bluuebunny/crossref_metadata_2025 huggingface dataset:
Selection of Models: Evolution and the Choice of Species for Translational Research
Authors: Bolker Jessica A.
Published: August 2019

Evolutionary thinking can inform the choice and assessment of model species in neuroscience, particularly when such models are intended to generate knowledge that will translate to humans. Avoiding errors that arise from oversimplified notions of phylogeny or genotype-phenotype mapping is one contribution; evolutionary biology also offers positive guidance. The challenge of finding adequate non-human models for translational research is particularly acute in neuroscience: neurobiological and behavioral phenotypes are complex and plastic, and many traits important in humans are absent, radically different, or difficult to assess in other species. Evolutionary perspectives help to articulate and address these challenges. Darwin’s description of “descent with modification” points to two aspects of evolution that can help us assess the matching between a prospective model species and its intended target. One is trees that represent the structure of phylogenetic relationships; the other is phenotypic traits, i.e. the unique characteristics of each species’ evolved biology and natural history. Mapping traits onto a phylogeny is the first step toward analyzing the source of similarities between a target and a potential model. Whether similar traits arise from shared ancestry or from adaptive convergence has important implications for what kinds of inferences can be justified, and for the likely translatability of findings. Evolution offers both a rich source of possible models, and guidance for choosing the best ones for a given purpose. Considering model choice from an evolutionary angle not only helps to answer the question “What species might be a good model for studying x?” but also suggests additional questions we should be asking to assess the utility of both potential and current models. Recognizing the diverse ways model organisms can function expands our search image as we seek species to study that can both extend general knowledge, and generate translatable insights relevant to human neurobiology and disease.
Coordination of Neuron Production in Mouse and Human Cerebral Cortex by the Homolog of Drosophila Mastermind Protein
Authors: Ayoub Albert E. , Dominguez Martin H. , Benoit Jaime , Ortega Juan Alberto , Radonjic Nevena , Zecevic Nada , Rakic Pasko
Published: August 2019

The coordination of progenitor self-renewal, neuronal production, and migration is essential to the normal development and evolution of the cerebral cortex. Numerous studies have shown that the Notch, Wnt/beta-catenin, and Neurogenin pathways contribute separately to progenitor expansion, neurogenesis, and neuronal migration, but it is unknown how these signals are coordinated. In vitro studies suggested that the mastermind-like 1 (MAML1) gene, homologue of the Drosophila mastermind, plays a role in coordinating the aforementioned signaling pathways, yet its role during cortical development remains largely unknown. Here we show that ectopic expression of dominant-negative MAML (dnMAML) causes exuberant neuronal production in the mouse cortex without disrupting neuronal migration. Comparing the transcriptional consequences of dnMAML and Neurog2 ectopic expression revealed a complex genetic network controlling the balance of progenitor expansion versus neuronal production. Manipulation of MAML and Neurog2 in cultured human cerebral stem cells exposed interactions with the same set of signaling pathways. Thus, our data suggest that evolutionary changes that affect the timing, tempo, and density of successive neuronal layers of the small lissencephalic rodent and large convoluted primate cerebral cortex depend on similar molecular mechanisms that act from the earliest developmental stages.
C-C Motif Chemokine Ligand 15 May Be a Useful Biomarker for Predicting the Prognosis of Patients with Chronic Hypersensitivity Pneumonitis
Authors: Watanabe Masako , Horimasu Yasushi , Iwamoto Hiroshi , Yamaguchi Kakuhiro , Sakamoto Shinjiro , Masuda Takeshi , Nakashima Taku , Miyamoto Shintaro , Ohshimo Shinichiro , Fujitaka Kazunori , Hamada Hironobu , Kohno Nobuoki , Hattori Noboru
Published: August 2019

Background: Chronic hypersensitivity pneumonitis (CHP) is characterized by lymphocytic inflammation and progressive fibrosis of the lung caused by a variety of inhaled antigens. Due to the difficulty of accurately diagnosing CHP, and the poor prognosis associated with the condition, a novel clinical biomarker is urgently needed. Objective: To investigate the usefulness of C-C motif chemokine ligand 15 (CCL15), which had been demonstrated to highly express in the lungs of CHP patients, as a clinical biomarker for CHP. Method: Immunohistochemical investigations were performed on lung tissue from CHP patients, and CCL15 levels in serum and bronchoalveolar lavage fluid (BALF) were measured via the enzyme-linked immunosorbent assay. Results: Immunohistochemistry investigations revealed high CCL15 expression in the lungs of CHP patients. Serum CCL15 levels in CHP patients (29.1 ± 2.1 μg/mL) were significantly higher than those of idiopathic pulmonary fibrosis patients (19.7 ± 1.3 μg/mL, p = 0.01) and healthy subjects (19.5 ± 1.7 μg/mL, p = 0.003). When BALF CCL15 level was divided by BALF albumin (Alb) level (BALF CCL15/Alb), it was significantly inversely correlated with forced vital capacity (β = –0.47, p = 0.0006), percentage of predicted carbon monoxide diffusion capacity of the lung (β = –0.41, p = 0.0048), and BALF lymphocyte count (β = –0.34, p = 0.01) in CHP patients. Multivariate Cox proportional hazards analysis revealed that high BALF CCL15/Alb and poor prognosis were statistically significantly independently correlated in CHP patients (HR 1.1, 95% CI 1.03–1.18, p = 0.004). Conclusion: The results of the current study suggest that CCL15 may be a useful prognostic biomarker for CHP. CCL15 was highly expressed in the lung tissue of CHP patients, and BALF CCL15/Alb was significantly associated with CHP prognosis.
Nocturnal Primate Communication: Ecology, Evolution and Conservation
Authors: Gursky Sharon , Nekaris K.A.I.
Published: August 2019

