bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma tau complements CSF tau and P‐tau in the diagnosis of Alzheimer's disease
Authors: Fossati Silvia , Ramos Cejudo Jaime , Debure Ludovic , Pirraglia Elizabeth , Sone Je Yeong , Li Yi , Chen Jingyun , Butler Tracy , Zetterberg Henrik , Blennow Kaj , de Leon Mony J.
Published: June 2019

Introduction

Plasma tau may be an accessible biomarker for Alzheimer's disease (AD), but the correlation between plasma and cerebrospinal fluid (CSF) tau and the value of combining plasma tau with CSF tau and phospho‐tau (P‐tau) are still unclear.

Methods

Plasma‐tau, CSF‐tau, and P‐tau were measured in 97 subjects, including elderly cognitively normal controls (n = 68) and patients with AD (n = 29) recruited at the NYU Center for Brain Health, with comprehensive neuropsychological and magnetic resonance imaging evaluations.

Results

Plasma tau was higher in patients with AD than cognitively normal controls (P < .001, area under the receiver operating characteristic curve = 0.79) similarly to CSF tau and CSF P‐tau and was negatively correlated with cognition in AD. Plasma and CSF tau measures were poorly correlated. Adding plasma tau to CSF tau or CSF P‐tau significantly increased the areas under the receiver operating characteristic curve from 0.80 and 0.82 to 0.87 and 0.88, respectively.

Discussion

Plasma tau is higher in AD independently from CSF‐tau. Importantly, adding plasma tau to CSF tau or P‐tau improves diagnostic accuracy, suggesting that plasma tau may represent a useful biomarker for AD, especially when added to CSF tau measures.
Preclinical studies of RUC-4, a novel platelet αIIbβ3 antagonist, in non-human primates and with human platelets
Authors: Vootukuri Spandana , Li Jihong , Nedelman Mark , Thomas Craig , Jiang Jiang-Kang , Babayeva Mariana , Coller Barry S.
Published: June 2019

Introduction:

We are developing the novel αIIbβ3 antagonist, RUC-4, for subcutaneously (SC)-administered first-point-of-medical-contact treatment for ST segment elevation myocardial infarction (STEMI).

Methods:

We studied the (1) pharmacokinetics (PK) of RUC-4 at 1.0, 1.93, and 3.86 mg/kg intravenous (IV), intramuscular (IM), and SC in non-human primates (NHPs); (2) impact of aspirin on RUC-4 IC50in human platelet-rich plasma (PRP); (3) effect of different anticoagulants on the RUC-4 IC50in human PRP; and (4) relationship between αIIbβ3 receptor blockade by RUC-4 and inhibition of ADP-induced platelet aggregation.

Results:

(1) All doses of RUC-4 were well tolerated, but animals demonstrated variable temporary bruising. IM and SC RUC-4 reached dose-dependent peak levels within 5–15 minutes, with T1/2s between 0.28 and 0.56 hours. Platelet aggregation studies in NHPs receiving IM RUC-4 demonstrated >80% inhibition of the initial slope of ADP-induced aggregation with all three doses 30 minutes post-dosing, with subsequent dose-dependent loss of inhibition over 4–5 hours. (2) The RUC-4 IC50for ADP-induced platelet aggregation was unaffected by aspirin treatment (40±9 nM vs 37±5 nM;p= 0.39). (3) The RUC-4 IC50was significantly higher in PRP prepared from D-phenylalanyl-prolyl-arginyl chloromethyl ketone (PPACK)-anticoagulated blood compared to citrate-anticoagulated blood using either thrombin receptor activating peptide (TRAP) (122±17 vs 66±25 nM;p= 0.05;n= 4) or ADP (102±22 vs 54±13;p<0.001;n= 5). (4) There was a close correspondence between receptor blockade and inhibition of ADP-induced platelet aggregation, with aggregation inhibition beginning with ~40% receptor blockade and becoming nearly complete at >80% receptor blockade.

Discussion:

Based on these results and others, RUC-4 has now progressed to formal preclinical toxicology studies.
Public Health Threats in Mass Gatherings: A Systematic Review
Authors: Karami Manoochehr , Doosti-Irani Amin , Ardalan Ali , Gohari-Ensaf Fathemeh , Berangi Zainab , Massad Eduardo , Rebi Yeganeh Mohammad , Asadi-Lari Mohsen , Gouya Mohammad Mehdi
Published: June 2019

Mass gatherings (MGs) are held throughout the world. The aim of this review was to assess and identify the health threats based on the type of the MG, type of diseases, and injuries. Research platforms such as Web of Science, Medline, and Scopus were searched through June 2017. All epidemiologic studies that investigated the health threats during the MGs, such as communicable diseases, injuries, high-risk behaviors, and environmental health problems, were included in this review. Out of 1264 references, 45 articles were included in the review.

