bluuebunny/crossref_metadata_2025 huggingface dataset:
VCF/Plotein: visualization and prioritization of genomic variants from human exome sequencing projects
Authors: Ossio Raul , Garcia-Salinas O Isaac , Anaya-Mancilla Diego Said , Garcia-Sotelo Jair S , Aguilar Luis A , Adams David J , Robles-Espinoza Carla Daniela
Published: May 2019

Motivation

Identifying disease-causing variants from exome sequencing projects remains a challenging task that often requires bioinformatics expertise. Here we describe a user-friendly graphical application that allows medical professionals and bench biologists to prioritize and visualize genetic variants from human exome sequencing data.

Results

We have implemented VCF/Plotein, a graphical, fully interactive web application able to display exome sequencing data in VCF format. Gene and variant information is extracted from Ensembl. Cross-referencing with external databases and application-based gene and variant filtering have also been implemented. All data processing is done locally by the user’s CPU to ensure the security of patient data.

Availability and implementation

Freely available on the web at https://vcfplotein.liigh.unam.mx. Website implemented in JavaScript using the Vue.js framework, with all major browsers supported. Source code freely available for download at https://github.com/raulossio/VCF-plotein.

Supplementary information

Supplementary data are available at Bioinformatics online.
Waning of Influenza Vaccine Protection: Exploring the Trade-offs of Changes in Vaccination Timing Among Older Adults
Authors: Ferdinands Jill M , Alyanak Elif , Reed Carrie , Fry Alicia M
Published: May 2019

Background

In recent studies of influenza vaccine effectiveness (VE), lower effectiveness with increasing time since vaccination was observed, raising the question of optimal vaccination timing. We sought to evaluate the estimated number of influenza-associated hospitalizations among older adults due to potential changes in vaccination timing.

Methods

Using empirical data and a health state transition model, we estimated change in influenza-associated hospitalizations predicted to occur among the US population aged ≥65 years if vaccination were delayed until October 1. We assumed the vaccination timing, coverage, and effectiveness observed in 2012–2013 as a prototypical influenza season, approximately 7% monthly waning of VE, and that between 0% and 50% of individuals who usually get vaccinated earlier than October failed to get vaccinated. We also assessed change in influenza-associated hospitalizations if vaccination uptake shifted substantially toward August and September.

Results

In a typical season, delaying vaccination until October increased influenza hospitalizations if more than 14% of older adults usually vaccinated in August and September failed to get vaccinated. The consequences of delayed vaccination depended heavily on influenza season timing, rate of waning, and overall VE. A shift toward vaccination in August and September led to, on average, an increase in influenza-associated hospitalizations, but this result was also sensitive to influenza season timing.

Conclusions

Consequences of delayed vaccination varied widely. Uncertainties about vaccine waning and effects of a delay on vaccine coverage suggest it is premature to change current vaccine recommendations, although it may be prudent to prevent a substantial shift toward early vaccination.
NuDist: An Efficient Local Search Algorithm for (Weighted) Partial MaxSAT
Authors: Lei Zhendong , Cai Shaowei
Published: May 2019

Maximum satisfiability (MaxSAT) is the optimization version of the satisfiability (SAT). Partial MaxSAT (PMS) generalizes SAT and MaxSAT by introducing hard and soft clauses, while Weighted PMS (WPMS) is the weighted version of PMS where each soft clause has a weight. These two problems have many important real-world applications. Local search is a popular method for solving (W)PMS. Recently, significant progress has been made in this direction by tailoring local search for (W)PMS, and a representative algorithm is the Dist algorithm. In this paper, we propose two ideas to improve Dist, including a clause-weighting scheme and a variable-selection heuristic. The resulting algorithm is called NuDist. Extensive experiments on PMS and WPMS benchmarks from the MaxSAT Evaluations (MSE) 2016 and 2017 show that NuDist significantly outperforms state-of-the-art local search solvers and performs better than state-of-the-art complete solvers including Open-WBO and WPM3 on MSE 2017 benchmarks. Also, empirical analyses confirm the effectiveness of the proposed ideas.
Deep Reinforcement Learning with Adaptive Update Target Combination
Authors: Xu Z , Cao L , Chen X
Published: May 2019

Simple and efficient exploration remains a core challenge in deep reinforcement learning. While many exploration methods can be applied to high-dimensional tasks, these methods manually adjust exploration parameters according to domain knowledge. This paper proposes a novel method that can automatically balance exploration and exploitation, as well as combine on-policy and off-policy update targets through a dynamic weighted way based on value difference. The proposed method does not directly affect the probability of a selected action but utilizes the value difference produced during the learning process to adjust update target for guiding the direction of agent’s learning. We demonstrate the performance of the proposed method on CartPole-v1, MountainCar-v0, and LunarLander-v2 classic control tasks from the OpenAI Gym. Empirical evaluation results show that by integrating on-policy and off-policy update targets dynamically, this method exhibits superior performance and stability than does the exclusive use of the update target.
Clinical outcomes in patients with primary stable microvascular angina: is the jury still out?
Authors: Lanza Gaetano Antonio , Crea Filippo , Kaski Juan Carlos
Published: May 2019