Auditory, visual and olfactory cues play varying roles in non-human primate communication, and these systems have been intensively studied over the last several decades. The use of vocalisations as a primary mode of communication has been the focus of much research, especially in attempts to understand the origins of human language, with a major focus on anthropoid primates and diurnal lemurs. Over the last decade, technological advances have allowed researchers to begin to conduct in-depth investigations into the communication systems exhibited by the nocturnal and cathemeral prosimian primates, including tarsiers, lemurs and lorises. Understanding how nocturnal prosimians use visual, olfactory and auditory cues is vital for reconstructing the origins of primate communication systems. In this special issue, we highlight some of the more exciting advances in the communication strategies of the prosimians. Contributions come from work conducted in Kenya, Tanzania, Senegal, Rwanda, Madagascar and the Indonesian islands of Java and Sulawesi. Topics will include: the description of novel ultrasonic vocalisations, including frequency and function of these newly discovered calls; the possible use of vocalisations to navigate and assemble at sleep sites; the importance of species-specific contact vocalisations for the identification of new species; the use of urinary and glandular signals to communicate and the methods developed to understand this complex communication in the field; the use of vocalisations for niche separation among nocturnal primates from mainland Africa and Madagascar; and whether or not we can use new technologies to discern whether prosimians use vocalisations for individual identification of group members. We discuss the importance of new field methods including novel equipment and techniques, the use of vocalisation to influence conservation practices and the importance of comparing across prosimian taxa to reconstruct the communication systems of our early primate ancestors.
Efficacy, Safety, and Tolerability of Switching from Oral Cholinesterase Inhibitors to Rivastigmine Transdermal Patch with 1-Step Titration in Patients with Mild to Moderate Alzheimer’s Disease: A 24-Week, Open-Label, Multicenter Study in Japan
Authors: Ueda Kengo , Katayama Sadao , Arai Tetsuaki , Furuta Nobuo , Ikebe Shinichiro , Ishida Yoshinori , Kanaya Kiyoshi , Ouma Shinji , Sakurai Hirofumi , Sugitani Masato , Takahashi Makio , Tanaka Toshihisa , Tsuno Norifumi , Wakutani Yosuke , Shekhawat Ankita , Das Gupta Ayan , Kiyose Kazuki , Toriyama Kazuhiro , Nakamura Yu
Published: August 2019

Background: Few studies have investigated treatment options for patients with Alzheimer’s disease (AD) showing a poor response to oral cholinesterase inhibitors (ChEIs) in Japan. Objective: To investigate the efficacy and safety of switching from oral ChEIs to rivastigmine transdermal patch in patients with AD. Methods: In this multicenter, open-label, phase IV study in outpatient clinics in Japan, patients with mild-moderate AD who had a poor response to or experienced difficulty in continuing donepezil or galantamine were switched to rivastigmine transdermal patch (5 cm2; loaded dose 9 mg, delivery rate 4.6 mg/24 h) with a 1-step titration in week 4 (10 cm2; loaded dose 18 mg, delivery rate 9.5 mg/24 h), which was continued for 4 weeks in the titration period and 16 weeks in a maintenance period. The primary endpoint was the change in Mini-Mental State Examination (MMSE) total score from baseline to week 24. Results: A total of 118 patients were enrolled and switched to rivastigmine, of which 102 completed the 24-week study. The MMSE total score was essentially unchanged during the study, with a least-square mean change (SD) of −0.35 (2.64) at week 24 (p = 0.1750). Exploratory analysis with a mixed-effect model comparing changes in MMSE between the pre- and post-switch periods suggested that switching to rivastigmine prevented a worsening of MMSE. Application site skin reactions/irritations occurred in 30.5% of patients overall, in 22.0% in the 8-week titration period, and in 10.2% in the 16-week maintenance period. Conclusion: Within-class switching from an oral ChEI to rivastigmine transdermal patch might be an efficacious and tolerable option for AD patients showing a poor or limited response to a prior oral ChEI.
Timing of Prenatal Magnetic Resonance Imaging in the Assessment of Congenital Diaphragmatic Hernia
Authors: Style Candace C. , Mehollin-Ray Amy R. , Verla Mariatu A. , Lau Patricio E. , Cruz Stephanie M. , Espinoza Jimmy , Lee Timothy C. , Fernandes Caraciolo J. , Keswani Sundeep G. , Olutoye Oluyinka O.
Published: August 2019

