bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of auxin homeostasis and response in nitrogen limitation and dark stimulation of adventitious root formation in petunia cuttings
Authors: Yang Huaiyu , Klopotek Yvonne , Hajirezaei Mohammad R , Zerche Siegfried , Franken Philipp , Druege Uwe
Published: June 2019

Background and Aims

Adventitious root (AR) formation in Petunia hybrida is inhibited by low nitrogen fertilization of stock plants but promoted by dark incubation of cuttings before planting. We investigated whether the plant hormone auxin is involved in nitrogen- and dark-mediated AR formation.

Methods

Concentrations of indole-3-acetic acid (IAA) and RNA accumulation of genes controlling auxin homeostasis and function were monitored in the stem base in response to high versus low nitrogen supply to stock plants and to temporal dark vs. light exposure of cuttings by use of GC-MS/MS, a petunia-specific microarray and quantitative RT-PCR. Auxin source capacity, polar auxin transport in cuttings and auxin concentration in the rooting zone were manipulated to investigate the functional contribution of auxin homeostasis and response to the effects of nitrogen fertilization and dark exposure on rooting.

Key Results

The nitrogen content of cuttings had only a marginal effect on IAA concentration in the stem base. Dark incubation enhanced the accumulation of IAA in the stem base during AR induction independent of nitrogen level. Early IAA accumulation in the dark depended on the upper shoot as an auxin source and was enhanced after apical IAA supply. Dark exposure stimulated RNA accumulation of auxin-related genes. In particular, expression of Ph-PIN1 and of genes controlling auxin signalling, including Ph-IAA14, Ph-ARF8, Ph-ARF10 and Ph-SAUR14, was enhanced, while the latter four were repressed in nitrogen-limited cuttings, particularly in the dark. Dark stimulation of rooting depended on polar auxin transport. Basal auxin application partially substituted the effect of dark exposure on rooting, whereas the auxin response of AR formation was strongly depressed by nitrogen limitation.

Conclusions

Increased auxin delivery from the upper shoot and enhanced auxin signalling in the stem base contribute to dark-stimulated AR formation, while nitrogen limitation inhibits AR formation downstream of the auxin signal.
Outbreeding and inbreeding strategies in herbaceous-shrubby communities in the Venezuelan Gran Sabana Plateau
Authors: Ramírez Nelson , Hokche Omaira
Published: June 2019

Breeding system, sexual system, temporal variation in sex expression and herkogamy were evaluated in seven herbaceous-shrubby communities from the Gran Sabana Plateau, Venezuela. This analysis was conducted considering the life form, substrate type, succulence, carbon metabolism, nutritional relation, successional stage, pollination system specificity and endemism of plant species. Of the 348 plant species studied, 73.8 % were hermaphrodite, 16.9 % were monoecious and 9.2 % were dioecious. Plant sexual systems such as dichogamy and herkogamy were associated with life form, nutritional relations, carbon metabolism and pollination systems. Most species were adichogamous, followed by protandrous and protogynous. Protandry was high for perennial herbs, annual herbs and trees, and protogyny was most frequent in perennial herbs. Protandrous and protogynous species were frequently anemophilous. Herkogamy was higher than non-herkogamy. Herkogamy was higher for trees, shrubs and liana; higher in monophilous and lower in anemophilous species. Most of the hermaphrodites were herkogamous and adichogamous species. In contrast, monoecy were commonly perennial herb and dichogamous species and frequently associated with anemophily. Dioecious species were trees and shrubs and with polyphilous pollination. Dioecy was the most frequent sexual system for endemic species. Hermaphrodite species were similarly distributed across plant communities. Monoecy was slightly higher for savanna and fallow than the other communities, and dioecy was higher for shrublands and secondary bushland. Most plant species were non-agamospermous, non-spontaneous self-pollinated and xenogamous. Partially self-incompatible dominated, followed by self-incompatible, partially cross-incompatible and the lowest frequency corresponded to cross-incompatible species. All these results are discussed in the context of evolutionary and ecological trends.
Association between pre-ablation bariatric surgery and atrial fibrillation recurrence in morbidly obese patients undergoing atrial fibrillation ablation
Authors: Donnellan Eoin , Wazni Oussama M , Kanj Mohamed , Baranowski Bryan , Cremer Paul , Harb Serge , McCarthy Cian P , McEvoy John W , Elshazly Mohamed B , Aagaard Philip , Tarakji Khaldoun G , Jaber Wael A , Schauer Philip R , Saliba Walid I
Published: June 2019

Aims

Obesity decreases arrhythmia-free survival after atrial fibrillation (AF) ablation by mechanisms that are not fully understood. We investigated the impact of pre-ablation bariatric surgery (BS) on AF recurrence after ablation.