Three main types of MGs include religious, festival, and sporting event; and fairs such as trade, book, and agricultural types were also reported in the selected studies. In the religious MGs, infectious diseases were the most common health threat. Road traffic accidents and environmental health problems were additional health threats. At MG sporting events, injuries were the most common health problems. Infectious diseases and alcohol and drug-related disorders were other reported public health concerns. In the festival MGs, alcohol and drug-related problems were commonly reported. This review showed that health threats vary, based on the type of mass gathering. The health organizers of MGs should consider the type of the MG and the health needs and safety of the participants to help them plan their action and provide the needed health care services.
Interpreting Past Human Mobility Patterns: A Model
Authors: Reiter Samantha S. , Frei Karin M.
Published: June 2019

In the last decade, the exponential increase in migration studies focusing on the mobility of groups and single individuals—mostly based on aDNA and strontium isotope analyses—has provided an important extra layer of information regarding past social dynamics. The current relatively large quantity of data and their constant increase provide an opportunity to examine human mobility in unprecedented detail. In short, the course of academic dialogue is changing from producing evidence for movement to examining differences or similarities in human mobilities across temporal and geographical barriers. Moreover, the amount and type of new data are beginning to provide new kinds of information that can help us grasp why that movement first came about. We present the first potential mobility model focusing on single individuals during different life stages based on in vivo movement patterns. We draw on previous studies in recent mobility research that provide a variety of case studies to illustrate the model. We hope that this model will prove valuable for future discussions regarding human mobility by integrating the present archaeological contextual discourse with the increasing body of data being produced.
Turbulent windprint on a liquid surface
Authors: Perrard Stéphane , Lozano-Durán Adrián , Rabaud Marc , Benzaquen Michael , Moisy Frédéric
Published: June 2019

We investigate the effect of a light turbulent wind on a liquid surface, below the onset of wave generation. In that regime, the liquid surface is populated by small disorganised deformations elongated in the streamwise direction. Formally identified recently by Paquier et al. (Phys. Fluids, vol. 27, 2015, art. 122103), the deformations that occur below the wave onset were named wrinkles. We provide here a theoretical framework for this regime, using the viscous response of a free liquid surface submitted to arbitrary normal and tangential interfacial stresses at its upper boundary. We relate the spatio-temporal spectrum of the surface deformations to that of the applied interfacial pressure and shear stress fluctuations. For that, we evaluate the spatio-temporal statistics of the turbulent forcing using direct numerical simulation of a turbulent channel flow, assuming no coupling between the air and the liquid flows. Combining theory and numerical simulation, we obtain synthetic wrinkles fields that reproduce the experimental observations. We show that the wrinkles are a multi-scale superposition of random wakes generated by the turbulent fluctuations. They result mainly from the nearly isotropic pressure fluctuations generated in the boundary layer, rather than from the elongated shear stress fluctuations. The wrinkle regime described in this paper naturally arises as the viscous-saturated asymptotic of the inviscid growth theory of Phillips (J. Fluid Mech., vol. 2 (05), 1957, pp. 417–445). We finally discuss the possible relation between wrinkles and the onset of regular quasi-monochromatic waves at larger wind velocity. Experiments indicate that the onset of regular waves increases with liquid viscosity. Our theory suggests that regular waves are triggered when the wrinkle amplitude reaches a fraction of the viscous sublayer thickness. This implies that the turbulent fluctuations near the onset may play a key role in the triggering of exponential wave growth.
The secondary instabilities of stationary cross-flow vortices in a Mach 6 swept wing flow
Authors: Xu Guoliang , Chen Jianqiang , Liu Gang , Dong Siwei , Fu Song
Published: June 2019

The secondary instabilities of stationary cross-flow vortices in a Mach 6 swept wing flow are studied using Floquet theory. High-frequency secondary instability modes of ‘y’ mode on top of stationary cross-flow vortices, and ‘z’ mode concentrating on the shoulder of the stationary cross-flow vortex are found. The most unstable secondary instability mode is always the ‘z’ mode as in incompressible swept wing flows. A new secondary instability mode concentrating on the trough of the stationary cross-flow vortex is found. The balance analysis of disturbance kinetic energy shows that the new mode belongs to the class of ‘y’ mode. The growth rate of the new ‘y’ mode located on the trough of the stationary cross-flow vortex is significantly larger than that of the ‘y’ mode on top of the stationary cross-flow vortex, and is comparable with the growth rate of the ‘z’ mode. It is also found that the new ‘y’ mode with higher frequency can evolve into the ‘z’ mode further downstream. The role of the pressure fluctuation term, including the pressure diffusion and pressure dilatation, in the energy production of secondary instability modes, is also investigated. It is shown that the pressure diffusion will only enhance the growth rate of the ‘z’ mode with higher frequency, but has little influence on other types of secondary instability mode. However, the pressure dilatation term arising from non-vanishing velocity divergence will reduce the growth rates of all secondary instability modes.
Ice scallops: a laboratory investigation of the ice–water interface
Authors: Bushuk Mitchell , Holland David M. , Stanton Timothy P. , Stern Alon , Gray Callum
Published: June 2019

Ice scallops are a small-scale (5–20 cm) quasi-periodic ripple pattern that occurs at the ice–water interface. Previous work has suggested that scallops form due to a self-reinforcing interaction between an evolving ice-surface geometry, an adjacent turbulent flow field and the resulting differential melt rates that occur along the interface. In this study, we perform a series of laboratory experiments in a refrigerated flume to quantitatively investigate the mechanisms of scallop formation and evolution in high resolution. Using particle image velocimetry, we probe an evolving ice–water boundary layer at sub-millimetre scales and 15 Hz frequency. Our data reveal three distinct regimes of ice–water interface evolution: a transition from flat to scalloped ice; an equilibrium scallop geometry; and an adjusting scallop interface. We find that scalloped-ice geometry produces a clear modification to the ice–water boundary layer, characterized by a time-mean recirculating eddy feature that forms in the scallop trough. Our primary finding is that scallops form due to a self-reinforcing feedback between the ice-interface geometry and shear production of turbulent kinetic energy in the flow interior. The length of this shear production zone is therefore hypothesized to set the scallop wavelength.
Interaction of a downslope gravity current with an internal wave
Authors: Ouillon Raphael , Meiburg Eckart , Ouellette Nicholas T. , Koseff Jeffrey R.
Published: June 2019