Several studies have demonstrated that angina chest pain in presence of normal or near normal coronary arteries (NCAs) is mainly related to coronary microvascular dysfunction (CMD). However, controversial findings exist about clinical outcome of these patients. In this article, we critically review characteristics and results of the main clinical studies reporting clinical outcome of stable patients with angina chest pain and non-obstructive coronary artery disease (NO-CAD). Published data indicate that clinical outcomes of these patients are heterogeneous, but those with strict criteria for primary stable microvascular angina (MVA, i.e. typical angina with NCAs mainly related to efforts) do not appear to have an increased mortality or risk of major coronary events. A major determinant of outcome in patients with MVA and NO-CAD seems instead related to non-critical atherosclerotic disease, the presence of which should suggest a more aggressive management of cardiovascular risk factors and preventive management. Future studies should assess whether CMD may have a relevant prognostic role in the latter clinical context and/or in other clinical settings of NO-CAD different from primary stable MVA.
The Armed Forces and Parliamentary Elections in the United Kingdom, 1885–1914
Authors: Keeling Peter M
Published: May 2019

This article discusses the electoral position of the British Army and Royal Navy during the period between the Third Reform Act and the outbreak of war in 1914, offering a ‘bottom up’ perspective on the history of civil–military relations. Drawing heavily from contemporary newspapers and electoral registers, it shows that in a number of constituencies soldiers and sailors held significant voting influence. Because soldiers were assumed to be natural Conservatives, the struggle between Tory and Liberal election agents over their registration sheds light on the nature of local party politics during this time, as well as the practical operation of what was a complex and unsympathetic electoral system. More broadly, it offers a case-study in ‘positive Unionism’, which challenges the view of the Conservative Party as an unbending opponent of franchise reform and, similarly, sheds light on the less democratic side of the Liberal Party. In terms of the armed forces themselves, the article argues that while the Army harboured a strong Unionist identity, the Navy was much less partisan in its voting habits; Irish soldiers proved themselves Liberal in sympathies. Overall, the article provides a fresh perspective on the position of the Army and Navy in British society during the late nineteenth and early twentieth centuries, and, in its conclusion, adds context to the 1918 Representation of the People Act.
The impact of centre volume on outcomes of orthotopic heart transplant in older recipients
Authors: Sultan Ibrahim , Gleason Thomas G , Kagawa Hiroshi , Keebler Mary , Mathier Michael , Kormos Robert L , Kilic Arman
Published: May 2019

OBJECTIVES

The aim of this study was to evaluate the impact of overall and older-recipient-specific centre volumes on outcomes of orthotopic heart transplant (OHT) in older recipients.

METHODS

Patients aged ≥60 years undergoing OHT were identified in the United Network for Organ Sharing (UNOS) registry. The primary outcome was 1-year post-OHT mortality. Secondary outcomes included the incidence and impact on 1-year survival of postoperative complications including infection, renal failure requiring dialysis and stroke. Patients were divided into equal size tertiles based on overall and older-recipient-specific OHT centre volumes.

RESULTS

A total of 5373 older recipients were identified. Mean overall and older-recipient-specific volumes were 27.5 ± 19.5 and 9.4 ± 7.3 OHT/year, respectively. Although overall and older-recipient-specific low-volume centres were at higher risk of mortality in separate multivariable analysis, only older-recipient-specific volume contributed significantly to post-OHT mortality in the combined multivariable analysis (P < 0.05). In the receiver operating characteristic analysis, an older-recipient-specific volume of 8 OHTs/year was identified as the most discriminative volume threshold for mortality (area under the receiver operating characteristic curve = 0.68). Although low older-recipient-specific volume centres did not have significantly higher incidences of postoperative complications, they had significantly worse 1-year survival rates compared to higher volume centres in patients with postoperative infection or dialysis (each P < 0.01).

CONCLUSIONS

This large-cohort analysis demonstrates that older-recipient-specific centre volume contributes to post-OHT outcomes in the older recipients more significantly than overall volume. This may be a consequence of higher older-recipient-specific volume centres to better manage specific complications in this patient population.
Experimental investigation and performance analysis of an Organic Rankine Cycle for low-temperature heat to electricity generation
Authors: Wei Lili , Ma Zhenjun , Gong Xuemei , Guo Xiujuan
Published: May 2019

This paper presents experimental investigation of low-temperature heat to electricity generation system based on Organic Rankine Cycle (ORC) using R152a as the working fluid. Both energy efficiency and exergy efficiency were analyzed based on the experiments. Although energy efficiency was low to 5.0% when the evaporating and cooling temperatures were 65°C and 11°C, respectively, the exergy efficiency reached 25%, which showed great competitiveness among low-temperature heat utilization technologies. To reveal the energy recovery proportion from the waste heat, both energy extraction efficiency and exergy extraction efficiency as well as energy and exergy loss paths were analyzed. When the heat source was 65°C, 14.9% of the maximum possible thermal energy in the heat source was absorbed by the organic working fluid, and 10.7% was transferred to the cooling medium. The power output contributed 0.64%. A total of 1.8% of the exergy in the heat stream flowed to the cooling medium. The start-up work takes dramatically 0.16% and 1.7% of energy and exergy, respectively. Other energy and exergy loss occurs due to the irreversibility of the heat transfer process and expansion process. Cascade ORC system could enlarge the temperature difference of the heat stream and raise the power output. However, the energy efficiency of the multi-stage ORC system is lower than single-stage system, since there was a downward trend of the temperature of heat source for the latter stage. ORC cycle can lower the temperature of heat source to 45°C.
China’s rising assertiveness and the decline in the East Asian regionalism narrative
Authors: Yeo Andrew
Published: May 2019

