bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of Adaptive Cognitive Control by Prefrontal High-Definition Transcranial Direct Current Stimulation in Older Adults
Authors: Gbadeyan Oyetunde , Steinhauser Marco , Hunold Alexander , Martin Andrew K , Haueisen Jens , Meinzer Marcus
Published: April 2019

Objective

Adaptive cognitive control frequently declines in advanced age. Because high-definition transcranial direct current stimulation (HD-tDCS) of the right dorsolateral prefrontal cortex (DLPFC) improved cognitive control in young adults, we investigated if this montage can also improve cognitive control in older individuals.

Method

In a double-blind, sham HD-tDCS controlled, cross-over design, 36 older participants received right DLPFC HD-tDCS during a visual flanker task. Conflict adaptation (CA) effects on response time (RT) and error rates (ER) assessed adaptive cognitive control. Biophysical modeling assessed the magnitude and distribution of induced current in older adults.

Results

Active HD-tDCS enhanced CA in older adults. However, this positive behavioral effect was limited to CA in ER. Similar to results obtained in healthy young adults, current modeling analysis demonstrated focal current delivery to the DLPFC with sufficient magnitude of the induced current to modulate neural function in older adults.

Discussion

This study confirms the effectiveness of HD-tDCS to modulate adaptive cognitive control in advanced age.
Duphold: scalable, depth-based annotation and curation of high-confidence structural variant calls
Authors: Pedersen Brent S , Quinlan Aaron R
Published: April 2019

Most structural variant (SV) detection methods use clusters of discordant read-pair and split-read alignments to identify variants yet do not integrate depth of sequence coverage as an additional means to support or refute putative events. Here, we present "duphold," a new method to efficiently annotate SV calls with sequence depth information that can add (or remove) confidence to SVs that are predicted to affect copy number. Duphold indicates not only the change in depth across the event but also the presence of a rapid change in depth relative to the regions surrounding the break-points. It uses a unique algorithm that allows the run time to be nearly independent of the number of variants. This performance is important for large, jointly called projects with many samples, each of which must be evaluated at thousands of sites. We show that filtering on duphold annotations can greatly improve the specificity of SV calls. Duphold can annotate SV predictions made from both short-read and long-read sequencing datasets. It is available under the MIT license at https://github.com/brentp/duphold.
Recent advances in understanding the effects of climate change on the world’s oceans
Authors: Hollowed Anne B , Barange Manuel , Garçon Véronique , Ito Shin-ichi , Link Jason S , Aricò Salvatore , Batchelder Harold , Brown Robin , Griffis Roger , Wawrzynski Wojciech
Published: April 2019

In June 2018, >600 scientists from over 50 countries attended the Fourth International Symposium on the Effects of Climate Change on the World’s Oceans (ECCWO-4). ECCWO-4 provided a forum for scientists to share information, build understanding, and advance responses to climate impacts on oceans and the many people, businesses and communities that depend on them. Seven Key Messages emerging from the symposium and relevant information from recently published literature are summarized. Recent scientific advances are improving our ability to understand, project, and assess the consequences of different levels of 21st century climate change for ocean ecosystems and ocean dependent communities. Outcomes of the symposium highlighted the need for on-going engagement with stakeholders, communities, and managers when considering the trade-offs associated with tactical and strategic opportunities for adaptation to climate change. Science informed adaptation frameworks that engage the public in their development are needed for effective management of marine resources in a changing climate. The summary provides a brief overview of the advances in climate-ocean science emerging from the symposium and provides context for the contributed papers within the broader socio-ecological advances of the discipline.
Pharmacokinetics of adjusted-dose 8-hourly lopinavir/ritonavir in HIV-infected children co-treated with rifampicin
Authors: Rabie Helena , Rawizza Holly , Zuidewind Peter , Winckler Jana , Zar Heather , Van Rie Annelies , Wiesner Lubbe , McIlleron Helen
Published: April 2019

Objectives

To evaluate the proportion of children with lopinavir Cmin ≥1 mg/L when receiving a novel 8-hourly lopinavir/ritonavir dosing strategy during rifampicin co-treatment.

Methods

HIV-infected children on lopinavir/ritonavir and rifampicin were enrolled in a prospective pharmacokinetic study. Children were switched from standard-of-care lopinavir/ritonavir-4:1 with additional ritonavir (1:1 ratio) twice daily to 8-hourly lopinavir/ritonavir-4:1 using weight-banded dosing. Rifampicin was dosed at 10–20 mg/kg/day. After 2 weeks, plasma samples were collected ∼2, 4, 6, 8 and 10 h after the morning lopinavir/ritonavir-4:1 dose, ALT was obtained to assess safety and treatment was switched back to standard of care. ClinicalTrials.gov registration number: NCT01637558.

Results

We recruited 11 children in two weight bands: 5 (45%) were 10–13.9 kg and received 20–24 mg/kg/dose of lopinavir and 6 (55%) children weighed 6–9.9 kg and received 20–23 mg/kg/dose of lopinavir. The median age was 15 months (IQR = 12.6–28.8 months). The median (IQR) lopinavir Cmin was 3.0 (0.1–5.5) mg/L. Seven (63.6%) of the 11 children had Cmin values ≥1 mg/L. Children with a lopinavir mg/kg dose below the median 21.5 were more likely to have Cmin <1 mg/L (P = 0.02). There was a strong positive correlation between lopinavir and ritonavir concentrations. No associations were found between lopinavir AUC2–10 and age, sex, weight, nutritional status or mg/kg/dose of lopinavir.

