bluuebunny/crossref_metadata_2025 huggingface dataset:
Additional Analytical Support for a New Method to Compute the Likelihood of Diversification Models
Authors: Laudanno Giovanni , Haegeman Bart , Etienne Rampal S.
Published: January 2020

Molecular phylogenies have been increasingly recognized as an important source of information on species diversification. For many models of macroevolution, analytical likelihood formulas have been derived to infer macroevolutionary parameters from phylogenies. A few years ago, a general framework to numerically compute such likelihood formulas was proposed, which accommodates models that allow speciation and/or extinction rates to depend on diversity. This framework calculates the likelihood as the probability of the diversification process being consistent with the phylogeny from the root to the tips. However, while some readers found the framework presented in Etienne et al. (Proc R Soc Lond B Biol Sci 279(1732):1300–1309, 2012) convincing, others still questioned it (personal communication), despite numerical evidence that for special cases the framework yields the same (i.e., within double precision) numerical value for the likelihood as analytical formulas do that were independently derived for these special cases. Here we prove analytically that the likelihoods calculated in the new framework are correct for all special cases with known analytical likelihood formula. Our results thus add substantial mathematical support for the overall coherence of the general framework.
How and What Can Humans Learn from Being in the Loop?
Authors: Abdel-Karim Benjamin M. , Pfeuffer Nicolas , Rohde Gernot , Hinz Oliver
Published: January 2020

This article discusses the counterpart of interactive machine learning, i.e., human learning while being in the loop in a human-machine collaboration. For such cases we propose the use of a Contradiction Matrix to assess the overlap and the contradictions of human and machine predictions. We show in a small-scaled user study with experts in the area of pneumology (1) that machine-learning based systems can classify X-rays with respect to diseases with a meaningful accuracy, (2) humans partly use contradictions to reconsider their initial diagnosis, and (3) that this leads to a higher overlap between human and machine diagnoses at the end of the collaboration situation. We argue that disclosure of information on diagnosis uncertainty can be beneficial to make the human expert reconsider her or his initial assessment which may ultimately result in a deliberate agreement. In the light of the observations from our project, it becomes apparent that collaborative learning in such a human-in-the-loop scenario could lead to mutual benefits for both human learning and interactive machine learning. Bearing the differences in reasoning and learning processes of humans and intelligent systems in mind, we argue that interdisciplinary research teams have the best chances at tackling this undertaking and generating valuable insights.
Synergies in Innovation: Lessons Learnt from Innovation Ethics for Responsible Innovation
Authors: Bourban Michel , Rochel Johan
Published: January 2020

This paper draws on the emerging field of innovation ethics (IE) to complement the more established field of responsible innovation (RI) by focusing on key ethical issues raised by technological innovations. One key limitation of influential frameworks of RI is that they tend to neglect some key ethical issues raised by innovation, as well as major normative dimensions of the notion of responsibility. We explain how IE could enrich RI by stressing the more important role that ethical analysis should play in RI. We focus on two transversal issues of IE: the issue of redrawing conceptual boundaries, especially the topic of the artificialization of the world, and the issue of responsibility, especially the notion of total responsibility. We address these two issues from the thematic perspective of IE, thereby generating lessons learnt for RI. These two examples are taken as illustrations and blueprint of the dialogue that should take place between the two fields.
Parametric study of dynamic inter-array cable systems for floating offshore wind turbines
Authors: Rentschler Manuel U. T. , Adam Frank , Chainho Paulo , Krügel Kilian , Vicente Pedro C.
Published: January 2020

The rapid emergence of the floating offshore wind sector requires the development of new technologies such as dynamic inter-array cables. This work gives an insight into the hydrostatic predesign of such a cable system looking from side view. Numerical analyses are performed to compare two umbilical shapes, namely catenary and lazy wave shape. In a parametric study, water depth and cable length are varied. As outcome, a unique and generalized recommendation for a first umbilical design is presented. Finally, an outlook to the dynamic analysis of umbilicals in future work is given.
Patient Input to Inform the Development of Central Nervous System Outcome Measures in Myotonic Dystrophy
Authors: White Molly
Published: January 2020

Myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2) are multisystem, genetic disorders caused by repeat expansions on chromosome 19 (DM1) and chromosome 3 (DM2). Although the effects of DM on the skeletal, cardiac, and smooth muscles, as well as the endocrine and central nervous systems, can be disabling, there are no disease-modifying therapies for the disorder. Following a process established by the US Food and Drug Administration (FDA) in 2012 known as the Patient-Focused Drug Development (PFDD) Initiative, Myotonic (formerly the Myotonic Dystrophy Foundation) has been conducting patient- and caregiver-inclusive sessions to explore disease burden as defined by patients and caregivers, and what affected individuals want most from potential new therapies. In September 2017, at Myotonic’s annual conference, a session titled “Bringing the Patient Voice to CNS-Targeting Drug Development in Myotonic Dystrophy” attracted some 350 members of the DM community. During the session, patients and caregivers described CNS disease symptoms, their impact on quality of life, and potential CNS-related targets that they considered important for drug development consideration. These included fatigue and daytime sleepiness; dysregulated sleep; cognitive deficits such as “brain fog,” memory and focus impairment, learning and attention difficulties, and time management challenges; emotional/psychological/behavioral difficulties, including impulsivity, apathy, antisocial behavior, personality changes, and depression; social difficulties, including disconnection, lack of awareness, and feelings of isolation; and general anxieties about the future and potential loss of independence. Improvements in memory and lessening of “brain fog” were considered particularly important.
Entanglements of matter and meaning: The importance of the philosophy of Karen Barad for environmental education
Authors: Brown Shae L. , Siegel Lisa , Blom Simone M.
Published: January 2020

