bluuebunny/crossref_metadata_2025 huggingface dataset:
101 Amyotrophic Lateral Sclerosis (ALS) - Not Just a Motor Disease? Isolated Bitter and Sweet Taste Loss in ALS
Authors: Ashary Ahmed A , Patel Dev N , Hirsch Alan R
Published: April 2020

Study Objective:

Specific taste quality deficits in ALS has not heretofore been described.

METHOD:

Case Study: A 71 year old right handed female presented with a two year course of progressive reduction in strength in her hands, arms and legs with difficulty tying shoe laces, opening jars, writing and walking. She described nocturnal muscle spasms involving all extremities. Gradually, over eight months prior to presentation, all food began to taste bad and horribly bitter. Associated with no appetite and a seven pounds weight loss.

RESULTS:

Abnormalities in Neurological examination: Cranial Nerve (CN) examination: CN IX and X: Gag absent bilaterally. Motor examination: Bulk: atrophy in thenar and hypothenar eminences and intrinsics in both upper extremities. Percussion induced fasciculation and myotonia in both shoulders and arms. Fasciculation of tongue with percussion myotonia of tongue. Strength: Intrinsic 4/5 in both upper extremities, 3/5 in abductor policis brevis bilaterally, 3/5 right gastrocnemius soleus, 4/5 bilateral anterior tibialis. Drift testing: left abductor digiti minimi sign. Gait: Heel and toe walking unstable with circumduction of left leg. Tandem gait unstable. Cerebellar: Holmes rebound phenomena positive in the left upper extremity. Deep tendon reflexes: 1+ left brachioradialis. 1+ left triceps. 3+ right ankle jerks. 0 left ankle jerk. Positive jaw jerk. Chemosensory Testing: Normosmia to: Alcohol Sniff Test (46), Pocket Smell Test (3/3) and Retronasal Smell Index (9). Taste Quadrant Testing: ageusia in the palate to sodium chloride and citric acid. Ageusia throughout the palate, tongue and whole mouth to sucrose and quinine hydrochloride. Fungiform papillae count: left 18, right 20 (normal). Lip biopsy (normal). MRI: T2 flair in bilateral corticospinal tracts, left greater than right in the spinal cord and the brain. EMG: fibrillation, positive waves with fasciculation in all four extremities. Voluntary contraction with polyphasic unstable motor unit action potentials.

CONCLUSION:

While Lang found no taste loss in ALS (Lang, 2011), Pelletier found reduction in intensity of taste to all modalities in different sectors of the tongue, but paradoxically demonstrated normogeusia in whole mouth taste perception (Pelletier, 2013). Pathological specimens of those with ALS revealed degeneration in the nucleus parabrachialis medialis and tractus trigeminothalamicus dorsalis (Oyanagi, 2015), suggesting that taste deficit may be due to central white matter abnormalities. Sweet taste is localized in the most posterior and rostral aspect of the right insular cortex, immediately adjacent to bitter (Prinster, 2017), suggesting a neighborhood effect phenomena. Weight loss in ALS may be due to sensory distortion and secondary impairment of appetite. It would be worthwhile to investigate those with ALS for evidence of otherwise overlooked gustatory deficits, correction of which may improve appetite and nutritional state.
103 Atypical Progressive Bulbar Palsy presenting with Dropped Head
Authors: Carvajal-González Alexander , Iglesias Antonio H
Published: April 2020

Introduction:

Typical amyotrophic lateral sclerosis (ALS) presents on neurological examination with specific signs of upper and lower motor neuron degeneration (Brooks et al, 1995), which can account for 85% of patients with ALS (Turner and Talbot, 2013). There are different types of clinical presentations, including progressive bulbar palsy (PBP), Limb-onset ALS, progressive muscular atrophy (PMA) and upper motor neuron (UMN) predominant ALS. PBP has mainly brainstem signs. There are a few case reports of dropped head syndrome in ALS, mainly in patients with the limb involvement variant.

Methods:

Case report

Results:

A 56 year old right-handed male, presented to the clinic with four months of dysphagia to liquids and solids, neck pain and progressive neck weakness causing constant drop head. No dysarthria or other neurological symptoms, no dyspnea. Neurological examination: Cranial Nerve (CN) CN XII: Nasal voice, bilateral atrophy of the tongue with tremor and fasciculations. Motor: Diffuse atrophy and decreased tone of the sternocleidomastoid and trapezii bilaterally, strength: 2/5 in neck flexors and extensors. Sensory: Hypoesthesia of the tongue. The rest of his neurological examination was normal. Labs: Routine blood work, thyroid function tests, collagen vascular work-up, and protein electrophoresis were normal. Creatine Phosphokinase (CPK) and Acetylcholine Receptor Antibodies (AChR Ab) were negative. Brain and Spinal Cord MRI: Showed mild brainstem, cerebellar and cervical spinal atrophy.

Conclusions:

Patients with ALS initially present with symptoms localized to the limbs or bulbar muscles. A very small percentage 1-2% of ALS patients had neck muscle weakness with head drop (Jokelainen et al, 1977; Gourie-Devi et al, 2003). However, in all the previously reported cases, the patients had limb involvement at the time of presentation which was absent in this case, and the head drop occurred after the onset of symptoms (Lange et al, 1986; Katz et al; 1996). Dropped head syndrome can be seen in inflammatory myopathies, myasthenia gravis, facioscapulohumeral muscular dystrophy, spinal muscular atrophy, nemaline myopathy and carnitine deficiency (Umapathy et al, 2003) but ALS should also be considered in patients with atypical presentations.
117 Impact of Antipsychotic Treatment Switching in Patients with Schizophrenia, Bipolar Disorder, and Major Depressive Disorder
Authors: Ayyagari Rajeev , Thomason Darren , Mu Fan , Philbin Michael , Carroll Benjamin
Published: April 2020

Study Objective:

To evaluate the risk of relapse for patients with schizophrenia (SZ), bipolar disorder (BP), and major depressive disorder (MDD) who switched antipsychotics compared with those who did not switch.

