bluuebunny/crossref_metadata_2025 huggingface dataset:
Melanin Concentrating Hormone Signaling Deficits in Schizophrenia: Association with Memory and Social Impairments and Abnormal Sensorimotor Gating
Authors: Vawter Marquis P , Schulmann Anton , Alhassen Lamees , Alhassen Wedad , Hamzeh Abdul Rezzak , Sakr Jasmine , Pauluk Lucas , Yoshimura Ryan , Wang Xuejie , Dai Qi , Sanathara Nayna , Civelli Olivier , Alachkar Amal
Published: September 2019

Background

Evidence from anatomical, pharmacological, and genetic studies supports a role for the neuropeptide melanin concentrating hormone (MCH) system in modulating emotional and cognitive functions. Genome wide association (GWA) studies revealed a potential association between the MCH receptor (MCHR1) gene locus and schizophrenia and the largest GWA study conducted to date shows a credible GWA.

Methods

We analyze MCHR1 and pro-melanin concentrating hormone (PMCH) RNA-Seq expression in the prefrontal cortex in schizophrenia patients and healthy controls. Disruptions in the MCH system were modeled in the mouse brain by germline deletion of MCHR1 and by conditional ablation of MCH expressing neurons using a Cre-inducible diphtheria toxin (iDTR) system.

Results

MCHR1 expression is decreased in the prefrontal cortex of schizophrenia samples (FDR p< 0.05, CommonMind and PsychEncode combined datasets, N = 901) while PMCH is below the detection threshold. MCHR1 expression decreased with aging (p = 6.6E-57) in human dorsolateral prefrontal cortex. The deletion of MCHR1 was found to lead to behavioral abnormalities mimicking schizophrenia-like phenotypes: hyperactivity, increased stereotypic and repetitive behavior, social impairment, impaired sensorimotor gating, and disrupted cognitive functions. Conditional ablation of PMCH neurons increased repetitive behavior and produced a deficit in sensorimotor gating.

Conclusions

Our study indicates that early disruption of the MCH system interferes with neurodevelopmental processes which may contribute to the pathogenesis of schizophrenia. Further neurobiological research on the developmental timing and circuits that are affected by MCH may lead to a therapeutic target for early prevention of schizophrenia.
A full treatment of peculiar velocities on the reionization light cone
Authors: Chapman Emma , Santos Mario G
Published: September 2019

Accurate simulations of the 21-cm signal from the Epoch of Reionization require the generation of maps at specific frequencies given the values of astrophysical and cosmological parameters. The peculiar velocities of the hydrogen atoms producing the 21-cm radiation result in a shift in the observed frequency of the 21-cm radiation and changes the amplitude of the signal itself. This is not an effect we can remove but instead needs to be accurately modelled to ensure we infer the correct physical parameters from an observation. We describe the full calculation of the distortion of the 21-cm signal, and propose a new code that integrates the 21-cm intensity along the line of sight for each individual light cone pixel to fully capture the intensity contributions from multiple redshifts. This algorithm naturally deals with the typical divergences found in standard approaches, allowing for large optical depths and 21-cm absorption events at high redshifts. We find the new method results in up to a 60 per cent decrease in power on the largest scales on the sky, and an increase of over 80 per cent on the smallest scales on the sky. We find that the new implementation of the light cone results in a longer tail of bright temperatures in the brightness temperature distribution, as a result of the successful circumventing of a previous cap that had to be implemented to avoid a divergence in the brightness temperature. We conclude that this full treatment of the evolution of the light cone pixel can be an important effect.
A novel approach for the analysis of the geometry involved in determining light curves of pulsars
Authors: Viganò Daniele , Torres Diego F
Published: September 2019

In this work, we introduce the use of the differential geometry Frenet–Serret equations to describe a magnetic line in a pulsar magnetosphere. These equations, which need to be solved numerically, fix the magnetic line in terms of their tangent, normal, and binormal vectors at each position, given assumptions on the radius of curvature and torsion. Once the representation of the magnetic line is defined, we provide the relevant set of transformations between reference frames; the ultimate aim is to express the map of the emission directions in the star corotating frame. In this frame, an emission map can be directly read as a light curve seen by observers located at a certain fixed angle with respect to the rotational axis. We provide a detailed step-by-step numerical recipe to obtain the emission map for a given emission process, and give a set of simplified benchmark tests. Key to our approach is that it offers a setting to achieve an effective description of the system’s geometry together with the radiation spectrum. This allows to compute multifrequency light curves produced by a specific radiation process (and not just geometry) in the pulsar magnetosphere, and intimately relates with averaged observables such as the spectral energy distribution.
Greek and Roman Logic
Authors: Finley Robby , Vlasits Justin , Vogt Katja Maria
Published: September 2019