Methods and results

In this retrospective observational cohort study, 239 consecutive morbidly obese patients (body mass index ≥40 kg/m2 or ≥35 kg/m2 with obesity-related complications) were followed for a mean of 22 months prior to ablation. Of these patients, 51 had BS prior to ablation, and our primary outcome was whether BS was associated with a lower rate of AF recurrence during follow-up. Adjustment for confounding was performed with multivariable Cox proportional hazard models and propensity-score based analyses. During a mean follow-up of 36 months after ablation, 10/51 patients (20%) in the BS group had recurrent AF compared with 114/188 (61%) in the non-BS group (P < 0.0001). In the BS group, 6 patients (12%) underwent repeat ablation compared with 77 patients (41%) in the non-BS group, (P < 0.0001). On multivariable analysis, the association between BS and lower AF recurrence remained significant. Similarly, after weighting and adjusting for the inverse probability of the propensity score, BS was still associated with a lower hazard of AF recurrence (hazard ratio 0.14, 95% confidence interval 0.05–0.39; P = 0.002).

Conclusion

Bariatric surgery is associated with a lower AF recurrence after ablation. Morbidly obese patients should be considered for BS prior to AF ablation, though prospective multicentre studies should be performed to confirm our novel finding.
Understanding the interactions between wind and trees: an introduction to the IUFRO 8th Wind and Trees Conference (2017)
Authors: Gardiner Barry , Achim Alexis , Nicoll Bruce , Ruel Jean-Claude
Published: June 2019

This paper discusses the advance in our understanding of the interaction between wind and trees over the last 25 years. It does this by comparing papers in this special issue of Forestry and a companion volume in Agricultural and Forest Meteorology, based on work presented at the 8th IUFRO Wind and Trees Conference in 2017, with papers published in book format after the 1st IUFRO Wind and Trees Conference in 1993. The analysis is divided into sections on ‘airflow and tree mechanics’, ‘forest management and ecology’, ‘tree adaptation and acclimation’ and ‘modelling and statistical techniques’. It is clear that in the last 25 years large advances have been made in our understanding of airflow and turbulence within and above forest canopies and the wind flow and wind loading around and on individual trees. There have also been important developments in the mechanistic and statistical modelling of wind damage risk to forests. Much of the progress has been aided by the enormous advances in measurement systems, computer power and modelling techniques. Furthermore, this knowledge is beginning to influence the approach to temperate and boreal forest management and the development of systems to mitigate the risk of wind damage. At the same time there has been a growing awareness of the ecological impact of wind in many forests around the world, including tropical forests. However, other areas of the effect of wind on trees have progressed much less in the last 25 years. This includes the process of fatiguing in the root-soil system, both during individual storms and over longer periods, and which is known to be a critical factor in the process of windthrow. In addition the exact nature of damage propagation within forests during a storm, and then in subsequent storms, has received relatively little attention although new studies using advanced computational methods are making advances. Of particular relevance, and despite the known critical importance of tree acclimation to the wind, there have been very few studies in the last 25 years on wind acclimation in full-size trees. This is an area of enormous importance in understanding how resistance to the wind varies for different species and between areas with different wind climates. In summary, overall much has been learnt since the 1st Wind and Trees conference but there remain many intriguing and exciting challenges ahead for this multi-disciplinary subject.
Isotropic scattering coefficient of the solid earth
Authors: Sato Haruo
Published: June 2019

The isotropic scattering model is a simple mathematical model of the radiative transfer theory (RTT) for the propagation of the wave energy density in random media. There have been many measurements of the isotropic scattering coefficient of the heterogeneous solid earth medium, where the target region varies from the lower and upper mantle, the crust, sediments, volcanoes, mines, rock samples and also the crust and the upper mantle of the moon. Reported isotropic scattering coefficients increase according to some power of frequency with some scatter. We know that the RTT is well approximated by the diffusion equation in the multiple scattering regime, where the equipartition is established. Then, the transport scattering coefficient effectively functions as an isotropic scattering coefficient even if the scattering coefficient derived by the Born approximation for the random velocity fluctuation is anisotropic. Recent review of the power spectral density functions of random velocity fluctuations in the solid earth revealed from various kinds of measurements shows that their spectral envelope is well approximated by the inverse cube of wavenumber for a wide range of wavenumbers (Sato, 2019). The transport scattering coefficient derived from the spectral envelope linearly increases with frequency, which well explains the observed isotropic scattering coefficients for a wide range of frequencies. However, some reported isotropic scattering coefficients show unusual behaviour: the isotropic scattering coefficient increases as depth decreases in the crust and the upper mantle of the earth and the moon, those beneath volcanoes are larger than those in the lithosphere, and that in a sandstone sample with a large porosity is larger than that in a gabbro sample with little porosity. Those differences may suggest possible scattering contribution of pores and cracks widely distributed in addition to the scattering by random velocity fluctuations.
Subducting slab morphology and mantle transition zone upwelling in double-slab subduction models with inward-dipping directions
Authors: Lyu Tianyang , Zhu Zhiyuan , Wu Benjun
Published: June 2019