Background:

Antipsychotics are commonly used for maintenance treatment of SZ, BP, and MDD but can have significant side effects, such as extrapyramidal symptoms (EPS). Adherence to treatment is important for reducing the risk of relapse, but fear of side effects may prompt medication switching.

Methods:

Medicaid claims from 6 US states spanning 6 years were retrospectively analyzed for antipsychotic switching versus non-switching. For all patients with SZ, BD or MDD and for the subset of patients who also had ≥1 EPS diagnosis during the baseline period, times to the following outcomes, during a 2-year study period were analyzed: underlying disease relapse, psychiatric relapse, all-cause emergency room (ER) visit, all-cause inpatient (IP) admission and EPS diagnosis.

Results:

Switchers (N=10,548) had a shorter time to disease relapse, other psychiatric relapse, IP admissions, ER visits, and EPS diagnosis (all, log-rank P<0.001) than non-switchers (N=31,644). Switchers reached the median for IP admission (21.50 months) vs non-switchers (not reached) and for ER visits (switchers, 9.07 months; non-switchers, 13.35 months). For disease relapse, other psychiatric relapse, and EPS diagnosis, <50% of patients had an event during the 2-year study period. Comparisons in a subgroup of patients with ≥1 EPS diagnosis revealed similar outcomes.

Conclusions:

These results show that disease and other psychiatric relapse, all-cause ER visits, IP admissions, and EPS diagnosis occurred earlier for switchers than for non-switchers, suggesting that switching is associated with an increased risk of relapse in patients with SZ, BP and MDD.

Funding Acknowledgements:

This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.
133 Toxic Psychosis: Follow-up After One Year of Treatment
Authors: Oriaifo Glen
Published: April 2020

Introduction:

Anti-NMDA (N-methyl-D-aspartate) receptor encephalitis often presents itself in psychiatric settings as first-break psychosis. I present a case of a 31-year-old female who returned to the clinic one year after being treated for NMDA receptor antibody encephalitis.

CASE REPORT:

Ms. C is a 31 y/o female who returned to the clinic after one year of being discharged from the hospital for NMDA-receptor encephalitis with positive serological NR1 antibodies. She was initially admitted to our inpatient psychiatric facility for an unspecified psychotic disorder complicated with seizure-like episodes. She was given various psychotropic medications without any improvement. She was moderately responsive to olanzapine and lorazepam. Her condition gradually worsened; she stopped communicating and became mute. Neurology consultation prompted work-up for encephalitis and the probable diagnosis of NMDA receptor encephalitis. She was subsequently treated with steroids, IVIG and then intrathecal rituximab and bortezomib. In addition to these aforementioned medications, she underwent a prophylactic oophorectomy and 10 ECT treatments for life threatening catatonia. After three weeks of this regimen, Ms. C recovered completely and was discharged home.

DISCUSSION:

This case adds to literature that suggests prompt diagnosis and management of NMDA receptor encephalitis significantly improves prognosis. Treatment should be initiated if the patient meets probable diagnostic criteria for NMDA receptor encephalitis. Similar to other cases in the literature, our patient’s symptom of catatonia improved with ECT administration. During Ms. C one year follow-up, no evidence of psychotic symptoms were appreciated. Family members reported that she had returned to her baseline cognitive function.
137 CME on Pharmacogenomics Testing Improves Knowledge, Competence, and Confidence Related to Implementing Testing in Practice
Authors: Lucero Katie S. , Chatterjee-Shin Piyali , Dermer Shari J.
Published: April 2020

Study Objective(s):

Pharmacogenomics (PGx) testing, in particular combinatorial PGx testing, represents a potential means for delivering personalized treatment selection for patients with psychiatric disorders. The goal of this educational intervention was to educate clinicians about the role of PGx testing in neuropsychiatric conditions such as MDD, how these novel tests may be implemented into clinical practice, and how results may be used to inform decision-making.

Method:

Psychiatrists (n=830) participated in an online enduring CME activity on PGx testing in psychiatric disorders

•

The format was a 30-minute 2-person discussion (launched December 7, 2018)

•

Data from this activity were collected for 30 days after launch

•

Effectiveness of education for the CME activities was analyzed using 3 multiple-choice and 1 self-efficacy question (5-point Likert-type scale), presented as pre-/post-CME repeated pairs

•

A paired samples t-test was conducted to examine improvements in mean confidence pre and post

Participant knowledge, competence, and confidence change in pre- to post-CME responses were calculated

Results:

Overall, 72% of psychiatrists (n=830) had knowledge or competence that was reinforced or improved as a result of education.