After a decade of vibrant scholarly and political discourse regarding the prospects of East Asian integration, the narrative of regionalism has lost its luster in favor of a darker regional narrative. Has the idea of East Asian regionalism come to pass, and if so, what explains the decline in the narrative of Asian regionalism both as a policy idea and as a research program? After providing empirical evidence tracking the rise and decline in scholarly publications and news articles regarding Asian regionalism, I present several plausible reasons explaining this decline. Among them, the perceived shift in Chinese strategic behavior, and in turn, the adoption of more pragmatic interpretations of Asian security practices – one defined by power balancing and institutional rivalry rather than community building – appears to have struck a major blow to the East Asia regional project.
Autotomy and running performance of fiddler crabs (Decapoda: Brachyura: Ocypodidae)
Authors: Martin Benjamin E
Published: May 2019

The sexually dimorphic, enlarged major claw is a notorious trait among male fiddler crabs, but comes with potential locomotor costs. Possessing the ability to autotomize the enlarged claw is thus potentially advantageous to not only to escape a predator’s grip, but also to increase running performance. Previous studies concluded that autotomy either has no effect or even a negative effect on running performance. If the claw does not aid in locomotion, then shedding the enlarged claw that accounts for 40% of a fiddler crab’s mass should positively affect running performance. I therefore investigated autotomy and running performance in the Atlantic sand fiddler crab Leptuca pugilator (Bosc, 1801) with a focus on improving upon the methods of previous studies. Crabs were given substantial recovery time between collection, running trials, and autotomy induction. Maximum sprint speed was assessed by running crabs on a 1 m sand and mud track where individuals were significantly faster after autotomy of the enlarged claw (N = 64, t63=-7.25, P < 0.001). Intact running velocity was furthermore a significant predictor of autotomized running velocity (R2 = 0.194, P < 0.001). This study is the first to show a significant increase in fiddler crab sprint velocity after autotomy on a flat surface, and I propose where methodological pitfalls may have occurred in previous studies.
Assessing Victim Participation during Sentencing at the International Criminal Court
Authors: Pérez-León-Acevedo Juan-Pablo
Published: May 2019

Although the academic literature has examined victim participation at the International Criminal Court (ICC), victim participation during the sentencing stage has remained a virtually unexplored topic. Thus, this article assesses the law and, in particular, the practice of the ICC on victim participation during sentencing in light of domestic/international criminal law and human rights law standards. Victim participation during the ICC sentencing stage, i.e. mainly written observations and sentencing hearing participation, is overall consistent with international and domestic criminal law standards, particularly with certain common law jurisdictions and with the Special Tribunal for Lebanon where the trial and sentencing stages are also divided. Additionally, victim participation during the ICC sentencing stage may arguably be justified under international human rights law, especially human rights case law. Importantly, the ICC has introduced some limitations to victim participation to safeguard the convicted person’s rights and procedural efficiency.
Political Agency, Oversight, and Bias: The Instrumental Value of Politicized Policymaking
Authors: Turner Ian R
Published: May 2019

We develop a theory of policymaking between an agent and an overseer, with a principal whose welfare is affected by agent-overseer interactions. The agent can increase the quality of policy outcomes through costly capacity investments. Oversight and agent bias jointly determine optimal agent capacity investments. We show that when oversight improves agent investment incentives the principal always benefits from an agent with biases opposite the overseer. Competing agent-overseer biases translate into higher quality policy outcomes than the principal could induce were she monitoring the agent. Effective oversight is necessary for these incentive effects. The results imply that political principals ought to consider the nature of the broader policymaking environment when appointing agents to make policy on their behalf and when designing managerial strategies aimed at motivating agents. (JEL D73, D82, H11)
Generalized spot auto-focusing method with a high-definition auto-correlation function in transmission electron microscopy
Authors: Isakozawa Shigeto , Baba Misuzu , Amano Junpei , Sakamoto Shohei , Baba Norio
Published: May 2019