Lithospheric plates on the Earth's surface interact with each other, producing distinctive structures comprising two descending slabs. Double-slab subduction with inward-dipping directions represents an important multiplate system that is not yet well understood. This paper presents 2-D numerical models that investigate the dynamic process of double-slab subduction with inward dipping, focussing on slab geometry and mantle transition zone upwelling flow. This unique double-slab configuration limits trench motion and causes steep downward slab movement, thus forming fold piles in the lower mantle and driving upward mantle flow between the slabs. The model results show the effects of lithospheric plate properties and lower-mantle viscosity on subducting plate kinematics, overriding plate stress and upward mantle flow beneath the overriding plate. Appropriate lower-mantle strength (such as an upper–lower mantle viscosity increase with a factor of 200) allows slabs to penetrate into the lower mantle with periodical buckling. While varying the length and thickness of a long overriding plate (≥2500) does not have a substantial effect on slab geometry, its viscosity has a marked impact on slab evolution and mantle flow pattern. When the overriding plate is strong, slabs exhibit an overturned geometry and hesitate to fold. Mantle transition zone upwelling velocity depends on the speed of descending slabs. The downward velocity of slabs with a large negative buoyancy (caused by thickness or density) is very fast, inducing a significant transition zone upwelling flow. A stiff slab slowly descends into the deep mantle, causing a small upward flow in the transition zone. In addition, the temporal variation of mantle upwelling velocity shows strong correlation with the evolution of slab folding geometry. In the double subduction system with inward-dipping directions, the mantle transition zone upwelling exhibits oscillatory rise with time. During the backward-folding stage, upwelling velocity reaches its local maximum. Our results provide new insights into the deep mantle source of intraplate volcanism in a three-plate interaction system such as the Southeast Asia region.
Structural insights into the mechanisms and specificities of IgG-active endoglycosidases
Authors: Du Jonathan J , Klontz Erik H , Guerin Marcelo E , Trastoy Beatriz , Sundberg Eric J
Published: June 2019

The conserved N-glycan on Asn297 of immunoglobulin G (IgG) has significant impacts on antibody effector functions, and is a frequent target for antibody engineering. Chemoenzymatic synthesis has emerged as a strategy for producing antibodies with homogenous glycosylation and improved effector functions. Central to this strategy is the use of enzymes with activity on the Asn297 glycan. EndoS and EndoS2, produced by Streptococcus pyogenes, are endoglycosidases with remarkable specificity for Asn297 glycosylation, making them ideal tools for chemoenzymatic synthesis. Although both enzymes are specific for IgG, EndoS2 recognizes a wider range of glycans than EndoS. Recent progress has been made in understanding the structural basis for their activities on antibodies. In this review, we examine the molecular mechanism of glycosidic bond cleavage by these enzymes and how specific point mutations convert them into glycosynthases. We also discuss the structural basis for differences in the glycan repertoire that IgG-active endoglycosidases recognize, which focuses on the structure of the loops within the glycoside hydrolase (GH) domain. Finally, we discuss the important contributions of carbohydrate binding modules (CBMs) to endoglycosidase activity, and how CBMs work in concert with GH domains to produce optimal activity on IgG.
A review of assessment indicators used by Healthy Municipalities and Communities Program in Latin America and the Caribbean region
Authors: Chaparro Raul , Melendi Santiago , Santero Marilina , Seijo Mariana , Elorriaga Natalia , Belizan Maria , Rubinstein Adolfo , Irazola Vilma
Published: June 2019

The Healthy Municipalities and Communities Strategy (HMCS) was developed by the Pan American Health Organization in 1990. Evaluation and monitoring are fundamental components of health promotion policies. The aim of this study is to explore the indicators used in Latin America and the Caribbean (LAC) countries to assess the performance of HMCS. We searched MEDLINE, EMBASE, LILACS, BVSDE and Google Advanced Search for documents published between January 2000 and April 2016. We included only documents with assessment indicators of the strategy. All articles were independently assessed for eligibility by pairs of reviewers. We classified the indicators with a supporting framework proposed by O’Neill and Simard (Choosing indicators to evaluate Healthy Cities projects: a political task? Health Promot Int 2006, 21, 145–152.). Local level indicators figured far more prominently among countries and were distributed both in projects and specific activities. Regarding the evolution of the HMCS, indicators were reported in the five levels of analysis (local projects and activities, provincial, national and international networks). Empowerment was represented through the presence of active community organizations and different methods of community participation (forums, open hearing and participation maps). Public policies (such as for tobacco cessation) and bylaws adherence and changes in school’s curricula regarding healthy eating were frequently mentioned. However, this review demonstrated that impact indicators related to lifestyle changes or built environment are not clearly defined and there is a lack of indicators to measure progress in achieving change in long-term outcomes in LAC. We highlight the importance of designing validated indicators for measuring the impact of health promotion policies in partnership with each country involved.
Chronic mTORC1 inhibition rescues behavioral and biochemical deficits resulting from neuronal Depdc5 loss in mice
Authors: Yuskaitis Christopher J , Rossitto Leigh-Ana , Gurnani Sarika , Bainbridge Elizabeth , Poduri Annapurna , Sahin Mustafa
Published: June 2019

