bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient Autonomy, Capacity, and Consent
Authors: Donnelly Mary , Berg Jessica
Published: July 2020

This chapter explores a number of key issues: the role of competence and capacity, advance directives, and decisions made for others. It analyses the ways these are treated in the United States and in selected European jurisdictions. National-level capacity legislation and human rights norms play a central role in Europe, which means that healthcare decisions in situations of impaired capacity operate in accordance with a national standard. In the United States, the legal framework is more state-based (rather than federal), and the courts have played a significant role, with both common law and legislation varying considerably across jurisdictions. Despite these differences, this chapter identifies some similar legal principles which have developed.
Introduction to Regulation of Professionals and Facilities
Authors: Madden Deirdre , Buck Isaac D.
Published: July 2020

This chapter briefly introduces the regulation of healthcare providers and facilities within the United States and Europe. It shows that even though the regimes differ in key areas, systems in the European Union and the United States share certain overlapping themes. Quality regulation in both systems seeks to prevent harm to patient health from occurring in the first place. Both European and American systems also face challenges posed by definitional limitations around the practice of medicine, and both employ different types of regulation (and softer incentives) in different scenarios. Nonetheless, the systems also differ in key ways. Most prominently, the American system has a more comprehensive and robust regulatory structure for hospitals and entities than some European systems, although there is wide divergence between national systems in Europe.
The Accuracy of Self-Judgments of Personality
Authors: Spain Jana S.
Published: July 2020

How accurate are self-judgments of personality traits? When it comes to judging our own enduring personality characteristics, are we hopelessly blind, deluded, and biased, or are we generally accurate? In order to answer these questions, this chapter reviews the empirical evidence regarding the accuracy of trait self-judgments. Although self-judgments are not always perfectly accurate, the majority of studies suggest that self-judgments of personality have considerable validity. Self-judgments of both narrow, specific traits and the broad personality factors of the Big Five agree with judgments provided by knowledgeable others and predict personality-relevant states, experiences, behaviors, and consequential life outcomes. Suggestions for improving the accuracy of our self-judgments and directions for future research on the accuracy of trait self-judgments are discussed.
Humanism and the Renaissance
Authors: Monfasani John
Published: July 2020

Both the Renaissance and humanism have anachronistically taken on meanings today that betray their historical reality. Emerging from the peculiar lay professional culture of medieval Italy, humanism joined in the Renaissance with other elements of medieval Italian culture to dominate the educated world of sixteenth- and seventeenth-century Europe. The Renaissance humanists constituted, in the words of Paul Oskar Kristeller, “a characteristic phase in what may be called the rhetorical tradition in Western culture.” Renaissance humanism created not an ideology or philosophy, but a dynamic set of educated interests and methods dominated by rhetorical and literary interests and focused on imitation of classical eloquence and literature. The humanists would in time powerfully reshape European learning, education, and, ultimately, self-conception. A non-trivial residue of Renaissance humanism is our understanding of the disciplines that make up the humanities and that we view as essential to educated culture.
Revolution and Counterrevolution in Guatemala
Authors: González-Izás Matilde
Published: July 2020

This article analyzes the dynamics of the participation of Guatemala’s Northwestern land-owning elites in the counterrevolution that led to the forceful deposing, in 1954, of the Arbenz administration. The Arbenz administration had introduced sweeping changes in Guatemalan society and thereby threatened the until-then unquestioned privileges of landowning provincial elites. Emphasis is placed on the perspective from which members of the National Liberation Movement understood the agrarian and labor reforms launched by the two governments of the 1944 Revolution as a communist plot and how they enrolled, as a result, in the National Liberation Army which participated in the coup and perpetrated repressive post-coup actions against those who had benefited from the reforms. This process leads the analysis to ponder over the problematic process in Guatemala of the transition from oligarchy to democracy.
States in Latin America
Authors: Brachet-Márquez Viviane
Published: July 2020

The idea that the study of national states is no longer useful due to globalization is questioned. The four chapters in the present section on the state in Latin America aim at deepening our knowledge of the responsibilities they shoulder and limitations they face.
Literacy and Academic Engagement in Learners Who Are Deaf and Hard of Hearing
Authors: Catalano Jennifer A.
Published: July 2020

Academic engagement is essential for achievement in literacy. Greater language and literacy gains are achieved when students are actively engaged in activities that intentionally build on the strengths, and strategically address the current limitations, of the individual child. In their early years, students who are deaf and hard of hearing (DHH) often experience delays in literacy development due to limited or delayed access to a comprehensive language. Despite academic struggles, DHH students are as engaged as their typically hearing peers in the classroom setting. However, they are given fewer opportunities to respond academically and spend less time reading at school in comparison to peers with typical hearing. Consequently, DHH students may be more passively engaged in their learning with fewer opportunities for active engagement in literacy instruction. Through a review of the literature on academic engagement in literacy instruction, this chapter emphasizes the importance of creating a learning environment that encourages active engagement and addresses the individual needs of DHH students. The chapter ends with a discussion of strategies and methods designed to support the engagement and literacy achievement of DHH students in terms of instructional arrangements, teacher behaviors, and academic responding.
Idealism
Authors: Pelczar Michael
Published: July 2020