Conclusions

These data do not support the use of 8-hourly lopinavir/ritonavir at studied doses. Evaluation of higher doses is needed to optimize treatment outcomes of TB and HIV in young children.
Unravelling ceftazidime/avibactam resistance of KPC-28, a KPC-2 variant lacking carbapenemase activity
Authors: Oueslati Saoussen , Iorga Bogdan I , Tlili Linda , Exilie Cynthia , Zavala Agustin , Dortet Laurent , Jousset Agnès B , Bernabeu Sandrine , Bonnin Rémy A , Naas Thierry
Published: April 2019

Background

KPC-like carbapenemases have spread worldwide with more than 30 variants identified that differ by single or double amino-acid substitutions.

Objectives

To describe the steady-state kinetic parameters of KPC-28, which differs from KPC-2 by a H274Y substitution and the deletion of two amino acids (Δ242-GT-243).

Methods

The blaKPC-2, blaKPC-3, blaKPC-14 and blaKPC-28 genes were cloned into a pTOPO vector for susceptibility testing or into pET41b for overexpression, purification and subsequent kinetic parameter (Km, kcat) determination. Molecular docking experiments were performed to explore the role of the amino-acid changes in the carbapenemase activity.

Results

Susceptibility testing revealed that Escherichia coli producing KPC-28 displayed MICs that were lower for carbapenems and higher for ceftazidime and ceftazidime/avibactam as compared with KPC-2. The catalytic efficiencies of KPC-28 and KPC-14 for imipenem were 700-fold and 200-fold lower, respectively, than those of KPC-2, suggesting that Δ242-GT-243 in KPC-28 and KPC-14 is responsible for reduced carbapenem hydrolysis. Similarly, the H274Y substitution resulted in KPC-28 in a 50-fold increase in ceftazidime hydrolysis that was strongly reversed by clavulanate.

Conclusions

We have shown that KPC-28 lacks carbapenemase activity, has increased ceftazidime hydrolytic activity and is strongly inhibited by clavulanate. KPC-28-producing E. coli isolates display an avibactam-resistant ESBL profile, which may be wrongly identified by molecular and immunochromatographic assays as the presence of a carbapenemase. Accordingly, confirmation of carbapenem hydrolysis will be mandatory with assays based solely on blaKPC gene or gene product detection.
Not just a cargo receptor for large cargoes; an emerging role of TANGO1 as an organizer of ER exit sites
Authors: Saito Kota , Maeda Miharu
Published: April 2019

Proteins synthesized within the endoplasmic reticulum (ER) are exported from ER exit sites via coat protein complex II (COPII)-coated vesicles. Although the mechanisms of COPII-vesicle formation at the ER exit sites are highly conserved among species, vertebrate cells secrete a wide range of materials, including collagens and chylomicrons, which form bulky structures within the ER that are too large to fit into conventional carriers. Transport ANd Golgi Organization 1 (TANGO1) was initially identified as a cargo receptor for collagens but has been recently rediscovered as an organizer of ER exit sites. We would like to review recent advances in the mechanism of large cargo secretion and organization of ER exit sites through the function of TANGO1.
Expectations of and recommendations for a cancer survivorship guideline in Japan: a literature review of guidelines for cancer survivorship
Authors: Okubo Ryo , Wada Saho , Shimizu Yoichi , Tsuji Katsunori , Hanai Akiko , Imai Kenjiro , Uchitomi Yosuke , Fujiwara Yasuhiro , Tsugane Shoichiro , Matsuoka Yutaka J
Published: April 2019

Literature review of guidelines for cancer survivorship indicated the necessity for guidelines on optimal care coordination of oncologists with other health care providers and promotion of a healthy lifestyle.
Survival Differences Between Males and Females Diagnosed With Childhood Cancer
Authors: Williams Lindsay A , Spector Logan G
Published: April 2019

Background

Males have worse survival for childhood cancer, but whether this disparity exists among all childhood cancer types is undescribed.

Methods

We estimated sex differences in survival for 18 cancers among children (0–19 years) in Surveillance, Epidemiology, and End Results 18 (2000–2014). We used Kaplan-Meier survival curves (log-rank P values) to characterize sex differences in survival and Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between sex and death for each cancer type. We used an inverse odds weighting method to determine whether the association between sex and death was mediated by stage of disease for solid tumors.

Results

Males had worse overall survival and a higher risk of death for acute lymphoblastic leukemia (HR = 1.24, 95% CI = 1.12 to 1.37), ependymoma (HR = 1.36, 95% CI = 1.05 to 1.77), neuroblastoma (HR = 1.28, 95% CI = 1.09 to 1.51), osteosarcoma (HR = 1.29, 95% CI = 1.08 to 1.53), thyroid carcinoma (HR = 3.25, 95% CI = 1.45 to 7.33), and malignant melanoma (HR = 1.97, 95% CI = 1.33 to 2.92) (all log-rank P values < .02). The association between sex and death was mediated by stage of disease for neuroblastoma (indirect HR = 1.12, 95% CI = 1.05 to 1.19), thyroid carcinoma (indirect HR = 1.24, 95% CI = 1.03 to 1.48), and malignant melanoma (indirect HR = 1.28, 95% CI = 1.10 to 1.49). For these six tumors, if male survival had been as good as female survival, 21% of male deaths and 13% of total deaths after these cancer diagnoses could have been avoided.