The spot auto-focusing (AF) method with a unique high-definition auto-correlation function (HD-ACF) proposed in the previous paper is improved and is now applicable to general specimens at a wide range of magnifications. According to the definition where the AF is defocused to obtain the highest resolution, the proposed method achieves the sharpest HD-ACF profile in the AF spot image. The relationship where the sharpest HD-ACF profile gives the highest resolution is theoretically explained, and practical AF examples for different specimens and magnifications are experimentally demonstrated. Specimens include a yeast cell thin section at 10-k magnification, a standard grating replica used as a ruler at 50-k, a crystal lattice of graphitized carbon at 400-k and a 60°-tilted thin section (yeast cell) at 10-k. Different procedures are prepared to actively identify the defocus position that gives the sharpest HD-ACF profile. Every AF result demonstrates the highest-resolution image.
Hilastērion (Rom. 3:25) and the Union of Divine Justice And Mercy. Part II: Atonement in the old Testament and in Romans 1–5
Authors: Hultgren Stephen
Published: May 2019

Part II of this study explains how the convergence of temple and martyrdom theologies demonstrated in Part I helps us understand ἱλαστήριον in the context of Romans 1–5. Biblical ‘atonement’ is multifaceted, comprehending expiation and forgiveness, as well as removal of divine wrath. In the LXX the ἱλάσκομαι word group is also complex, retaining propitiatory overtones from classical usage (although it may often be better to speak of God removing his own wrath), while taking on the additional meaning of expiation and forgiveness. The Pentateuchal ἱλαστήριον is a ‘place’ for such ‘atonement’. Amidst many proposals, ‘the place of atonement’ with allusion to the כַּפֹּרֶת remains the most likely meaning for ἱλαστήριον in Rom. 3:25. Christ is the ‘place’ where divine justice and mercy meet. His death is the visible manifestation of divine justice, the consequence of humanity’s collective sin, which was ‘building up’ towards a permanent breach in the relationship between God and humanity. Christ’s death is also a ransom and the means by which God objectively removes sin and so frees humanity from death. Paul radically reconfigured martyrdom theology, which offered a way of thinking about how divine justice and mercy can meet in the death of a person.
Alliance in Adult Psychotherapy
Authors: Flückiger Christoph , Del Re A. C. , Wampold Bruce E. , Horvath Adam O.
Published: May 2019

The alliance continues to be one of the most investigated variables related to success in psychotherapy. In this chapter, the authors define and illustrate the alliance (also conceptualized as therapeutic alliance or working alliance) and then present a meta-analysis of 295 independent studies that covered more than 30,000 patients for face-to-face psychotherapy as well as Internet-based psychotherapy. The relation of the alliance and treatment outcome was investigated using three-level meta-analysis with random-effects. The overall alliance–outcome association for face-to-face psychotherapy was r = .278 (equivalent of d = .579). The correlation for internet-based psychotherapy was approximately the same (r = .275, k = 23). These results confirm the robustness of the positive relation between the alliance and outcome. This relation remains consistent across assessor perspectives, alliance and outcome measures, treatment approaches, patient characteristics, and countries. The chapter concludes with research limitations, diversity considerations, and therapeutic practices.
Alliance in Child and Adolescent Psychotherapy
Authors: Karver Marc S. , De Nadai Alessandro S. , Monahan Maureen , Shirk Stephen R.
Published: May 2019

In youth treatment, the alliance has been defined and measured as a consensual or collaborative bond. This chapter reviews varied definitions of the alliance, enumerates its frequent measures, and presents clinical examples. The authors provide a meta-analytic review on the relation between the therapeutic alliance and treatment outcome in child and adolescent psychotherapy. The meta-analysis of 43 studies revealed a weighted random effect size of r = .20, which is a small to medium effect consistent with the adult alliance literature and with prior youth meta-analyses. Multiple moderators of the alliance–outcome association were found, including diagnosis class, study design, and outcome rater. Research limitations, patient contributions, and diversity considerations follow. The chapter concludes with research-informed practices for building and maintaining the therapeutic alliance with youth.
Alliances in Couple and Family Therapy
Authors: Friedlander Myrna L. , Escudero Valentín , Welmers-van de Poll Marianne J. , Heatherington Laurie
Published: May 2019

This chapter reviews meta-analytic evidence for the alliance-outcome relation in couple and family therapy (CFT). The authors describe the unique features of CFT alliances and their measurement, followed by case descriptions. A meta-analysis of 48 studies (Ns = 2,568 families, 1,545 couples, and 491 effect sizes) found r = .297. In another analysis with 7 independent samples and 31 effect sizes, the split alliance–outcome association was also significant, r = .316, indicating that the more split or unbalanced the alliance, the poorer the outcome. Moderator analyses showed that alliance–outcome associations did not differ for couple versus family therapy, but correlations were significantly stronger in samples with younger problem children, older adults, proportionally more male youth and adults, and when the families voluntarily sought help (as compared to involuntary or mandated families). The chapter concludes with research-informed strategies for building and sustaining strong alliances in CFT.
Cohesion in Group Therapy
Authors: Burlingame Gary M. , McClendon Debra Theobald , Yang Chongming
Published: May 2019