Following education:

*

56% and 12% of psychiatrists had reinforcement and improvement, respectively, in knowledge related to the clinical benefits of PGx-guided treatment strategies

•

61% and 8% of psychiatrists had reinforcement and improvement, respectively, in competence related to interpreting PGx tests for patients with neuropsychiatric disorders

•

Within the group of psychiatrists with reinforced and improved knowledge/competence, there was a 30% increase in their confidence using PGx tests to help guide treatment decisions for patients with major depressive disorder (MDD) (M pre=2.14, post=2.77, scale 1 to 5)

•

Confidence in the use of PGx testing was correlated with likelihood of considering PGx testing for patients with MDD

Conclusions:

Online CME aided in psychiatrists’ knowledge, competence, and confidence in using pharmacogenomics testing in patients with psychiatric disorders.

Funding Acknowledgements:

Supported by an independent educational grant from Myriad Neuroscience, formerly Assurex Health
152 Development of Deutetrabenazine as a Potential New Non-Antipsychotic Treatment for Tourette Syndrome in Children and Adolescents
Authors: Jankovic Joseph , Coffey Barbara , Claassen Daniel O. , Stamler David , Gertz Barry J. , Garofalo Elisabeth A. , Wieman Maria , Gordon Mark Forrest , Savola Juha-Matti
Published: April 2020

Background:

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the hyperkinetic movements of motor and phonic tics manifested in young age. Currently approved treatments in the United States are antipsychotics: haloperidol, pimozide, and aripiprazole, which are associated with serious side effects, including tardive dyskinesia (TD). Deutetrabenazine, a vesicular monoamine transporter type 2 (VMAT2) inhibitor, was approved in 2017 by the US FDA for the treatment of chorea associated with Huntington’s disease and TD. Three ongoing studies (Alternatives for Reducing Tics in TS [ARTISTS]) are evaluating the efficacy, safety, and tolerability of deutetrabenazine in reducing tics in TS in children and adolescents (age 6-16 years).

Methods:

ARTISTS 1, a phase 2/3, response-driven, dose-titration, placebo-controlled study, randomizes patients (N=116) 1:1 to deutetrabenazine or placebo for 12 weeks. ARTISTS 2, a phase 3, fixed-dose study, randomizes patients (N=150) 1:1:1 to deutetrabenazine high or low dose, or placebo for 8 weeks. The primary efficacy outcome in these pivotal studies is change from baseline to end of treatment in the Total Tic Score (TTS) of the Yale Global Tic Severity Scale (YGTSS). Additional efficacy endpoints and safety/tolerability are also evaluated. ARTISTS is a 56-week, open-label, single-arm, long-term safety/tolerability study in patients who have successfully completed either ARTISTS 1 or ARTISTS 2.

Results:

Not available yet.

Conclusion:

TS can have potentially long-term life impact, and there remains unmet medical need for effective and well-tolerated treatments. Three ARTISTS studies will evaluate the efficacy, safety, and tolerability of deutetrabenazine in patients with tics in TS.

Funding Acknowledgements:

The studies are sponsored by Teva Pharmaceuticals and operationalized by Teva’s development partner, Nuvelution TS Pharma INC.
153 A Lost Family Secret Masquerading as Schizoaffective Disorder and Traumatic Brain Injury. The Atypical, Non-Choreiform Subtype of Huntington’s Disease
Authors: Matzkin Gideon , Katz Rebecca , Rahm Sage , Kanakrieh Yasin , Undavia Anishee , Gilman Megan
Published: April 2020

Title:

A Lost Family Secret Masquerading as Schizoaffective Disorder and Traumatic Brain Injury A Atypical, Non-Choreiform Subtype of Huntington’s Disease.

Study Objectives:

1

Describe a case of an atypical presentation of Huntington’s Disease who presented to our acute inpatient setting with the diagnoses of schizoaffective disorder and traumatic brain injury.

2

Recognize the importance of identifying medical/neurological disease that may be masked by psychiatric symptoms.

3

Identify areas for improvement for patient-doctor-caregiver communication.

Method:

Direct patient care, chart review, expert consultation and collateral biographical information obtained from multidisciplinary sources. Performed at Albert Einstein Medical Center, Philadelphia, Pennsylvania.

Results:

After re-evaluation of a patient discharged from our care with inconclusive MRI brain imaging, it was discovered with prior genetic testing that his unique presentation was in fact an atypical form of Huntington’s Disease with 46 CAG on the IT15 allele 1 on chromosome 4 which is greater than the >36 repeats required for a diagnosis of Huntington’s disease.

Conclusions:

A thorough history taking and willingness to question an admitting psychiatric diagnosis is an important skill for any clinician. We favored our patient’s diagnosis of schizoaffective disorder due to the circumstances of his arrival and his atypical presentation of Huntington’s disease without the characteristic choreiform movements. His bizarre mannerisms were attributed to his history of TBI and psychotic illness. Oddly enough, the initial medications on which the patient presented were consistent with those often prescribed for the psychotic and mood symptoms of HD, and it is possible that his prior providers may have been treating him but failed to fully educate the patient on the nature of his disease. Although many of the treatments are similar, we felt that the patient was owed an answer about the truth underlying his condition so that he could prepare for the natural course of his illness and be allowed to seek out anything that could delay or reverse his illness. Huntington’s disease is known by its stereotypical choreiform movements; however, the psychiatric co-manifestations may present in up to 10 percent of HD patients with the atypical form which has less-pronounced movement abnormalities and can be interpreted as a psychiatric illness, while overlooking the underlying neurological pathology. Currently, many of the tests are cost prohibitive and require persistence to obtain genetic testing and detailed radiological imaging, but as medical providers, we are ultimately responsible for helping our patients overcome these barriers to offer them the best and most comprehensive care.
154 Functioning in de Novo and Rollover Patients with Bipolar I Disorder Receiving Aripiprazole Once-monthly in a 52-Week, Open-label Study
Authors: Madera Jessica J , Such Pedro , Chen Maxine , Baker Ross A
Published: April 2020