We investigate the interaction of a downslope gravity current with an internal wave propagating along a two-layer density jump. Direct numerical simulations confirm earlier experimental findings of a reduced gravity current mass flux, as well as the partial removal of the gravity current head from its body by large-amplitude waves (Hogg et al., Environ. Fluid Mech., vol. 18 (2), 2018, pp. 383–394). The current is observed to split into an intrusion of diluted fluid that propagates along the interface and a hyperpycnal current that continues to move downslope. The simulations provide detailed quantitative information on the energy budget components and the mixing dynamics of the current–wave interaction, which demonstrates the existence of two distinct parameter regimes. Small-amplitude waves affect the current in a largely transient fashion, so that the post-interaction properties of the current approach those in the absence of a wave. Large-amplitude waves, on the other hand, perform a sufficiently large amount of work on the gravity current fluid so as to modify its properties over the long term. The ‘decapitation’ of the current by large waves, along with the associated formation of an upslope current, enhance both viscous dissipation and irreversible mixing, thereby strongly reducing the available potential energy of the flow.
The gig economy: a hypothetical contract analysis
Authors: Moore Marc T
Published: June 2019

Gig work and other flexible labour practices have been subject to unprecedented levels of attention recently. While this topic has attracted significant interest from employment lawyers, it remains relatively underexplored from other pertinent legal and inter-disciplinary angles. This paper will adopt an alternative perspective on flexible work inspired by Coase's theory of the firm. Focusing on the implications of flexible work for the relative allocation of control, risk and reward within the firm, it will highlight how both task-oriented (gig) and on-demand (casual) work practices typically entail workers assuming most of the positional disadvantages associated with orthodox employment and self-employment, while enjoying none or few of the corresponding advantages. Using a hypothetical contract analysis, it will highlight the structural similarity between flexible work and unsecured financial investments in business firms by reference to key strands of institutional economics and law and finance literature. On this basis, it will enquire as to optimal forms of compensation that rational flexible workers can (counter-factually) be regarded as bargaining for in the absence of impediments to efficient contracting, and as the price for trading off their traditional employment guarantees.
Late Quaternary vertebrates from the Upper Gunnison Basin, Colorado, and small-mammal community resilience to climate change since the last glacial maximum
Authors: Emslie Steven D. , Meltzer David J.
Published: June 2019

The Upper Gunnison Basin (UGB), Colorado, is a montane region characterized by unusual physiography and topographic isolation. Excavations of three caves in the UGB provide one of the most diverse records of high-elevation late Quaternary vertebrates in North America. The localities, Haystack Cave (2450 m above sea level [m asl]), Cement Creek Cave (2860 m asl), and Signature Cave (3055 m asl), together provide a near-continuous record of vertebrate communities that extends from before the last glacial maximum to the present. These communities largely represent a sagebrush (Artemisiaspp.) steppe-tundra environment that prevailed throughout the UGB in the late Pleistocene. At least five taxa of extinct large mammals disappear from the UGB by the Early Holocene; one small mammal (the short-faced skunkBrachyprotomacf.B.brevimala) also became extinct. The fossil record further indicates that only four small extant mammals (Sorex preblei,Dicrostonyxsp.,Lemmiscus curtatus, andUrocitellus elegans) were extirpated from the UGB by the Early Holocene, in part because of community restructuring and loss of open habitats with expansion of forests to higher elevations. An analysis of taxonomic richness and evenness at Cement Creek Cave indicates high resilience in the small mammal community despite major climate shifts over the past 40,000+ yr.
Chronology and Plant Utilization from the Earliest Walled Settlement in the Hexi Corridor, Northwestern China
Authors: Liu Fengwen , Li Haiming , Cui Yifu , Yang Yishi , Lee Harry F , Ding Detian , Hou Yunguang , Dong Guanghui
Published: June 2019

The development and subsistence strategies adopted in ancient settlements are crucial to the understanding of long-term human–environmental interaction in the past. Here, we reassess the chronology of the ancient walled settlement of Sanjiao in the Hexi Corridor in northwestern China through accelerator mass spectrometry radiocarbon (AMS14C) dating and explore the subsistence of the settlers inside through the identification of carbonized seeds and charcoal. In addition, high-resolution paleoclimate records in the Hexi Corridor and nearby regions are employed to explore the reason for the construction of Sanjiao. Our results show that Sanjiao was built around 828 cal BC and remained inhabited through 384–116 cal BC. This indicates Sanjiao is the earliest known walled settlement in the Hexi Corridor. Ancient people at Sanjiao consumed crops such as barley, broomcorn millet, and foxtail millet, and used wood fromTamarix chinensis,Tamarix,Salix,Picea,Hippophae,Betulaceae, andPoaceaeas fuel. The construction date of Sanjiao correlates with climate deterioration and social upheavals in the Hexi Corridor, potentially suggesting a defensive purpose for the site.
Moral Revolutions: The Politics of Piety in the Ottoman Empire Reimagined
Authors: Shafir Nir
Published: June 2019