Conclusions

Consideration of molecular tumor and clinical data may help identify mechanisms underlying the male excess in death after childhood cancer for the aforementioned cancers.
Cognitive–Behavioral Therapy for Sexual and Gender Minority Youth Mental Health
Authors: Craig Shelley L. , Austin Ashley , Alessi Edward J.
Published: April 2019

Lesbian, gay, bisexual, and transgender (LGBT) youth exist in a developmental context of emerging and shifting identities. This chapter reviews the mental health disparities experienced by LGBT youth. It examines their experiences of minority stress and considers the impact of their family and peer relationships on their identities. Also included is a discussion of affirmative cognitive–behavioral therapy (A-CBT) for LGBT youth, containing detailed clinical examples. The chapter concludes with emerging trends for evidence-based mental health practice with LGBT youth, such as a focus on resilience and the use of information and communication technologies.
Evidence-Based Alcohol and Substance Use Disorder Treatment with Sexual and Gender Minorities
Authors: Carrico Adam W. , Gómez Walter , Reback Cathy J.
Published: April 2019

Although sexual and gender minority (SGM) populations remain at markedly elevated risk for developing alcohol and substance use disorders, relatively few substance use disorder treatment programs provide culturally tailored services. This chapter provides an overview of alcohol and substance use disparities as well as reviews evidence-based interventions in distinct SGM populations. In general, clinical research has focused on culturally tailoring evidence-based substance use disorder treatments such as cognitive–behavioral therapy and motivational interviewing with modest success. Further clinical research should develop and test novel substance use disorder intervention approaches that address minority stress processes as key triggers for unhealthy alcohol consumption and substance use. Clinical research is also needed to address the disparities in unhealthy drinking among sexual minority women as well as alcohol and substance use disparities in transgender individuals. Recommendations are provided to optimize the effectiveness and scalability of existing evidence-based treatments targeting alcohol and substance use disorders in SGM populations.
Group-Based Cognitive–Behavioral Therapies with Sexual Minority Clients
Authors: Cohen Jeffrey M. , Newman Michelle G.
Published: April 2019

Sexual minorities face unique threats to psychological well-being that are primarily social in nature. These minority stressors include negative social exchanges at both the structural and interpersonal levels. Minority stress results in psychiatric distress; however, sexual minorities display increased self-esteem and decreased anxiety and depression when in proximity to other sexual minorities. This suggests group-based psychotherapy may be a uniquely effective treatment for the mental health of sexual minority clients. Group-based cognitive–behavioral therapies (CBTs), inclusive of traditional and third-wave modalities, enjoy a robust evidence base. This chapter reviews the evidence for group-based CBTs with sexual minorities, and it offers recommendations for the adaptation of group-based CBTs for work with sexual minorities. An illustrative example of a CBT group that was delivered to sexual minority adolescents is provided.
“How Am I Supposed to Treat These Cases?” Working with Families Struggling with Entrenched Parent–Child Contact Problems
Authors: Fidler Barbara J. , Deutsch Robin , Polak Shely
Published: April 2019

Effective family interventions when children resist or reject contact with a parent in highly conflicted coparenting cases continue to pose significant challenges for mental health professionals, lawyers, and the courts. There is no consensus within the social science research literature on how best to identify, assess, and clinically respond to situations involving resist-refuse dynamics, which are multifaceted in causation and require clinical and often legal remedies. This chapter differentiates parent–child contact problems on a continuum by nature and severity, provides a triaged model of differentiated clinical and legal approaches, and briefly summarizes the existing research on the efficacy of existing interventions. A moderately severe case example is presented to illustrate screening, assessment, and treatment plan development, the application of Multifaceted Family Therapy, and coordinated legal interventions.
Professional Ethics in a Legal Context
Authors: Berman Paul C. , Killeen Katherine W.
Published: April 2019

This chapter discusses essential ethical issues for therapists who provide mental health services in a legal context. The application of ethical concepts in general clinical cases may change when the litigation context or the expectations of attorneys and the court enter the mix. Conversely, clinicians may need to educate legal professionals about mental health professional obligations that transcend context. Failure to navigate these issues may lead to disruption of therapy, failed treatment, harm to the family, and legal or ethical problems for clinicians. Guided by the Association of Family and Conciliation Courts’ Guidelines for Court-Involved Therapy and other professional guidelines, this chapter highlights considerations for delivering ethically sound therapies for children and families involved in the courts.
Attunement with Exercise (AWE)
Authors: Calogero Rachel M. , Tylka Tracy L. , McGilley Beth Hartman , Pedrotty-Stump Kelly N.
Published: April 2019

This chapter draws from the authors’ clinical work with women with eating disorders, as well as theories of embodiment and mindfulness, to reveal the attunement with exercise (AWE) construct. AWE represents physical activities that shift away from dysfunctional forms of exercise to cultivate more positively embodied physical experiences, such as mindful attention, self-compassion, self-acceptance, joyful movement, body connection, and reliance on internal cues to determine when, what, where, why, and how to exercise. The chapter reviews the conceptual model of AWE, which entails exercising from a foundation of safety, focusing on the process of exercise rather than any outcome, and experiencing joy from exercise. Next, the chapter introduces the AWE Scale, which has been shown to yield reliable and valid scores in community and college samples of women and men. The chapter ends with a discussion of how to cultivate AWE as an embodied practice, with yoga provided as an illustration.
Adolescent Female Desire
Authors: Lamb Sharon , Koven Julie
Published: April 2019