Introduction:

Long-term maintenance treatment is essential in management of bipolar I disorder (BP-I) to achieve mood stability, prevent recurrence of mood episodes and improve functioning. Aripiprazole once-monthly 400 mg (AOM 400) is a long-acting formulation of aripiprazole for maintenance treatment of BP-I. In a double-blind, placebo-controlled, randomized withdrawal study in adult patients with BP-I after a manic episode (NCT01567527), AOM 400 delayed time to and reduced rate of recurrence of mood episodes and was safe and well tolerated (1). In an open-label, long-term safety study (NCT01710709), AOM 400 was safe and effective as long-term maintenance treatment (2).

Objective:

To evaluate the effect of long-term AOM 400 maintenance treatment on manic and depressive symptoms in BP-I patients from the open-label, long term safety study.

Methods:

Manic and depressive symptoms were assessed post-hoc by analysis of change from study entry in the Young-Mania Rating Scale (YMRS) and Montgomery-Åsberg Depression Rating Scale (MADRS) total scores and line item scores. The mean changes from baseline at last visit in YMRS and MADRS total scores, and single items were calculated using descriptive statistics, using last observation carried forward for total scores and observed cases for single items.

Results:

A total of 464 patients entered the maintenance phase: 379 were de novo and 85 were rollover patients who completed the double-blind, placebo-controlled withdrawal study. Overall, 63% (291/464) completed 52 weeks of open-label treatment. Mean YMRS and MADRS total scores were minimally changed from baseline (YMRS: 2.31, endpoint change -0.30; MADRS: 3.23, endpoint change +1.24) across the study in the total population.

Conclusion:

Patients entering an open-label safety study with stable manic and depressive symptoms maintained stability in both types of symptoms, as shown by minimal mean changes from baseline in YMRS and MADRS scores, suggesting that treatment with AOM 400 is effective in preventing re-emergence of both manic and depressive symptoms.

Funding Acknowledgements:

The study was supported by Otsuka Pharmaceutical Development & Commercialization, Inc.
174 Catatonia Complicated by Encephalopathy-Diagnostic and Treatment Challenges
Authors: Jadapalle Sree Latha Krishna
Published: April 2020

The term Catatonia was coined by Kraepelin in 1893 and was categorized as a subtype of dementia praecox. Bleuler in 1906 redefined it as catatonic Schizophrenia. Over the period of time by accumulating evidence of various case reports and studies its apparent that catatonia is not only seen in Schizophrenia, Affective disorders but is also seen secondary to various medical problems. There is very limited literature describing catatonia in the presence of neurological problems like Encephalopathy. The pathophysiology of Catatonia remains unclear. Given the involvement of common substrates like GABA, Dopamine and glutamate that are altered in many neurological problems and catatonia the differentiation and treatment become complicated.

METHOD:

We present the case of a 32-year-old male with bipolar II disorder, who was initially went through elective cholecystectomy complicated by bowel perforation and septic shock. Patient had to be intubated and had complicated ICU stay. Various consultation services including Neurology, Infectious disease, psychiatry, Intensivist got involved to address the multiple medical comorbidities like sepsis, encephalopathy and apathy. In spite of improving EEG showing resolving encephalopathy patient remained mute, immobile, not following any instructions, with no oral intake. All imaging including CT scan and MRI repeated 3 times over the period of time were negative. Patient’s psychiatric medications that includes Wellbutrin was held to minimize the risk of seizures. Patient’s neuro exam had positive Babinski and pupils dilated. He also had autonomic dysfunction. There were no clear-cut symptoms to enable us differentiating hypoxic brain injury and Malignant catatonia. We considered the differential diagnosis of Catatonia and initiated Ativan IV challenge.

RESULTS:

The patient was reassessed one hour after administration of lorazepam. He displayed slight response to Ativan by moving his fingers in the first 24 hrs. We had to continue to titrate the Ativan to very high doses in the period of 3 weeks with a very slow but good response.

CONCLUSION:

This case reflects the intricacy in diagnosing Catatonia complicated by Encephalopathy and the challenges in its treatment. We want to add on to the current literature on Catatonia masked by multiple medical comorbidities and the challenges of treatment
185 The Safety and Tolerability of Lumateperone 42 mg for the Treatment of Schizophrenia: A Pooled Analysis of 3 Randomized Placebo-Controlled Trials
Authors: Kane John M , Vanover Kimberly E , Durgam Suresh , Davis Robert , Satlin Andrew , Rowe William , Mates Sharon , Tamminga Carol
Published: April 2020

Introduction:

Lumateperone (ITI-007) is in late-phase clinical development for schizophrenia. Lumateperone has a unique mechanism of action that modulates serotonin, dopamine, and glutamate neurotransmission. This pooled analysis of lumateperone in 3 randomized, double-blind, placebo-controlled studies was conducted to evaluate the safety and tolerability of lumateperone 42mg (ITI-007 60mg).

Methods:

Data were pooled from the 3 controlled late-phase studies of lumateperone 42mg in patients with acute exacerbation of schizophrenia. Safety assessments of all patients who received at least one dose of any treatment included treatment-emergent adverse events (TEAEs), changes in laboratory parameters, extrapyramidal symptoms (EPS), and vital signs.