Introduction: Fetal magnetic resonance imaging (MRI) has been used to stratify severity of congenital diaphragmatic hernia (CDH) after ultrasound diagnosis. The purpose of this study was to determine if timing of MRI influenced prediction of severity of outcome in CDH. Methods: A single institution retrospective review of all CDH referred to our institution from February 2004 to May 2017 was performed. Patients were included if they underwent at least 2 fetal MRIs prior to delivery. Prenatal MRI indices including observed-to-expected total fetal lung volume (o/e TFLV) were evaluated. Indices were categorized by trimester, either 2nd (20–27 weeks gestation) or 3rd trimester (>28 weeks gestation) and further analyzed for outcome predictability. Primary outcomes were survival, extracorporeal membrane oxygenation (ECMO), and pulmonary hypertension (PAH). Student t test and logistic and linear regression were used for data analyses. Results: Of 256 fetuses evaluated for CDH, 197 were further characterized by MRI with 57 having both an MRI in the 2nd and 3rd trimesters. There was an average of 9.95 weeks (±4.3) between the 1st and 2nd MRI. Second trimester o/e TFLV was the only independent predictor of survival by logistic regression (OR 0.890, p < 0.01). Third trimester MRI derived lung volumes were associated with, and independent predictors of, severity of PAH and need for ECMO. Interval TFLV growth was a strong predictor of PAH postnatally (OR 0.361, p < 0.01). Overall cohort survival was 79%. Conclusion: Accuracy of MRI lung volumes to predict outcomes is dependent on the ­gestational age at the time of exam. While MRI lung volumes at either the 2nd or 3rd trimester are predictive of morbidity, 2nd trimester lung volumes strongly correlated with mortality.
Magnetic Resonance Fingerprinting to Characterize Childhood and Young Adult Brain Tumors
Authors: de Blank Peter , Badve Chaitra , Gold Deborah Rukin , Stearns Duncan , Sunshine Jeffrey , Dastmalchian Sara , Tomei Krystal , Sloan Andrew E. , Barnholtz-Sloan Jill S. , Lane Adam , Griswold Mark , Gulani Vikas , Ma Dan
Published: August 2019

Object: Magnetic resonance fingerprinting (MRF) allows rapid, simultaneous mapping of T1 and T2 relaxation times and may be an important diagnostic tool to measure tissue characteristics in pediatric brain tumors. We examined children and young adults with primary brain tumors to determine whether MRF can discriminate tumor from normal-appearing white matter and distinguish tumor grade. Methods: MRF was performed in 23 patients (14 children and 9 young adults) with brain tumors (19 low-grade glioma, 4 high-grade tumors). T1 and T2 values were recorded in regions of solid tumor (ST), peritumoral white matter (PWM), and contralateral white matter (CWM). Nonparametric tests were used for comparison between groups and regions. Results: Median scan time for MRF and a sequence for tumor localization was 11 min. MRF-derived T1 and T2 values distinguished ST from CWM (T1: 1,444 ± 254 ms vs. 938 ± 96 ms, p = 0.0002; T2: 61 ± 22 ms vs. 38 ± 9 ms, p = 0.0003) and separated high-grade tumors from low-grade tumors (T1: 1,863 ± 70 ms vs. 1,355 ± 187 ms, p = 0.007; T2: 90 ± 13 ms vs. 56 ± 19 ms, p = 0.013). PWM was distinct from CWM (T1: 1,261 ± 359 ms vs. 933 ± 104 ms, p = 0.0008; T2: 65 ± 51 ms vs. 38 ± 8 ms, p = 0.008), as well as from tumor (T1: 1,261 ± 371 ms vs. 1,462 ± 248 ms, p = 0.047). Conclusions: MRF is a fast sequence that can rapidly distinguish important tissue components in pediatric brain tumor patients. MRF-derived T1 and T2 distinguished tumor from normal-appearing white matter, differentiated tumor grade, and found abnormalities in peritumoral regions. MRF may be useful for rapid quantitative measurement of tissue characteristics and distinguish tumor grade in children and young adults with brain tumors.
Gene Expression in the Supporting Cells at the Onset of Meiosis in Rabbit Gonads
Authors: Díaz-Hernández Verónica , Caldelas Ivette , Merchant-Larios Horacio
Published: August 2019

Subsequent to somatic gonadal sexual differentiation, germ cells enter meiosis or mitotic arrest in the ovary or testis, respectively. Among mice, these processes occur almost synchronically in fetal gonads and depend, among other factors, on the levels of retinoic acid (RA). In contrast to those in mice, rabbit germ cells enter meiosis or mitotic arrest after birth and coexist with proliferating germ cells. Here, we studied the somatic cell context in which germ cells enter meiosis or mitotic arrest in the rabbit. Using confocal immunofluorescence and real-time PCR, we studied the expression profiles of ALDH1A1 and ALDH1A2 and, comprising 2 genes required for RA synthesis, 2 meiosis markers STRA8 and SYCP3 as well as 2 genes involved in meiosis inhibition, CYP26B1 and NANOS2. We found that although both meiosis and mitotic arrest initiate after birth, these 2 processes are regulated in a way similar to the human fetal gonad. Current results reinforce the value of the neonatal rabbit gonad as an alternative experimental model for analyzing the direct effect of environmental factors during critical stages of germ cell establishment.
Direct Amplification of Tissue Factor:Factor VIIa Procoagulant Activity by Bile Acids Drives Intrahepatic Coagulation
Authors: Baker Kevin S. , Kopec Anna K. , Pant Asmita , Poole Lauren G. , Cline-Fedewa Holly , Ivkovich Dora , Olyaee Mojtaba , Woolbright Benjamin L. , Miszta Adam , Jaeschke Hartmut , Wolberg Alisa S. , Luyendyk James P.
Published: August 2019

Objective:

Regulation of TF (tissue factor):FVIIa (coagulation factor VIIa) complex procoagulant activity is especially critical in tissues where plasma can contact TF-expressing cells. One example is the liver, where hepatocytes are routinely exposed to plasma because of the fenestrated sinusoidal endothelium. Although liver-associated TF contributes to coagulation, the mechanisms controlling the TF:FVIIa complex activity in this tissue are not known.