Over the sixteenth and seventeenth centuries an immense body of morality literature emerged in the Ottoman Empire as part of a widespread turn to piety. This article draws upon the anthropology of Islamic revival and secularism to reassess this literature's importance and propose a new view of the history of political thought in the empire. It does so through a close analysis of a fundamental concept of Ottoman political life: “naṣīḥat,”or “advice.” Historians have used “advice books” to counter the presumption that the Ottoman Empire declined after the sixteenth century, but in doing so they have overlooked the concept's broader meaning as “morally corrective criticism.” I analyze two competing visions ofnaṣīḥatat the turn of the eighteenth century to reveal how the concept was deployed to politically transform the empire by reforming its subjects’ morality. One was a campaign by the chief jurist Feyżullah Efendi to educate every Muslim in the basic tenets of Islam. The other was a wildly popular “advice book” written by the poet Nābī to his son that both explicates a new moral code and declares the empire's government and institutions illegitimate. Both transformed politics by requiring that all subjects be responsible moral, and therefore political, actors. The pietistic turn, I argue, turned domestic spaces into political battlegrounds and ultimately created new, individualistic political subjectivities. This, though, requires challenging functionalist conceptions of the relationship between religion and politics and the secularist inclination among historians to relegate morality to the private sphere.
Hijacked: Piracy and Economies of Protection in the Western Indian Ocean
Authors: Dua Jatin
Published: June 2019

From 2007–2012, a dramatic upsurge in maritime piracy off the coast of Somalia captivated global attention. Over three hundred merchant vessels and some three thousand seafarers were held hostage with ransom amounts ranging from $200,000 to $10 million being paid to release these ships. Somali piracy operated exclusively on a kidnap-and-ransom model with crew, cargo, and ship held captive until a ransom was secured. Ransom, unlike theft or seizure, requires willing parties and systems of exchange. Ransom economies, therefore, bring together disparate actors and make visible the centrality of protection as a mode of accumulation and jurisdiction. As an analytic, this article proposes an anthropology ofprotectionto undercut divides between legality and illegality, trade and finance, piracy and counter piracy. It argues that protection is key to apprehending processes of mobility and interruption central to global capitalism.
The Fight for Inheritances in the Papal States during the Restoration, 1814–1830
Authors: KORTEN CHRISTOPHER
Published: June 2019

This article looks at a common societal feature – the inheritance – examining how it became a prized source of income following the French Revolution and, therefore, a divisive element. The Restoration in the Papal States (1814–30) produced unexpected legal battles over the right of inheritances; family members as well as the monasteries of ex-religious, secularised during the Napoleonic period in Italy, contested the beneficiary status of wills. Such was the frequency and acrimony of the disputes that a special commission was created in 1827 to curb future debate. All told, these legal battles favoured ecclesiastical institutions over secular or family interests, and loosened the bonds between the Catholic Church and society during the Risorgimento.
Nudging to get our food choices on a sustainable track
Authors: Vandenbroele J. , Vermeir I. , Geuens M. , Slabbinck H. , Van Kerckhove A.
Published: June 2019

Food production is one of the major contributors to environmental damage. Adaptations in our food choices are needed to preserve resources for the needs of future generations. More sustainable consumption patterns have been encouraged by economic incentives, laws, education and communication campaigns. Nonetheless, consumers still find difficulties in trying to change their current food habits. This review takes a behavioural approach in encouraging sustainable food choices among consumers. From a nudging perspective, many behavioural changes can be encouraged in a non-obtrusive way by adapting the complex food environment in which consumers are operating. These interventions do not restrict consumers' choices but rather adapt the choice architecture wherein food decisions are made. Drawing on the literature from diverse theoretical perspectives, we provide an overview of the application of nudging for more sustainable food choices and highlight where more research is needed. More specifically, we discuss research that used nudging to engender cognitive impact (i.e. the use of labels or visibility enhancements), affective responses (i.e. sensorial and social influence cues) and behavioural effects (i.e. adjustments in convenience and product size). We conclude that this review only shows the tip of the iceberg of the research on nudging and sustainable consumption that is likely forthcoming in the next few years, following the successes of nudging applications in other domains. Nonetheless, each individual nudging intervention requires careful examination. Personal predispositions towards the environment should be considered when designing interventions, demonstrating the complementarity of nudging with education on sustainable consumption.
Symptom profiling for infectious intestinal disease (IID): a secondary data analysis of the IID2 study
Authors: Donaldson A. L. , Clough H. E. , O'Brien S. J. , Harris J. P.
Published: June 2019