The development of healthy female sexuality is a complex and multidimensional process. In understanding female adolescent sexual development, we must understand both the suppression and the celebration of female desire in its historical and structural contexts. Feminist theorists have long studied the suppression of desire and connected that desire to both subjectivity and agency. However, desire remains an elusive concept. This chapter reviews the history of desire and sexual freedom, looks at three historical and institutional influences over adolescent sexual desire (gender inequality, education, and the media), and then interrogates the idea of sexual agency to understand how adolescents and young women conceive of sexual agency today in a neoliberal context. The chapter ends with suggestions for practice, education, and activism to help promote healthier female sexual development.
Promoting Positive Body Image and Embodiment in Schools
Authors: Yager Zali
Published: April 2019

Body image programming has been implemented in schools to varying degrees of success, but to date, no programs specific to positive body image have been developed and evaluated. This chapter reviews programs that have been effective in improving body image to determine whether the elements of positive body image and embodiment have been present in program content. Some elements of positive body image, such as media literacy and critiquing stereotypes, were present in all five programs conducted with children (<12 years), and all eight programs conducted with adolescents (13–18 years). Additionally, agency (through activism and voice) and broadly conceptualizing beauty were often present in children’s programs, and resisting objectification and agency were often present in adolescent programs. Only one program included the Body Appreciation Scale as a measure of program effectiveness. Potential future directions for programs are discussed, including the incorporation of positive movement, mindfulness, and self-compassion.
Cognitive Dissonance–Based Interventions to Facilitate Positive Body Image and Embodiment
Authors: Halliwell Emma , Diedrichs Phillippa C.
Published: April 2019

Cognitive dissonance–based interventions (CDIs) emerge in meta-analyses as the most effective selective eating disorder prevention and body acceptance programs. This chapter examines whether CDIs can also be used to promote aspects of positive body image and embodiment. Theoretical links between CDI content and positive body image are discussed. Also, the small body of empirical research that has evaluated the impact of CDI on aspects of positive body image is reviewed. The chapter argues that CDI could offer a useful tool to promote positive body image. Some revisions may be beneficial. However, it is critical that changes are evaluated in randomized controlled trials to ensure that the effectiveness of CDIs is not compromised by these adaptations.
Policy Initiatives to Promote Positive Embodiment and Reduce Weight Stigma
Authors: Puhl Rebecca M. , Himmelstein Mary S.
Published: April 2019

Weight-based stigma and discrimination exist toward individuals whose body size deviates from stringent societal ideals of thinness. Growing concerns about the prevalence and damaging consequences of weight-based bullying, stigma, and discrimination have led to increasing calls for policy measures to protect people from weight-based prejudice on a broader scale. This chapter reviews policy and legal efforts that have been proposed or implemented to facilitate positive embodiment for youth and adults, including evidence on public attitudes about policies and laws that aim to reduce weight-based bullying and discrimination. In addition, policy initiatives and research evidence in North America, Europe, and other parts of the world are highlighted, including the strengths and limitations of these efforts. Directions for future policy research and advocacy efforts are identified that can improve on existing legal initiatives to promote equitable treatment of individuals of diverse body sizes.
Self-Management
Authors: Briesch Amy M. , Donaldson Aberdine R. , Abdulkerim Noora
Published: April 2019

Within the literature, the term self-management has been used to refer generally to a number of methods that can be used to help children manage their own behavior (e.g. self-regulation, self-modeling). The focus in this chapter, however, is more specifically on those interventions in which, at the core, students are taught to observe and record their own behavior, or what has been called self-monitoring. This chapter discusses various ways in which self-management may be used as a Tier II intervention for students with identified behavioral needs. Although this intervention approach may be used with students across all grade levels, there are important modifications that must be made in order to ensure developmental appropriateness, which are discussed later in the chapter. The chapter begins, however, by outlining the various intervention components that may be combined to form a comprehensive self-management intervention.
Behavior Contracts
Authors: Davis Heather S. , Hidalgo Rovi
Published: April 2019

In schools, behavior contracts typically specify a contingency of reinforcement that is satisfied if students meet specific behavior goals. Behavior contracts, also called contingency contracts, are supported by over forty years of research documenting their effectiveness in promoting individual behavior change across a variety of educational settings. The use of behavior contracts in schools often focuses on decreasing problem behaviors and increasing academic responding for students in general and special education settings. Contingencies developed within behavior contracts outline an expected behavior or completion of a task contingent upon a reward. This chapter provides information on behavior contract components, supporting behavioral principles, student populations for which contracts might be most effective, how to develop an effective behavior contract, and guidelines and considerations from research on implementing behavior contracts in applied settings.
Tier III Basics
Authors: Hawkins Renee O. , Collins Tai A. , Luevano Carla , Faler Amanda
Published: April 2019