Cohesion is the most popular relationship construct in the group therapy literature. This chapter reviews common definitions of cohesion and the most frequently studied measures. The authors also discuss a measure that may clarify group relations using two latent factors (quality and structure) to explain common variance among frequently used group relationship instruments. The results of a meta-analysis examining the relation between group cohesion and treatment outcome in 55 studies are presented. Results indicate that the weighted aggregate correlation between cohesion and treatment outcome was statistically significant r = .26, reflecting a moderate effect size (d = .56). Six moderator variables were found to significantly predict the magnitude of the cohesion–outcome association (type of outcome measure, leader interventions to increase cohesion, theoretical orientation, type of group, emphasis on group interaction, dose or number of group sessions). Patient contributions, diversity considerations, and evidence-based therapeutic practices are highlighted.
Collecting and Delivering Client Feedback
Authors: Lambert Michael J. , Whipple Jason L. , Kleinstäuber Maria
Published: May 2019

This meta-analysis examines the impact of measuring, monitoring, and feeding back information on client progress to clinicians while they deliver psychotherapy. It considers the effects of the two most frequently studied routine outcome monitoring practices: the Partners for Change Outcome System and the Outcome Questionnaire System. Meta-analyses of 24 studies produced effect sizes from small to moderate. Feedback practices reduced deterioration rates and nearly doubled clinically significant/reliable change rates in clients who were predicted to have a poor outcome. Clinical examples, diversity considerations, and therapeutic advances are provided.
Gender Identity
Authors: Budge Stephanie L. , Moradi Bonnie
Published: May 2019

This chapter reviews the research evidence on the effectiveness of attending to clients’ gender identity in psychotherapy. It begins with definitions and measures of gender identity and provides clinical examples. A literature search did not yield studies that fit the authors’ search criteria; thus meta-analyses were not conducted. Instead, the authors conducted a content analysis of the 10 qualitative and quantitative studies on psychotherapy with transgender individuals. The chapter concludes by highlighting the limitations of the research base, describing diversity considerations, and recommending therapeutic practices that attend to gender, gendered systems of power, oppression, and privilege.
Personalizing Psychotherapy: Results, Conclusions, and Practices
Authors: Norcross John C. , Wampold Bruce E.
Published: May 2019

The chapter concludes the third edition of the book by summarizing what works and what does not in psychotherapy responsiveness and treatment adaptations. The authors present the Task Force conclusions and 28 recommendations for training, practice, research, and policy. The authors conclude that adapting psychotherapy in ways reviewed in this book demonstrably improves treatment outcomes and prevents premature deterioration.
Diagnosis of Sport Concussion
Authors: Brody David L.
Published: May 2019

In the setting of a sporting event, it is much more likely that the event itself and its effects on the patient will have been directly witnessed. Get a collateral source history from those who actually observed the event:

Consider using the Sport Concussion Assessment Tool 5th Edition (SCAT5) to guide a standard acute evaluation of sport-related concussion.

Consider performing a short screening test such as the VOMS (Vestibular Ocular Motor Screening).
Excessive Sleepiness
Authors: Brody David L.
Published: May 2019

The definition of clinically important hypersomnia is excessive sleep that interferes with other aspects of life. Take a careful history, including from the collateral source. Administer the Epworth sleepiness scale to assess severity. Restrict driving if necessary: A severely hypersomnolent driver can be just as dangerous as an epileptic driver. Refer for an overnight polysomnogram (“sleep study”) at a licensed sleep lab, then treat any underlying disorders causing poor-quality sleep. Assess for depression and if appropriate, treat with an activating antidepressant. Take a careful medication history for substances that can cause hypersomnia and stop them if possible. Rule out a systemic cause. If these are not present or hypersomnia is still impairing after treatment, consider prescribing a very gradually progressive exercise program, a trial of caffeine, modafinil, or a direct stimulant in the most refractory cases.
Executive Dysfunction
Authors: Brody David L.
Published: May 2019

Problems with organization, planning, strategy decisions, mental flexibility, optimizing risk/reward relationships, intiation, prioritizing, and goal setting are often called executive dysfunction. Collateral history and neuropsychological testing will help sort out the nature of the impairment but treat the patient, not the test result. Reduce barriers to optimal cognitive function: Optimize sleep; treat chronic pain; taper or stop cognitively impairing medications; stop alcohol and illicit drugs; prescribe moderate cardiovascular exercise; and refer to speech therapy and occupational therapy for executive function training. There are no specific pharmacological treatments for executive function. Consider trials of caffeine, stimulants, donepezil or rivastigmine, modafinil, or dopaminergic agents.
Parkinsonism
Authors: Brody David L.
Published: May 2019

The classic triad of parkinsonism includes bradykinesia (slowness of movement and speech), rigidity (increased resistance of the arms, legs, neck, and torso to passive movement), and tremor (typically in the hands or arms, present at rest, but not with movement). Parkinsonism can be a delayed consequence of multiple concussions. It is not likely to be caused by a single concussion. Parkinsonism is sometimes, but not always part of chronic traumatic encephalopathy. If the patient has parkinsonism, the first priority is to determine whether there is a reversible cause, most commonly a medication. If the patient has parkinsonism not due to a reversible cause, consider pharmacological treatment with

carbidopa–levodopa or a dopamine agonist. Also refer to physical therapy for balance training and education on how to reduce fall risk. Importantly, multiple concussion-related parkinsonism is not the same as Parkinson’s disease. Injury-related parkinsonism does not usually get worse over time and can stay stable over decades.
Hearing Problems
Authors: Brody David L.
Published: May 2019