Less than half of stool samples from people symptomatic with infectious intestinal disease (IID) will identify a causative organism. A secondary data analysis was undertaken to explore whether symptomology alone could be used to make inferences about causative organisms. Data were utilised from the Second Study of Infectious Intestinal Disease in the Community. A total of 844 cases were analysed. Few symptoms differentiated individual pathogens, but grouping pathogens together showed that viral IID was more likely when symptom onset was in winter (odds ratio (OR) 2.08, 95% confidence interval (CI) 1.16–3.75) or spring (OR 1.92, 95% CI 1.11–3.33), the patient was aged under 5 years (OR 3.63, 95% CI 2.24–6.03) and there was loss of appetite (OR 2.19, 95% CI 1.29–3.72). The odds of bacterial IID were higher with diarrhoea in the absence of vomiting (OR 3.54, 95% CI 2.37–5.32), diarrhoea which persisted for >3 days (OR 2.69, 95% CI 1.82–3.99), bloody diarrhoea (OR 4.17, 95% CI 1.63–11.83) and fever (OR 1.67, 95% CI 1.11–2.53). Symptom profiles could be of value to help guide clinicians and public health professionals in the management of IID, in the absence of microbiological confirmation.
Is it worth it to cryopreserve embryos with blastulation delay at day 5?
Authors: Montjean D. , Pauly V. , Gervoise-Boyer M. , Amar-Hoffet Aurélie , Geoffroy-Siraudin C. , Boyer P
Published: June 2019

This is a retrospective study over a 5-year period. In total, 3139 embryos were individually cryopreserved (Cryotop®) and warmed using the Kitazato vitrification/warming kit. They were classified into three categories based on their expansion degree. Transfer, implantation and pregnancy rates were assessed for each embryo category and compared using SPSS (Statistical Package for the Social Sciences) software. In total, 1139 couples enrolled in infertility treatment programme benefitted from embryo vitrification at day 5. After warming, embryos belonging to the three categories showed similar success rates. Although there was a trend towards better outcomes when grade 3 embryos were transferred, the differences did not reach statistical significance: implantation rates (n fetal sac/n embryo transferred) grade 1: 21.9%, grade 2: 22.7% and grade 3: 30.3% (=0.19). Pregnancy rate (n clinical pregnancy/n transfer) (21.9%, 22.7%, 30.3%, respectively; P=0.11). Miscarriage rate was not statistically different in the three categories (14.5%, 20.4%, 20%, respectively, P=0.51). Our overall results show that it is worth vitrifying slow kinetics embryos as they provide a non-negligible chance to give rise to a pregnancy.
Neurocognition and social cognition training as treatments for violence and aggression in people with severe mental illness
Authors: Jones Mackenzie T. , Harvey Philip D.
Published: June 2019

Aggressive and violent behavior, including both verbal and physical aggression, have considerable adverse consequences for people with schizophrenia. There are several potential causes of violent behavior on the part of people with severe mental illness, which include intellectual impairments, cognitive and social-cognitive deficits, skills deficits, substance abuse, antisocial features, and specific psychotic features. This review explores the interventions that have been tested to this date. Computerized Cognitive Training (CCT) or Computerized Social-Cognitive Training (CSCT) have been associated with reductions in violence. Combined CCT and CSCT have been found to improve social cognition and neurocognition, as well as everyday functioning when combined with rehabilitation interventions. These interventions have been shown to reduce violence in schizophrenia patients across multiple environments, including forensic settings. The reductions in violence and aggression have manifested in various ways, including reduced violent thinking and behavior, reduced physical and violent assaults, and reduced disruptive and aggressive behaviors. Effects of cognitive training may be associated with improvements in problem-solving and the increased ability to deploy alternative strategies. The effect of social cognition training on violence reduction appears to be direct, with improvements in violence related to the extent of improvement in social cognition. There are still remaining issues to be addressed in the use of CCT and CSCT, and the benefits should not be overstated; however, the results of these interventions are very promising.
Contextual factors influencing the implementation of innovations in community-based primary health care: the experience of 12 Canadian research teams
Authors: Ploeg Jenny , Wong Sabrina T. , Hassani Kasra , Yous Marie-Lee , Fortin Martin , Kendall Claire , Liddy Clare , Markle-Reid Maureen , Petrovic Bojana , Dionne Emilie , Scott Cathie M. , Wodchis Walter P.
Published: June 2019

The objectives of this paper are to: (1) identify contextual factors such as policy that impacted the implementation of community-based primary health care (CBPHC) innovations among 12 Canadian research teams and (2) describe strategies used by the teams to address contextual factors influencing implementation of CBPHC innovations. In primary care settings, consideration of contextual factors when implementing change has been recognized as critically important to success. However, contextual factors are rarely recorded, analyzed or considered when implementing change. The lack of consideration of contextual factors has negative implications not only for successfully implementing primary health care (PHC) innovations, but also for their sustainability and scalability. For this evaluation, data collection was conducted using self-administered questionnaires and follow-up telephone interviews with team representatives. We used a combination of directed and conventional content analysis approaches to analyze the questionnaire and interview data. Representatives from all 12 teams completed the questionnaire and 11 teams participated in the interviews; 40 individuals participated in this evaluation. Four themes representing contextual factors that impacted the implementation of CBPHC innovations were identified: (I) diversity of jurisdictions (II) complexity of interactions and collaborations (III) policy, and (IV) the multifaceted nature of PHC. The teams used six strategies to address these contextual factors including: (1) conduct an environmental scan at the beginning (2) maintaining engagement among partners and stakeholders by encouraging open and inclusive communication; (3) contextualizing the innovation for different settings; (4) anticipating and addressing changes, delays, and the need for additional resources; (5) fostering a culture of research and innovation among partners and stakeholders; and (6) ensuring information about the innovation is widely available. Implementing CBPHC innovations across jurisdictions is complex and involves navigating through multiple contextual factors. Awareness of the dynamic nature of context should be considered when implementing innovations.
A neural network extension of the Lee–Carter model to multiple populations
Authors: Richman Ronald , Wüthrich Mario V.
Published: June 2019