The rich and innovative ideas of quantum physicist and feminist theorist Karen Barad have much to offer environmental educators in terms of practical theories for teaching and learning. This article shares insights gained from a facilitated conversation at the Australian Association for Environmental Education (AAEE) Conference Research Symposium, and offers an introduction to Barad’s theories for environmental educators. At this time of challenging planetary imperatives, environmental education is increasingly called upon to contribute to students’ understanding of connectedness, and Barad’s theory ofagential realismprovides a way to think about, articulate and engage with connectedness as inherent within the world rather than something we need to create. By consideringentanglementas a fundamental state, we understand that separateness is not the original state of being. This shift in perspective supports a subtle yet powerful approach to knowledge, communication and collaboration, understanding difference as integral within the world’s entangled becoming. The convened conversation sought to explore Barad’s thinking by defining and discussing the concepts ofagential realism,intra-action,material-discursivity,phenomenaanddiffraction. Barad’s ideas were used to collectively explore what it means to be intraconnected and entangled in today’s world, and specifically how these concepts and experiences relate to our work and lives as environmental educators and researchers.
Static test of a variable stiffness thermoplastic composite wingbox under shear, bending and torsion
Authors: Zucco G. , Oliveri V. , Rouhi M. , Telford R. , Clancy G. , McHale C. , O’Higgins R. , Young T.M. , Weaver P.M. , Peeters D.
Published: January 2020

Automated manufacturing of thermoplastic composites has found increased interest in aerospace applications over the past three decades because of its great potential in low-cost, high rate, repeatable production of high performance composite structures. Experimental validation is a key element in the development of structures made using this emerging technology. In this work, a
$750\times640\times240$
mm variable-stiffness unitised integrated-stiffener out-of-autoclave thermoplastic composite wingbox is tested for a combined shear-bending-torsion induced buckling load. The wingbox is manufactured by in-situ consolidation using a laser-assisted automated tape placement technique. It is made and tested as a demonstrator section located at 85% of the wing semi-span of a B-737/A320 sized aircraft. A bespoke in-house test rig and two aluminium dummy wingboxes are also designed and manufactured for testing the wingbox assembly which spans more than 3m. Prior to testing, the wingbox assembly and the test rig were analysed using a high fidelity finite element method to minimise the failure risk due to the applied load case. The experimental test results of the wingbox are also compared with the predictions made by a numerical study performed by nonlinear finite element analysis showing less than 5% difference in load-displacement behaviour and buckling load and full agreement in predicting the buckling mode shape.
Internet addiction in high school and university students: an evaluation in terms of various psychological, social and personal variables
Authors: Odaci Hatice , Değerli Fatma Irem , Cikrikci Neslihan
Published: January 2020

The purpose of this research was to examine internet addiction among high school and university students in terms of interpersonal relationships, automatic thoughts and problem-solving skills. The sample of the study comprised a total of 480 participants: 195 (40.6%) high school and 285 (59.4%) university students. Females constituted 53.3% (256) of the participants and males 46.7% (224). In addition to a Personal Information Form, the Interpersonal Relationship Styles Scale, Automatic Thoughts Scale, Problem Solving Inventory and Internet Addiction Scale, for which validity, reliability and adaptation studies were performed, were used for data collection. A significant difference was determined between the groups with no or limited symptoms of internet addiction in terms of inhibitory interpersonal relationship styles, automatic thoughts and problem-solving skills. Inhibitory interpersonal relationships, automatic thoughts and problem-solving skills were identified as predictive of internet addiction.
ON A CLOSE-TO-CONVEX ANALOGUE OF CERTAIN STARLIKE FUNCTIONS
Authors: ALLU VASUDEVARAO , SOKÓŁ JANUSZ , THOMAS DEREK K.
Published: January 2020

For $f$ analytic in the unit disk $\mathbb{D}$, we consider the close-to-convex analogue of a class of starlike functions introduced by R. Singh [‘On a class of star-like functions’, Compos. Math.19(1) (1968), 78–82]. This class of functions is defined by $|zf^{\prime }(z)/g(z)-1|<1$ for $z\in \mathbb{D}$, where $g$ is starlike in $\mathbb{D}$. Coefficient and other results are obtained for this class of functions.
BEYOND THE NATION-STATE: A NETWORK ANALYSIS OF JEWISH EMIGRATION FROM NORTHERN MOROCCO TO ISRAEL
Authors: Moreno Aviad
Published: January 2020

The post-1948 mass migration of Jews from Arab Muslim countries to Israel is widely seen by scholars as a direct result of decolonization and rising nationalism across the Middle East and North Africa, coupled with the emigration and immigration policies of regional powers. In this article I draw on local histories of northern Morocco to critique the existing literature. I apply new methods to reconceptualize that migratory experience as shaped by social and cultural processes, albeit ones that interacted with nationalist state policies. I provide a multilayered macro- and microanalysis of the process of Jewish emigration from northern Morocco and point to the transregional, interpersonal, communal, and institutional networks that jointly shaped the dynamic character and pace of migration to Israel (and to Europe and the Americas) among local Jews.
Eurytrema coelomaticum: updated morphology of adult worms using advanced microscopy experiments
Authors: Leite K.G. , Lopes-Torres E.J. , Souza J.G.R. , Neves R.H. , Gomes D.C. , Machado-Silva J.R.
Published: January 2020