Metaphysical idealism is the mirror-image of physicalism about the mental: where physicalists contend that the mental facts of our world supervene on the physical facts (but not vice versa), idealists contend that the physical facts of our world supervene on the mental facts (but not vice versa). Like physicalism, idealism is a kind of monism. According to idealists, the fundamental features of our world (or at least its fundamental contingent features) are all of one kind—the mental kind. Unlike physicalists, however, idealists try to achieve monism without reducing consciousness to something ostensibly more basic, or identifying consciousness with something that we previously didn’t realize was consciousness (like brain states). This chapter attempts to defend idealism as a more attractive position than is often thought in current philosophy of mind.
A Priori Physicalism
Authors: Jackson Frank
Published: July 2020

Physicalism is a thesis in metaphysics: the nature of the mind and its states are such that we need no more than the physical properties to give a complete account of them. According to a priori physicalism, this thesis in metaphysics implies a thesis about a priori entailment. If the thesis in metaphysics is true, a sufficiently rich account of a subject—you, me, or … —given in physical terms a priori entails how that subject is mentally. Why do some physicalists want to make things difficult for themselves by embracing a priori physicalism; why do they believe that a posteriori physicalism—a prima facie less demanding version of physicalism—is not an option? This is the topic of this chapter. As we will see, there are a number of reasons that have or might be given.
Self-Representationalist Theories of Consciousness
Authors: McClelland Tom
Published: July 2020

Self-Representationalists hold that conscious mental states are conscious in virtue of suitably representing themselves, and that awareness of a mental state is achieved by representing oneself as being in that state. Where Higher-Order Representationalists claim that awareness of a mental state is conferred by a distinct mental state that represents it, Self-Representationalists instead argue that conscious mental states represent themselves. This chapter explores why Self-Representationalists make this move away from Higher-Order Representationalists and describes the internal divisions among Self-Representationalist theories. These divisions concern: whether conscious states have distinguishable components corresponding to their lower-order and higher-order content; whether the higher-order component of a conscious state (if such there is) is itself represented by that state. The challenges faced by Self-Representationalist include: the threat of collapsing into a Higher-Order Representationalist theory; the worry that the proposed self-representing states resist naturalization; and the danger of failing to accommodate the intimate contact we have with our own conscious states.
The Epistemic Approach to the Problem of Consciousness
Authors: Stoljar Daniel
Published: July 2020

According to the epistemic view of the hard problem of consciousness, we are ignorant at least for the time being of something important and relevant when it comes to the hard problem, and this fact has a significant implication for its solution. This chapter outlines one version of the view before considering two objections. The first is that, while we may be ignorant of various features of the world, we are not ignorant of any feature that is relevant to the hard problem. The second is that, even if the epistemic approach is true, properly understood it is not an answer to the hard problem; indeed, it is no contribution to that problem at all. The chapter concludes with some brief reflections on why the epistemic approach, despite its attractiveness, remains a minority view in contemporary philosophy of mind.
Consciousness, Introspection, and Subjective Measures
Authors: Spener Maja
Published: July 2020

In recent years, the divide between conscious and unconscious perception has been the focus of a thriving research area in the science of consciousness. Subjective measures, frequently referred to as ‘introspective measures’, play a prominent role in this literature and have been the subject of intense criticism. This chapter discusses the main types of subjective measures used in current-day science of consciousness. I explain the key worry about such measures, namely the problem of a putatively ever-present response bias. I then turn to the question of whether subjective measures of consciousness are introspective. I show that there is no clear answer to this question, as proponents of subjective measures do not employ a worked out notion of subjective access. In turn, as I explain, this makes the problem of response bias less tractable than it might otherwise be.
Non-Visual Perception
Authors: O'Callaghan Casey
Published: July 2020

This chapter addresses perceptual consciousness beyond vision. An impressive reach of human perceptual consciousness is non-visual. From this perspective, it is odd that philosophers have so persistently focused on visual forms at the expense of others. This oversight has potential costs. Nothing guarantees that claims about perceptual consciousness or its phenomenology founded on vision alone generalize to non-visual ways of perceiving. Moreover, critical features may be missed by dwelling on vision. If we are after a general and comprehensive account of perceptual consciousness and its phenomenology, it is poor methodology to focus exclusively on vision. This chapter aims to provide the background that is relevant to understanding and appreciating the significance of varieties of consciousness associated with other sensory modalities, such as hearing, touch, smell, and taste.
Electrophysiology
Authors: Jacobsen Thomas , Klein Stina
Published: July 2020