Within multi-tiered systems of support (MTSS), including Positive Behavioral Intervention and Supports (PBIS) and Response to Intervention (RTI) models, Tier III represents the most intense level of intervention. Interventions at Tier III are highly individualized, with a specific student in mind, and carefully consider the context of behavior, including function, for intervention planning. Given the intense and individualized nature of Tier III interventions, it follows that these efforts are reserved for students with the most significant needs. It estimated that 1%–5% of students require Tier III intervention for behavior. This chapter describes the distinguishing features of Tier III, discusses issues related to the transition from Tier II to Tier III, overviews appropriate assessment and progress-monitoring methods, outlines effective intervention approaches, and provides general guidelines for implementation of Tier III services.
Target Social Skills Training for Idiosyncratic Behaviors, Aggression, and Noncompliance
Authors: O’Handley Roderick D. , Sabey Christian V.
Published: April 2019

Whereas previous chapters have described research and implementation of social skills training at the class-wide (Tier I) and small group (Tier II) level, this chapter focuses on the implementation of social skills training for idiosyncratic and severe behaviors. It is estimated that 1%–5% of students will require the most intensive (Tier III) behavioral support. As a result, it is necessary to identify behavior change strategies that promote appropriate social behavior in students who exhibit severe aggression and other disruptive behaviors. Specific strategies reviewed in this chapter include functional communication training (FCT), differential reinforcement, and video modeling. Information about implementation considerations is also provided.
Epidemiology of Pediatric Irritability
Authors: Salum Giovanni Abrahão
Published: April 2019

Irritability is a trait, continuously distributed in the population, that might reach pathological levels such as those presented in a disruptive mood dysregulation disorder (DMDD) diagnosis. In this chapter, the author reviews the epidemiology of irritability as a dimension and the epidemiology of DMDD as the diagnostic category that most explicitly captures the clinical features of pathological irritability. Dimensional analysis includes the prevalence of the core features of trait irritability, the trait distribution, levels of co-occurrence of irritability with other traits, and cutoffs that separate normative irritability from problem indicators. Categorical analysis includes a literature review with meta-analysis summarizing the prevalence rates of DMDD and developmental effects on DMDD prevalence, risk factors for this disorder, and co-occurrence patterns with other mental disorders. The author also discusses the current challenges of epidemiological research in pediatric irritability.
Measurement of Irritability in Children and Adolescents
Authors: Ametti Merelise , Althoff Robert R.
Published: April 2019

While irritability is a symptom included in multiple DSM psychiatric illnesses, it has remained an ill-defined and underresearched phenomenon until relatively recently. There have been multiple attempts made to measure irritability in childhood and adolescence. The purpose of this chapter is to provide an overview of the various approaches used in the measurement and empirical study of pediatric irritability. In this chapter, the authors describe attempts at measuring irritability with standardized diagnostic interviews, and then discuss how variable- and person-centered statistical models have shaped these earliest measures. The authors discuss models and measures that are emerging, including the construct of disruptive mood dysregulation disorder as well as measures such as the Affective Reactivity Index and the Child Behavior Checklist-Dysregulation Profile. They conclude that, given the transdiagnostic nature of irritability, efforts should be made to understand the relationship of irritability to various forms of developmental psychopathology using multiple methods.
Pharmacological Treatment of Pediatric Irritability
Authors: Dickstein Daniel P. , Christensen Rachel E.
Published: April 2019

Irritability is among the most common and impairing mental health issues affecting children today, with research showing that the consequences of irritability last into adulthood. Advancing how we treat irritability, including with medications, thus should be a top public health priority, germane to all those working with children and adults, and not just restricted to mental health settings. In this chapter, the authors review general principles of using medication to treat irritability in children. Then, they provide the latest information about the pharmacological treatment of irritability. In doing so, they draw on published studies of disorders involving irritability, including bipolar disorder (BD), unipolar major depressive disorder (MDD), attention deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), intermittent explosive disorder (IED), and autism spectrum disorder (ASD). While there is ample room for innovative ways to assess and treat irritability in children, at present, clinicians should carefully assess the child, develop a working hypothesis for what disorder(s) involving irritability are present, use evidence-based treatments to address those problems, and then reassess for improvement, worsening, side effects, or how these longitudinal data shapes working diagnoses.
The fate of planetesimal discs in young open clusters: implications for 1I/’Oumuamua, the Kuiper belt, the Oort cloud, and more
Authors: Hands T O , Dehnen W , Gration A , Stadel J , Moore B
Published: April 2019

We perform N-body simulations of the early phases of open cluster evolution including a large population of planetesimals, initially arranged in Kuiper-belt like discs around each star. Using a new, fourth-order, and time-reversible N-body code on Graphics Processing Units (GPUs), we evolve the whole system under the stellar gravity, i.e. treating planetesimals as test particles, and consider two types of initial cluster models, similar to IC348 and the Hyades, respectively. In both cases, planetesimals can be dynamically excited, transferred between stars, or liberated to become free-floating (such as A/2017 U1 or ’Oumuamua) during the early cluster evolution. We find that planetesimals captured from another star are not necessarily dynamically distinct from those native to a star. After an encounter, both native and captured planetesimals can exhibit aligned periastrons, qualitatively similar to that seen in the Solar system and commonly thought to be the signature of Planet 9. We discuss the implications of our results for both our Solar system and exoplanetary systems.
CmTCP20 Plays a Key Role in Nitrate and Auxin Signaling-Regulated Lateral Root Development in Chrysanthemum
Authors: Fan Hong-Mei , Sun Cui-Hui , Wen Li-Zhu , Liu Bo-Wen , Ren Hong , Sun Xia , Ma Fang-Fang , Zheng Cheng-Shu
Published: April 2019