Eurytrema coelomaticum is a digenean flatworm of ruminants that is the causative agent of eurytrematosis, a disease of veterinary health concern. Although modern techniques of morphological analysis have provided new insights about the morphology and anatomy of parasitic helminths, most studies on E. coelomaticum adults are based on conventional light microscopy. In the present study, a combined approach using brightfield, fluorescence, confocal and scanning electron microscopies (SEMs), together with the cryofracture technique, have updated morphological data on E. coelomaticum recovered from cattle in Rio de Janeiro State, Brazil. Light microscopy confirmed the presence of several structures present in the current description, such as suckers, pharynx, oesophagus, intestinal bifurcation and the cirrus-sac. Fluorescence stereomicroscopy revealed for the first time the cubic crystal protein inclusions in the forebody, which were further detailed by confocal and SEMs. Confocal microscopy provided detailed information of the muscular architecture associated with the attachment structures (suckers), digestive system (pharynx and oesophagus), egg-forming complex (ovary, Mehlis’ gland and Laurer's canal) and male reproductive system, which are similar to those found in other digenean flukes. SEM images of cryofractured parasites showed mucus and developing eggs within uterine loops. It was demonstrated that the combination of advanced tools generated complementary information, confirming the importance of experimental morphology in parasitology. Therefore, the knowledge of the adult structural organization of E. coelomaticum was improved and this work has contributed to propose new morphological criteria to evaluate the effects of antiparasitic drugs on flukes of medical and veterinary importance.
Using lizards to evaluate the influence of average abundance on the variance of endoparasites in semiarid areas: dispersion and assemblage structure
Authors: Araujo Filho J.A. , Teixeira A.A.M. , Teles D.A. , Rocha S.M. , Almeida W.O. , Mesquita D.O. , Lacerda A.C.F.
Published: January 2020

The distribution of parasites within host populations and communities, and the mechanisms responsible for these patterns, are poorly understood aspects of wildlife parasitology. Here, we evaluate the influence of the average abundance of endoparasite variance, using endoparasites of lizards from the Caatinga domain (semiarid region), north-eastern Brazil. We hypothesized that, due to the high number of generalist endoparasite species, they may occur randomly throughout host populations in an aggregate pattern. In addition, we evaluated the degree to which sample variance is influenced by the average abundance of endoparasite species, patterns of co-occurrence and dominance among endoparasite species and similarities between abundance and the richness of endoparasite infracommunities in several host species. Between September 2015 and February 2016, 2141 lizards (1233 infected) from 16 species were collected from six Caatinga areas. In total, 25,687 endoparasites were collected, which belonged to 13 species including nematodes, pentastomids, cestodes, trematodes and acanthocephalans. Parasite–host associations documented here included 39 newly identified interactions. Endoparasites occurred in a typical aggregate pattern of distribution within their hosts; there was no measurable preference related to the acquisition of hosts by endoparasites. Despite the new records, endoparasites found were commonly associated with lizards in Caatinga environments, which may reflect fauna composed of generalist endoparasite species.
Comparison of endoscopic butterfly-inlay versus endoscopic push-through myringoplasty in repairing anterior perforations of the tympanic membrane
Authors: Gülşen S , Erden B
Published: January 2020

Objective

The aim of the present study was to evaluate the surgical and functional results of endoscopic butterfly-inlay cartilage myringoplasty and endoscopic push-through myringoplasty in the treatment of anterior perforation of the tympanic membrane.

Method

This open-label randomised clinical study was conducted on 71 patients with small- and medium-sized anterior perforations of the tympanic membrane. Graft success rate, hearing results, operative time and complications were analysed.

Results

Graft success rates for endoscopic butterfly-inlay cartilage myringoplasty and endoscopic push-through myringoplasty were 94.1 and 91.8 per cent, respectively (p > 0.05). Post-operative air–bone gap values significantly improved in both the endoscopic butterfly-inlay cartilage myringoplasty and endoscopic push-through myringoplasty groups. The average operative time was significantly shorter in the endoscopic butterfly-inlay cartilage myringoplasty group (31.5 minutes) compared to the endoscopic push-through myringoplasty group (41.7 minutes; p < 0.05).

Conclusion

When compared with the endoscopic push-through myringoplasty, the endoscopic butterfly-inlay cartilage myringoplasty technique, which is technically easier to perform, does not require packing and has a shorter operating time. It is a reasonable approach for repair of anterior perforations of the tympanic membrane.
Life history traits and interactions of Stylops advarians (Strepsiptera) with its bee host, Andrena milwaukeensis
Authors: Balzer Zach S. , Davis Arthur R.
Published: January 2020