One important method that can be applied for gaining an understanding of the implementation of aesthetics in the brain is that of electrophysiology. Cognitive electrophysiology, in particular, allows the identification of components in a mental processing architecture. The present chapter reviews findings in the neurocognitive psychology of aesthetics, or neuroaesthetics, that have been obtained with the method of event-related brain potentials (ERPs), as derived from the human electroencephalogram (EEG). The cognitive-perceptual bases, as well as affective sub-stages of aesthetic processing have been investigated, and those are described here. The ERP method allows for the identification of mental processing modes in cognitive and aesthetic processing. It also provides an assessment of the mental chronometry of cognitive and affective stages in aesthetic appreciation. As the work described here shows, distinct processes in the brain are engaged in aesthetic judgments.
Noninvasive Brain Stimulation Contribution to Research in Neuroaesthetics
Authors: Cattaneo Zaira
Published: July 2020

Noninvasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES), are largely employed in cognitive neuroscience to investigate the brain–behavior relationship. During the last decade, non-invasive brain stimulation techniques have been increasingly employed in the field of neuroaesthetics research to shed light on the possible causal role of different brain regions contributing to aesthetic appreciation. This chapter provides a synthetic description of mechanisms of actions of TMS and different types of tES, and reviews recent NIBS studies that have shed light on the neural underpinning of aesthetic evaluation of (visual) artworks. The chapter also considers methodological limitations of the reviewed studies and the future potential for non-invasive brain stimulation to significantly contribute to the understanding of the neural bases of visual aesthetic experiences.
Aesthetic Sensitivity
Authors: Myszkowski Nils
Published: July 2020

Since the beginning of the time when researchers have endeavored to understand and identify giftedness and individual ability, they have been attentive to how individuals differ in their capacity to recognize aesthetic quality—a construct that is frequently referred to as aesthetic sensitivity. In this chapter, I first attempt to clarify what the intricate construct of aesthetic sensitivity refers to—and what it does not. Then, I briefly depict the century-old history of research on the topic. Later, I examine the main challenges that arise from the accurate measurement of aesthetic sensitivity, and the strategies used to face such challenges. Afterwards, I discuss the relations between aesthetic sensitivity and mental ability, as well as with personality. I later discuss the training and development of aesthetic sensitivity. Finally, I review the current limitations of—and propose future directions for—research on the topic.
Signs and Symbols
Authors: Piquette Kathryn E.
Published: July 2020

The human ability to represent concepts through image-making seems pivotal for enabling the formation of complex cultures. This chapter is concerned with the important but permeable boundaries between and around the categories of ‘art’ and ‘writing’. The writing:art/sign:symbol distinction has been fundamental to the location of the survey points forming the boundaries between archaeology and its siblings, e.g. philology, classics and ancient history, and to some extent anthropology. Contemporary notions of art and writing are contrasted with those of past societies and how image-bearing objects differ from other kinds of material culture. The question of when a drawing of something becomes part of a writing system and the types of literacy required to understand linguistic signs are also considered. Sociological and anthropological approaches to art and contemporary theories of visual culture are evaluated for the ways in which these can contribute to archaeological discourse on sign and symbol as a branch of material culture studies.
Twenty Years after: Statute of Limitations and the Asymmetric Burdens of Justice in Northern Ireland and Post-war Germany
Authors: Chung C K Martin
Published: July 2020

In 2018, that is 20 years after the conclusion of the Belfast Agreement ending the 30-year conflict in Northern Ireland known as the ‘Troubles’, the UK Government started a consultation on dealing with its legacy. The House of Commons Defence Committee proposes the enactment of a statute of limitations to shield veterans from further investigations into Troubles-related crimes. It would represent a ‘balanced’ approach to justice, as some paramilitary combatants had also received de facto amnesty through various schemes. This article argues that given the involvement of the British state in the historical conflict, a ‘balanced’ approach to dealing with the past is inadequate. Drawing on parallel parliamentary debates in Germany that began around 1965, that is also 20 years after the end of conflict, the article makes the case that an asymmetric approach is both promising and necessary for the reconciliation process to move forward.
Relationship of George Floyd protests to increases in COVID-19 cases using event study methodology
Authors: Valentine Randall , Valentine Dawn , Valentine Jimmie L
Published: July 2020

Background

Protests ignited by the George Floyd incident were examined for any significant impact on COVID-19 infection rates in select US cities.

Methods

Eight US cities were studied in which protestors in the tens of thousands were reported. Only cities that reside in states whose stay-at-home orders had been rescinded or expired for a minimum of 30 days were included in the sample to account for impact of growth rates solely due to economies reopening. Event study methodology was used with a 30-day estimation period to examine whether growth in COVID-19 infection rates was significant.

Results

In the eight cities analyzed, all had positive abnormal growth in infection rate. In six of the eight cities, infection rate growth was positive and significant.