The most common hearing problems after concussion are hypersensitivity to sound, tinnitus (ringing in the ears), and hearing loss. Excessive sensitivity to sound can be due to migraine, damage to the ear and auditory nerve, or neuropathic pain. Refer to ear, nose, and throat (ENT) specialist for an evaluation of the middle and inner ear. Consider trials of migraine abortive agents (e.g., triptans) and neuropathic pain agents (e.g., pregabalin). For tinnitus, if an audiogram reveals hearing loss, refer to ENT. Treatment from a specialized therapist team including an audiologist and psychologist may improve tinnitus outcomes. Assess for medications that adversely affect the inner ear and reduce them if possible. Test thyroid function. Consider a magnetic resonance imaging (MRI) scan of the brain to make sure that the concussion didn’t unmask another problem, such as a tumor or vascular malformation. A complaint of hearing loss can mean several things: true hearing loss due to middle or inner ear damage, attention deficit, or a language problem such as aphasia. Obtain an audiogram, and if it is abnormal, refer to ENT, assess for attention deficit, and test for receptive aphasia.
Seizures
Authors: Brody David L.
Published: May 2019

Concussion rarely causes recurrent seizures. A patient with a brief seizure that occurs within the first 30 minutes of concussion does not need to be treated with antiepileptics or have driving restrictions. However, a seizure occurring later than 30 minutes after the injury, a seizure that lasts more than 1 minute, or a seizure after concussion in a patient with a previous seizure disorder requires a different approach. Consider hospital observation, brain magnetic resonance imaging (MRI), electroencephalogram (EEG), laboratory studies, assessment for infection, and a screen for drug and alcohol use or withdrawal. If seizures need to be treated, the best approach often includes mood stabilizing medications with minimal cognitively impairing side effects. An oxcarbazepine (Trileptal) bridge during lamotrigine (Lamictal) titration is a reasonable choice. Carbamazepine generic is a good option when cost is an issue. Levetiracetam (Keppra) often causes mood dysregulation in concussion patients.
Psychosis
Authors: Brody David L.
Published: May 2019

New onset hallucinations and delusions are rare after isolated concussion and should trigger a search for other causes: Schizophrenia (relatively common in young adults), drug abuse, alcohol or drug withdrawal, and delirium due to infection or sleep deprivation should be considered. Importantly, if the psychosis is dangerous or potentially dangerous, think about safety first. This may require inpatient admission to a psychiatric service. If outpatient treatment is required, atypical antipsychotics should be used in as low a dose as possible to minimize cognitive side effects. Aripiprazole (Abilify) is associated with less weight gain than other atypical antipsychotics. Risperidone (Risperdal) is the least expensive. Quetiapine (Seroquel), or rarely Clozaril, are the best choices when parkinsonism is a comorbidity.
Return to Contact Sports
Authors: Brody David L.
Published: May 2019

Published guidelines on return to play apply to simple concussions: (1) No return to play in the same 24-hour period as the concussion. (2) Graded, stepwise increases in activity guided by symptoms over approximately 6 to 10 days. (3) No difference in return to play for elite versus nonelite athletes. (4) Brief convulsions or posturing at the time of concussion does not indicate higher than normal risk of seizures and requires no specific management.

After 2 weeks in adults and 4 weeks in children, more rest is not likely to help. At that point, it is reasonable to start active interventions. For more complex concussions, discourage the patient from returning to contact sports until all of the following are true: The symptoms are all in the mild range or resolved, the collateral source verifies that the patient’s behavior is back to normal, the patient has been able to return to school or work (for nonprofessional athletes), balance is back to normal, and the patient passes a physical therapist-directed moderate exercise test. Many complex concussion patients will decide not to return to contact sports at all if their long-term well-being depends more on their work and interpersonal relationships than on their athletic performance.
Concussion in Adolescents
Authors: Brody David L.
Published: May 2019

Adolescents should follow the no return to play for 24 hours rule strictly to improve outcomes and reduce risk of second impact syndrome. Because adolescents may be less able to make good judgments about their own abilities than adults, the collateral source becomes even more important than usual. Address questions about drug and alcohol use privately and give advice without the parents present. Peer influences may have a big impact on decision-making. Obtain collateral history from peers and educate peers as well as parents. Preexisting attention deficit, learning disabilities, and mood instability can get substantially worse after concussion and may require intensified treatment. For patients on the cusp of starting to drive, consider advising extra caution: go back to the beginning of driver’s education and get a professional driving evaluation. Consider preemptively addressing questions that the adolescent may be afraid to ask or cannot formulate accurately.
Staffing
Authors: Brody David L.
Published: May 2019

Pick the right people: a concussion clinic requires greater than average interpersonal skills to handle patients with mood instability and cognitive impairment. The clinic administrator needs to have good judgment. The administrator needs to be able to determine whether to contact the provider right away for an urgent issue, whether to recommend that the patient go straight to an emergency department, or whether a patient would be more appropriate for another clinic. Train the staff well right from the beginning and keep them happy to build team dynamics and reduce turnover. Options to enhance available care include an in-clinic physical therapist to perform balance testing and exertional testing, a social worker to coordinate care, and an in-clinic psychometrician to perform brief cognitive testing.
Neocortical Microcircuits
Authors: DeFelipe Javier , Rudy Bernardo
Published: May 2019