Specimens of Stylops advarians were sampled by collecting foraging bees of Andrena milwaukeensis along the South Saskatchewan River within Saskatoon, Saskatchewan. As the foraging season progressed from early May till late June over three consecutive years (2016–2018), most stylopized bees possessed endoparasitic adult (neotenic) females of S. advarians protruding from the bee gaster's dorsum. In contrast, very few adult bees stylopized by male puparia, and no free-living males, were encountered. Over the sampling period, prevalence remained around 22% each year; mean intensity was 1.2 (range of 1–3 female parasites per bee); and parasite abundance was 0.27. Also newly reported for Stylops is the occurrence of one bee bearing four Stylops (two neotenic females and two males with puparia), plus another bee with a male puparium extruded from its gaster's sternites. Around 2 May each year, a high proportion of the earliest captured female bees were stylopized. However, non-stylopized female bees typically were not encountered until about 10 days later, suggesting the parasites manipulate female bee hosts to emerge earlier, in close synchrony to male bee emergence. First-instar larvae of S. advarians appeared from 22–25 May, indicating that adults of S. advarians matured and mated at similar times each season.
Detection methods and prevalence of transmission stages of Toxoplasma gondii, Giardia duodenalis and Cryptosporidium spp. in fresh vegetables: a review
Authors: Berrouch Salma , Escotte-Binet Sandie , Harrak Rajae , Huguenin Antoine , Flori Pierre , Favennec Loïc , Villena Isabelle , Hafid Jamaleddine
Published: January 2020

One of the ways of human parasitic infection is the accidental ingestion of vegetables contaminated with parasites, which represents a major human health hazard. This non-exhaustive review aims to evaluate studies carried out on five types of vegetables (lettuce, parsley, coriander, carrot and radish) since 2000, particularly the methods used for recovery, concentration, detection and identification of protozoan parasites such as Toxoplasma gondii, Giardia duodenalis and Cryptosporidium spp., and the results of each work. Various studies have determined the presence of pathogenic parasites in fresh vegetables with different rates; this variation in rate depends particularly on the detection method used which is related to each parasite and each vegetable type. The variation in parasitic prevalence in food could be due to different factors such as the geographical location, the size of analysed samples and the methods used for parasite detection.
Antarctica and Africa: Narrating alternate futures
Authors: Lavery Charne
Published: January 2020

Africa has been marginalised in the history of Antarctica, a politics of exclusion (with the exception of Apartheid South Africa) reflected unsurprisingly by a dearth of imaginative, cultural and literary engagement. But, in addition to paleontological and geophysical links, Antarctica has increasing interrelationship with Africa’s climactic future. Africa is widely predicted to be the continent worst affected by climate change, and Antarctica and its surrounding Southern Ocean are uniquely implicated as crucial mediators for changing global climate and currents, rainfall patterns, and sea level rise. This paper proposes that there are in fact several ways of imagining the far South from Africa in literary and cultural terms. One is to read against the grain for southern-directed perspectives in existing African literature and the arts, from southern coastlines looking south; another is to reexamine both familiar and new, speculative narratives of African weather – drought, flood and change – for their Antarctic entanglements. In the context of ongoing work on postcolonial Antarctica and calls to decolonise Antarctic studies – such readings can begin to bridge the Antarctica–Africa divide.
Older Adults’ Views on the Repositioning of Primary and Community Care
Authors: Hulko Wendy , Mirza Noeman , Seeley Lori
Published: January 2020

Older adults are rarely consulted on health care restructuring. To address this gap, our study explored older adults’ views on “repositioning”, a restructuring initiative to support independent living for older adults with complex chronic disease (CCD). We collected and analysed data from 83 older adults living in one small city and nine rural small towns where “repositioning” of primary and community care was occurring. Average participant age was 75 years; 56 (67%) were women, 44 (53%) had CCD, and 20 (24%) identified as Indigenous or South Asian. The four themes were: unfamiliarity with repositioning; optimism versus skepticism; improving primary and community care (through better home care, improved transportation, and more doctors); and, playing an active role to effect change. For repositioning to be successful, diverse service users must be fully included; rural-dwelling older adults’ priorities for primary and community care need to be addressed, rather than using a “cookie-cutter” approach.
Willem Banning and the Reform of Socialism in the Netherlands
Authors: Molendijk Arie L.
Published: January 2020

In 1947 the liberal Protestant minister Willem Banning drafted a new programme for the Labour Party, in which the party dropped the Marxist view of history and class struggle. New Labour in the Netherlands was envisioned as a party that strove for a democratic and just society. Banning's role in reforming the Labour Party was part of his broader project of breaking down structures of socio-political segregation that had existed since the end of the nineteenth century. Banning argued that the Labour Party had to abandon its atheist ideology to open up to Protestants and Catholics. This article will examine Banning's views and ideals and show how he contributed to the transformation of Labour into a social democratic party and seek answer to the question: how could a liberal Protestant minister become the main ideologue of the Labour Party?
Establishment of a feeder and serum-free culture system for human embryonic stem cells
Authors: Wang LiYun , Zhang RuiNa , Ma RongHua , Jia GongXue , Jian ShengYan , Zeng XiangHui , Xiong ZhengFang , Li BinYe , Li Chen , Lv ZhenZhen , Bai Xue
Published: January 2020