In ancient philosophy, there is no discipline called “logic” in the contemporary sense of “the study of formally valid arguments.” Rather, once a subfield of philosophy comes to be called “logic,” namely in Hellenistic philosophy, the field includes (among other things) epistemology, normative epistemology, philosophy of language, the theory of truth, and what we call logic today. This entry aims to examine ancient theorizing that makes contact with the contemporary conception. Thus, we will here emphasize the theories of the “syllogism” in the Aristotelian and Stoic traditions. However, because the context in which these theories were developed and discussed were deeply epistemological in nature, we will also include references to the areas of epistemological theorizing that bear directly on theories of the syllogism, particularly concerning “demonstration.” Similarly, we will include literature that discusses the principles governing logic and the components that make up arguments, which are topics that might now fall under the headings of philosophy of logic or non-classical logic. This includes discussions of problems and paradoxes that connect to contemporary logic and which historically spurred developments of logical method. For example, there is great interest among ancient philosophers in the question of whether all statements have truth-values. Relevant themes here include future contingents, paradoxes of vagueness, and semantic paradoxes like the liar. We also include discussion of the paradoxes of the infinite for similar reasons, since solutions have introduced sophisticated tools of logical analysis and there are a range of related, modern philosophical concerns about the application of some logical principles in infinite domains. Our criterion excludes, however, many of the themes that Hellenistic philosophers consider part of logic, in particular, it excludes epistemology and metaphysical questions about truth. Ancient philosophers do not write treatises “On Logic,” where the topic would be what today counts as logic. Instead, arguments and theories that count as “logic” by our criterion are found in a wide range of texts. For the most part, our entry follows chronology, tracing ancient logic from its beginnings to Late Antiquity. However, some themes are discussed in several eras of ancient logic; ancient logicians engage closely with each other’s views. Accordingly, relevant publications address several authors and periods in conjunction. These contributions are listed in three thematic sections at the end of our entry.
Margaret More Roper
Authors: Goodrich Jaime
Published: September 2019

Margaret More Roper (b. 1505–d. 1544) was the eldest daughter of Sir Thomas More and Jane Colt, More’s first wife. More was a vocal proponent of humanism, and he set up a school in his home to teach his four children—Margaret, Elizabeth, Cicely, and John—Latin and Greek as well as arithmetic, astronomy, philosophy, and theology. While More’s commitment to educating his daughters was truly pioneering, it did not reflect a proto-feminist commitment to women’s equality. Rather, More aimed to enhance all of his children’s piety, and to prepare his daughters in particular for their domestic roles as wives and mothers. By all accounts, Roper was the star pupil of this school, and she gained a national and even international reputation as one of the foremost learned women in England. Roper exchanged letters with the prominent humanist scholar Desiderius Erasmus, who dedicated to her his commentary on two hymns by Prudentius (1523). Perhaps in response to this compliment, Roper translated Erasmus’s treatise on the Lord’s Prayer (A Devout Treatise upon the Pater Noster, 1524) from Latin into English. Published quasi-anonymously, this text popularized Erasmian piety in the vernacular while also advocating for the value of women’s education according to humanist tenets. Roper also drew on her classical learning to compose a number of works in Latin that have since been lost: letters to her father and Erasmus, declamations, and poetry. In 1521 she married William Roper, a lawyer and a friend of her father, and she soon became a mother, giving birth to five children: Elizabeth, Mary, Thomas, Margaret, and Anthony. Like her father, Margaret Roper educated her children according to humanist standards, and her daughter Mary Basset became known in her own right for her English translations of Latin and Greek works. As Thomas More’s favorite daughter, Roper also played an important role in his personal piety and his final years. She alone washed the hair shirt that More wore for devotional purposes, and only she was allowed to visit him after he was imprisoned in the Tower for refusing to accept Henry VIII’s marriage to Anne Boleyn. Three of the English letters that she wrote during his incarceration are extant, including the important Alington letter, which dramatically recounts her unsuccessful efforts to persuade More to change his mind. After More’s execution, she preserved his writings and his severed head, safeguarding his legacy until her own death in 1544.
Colonial Legal History of Peru
Authors: Dueñas Alcira , Honores Renzo
Published: September 2019

After about 150 years of institutional history, historians, legal anthropologists, and lawyers shifted the focus of legal history to social analysis and effects of laws, institutions, and legal practices, opening a fruitful dialogue between legal and social history on the role of subaltern agents. These new studies sought to move away from institutional history and its formalist gloss of laws and institutions as the only relevant structures and issues in legal history. These scholars reconceptualized the law as an instrument of negotiation and assertion of the rights that both elites and plebeians used before the courts. As such, the law was seen as a complex landscape of social, cultural, and political factors beyond the traditional “written rule.” Law scholars have called for the need to restore law to its historical and cultural context, thus reclaiming a space for legal history and the anthropology of law within the schools of law in Peru. The legal instrument was also part of the Spanish imperial project. As is well known, Spain expanded its extraterritorial power through complex and plural laws and a legal bureaucracy. Social and legal historians have demonstrated that Spaniards and Portuguese in the Americas used laws to secure the possession of new lands and other sources of wealth, but subaltern groups also contested imperial power legally. Ethnohistorical approaches thus entered the field of legal history, showing how Amerindians seized upon their legal right to contest Spanish policies and the actions of authorities and colonists in courts of law at the local and regional levels, and at the highest level of the Council of the Indies. Afro-Peruvian women and men, as well as members of the castas (racially mixed groups), used the legal system extensively as well, and their legal and rhetorical strategies enriched the legal history of colonial Peru. Social historians of the Andes have also diversified the range of conventional sources incorporating notarial records, judicial proceedings, ecclesiastical registers, and Inquisition documents, among others, to the corpus of their primary sources. The result has been a body of literature that identified the diversity and plurality in the production of legal phenomena in Spanish America as the subaltern groups (caciques [Indigenous chiefs], as well as Amerindian and Afro-Peruvian women and men) entered the colonial legal forum and engaged its discourses. By necessity, however, this bibliography is selective, and authors are featured in different sections.
Law-Making by Non-State Actors
Authors: Masiko Timothy , Footer Mary E.
Published: September 2019