Conclusions

In this study, it was apparent that violations of Centers for Disease Control and Prevention (CDC)-recommended social distancing guidelines caused a significant increase in infection rates. The data suggest that to slow the spread of COVID-19, CDC guidelines must be followed in protest situations.
Metastatic Mimics of Primary Cutaneous Lesions: Averting Diagnostic Pitfalls With Significant Repercussions
Authors: Olson Luke C. , LeBlanc Robert E. , Momtahen Shabnam , Sriharan Aravindhan , Yan Shaofeng , Linos Konstantinos
Published: July 2020

Cutaneous metastases by solid malignancies often signify advanced disease and portend severely limited survival. Appropriate diagnosis of these lesions is particularly hampered when they closely resemble primary cutaneous tumors. In this article, we present two diagnostically challenging cases of metastatic lesions to the scalp bearing striking histologic resemblance to primary cutaneous neoplasms. One case of a metastatic urothelial carcinoma showed epidermotropism as well as histologic and immunohistochemical features virtually indistinguishable from those of a poorly differentiated squamous cell carcinoma. Next generation sequencing was performed on both the primary urothelial carcinoma and scalp malignancy revealing an identical BRAF p. S467L somatic mutation, confirming the diagnosis. Another case of metastatic renal cell carcinoma showed clinical and histomorphologic features highly reminiscent of a pyogenic granuloma. These cases demonstrate the potential of metastatic lesions to assume a myriad array of innocuous disguises and underscore the vigilance required to avoid misdiagnosis. In addition, we highlight the emerging role of molecular strategies in resolving these problematic cases.
The Effect of Unilateral Vestibular Loss on Standing Balance During Postural Threat
Authors: Cleworth Taylor W. , Allum John H. J. , Luu M. John , Lea Jane , Westerberg Brian W. , Carpenter Mark G.
Published: July 2020

Objective:

Vestibular deficit patients have an increased fall risk and fear of falling. Postural threat, known to increase balance-related fear and anxiety, influences vestibular gains during quiet standing in young healthy adults. The current study examined whether there is a similar relationship for peripheral unilateral vestibular loss (UVL) patients in comparison to age-matched healthy controls (HC).

Setting:

University laboratory.

Study Design:

Prospective laboratory study.

Patients and Controls:

Eleven UVL patients, nine with vestibular neurectomy. Eleven aged-matched HCs.

Main Outcome Measures:

Subjects stood on a hydraulic lift placed at two heights: low (0.8 m, away from the edge) and high (3.2 m, at the edge). Amplitude (root mean square), mean power frequency (MPF), and mean position were analyzed for center of foot pressure (COP) and 90% ranges for angle amplitude and velocity for trunk sway.

Results:

Group interactions were strongest for anterior-posterior (AP) COP and trunk pitch angle. AP lean away from the edge was greater in HCs than UVLs. HCs, but not UVLs had a decrease in root mean square AP COP with height. Trunk pitch sway was changed similarly. Both groups had increased trunk pitch velocity at height. Changes with height were less for roll: MPF of lateral COP increased with height for UVLs with no changes for HCs, and trunk roll amplitude decreased for both groups.

Conclusions:

This report provides evidence for a differential effect of height induced postural threat on balance control between UVLs and HCs presumably due to the reduced vestibular-spinal gain in UVL subjects.
Treatment of the tibial pilon fractures using the antero-medial fibula approach
Authors: Ren Dong , Wang Tianci , Liu Yueju , Liu Pengbo , Wang Pengcheng
Published: July 2020

Pilon fractures are always results of the high-energy trauma. They are often accompanied with serious soft tissue injury, and tension blisters happened in most cases. For comminuted fractures and poor soft tissue, how to select the incision is challenging. This study aimed to explore the outcomes of the treatment of ten 43-B/C pilon fractures using an anteromedial fibula approach.

Ten closed pilon fractures combined with fibula fractures were treated in our hospital from January 2015 to July 2016. Six cases were AO/OTA type 43-B and 4 cases were 43-C, including 9 males and 1 female with a mean age of 36.3 years (range: 20–60 years). When the skin wrinkled, all patients were treated by the senior authors with open reduction and internal fixation using an anteromedial fibula approach. Postoperatively, patients were followed up at 1 month, 3 months, 6 months, 12 months, and 18 months, respectively. The incision healing, the American Orthopedic Foot and Ankle Society scores and fracture healing were recorded to get a comprehensive evaluation of the effect for the incision.

All patients were followed from 9 to 18 months (average: 14.1 months). Anatomic reduction was achieved in 7 cases and satisfactory in 3 cases by the Burwell–Charnley radiological criteria evaluation. All patients had complete retention of the dorsal extensor tendon sheath. The most incisions had a good healing without necrosis at 2 weeks after surgery except 1 case. The factures were healed at a range of 12 to 18 weeks (average: 13.7 ± 1.2 weeks). The American Orthopedic Foot and Ankle Society scores were excellent in 7 cases and good in 3 cases at 1 year after surgery (average: 85.6 ± 4.2 points). The satisfactory outcomes were achieved in most patients.

The anteromedial fibula approach used for pilon fractures can lead to an effective exposure and allow fixation of tibia and fibula fractures with minimal soft tissue injury. It is a safe, simple, and effective approach that allows for satisfactory functional rehabilitation of the ankle joint.