Lateral root (LR) formation and development play a vital role in plant development by permitting the establishment of branched root systems. It is well known that nutrient availability controls LR development. Moreover, LR development is fine-tuned by a myriad of hormonal signals. Many transcription factors (TFs) participate in LR development. Here, we discuss the TFs involved in the nitrate and auxin signaling pathways and how these function in the regulation of LR formation and development in chrysanthemum. AtTCP20 is a plant-specific TF, which can modulate LR development in response to nitrate. The roles of CmTCP20 in LR development were identified by overexpression in chrysanthemum and heterologous expression in Arabidopsis. Overexpression of CmTCP20 significantly increased the number and average length of LRs compared with the wild type in chrysanthemum and Arabidopsis. We also found that CmTCP20 positively influenced auxin accumulation in the LRs at least partly by improving auxin biosynthesis, transport and response, thereby promoting LR development. Moreover, we found that CmTCP20 interacts with an auxin response factor, CmARF8, which also can be induced by nitrate and combined to proximal sites in the upstream promoter region of CmCYCB1;1 to positively regulate the cell cycle. The CmTCP20-CmARF8 heterodimer links nitrate and auxin signaling and converts cell-cycle signals to regulate LR initiation and growth.
Gibberellins Play a Role in Regulating Tomato Fruit Ripening
Authors: Li Hu , Wu Han , Qi Qi , Li Huihui , Li Zhifei , Chen Shen , Ding Qiangqiang , Wang Quanzhi , Yan Zhiming , Gai Ying , Jiang Xiangning , Ding Jing , Gu Tingting , Hou Xilin , Richard McAvoy , Zhao Yunde , Li Yi
Published: April 2019

Although exogenous applications of gibberellins (GAs) delay tomato ripening, the regulatory mechanisms of GAs in the process have never been well recognized. Here, we report that the concentration of endogenous GAs is declined before the increase of ethylene production in mature-green to breaker stage fruits. We further demonstrate that reductions in GA levels via overexpression of a GA catabolism gene SlGA2ox1 specifically in fruit tissues lead to early ripening. Consistently, we have also observed that application of a GA biosynthetic inhibitor, prohexadione-calcium, at the mature-green stage accelerates fruit ripening, while exogenous GA3 application delays the process. Furthermore, we demonstrate that ethylene biosynthetic gene expressions and ethylene production are activated prematurely in GA-deficient fruits but delayed/reduced in exogenous GA3-treated WT fruits. We also show that the GA deficiency-mediated activation of ethylene biosynthesis is due to the activation of the ripening regulator genes RIN, NOR and CNR. In conclusion, our results demonstrate that GAs play a negative role in tomato fruit ripening.
Genome-Wide Analysis of Phospholipase D Gene Family and Profiling of Phospholipids under Abiotic Stresses in Brassica napus
Authors: Lu Shaoping , Fadlalla Tarig , Tang Shan , Li Long , Ali Usman , Li Qing , Guo Liang
Published: April 2019

Oil crop Brassica napus is subjected to environmental stresses such as drought, cold and salt. Phospholipase Ds (PLDs) have vital roles in regulation of plant growth, development and stress tolerance. In this study, 32 BnaPLD genes were identified and classified into six subgroups depending on the conserved protein structures. High similarity in gene and protein structures exists between BnaPLDs and AtPLDs. Gene expression analysis showed that BnaPLDα1s and BnaPLDδs had higher expression than other PLDs. BnaPLDα1 and BnaPLDδ were significantly induced by abiotic stresses including dehydration, NaCl, abscisic acid (ABA) and 4ï¿½C. Lipidomic analysis showed that the content of main membrane phospholipids decreased gradually under stresses, except phosphatidylglycerol increased under the treatment of ABA and phosphatidylethanolamine increased under 4ï¿½C. Correspondingly, their product of phosphatidic acid increased often with a transient peak at 8 h. The plant height of mutants of PLDα1 was significantly reduced. Agronomic traits such as yield, seed number, silique number and branches were significantly impaired in PLDα1 mutants. These results indicate that there is a large family of PLD genes in B. napus, especially BnaPLDα1s and BnaPLDδs may play important roles in membrane lipids remodeling and maintaining of the growth and stress tolerance of B. napus.
Sperm Entry into the Egg Cell Induces the Progression of Karyogamy in Rice Zygotes
Authors: Ohnishi Yukinosuke , Kokubu Iwao , Kinoshita Tetsu , Okamoto Takashi
Published: April 2019

Karyogamy is a prerequisite event for plant embryogenesis, in which dynamic changes in nuclear architecture and the establishment of appropriate gene expression patterns must occur. However, the precise role of the male and female gametes in the progression of karyogamy still remains elusive. Here, we show that the sperm cell possesses the unique property to drive steady and swift nuclear fusion. When we fertilized egg cells with sperm cells in vitro, the immediate fusion of the male and female nuclei in the zygote progressed. This rapid nuclear fusion did not occur when two egg cells were artificially fused. However, the nuclear fusion of two egg nuclei could be accelerated by additional sperm entry or the exogenous application of calcium, suggesting that possible increase of cytosolic Ca2+ level via sperm entry into the egg cell efficiently can facilitate karyogamy. In contrast to zygotes, the egg–egg fusion cells failed to proliferate beyond an early developmental stage. Our transcriptional analyses also revealed the rapid activation of zygotic genes in zygotes, whereas there was no expression in fused cells without the male contribution. Thus, the male sperm cell has the ability to cause immediate karyogamy and to establish appropriate gene expression patterns in the zygote.
Fillings and fittings of unit cotangent bundles of odd-dimensional spheres
Authors: Kwon Myeonggi , Zehmisch Kai
Published: April 2019