The Lee–Carter (LC) model is a basic approach to forecasting mortality rates of a single population. Although extensions of the LC model to forecasting rates for multiple populations have recently been proposed, the structure of these extended models is hard to justify and the models are often difficult to calibrate, relying on customised optimisation schemes. Based on the paradigm of representation learning, we extend the LCmodel to multiple populations using neural networks, which automatically select an optimal model structure. We fit this model to mortality rates since 1950 for all countries in the Human Mortality Database and observe that the out-of-sample forecasting performance of the model is highly competitive.
Influence of weed size on herbicide interactions for Enlist™ and Roundup Ready® Xtend® technologies
Authors: Meyer Chris J. , Norsworthy Jason K.
Published: June 2019

Weed size can nfluence herbicide performance and herbicide interactions in mixtures. To control a broad range of species in soybean or cotton, POST herbicide mixtures will likely be commonplace in Roundup Ready® XtendFlex® and Enlist™ technologies. The impact of weed size on herbicide interactions that could occur in Roundup Ready XtendFlex or Enlist crops was assessed in two field experiments conducted in 2015 and 2016 at the Northeast Research and Extension Center in Keiser, AR. Combinations of glufosinate, glyphosate, dicamba, and 2,4-D were applied to either 10-cm or 30-cm weeds and evaluated for percent weed control, height reduction, and density reduction, collected 5 wk after treatment. Colby’s method was used to analyze treatments for herbicide interactions for control of barnyardgrass, Palmer amaranth, and pitted morningglory. Antagonism was identified with at least one treatment on all species. Almost all treatments were antagonistic for percent weed control, height reduction, and density reduction on barnyardgrass. When glyphosate in mixture with 2,4-D or dicamba was applied to 30-cm barnyardgrass, control declined 9% for both mixtures relative to glyphosate alone. Glufosinate plus glyphosate was antagonistic when applied to both 30-cm pitted morningglory and barnyardgrass. Glufosinate plus dicamba provided less control and density reduction of Palmer amaranth than what was expected from Colby’s equation. Overall, antagonism was more likely to be identified when applications were made to 30-cm weeds compared with 10-cm weeds. The utility of a given herbicide mixture will depend on the species present in the field and the size of those species at the time of application.
Exploring the Importance of the Mindoro‐Sibutu Pathway to the Upper‐Layer Circulation of the South China Sea and the Indonesian Throughflow
Authors: Li Mingting , Wei Jun , Wang Dongxiao , Gordon Arnold L. , Yang Song , Malanotte‐Rizzoli Paola , Jiang Guoqing
Published: June 2019

Using a high‐resolution (0.1° × 0.1°) regional ocean model, this study investigates the impact of strait transport variability on the South China Sea (SCS) circulation and Indonesian throughflow, with a focus on the Mindoro‐Sibutu pathway via the Sulu Sea, upon closing various straits within the Maritime Continent. Closing the Sibutu Strait reduces the Luzon Strait throughflow into the SCS by 75%, and the Mindoro–Sibutu deep exchange is reversed, thus flowing into the SCS. No significant change occurs over the shallow Sunda Shelf of the southern SCS, which is primarily driven by local monsoon winds. The impact of closing the Karimata Strait is limited to the Sunda Shelf and the Java Sea. The Sibutu Strait throughflow is fundamental in governing the SCS's low salinity, buoyancy, and upper layer injection into the Makassar Strait, which is the primary component of the Indonesian throughflow, thus inhibiting the transport within the upper 200 m of the throughflow. Closing both the Sibutu and Karimata Straits increases the southward Makassar Strait throughflow transport by ~3 Sv, which is derived entirely from the Mindanao Current.
Honoring Volcanologist David Johnston as a Hero and a Human
Authors: Cartier Kimberly
Published: June 2019

A new biography details the life and legacy of the scientist who died on Mount St. Helens.
Lithospheric Structure and Evolution of Southern Africa: Constraints From Joint Inversion of Rayleigh Wave Dispersion and Receiver Functions
Authors: Wang Tuo , Gao Stephen S. , Dai Yuhang , Yang Qiuyue , Liu Kelly H.
Published: June 2019

We conduct a joint inversion of teleseismic receiver functions and Rayleigh wave phase velocity dispersion from both ambient noise and earthquakes using data from 79 seismic stations in southern Africa, which is home to some of the world's oldest cratons and orogenic belts. The area has experienced two of the largest igneous activities in the world (the Okavango dyke swarm and Bushveld mafic intrusion) and thus is an ideal locale for investigating continental formation and evolution. The resulting 3‐D shear wave velocities for the depth range of 0–100 km and crustal thickness measurements show a clear spatial correspondence with known geological features observed on the surface. Higher than normal mantle velocities found beneath the southern part of the Kaapvaal craton are consistent with the basalt removal model for the formation of cratonic lithosphere. In contrast, the Bushveld complex situated within the northern part of the craton is characterized by a thicker crust and higher crustalVp/Vsbut lower mantle velocities, which are indicative of crustal underplating of mafic materials and lithospheric refertilization by the world's largest layered mafic igneous intrusion. The thickened crust and relatively low elevation observed in the Limpopo belt, which is a late Archean collisional zone between the Kaapvaal and Zimbabwe cratons, can be explained by eclogitization of the basaltic lower crust. The study also finds evidence for the presence of a stalled segment of oceanic lithosphere beneath the southern margin of the Proterozoic Namaqua‐Natal mobile belt.
Controls on the Width of Tropical Precipitation and Its Contraction Under Global Warming
Authors: Donohoe A. , Atwood A. R. , Byrne M. P.
Published: June 2019