Level of evidence:

therapeutic Level IV.
Characteristics and prognosis of primary malignant melanoma of the esophagus
Authors: Chen Hengchi , Fu Qiang , Sun Kelin
Published: July 2020

Primary malignant melanoma of esophagus (PMME) is a rare malignant tumor of esophagus. This study aimed to investigate the clinic pathologic characteristics and analyze the factors that might affect the prognosis of PMME patients.

A total of 20 PMME patients who underwent surgical treatment in our hospital from 1975 to 2017 were analyzed. The clinical data, surgical and pathologic features of all patients were collected.

For 20 PMME patients, the average age was 57.3 ± 10.7 years, and the male patients account for 75%. Most of the tumors (95%) were located in the middle and lower of the esophagus. There were 7 patients with primary tumor invasion beyond the muscular layer (T3 + T4) and 10 patients with lymph node metastasis (LNM). The median survival time of 20 patients was 12 months, and the 1-year and 5-year survival rates were 50% and 16.9%, respectively. The probability of LNM in tumors confined to submucosa (T1) and myometrium (T2) was lower than that in tumors with deeper invasion (T3, T4) (P = .035). Multivariate analysis showed that tumor node metastasis (TNM) staging was the independent prognostic factor for survival of PMME patients (hazard ratio [95% confidence interval], 4.15 [1.36–12.67]; P = .012).

For PMME patients, tumors with deeper invasion were more likely to have LNM, and TNM staging was an independent predictor of prognosis for survival. Early detection of the disease and radical resection of the tumor are critical for better survival of the PMME patients.
Clinical Presentation, Treatment, and Outcome of Parathyroid Carcinoma
Authors: Lenschow Christina , Schrägle Sina , Kircher Stefan , Lorenz Kerstin , Machens Andreas , Dralle Henning , Riss Philipp , Scheuba Christian , Pfestroff Andreas , Spitzweg Christine , Zielke Andreas , Nießen Anna , Dotzenrath Cornelia , Riemann Burkhard , Quinkler Marcus , Vorländer Christian , Zahn Alexandra , Raue Friedhelm , Chiapponi Costanza , Iwen Karl Alexander , Steinmüller Thomas , Kroiss Matthias , Schlegel Nicolas
Published: July 2020

Objective:

In this retrospective cohort study, we describe the clinical presentation and workup of parathyroid carcinoma (PC) and determine its clinical prognostic parameters. Primary outcome was recurrence free survival.

Summary Background Data:

PC is an orphan malignancy for which diagnostic workup and treatment is not established.

Methods:

Eighty-three patients were diagnosed with PC between 1986 and 2018. Disease-specific and recurrence-free survivals were estimated with the Kaplan-Meier method. Risk factors for recurrence were identified by binary logistic regression with adjustment for age and sex. Thirty-nine tumors underwent central histopathological review.

Results:

Renal (39.8%), gastrointestinal (24.1%), bone (22.9%), and psychiatric (19.3%) symptoms were the most common symptoms. Surgical treatment was heterogeneous [parathyroidectomy [PTx)] alone: 22.9%; PTx and hemithyroidectomy: 24.1%; en bloc resection 15.7%; others 37.3%] and complications of surgery were frequent (recurrent laryngeal nerve palsy 25.3%; hypoparathyroidism 6%). Recurrence of PC was observed in 32 of 83 cases. In univariate analysis, rate of recurrence was reduced when extended initial surgery had been performed (P = 0.04). In multivariate analysis low T status [odds ratio (OR) = 2.65, 95% confidence interval (CI) 1.02–6.88, P = 0.045], N0 stage at initial diagnosis (OR = 6.32, 95% CI 1.33–30.01, P = 0.02), Ki-67 <10% (OR = 14.07, 95% CI 2.09–94.9, P = 0.007), and postoperative biochemical remission (OR = 0.023, 95% CI 0.001–0.52, P = 0.018) were beneficial prognostic parameters for recurrence-free survival.

Conclusion:

Despite a favorable overall prognosis, PC shows high rates of recurrence leading to repeated surgery and postoperative recurrent laryngeal nerve palsy and hypoparathyroidism. In view of the reduced recurrence rate in cases of extended surgery, ipsilateral completion surgery may be considered when PC is confirmed.
Machine learning for classification and prediction of brain diseases: recent advances and upcoming challenges
Authors: Burgos Ninon , Colliot Olivier
Published: July 2020

Purpose of review

Machine learning is an artificial intelligence technique that allows computers to perform a task without being explicitly programmed. Machine learning can be used to assist diagnosis and prognosis of brain disorders. Although the earliest articles date from more than ten years ago, research increases at a very fast pace.

Recent findings

Recent works using machine learning for diagnosis have moved from classification of a given disease versus controls to differential diagnosis. Intense research has been devoted to the prediction of the future patient state. Although a lot of earlier works focused on neuroimaging as data source, the current trend is on the integration of multimodal data. In terms of targeted diseases, dementia remains dominant but approaches have been developed for a wide variety of neurological and psychiatric diseases.