International law is a set of norms that covers the general procedures and institutions for the conduct of international relations. Its general function is to safeguard international peace, security, and justice in relations between states. As its name suggests, it is concerned with relationships between states, and that makes states the main actors or subjects of international law. As international law continues to evolve, however, the subjects of international law have broadened and changed. This has inevitably led to an evolution in the law-making process. Classically international rules could only be made by states, mainly by treaty or through international custom. More recently, the sources of law have expanded, as have the makers of international law. The classical sources of international law, stated in Article 38(1) of the Statute establishing the International Court of Justice (international conventions, international custom, general principles of law, and judicial decisions and teachings of highly qualified publicists), remain relevant, and new sources, principally ‘soft law,’ are gaining ground. In addition, non-state actors (NSAs) are becoming increasingly relevant, not just as subjects of international law but as participants in the law-making process. NSAs include international organizations, international and domestic judicial and quasi-judicial bodies, hybrid bodies, Civil Society, the private sector, and others. While previously and indeed currently in many spheres of international law international rules were only enforceable by and against states, it is increasingly common for NSAs to enjoy rights of audience before courts and tribunals, and also to participate in the law-making progress in various capacities. This has been through the creation of new customary international law, laying down new rules through the determination of disputes, the operation of soft law, and even the conclusion of treaties that bind states. The readings below start from a more general coverage of law-making to specific works about law-making by NSAs. They have been selected, as far as possible, to blend classical writings with current and recent research on the subject of law-making. Wherever possible, they include writings by practitioners in their relevant areas, such as judges and academics or legal counsel in and before judicial bodies. A note on terminology: many publications use the term “lawmaking” rather than “law-making”. Where in the original title of the publication the word “lawmaking” is used or else the words “law” and “making” appear disjunctively, it has been retained; otherwise, the word “law-making” is used.
Creativity at Work
Authors: Potočnik Kristina
Published: September 2019

Creativity at work is the process of generating novel and useful ideas to either introduce new products, processes, or services in the workplace or improve the existing ones. As such, creativity at work has been considered essential for improving organizational performance and making businesses flourish. Importantly, creativity at work has to be distinguished from workplace innovation. Oftentimes both terms are used interchangeably, although innovation in the workplace also covers the process of implementation of novel and useful ideas (as opposed to only production of such ideas). The most straightforward way of distinguishing between both concepts is to employ adequate measures to operationalize creativity and innovation at work. Based on the premise that the more creativity that is produced at work the better, the existing research has drawn on different theoretical approaches to tease out what individual and contextual factors enhance creativity at work (or at least do not inhibit it). There is also vast research on how creativity is produced and managed in context of work teams in order to understand how groups of employees work together to generate novel and useful ideas for organizational improvement. In sum, creativity at work is about producing novel and useful ideas, which constitutes the first stage of the innovation process. This can be developed and managed by drawing upon individual employee characteristics that are conducive to creativity as well as designing the work context in a way that enhances creativity. This piece is organized around these topics and aims to provide a guide to some of the key texts in the field.
Sleep stage dynamics in young patients with sleep bruxism
Authors: Kishi Akifumi , Haraki Shingo , Toyota Risa , Shiraishi Yuki , Kamimura Mayo , Taniike Masako , Yatani Hirofumi , Kato Takafumi
Published: September 2019

Study Objectives

We hypothesized that sleep stage dynamics are different in patients with sleep bruxism (SB) and that these changes are associated with the occurrence of rhythmic masticatory muscle activity (RMMA).

Methods

Fifteen healthy controls and 15 patients with SB underwent overnight polysomnography. Sleep variables and survival curves of continuous runs of each sleep stage were compared between the groups. Stage transition dynamics and the probability of stage fragmentation were analyzed for three epochs before and after the epoch with RMMA. Survival curves of continuous runs of each sleep stage, terminated with or without RMMA, were also compared.

Results

There were no significant differences in sleep variables between the groups, except for shorter sleep latency, shorter rapid eye movement (REM) latency, and longer total N1 duration in SB patients than in controls. REM sleep and N2 were significantly less continuous in SB patients than in controls. In the SB group, stage fragmentation probability was significantly increased for the epoch with RMMA compared with the baseline for all stages. Meanwhile, the occurrence of RMMA did not affect the continuity of N2 or REM; however, the occurrence of RMMA was preceded by more continuous N3 runs.