Stem cells are an immortal cell population capable of self-renewal; they are essential for human development and ageing and are a major focus of research in regenerative medicine. Despite considerable progress in differentiation of stem cellsin vitro, culture conditions require further optimization to maximize the potential for multicellular differentiation during expansion. The aim of this study was to develop a feeder-free, serum-free culture method for human embryonic stem cells (hESCs), to establish optimal conditions for hESC proliferation, and to determine the biological characteristics of the resulting hESCs. The H9 hESC line was cultured using a homemade serum-free, feeder-free culture system, and growth was observed. The expression of pluripotency proteins (OCT4, NANOG, SOX2, LIN28, SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81) in hESCs was determined by immunofluorescence and western blotting. The mRNA expression levels of genes encoding nestin, brachyury and α-fetoprotein in differentiated H9 cells were determined by RT-PCR. The newly developed culture system resulted in classical hESC colonies that were round or elliptical in shape, with clear and neat boundaries. The expression of pluripotency proteins was increased, and the genes encoding nestin, brachyury, and α-fetoprotein were expressed in H9 cells, suggesting that the cells maintainedin vitrodifferentiation capacity. Our culture system containing a unique set of components, with animal-derived substances, maintained the self-renewal potential and pluripotency of H9 cells for eight passages. Further optimization of this system may expand the clinical application of hESCs.
Cardiac functions and aortic elasticity in children with inflammatory bowel disease: effect of age at disease onset
Authors: Erolu Elif , Polat Esra
Published: January 2020

Aim:

Childhood onset inflammatory bowel disease is more aggressive and has rapidly progressive clinical course than adult inflammatory bowel disease. Early-onset inflammatory bowel disease has more severe clinical progression as a subspecialised group of monogenic inflammatory bowel disease. We studied cardiac functions and aortic elasticity in children with early- and late-onset inflammatory bowel disease in remission period.

Methods:

Thirty-three paediatric patients were divided into subgroups according to age of disease onset (<10 and >10 years of age). Twenty-five healthy children were admitted as control group. M-Mode echocardiography and pulsed wave Doppler echocardiography were performed. Strain, distensibility, stiffness index of ascending, and abdominal aorta were evaluated.

Results:

Interventricular septum (mm) and left ventricular end-systolic diameter were higher (6.9 ± 1.2, 26.2 ± 4.6) in early-onset inflammatory bowel disease patients than control patients (6.1 ± 1.27, 22.7 ± 4.12) (p = 0.050, p = 0.050). Mitral E/E′ ratio and myocardial performance index were increased in inflammatory bowel disease and early-onset inflammatory bowel disease groups than control group (p = 0.046, p = 0.04; p = 0.023, p = 0.033). Diastolic functions were found to be impaired in inflammatory bowel disease and early-onset inflammatory bowel disease groups according to control group, while there was no difference between late-onset inflammatory bowel disease and control groups in terms of diastolic functions. Mitral E/A ratio was lower in inflammatory bowel disease patients and early-onset inflammatory bowel disease patients (1.46 ± 0.32, 1.4 ± 0.21) than control patients (1.70 ± 0.27) (p = 0.013, p = 0.004). Aortic elasticity did not differ between groups.

Conclusion:

Chronic low-grade inflammation has effects on left ventricular diameters and diastolic function in remission period. Aortic elasticity is not affected in our study groups.
Single-dose pharmacokinetics of amphetamine extended-release tablets compared with amphetamine extended-release oral suspension
Authors: Pardo Antonio , Kando Judith C. , King Thomas R. , Rafla Eman , Herman Barry K.
Published: January 2020

Objective

Evaluate the relative bioavailability of single-dose amphetamine extended-release tablet (AMPH ER TAB) 20 mg, swallowed whole or chewed, and amphetamine extended-release oral suspension (AMPH EROS) 2.5 mg/mL; evaluate food effect on AMPH ER TAB.

Methods

Healthy volunteers (18–55 years) were randomized to 1 dose of AMPH ER TAB 20 mg swallowed (fasted), chewed (fed/fasted), or 20 mg AMPH EROS (fasted). A crossover study design was used. Plasma samples were collected each period predose and at time points to 60 hours postdose. d- and l-amphetamine were measured and pharmacokinetic (PK) was calculated (90% confidence intervals of the ratios of the plasma levels) for AUC0-t, AUC0-∞, and Cmax. Comparative relative bioavailability between formulations was determined when ratios were within 80% and 125%. Safety was also assessed.

Results

Thirty-two subjects completed the study. AMPH ER TAB swallowed versus AMPH EROS (fasted): for d- and l-amphetamine, the total and peak exposure was similar: d: AUC0-t: 100.68% to 108.08%, AUC0-∞: 101.47% to 109.52%, Cmax: 98.10% to 103.17%; l: AUC0-t: 100.31% to 108.57%, AUC0-∞: 101.27% to 111.09%, Cmax: 98.2% to 103.37%. For d- and l-amphetamine when the tablet is swallowed whole, Tmax was 5.00 hours (with a range of 2.00–9.00 hours). AMPH ER TAB chewed versus AMPH EROS (fasted): for d- and l-amphetamine, the total and peak exposure was similar: d: AUC0-t: 99.23% to 106.62%, AUC0-∞: 99.58% to 107.59%, Cmax: 99.91% to 105.14%; l: AUC0-t: 98.16% to 106.35%, AUC0-∞: 98.44% to 108.11%, Cmax: 99.53% to 104.75%. For d- and l-amphetamine when the tablet has been chewed, Tmax was 5.00 hours (with a range of 3.00-7.00 hours). PK results were similar for patients in the fasted and fed groups, indicative of no presence of food effect. No serious adverse events (AEs) were reported, overall AE profiles between the tablet and oral suspension were comparable without any unanticipated safety concerns.