Approach and Results:

Common bile duct ligation in mice triggered rapid hepatocyte TF-dependent intrahepatic coagulation coincident with increased plasma bile acids, which occurred at a time before observable liver damage. Similarly, plasma TAT (thrombin-antithrombin) levels increased in cholestatic patients without concurrent hepatocellular injury. Pathologically relevant concentrations of the bile acid glycochenodeoxycholic acid rapidly increased hepatocyte TF-dependent procoagulant activity in vitro, independent of de novo TF synthesis and necrotic or apoptotic cell death. Glycochenodeoxycholic acid increased hepatocyte TF activity even in the presence of the phosphatidylserine-blocking protein lactadherin. Interestingly, glycochenodeoxycholic acid and taurochenodeoxycholic acid increased the procoagulant activity of the TF:FVIIa complex relipidated in unilamellar phosphatidylcholine vesicles, which was linked to an apparent decrease in the K
m
for FX (coagulation factor X). Notably, the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, a bile acid structural analog, did not increase relipidated TF:FVIIa activity. Bile acids directly enhanced factor X activation by recombinant soluble TF:FVIIa complex but had no effect on FVIIa alone.

Conclusions:

The results indicate that bile acids directly accelerate TF:FVIIa–driven coagulation reactions, suggesting a novel mechanism whereby elevation in a physiological mediator can directly increase TF:FVIIa procoagulant activity.
Intravenous Tissue Plasminogen Activator in Stroke Mimics
Authors: Ali-Ahmed Fatima , Federspiel Jerome J. , Liang Li , Xu Haolin , Sevilis Theresa , Hernandez Adrian F. , Kosinski Andrzej S. , Prvu Bettger Janet , Smith Eric E. , Bhatt Deepak L. , Schwamm Lee H. , Fonarow Gregg C. , Peterson Eric D. , Xian Ying
Published: August 2019

Background:

The necessity for rapid evaluation and treatment of acute ischemic stroke with intravenous tPA (tissue-type plasminogen activator) may increase the risk of administrating tPA to patients presenting with noncerebrovascular conditions that closely resemble stroke (stroke mimics). However, there are limited data on thrombolysis safety in stroke mimics.

Methods and Results:

Using data from the Get With The Guidelines–Stroke Registry, we identified 72 582 patients with suspected ischemic stroke treated with tPA from 485 US hospitals between January 2010 and December 2017. We documented the use of tPA in stroke mimics, defined as patients who present with stroke-like symptoms, but after workup are determined not to have suffered from a stroke or transient ischemic attack, and compared characteristics and outcomes in stroke mimics versus those with ischemic stroke. Overall, 3.5% of tPA treatments were given to stroke mimics. Among them, 38.2% had a final nonstroke diagnoses of migraine, functional disorder, seizure, and electrolyte or metabolic imbalance. Compared with tPA-treated true ischemic strokes, tPA-treated mimics were younger (median 54 versus 71 years), had a less severe National Institute of Health Stroke Scale (median 6 versus 8), and a lower prevalence of cardiovascular risk factors, except for a higher prevalence of prior stroke/transient ischemic attack (31.3% versus 26.1%, all
P
<0.001). The rate of symptomatic intracranial hemorrhage was lower in stroke mimics (0.4%) as compared with 3.5% in ischemic strokes (adjusted odds ratio, 0.29; 95% CI, 0.17–0.50). In-hospital mortality rate was significantly lower in stroke mimics (0.8% versus 6.2%, adjusted odds ratio, 0.31; 95% CI, 0.20–0.49). Patients with stroke mimics were more likely to be discharged to home (83.8% versus 49.3%, adjusted odds ratio, 2.97; 95% CI, 2.59–3.42) and to ambulate independently at discharge (78.6% versus 50.6%, adjusted odds ratio, 1.86; 95% CI, 1.61–2.14).

Conclusions:

In this large cohort of patients treated with tPA, relatively few patients who received tPA for presumed stroke were ultimately not diagnosed with a stroke or transient ischemic attack. The complication rates associated with tPA in stroke mimics were low. Despite the potential risk of administering tPA to stroke mimics, opportunity remains for continued improvement in the rapid and accurate diagnosis and treatment of ischemic stroke.
Joint Shock/Death Risk Prediction Model for Patients Considering Implantable Cardioverter-Defibrillators
Authors: Reeder Harrison T. , Shen Changyu , Buxton Alfred E. , Haneuse Sebastien J. , Kramer Daniel B.
Published: August 2019

Background:

The risk of death or appropriate therapy varies widely among recipients of implantable cardioverter-defibrillators (ICDs). The goals of this study were to develop a risk prediction tool that jointly considers future outcome probabilities of ICD shock and death.

Methods and Results:

We performed a secondary analysis of patients receiving ICDs as part of the SCD-HeFT trial (Sudden Cardiac Death in Heart Failure Trial). We applied an illness-death regression model to jointly model both ICD shocks and death under the semi-competing risks framework, which predicts for each patient their probability of having received ICD shocks, dying, or both at any given point in time. Among 803 ICD recipients (mean age, 60 years; 23% women) followed for a median of 41.1 months, 430 (53.5%) patients completed the study without dying or receiving an ICD shock, 206 (25.7%) received at least 1 shock but survived, 113 (14.1%) died before experiencing a shock, and 54 (6.7%) received at least 1 shock and subsequently died. Predicted outcome probabilities based on baseline demographic and clinical variables reveal substantial heterogeneity in joint shock and death risks, both between patients at each time point and for each single patient across time. Overall, predictive performance for ICD shock and death individually was adequate, based on area under the curve at 5 years of 0.65 for shocks and of 0.79 for death.