Conclusions

Sleep stage dynamics differed between SB patients and controls. RMMA does not result in sleep disruption but is likely associated with dissipation of sleep pressure. Less continuity of REM sleep in SB may provide insights into the underlying pathophysiological mechanisms of SB, which may be related to REM sleep processes such as cortical desynchronized states or brainstem activation.
Modeling the cardiometabolic benefits of sleep in older women: exploring the 24-hour day
Authors: Full Kelsie M , Gallo Linda C , Malhotra Atul , Bellettiere John , Kerr Jacqueline , Arredondo Elva , Stone Katie L , Zaslavsky Oleg , Lewis Cora E , Lin Xiaochen , Lacroix Andrea Z
Published: September 2019

Study Objectives

Activities throughout the day, including sleep, sedentary behavior (SB), light-intensity physical activity (LIPA), and moderate to vigorous physical activity (MVPA) are independently associated with cardiometabolic health. Few studies have examined interrelationships between sleep and 24-hour activity and associations with cardiometabolic risk. The objective of this study is to understand how replacing time in SB, LIPA, or MVPA with sleep impacts cardiometabolic risk.

Methods

Women’s Health Initiative OPACH Study participants (N = 3329; mean age = 78.5 ± 6) wore ActiGraph GT3X+ accelerometers 24 hours/7 days. Adjusted linear regression estimated the relationship between sleep duration and cardiometabolic markers. Separately for shorter (<8 hours) and longer (≥8 hours) sleepers, isotemporal substitution models estimated the cross-sectional associations with cardiometabolic markers with reallocating time in daytime activities to or from sleep.

Results

Longer sleep duration was associated with higher insulin, HOMA-IR, glucose, total cholesterol, and triglycerides (all p < 0.05). The associations between sleep duration and C-reactive protein, waist circumference, and body mass index (BMI) were U-shaped (both p < 0.05). For shorter sleepers, reallocating 33 minutes of MVPA to sleep was associated with higher values of insulin, HOMA-IR, glucose, triglycerides, waist circumference, and BMI (0.7%–11.5%). Replacing 91 minutes of SB time with sleep was associated with lower waist circumference and BMI (−1.3%, −1.8%). For long sleepers, shifting 91 minutes of sleep to SB was associated with higher waist circumference and BMI (1.3%, 1.4%).

Conclusions

This is one of the first isotemporal analyses to include objectively measured sleep duration. Results illuminate possible cardiometabolic risks and benefits of reallocating time to or from sleep.
Association of sleep-disordered breathing with total healthcare costs and utilization in older men: the Outcomes of Sleep Disorders in Older Men (MrOS Sleep) study
Authors: Vo Tien N , Kats Allyson M , Langsetmo Lisa , Taylor Brent C , Schousboe John T , Redline Susan , Kunisaki Ken M , Stone Katie L , Ensrud Kristine E
Published: September 2019

Study Objectives

To determine the associations of sleep-disordered breathing (SDB) with subsequent healthcare costs and utilization including inpatient and post-acute care facility stays among community-dwelling older men.

Methods

Participants were 1,316 men (mean age 76.1 [SD = 5.7] years) in the Outcomes of Sleep Disorders in Older Men (MrOS sleep) study (from December 2003 to March 2005), who were enrolled in a Medicare Fee-For-Service plan. Primary SDB measures including apnea hypopnea index (AHI) and oxygen desaturation index (ODI) were collected using in-home level 2 polysomnography. Incident healthcare costs and utilization were determined from claims data in the subsequent 3-year period post-MrOS sleep visit.

Results

Five hundred and twenty-nine (40.2%) men had at least one hospitalization in the 3-year period. Compared with those without sleep apnea (AHI < 5/hour), men with moderate to severe sleep apnea (AHI ≥ 15/hour) had a higher odds of all-cause hospitalization (odds ratio [OR] adjusted for age and site 1.43, 95% confidence interval [CI]: 1.07–1.90). This association was slightly attenuated after further adjustment for traditional prognostic factors including education, body mass index, comorbid medical conditions, and health status (OR = 1.36; 95% CI: 1.01–1.83). Similar associations were observed for ODI. However, measures of SDB were not related to subsequent healthcare costs (total or outpatient) or odds of post-acute skilled nursing facility stay.

Conclusions

Older men with SDB have an increased risk of hospitalization, not entirely explained by the greater prevalence of comorbid conditions, but not higher subsequent total healthcare costs. These findings indicate a need to evaluate the impact of SDB treatment on subsequent healthcare utilization.
Behavioral-educational sleep interventions for pediatric epilepsy: a randomized controlled trial
Authors: Tsai Shao-Yu , Lee Wang-Tso , Lee Chien-Chang , Jeng Suh-Fang , Weng Wen-Chin
Published: September 2019

Study Objectives

To evaluate the effect of a clinic-based, behavioral-educational sleep intervention on sleep of children with epilepsy, maternal knowledge about childhood sleep, and maternal sleep quality.