Climate models robustly and unanimously simulate narrowing of the intense tropical precipitation under greenhouse gas forcing. We argue that the meridional width of tropical precipitation is controlled by the seasonal meridional range of the Intertropical Convergence Zone (ITCZ). The contraction of tropical precipitation under greenhouse forcing results from a reduced seasonal range of ITCZ migration. An energetic theory—similar to the energetic theory for ITCZ shifts based on the hemispheric contrast of energy input to the atmosphere—is developed. The meridional width of tropical precipitation is proportional to the seasonal range of the interhemispheric contrast in atmospheric heating divided by the efficiency of atmospheric cross‐equatorial heat transport. Climate models are biased toward overly expansive tropical precipitation resulting from an exaggerated seasonal atmospheric heating. The robust contraction of tropical precipitation under global warming results from increased efficiency of interhemispheric energy transport consistent with enhanced gross moist stability of the tropical atmosphere.
Thermal Weakening, Convergent Flow, and Vertical Heat Transport in the Northeast Greenland Ice Stream Shear Margins
Authors: Holschuh N. , Lilien D. A. , Christianson K.
Published: June 2019

Ice streams are bounded by abrupt transitions in speed called shear margins. Some shear margins are fixed by subglacial topography, but others are thought to be self‐organizing, evolving by thermal feedback to ice viscosity and basal drag which govern the stress balance of ice sheets. Resistive stresses (and properties governing shear‐margin formation) manifest nonuniquely at the surface, motivating the use of subsurface observations to constrain ice sheet models. In this study, we use ice‐penetrating radar data to evaluate three 3‐D thermomechanical models of the Northeast Greenland Ice Stream, focusing on model reproductions of ice temperature (a primary control on viscosity) and subsurface velocity. Data/model agreement indicates elevated temperatures in the Northeast Greenland Ice Stream margins, with depth‐averaged temperatures between 2 °C and 6 °C warmer in the southeast margin compared to ice in streaming flow, driven by vertical heat transport rather than shear heating. This work highlights complexity in ice divergence across stagnant/streaming transitions.
Impact of polymorphism on the optoelectronic properties of a low-bandgap semiconducting polymer
Authors: Li Mengmeng , Balawi Ahmed Hesham , Leenaers Pieter J. , Ning Lu , Heintges Gaël H. L. , Marszalek Tomasz , Pisula Wojciech , Wienk Martijn M. , Meskers Stefan C. J. , Yi Yuanping , Laquai Frédéric , Janssen René A. J.
Published: June 2019

Polymorphism of organic semiconducting materials exerts critical effects on their physical properties such as optical absorption, emission and electrical conductivity, and provides an excellent platform for investigating structure–property relations. It is, however, challenging to efficiently tune the polymorphism of conjugated polymers in aggregated, semi-crystalline phases due to their conformational freedom and anisotropic nature. Here, two distinctly different semi-crystalline polymorphs (β1 and β2) of a low-bandgap diketopyrrolopyrrole polymer are formed through controlling the solvent quality, as evidenced by spectroscopic, structural, thermal and charge transport studies. Compared to β1, the β2 polymorph exhibits a lower optical band gap, an enhanced photoluminescence, a reduced π-stacking distance, a higher hole mobility in field-effect transistors and improved photocurrent generation in polymer solar cells. The β1 and β2 polymorphs provide insights into the control of polymer self-organization for plastic electronics and hold potential for developing programmable ink formulations for next-generation electronic devices.
Marrying chemistry with biology by combining on-chip solution-based combinatorial synthesis and cellular screening
Authors: Benz Maximilian , Molla Mijanur R. , Böser Alexander , Rosenfeld Alisa , Levkin Pavel A.
Published: June 2019

Drug development often relies on high-throughput cell-based screening of large compound libraries. However, the lack of miniaturized and parallelized methodologies in chemistry as well as strict separation and incompatibility of the synthesis of bioactive compounds from their biological screenings makes this process expensive and inefficient. Here, we demonstrate an on-chip platform that combines solution-based synthesis of compound libraries with high-throughput biological screenings (chemBIOS). The chemBIOS platform is compatible with both organic solvents required for the synthesis and aqueous solutions necessary for biological screenings. We use the chemBIOS platform to perform 75 parallel, three-component reactions to synthesize a library of lipidoids, followed by characterization via MALDI-MS, on-chip formation of lipoplexes, and on-chip cell screening. The entire process from the library synthesis to cell screening takes only 3 days and about 1 mL of total solutions, demonstrating the potential of the chemBIOS technology to increase efficiency and accelerate screenings and drug development.
Chromatin organization in the female mouse brain fluctuates across the oestrous cycle
Authors: Jaric Ivana , Rocks Devin , Greally John M. , Suzuki Masako , Kundakovic Marija
Published: June 2019