Machine learning is extremely promising for assisting diagnosis and prognosis in brain disorders. Nevertheless, we argue that key challenges remain to be addressed by the community for bringing these tools in clinical routine: good practices regarding validation and reproducible research need to be more widely adopted; extensive generalization studies are required; interpretable models are needed to overcome the limitations of black-box approaches.
The Efficacy and Safety of Piribedil Relative to Pramipexole for the Treatment of Early Parkinson Disease: A Systematic Literature Review and Network Meta-Analysis
Authors: Chen Xianwen , Ren Cuiping , Li Juan , Wang Shangpei , Dron Louis , Harari Ofir , Whittington Craig
Published: July 2020

Objectives

Patients with early Parkinson disease (PD) frequently defer initiation of levodopa treatment to minimize long-term complications. Nonergoline dopamine agonists, such as pramipexole and piribedil, are frequent first-line therapies for early PD patients, yet limited head-to-head randomized controlled trial (RCT) evidence exists for dopamine agonists in this population. We therefore conducted a systematic literature review and network meta-analysis.

Methods

MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were systematically searched (until January 7, 2020), identifying RCTs assessing the efficacy of piribedil or pramipexole in early PD. Eligible trial data were incorporated into fixed- and random-effects Bayesian network meta-analyses.

Results

No RCTs were identified directly comparing piribedil with pramipexole, but 6 trials provided data for pramipexole versus placebo and 2 compared piribedil versus placebo, facilitating indirect comparisons. Across all time points assessed, no significant differences were found between pramipexole and piribedil for change in the Unified Parkinson's Disease Rating Scale (UPDRS) score from baseline. Piribedil and pramipexole demonstrated superiority relative to placebo for UPDRS II/III change at weeks 22 to 30. No significant differences were noted between the treatments at weeks 20 to 35 for anxiety, constipation, hypotension, nausea, and somnolence. Sensitivity analyses on adjustment for dose titration periods and baseline risk yielded the same pattern of results.

Conclusions

No significant differences were found for pramipexole versus piribedil in the UPDRS II/III scores from baseline in early PD, with similar safety profiles.
The functional relevance of task-state functional connectivity
Authors: Cole Michael W. , Ito Takuya , Cocuzza Carrisa , Sanchez-Romero Ruben
Published: July 2020

Resting-state functional connectivity has provided substantial insight into intrinsic brain network organization, yet the functional importance of task-related change from that intrinsic network organization remains unclear. Indeed, such task-related changes are known to be small, suggesting they may have only minimal functional relevance. Alternatively, despite their small amplitude, these task-related changes may be essential for the human brain’s ability to adaptively alter its functionality via rapid changes in inter-regional relationships. We utilized activity flow mapping – an approach for building empirically-derived network models – to quantify the functional importance of task-state functional connectivity (above and beyond resting-state functional connectivity) in shaping cognitive task activations in the (female and male) human brain. We found that task-state functional connectivity could be used to better predict independent fMRI activations across all 24 task conditions and all 360 cortical regions tested. Further, we found that prediction accuracy was strongly driven by individual-specific functional connectivity patterns, while functional connectivity patterns from other tasks (task-general functional connectivity) still improved predictions beyond resting-state functional connectivity. Additionally, since activity flow models simulate how task-evoked activations (which underlie behavior) are generated, these results may provide mechanistic insight into why prior studies found correlations between task-state functional connectivity and individual differences in behavior. These findings suggest that task-related changes to functional connections play an important role in dynamically reshaping brain network organization, shifting the flow of neural activity during task performance.

Significance Statement

Human cognition is highly dynamic, yet the human brain’s functional network organization is highly similar across rest and task states. We hypothesized that, despite this overall network stability, task-related changes from the brain’s intrinsic (resting-state) network organization strongly contribute to brain activations during cognitive task performance. Given that cognitive task activations emerge through network interactions, we leveraged connectivity-based models to predict independent cognitive task activations using resting-state versus task-state functional connectivity. This revealed that task-related changes in functional network organization increased prediction accuracy of cognitive task activations substantially, demonstrating their likely functional relevance for dynamic cognitive processes despite the small size of these task-related network changes.
Quantifying the effects of switchgrass (Panicum virgatum) on deep organic C stocks using natural abundance14C in three marginal soils
Authors: Slessarev Eric W. , Nuccio Erin E. , McFarlane Karis J. , Ramon Christina , Saha Malay , Firestone Mary K. , Pett-Ridge Jennifer
Published: July 2020