Methods

A total of 100 toddlers and preschool-age children with epilepsy (1.5–6 years, 55% boys) and their parents were randomized to receive sleep intervention (n = 50) or usual care with attention (n = 50). Outcomes were assessed at baseline, 3, 6, and 12 months after intervention with the use of objective actigraphy, Children’s Sleep Habits Questionnaire, Parents’ Sleep Knowledge Inventory, and Pittsburgh Sleep Quality Index. Intervention effects were examined using general linear models for repeated measurements to compare the mean change in outcomes from baseline to 12 months post-intervention between the two groups.

Results

Sleep intervention resulted in children having greater sleep efficiency by 2.03% compared with the usual care group (95% CI = 0.20% to 3.86%; p = .03). Children in the intervention group also had significantly longer total nighttime sleep as objectively assessed by actigraphy than did those in the usual care group, with an adjusted mean difference of 16.13 minutes (95% CI = 0.24% to 32.03%; p = .04). No intervention effects were observed for maternal knowledge about childhood sleep, and maternal sleep quality.

Conclusion

Sleep intervention provided during routine neurologic visits results in significant, measurable, and sustained benefits in sleep quality and quantity in children with epilepsy. Future trials are warranted to evaluate whether improvements in sleep could impact health-related quality of life or other aspects of functioning in children with epilepsy.

Clinical Trial

This trial has been registered at www.clinicaltrials.gov (trial name: Sleep Intervention for Pediatric Epilepsy; registration number: NCT02514291).
Slow-frequency electroencephalography activity during wake and sleep in obesity hypoventilation syndrome
Authors: Sivam Sheila , Poon Joseph , Wong Keith K H , Yee Brendon J , Piper Amanda J , D’Rozario Angela L , Wang David , Grunstein Ronald R
Published: September 2019

Study Objective

Neurophysiological activity during wake and sleep states in obesity hypoventilation (OHS) and its relationship with neurocognitive function is not well understood. This study compared OHS with equally obese obstructive sleep apnea (OSA) patients, with similar apnea-hypopnea indices.

Methods

Resting wake and overnight sleep electroencephalography (EEG) recordings, neurocognitive tests, and sleepiness, depression and anxiety scores were assessed before and after 3 months of positive airway pressure (PAP) therapy in 15 OHS and 36 OSA patients.

Results

Pretreatment, greater slow frequency EEG activity during wake and sleep states (increased delta-alpha ratio during sleep, and theta power during awake) was observed in the OHS group compared to the OSA group. EEG slowing was correlated with poorer performance on the psychomotor vigilance task (slowest 10% of reciprocal reaction times, psychomotor vigilance test [PVT SRRT], primary outcome), and worse sleep-related hypoxemia measures in OHS. There was no between-group significant difference in PVT performance at pre or post-treatment. Similarly, despite both groups demonstrating improved sleepiness, anxiety and depression scores with PAP therapy, there were no differences in treatment response between the OSA and OHS groups.

Conclusion

Patients with OHS have greater slow frequency EEG activity during sleep and wake than equally obese patients with OSA. Greater EEG slowing was associated with worse vigilance and lower oxygenation during sleep.

Clinical Trial

This trial was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12615000122550).
Cerebrospinal fluid biomarkers of neurodegeneration in narcolepsy type 1
Authors: Baiardi Simone , Pizza Fabio , Polischi Barbara , Moresco Monica , Abu-Rumeileh Samir , Plazzi Giuseppe , Parchi Piero
Published: September 2019

Study Objectives

To measure the levels of five neurodegenerative biomarkers in the cerebrospinal fluid (CSF) of patients with narcolepsy type 1 (NT1) with variable disease duration.

Methods

Following a standardized protocol of CSF collection and storage, we measured CSF total- and phosphorylated-tau, amyloid-beta 1–40 and 1–42, and neurofilament light chain (NfL) proteins in 30 nonneurological controls and 36 subjects with NT1, including 14 patients with recent disease onset (i.e. ≤12 months, short disease duration group).

Results

CSF levels of all biomarkers were similar in NT1 subjects and controls. The comparison between NT1 with short and long disease duration only revealed slightly higher levels of CSF amyloid-beta 1–40 in the former group (median 9,549.5, interquartile range [IQR] 7,064.2–11,525.0 vs. 6,870.0, IQR 5,133.7–9,951.2, p = 0.043). CSF storage time did not influence the levels of the tested biomarkers.

Conclusions

The measurement of CSF total-tau, phosphorylated-tau, amyloid-beta 1–40 and 1–42, and NfL proteins is not informative in NT1.
Analysis of patients with obstructive sleep apnea with and without pharyngeal myopathy using brain neuroimaging
Authors: Baima Camila Bonfanti , Fim Natália Castro , Alves Karen Fernanda , Resende Luiz Antonio de Lima , Fonseca Ronaldo Guimarães , Betting Luiz Eduardo
Published: September 2019

Study Objectives

Elements impairing upper airway anatomy or muscle function (e.g. pharyngeal neuromyopathy) contribute to obstructive sleep apnea syndrome (OSAS). Structural brain imaging may differ in patients with OSAS according to dilator muscle dysfunction. Magnetic resonance imaging (MRI) with voxel-based morphometry (VBM) and surface-based morphometry (SBM) was used to investigate this hypothesis.