Conclusions:

Our analysis of outcomes after ICD implantation provides an alternative predictive model for individual risk of death or ICD shocks. If validated, this may provide a useful tool for individualized counseling regarding likely outcomes after device implantation, while also informing the design of further studies to focus the clinical effectiveness and cost-effectiveness of ICD therapy.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT00000609.
Sex Differences in Outcome After Endovascular Stroke Therapy for Acute Ischemic Stroke
Authors: Sheth Sunil A. , Lee Songmi , Warach Steven J. , Gralla Jan , Jahan Reza , Goyal Mayank , Nogueira Raul G. , Zaidat Osama O. , Pereira Vitor M. , Siddiqui Adnan , Lutsep Helmi , Liebeskind David S. , McCullough Louise D. , Saver Jeffrey L.
Published: August 2019

Background and Purpose—

We determined the effect of sex on outcome after endovascular stroke thrombectomy in acute ischemic stroke, including lifelong disability outcomes.

Methods—

We analyzed patients treated with the Solitaire stent retriever in the combined SWIFT (Solitaire FR With the Intention for Thrombectomy), STAR (Solitaire FR Thrombectomy for Acute Revascularization), and SWIFT PRIME (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment) cohorts. Ordinal and logistic regression were used to examine known factors influencing outcome after endovascular stroke thrombectomy and study the effect of sex on the association between these factors and outcomes, including age and time to reperfusion. Years of optimal life after thrombectomy were defined as disability-adjusted life years and calculated by projecting disability through adjusted poststroke life expectancy by sex.

Results—

Among 389 patients treated with endovascular stroke thrombectomy, 55% were females, and median National Institutes of Health Stroke Scale was 17 (interquartile range, 8–28). There were no differences between females versus males in presenting deficit severity (National Institutes of Health Stroke Scale score, 17 versus 17,
P
=0.21), occlusion location (69% versus 64% M1,
P
=0.62), presenting infarct extent (Alberta Stroke Program Early CT Score 8 versus 8,
P
=0.24), rate of substantial reperfusion (Thrombolysis in Cerebral Infarction 2b/3, 87% versus 83%,
P
=0.37), onset to reperfusion time (294 versus 302 minutes,
P
=0.46). Despite older ages (69 versus 64,
P
<0.001) and higher rate of atrial fibrillation (45% versus 30%,
P
=0.002) for females compared with males, adjusted rates of functional independence at 90 days were similar (odds ratio, 1.0; 95% CI, 0.6–1.6). After adjusting for age at presentation and stroke severity, females had more years of optimal life (disability-adjusted life year) after endovascular stroke thrombectomy, 10.6 versus 8.5 years (
P
<0.001).

Conclusions—

Despite greater age and higher rate of atrial fibrillation, females experienced comparable functional outcomes and greater years of optimal life after intervention compared with males.
Sex Differences in Long-Term Quality of Life Among Survivors After Stroke in the INSTRUCT
Authors: Phan Hoang T. , Blizzard Christopher L. , Reeves Mathew J. , Thrift Amanda G. , Cadilhac Dominique A. , Sturm Jonathan , Heeley Emma , Otahal Petr , Rothwell Peter , Anderson Craig S. , Parmar Priya , Krishnamurthi Rita , Barker-Collo Suzanne , Feigin Valery , Gall Seana
Published: August 2019

Background and Purpose—

Women are reported to have poorer health-related quality of life (HRQoL) after stroke than men, but the underlying reasons are uncertain. We investigated factors contributing to the sex differences.

Methods—

Individual participant data on 4288 first-ever strokes (1996–2013) were obtained from 4 high-quality population-based incidence studies from Australasia and Europe. HRQoL utility scores among survivors after stroke (range from negative scores=worse than death to 1=perfect health) were calculated from 3 scales including European Quality of Life-5 Dimensions, Short-Form 6-Dimension, and Assessment of Quality of Life at 1 year (3 studies; n=1210) and 5 years (3 studies; n=1057). Quantile regression was used to estimate the median differences in HRQoL for women compared to men with adjustment for covariates. Study factors included sociodemographics, prestroke dependency, stroke-related factors (eg, stroke severity), comorbidities, and poststroke depression. Study-specific median differences were combined into pooled estimates using random-effect meta-analysis.

Results—

Women had lower pooled HRQoL than men (median difference
unadjusted
1 year, −0.147; 95% CI, −0.258 to −0.036; 5 years, −0.090; 95% CI, −0.119 to −0.062). After adjustment for age, stroke severity, prestroke dependency, and depression, these pooled median differences were attenuated, more greatly at 1 year (−0.067; 95% CI, −0.111 to −0.022) than at 5 years (−0.085; 95% CI, −0.135 to −0.034).

Conclusions—

Women consistently exhibited poorer HRQoL after stroke than men. This was partly attributable to women’s advanced age, more severe strokes, prestroke dependency, and poststroke depression, suggesting targets to reduce the differences. There was some evidence of residual differences in HRQoL between sexes but they were small and unlikely to be clinically significant.
Infection During Delivery Hospitalization and Risk of Readmission for Postpartum Stroke
Authors: Miller Eliza C. , Wen Timothy , Elkind Mitchell S.V. , Friedman Alexander M. , Boehme Amelia K.
Published: August 2019

Background and Purpose—

Most cases of pregnancy-related ischemic stroke (IS) and hemorrhagic stroke (HS) occur postpartum. Infections have been identified as a trigger for strokes in young people and have been associated with strokes during delivery hospitalizations, but a temporal relationship has been difficult to establish. We hypothesized that infections diagnosed during a delivery admission would be associated with an increased risk of readmission for postpartum stroke.