DEPDC5 is now recognized as one of the genes most often implicated in familial/inherited focal epilepsy and brain malformations. Individuals with pathogenic variants in DEPDC5 are at risk for epilepsy, associated neuropsychiatric comorbidities and sudden unexplained death in epilepsy. Depdc5flox/flox-Syn1Cre (Depdc5cc+) neuronal-specific Depdc5 knockout mice exhibit seizures and neuronal mTORC1 hyperactivation. It is not known if Depdc5cc+ mice have a hyperactivity/anxiety phenotype, die early from terminal seizures or whether mTOR inhibitors rescue DEPDC5-related seizures and associated comorbidities. Herein, we report that Depdc5cc+ mice were hyperactive in open-field testing but did not display anxiety-like behaviors on the elevated-plus maze. Unlike many other mTOR-related models, Depdc5cc+ mice had minimal epileptiform activity and rare seizures prior to seizure-induced death, as confirmed by video-EEG monitoring. Treatment with the mTORC1 inhibitor rapamycin starting after 3 weeks of age significantly prolonged the survival of Depdc5cc+ mice and partially rescued the behavioral hyperactivity. Rapamycin decreased the enlarged brain size of Depdc5cc+ mice with corresponding decrease in neuronal soma size. Loss of Depdc5 led to a decrease in the other GATOR1 protein levels (NPRL2 and NPRL3). Rapamycin failed to rescue GATOR1 protein levels but rather rescued downstream mTORC1 hyperactivity as measured by phosphorylation of S6. Collectively, our data provide the first evidence of behavioral alterations in mice with Depdc5 loss and support mTOR inhibition as a rational therapeutic strategy for DEPDC5-related epilepsy in humans.
3D Digitization in Functional Morphology: Where is the Point of Diminishing Returns?
Authors: Santana Sharlene E , Arbour Jessica H , Curtis Abigail A , Stanchak Kathryn E
Published: June 2019

Modern computational and imaging methods are revolutionizing the fields of comparative morphology, biomechanics, and ecomorphology. In particular, imaging tools such as X-ray micro computed tomography (µCT) and diffusible iodine-based contrast enhanced CT allow observing and measuring small and/or otherwise inaccessible anatomical structures, and creating highly accurate three-dimensional (3D) renditions that can be used in biomechanical modeling and tests of functional or evolutionary hypotheses. But, do the larger datasets generated through 3D digitization always confer greater power to uncover functional or evolutionary patterns, when compared with more traditional methodologies? And, if so, why? Here, we contrast the advantages and challenges of using data generated via (3D) CT methods versus more traditional (2D) approaches in the study of skull macroevolution and feeding functional morphology in bats. First, we test for the effect of dimensionality and landmark number on inferences of adaptive shifts during cranial evolution by contrasting results from 3D versus 2D geometric morphometric datasets of bat crania. We find sharp differences between results generated from the 3D versus some of the 2D datasets (xy, yz, ventral, and frontal), which appear to be primarily driven by the loss of critical dimensions of morphological variation rather than number of landmarks. Second, we examine differences in accuracy and precision among 2D and 3D predictive models of bite force by comparing three skull lever models that differ in the sources of skull and muscle anatomical data. We find that a 3D model that relies on skull µCT scans and muscle data partly derived from diceCT is slightly more accurate than models based on skull photographs or skull µCT and muscle data fully derived from dissections. However, the benefit of using the diceCT-informed model is modest given the effort it currently takes to virtually dissect muscles from CT scans. By contrasting traditional and modern tools, we illustrate when and why 3D datasets may be preferable over 2D data, and vice versa, and how different methodologies can complement each other in comparative analyses of morphological function and evolution.
Hubris, constitutionalism, and “the indissoluble unity of the Spanish nation”: The repression of Catalan secessionist referenda in Spanish constitutional law
Authors: López Bofill Hèctor
Published: June 2019

This article analyzes the struggles of the Catalan government to organize a referendum on secession and the constitutional framework invoked by the Spanish central authorities to prohibit it. The repression of secessionist referenda within the Spanish constitutional framework triggers several problematic questions concerning the role of constitutional supremacy in handling subnational secessionist challenges developed under a pacific and democratic framework. The article offers a comparison between the Spanish-Catalan case and other examples of secessionist referenda within liberal democracies, underscoring that the Spanish solution of repressing such referenda through criminal law is unique in the liberal democratic context. The article also offers a description of the political, historical, and legal circumstances surrounding the Spanish central authorities’ actions that explains the Spanish constitutional response to both the Catalan Consultation held on November 9, 2014, and the referendum on Catalan independence held on October 1, 2017. The article concludes by arguing that the prohibition of the Catalan referendum initiatives on independence and their subsequent prosecution through criminal law may cripple the basic pillars of the Spanish liberal democracy designed under the 1978 Spanish Constitution.
Surgical management of renovascular hypertension in children and young adults: a 13-year experience
Authors: Peker Oktay , Aki Fazil Tuncay , Kumbasar Ulas , Guvener Murat , Yılmaz Mustafa , Dogan Rıza , Ozaltin Fatih , Duzova Ali , Topaloglu Rezan , Peynircioglu Bora , Demircin Metin
Published: June 2019

OBJECTIVES

In this study, we aimed to evaluate the early and mid-term outcomes of surgery for renovascular hypertension (RVH) at our institution, within the last 13 years.

METHODS

We retrospectively reviewed 19 patients who underwent surgery for RVH, between 2005 and 2017. The age at operation, clinical characteristics, cause of arterial stenosis, diagnostic workup, surgical management and outcomes during the follow-up were analysed. The continuous variables were expressed as mean ± standard deviation.