Perennial bioenergy crops have been shown to increase soil organic carbon (SOC) stocks, potentially offsetting anthropogenic C emissions. The effects of perennial bioenergy crops on SOC are typically assessed at shallow depths (< 30 cm), but the deep root systems of these crops may also have substantial effects on SOC stocks at greater depths. We hypothesized that deep (> 30 cm) soil organic carbon (SOC) stocks would be greater under bioenergy crops relative to stocks under shallow-rooted conventional crop cover. To test this, we sampled soils to between 1- and 3-meters depth at three sites in Oklahoma with 10-20 year old switchgrass (Panicum virgatum) stands, and collected paired samples from nearby fields cultivated with shallow rooted annual crops. We measured root biomass, total organic C,14C,13C, and other soil properties in three replicate soil cores in each field and used a mixing model to estimate the proportion of recently fixed C under switchgrass based on14C. The subsoil C stock under switchgrass (defined over 500-1500 kg m-2equivalent soil mass, approximately 30-100 cm depth) exceeded the subsoil stock in neighboring fields by 1.5 kg C m-2at a sandy loam site, 0.6 kg C m-2at a site with loam soils, and showed no significant difference at a third site with clay soils. Using the mixing model, we estimated that additional SOC introduced after switchgrass cultivation comprised 31% of the subsoil C stock at the sandy loam site, 22% at the loam site, and 0% at the clay site. These results suggest that switchgrass can contribute significantly to subsoil organic C—but also indicated that this effect varies across sites. Our analysis shows that agricultural strategies that emphasize deep-rooted grass cultivars can increase soil C relative to conventional crops while expanding energy biomass production on marginal lands.
Antagonistic Co-contraction Can Minimize Muscular Effort in Systems with Uncertainty
Authors: Koelewijn Anne D. , van den Bogert Antonie J.
Published: July 2020

Muscular co-contraction of antagonistic muscle pairs is often observed in human movement, but it is considered inefficient and it can currently not be predicted in simulations where muscular effort or metabolic energy is minimized. Here, we investigated the relationship between minimizing effort and muscular co-contraction in systems with random uncertainty to see if muscular co-contraction can minimize effort in such system. We also investigated the effect of time delay in the muscle, by varying the time delay in the neural control as well as the activation time constant. We solved optimal control problems for a one-degree-of-freedom pendulum actuated by two identical antagonistic muscles, using forward shooting, to find controller parameters that minimized muscular effort while the pendulum remained upright in the presence of noise added to the moment at the base of the pendulum. We compared a controller with and without feedforward control. Task precision was defined by bounding the root mean square deviation from the upright position, while different perturbation levels defined task difficulty. We found that effort was minimized when the feedforward control was nonzero, even when feedforward control was not necessary to perform the task, which indicates that co-contraction can minimize effort in systems with uncertainty. We also found that the optimal level of co-contraction increased with time delay, both when the activation time constant was increased and when neural time delay was added. Furthermore, we found that for controllers with a neural time delay, a different trajectory was optimal for a controller with feedforward control than for one without, which indicates that simulation trajectories are dependent on the controller architecture. Future movement predictions should therefore account for uncertainty in dynamics and control, and carefully choose the controller architecture. The ability of models to predict co-contraction from effort or energy minimization has important clinical and sports applications. If co-contraction is undesirable, one should aim to remove the cause of co-contraction rather than the co-contraction itself.
Activation of endogenous retroviruses during brain development causes neuroinflammation
Authors: Jönsson Marie E , Garza Raquel , Sharma Yogita , Petri Rebecca , Södersten Erik , Johansson Jenny G , Johansson Pia A , Atacho Diahann AM , Pircs Karolina , Madsen Sofia , Yudovich David , Ramakrishnan Ramprasad , Holmberg Johan , Larsson Jonas , Jern Patric , Jakobsson Johan
Published: July 2020

Endogenous retroviruses (ERVs) make up a large fraction of mammalian genomes and are thought to contribute to human disease, including brain disorders. In the brain, aberrant activation of ERVs is a potential trigger for neuroinflammation, but mechanistic insight into this phenomenon remains lacking. Using CRISPR/Cas9-based gene disruption of the epigenetic co-repressor protein Trim28, we found a dynamic H3K9me3-dependent regulation of ERVs in proliferating neural progenitor cells (NPCs), but not in adult neurons.In vivodeletion ofTrim28in cortical NPCs during mouse brain development resulted in viable offspring expressing high levels of ERV expression in excitatory neurons in the adult brain. Neuronal ERV expression was linked to inflammation, including activated microglia, and aggregates of ERV-derived proteins. This study demonstrates that brain development is a critical period for the silencing of ERVs and provides causalin vivoevidence demonstrating that transcriptional activation of ERV in neurons results in neuroinflammation.
Gene-based mapping of trehalose biosynthetic pathway genes reveals association with source- and sink-related yield traits in a spring wheat panel
Authors: Lyra Danilo H. , Griffiths Cara A. , Watson Amy , Joynson Ryan , Molero Gemma , Igna Alina-Andrada , Hassani-Pak Keywan , Reynolds Matthew P. , Hall Anthony , Paul Matthew J.
Published: July 2020