Results:

The safety population comprised 1,073 patients (placebo [n=412], lumateperone 42mg [n=406], risperidone [n=255]). TEAEs that occurred in the lumateperone 42mg group at a rate of ≥5% and twice placebo were somnolence/sedation (24.1% vs 10.0%) and dry mouth (5.9% vs 2.2%). Rates of discontinuation due to TEAEs with lumateperone 42mg (0.5%) were similar to placebo (0.5%) and lower than risperidone (4.7%). Mean change in weight and rates of EPS-related TEAEs were less for lumateperone 42mg and placebo patients than risperidone patients. Mean change from baseline in metabolic parameters were similar or smaller for lumateperone 42mg vs placebo. Mean changes were notably higher in risperidone patients vs lumateperone 42mg and placebo for glucose, cholesterol, triglycerides, and prolactin.

Conclusion:

In this pooled analysis, lumateperone 42mg showed good tolerability with potential benefits over risperidone for metabolic, prolactin, and EPS risks. The only TEAE that occurred in >10% of lumateperone patients was somnolence/sedation, which was impacted by morning administration; in subsequent studies that administered lumateperone in the evening, somnolence/sedation rates were markedly reduced. These results suggest that lumateperone 42mg may be a promising new treatment for schizophrenia.

Funding Acknowledgements:

Supported by funding from Intra-Cellular Therapies, Inc.
Contribution of executive functions to eating behaviours in obesity and eating disorders
Authors: Segura-Serralta Mara , Ciscar Sonia , Blasco Lorena , Oltra-Cucarella Javier , Roncero María , Espert Raúl , Elvira Vicente , Pinedo-Esteban Rosa , Perpiñá Conxa
Published: April 2020

Background:

Patients with eating disorders (ED) or obesity show difficulties in tasks assessing decision-making, set-shifting abilities and central coherence.

Aims:

The aim of this study was to explore executive functions in eating and weight-related problems, ranging from restricting types of ED to obesity.

Method:

Two hundred and eighty-eight female participants (75 with obesity; 149 with ED: 76 with restrictive eating, 73 with bingeing-purging symptoms; and 64 healthy controls) were administered the Wisconsin Card Sorting Test, the Iowa Gambling Task, and the Group Embedded Figures Test to assess set-shifting, decision-making and central coherence, respectively.

Results:

Participants with either obesity or ED performed poorly on tests measuring executive functioning compared with healthy controls, even after controlling for age and intelligence. Both participants with obesity and participants with ED showed a preference for global information processing.

Conclusions:

The findings suggest that treatments for obesity and ED would benefit from addressing difficulties in cognitive functioning, in addition to the more evident clinical symptoms related to eating, body weight and shape.
ECEP: historical corpora, historical phonology and historical pronouncing dictionaries
Authors: YÁÑEZ-BOUZA NURIA
Published: April 2020

This article presents theEighteenth-Century English Phonology Database(ECEP) in the context of historical phonology and historical corpora. The eighteenth century witnessed the proliferation of works on elocution and orthoepy and yet the field lacks searchable digital sources comparable to those available in other disciplines like historical syntax or historical pragmatics. Because of this and for other reasons such as the difficulty in deciphering idiosyncratic notation systems in the original materials, there has been a certain disregard for the study of eighteenth-century phonological evidence. The ECEP database aims to redress this absence of research material by collecting data from eighteenth-century pronouncing dictionaries in the form of IPA transcriptions (c.1,600 different example words totallingc.17,600 transcriptions) and supplementary metadata, with a view to facilitating systematic analyses of phonological, chronological and geographic patterns, and also normative attitudes. The richness of the contents in ECEP will thus be of interest to phonologists, dialectologists and language variationists from the historical as well as the synchronic perspective, in that eighteenth-century orthoepists laid the ground for what became ‘Received Pronunciation’. Methodologically, the compilation of the ECEP database aims to contribute to the thriving field of corpus linguistics with a new research tool for the study of the history of English.
The Ineffable Conservative Revolution: The Crisis of Language as a Motive for Weimar's Radical Right
Authors: Bures Eliah
Published: April 2020

This article provides a new look at Weimar Germany's Conservative Revolution by exploring its suspicion of conceptual and discursive language. It argues that Conservative Revolutionaries not only disdained intellectualism and public discourse; they also extolled their presumed opposites—instinct, intuition, self-evidence—as crucial ingredients in an “ineffable nationalism” which held that a true nation is based on unexpressed or difficult-to-articulate feelings and values. The origins of this ideology are found in a modernist crisis of representation and in sociological accounts of traditional “organic” communities. These themes were politicized by World War I, whose seeming incommunicability magnified the problem of representation and made the unspoken harmony of wartime comradeship an attractive model for a revitalized national community. The article's final section examines the early writings of Ernst Jünger in order to show in detail how these issues came together to create the Conservative Revolutionary mind.
Conceptualising equity in the impact evaluation of chronic disease management programmes: a capabilities approach
Authors: Tapager Ina , Hansen Kristian Schultz , Vrangbæk Karsten
Published: April 2020