Methods

Eighteen patients with OSAS and 32 controls underwent 3T brain MRI. T1 volumetric images were used for structural analysis. Pharyngeal electroneuromyography was performed; patients with OSAS were classified as with or without neuromyopathy. VBM and SBM analyses were conducted using SPM12 and CAT12 software. Image processing was standard. Cortical surface parameters and gray and white matter volumes from participants with OSAS with and without neuromyopathy were compared with those from controls.

Results

Eleven patients had OSAS with neuromyopathy and seven patients had OSAS without neuromyopathy (normal pharyngeal electroneuromyography). Comparing these groups to the controls, VBM revealed: four clusters (total volume 15,368 mm3) for patients with neuromyopathy, the largest cluster in the left cerebellum (9,263 mm3, p = 0.0001), and three clusters (total 8,971 mm3) for patients without neuromyopathy, the largest cluster in the left cerebellum (5,017 mm3, p = 0.002). Patients with OSAS with neuromyopathy showed increased proportion of atrophy (p < 0.0001). SBM showed abnormalities in patients without neuromyopathy (decreased cortical thickness, left precentral gyrus [672 vertices, p = 0.04]; increased cortical complexity, right middle temporal gyrus [578 vertices, p = 0.032]).

Conclusion

Damaged areas were larger in patients with OSAS with than in those without neuromyopathy, suggesting differences in brain involvement. Patients with OSAS and neuromyopathy may be more susceptible to cerebral damage.
Short-term sleep deprivation in mice induces B cell migration to the brain compartment
Authors: Korin Ben , Avraham Shimrit , Azulay-Debby Hilla , Farfara Dorit , Hakim Fahed , Rolls Asya
Published: September 2019

Increasing evidence highlight the involvement of immune cells in brain activity and its dysfunction. The brain’s immune compartment is a dynamic ensemble of cells that can fluctuate even in naive animals. However, the dynamics and factors that can affect the composition of immune cells in the naive brain are largely unknown. Here, we examined whether acute sleep deprivation can affect the brain’s immune compartment (parenchyma, meninges, and choroid plexus). Using high-dimensional mass cytometry analysis, we broadly characterized the effects of short-term sleep deprivation on the immune composition in the mouse brain. We found that after 6 h of sleep deprivation, there was a significant increase in the abundance of B cells in the brain compartment. This effect can be accounted for, at least in part, by the elevated expression of the migration-related receptor, CXCR5, on B cells and its ligand, cxcl13, in the meninges following sleep deprivation. Thus, our study reveals that short-term sleep deprivation affects the brain’s immune compartment, offering a new insight into how sleep disorders can affect brain function and potentially contribute to neurodegeneration and neuroinflammation.
Emotion dysregulation in idiopathic rapid eye movement sleep behavior disorder
Authors: Jun Jin-Sun , Kim Ryul , Jung Hye-Min , Byun Jung-Ick , Seok Jin Myoung , Kim Tae-Joon , Lim Jung-Ah , Sunwoo Jun-Sang , Kim Han-Joon , Schenck Carlos H , Yang Kwang Ik , Jung Ki-Young
Published: September 2019

Study Objectives

To characterize emotion regulation strategies in patients with idiopathic REM sleep behavior disorder (iRBD) and to explore whether these strategies are associated with clinical symptoms.

Methods

In this cross-sectional multicenter study, a total of 94 polysomnography-confirmed iRBD patients (mean age, 67.6 years; men, 56%) and 50 healthy controls (mean age, 65.4 years; men, 48%) completed the Cognitive Emotion Regulation Questionnaire (CERQ), the Korean version of the RBD questionnaire-Hong Kong (RBDQ-KR), the Buss-Durkee Hostility Inventory (BDHI), the second edition of the Beck Depression Inventory (BDI-II), and the Korean version of the Montreal Cognitive Assessment (MoCA-K).

Results

The iRBD group had lower CERQ adaptive scores than the control group, whereas the CERQ maladaptive scores were not significantly different between the groups. Among the CERQ adaptive subscales, the scores for positive refocusing, refocusing on planning, and positive reappraisal were significantly lower in the iRBD group than in the control group. Higher CERQ adaptive scores were correlated with lower scores on RBDQ-KR factor 1 (dream-related) and the BDI-II and higher MoCA-K scores but were not correlated with RBDQ-KR factor 2 (behavioral manifestation) or BDHI scores. Among the dream content-related items of RBDQ-KR factor 1, the CERQ adaptive score was associated only with frequent nightmares. No correlation was found between CERQ maladaptive scores and any variable except for a positive correlation with BDI-II scores.