We introduce the concept of fittings to symplectic fillings of the unit cotangent bundle of odd-dimensional spheres. Assuming symplectic asphericity we show that all fittings are diffeomorphic to the respective unit co-disc bundle.
Gout and hyperuricaemia in the USA: prevalence and trends
Authors: Singh Gurkirpal , Lingala Bharathi , Mithal Alka
Published: April 2019

Objectives

Several recent observations have suggested that the prevalence of gout may be increasing worldwide, but there are no recent data from the USA. We analysed the prevalence of hyperuricaemia and gout in the US population from 2007–08 to 2015–16.

Methods

We studied adults ⩾20 years of age from the National Health and Nutrition Examination Survey from 2007–08 to 2015–16. Persons with gout were identified from the home interview question ‘Has a doctor or other health professional ever told you that you had gout?’ Hyperuricaemia was defined as a serum urate level >0.40 mmol/l (6.8 mg/dl) (supersaturation levels at physiological temperatures and pH).

Results

In 2015–16, the overall prevalence of gout among US adults was 3.9%, corresponding to a total affected population of 9.2 million. Hyperuricaemia (>0.40 mmol/l or 6.8 mg/dl) was seen in 14.6% of the US population (estimated 32.5 million individuals). No significant trends were identified in the age-adjusted prevalence of gout and hyperuricaemia. Statistical comparisons between 2007–08 and 2015–16 age-adjusted rates were not significant.

Conclusion

While the age-adjusted prevalence of gout and hyperuricaemia has remained unchanged in the most recent decade from 2007–08 to 2015–16, the estimated total number of persons with self-reported gout has increased from 8.3 million to 9.2 million. The age-adjusted prevalence of hyperuricaemia has declined slightly, but the total number of affected individuals is virtually identical (32.5 million in 2015–16 compared with 32.1 million in 2007–08).
The Oxford Spherical Mill for Metaphyseal Debridement in Open Epiphyseal Reduction and Internal Fixation for Slipped Capital Femoral Epiphysis
Authors: Lloyd Thomas , Duncan James , Kothari Alpesh , Elkhouly Amr , Davies Nev
Published: April 2019

Slipped capital femoral epiphysis (SCFE) is an adolescent hip disorder characterized by displacement of the proximal femoral epiphysis relative to the metaphysis. The aim of treatment is to stabilize the proximal epiphysis, avoid further displacement and prevent femoral head osteonecrosis. Open reduction and internal fixation is often required to treat chronic and severe SCFE, typically using a Modified Dunn procedure. This allows anterior access to the proximal femur, epiphyseal mobilization and metaphyseal debridement of cervical callus. Debriding the cervical callus concentrically to allow accurate relocation of the epiphysis on the metaphysis can be challenging. This article describes the benefits of using the Oxford Spherical Mill from a partial knee replacement system to assist with metaphyseal debridement during open epiphyseal reduction and internal fixation for SCFE.
Tuck-In Tenon Patch Graft in Corneal Perforation
Authors: Sharma Namrata , Singhal Deepali , Maharana Prafulla Kumar , Vajpayee Rasik B.
Published: April 2019

Purpose:

To describe the outcomes of tuck-in tenon patch graft (TPG) in the management of corneal perforation up to 5-mm size.

Methods:

Thirty-one cases of sterile corneal perforation (3–5 mm) underwent autologous TPG. The technique included, freshening of the edges, measuring the size of defect, creating a 360-degree stromal pocket around the perforation margin, harvesting the tenon graft followed by tucking into the stromal pocket, and application of cyanoacrylate glue or suturing the graft using 10-0 monofilament nylon suture. The main outcome measure was rate of healing (percentage of cases healed).

Results:

The mean age was 52.3 ± 8.9 years with 22 male and 9 female patients. The various etiologies of corneal perforation included trauma (n = 10), neurotrophic keratitis (n = 11), and peripheral ulcerative keratitis (n = 10). The mean size of corneal perforation was 4.2 ± 0.6 mm (range 3–5 mm). The mean duration of epithelial healing was 25.7 ± 6.7 days. Best-corrected visual acuity improved from 1.8 ± 0.4 to 1.2 ± 0.4 logarithm of the minimum angle of resolution units at 4 weeks after surgery (P ≤ 0.01). Twenty-seven (87.1%) cases healed with formation of a leucomatous scar at 16.9 ± 2.7 weeks, whereas 4 cases had a flat anterior chamber. In three-fourths of the cases, a corneal graft was performed. In one case, graft resuturing was performed for post-op aqueous leak, which healed with the formation of a corneo-iridic scar.