Chronic diseases are highly important for the future level and distribution of health and well-being in western societies. Consequently, it seems pertinent to assess not only efficiency of chronic care but also its impact on health equity. However, operationalisation of health equity has proven a challenging task. Challenges include identifying a relevant and measurable evaluative space. Various schools of thought in health economics have identified different outcomes of interest for equity assessment, with capabilities as a proposed alternative to more conventional economic conceptualisations. The aim of this paper is to contribute to the conceptualisation of health equity evaluation in the context of chronic disease management. We do this by firstly introducing an equity enquiry framework incorporating the capabilities approach. Secondly, we demonstrate the application and relevance of this framework through a content analysis of equity-related principles and aims in national chronic disease management guidelines and the national diabetes action plan in Denmark. Finally, we discuss how conceptualisations of equity focused on capabilities may be used in evaluation by scoping relevant operationalisations. A promising way forward in the context of chronic care evaluation may emerge from a combination of concepts of capabilities developed in economics, health sciences and psychology.
Improvisation and Value in Rock, 1966
Authors: BRACKETT DAVID
Published: April 2020

The mid-1960s has figured as a central period in the historiography of popular music, but the role of improvisation has been little discussed. This article argues that issues of improvisation and value are crucial to understanding the emergence of a high-low split within popular music, a division that figures prominently in criticism and fan discourse up to the present day. This new stratification within popular music made it possible for rock to acquire critical prestige relative to other popular music genres. The formation of rock also relied on its association with a primarily white, male, middle-class demographic. This article demonstrates that rock's prestige rests simultaneously on maintaining this narrow demographic profile while locating aesthetic and spiritual value in musical practices coming from elsewhere (in terms of geography, race, or cultural hierarchy): blues, Indian classical music, jazz. The socio-musical transformation in which improvisation played such an important role is explored through a survey of recordings and an analysis of the development of rock criticism in 1966, the year in which a new constellation of aesthetics, politics, and musical style crystallized.
The tissue-specific aspect of genome-wide DNA methylation in newborn and placental tissues: implications for epigenetic epidemiologic studies
Authors: Herzog Emilie M. , Eggink Alex J. , Willemsen Sten P. , Slieker Roderick C. , Felix Janine F. , Stubbs Andrew P. , van der Spek Peter J. , van Meurs Joyce B. J. , Heijmans Bastiaan T. , Steegers-Theunissen Régine P. M.
Published: April 2020

Epigenetic programming is essential for lineage differentiation, embryogenesis and placentation in early pregnancy. In epigenetic association studies, DNA methylation is often examined in DNA derived from white blood cells, although its validity to other tissues of interest remains questionable. Therefore, we investigated the tissue specificity of epigenome-wide DNA methylation in newborn and placental tissues. Umbilical cord white blood cells (UC-WBC, n = 25), umbilical cord blood mononuclear cells (UC-MNC, n = 10), human umbilical vein endothelial cells (HUVEC, n = 25) and placental tissue (n = 25) were obtained from 36 uncomplicated pregnancies. Genome-wide DNA methylation was measured by the Illumina HumanMethylation450K BeadChip. Using UC-WBC as a reference tissue, we identified 3595 HUVEC tissue-specific differentially methylated regions (tDMRs) and 11,938 placental tDMRs. Functional enrichment analysis showed that HUVEC and placental tDMRs were involved in embryogenesis, vascular development and regulation of gene expression. No tDMRs were identified in UC-MNC. In conclusion, the extensive amount of genome-wide HUVEC and placental tDMRs underlines the relevance of tissue-specific approaches in future epigenetic association studies, or the use of validated representative tissues for a certain disease of interest, if available. To this purpose, we herewith provide a relevant dataset of paired, tissue-specific, genome-wide methylation measurements in newborn tissues.
Weed control and soybean injury from preplant vs. preemergence herbicide applications
Authors: Priess Grant L. , Norsworthy Jason K. , Roberts Trenton L. , Gbur Edward E.
Published: April 2020

Palmer amaranth is one of the most troublesome weeds of soybean in the United States. To effectively control this weed it is necessary to optimize timing of PRE residual herbicides to mitigate Palmer amaranth emergence. Field studies were conducted in 5 site-years to assess the effect of application timing 12 to 16 d prior to planting (preplant) and at planting (PRE) on soybean injury and longevity of Palmer amaranth control using five residual herbicide treatments. A reduction in longevity of Palmer amaranth control was observed whenS-metolachlor + metribuzin and flumioxazin + chlorimuron-ethyl were applied preplant vs. PRE in 2 of the 5 site years. Sulfentrazone, sulfentrazone + cloransulam-methyl, and saflufenacil + dimethenamid-P + pyroxasulfone + metribuzin did not reduce longevity of Palmer amaranth control when applied preplant vs. PRE in all 5 site-years. Visible estimates of soybean injury were lower at 21 d after planting when herbicides were applied 12 to 16 d preplant vs. PRE. These findings suggest that preplant applications can be used to reduce the potential for crop injury and may not result in reduced longevity of control when herbicides with a prolonged residual activity are used. Preplant herbicides increase the likelihood of the residuals being activated prior to subsequent weed emergence as opposed to PRE herbicides applied at soybean planting.
Tracer Exchange Across the Stratified Inner‐Shelf Driven by Transient Rip‐Currents and Diurnal Surface Heat Fluxes
Authors: Grimes D. J. , Feddersen F. , Kumar N.
Published: April 2020