Conclusions

Our results provide evidence of emotion regulation deficits in iRBD patients. Furthermore, these results were linked to dream-related factors, especially nightmares, along with depressive symptoms and cognitive impairment.
Sleep quality, insomnia, and internalizing difficulties in adolescents: insights from a twin study
Authors: Madrid-Valero Juan J , Ronald Angelica , Shakeshaft Nicholas , Schofield Kerry , Malanchini Margherita , Gregory Alice M
Published: September 2019

Study Objectives

There is a well-established association between poor sleep quality and internalizing traits. This relationship has previously been studied using a twin design. However, when it comes to adolescence, there is a paucity of twin studies that have investigated this relationship, despite the importance of this developmental stage for both the development of poor sleep quality and internalizing symptoms. Additionally, anxiety sensitivity, which is commonly associated with poor sleep quality, has not been studied in this context. Our objective was to estimate genetic and environmental influences on the relationships between insomnia, poor sleep quality, and internalizing symptoms in adolescence.

Methods

Insomnia, poor sleep quality, depression, anxiety, and anxiety sensitivity traits were measured in a sample of 5111 twin pairs from the Twins Early Development Study, born between 1994 and 1996 (mean age 16.32 years [SD = 0.68]).

Results

A moderate proportion of the variance for the different variables (.29–.42) was explained by genetic factors. Associations between sleep and internalizing variables were moderate (r = .34–.46) and there was a large genetic overlap between these variables (rA= .51–.73).

Conclusion

This study adds novel information by showing that there are large genetic correlations between sleep disturbances and internalizing symptoms in adolescence.
Selective activation of serotoninergic dorsal raphe neurons facilitates sleep through anxiolysis
Authors: Venner Anne , Broadhurst Rebecca Y , Sohn Lauren T , Todd William D , Fuller Patrick M
Published: September 2019

A role for the brain’s serotoninergic (5HT) system in the regulation of sleep and wakefulness has been long suggested. Yet, previous studies employing pharmacological, lesion and genetically driven approaches have produced inconsistent findings, leaving 5HT’s role in sleep-wake regulation incompletely understood. Here we sought to define the specific contribution of 5HT neurons within the dorsal raphe nucleus (DRN5HT) to sleep and arousal control. To do this, we employed a chemogenetic strategy to selectively and acutely activate DRN5HT neurons and monitored sleep-wake using electroencephalogram recordings. We additionally assessed indices of anxiety using the open field and elevated plus maze behavioral tests and employed telemetric-based recordings to test effects of acute DRN5HT activation on body temperature and locomotor activity. Our findings indicate that the DRN5HT cell population may not modulate sleep-wake per se, but rather that its activation has apparent anxiolytic properties, suggesting the more nuanced view that DRN5HT neurons are sleep permissive under circumstances that produce anxiety or stress.
Tensions in Assessment: The Realities of Entrustment in Internal Medicine
Authors: Melvin Lindsay , Rassos James , Stroud Lynfa , Ginsburg Shiphra
Published: September 2019

Purpose

A key unit of assessment in competency-based medical education (CBME) is the entrustable professional activity. The variations in how entrustment is perceived and enacted across specialties are not well understood. This study aimed to develop a thorough understanding of the process, concept, and language of entrustment as it pertains to internal medicine (IM).

Method

Attending supervisors of IM trainees on the clinical teaching unit were purposively sampled. Sixteen semistructured interviews were conducted and analyzed using constructivist grounded theory. The study was conducted at the University of Toronto from January to September 2018.

Results

Five major themes were elucidated. First, the concepts of entrustment, trust, and competence are not easily distinguished and sometimes conflated. Second, entrustment decisions are not made by attendings, but rather are often automatic and predetermined by program or trainee level. Third, entrustment is not a discrete, point-in-time assessment due to longitudinality of tasks and supervisor relationships with trainees. Fourth, entrustment scale language does not reflect attendings’ decision making. Fifth, entrustment decisions affect the attending more than the resident.

Conclusions

A tension arises between the need for a common language of CBME and the need for authentic representation of supervision within each specialty. With new assessment instruments required to operationalize the tenets of CBME, it becomes critically important to understand the nuanced and specialty-specific language of entrustment to ensure validity of assessments.
The Homeless Hospital Liaison Program: An Interprofessional Program to Improve Students’ Skills at Facilitating Transitions of Care for Patients Experiencing Homelessness
Authors: Gill Frances , Appley Maya , Nix Linda , Green Georgiana , Gribbon Madeline , Divagaran Adhira , Huo Samantha , Avegno Jennifer , Jones Catherine
Published: September 2019

Problem

Traditional medical school curricula lack specific training on caring for individuals experiencing homelessness, and the literature suggests that medical students’ attitudes toward these individuals become increasingly negative during medical school.

Approach

To increase discharge planning support for individuals experiencing homelessness, the Homeless Hospital Liaison (HHL) program was developed at the University Medical Center New Orleans in January 2017–May 2017. Student liaisons are recruited from all 4 years of medical school and a graduate-level social work program. Liaisons administer a social needs questionnaire to assess patients’ connections to services and identify gaps in care, coordinate with hospital social workers to avoid duplicating work, coordinate with the medical team, help patients complete any needed documentation or applications for social benefits, provide patients with referrals to outpatient resources, and provide patients assistance with a variety of basic needs.

Outcomes

As of December 2017, HHL has trained 70 students (65 medical students and 5 social work students) to serve as liaisons and has enrolled 99 patients. For the majority of these patients, student liaisons were able to facilitate successful referrals to community-based services.