Male and female brains differ significantly in both health and disease, and yet the female brain has been understudied. Sex-hormone fluctuations make the female brain particularly dynamic and are likely to confer female-specific risks for neuropsychiatric disorders. The molecular mechanisms underlying the dynamic nature of the female brain structure and function are unknown. Here we show that neuronal chromatin organization in the female ventral hippocampus of mouse fluctuates with the oestrous cycle. We find chromatin organizational changes associated with the transcriptional activity of genes important for neuronal function and behaviour. We link these chromatin dynamics to variation in anxiety-related behaviour and brain structure. Our findings implicate an immediate-early gene product, Egr1, as part of the mechanism mediating oestrous cycle-dependent chromatin and transcriptional changes. This study reveals extreme, sex-specific dynamism of the neuronal epigenome, and establishes a foundation for the development of sex-specific treatments for disorders such as anxiety and depression.
Early evidence of molariform hypsodonty in a Triassic stem-mammal
Authors: Melo Tomaz P. , Ribeiro Ana Maria , Martinelli Agustín G. , Soares Marina Bento
Published: June 2019

Hypsodonty, the occurrence of high-crowned teeth, is widespread among mammals with diets rich in abrasive material, such as plants or soil, because it increases the durability of dentitions against wear. Hypsodont postcanine teeth evolved independently in multiple mammalian lineages and in the closely related mammaliaforms since the Jurassic period. Here, we report the oldest record, to our knowledge, of hypsodont postcanines in the non-mammaliaform stem-mammal, Menadon besairiei, from the early Late Triassic. The postcanines are long and columnar, with open roots. They were not replaced in older individuals and remained functional after the total wear of the crown enamel. Dental histology suggests that, convergently to hypsodont mammals, wear was compensated by the prolonged growth of each postcanine, resulting in dentine hypsodont teeth most similar to extant xenarthran mammals. These findings highlight the constraints imposed by limited tooth replacement and tooth wear in the evolutionary trajectories of herbivorous mammals and stem-mammals.
A neurotoxin that specifically targets Anopheles mosquitoes
Authors: Contreras Estefania , Masuyer Geoffrey , Qureshi Nadia , Chawla Swati , Dhillon Harpal S. , Lee Han Lim , Chen Jianwu , Stenmark Pål , Gill Sarjeet S.
Published: June 2019

Clostridial neurotoxins, including tetanus and botulinum neurotoxins, generally target vertebrates. We show here that this family of toxins has a much broader host spectrum, by identifying PMP1, a clostridial-like neurotoxin that selectively targets anopheline mosquitoes. Isolation of PMP1 from Paraclostridium bifermentans strains collected in anopheline endemic areas on two continents indicates it is widely distributed. The toxin likely evolved from an ancestral form that targets the nervous system of similar organisms, using a common mechanism that disrupts SNARE-mediated exocytosis. It cleaves the mosquito syntaxin and employs a unique receptor recognition strategy. Our research has an important impact on the study of the evolution of clostridial neurotoxins and provides the basis for the use of P. bifermentans strains and PMP1 as innovative, environmentally friendly approaches to reduce malaria through anopheline control.
TSPAN8 promotes cancer cell stemness via activation of sonic Hedgehog signaling
Authors: Zhu Rongxuan , Gires Olivier , Zhu Liqun , Liu Jun , Li Junjian , Yang Hao , Ju Gaoda , Huang Jing , Ge Weiyu , Chen Yi , Lu Zhimin , Wang Hongxia
Published: June 2019

Cancer stem cells (CSCs) represent a major source of treatment resistance and tumor progression. However, regulation of CSCs stemness is not entirely understood. Here, we report that TSPAN8 expression is upregulated in breast CSCs, promotes the expression of the stemness gene NANOG, OCT4, and ALDHA1, and correlates with therapeutic resistance. Mechanistically, TSPAN8 interacts with PTCH1 and inhibits the degradation of the SHH/PTCH1 complex through recruitment of deubiquitinating enzyme ATXN3. This results in the translocation of SMO to cilia, downstream gene expression, resistance of CSCs to chemotherapeutic agents, and enhances tumor formation in mice. Accordingly, expression levels of TSPAN8, PTCH1, SHH, and ATXN3 are positively correlated in human breast cancer specimens, and high TSPAN8 and ATXN3 expression levels correlate with poor prognosis. These findings reveal a molecular basis of TSPAN8-enhanced Sonic Hedgehog signaling and highlight a role for TSPAN8 in promoting cancer stemness.
DNA double-strand breaks in telophase lead to coalescence between segregated sister chromatid loci
Authors: Ayra-Plasencia Jessel , Machín Félix
Published: June 2019

DNA double strand breaks (DSBs) pose a high risk for genome integrity. Cells repair DSBs through homologous recombination (HR) when a sister chromatid is available. HR is upregulated by the cycling dependent kinase (CDK) despite the paradox of telophase, where CDK is high but a sister chromatid is not nearby. Here we study in the budding yeast the response to DSBs in telophase, and find they activate the DNA damage checkpoint (DDC), leading to a telophase-to-G1 delay. Outstandingly, we observe a partial reversion of sister chromatid segregation, which includes approximation of segregated material, de novo formation of anaphase bridges, and coalescence between sister loci. We finally show that DSBs promote a massive change in the dynamics of telophase microtubules (MTs), together with dephosphorylation and relocalization of kinesin-5 Cin8. We propose that chromosome segregation is not irreversible and that DSB repair using the sister chromatid is possible in telophase.