RESULTS

Twelve female and 7 male patients underwent surgery for RVH. Their mean age was 17.07 ± 11.9 years (range 4–42 years). Nine patients had renal arterial stenosis, and 10 patients had midaortic syndrome (MAS). Aortorenal bypass with the saphenous vein was performed in 6 patients with renal arterial stenosis and 1 patient with MAS. An isolated thoracic aorta-abdominal aortic bypass was performed in 1 patient with MAS, and thoracic aorta-abdominal aortic bypass combined with unilateral aortarenal bypass was performed in 9 patients with MAS. The other surgical procedures performed were 2 autotransplantations and 2 unilateral nephrectomies. Among the patients with MAS, 4 underwent reoperation. The mean follow-up duration was 45.58 ± 32.7 months. Hypertension was cured in 3 patients and improved in 14 patients. The postoperative follow-up creatinine levels were similar to preoperative creatinine levels. All bypasses were patent on mid-term follow-up. One patient who underwent aortorenal bypass died 14 months postoperatively.

CONCLUSIONS

Surgical management is a suitable option for patients with RVH, who were unresponsive to medical and/or endovascular management. Surgical methods are safe and effective in children and young adults with RVH.
Successful preservation and transplant of warm ischaemic lungs from controlled donors after circulatory death by prolonged in situ ventilation during normothermic regional perfusion of abdominal organs
Authors: Palleschi Alessandro , Tosi Davide , Rosso Lorenzo , Zanella Alberto , De Carlis Riccardo , Zanierato Marinella , Benazzi Elena , Tarsia Paolo , Colledan Michele , Nosotti Mario
Published: June 2019

OBJECTIVES

Donation after circulatory death (DCD) potentially provides transplantable lungs suitable for a transplant, but in Italy, the need for 20 min of a no-touch period after cardiac arrest for legal declaration of death poses real challenges to organ preservation.

METHODS

This is a single-institution, retrospective study using data collected prospectively between October and December 2017. After the approval of the multidisciplinary DCD study group of Regione Lombardia, Maastricht category III DCD donors became eligible for combined procurement of lungs and abdominal organs. Our group subsequently established a dedicated technical protocol. Our protocol consists of a non-rapid normothermic open-lung procurement process that takes place during abdominal normothermic regional perfusion, namely without pleural topical cooling before the start of pneumoplegia. After the lung is procured according to the technique described in the article, lung function is evaluated by ex vivo lung perfusion, which is run with the low-flow, open atrium, low haematocrit technique.

RESULTS

During the study, we managed 5 controlled DCDs. In 3 cases, the lungs were successfully transplanted. All 3 patients are alive after 1 year, with good respiratory function.

CONCLUSIONS

Our approach resulted in adequate lung preservation and successful transplants without detrimental effects on abdominal organ procurement, confirming the possibility of overcoming the obstacle of a long no-touch period in a DCD setting.
Stable Manifolds of Two-dimensional Biholomorphisms Asymptotic to Formal Curves
Authors: López-Hernanz Lorena , Raissy Jasmin , Ribón Javier , Sanz-Sánchez Fernando
Published: June 2019

Let $F\in\, \textrm{Diff}\, ({\mathbb{C}}^2, 0)$ be a germ of a holomorphic diffeomorphism and let $\Gamma $ be an invariant formal curve of $F$. Assume that the restricted diffeomorphism $F|_\Gamma $ is either hyperbolic attracting or rationally neutral non-periodic (these are the conditions that the diffeomorphism $F|_\Gamma $ should satisfy, if $\Gamma $ were convergent, in order to have orbits converging to the origin). Then we prove that $F$ has finitely many stable manifolds, either open domains or parabolic curves, consisting of and containing all converging orbits asymptotic to $\Gamma $. Our results generalize to the case where $\Gamma $ is a formal periodic curve of $F$.
Efficacy and pharmacodynamics of niraparib in BRCA-mutant and wild-type intracranial triple-negative breast cancer murine models
Authors: Sambade Maria J , Van Swearingen Amanda E D , McClure Marni B , Deal Allison M , Santos Charlene , Sun Kaiming , Wang Jing , Mikule Keith , Anders Carey K
Published: June 2019

Background

Despite the poor prognosis of triple-negative breast cancer (TNBC) brain metastases, there are no approved systemic therapies. We explored the DNA-damaging poly(ADP-ribose) polymerase inhibitor (PARPi) niraparib in intracranial mouse models of breast cancer susceptibility protein (BRCA)-mutant TNBC.

Methods

Mice bearing intracranial human-derived TNBC cell lines (SUM149, MDA-MB-231Br, or MDA-MB-436) were treated with niraparib and monitored for survival; intracranial tissues were analyzed for PAR levels and niraparib concentration by mass spectrometry. RNASeq data of primary breast cancers using The Cancer Genome Atlas were analyzed for DNA damage signatures. Combined RAD51 and PARP inhibition in TNBC cell lines was assessed in vitro by colony-forming assays.

Results

Daily niraparib increased median survival and decreased tumor burden in the BRCA-mutant MDA-MB-436 model, but not in the BRCA-mutant SUM149 or BRCA-wild-type MDA-MB-231Br models despite high concentrations in intracranial tumors. RAD51 inhibitor B02 was shown to sensitize all cell lines to PARP inhibition (PARPi). In the analysis of BRCA-mutant primary human TNBCs, gene expression predictors of PARPi sensitivity and DNA repair signatures demonstrate widespread heterogeneity, which may explain the differential response to PARPi. Interestingly, these signatures are significantly correlated to RAD51 expression including PARPi sensitivity (R2 = 0.602, R2= 0.758).

