bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiology of Face-to-Face Competition
Authors: Mazur Allan
Published: March 2018

Face-to-face competition for rank in human status hierarchies is similar to “dominance competition” in other primate species, particularly the African apes. Each individual has signs or signals showing that it has or ought to have high or low status. Group members may accept these signs at face value, or one individual may challenge another for high rank. Among apes and humans, such dominance contests are usually nonviolent, often taking the form of an exchange of stressful signals. Eventually, one contestant withdraws or concedes the higher rank, thus lowering the stress level. Serious competition with important stakes is influenced by a physiological substrate of the hormones testosterone and cortisol and the enzyme α-amylase. Among humans, language is an important channel for exchanging dominant and deferent signals. Apart from the physiological substrate, instantaneous stress responses underlie status allocation. These mechanisms are illustrated with recent experimental results.
How Evolutionary Psychology Can Contribute to Group Process Research
Authors: Whitmeyer Joseph M.
Published: March 2018

Conceptions of the human individual lie at the heart of all group process theories. Applying evolutionary reasoning—reasoning concerning what predispositions are likely to have evolved—to those conceptions can make the conceptions more accurate and thus improve theories based on them. This chapter discusses exchange processes, identity processes, and status processes. For exchange processes, evolutionary reasoning suggests numerous predispositions that would affect exchange, many to cope with the problem of cheating by others and ourselves. In fact, evolutionary reasoning suggests that concerns with our own identity may exist principally to improve our exchange outcomes. Concerning status processes, evolutionary reasoning suggests that awarding prestige must have evolved in the context of exchange, such that the person receiving prestige also incurs performance obligations. These points and others lead to several suggestions of areas for future research and specific predictions.
GABAA Receptor Physiology and Pharmacology
Authors: Wallner Martin , Lindemeyer A. Kerstin , Olsen Richard W.
Published: March 2018

GABAA receptors (GABAARs) are the main inhibitory neurotransmitter receptors and mediate rapid synaptic as well as slow extrasynaptic inhibitory neurotransmission. Structurally, GABAARs are ligand-gated ion channels formed by a total of 19 homologous subunits, each with four transmembrane domains assembled as pentamers, forming a GABA-gated Cl– channels. The major classical synaptic GABAAR subtypes are formed by 2α2β and a γ subunit, with six different possible α subunits, three different β subunits, and three γ subunits, with the most abundant subtype, α1β2γ2 receptors. More recently, highly GABA-sensitive extrasynaptic δ subunit-containing receptors that are persistently (tonically) activated by low ambient levels of GABA have entered the limelight. GABAARs are targets for sedative/hypnotic and anxiolytic drugs (e.g., benzodiazepines [BZs] and other BZ site ligands), as well as general anesthetics (e.g., etomidate, propofol, barbiturate, and neurosteroid anesthetics, and possibly volatile agents and long-chain alcohols), and also are important targets for alcohol actions.
Public Heritage in the Symbiocene
Authors: Albrecht Glenn A.
Published: March 2018

The chapter argues that all forms of heritage are at risk from population and development pressures within the Anthropocene. We lose our sense of place in the age of solastalgia, as natural and built heritage, the integral parts of loved home environments, are lost. No amount of citizen collaboration or soliphilia can save heritage from desolation when government and corporate power values profit over all other forms of value. The concept of the Symbiocene is proposed as an antidote to the Anthropocene. However, in the Symbiocene, heritage will remain an ironic and elusive experience. This is because the full reunification of human praxis with life support systems will produce almost no distinctive signature on Earth that could be highlighted as exclusively “human” heritage. Heritage as something that defies the natural “beauty of decay” will be a deliberate, educative act of creation.
Role of Eukaryotic Initiation Factor eIF2B in Vanishing White Matter Disease
Authors: Abbink Truus E. M. , Wisse Lisanne E. , Wang Xuemin , Proud Christopher G.
Published: March 2018

Vanishing white matter (VWM) disease is a recessive disorder characterized by gradual loss of white matter and of myelin. Its clinical severity is high variable. VWM is caused by mutations in any one of the five genes encoding subunits of eukaryotic initiation factor 2B (eIF2B), a ubiquitous, multimeric protein that plays crucial roles in protein synthesis and its control. There are now known to be at least 160 mutations in eIF2B genes that lead to VWM. Where tested, most mutations impair the activity or integrity of the eIF2B complex. However, it remains unclear how and why defects in eIF2B lead to VWM. This article discusses recent advances in understanding the structure and functions of eIF2B and the pathogenic basis of VWM.
Evidentiality in Nakh-Daghestanian Languages
Authors: Forker Diana
Published: March 2018

This chapter is focused on the formal expression of evidentiality in Nakh-Daghestanian languages (Russia, Caucasus) and on the semantic distinctions available for evidentials. The vast majority of Nakh-Daghestanian languages express evidentiality in one way or another through grammatical means, but there are also many evidential strategies attested. Verbal evidentiality mainly shows up as one meaning of the perfect series and in inferential constructions with light verbs such as ‘find’, ‘stay’, or ‘be, become’. In addition, some languages have evidential enclitics and suffixes. The evidential meanings expressed are mostly indirect evidentiality, including hearsay and inference. The chapter also presents a short overview of related constructions such as conjunct-/disjunct-marking and epistemic modality.
Evidentiality in Bodic Languages
Authors: Hyslop Gwendoyn
Published: March 2018