Conclusions

Single doses of AMPH ER TAB for both d- and l-amphetamine demonstrated comparable bioavailability to a 20 mg dose of AMPH EROS, 2.5 mg/mL under fasted conditions when chewed and swallowed whole, and demonstrated equivalent peak and overall exposure without apparent food effect. AMPH ER TAB was well-tolerated and consistent with adverse events noted in other amphetamine formulations.
Women’s Experiences of Homelessness: A Longitudinal Study
Authors: Bretherton Joanne
Published: January 2020

Drawing on the results of a qualitative longitudinal analysis of the experiences of homeless people using an employment related programme in the UK, this article explores the experiences of homeless women. Research focused on women’s trajectories through homelessness remains unusual and this comparatively large study provided an opportunity to look at a group of homeless women over time. The results from 136 in-depth interviews with forty-seven homeless women are reported. The interviews explored their lives prior to becoming homeless, their routes into homelessness and their trajectories through and out of homelessness. The article does not compare experiences across gender, focusing solely on women, because the existing evidence base focuses largely on the experiences of lone homeless men. The goals of the article are twofold, first to add to the existing evidence on women’s experiences of homelessness and second to add to emergent debates on whether gender is associated with differentiated trajectories through homelessness.
COMPARISON OF LOCAL RELATIVE CHARACTERS AND THE ICHINO–IKEDA CONJECTURE FOR UNITARY GROUPS
Authors: Beuzart-Plessis Raphaël
Published: January 2020

In this paper, we prove a conjecture of Wei Zhang on comparison of certain local relative characters from which we draw some consequences for the Ichino–Ikeda conjecture for unitary groups.
Evidences of Plug Pressurization Enhancing Magma Fragmentation During the September 2016 Basaltic Eruption at Piton de la Fournaise (La Réunion Island, France)
Authors: Thivet Simon , Gurioli Lucia , Di Muro Andrea , Derrien Allan , Ferrazzini Valérie , Gouhier Mathieu , Coppola Diego , Galle Bo , Arellano Santiago
Published: January 2020

In September 2016, Piton de la Fournaise volcano, well known for its effusive and Hawaiian fountaining activity, produced, at the end of the eruption, an unusual phase of pulsating ash and bomb emission. Integration of geophysical data, with textural and petrological analysis of the samples, allowed us to constrain the main factors that controlled this sudden shift in activity, potentially dangerous for the tourist population that usually approach these “gentle” eruptive sites. Volcanic tremor, lava discharge rates, fountain heights, and SO2 emission changed rapidly during the eruption. Grain size and componentry of the tephra beds evolved from unimodal all along the sequence to bimodal on the last day of the activity, reflecting the contribution of both Hawaiian fountaining at the main vent (Vent A) and transient explosive activity at the second vent (Vent B). Hawaiian fountaining produced highly vesicular and almost microlite‐free tephra (golden pumice and fluidal scoria) while transient explosive activity emitted denser and crystal‐rich tephra (sideromelane and tachylite scoria) sometimes mingled with vesicular fragments. Permeability measurements on lapilli and bomb‐sized samples reveal that golden pumice and fluidal scoria were more gas‐permeable than the sideromelane and tachylite ones, while textural and chemical analyses of the ash support the hypothesis that these sideromelane and tachylite components were inherited from the subsurface crystallization of the initial golden pumice and fluidal scoria components. We thus suggest that Vent B accumulated a plug of degassed, cooled, and low‐permeable magma, which modulated overpressure pulses under the late input of ascending magma.
Changing Flow Paths Caused by Simultaneous Shearing and Fracturing Observed During Hydraulic Stimulation
Authors: Krietsch H. , Villiger L. , Doetsch J. , Gischig V. , Evans K. F. , Brixel B. , Jalali M. R. , Loew S. , Giardini D. , Amann F.
Published: January 2020

We monitored the seismohydromechanical rock mass response to high‐pressure fluid injection during a decameter‐scale hydraulic stimulation experiment in crystalline rock at the Grimsel Test Site, Switzerland. Time series recorded at two pressure monitoring locations show abrupt pressure increases that change in amplitude and appearance between subsequent stimulation cycles. Induced seismicity correlates with the propagation of one of these pressure fronts. Deformation data along the same shear zone shows permanent fracture dislocation preceded by strong transient fracture opening. We interpret these observations as nonlinear pressure diffusion along flow channels that reorganize in response to hydromechanical effects during stimulation. Combining these observations with the in situ stress field estimated before stimulation, we argue that the underlying hydromechanical processes involve mixed‐mode stimulation with both Mode I and II/III fracture dislocation.
Detections of Water Vapor Increase Over the North Polar Troughs on Mars as Observed by CRISM
Authors: Khayat Alain SJ. , Smith Michael D. , Guzewich Scott D.
Published: January 2020

The Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) onboard the Mars Reconnaissance Orbiter has been observing the north polar layered deposits (NPLD) of Mars. Polar wind circulations are instrumental in shaping the NPLD. In particular, the downslope (katabatic) flows help carve the spiral‐shaped geological depressions, known as the polar troughs, and appropriate environmental conditions develop katabatic jumps that favor substantial water abundance changes over the troughs. Utilizing CRISM retrievals, we report the first observational evidence of the sharp increase in the water vapor abundance over polar troughs on Mars at high resolution (~320 m). This has a direct influence on the dynamic evolution of ice migration in the northern polar cap, the major source of atmospheric water on Mars.
The Potential Impact of Nuclear Conflict on Ocean Acidification
Authors: Lovenduski Nicole S. , Harrison Cheryl S. , Olivarez Holly , Bardeen Charles G. , Toon Owen B. , Coupe Joshua , Robock Alan , Rohr Tyler , Stevenson Samantha
Published: January 2020