Conclusions

Niraparib penetrates intracranial tumor tissues in mouse models of TNBC with impressive single-agent efficacy in BRCA-mutant MDA-MB-436. Clinical evaluation of niraparib to treat TNBC brain metastases, an unmet clinical need desperate for improved therapies, is warranted. Further compromising DNA repair through RAD51 inhibition may further augment TNBC’s response to PARPi.
Rabies Encephalitis With Myocarditis Mimicking ST-Elevation Myocardial Infarction
Authors: Park Stacy C , Crane Ian M , Pal Kavita , Cagnina R Elaine
Published: June 2019

Rabies virus infection remains a significant public health threat particularly in developing countries without effective canine vaccination programs. After symptoms develop, there is no effective treatment and mortality approaches 100%. In countries such as the United States where human rabies remains rare, initial diagnosis is often delayed. In this study, we describe a case of rabies encephalitis presenting with concern for acute ST-elevation myocardial infarction (STEMI) based on electrocardiogram, laboratory, and exam findings and briefly review the known literature on cardiac involvement of rabies virus infection.
Pasture chemoscapes and their ecological services
Authors: Villalba Juan J , Beauchemin Karen A , Gregorini Pablo , MacAdam Jennifer W
Published: June 2019

Ruminant livestock-production systems are between a rock and a hard place; they are experiencing increasing societal pressure to reduce environmental impacts in a world that demands increased food supply. Recent improvements in the understanding of the nutritional ecology of livestock by scientists may help livestock producers respond to these seemingly contradictory demands. Forages are nutrition and pharmacy centers with primary (nutrients) and plant secondary compounds (PSC; pharmaceuticals, nutraceuticals), which can provide multiple services for the proper functioning of agroecosystems. Legumes with lower contents of fiber and higher contents of nonstructural carbohydrates, coupled with different types and concentrations of PSC (e.g., condensed tannins, terpenes), create a diverse array of chemicals in the landscape (i.e., the “chemoscape”) with the potential to enhance livestock nutrition, health and welfare relative to foodscapes dominated by grasses and other conventional feeds. These PSC-containing plants may reduce methane emissions and nitrogen (N) excretion from animals while increasing animal growth rate compared with swards dominated by grasses, and provide meat quality that appeals to consumers. Condensed tannins from sainfoin and saponins from alfalfa and manure of cattle consuming these forages also reduce N mobilization in soils, reduce nutrient leaching, and increase plant-available N stores for future use. The challenge for future pastoral production systems is to design multifunctional spatiotemporal arrangements of forages with “ideal” chemical diversity for specific ecoregions, aiming to achieve sustainability while increasing production goals and improving ecosystem services. Thus, the objective of this review is to stimulate the quest for chemically and taxonomically diverse pastoral feeding systems that optimize overall productivity; reduce environmental impacts; and enhance livestock, soil, and human health.
Birth weight threshold for identifying piglets at risk for preweaning mortality
Authors: Feldpausch Julie A , Jourquin Jan , Bergstrom Jon R , Bargen Jason L , Bokenkroger Courtney D , Davis Duane L , Gonzalez John M , Nelssen Jim L , Puls Christopher L , Trout William E , Ritter Matthew J
Published: June 2019

Several studies have suggested there is a critical relationship between piglet birth weight and preweaning mortality. Thus, the objective of the current work was to identify a birth weight threshold value for preweaning mortality. Birth weight and survival data from two studies involving a combined total of 4,068 piglets from 394 litters on four commercial farms (three European, one U.S.) were compiled for a pooled, multistudy analysis. Overall preweaning mortality across the two studies was 12.2%. Key variables used in the analysis were piglet birth weight (measured within 24 h of birth) and corresponding survival outcome (dead or live) by weaning at 3–4 wk of age. A mixed effects logistic regression model was fit to estimate the relationship between preweaning mortality and birth weight. A random effect of study was included to account for overall differences in mortality between the two studies. A piecewise linear predictor was selected to best represent the drastic decrease in preweaning mortality found as birth weight increased in the range of 0.5–1.0 kg and the less extreme change in weight above 1.0 kg. The change point of the birth weight and preweaning mortality model was determined by comparing model fit based on maximizing the likelihood over the interval ranging from 0.5 to 2.3 kg birth weight. Results from the analysis showed a curvilinear relationship between birth weight and preweaning mortality where the birth weight change point value or threshold value was 1.11 kg. In the combined data set, 15.2% of pigs had birth weights ≤1.11 kg. This subpopulation of pigs had a 34.4% preweaning mortality rate and represented 43% of total preweaning mortalities. These findings imply interventions targeted at reducing the incidence of piglets with birth weights ≤1.11 kg have potential to improve piglet survivability. Additional research is needed to validate 1.11 kg as the birth weight threshold for increased risk of preweaning mortality.
Software technology in CISG contracts
Authors: Muñoz Edgardo
Published: June 2019