Throughout the history of neuroscience, scientists have been trying to generate simplified diagrams of the cerebral cortex that represent the main cellular components and their possible connections. New methods of studying the physiology and connectivity of cortical circuits have been combined with computational neuroscience and computer simulations in order to make it possible to learn more about the role of each element in the input-output circuit. The ultimate goal is to try to understand the functional implications of cortical organization using more detailed circuit diagrams than previously possible. This is a particularly difficult task when dealing with the neocortex, not only because of its complexity, but also because of the variations observed between different cortical areas and across species. This chapter will deal with general aspects of the main neuronal components of the neocortex and the way in which these components are interconnected in a general, basic microcircuit.
Barrel Cortex
Authors: Svoboda Karel , Yu Jianing
Published: May 2019

Over the past two decades, the barrel cortex has emerged as a major model system for the analysis of the structure, function, and experience-dependent plasticity of neocortical circuits. Driven by the availability of transgenic animals expressing fluorescent proteins and protein effectors in specific cell types, circuit studies of the barrel cortex are now mostly performed in mice. The cortical layers, cell types, and the intralaminar connectivity are similar in mice and rats. This chapter combines information gained from experiments in both species, but all quantitative data pertain to the mouse barrel cortex. We summarize current knowledge about the inputs, outputs and local circuits of the barrel cortex. Special emphasis is placed on the structure and function of layer 4, which may currently be the best understood cortical circuit. Circuit principles derived from layer 4 likely apply to cortical circuits in general.
Inhibitory Mechanisms in the Motor Cortical Circuit
Authors: Merchant Hugo , Georgopoulos Apostolos P.
Published: May 2019

Inhibitory mechanisms are crucial for the integrated operation of the motor cortical circuit. Local inhibition is exerted by interneurons that are GABAergic, nonpyramidal cells with short, nonprojecting axons. Interneurons can be classified into at least two groups: fast-spiking (FS) neurons and instrinsic bursting (IB) neurons. In the primary motor cortex, FS cells may sculpe the tuning dispersion of directionally selective putative pyramidal cells during reaching in behaving monkeys. Analysis of putative interneuronal activity also allowed to discard the role of inhibition as a gating mechanism in motor control. The development of high-density, semichronic electrode systems for extracellular recordings in behaving primates will allow a closer investigation of the role of interneuronal inhibition in directional tuning and voluntary motor control. The results discussed in this chapter agree with the authors’ proposal that local inhibitory mechanisms may be intimately involved in controlling the directional accuracy and speed of the reaching movement.
Prefrontal Cortex
Authors: Wang Xiao-Jing
Published: May 2019

The prefrontal cortex (PFC) circuits are characterized by several distinct features. First, the input–output connections of a PFC circuit with the rest of the brain are extraordinarily extensive. In the primates, pyramidal neurons in PFC are greatly more spinous than in the primary sensory areas, so they have a much larger capacity for synaptic integration. Second, PFC areas are endowed with strong intrinsic recurrent connections that are sufficient to generate reverberatory activity underlying working memory and decision-making. Third, excitation and inhibition are balanced dynamically. Unlike early sensory cortical areas, in the frontal areas of both monkey and mouse, the synaptic inhibitory circuit is predominated by GABAergic cell subclasses that are dedicated to controlling inputs to, rather than outputs from, pyramidal neurons, likely reflecting the functional demand of selectively gating input pathways into the PFC in accordance with the behavioral context and goals.
Circuitry of the Lateral Geniculate Nucleus
Authors: Sherman S. Murray
Published: May 2019

The circuitry of the thalamus is among the most thoroughly studied and best understood exemplars of functional connectivity in the brain. This chapter shall focus on the A laminae of the cat’s lateral geniculate nucleus (LGN), which represents the relay of retinal input to the cortex, because this has proved to be an excellent model for the thalamus. There are two major payoffs for understanding this circuit: the basic plan revealed by LGN circuitry seems to be applied throughout the thalamus, with some relatively minor modifications, so this provides general insights into overall thalamic functioning; and many circuit principles first appreciated in the LGN apply to other brain circuits.
Thalamocortical Networks
Authors: McCormick David A.
Published: May 2019

The thalamus and cerebral cortex are intimately linked through strong topographical connections, not only from the thalamus to the cortex, but also from the cortex back to the thalamus. As in many parts of the brain, the basic circuit of thalamocortical connectivity is relatively simple, although intracortical and corticocortical connectivity provides a high level of complexity. One of the basic operations of the thalamocortical network is the generation of rhythmic oscillations, which are now relatively well understood. In the normal brain, these thalamocortical oscillations typically occur during sleep, although their pathological counterparts may appear as seizures during sleep or waking. Unfortunately, the normal function of reciprocal thalamocortical connectivity during the waking state is still unknown. Even so, focused research is yielding insights into the properties of each of the cellular and synaptic components of these networks and how they interact to perform circuitwide operations.
Templates for Neural Dynamics in the Striatum: Striosomes and Matrisomes
Authors: Graybiel Ann M.
Published: May 2019

