screened for their antimicrobial susceptibility profiles. The probability of detecting E. coli and the number of fingerprint types detected per sample, as well as the phylogroup membership of the isolates and their antimicrobial sensitivity profiles varied, with one or more of retailer, store, meat type, season and husbandry. The results of this study demonstrate that poultry meat products are likely to be contaminated with a genetically diverse community of E. coli and suggest that factors relating to the nature of the meat product and distribution chain are determinants of the observed diversity. [ABSTRACT FROM AUTHOR]

Abstract: Acoustically driven atomization from the broad perspective of materials choice, vibration mode, and fluid characteristics is considered to identify a simple method for improving both the understanding of the atomization phenomena and the overall efficiency of atomization. Whether by the definition of a “figure of merit” (a function of the transducer quality factor and electromechanical coupling coefficient), its output vibration displacement at a given input power, or the fluid flow rate during atomization, it is found that the combination of single‐crystal 127.86° Y‐rotated lithium niobate and thickness‐mode vibration produces an order of magnitude greater atomization flow rate and efficiency in comparison to all known atomizers, including classic lead zirconate‐based devices and newer, Rayleigh wave or Rayleigh/Lamb spurious‐mode‐based devices alike. By using this improved approach, for the first time, fluids with viscosities up to 48 cP are reported to be atomized, and an atomization Reynolds number ReA is defined which can be used to both predict the atomization flow rate for ReA ≳ 40 and the inability to atomize a given fluid at a particular vibration amplitude when ReA ≲ 40. [ABSTRACT FROM AUTHOR]

Summary: Ebolaviruses (family Filoviridae, order Mononegavirales) cause often fatal, haemorrhagic fever in primates including humans. Pigs have been identified as a species susceptible to Reston ebolavirus (RESTV) infection, with indicated transmission to humans in the Philippines; however, their role during Ebola outbreaks in Africa needs to be clarified. To perform surveillance studies, detection of ebolavirus requires a prerequisite validation of viral RNA and antibody detection methods in swine samples. These diagnostic tests also need to be suitable for deployment to low‐level containment laboratories. In this study, we developed a set of tests for detection of antibodies against Zaire ebolavirus (EBOV) in swine. Recombinant EBOV nucleoprotein was produced using a baculovirus expression system for indirect ELISA development. Evaluation of this assay was performed using laboratory and field samples, achieving a diagnostic specificity of 99%. Importantly, the indirect ELISA was able to detect antibodies to EBOV at 7 dpi, 3 days earlier than virus neutralization tests (VNT). The format of the VNT in this work was modified to a microtitre plaque reduction neutralization assay (miPRNT) complemented with immunostaining to provide a more rapid and highly specific assay. Finally, a confirmatory immunoblot assay was generated to supplement the indirect ELISA results. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and objective Dyspnoea in pulmonary embolism ( PE) remains poorly characterized. Little is known about how to measure intensity or about the underlying mechanisms that may be related to ventilatory abnormalities, alveolar dead space ventilation or modulating factors such as psychological modulate. We hypothesized that dyspnoea would mainly be associated with pulmonary vascular obstruction and its pathophysiological consequences, while the sensory-affective domain of dyspnoea would be influenced by other factors. Methods We undertook a prospective study of 90 consecutive non-obese patients (mean ± SD age: 49 ± 16 years, 41 women) without cardiorespiratory disease. All patients were hospitalized with symptoms for <15 days and a confirmed PE (multi-detector computed tomography ( MDCT) scan, n = 87 and high-probability ventilation/perfusion scan, n = 3). Patients underwent assessment of dyspnoea using the Borg score, modified Medical Research Council ( mMRC) scale, assessment of psychological trait, state of anxiety and depression and chest pain via the Visual Analogical Scale at the time of maximum dyspnoea. Functional evaluations such as the quantitative ventilation-perfusion lung scan, echocardiography, alveolar dead space fraction and tidal ventilation measurements were completed within 48 h of admission. Results Multivariate analyses demonstrated that dyspnoea was mainly linked to pulmonary vascular obstruction and/or its consequences such as raised pulmonary arterial pressure and chest pain. The sensory-affective domain of dyspnoea showed additional determinants such as age, depression and breathing variability. Conclusion Dyspnoea is mainly related to vascular consequences of PE such as increased pulmonary arterial pressure or chest pain. The sensory-affective domain of dyspnoea also correlates with age, depression and breathing variability. [ABSTRACT FROM AUTHOR]

Syndromic thoracic aortic aneurysm and dissection ( TAAD) can suggest Marfan, vascular Ehlers-Danlos or Loeys-Dietz ( LDS) syndromes. Several of the TGFβ-pathway-related genes predispose to different types of LDS. Heterozygous loss-of-function variations in TGFβ 2 have been shown to be responsible for a novel form of syndromic TAAD associated with an impairment of the mitral valve and cerebrovascular disease called Loeys-Dietz syndrome type 4 (LDS4). We report the clinical characterization of a LDS4 French family with sudden deaths and diffuse vascular lesions, caused by a frameshift mutation in TGFβ 2 gene: c.[995del]; p.(Leu332TrpfsTer27). Clinical characteristics include aneurysm of aortic sinus, skeletal and cutaneous features compatible with a syndromic form of TAAD (joint hypermobility, scoliosis, and easy bruises), intracranial aneurysms and rare mitral valve involvement. Iliac aneurysms, systemic medium caliber arteries dissections, and mild developmental delay were present in the family, and have not been described in LDS4. Phenotypic variability was also an important finding, including absence of clinical vascular events at advanced age in one case. Our data expand the phenotype of LDS4: we confirm that TGFβ 2 mutations are responsible for true LDS syndrome with non-specific features of connective tissue disorders and diffuse vascular lesions. Adapted vascular follow up and prevention has to be proposed for these patients. [ABSTRACT FROM AUTHOR]