Exchange across the surf‐zone and inner‐shelf affects coastal water quality and larval recruitment. Surf‐zone generated transient rip‐currents (TRC) exchange shoreline released tracers onto and across a stratified inner‐shelf. Surface heat fluxes (SHF) modify inner‐shelf stratification and surf‐zone temperature, relative to the inner‐shelf, inducing nearshore thermally driven exchange. The coupled effect of TRC and diurnal SHF forcing on cross‐shore exchange is evaluated using idealized model surf‐zone tracer releases with TRC‐only, SHF‐only, and combined SHF+TRC forcing. For conditions representing Fall in Southern California, the TRC mechanism dominates cross‐shore exchange, relative to SHF, to 12LSZ offshore (LSZ  = 100 m is the surf‐zone width). Tracer and velocity derived estimates of exchange velocity indicate that the TRC cross–inner‐shelf exchange mechanism is due to an alongshore mean baroclinic flow setup by TRC vertical mixing of inner‐shelf stratification.
Evaluation of an Improved Convective Triggering Function: Observational Evidence and SCM Tests
Authors: Wang Yi‐Chi , Xie Shaocheng , Tang Shuaiqi , Lin Wuyin
Published: April 2020

This study provides a strong observational support for a recently developed convective triggering function that uses the large‐scale dynamic convective available potential energy (dCAPE) as a constraint combined with an unrestricted air parcel launch level (ULL) to relax the unrealistic strong coupling of convection to surface heating and capture nocturnal elevated convection. Both case study and statistical analysis are conducted using the observations collected from the Department of Energy's Atmospheric Radiation Measurement program at its Southern Great Plains and Manaus (MAO) sites. They show that dCAPE has a much stronger correlation with precipitation than convective available potential energy, and ULL is essential to detect elevated convection above boundary layer under both midlatitude and tropical conditions and for both afternoon and nighttime deep convection regimes. Sensitivity tests with the single‐column model (SCM) of the Department of Energy's Energy Exascale Earth System Model indicate that the role of dCAPE in suppressing daytime convection is more effective for tropical convection than midlatitude convection. Even though the dCAPE can suppress the overestimated convection, ULL plays a much bigger role in improving the diurnal cycle of precipitation than dCAPE. It not only helps capture nocturnal elevated convection but also significantly removes the spurious morning precipitation seen in the default model, due to the release of unstable energy at night. However, the use of ULL has led to an overestimation of light‐to‐moderate precipitation (1–10 mm/day) due to more convection being triggered above boundary layer.
In Situ Synchrotron X‐Ray Microtomography Observations of Fracture Network Evolution of Coal Due to Waterflooding
Authors: Zhang Guanglei , Ranjith P. G. , Li Dongyin , Wanniarachchi W. A. M. , Zhang Beining
Published: April 2020

Water adsorption on coal plays a significant role in the process of CO2 sequestration and enhanced coalbed methane recovery. Direct evidence of how coal adsorbs water and swells, affecting permeability, is still limited. Here, we studied the impact of waterflooding on fracture networks in coal by means of in situ synchrotron X‐ray microtomography combined with permeability measurements. We demonstrated that swelling‐induced fracture closure was responsible for an order of magnitude permeability reduction after waterflooding for over 4 days. Permeability loss was found to be time dependent, following a logistic function, and about 80% permeability reduction happened in the first 24 hr. There were probably three driven forces for water uptake, including hydrodynamic forces in fractures and macropores, capillary forces in micropores, and diffusion from micropores into deeper coal matrix. Swelling of coal matrix narrowed down and even closed the fractures and as a result weakened fracture connectivity. Residual fractures were mainly mineral‐supported fractures, which have strong resistance to swelling‐induced stresses.
Equatorial Deep Jets and Their Influence on the Mean Equatorial Circulation in an Idealized Ocean Model Forced by Intraseasonal Momentum Flux Convergence
Authors: Bastin Swantje , Claus Martin , Brandt Peter , Greatbatch Richard J.
Published: April 2020

Equatorial deep jets (EDJ) are vertically stacked, downward propagating zonal currents that alternate in direction with depth. In the tropical Atlantic, they have been shown to influence both surface conditions and tracer variability. Despite their importance, the EDJ are absent in most ocean models. Here we show that EDJ can be generated in an idealized ocean model when the model is driven only by the convergence of the meridional flux of intraseasonal zonal momentum diagnosed from a companion model run driven by steady wind forcing, corroborating the recent theory that intraseasonal momentum flux convergence maintains the EDJ. Additionally, the EDJ in our model nonlinearly generate mean zonal currents at intermediate depths that show similarities in structure to the observed circulation in the deep equatorial Atlantic, indicating their importance for simulating the tropical ocean mean state.
On the Effectiveness of LID Infrastructures for the Attenuation of Urban Flooding at the Catchment Scale
Authors: Fiori A. , Volpi E.
Published: April 2020

The efficacy of low‐impact development (LID) toward the attenuation of urban flood at the catchment scale is still an unsolved question. This work aims at providing insight into the effectiveness of LID at the catchment scale by a simple hydrological modeling approach that allows for an analytical solution. The paper focuses on LID design, investigating the peak discharge at the catchment outlet as a function of the return period of the rainfall event under unaltered and retrofitted conditions. The model captures the most important effects of LID on flood, that is, the temporal shift and attenuation of water discharge and the decrease of water volume conveyed by the drainage network due to increased hydrological losses. It is found that LID is likely more effective in reducing peak discharge at the local scale, while the effectiveness decreases with increasing catchment size. For some configurations, for example, when retrofit is performed in downstream areas, closer to the outlet, LID may even worsen the flood risk. The effectiveness of LID depends on the combination of several factors, including the fractional area covered by the LID infrastructures, their distribution within the catchment, and their hydraulic properties, as compared with the general hydraulic features of the catchment (network dispersion, detention, lag time, etc.). As a consequence, the LID design should be carried out considering all the relevant scales of the problem, from the local one, at which the LID infrastructure is implemented, to the catchment scale, and the discharge at the outlet in particular, in a comprehensive perspective.
Splicing factor proline- and glutamine-rich (SFPQ) protein regulates platinum response in ovarian cancer-modulating SRSF2 activity
Authors: Pellarin Ilenia , Dall’Acqua Alessandra , Gambelli Alice , Pellizzari Ilenia , D’Andrea Sara , Sonego Maura , Lorenzon Ilaria , Schiappacassi Monica , Belletti Barbara , Baldassarre Gustavo
Published: April 2020