Software technology has changed the way businesses operate and the items traded globally. These advances demand a fast and adequate evolution of the law. This paper supports the view that the CISG is equipped with the rules needed to address recent changes in software technology; it demonstrates how the general legal principles, upon which the CISG is based, may serve to achieve a proper interpretation and supplementation of this uniform sales law. The author submits, for instance, that a dynamic notion of goods, which includes software, can be revealed by considering the parties’ main obligations under the Convention. In addition, he advocates for a modern understanding of CISG terms in order to apply the rules on contract formation to new realities. Finally, he highlights some performance issues that may arise in the sale of software, including specific methods of examination, and of giving notice of any lack of conformity.
The impact of technology on access to law and the concomitant repercussions: past, present, and the future (from the 1980s to present time)
Authors: Tajti Tibor
Published: June 2019

That technology increasingly impacts everything that is linked to law—from access to law, legal education, the services provided by the legal industry, and, increasingly, even adjudication (in-court or via alternative dispute resolution)—is a fact. The role that technology plays in these contexts varies, yet one may safely presume that the influence will intensify. In order to reflect on the future, this article canvasses and tries to draw some conclusions based on the comparison of accessibility to foreign and local law in the hard copy versus the digital and Internet-based, as well as the recently unfolding era of algorithms. The examples range from the curious encounter of Central and Eastern European socialist enterprises and law students with punitive damages and strict tortious liability known in the USA through the most recent launching of the first transnational letter of credit transaction exploiting blockchain technology. The advancements generated by technology advancements in these three stages are then reflected upon primarily from the perspectives of (i) researchers and lecturers of law as well as legal education; (ii) company boards and managements (especially foreign market-oriented business firms) formulating their business policies; and (iii) regulators as well as law and policy-makers. The article concludes with thoughts on the broader implications of enhanced access to law. In particular, it posits that technology has made the shift from ‘mechanical’ to ‘analytic access to law’ possible. Yet it also raises the more fundamental question of whether the advancements denote, and the selected examples properly illustrate, that a more fundamental shift is unfolding: a shift from governance by law to governance by technology?
More than Serendipity: The Potential to Manage Soil Carbon and Emissions While Promoting Low-Input Agriculture with Serendipitoid Mycorrhizae
Authors: Craven Kelly D. , Ray Prasun
Published: June 2019

Organic matter (OM) has a tremendous influence on the biological, chemical, and physical properties of soils, making it a vital component of healthy agricultural systems. Release of the nutrients locked within soil OM requires the activity of soil microorganisms, primarily decomposers, to transform it into nutritive forms that can be used by other microbes and plants. OM turnover is a good thing, as it liberates the locked up nutrients. However, when this liberation is accomplished by free-living decomposer communities, i.e., those not typically forming relationships with plants, the carbon may be used mostly to form microbial biomass and the rest respired as CO2, thereby aggravating greenhouse gas emission. Serendipitoid fungi (e.g., Serendipita spp.) are soil-dwelling basidiomycetes, known for decades to form mycorrhizal associations with wide variety of plant species. We hypothesize that serendipitoid fungi are capable of decomposing OM in a manner akin to free-living decomposer communities. However, serendipitoid fungi are capable of colonizing the root systems of plant community members, potentially restricting access to nutritional stores in the soil, thus imparting efficiency to the system and limiting unnecessary losses. From our perspective, this is a more rational, resilient, and ultimately more sustainable strategy than the annual addition of inorganic forms of micro- and macronutrients. Using microbes like Serendipita spp. in this manner could ultimately make the system less susceptible to nutritional fluxes that may influence productivity and stress tolerance in our crop plants.
Postoperative Delirium and Postoperative Cognitive Dysfunction
Authors: Daiello Lori A. , Racine Annie M. , Yun Gou Ray , Marcantonio Edward R. , Xie Zhongcong , Kunze Lisa J. , Vlassakov Kamen V. , Inouye Sharon K. , Jones Richard N. ,   for the SAGES Study Group
Published: June 2019

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Background

Postoperative delirium and postoperative cognitive dysfunction share risk factors and may co-occur, but their relationship is not well established. The primary goals of this study were to describe the prevalence of postoperative cognitive dysfunction and to investigate its association with in-hospital delirium. The authors hypothesized that delirium would be a significant risk factor for postoperative cognitive dysfunction during follow-up.

Methods

This study used data from an observational study of cognitive outcomes after major noncardiac surgery, the Successful Aging after Elective Surgery study. Postoperative delirium was evaluated each hospital day with confusion assessment method–based interviews supplemented by chart reviews. Postoperative cognitive dysfunction was determined using methods adapted from the International Study of Postoperative Cognitive Dysfunction. Associations between delirium and postoperative cognitive dysfunction were examined at 1, 2, and 6 months.

Results

One hundred thirty-four of 560 participants (24%) developed delirium during hospitalization. Slightly fewer than half (47%, 256 of 548) met the International Study of Postoperative Cognitive Dysfunction-defined threshold for postoperative cognitive dysfunction at 1 month, but this proportion decreased at 2 months (23%, 123 of 536) and 6 months (16%, 85 of 528). At each follow-up, the level of agreement between delirium and postoperative cognitive dysfunction was poor (kappa less than .08) and correlations were small (r less than .16). The relative risk of postoperative cognitive dysfunction was significantly elevated for patients with a history of postoperative delirium at 1 month (relative risk = 1.34; 95% CI, 1.07–1.67), but not 2 months (relative risk = 1.08; 95% CI, 0.72–1.64), or 6 months (relative risk = 1.21; 95% CI, 0.71–2.09).