Methods—

We conducted a retrospective cohort study using the Healthcare Cost and Utilization Project’s National Readmissions Database from 2010 to 2014. Using weighted survey design Poisson regression analysis, we calculated adjusted risk ratios (aRR) and 95% CI for the association between infection during delivery admission and 30-day postpartum readmission for IS or HS.

Results—

Out of 17.2 million delivery admissions during the study period, 2128 were readmitted within 30 days for a stroke of any type. There were 1189 HS (intracerebral hemorrhage or subarachnoid hemorrhage) and 720 IS, and the remainder unspecified pregnancy-related stroke. Adjusting for age and comorbidities, women with delivery infections were at higher risk of readmission for postpartum stroke of any type (aRR, 1.19; 95% CI, 1.01–1.41). Women with infections had higher risk of readmission for postpartum IS (aRR, 1.75; 95% CI, 1.37–2.22), but not for postpartum HS (aRR, 0.96; 95% CI, 0.75–1.23). The effect of infection on 30-day IS readmission was larger in women without hypertensive disorders of pregnancy (aRR, 2.0; 95% CI, 1.55–2.69 in women without hypertensive disorders of pregnancy versus aRR, 1.47; 95% CI, 0.9–2.38 in women with hypertensive disorders of pregnancy,
P
value for interaction=0.09).

Conclusions—

Infection during delivery hospitalization was associated with increased risk of readmission for IS, but not HS, within 30 days postpartum, particularly in women without hypertensive disorders of pregnancy. Infection may play a role in triggering postpartum IS even in the absence of other risk factors.
The Art of a Life Adapting: Drawing and Healing
Authors: Fremantle Chris
Published: August 2019

The author, a practice-led researcher and cultural producer, draws on his experience of cancer treatment and his use of art as a way to make hidden features visible. He relates this to the larger intersubjective and social questions of cancer as an overwhelming force affecting society. Approaches in art, including improvisation, are relevant to adaptation, a process that is necessary for living with cancer.
The hidden repertoire of brain dynamics and dysfunction
Authors: McIntosh Anthony R. , Jirsa Viktor K.
Published: August 2019

The purpose of this paper is to describe a framework for the understanding of rules that govern how neural system dynamics are coordinated to produce behavior. The framework, structured flows on manifolds (SFM), posits that neural processes are flows depicting system interactions that occur on relatively low-dimension manifolds, which constrain possible functional configurations. Although this is a general framework, we focus on the application to brain disorders. We first explain the Epileptor, a phenomenological computational model showing fast and slow dynamics, but also a hidden repertoire whose expression is similar to refractory status epilepticus . We suggest that epilepsy represents an innate brain state whose potential may be realized only under certain circumstances. Conversely, deficits from damage or disease processes, such as stroke or dementia, may reflect both the disease process per se and the adaptation of the brain. SFM uniquely captures both scenarios. Finally, we link neuromodulation effects and switches in functional network configurations to fast and slow dynamics that coordinate the expression of SFM in the context of cognition. The tools to measure and model SFM already exist, giving researchers access to the dynamics of neural processes that support the concomitant dynamics of the cognitive and behavioral processes.
Law of Peace and Children’s Right to have Rights
Authors: Field Sarah M.
Published: August 2019

International law’s affirmation of everyone’s right to have rights came into being through a peacemaking process. Its deprivation continues to typify the emergent context that brings peace processes into being – and for some cohorts of the people, namely children, the process itself. The right is intuitively seductive. It resonates as self-evident: an inexorable abstraction of having rights. Yet it is also enigmatic and challenging to concretise. What is its content? What substantive rights are expressive of this right? What is their scope in peacemaking? And why is it – above for example more corporeal rights – so fundamental? Guided by these questions, the paper begins by reflecting on the right as crystallised by Hannah Arendt: it then shifts to reflecting on, first, its expression in international law and, second, its interrelations with the law of peace. In doing so, it yields legal and political opportunities for ensuring the right in peacemaking, and imagines a framework of evolving measures for bringing the right to life in the staged process. The paper concludes by arguing renewing engagement with this understated right offers a beacon for guiding responses to the complex child rights challenges yielded by peacemaking – and our interdependent and fragile twenty-first century world more generally.
The Role of Children’s Rights in Regulating Digital Advertising
Authors: Verdoodt Valerie
Published: August 2019

An important domain in which children’s rights are reconfigured by internet use, is digital advertising. New advertising formats such as advergames, personalised and integrated advertising have permeated the online environments in which children play, communicate and search for information. The often immersive, interactive and increasingly personalised nature of these advertising formats makes it difficult for children to recognise and make informed and well-balanced commercial decisions. This raises particular issues from a children’s rights perspective, including, inter alia, their rights to development (Article 6, uncrc), privacy (Article 16, uncrc), protection against economic exploitation (Article 32, uncrc), freedom of thought (Article 17, uncrc) and education (Article 28, uncrc). The paper addresses this reconfiguration by translating the general principles and the provisions of the United Nations Convention on the Rights of the Child into the specific context of digital advertising. Moreover, it considers the different dimensions of the rights (i.e. protection, participation and provision) and how the commercialisation affects children and how their rights are exercised.
Canada’s Detention of Children in Immigration Holding Centres
Authors: Ward Tyler Dickens , Raphael Dennis
Published: August 2019