The striatum appears to be a relatively simple forebrain region compared to the overlying neocortex, with its horizontal layers and vertical columns. In fact, the striatum in mammals has a sophisticated architecture of its own. This large subcortical region is now suspected of having a major influence on how the neocortex carries out its own functions—even functions related to human language. Furthermore, abnormalities in the striatum are increasingly being discovered in human disorders affecting both cognitive and motor functions. It is, as a consequence, increasingly difficult to see the neocortex as a higher structure and the striatum as a lower structure in terms of their influence on behavior. The chapter is not a full review of this topic, but it points out some findings from the author’s laboratory that hint at such functions for the striosomal system.
Entorhinal Cortex
Authors: Moser Edvard I. , Witter Menno P. , Moser May-Britt
Published: May 2019

While decades of study have unraveled some of the basic principles of hippocampal structure and function, the adjacent entorhinal cortex (EC) has remained terra incognita in many respects. Recent studies suggest that the medial part of the entorhinal cortex is part of a two-dimensional metric map of the animal’s changing location in the environment. A key component of this map is the grid cell, which fires selectively at hexagonally spaced positions in the animal’s environment. Grid cells colocalize with other recently discovered medial entorhinal cell types, such as head direction cells, conjunctive grid × head direction cells, border cells, and speed cells. This chapter provides an overview of these functional cell types, their possible relationship to morphological cell types, the intrinsic architecture of the system (including laminar, longitudinal, and modular organization), and the extrinsic connectivity and possible function of both the medial and lateral subdivisions of the entorhinal cortex.
Retina: Microcircuits for Daylight, Twilight, and Starlight Vision
Authors: Demb Jonathan B. , Singer Joshua H.
Published: May 2019

Over the course of the day, light intensity can vary by 10 billion-fold, but a retinal ganglion cell’s spike rate can change only by 100-fold. To cover the huge intensity range, two fundamentally different retinal circuits are required: a cone bipolar circuit for transmitting graded photoreceptor signals and a rod bipolar circuit capable of transmitting binary signals. By using gap junctions, the two circuits can share key neural elements. Such an efficient use of circuitry is critical in a neural tissue that is constrained to be thin and transparent.
Olfactory Microcircuits in Drosophila Melanogaster
Authors: Rybak Jürgen , Hansson Bill S.
Published: May 2019

In the vinegar fly (Drosophila melanogaster), the neuronal pathway that processes olfactory information is organized into multiple layers: a peripheral set of olfactory sensory neurons (OSNs); the primary olfactory center, or antennal lobe (AL); and two second-order neuropils, the mushroom body (MB) and lateral horn (LH). Odorants are detected by the dendrites of OSNs housed in sensilla on the maxillary palps and antennae. The OSN axons converge onto spherical synaptic neuropil within the AL termed glomeruli. OSNs that express the same odorant receptor project to the same glomerulus in a one-to-one fashion, forming discrete olfactory pathways. In the AL, a network of local interneurons (LNs) and projection neurons (PNs) contribute to the first-order processing within the glomeruli. Two types of PNs constitute the principal, parallel output pathways made by PN axons that end in the second-order neuropils of the MB and LH: uniglomerular PNs (uPNs) and multiglomerular PNs (mPNs).
Cochlear Nucleus
Authors: Young Eric D. , Oertel Donata
Published: May 2019

Neuronal circuits in the brainstem convert the output of the ear, which carries the acoustic properties of ongoing sound, to a representation of the acoustic environment that can be used by the thalamocortical system. Most important, brainstem circuits reflect the way the brain uses acoustic cues to determine where sounds arise and what they mean. The circuits merge the separate representations of sound in the two ears and stabilize them in the face of disturbances such as loudness fluctuation or background noise. Embedded in these systems are some specialized analyses that are driven by the need to resolve tiny differences in the time and intensity of sounds at the two ears and to resolve rapid temporal fluctuations in sounds like the sequence of notes in music or the sequence of syllables in speech.
Cerebellar Cortex
Authors: Ito Masao
Published: May 2019

The microcircuit in the cerebellum is characterized by the relative simplicity, precision, and geometric beauty of its arrangement. Its structure is identical throughout the cerebellar cortex except for some regional differences. The cerebellar cortex has three layers (molecular layer, Purkinje cell layer, and granular layer) and can be divided into more than 100 subareas by horizontal grooves and longitudinal bands. Each subarea can be further subdivided into a number of microzones (there could be 10,000 microzones in the human cerebellum). A microzone, in combination with a small portion of the interior olive, and in some regions, also with that of the parvocellular red nucleus, consists of a microcomplex, a functional unit of the cerebellum. Structural and functional data of neuronal elements and their connections in the cerebellar microcircuit have been. Theoretical models have been proposed to explain how the cerebellar microcircuit operates and generates unique functions.