We demonstrate that the global cooling resulting from a range of nuclear conflict scenarios would temporarily increase the pH in the surface ocean by up to 0.06 units over a 5‐year period, briefly alleviating the decline in pH associated with ocean acidification. Conversely, the global cooling dissolves atmospheric carbon into the upper ocean, driving a 0.1 to 0.3 unit decrease in the aragonite saturation state (
) that persists for
10 years. The peak anomaly in pH occurs 2 years post conflict, while the
anomaly peaks 4‐ to 5‐years post conflict. The decrease in
would exacerbate a primary threat of ocean acidification: the inability of marine calcifying organisms to maintain their shells/skeletons in a corrosive environment. Our results are based on sensitivity simulations conducted with a state‐of‐the‐art Earth system model integrated under various black carbon (soot) external forcings. Our findings suggest that regional nuclear conflict may have ramifications for global ocean acidification.
Evidence for auxiliary anaerobic metabolism in obligately aerobic Zetaproteobacteria
Authors: Jain Abhiney , Gralnick Jeffrey A
Published: January 2020

Zetaproteobacteria are obligate chemolithoautotrophs that oxidize Fe(II) as an electron and energy source, and play significant roles in nutrient cycling and primary production in the marine biosphere. Zetaproteobacteria thrive under microoxic conditions near oxic–anoxic interfaces, where they catalyze Fe(II) oxidation faster than the abiotic reaction with oxygen. Neutrophilic Fe(II) oxidizing bacteria produce copious amounts of insoluble iron oxyhydroxides as a by-product of their metabolism. Oxygen consumption by aerobic respiration and formation of iron oxyhydroxides at oxic–anoxic interfaces can result in periods of oxygen limitation for bacterial cells. Under laboratory conditions, all Zetaproteobacteria isolates have been shown to strictly require oxygen as an electron acceptor for growth, and anaerobic metabolism has not been observed. However, genomic analyses indicate a range of potential anaerobic pathways present in Zetaproteobacteria. Heterologous expression of proteins from Mariprofundus ferrooxydans PV-1, including pyruvate formate lyase and acetate kinase, further support a capacity for anaerobic metabolism. Here we define auxiliary anaerobic metabolism as a mechanism to provide maintenance energy to cells and suggest that it provides a survival advantage to Zetaproteobacteria in environments with fluctuating oxygen availability.
L-Plastin deficiency produces increased trabecular bone due to attenuation of sealing ring formation and osteoclast dysfunction
Authors: Chellaiah Meenakshi A. , Moorer Megan C. , Majumdar Sunipa , Aljohani Hanan , Morley Sharon C. , Yingling Vanessa , Stains Joseph P.
Published: January 2020

Bone resorption requires the formation of complex, actin-rich cytoskeletal structures. During the early phase of sealing ring formation by osteoclasts, L-plastin regulates actin-bundling to form the nascent sealing zones (NSZ). Here, we show that L-plastin knockout mice produce osteoclasts that are deficient in the formation of NSZs, are hyporesorptive, and make superficial resorption pits in vitro. Transduction of TAT-fused full-length L-plastin peptide into osteoclasts from L-plastin knockout mice rescued the formation of nascent sealing zones and sealing rings in a time-dependent manner. This response was not observed with mutated full-length L-plastin (Ser-5 and -7 to Ala-5 and -7) peptide. In contrast to the observed defect in the NSZ, L-plastin deficiency did not affect podosome formation or adhesion of osteoclasts in vitro or in vivo. Histomorphometry analyses in 8- and 12-week-old female L-plastin knockout mice demonstrated a decrease in eroded perimeters and an increase in trabecular bone density, without a change in bone formation by osteoblasts. This decrease in eroded perimeters supports that osteoclast function is attenuated in L-plastin knockouts. Micro-CT analyses confirmed a marked increase in trabecular bone mass. In conclusion, female L-plastin knockout mice had increased trabecular bone density due to impaired bone resorption by osteoclasts. L-plastin could be a potential target for therapeutic interventions to treat trabecular bone loss.
Characterization of virus-mediated immunogenic cancer cell death and the consequences for oncolytic virus-based immunotherapy of cancer
Authors: Ma Jing , Ramachandran Mohanraj , Jin Chuan , Quijano-Rubio Clara , Martikainen Miika , Yu Di , Essand Magnus
Published: January 2020