Between 2015–2016, 201 children were held in detention in the Toronto Immigration Holding Centre (Canada Border Services Agency, 2017). There may have been even more held across Canada, but these figures are unavailable. Child detention is illegal under international law and causes serious mental, physical, and emotional health complications. In this article we discuss Canada’s detention of children drawing upon scholarship in the areas of (a) human rights and the law; (b) children’s health and health equity; and (c) the political economy of the welfare state. The paper provides alternatives to Canadian practices by describing child detention best practices.
Protected or Neglected?
Authors: Riekkinen Mariya , Adilghazi Serikhan , Tasbulatova Aliya
Published: August 2019

The aim of this article is to study the nexus between the autonomy of minors in implementing the right to peaceful assembly and the best interests of the child in safety. We consider the issue, taking Russia as an example, where the past tradition of denying children’s legal personality still surfaces in modern legislation dealing with the rights of the child. Pursuing child-sensitive practices of minors’ participation in protest are of special importance for Russia, where the legislation uses the term, “the legitimate interest of the child”, different in scope to, “the best interests of the child”. Our meta-question, hence, is whether the legal system of the Russian Federation allows full respect for minors’ autonomy in implementing participation rights while adequately addressing vulnerability of children. The article scrutinises a body of rules governing participation of under-aged persons in protest rallies which are stipulated by constitutional and administrative law going back to the practices of the Soviet era and referring to the standards of international law.
Biblical Geography
Authors: den Hollander August
Published: August 2019

Maps in Dutch printed Bibles made their debut when the Bible was first printed in large folio format in the Low Countries. The first complete Dutch Bible in the folio format that appeared on the market, by Jacob van Liesvelt in 1526, already included a map. This was a map of the Exodus, the Israelites’ journey through the desert from the land of Egypt to the promised land of Canaan. In the course of the second half of the sixteenth century, additional maps appeared in Bibles published in the Low Countries. In the sixteenth century, maps are found in both Catholic and Protestant Bibles.
On the Sound Change PGmc /hʷ/ > /f/, the Etymology of Du lijfeigen, and the Malberg Gloss leodardi
Authors: Postma Gertjan
Published: August 2019

A well-known exception to Grimm’s Law, /kʷ/ > /f/ instead of /kʷ/ > /hʷ/, is taken as a starting point and its reflexes in Middle Dutch and Sal-Frankic are discussed. As to the PIE root *leikʷ-, MD and MLG līf- in the compounds līfeigen ‘owned by the fief’, līftuht ‘feudal law’, and līfcōp ‘feudal transaction fee’ is identified as derived from this root under a regular sound change, which is coined Uhlenbeck’s Law. Uhlenbeck’s Law acts as a resolution of a pansyllabic constraint, not a constraint on roots. As to Sal-Frankic, the new etymology of SF leo- ‘related to the tenements’’, and by extention ‘agricultural’, sheds new light on the structure of the Lex Salica. It is argued that the tripartite manorial system of land tenure has reflexes in juridical terminology of this archaic legal document.
Der Fall Gregorius
Authors: Langbroek Erika , Brands Francis
Published: August 2019

It may be that the French and German authors of La vie du pape Grégoire and Gregorius were so influenced by classical texts as part of their education that these Gregorian legends contain motifs and structural elements of a classical comedy or tragedy. Therefore these legends are compared with twelve comedies by Plautus and Terence.
Über die Schönheit des ‚Jüngeren Titurel‘
Authors: Neukirchen Thomas
Published: August 2019

There are convincing reasons to see the ‘Younger Titurel’ not as a continuation of the ‘Titurel’ Fragments, but as a critical supplement, completion and perfection of Wolfram von Eschenbach’s ‘Parzival’. It is against this backdrop that we need to explain the ‘Younger Titurel’ taking up and correcting Wolfram’s ‘Titurel’ verses. This article will provide such an explanation. It starts from the premise that Albrecht does not only critically distance himself from Wolframs narration, but also from the superficial form of the ‘Parzival’ and ‘Titurel’. From his perspective, the narrative form of ‘Parzival’ was inappropriate. This opinion manifests itself in the harmonized verse of YT. Through its claim to beauty, it promises to bestow a capacity for knowledge which is directed towards the Good. In that regard, the ‘Younger Titurel’ is a noëtic novel.
The Regional Life of Geopolitical Conflict: The Case of Odes(s)a Oblast
Authors: Richardson Tanya
Published: August 2019

When the events known as the “Russian Spring” began in the aftermath of Ukraine’s Euromaidan Revolution in February 2014, Odessa oblast seemed like it would be particularly vulnerable to separatist activity. This paper offers a tentative explanation for why Odessa oblast escaped war in the 2014–15 phase of the Russia-Ukraine conflict. To do so, it chronicles events in Odessa oblast between fall 2013 and spring 2015 drawing on secondary sources such as news articles, blogs, social media posts, YouTube footage, official statements, and reports. Odessa-based elites’ decision to support Ukrainian sovereignty was an important factor hindering the realization of a Donetsk or Luhansk scenario. However, the weak Oblast Administration in the spring of 2014 and the upcoming mayoral elections created a volatile environment that various individuals (oligarchs, politicians, criminal networks) exploited to maintain or enhance their influence in the region. The internationalization of the conflict in the spring of 2014 presented Odessans with stark existential choices which undermined the city’s violence-avoiding dispute resolution techniques and culminated in the violence on May 2.
The Crimean Exception: Modern Politics as Hostage of the Imperial Past
Authors: Yekelchyk Serhy
Published: August 2019