Conclusions

Delirium significantly increased the risk of postoperative cognitive dysfunction in the first postoperative month; this relationship did not hold in longer-term follow-up. At each evaluation, postoperative cognitive dysfunction was more common among patients without delirium. Postoperative delirium and postoperative cognitive dysfunction may be distinct manifestations of perioperative neurocognitive deficits.
Isoflurane Modulates Hippocampal Cornu Ammonis Pyramidal Neuron Excitability by Inhibition of Both Transient and Persistent Sodium Currents in Mice
Authors: Zhao Wenling , Zhang Mingyue , Liu Jin , Liang Peng , Wang Rurong , Hemmings Hugh C. , Zhou Cheng
Published: June 2019

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Background

Volatile anesthetics inhibit presynaptic voltage-gated sodium channels to reduce neurotransmitter release, but their effects on excitatory neuron excitability by sodium current inhibition are unclear. The authors hypothesized that inhibition of transient and persistent neuronal sodium currents by the volatile anesthetic isoflurane contributes to reduced hippocampal pyramidal neuron excitability.

Methods

Whole-cell patch-clamp recordings of sodium currents of hippocampal cornu ammonis pyramidal neurons were performed in acute mouse brain slices. The actions of isoflurane on both transient and persistent sodium currents were analyzed at clinically relevant concentrations of isoflurane.

Results

The median inhibitory concentration of isoflurane for inhibition of transient sodium currents was 1.0 ± 0.3 mM (~3.7 minimum alveolar concentration [MAC]) from a physiologic holding potential of −70 mV. Currents from a hyperpolarized holding potential of −120 mV were minimally inhibited (median inhibitory concentration = 3.6 ± 0.7 mM, ~13.3 MAC). Isoflurane (0.55 mM; ~2 MAC) shifted the voltage-dependence of steady-state inactivation by −6.5 ± 1.0 mV (n = 11, P < 0.0001), but did not affect the voltage-dependence of activation. Isoflurane increased the time constant for sodium channel recovery from 7.5 ± 0.6 to 12.7 ± 1.3 ms (n = 13, P < 0.001). Isoflurane also reduced persistent sodium current density (median inhibitory concentration = 0.4 ± 0.1 mM, ~1.5 MAC) and resurgent currents. Isoflurane (0.55 mM; ~2 MAC) reduced action potential amplitude, and hyperpolarized resting membrane potential from −54.6 ± 2.3 to −58.7 ± 2.1 mV (n = 16, P = 0.001).

Conclusions

Isoflurane at clinically relevant concentrations inhibits both transient and persistent sodium currents in hippocampal cornu ammonis pyramidal neurons. These mechanisms may contribute to reductions in both hippocampal neuron excitability and synaptic neurotransmission.
Repeated Cross-sectional Surveys of Burnout, Distress, and Depression among Anesthesiology Residents and First-year Graduates
Authors: Sun Huaping , Warner David O. , Macario Alex , Zhou Yan , Culley Deborah J. , Keegan Mark T.
Published: June 2019

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Background

This repeated cross-sectional survey study was conducted to determine the prevalence of, and factors associated with, burnout, distress, and depression among anesthesiology residents and first-year graduates. We hypothesized that heavy workload and student debt burden were associated with a higher risk of physician burnout, distress, and depression, and that perception of having adequate workplace resources, work–life balance, and social support were associated with a lower risk.

Methods

Physicians beginning U.S. anesthesiology residency between 2013 and 2016 were invited to take online surveys annually from their clinical anesthesia year 1 to 1 yr after residency graduation. The Maslach Burnout Inventory, the Physician Well-Being Index, and the Harvard Department of Psychiatry/National Depression Screening Day Scale were used to measure burnout, distress, and depression, respectively. Logistic regression analyses were conducted to examine whether self-reported demographics, personal, and professional factors were associated with the risk of burnout, distress, and depression.

Results

The response rate was 36% (5,295 of 14,529). The prevalence of burnout, distress, and depression was 51% (2,531 of 4,966), 32% (1,575 of 4,941), and 12% (565 of 4,840), respectively. Factors associated with a lower risk of all three outcomes included respondents’ perceived workplace resource availability, (odds ratio = 0.51 [95% CI, 0.45 to 0.57] for burnout; 0.51 [95% CI, 0.45 to 0.56] for distress; 0.52 [95% CI, 0.45 to 0.60] for depression) and perceived ability to maintain work–life balance (0.61 [95% CI, 0.56 to 0.67] for burnout; 0.50 [95% CI, 0.46 to 0.55] for distress; 0.58 [95% CI, 0.51 to 0.65] for depression). A greater number of hours worked per week and a higher amount of student debt were associated with a higher risk of distress and depression, but not burnout.

Conclusions

Burnout, distress, and depression are notable among anesthesiology residents. Perceived institutional support, work–life balance, strength of social support, workload, and student debt impact physician well-being.