Conclusions:

TPG is a safe, simple, inexpensive, and an effective technique for the management of corneal perforations. The advantages include the autologous nature of the graft, cost effectiveness, and easy availability.
Hepatitis C therapy with direct antiviral agents in patients with advanced chronic kidney disease: real-world experience of the German Hepatitis C-Registry (Deutsches Hepatitis C-Register)
Authors: Wiegand Johannes , Buggisch Peter , Mauss Stefan , Boeker Klaus H.W. , Klinker Hartwig , Müller Tobias , Günther Rainer , Serfert Yvonne , Manns Michael P. , Zeuzem Stefan , Berg Thomas , Hinrichsen Holger , C-Registry German Hepatitis
Published: April 2019

Background

Direct-acting antiviral agents (DAAs) have revolutionized treatment of chronic hepatitis C in patients with normal glomerular filtration rate (GFR). However, patients with impaired kidney function have been excluded from several clinical trials. We, therefore, investigated the use, effectiveness, and tolerability of DAAs in patients with GFR less than 30 ml/min in the real-world setting.

Patients and methods

An analysis was done within the German Hepatitis C-Registry on 5733 patients including 46 individuals with a baseline GFR less than 30 ml/min treated with sofosbuvir-based (61%) or paritaprevir/ritonavir-based (39%) regimens.

Results

Sustained virological response 12 rates did not differ significantly between patients with baseline GFR less than 30 versus more than 30 ml/min (91 vs. 96%). Nine individuals with a baseline GFR more than 30 ml/min presented with a GFR less than 30 ml/min at the end of treatment. GFR improvement from less than 30 ml/min to more than 30 ml/min was observed in 9/46 cases. Adverse events did not differ in patients with GFR less than 30 versus more than 30 ml/min. However, serious adverse events were significantly more frequent in individuals with GFR less than 30 ml/min and associated with ribavirin.

Conclusion

Different DAA therapies can be safely used with high sustained virological response rates in patients with GFR less than 30 ml/min. Ribavirin has to be avoided because of poor tolerability.
Utility of Metabolic Parameters on FDG PET/CT in the Classification of Early-Stage Lung Adenocarcinoma
Authors: Iwano Shingo , Ito Shinji , Kamiya Shinichiro , Ito Rintaro , Kato Katsuhiko , Naganawa Shinji
Published: April 2019

Purpose

This paper aims to explore the role of a metabolic parameter on18F-FDG-PET/CT for clinical T-classification in early-stage adenocarcinoma.

Patients and Methods

One hundred six surgically resected pathological TNM stage (p-stage) 0/I lung adenocarcinomas were retrospectively reviewed. The solid size (SS) measured on thin-section CT and the pathological invasive size (IS) of tumors were recorded. The SUVmax and metabolic tumor volume with SUV ≥1.0 (MTV1.0) derived from PET/CT data were measured on a workstation, and the metabolic tumor diameter with SUV ≥1.0 (MTD1.0) was calculated automatically from MTV1.0. For the correlations between the IS and the SS, MTD1.0, or SUVmax, Pearson's correlation coefficients were compared using the Meng-Rosenthal-Rubin method. Additionally, the reproducibility between the clinical TNM stage (c-stage), based on the SS or MTD1.0, and the p-stage was analyzed using the kappa coefficient (k).

Results

For the correlations between the IS and the other parameters, Pearson correlation coefficient was 0.630 for the SS, 0.600 for the SUVmax, and 0.725 for MTD1.0. MTD1.0correlated significantly and more strongly with the IS than the SS and the SUVmax did (P= 0.040, andP= 0.008, respectively). The reproducibility between p-stage and c-stage based on the SS was moderate (k = 0.529,P< 0.001), whereas that between p-stage and c-stage based on MTD1.0was substantial (k = 0.676,P< 0.001).

Conclusions

MTD1.0on FDG-PET/CT was correlated significantly and more strongly with the pathological IS in lung adenocarcinomas than with the SS on thin-section CT. FDG-PET/CT could classify more precisely early-stage lung adenocarcinoma than the presently used T-classification based on thin-section CT findings.
Teaching Written Expression to Students With Autism Spectrum Disorder and Complex Communication Needs
Authors: Pennington Robert C. , Carpenter Megan
Published: April 2019

Written expression is critical to the full participation of individuals with autism spectrum disorder and complex communication needs in a wide range of educational and community contexts. Unfortunately, the extant research on teaching writing to this unique population is limited and, thus, provides little guidance to practitioners in the design of instruction. In this article, the authors present a set of recommendations extracted from the available research literature on teaching writing to students with autism spectrum disorder, offer examples of their successful application, and suggest areas of future research.
Growing from a few cells: combined effects of initial stochasticity and cell-to-cell variability
Authors: Barizien A. , Suryateja Jammalamadaka M. S. , Amselem G. , Baroud Charles N.
Published: April 2019

The growth of a cell population from a large inoculum appears deterministic, although the division process is stochastic at the single-cell level. Microfluidic observations, however, display wide variations in the growth of small populations. Here we combine theory, simulations and experiments to explore the link between single-cell stochasticity and the growth of a population starting from a small number of individuals. The study yields descriptors of the probability distribution function (PDF) of the population size under three sources of stochasticity: cell-to-cell variability, uncertainty in the number of initial cells and generation-dependent division times. The PDF, rescaled to account for the exponential growth of the population, is found to converge to a stationary distribution. All moments of the PDF grow exponentially with the same growth rate, which depends solely on cell-to-cell variability. The shape of the PDF, however, contains the signature of all sources of stochasticity, and is dominated by the early stages of growth, and not by the cell-to-cell variability. Thus, probabilistic predictions of the growth of bacterial populations can be obtained with implications for both naturally occurring conditions and technological applications of single-cell microfluidics.