In epithelial ovarian cancer (EOC), response to platinum (PT)-based chemotherapy dictates subsequent treatments and predicts patients’ prognosis. Alternative splicing is often deregulated in human cancers and can be altered by chemotherapy. Whether and how changes in alternative splicing regulation could impact on the response of EOC to PT-based chemotherapy is still not clarified. We identified the splicing factor proline and glutamine rich (SFPQ) as a critical mediator of response to PT in an unbiased functional genomic screening in EOC cells and, using a large cohort of primary and recurrent EOC samples, we observed that it is frequently overexpressed in recurrent PT-treated samples and that its overexpression correlates with PT resistance. At mechanistic level, we show that, under PT treatment, SFPQ, in complex with p54nrb, binds and regulates the activity of the splicing factor SRSF2. SFPQ/p54nrb complex decreases SRSF2 binding to caspase-9 RNA, favoring the expression of its alternative spliced antiapoptotic form. As a consequence, SFPQ/p54nrb protects cells from PT-induced death, eventually contributing to chemoresistance. Overall, our work unveils a previously unreported SFPQ/p54nrb/SRSF2 pathway that in EOC cells plays a central role in regulating alternative splicing and PT-induced apoptosis and that could result in the design of new possible ways of intervention to overcome PT resistance.
Genetic trajectory and immune microenvironment of lung-specific oligometastatic colorectal cancer
Authors: Ottaiano Alessandro , Circelli Luisa , Lombardi Angela , Scala Stefania , Martucci Nicola , Galon Jerome , Buonanno Manuela , Scognamiglio Giosuè , Botti Gerardo , Hermitte Fabienne , Savarese Giovanni , D’Amore Luigi , Tatangelo Fabiana , Di Mauro Annabella , Liguori Giuseppina , Trotta Anna Maria , Napolitano Maria , Capozzi Monica , Tafuto Salvatore , Perri Francesco , La Rocca Antonello , Caraglia Michele , Nasti Guglielmo
Published: April 2020

Genetics and immunologic dynamics pushing the evolution of colorectal cancer (CRC) from the primary tumor to the metastases are largely unknown; cancer heterogeneity makes challenging both therapy and mechanistic studies. We selected patients developing CRC with lung-limited metastatic disease as only illness during their life in order to find any relevant genotype–phenotype relationship. Analysis of 523 cancer-relevant genes and of immune cells infiltration in primary and metastatic tissues revealed atypical genomic trajectories (TMB decrease, KRAS and SMAD4 regressive mutations), specific genetic events (ERBB2 point mutations) and scarce T-cell infiltration. These insights provide novel information in oligometastatic CRC biology and new perspectives for cancer monitoring and anti-cancer therapeutic strategies.
Power laws in pressure-induced structural change of glasses
Authors: Zhang Huijun , Qiao Kaiyao , Han Yilong
Published: April 2020

Many glasses exhibit fractional power law (FPL) between the mean atomic volume va and the first diffraction peak position q1, i.e. $$v_{\mathrm{a}} \propto q_1^{ - d}$$

v

a

∝

q

1

−
d

with d ≃ 2.5 deviating from the space dimension D = 3, under compression or composition change. What structural change causes such FPL and whether the FPL and d are universal remain controversial. Here our simulations show that the FPL holds in both two- and three-dimensional glasses under compression when the particle interaction has two length scales which can induce nonuniform local deformations. The exponent d is not universal, but varies linearly with the deformable part of soft particles. In particular, we reveal an unexpected crossover regime with d > D from crystal behavior (d = D) to glass behavior (d < D). The results are explained by two types of bond deformation. We further discover FPLs in real space from the radial distribution functions, which correspond to the FPLs in reciprocal space.
Marine resource abundance drove pre-agricultural population increase in Stone Age Scandinavia
Authors: Lewis J. P. , Ryves D. B. , Rasmussen P. , Olsen J. , van der Sluis L. G. , Reimer P. J. , Knudsen K.-.L. , McGowan S. , Anderson N. J. , Juggins S.
Published: April 2020

How climate and ecology affect key cultural transformations remains debated in the context of long-term socio-cultural development because of spatially and temporally disjunct climate and archaeological records. The introduction of agriculture triggered a major population increase across Europe. However, in Southern Scandinavia it was preceded by ~500 years of sustained population growth. Here we show that this growth was driven by long-term enhanced marine production conditioned by the Holocene Thermal Maximum, a time of elevated temperature, sea level and salinity across coastal waters. We identify two periods of increased marine production across trophic levels (P1 7600–7100 and P2 6400–5900 cal. yr BP) that coincide with markedly increased mollusc collection and accumulation of shell middens, indicating greater marine resource availability. Between ~7600–5900 BP, intense exploitation of a warmer, more productive marine environment by Mesolithic hunter-gatherers drove cultural development, including maritime technological innovation, and from ca. 6400–5900 BP, underpinned a ~four-fold human population growth.