Next Steps

Future directions of the HHL program include developing a formal, staffed consult service at the hospital (e.g., the HHL program was awarded hospital funding for 2 full-time staff in the summer of 2019, which will increase the HHL’s capacity); assessing the program’s effect on student knowledge, attitudes, and proficiency related to individuals experiencing homelessness and/or interprofessional collaboration; and assessing the impact of the program on patients’ experiences.
Sarcoid-like Reaction Discovered on EBUS-TBNA of Intrathoracic Lymph Nodes During Immunotherapy for Metastatic Melanoma
Authors: Frohlich Michael , Wang Hangjun , Sakr Lama
Published: September 2019

The use of immune checkpoint inhibitors has dramatically improved outcomes for patients with advanced melanoma and other malignancies. Checkpoint inhibitors are associated with a unique set of toxicities collectively known as immune-related adverse events, the incidence of which is rising in parallel with their increasing use in clinical practice. Immune-related adverse events are widely variable in their presentation and can affect virtually any organ system in the body. Sarcoid-like reactions in patients being treated with immune checkpoint inhibitors are rare and are typically multisystemic in nature with isolated pulmonary involvement representing only a small minority of cases reported in the literature. Herein we describe 2 patients who developed progressively enlarging lymphadenopathy while receiving checkpoint inhibitors for metastatic melanoma. Both patients were initially noted to have an excellent clinical response to immunotherapy but their treatment was interrupted pending further investigation as they were suspected to have progressive disease. They were ultimately diagnosed with sarcoid-like reactions after an endobronchial ultrasound-guided lymph node biopsy revealed noncaseating granulomas and were able to resume their immunotherapy without any further interventions or negative effect on their disease course. These 2 cases illustrate the importance of obtaining a tissue diagnosis when imaging reveals enlarging lymph nodes while on immunotherapy for solid malignancies as the differential diagnosis includes benign entities such as sarcoid-like reactions in addition to disease progression. Timely diagnosis through minimally invasive tissue sampling techniques, such as endobronchial ultrasound, can help rule out malignant etiologies of lymphadenopathy and minimize interruptions in treatment.
Identification of robust reference genes for studies of gene expression in FFPE melanoma samples and melanoma cell lines
Authors: Christensen Julie N. , Schmidt Henrik , Steiniche Torben , Madsen Mette
Published: September 2019

There is an urgent need for novel diagnostic melanoma biomarkers that can predict increased risk of metastasis at an early stage. Relative quantification of gene expression is the preferred method for quantitative validation of potential biomarkers. However, this approach relies on robust tissue-specific reference genes. In the melanoma field, this has been an obstacle due to lack of validated reference genes. Accordingly, we aimed to identify robust reference genes for normalization of gene expression in melanoma. The robustness of 24 candidate reference genes was evaluated across 80 formalin-fixed paraffin-embedded melanomas of different thickness, −/+ ulceration, −/+ reported cases of metastases and of different BRAF mutation status using quantitative real-time PCR. The expression of the same genes and their robustness as normalizers was furthermore evaluated across a number of melanoma cell lines. We show that housekeeping genes like GAPDH do not qualify as stand-alone normalizers of genes expression in melanoma. Instead, we have as the first identified a panel of robust reference genes for normalization of gene expression in melanoma tumors and cultured melanoma cells. We recommend using a geometric mean of the expression of CLTA, MRPL19 and ACTB for normalization of gene expression in melanomas and a geometric mean of the expression of CASC3 and RPS2 for normalization of gene expression in melanoma cell lines. Normalization, according to our recommendation will allow for quantitative validation of potential novel melanoma biomarkers by quantitative real-time PCR.
Analysis of Care Coordination Needs for Families of Children with Special Health Care Needs
Authors: Roman Susan B. , Dworkin Paul H. , Dickinson Patricia , Rogers Steven C.
Published: September 2019

Objectives:

To identify the diverse services required by families of children with special health care needs (CSHCN) and identify the specific care coordination (CC) efforts associated with the most common types of observed diagnoses. Requested services were categorized into specific sectors, and CC efforts were quantified by observed diagnoses and defined sectors.

Methods:

CC service data were extracted and analyzed from patient encounters over 4 years (2009–2013) in a department database. This included descriptive information about referrals and linkages to medical, dental, and behavioral health providers and to state, private, and community agencies. Diagnostic classifications and CC sectors were defined to enable categorization.

Results:

A total of 2682 CSHCN records were reviewed. The majority (59%) required services/resources in 1 to 2 sectors, 24% required services/resources in 3 to 5 sectors, and 17% required services/resources in 6 or more sectors. Including informational service, the most frequently required sectors across the study population were education, financial, medical/dental, social connections, and advocacy. Children diagnosed with autism spectrum disorder had the highest needs across all sectors.

Conclusion:

Most CSHCN and their families use a substantial amount of CC time and effort to secure services from diverse sectors. High-quality and efficient CC requires an understanding of the specific needs of these CSHCN and their families and how to link them to a diverse array of services and resources.