Trehalose 6-phosphate (T6P) signalling regulates carbon use and allocation and is a target to improve crop yields. However, the specific contributions of trehalose phosphate synthase (TPS) and trehalose phosphate phosphatase (TPP) genes to source- and sink-related traits remain largely unknown. We used exome-capture sequencing on TPS and TPP genes to estimate and partition the genetic variation of yield-related traits in a spring wheat (Triticum aestivum) breeding panel with diverse genetic heritage. Twelve phenotypes were directly correlated to TPS and TPP genes including final biomass (source) and spikes and grain numbers and grain filling traits (sink) showing indications of both positive and negative gene selection. Additionally, individual genes explained a substantial proportion of heritability (e.g. 3, 12, and 18% of the variance in gene homeologues most closely related to ArabidopsisTPS1for final biomass), indicating a considerable contribution of this regulatory pathway to the phenotypic variation. Most importantly, two significant missense point mutations in the exon 6 of theTPS1gene on chromosome 1D substantially increased plant height and peduncle length which was inversely related to grains per m2. Gene-based prediction resulted in significant gains of predictive ability (6% improvement) for grain weight when gene effects were combined with the whole genome markers, potentially helping breeding programs in designing strategic crosses. ThreeTPS1homeologues were particularly significant in trait variation. Our study has generated a wealth of information on the role of natural variation of TPS and TPP genes related to yield potential.
Mapping the Role of AcrAB-TolC Efflux Pumps in the Evolution of Antibiotic Resistance Reveals Near-MIC Treatments Facilitate Resistance Acquisition
Authors: Langevin Ariel M. , El Meouche Imane , Dunlop Mary J.
Published: July 2020

Antibiotic resistance has become a major public health concern as bacteria evolve to evade drugs, leading to recurring infections and a decrease in antibiotic efficacy. Systematic efforts have revealed mechanisms involved in resistance; yet, in many cases, how these specific mechanisms accelerate or slow the evolution of resistance remains unclear. Here, we conducted a systematic study of the impact of the AcrAB-TolC efflux pump on the evolution of antibiotic resistance. We mapped how population growth rate and resistance change over time as a function of both the antibiotic concentration and the parent strain’s genetic background. We compared the wild type strain to a strain overexpressing AcrAB-TolC pumps and a strain lacking functional pumps. In all cases, resistance emerged when cultures were treated with chloramphenicol concentrations near the MIC of their respective parent strain. The genetic background of the parent strain also influenced resistance acquisition. The wild type strain evolved resistance within 24 h through mutations in theacrABoperon and its associated regulators. Meanwhile, the strain overexpressing AcrAB-TolC evolved resistance more slowly than the wild type strain; this strain achieved resistance in part through point mutations inacrBand theacrABpromoter. Surprisingly, the strain without functional AcrAB-TolC efflux pumps still gained resistance, which it achieved through upregulation of redundant efflux pumps. Overall, our results suggest that treatment conditions just above the MIC pose the largest risk for the evolution of resistance and that AcrAB-TolC efflux pumps impact the pathway by which chloramphenicol resistance is achieved.

IMPORTANCE

Combatting the rise of antibiotic resistance is a significant challenge. Efflux pumps are an important contributor to drug resistance; they exist across many cell types and can export numerous classes of antibiotics. Cells can regulate pump expression to maintain low intracellular drug concentrations. Here, we explored how resistance emerged depending on the antibiotic concentration, as well as the presence of efflux pumps and their regulators. We found that treatments near antibiotic concentrations that inhibit the parent strain’s growth were most likely to promote resistance. While wild type, pump overexpression, and pump knock out strains were all able to evolve resistance, they differed in the absolute level of resistance evolved, the speed at which they achieved resistance, and the genetic pathways involved. These results indicate that specific treatment regimens may be especially problematic for the evolution of resistance and that the strain background can influence how resistance is achieved.
Knockout of the serotonin transporter in the rat mildly modulates decisional anhedonia
Authors: Guo Chao Ciu-Gwok , Verheij Michel MM , Homberg Judith R
Published: July 2020

Serotonin transporter gene variance has long been considered an essential factor contributing to depression. However, meta-analyses yielded inconsistent findings recently, asking for further understanding of the link between the gene and depression-related symptoms. One key feature of depression is anhedonia. While data exist on the effect of serotonin transporter gene knockout (5-HTT-/-) in rodents on consummatory and anticipatory anhedonia, with mixed outcomes, the effect on decisional anhedonia has not been investigated thus far. Here, we tested whether 5-HTT-/-contributes to decisional anhedonia. To this end, we established a novel touchscreen-based “go/go” task of visual decision-making. During the learning of stimulus discrimination, 5-HTT+/+rats performed more optimal decision-making compared to 5-HTT-/-rats at the beginning, but this difference did not persist throughout the learning period. During stimulus generalization, the generalization curves were similar between both genotypes and did not alter as the learning progress. Interestingly, the response time in 5-HTT+/+rats increased as the session increased in general, while 5-HTT-/-rats tended to decrease. The response time difference might indicate that 5-HTT-/-rats altered willingness to exert cognitive effort to the categorization of generalization stimuli. These results suggest that the effect of 5-HTT ablation on decisional anhedonia is mild and interacts with learning, explaining the discrepant findings on the link between 5-HTT gene and depression.