The author proposes a new perspective on the political mobilization of ethnic Russians in the Crimea as reactive settler nationalism. After the Russian imperial conquest of the peninsula and the gradual displacement of the Crimean Tatars, the 1917 Revolution galvanized the Tatar national movement, which entered into an alliance with the Ukrainian one. A similar situation developed in the late 1980s, when the peninsula’s Russian ethnic majority found itself threatened by the loss of status and land in what could become a Tatar autonomy within Ukraine. Based on the implicit approval of Stalin’s genocidal deportation of the Crimean Tatars in 1944, the political mobilization of ethnic Russians in the 1990s made the Crimea an easy target for Russian annexation, which, however, took place twenty years later because of Russia’s internal reasons and the Euromaidan Revolution being perceived as a threat to the Putin regime.
Intentional language change and the connection between mixed languages and genderlects
Authors: Bakker Peter
Published: August 2019

This paper links genderlects and mixed languages. Both may have their roots in a gender dichotomy, where two distinct populations come together and blend into a new one, with different linguistic consequences. Mixed languages are generally assumed to be the result of deliberate or conscious language change and often come about as the result of an act of identity, connected to the birth of a new social or ethnic group. Societies or ethnic groups that are the result of mixed marriages may develop a mixed language or a genderlect. I show that there is a connection between the two, as proven in one specific case: a mixed language developed into a genderlect over several centuries. Typically, mixed languages combine elements from two languages with results that are so unusual that they are clearly not the result of normal language change, i.e. they are not outcomes of regular transmission between generations. Certain combinations found in genderlects show parallel patterns, for example in having personal pronouns or deictic elements that derive from other languages. Comparative evidence based on structural parallels suggests that some such genderlects (though not necessarily all) derive from deliberate changes by earlier generations. In this paper, I also investigate whether there is a link between societies with socially quite different roles for men and women, and societies with a genderlect, and find that such a link does not seem to exist.
What multiethnolects reveal about creole genesis
Authors: McWhorter John
Published: August 2019

Recent theories of creole genesis propose that creole languages did not emerge via the expansion of pidgin varieties (DeGraff, 2001; Mufwene, 2001, 2008). This paper argues that the multiethnolects that have formed in many European cities constitute a demonstration case of the genesis scenario these new creolist theories reconstruct. Crucially, however, the multiethnolects, while displaying a modest degree of grammatical simplification and restructuring, exhibit this to nothing approaching the degree that creoles do. This supports the idea that creoles form from a break in transmission rather than simply hybridization.
The tune drives the text
Authors: Roettger Timo B. , Grice Martine
Published: August 2019

In recent years there has been increasing recognition of the vital role of intonation in speech communication. While contemporary models represent intonation—the tune—and the text that bears it on separate autonomous tiers, this paper distils previously unconnected findings across diverse languages that point to important interactions between these two tiers. These interactions often involve vowels, which, given their rich harmonic structure, lend themselves particularly well to the transmission of pitch. Existing vowels can be lengthened, new vowels can be inserted and loss of their voicing can be blocked. The negotiation between tune and text ensures that pragmatic information is accurately transmitted and possibly plays a role in the typology of phonological systems.
Review of the genus Phormidesmis (Cyanobacteria) based on environmental, morphological, and molecular data with description of a new genus Leptodesmis

Authors: RAABOVÁ LENKA , KOVACIK LUBOMIR , ELSTER JOSEF , STRUNECKÝ OTAKAR
Published: August 2019

Very thin filamentous cyanobacteria are ubiquitous in a wide range of environments. For many years they were traditionally studied according to their morphological properties only. With the introduction of additional taxonomic methods (cytomorphological analyses, molecular sequencing, exact ecological studies, better data about phytogeographical distribution), traditional genera such as Leptolyngbya and Phormidium were found to be polyphyletic. Phormidesmis belonged to a newly formed genus that was supposed to explain the variability of such very thin simple filamentous cyanobacteria. However, even after definition of Phormidesmis based on distinct cytomorphological and phylogenetic traits, the variability within this genus remained unresolved. Here we analyzed 26 Phormidesmis strains to describe the variability within this genus, classified two new species (P. arctica and P. communis) and transferred Leptolyngbya nigrescens into P. nigrescens. A tabular review of Phormidesmis species is included. The diacritical features of all these species are: width up to 1–4 µm, barrel-shaped cells, which can be shorter or slightly longer than wide, with apparent constrictions at the cross-walls. Our study shows that Phormidesmis is a morphologically and genetically well-defined genus with a global distribution. A newly described genus Leptodesmis has significant morphological similarities both with Phormidesmis and Leptolyngbya, however with intermediate phylogenetic position with significant divergence in 16S rRNA gene. Leptodesmis is cryptic both to Phormidesmis and Leptolyngbya. In the initial part of the life cycle resembles Leptolyngbya, the appearance of older trichomes change to Phormidesmis like morphology.
Impatiens kamrupana (Balsaminaceae): a new species from Assam, India

Authors: BORAH SOURAVJYOTI , SARMA JATINDRA , GOGOI RAJIB
Published: August 2019

Impatiens kamrupana, a new species from Assam, northeast India is described. The new species is easily distinguished from its allied taxa by its bicoloured, white and purple flowers and sub-bucciniform lower sepal with straight to slightly curved spur.
The identity of Onosma liui (Boraginaceae) from Sichuan, China

Authors: HE YI , LIU DANHUI , WU KAI , LIU QUAN-RU
Published: August 2019

Examination of specimens, literature and critical field survey has shown that Onosma liui is conspecific with O. maaikangensis, an endemic species distributed in Western Sichuan and Eastern Xizang, China. Therefore, we place the former in synonymy with the latter.