Oncolytic viruses have the potential to induce immunogenic cell death (ICD) that may provoke potent and long-lasting anti-cancer immunity. Here we aimed to characterize the ICD-inducing ability of wild-type Adenovirus (Ad), Semliki Forest virus (SFV) and Vaccinia virus (VV). We did so by investigating the cell death and immune-activating properties of virus-killed tumor cells. Ad-infection of tumor cells primarily activates autophagy, but also activate events of necroptotic and pyroptotic cell death. SFV infection on the other hand primarily activates immunogenic apoptosis while VV activates necroptosis. All viruses mediated lysis of tumor cells leading to the release of danger-associated molecular patterns, triggering of phagocytosis and maturation of dendritic cells (DCs). However, only SFV-infected tumor cells triggered significant T helper type 1 (Th1)-cytokine release by DCs and induced antigen-specific T-cell activation. Our results elucidate cell death processes activated upon Ad, SFV, and VV infection and their potential to induce T cell-mediated anti-tumor immune responses. This knowledge provides important insight for the choice and design of therapeutically successful virus-based immunotherapies.
TNAP inhibition attenuates cardiac fibrosis induced by myocardial infarction through deactivating TGF-β1/Smads and activating P53 signaling pathways
Authors: Gao Lei , Wang Li-you , Liu Zhi-qiang , Jiang Dan , Wu Shi-yong , Guo Yu-qian , Tao Hong-mei , Sun Min , You Lin-na , Qin Shu , Cheng Xiao-cheng , Xie Jun-shi , Chang Guang-lei , Zhang Dong-ying
Published: January 2020

Tissue nonspecific alkaline phosphatase (TNAP) is expressed widely in different tissues, modulating functions of metabolism and inflammation. However, the effect of TNAP on cardiac fibrosis remains controversial and needs to be further studied. The present study aims to investigate the role of TNAP on myocardial infarction (MI)-induced fibrosis and its mechanism. TNAP was upregulated in patients with MI, both in serum and injured hearts, and predicted in-hospital mortality. TNAP was also significantly upregulated after MI in rats, mostly in the border zone of the infarcted hearts combined with collagen synthesis. Administration of TNAP inhibitor, tetramisole, markedly improved cardiac function and fibrosis after MI. In the primary cultures of neonatal rat cardiac fibroblasts (CFs), TNAP inhibition significantly attenuated migration, differentiation, and expression of collagen-related genes. The TGF-β1/Smads signaling suppression, and p-AMPK and p53 upregulation were involved in the process. When p53 inhibitor was administered, the antifibrotic effect of TNAP inhibition can be blocked. This study provides a direct evidence that inhibition of TNAP might be a novel regulator in cardiac fibrosis and exert an antifibrotic effect mainly through AMPK-TGF-β1/Smads and p53 signals.
RETRACTED ARTICLE: Exosome-transmitted miR-567 reverses trastuzumab resistance by inhibiting ATG5 in breast cancer
Authors: Han Mingli , Hu Jianguo , Lu Pengwei , Cao Hui , Yu Chao , Li Xiangke , Qian Xueke , Yang Xue , Yang Yunqing , Han Na , Dou Dongwei , Zhang Fan , Ye Mulin , Yang Changcheng , Gu Yuanting , Dong Huaying
Published: January 2020

Trastuzumab is commonly used in the treatment of human epidermal growth factor receptor-2 positive (HER-2+) breast cancer, but its efficacy is often limited by the emergence of chemoresistance. Recent studies indicate that exosomes act as vehicles for exchange of genetic cargo between heterogeneous populations of tumor cells, engendering a transmitted drug resistance for cancer development and progression. However, the specific contribution of breast cancer-derived exosomes is poorly understood. In this study, publicly available expression profiling data from breast cancer and bioinformatics analyses were used to screen potential miRNAs in trastuzumab resistance. A series of gain- or loss-functional assays were performed to define the function of miR-567 and ATG5 in trastuzumab resistance and autophagy, both in vitro and in vivo. Our results showed that miR-567 was significantly decreased in trastuzumab-resistant patients compared with responding patients. Moreover, miR-567 was also downregulated in trastuzumab-resistant cells compared with parental cells. Overexpression of miR-567 reversed chemoresistance, whereas silence of miR-567 induced trastuzumab resistance, both in vitro and in vivo. In addition, enhanced miR-567 could be packaged into exosomes, incorporated into receipt cells, suppressing autophagy and reversed chemoresistance by targeting ATG5. To conclude, exosomal miR-567 plays a key role in reversing trastuzumab resistance via regulating autophagy, indicating it may be a promising therapeutic target and prognostic indicator for breast cancer patients.
The negative cofactor 2 complex is a key regulator of drug resistance in Aspergillus fumigatus
Authors: Furukawa Takanori , van Rhijn Norman , Fraczek Marcin , Gsaller Fabio , Davies Emma , Carr Paul , Gago Sara , Fortune-Grant Rachael , Rahman Sayema , Gilsenan Jane Mabey , Houlder Emma , Kowalski Caitlin H. , Raj Shriya , Paul Sanjoy , Cook Peter , Parker Josie E. , Kelly Steve , Cramer Robert A. , Latgé Jean-Paul , Moye-Rowley Scott , Bignell Elaine , Bowyer Paul , Bromley Michael J.
Published: January 2020

The frequency of antifungal resistance, particularly to the azole class of ergosterol biosynthetic inhibitors, is a growing global health problem. Survival rates for those infected with resistant isolates are exceptionally low. Beyond modification of the drug target, our understanding of the molecular basis of azole resistance in the fungal pathogen Aspergillus fumigatus is limited. We reasoned that clinically relevant antifungal resistance could derive from transcriptional rewiring, promoting drug resistance without concomitant reductions in pathogenicity. Here we report a genome-wide annotation of transcriptional regulators in A. fumigatus and construction of a library of 484 transcription factor null mutants. We identify 12 regulators that have a demonstrable role in itraconazole susceptibility and show that loss of the negative cofactor 2 complex leads to resistance, not only to the azoles but also the salvage therapeutics amphotericin B and terbinafine without significantly affecting pathogenicity.