The Bodic group of Tibeto-Burman languages infamously code a wide range of epistemological categories, including evidentiality (source of knowledge) and perhaps more contentiously mirativity (expectations of knowledge), and egophoricity (access to knowledge). This chapter investigates these interrelated related epistemological categories in a range of Bodic languages, including but not limited to Darma (Himalayish; Uttarkhand, India), Manange (Tamangic; Nepal), Magar and Kham (Magaric; Nepal), Newaric (Nepal), various Tibetic languages, and Kurtöp (East Bodish; Bhutan). Mirativity appears to be widely found throughout the region, followed by egophoricity and evidentiality. In terms of evidentiality itself, Bodic languages commonly encode oral source of knowledge and less commonly encode indirect source of knowledge. Despite the close cognitive relationship between evidentiality, mirativity, and egophoricity, Bodic languages demonstrate that these categories are distinct.
Evidentiality and Language Contact
Authors: Aikhenvald Alexandra Y.
Published: March 2018

Evidentials, as a grammatical means of overtly expressing information source, play a pivotal role in communication, cognition, and speakers’ status within a community. This accounts for their frequent spread in language contact situations. Evidentials often develop as a consequence of areal diffusion. A language surrounded by languages without evidential distinctions is likely to lose evidentials. Evidentials are among the defining features of a number of well-established linguistic areas, among them the Balkans, the Caucasus, and the Baltic region in Eurasia, and the Vaupés River Basin linguistic area in Amazonia. They have made their way into a number of contact varieties of major European languages, including Spanish and Portuguese. An obsolescent language may lose or restructure its evidentiality system depending on the dominant language speakers are shifting to. Further factors propitious for a spread of evidentials in language contact include multilingualism and shared discourse genres and speech practices.
Edmund Husserl
Authors: de Monticelli Roberta
Published: March 2018

Edmund Husserl’s relevance for phenomenological psychopathology and psychiatry hinges in part on the foundational and methodological aspects of his philosophy, as rooted both in Gestalt psychology and experimental phenomenology of perception and thought. A second distinctive reason for his persisting and increasing significance lies in his Socratic quest for the foundations of meaning, order, value, and coherence within ordinary experience, which still provide clinicians with concepts to focus abnormal patterns on all these parameters. Besides this twofold renewed framework of clinical theory, Husserl’s analyses of consciousness and personhood deliver a series of categories and distinctions still in use in best diagnostic and clinical practices.
The Role of Psychology According to Edith Stein
Authors: Bello Angela Ales
Published: March 2018

To understand the role of psychology as science according Edith Stein, we have to clarify the main features of her philosophical anthropology. Through the phenomenological analysis of the lived experiences she discovers the complex structure of the human being: the bodily, the psychic, and the spiritual life. The psychic level is ruled by causality, but it is different from the causality that we find in the nature, because it is not deterministic. In the psyche there is also an implicit motivation, but the explicit one is present in the spiritual life. For this reason, according to her, psychology, even if it is the science of the psyche, cannot avoid dealing with the spiritual aspect of the human being. Stein’s position is very important in order to grasp the limits of a psychology that follows the model of natural sciences.
Genetic Phenomenology
Authors: Steinbock Anthony
Published: March 2018

This article presents the dimension of genetic phenomenology within the thought of Edmund Husserl. It introduces the relation of phenomenological matters and methods, and outlines the possible spheres of phenomenology: static, genetic, and generative. It then explores the co-emergence of static and genetic phenomenological methods and describes the matters that are peculiar to each. By focusing specifically on genetic phenomenological method, the article describes key genetic phenomena, such as normality and abnormality as they concern the constitution of lived sense, embodied existence, and subjectivity. After explaining in what way the normal and the pathological express the concordance or harmony and disharmony in the development of meaning, it describes the original notion of the optimal as a new notion of normality in phenomenology, as well as the ways in which some norms can be transcended from within optimal experience. The article concludes by elaborating the relation between stasis and genesis.
Phenomenological Psychopathology, Neuroscience, Psychiatric Disorders, and the Intentional Arc
Authors: Gillett Grant , Seniuk Patrick
Published: March 2018

This article combines an evolutionary perspective with phenomenological philosophy of Merleau-Ponty. Neuroscience addresses the way the brain connects individuals to domains of adaptation, while Merleau-Ponty’s philosophy of perception explores the way sense situates humans the world. In particular, his concept “the intentional arc” captures the basic structure of embodied mental life through purposeful action. The processes of “sedimentation” and the neuroscience of ontogeny offer a perspective on the development of cortical and subcortical neural circuits that are in to-and-fro communication with the lived body. This dynamic sheds light on the genesis of a psychological life, structures of attunement, and capacity for adaptation to the world, which are all vulnerable to disruption in psychiatric disorder.
The Archaeologist’s Evangeline
Authors: Fowler Jonathan
Published: March 2018

The French colony of Acadia, located in what is now the Maritime Provinces of Canada and part of the State of Maine, has long attracted the attention of writers and scholars. Immigrating to the region in the early seventeenth century, the Acadian colonists established a viable agricultural economy without alienating the region’s indigenous peoples. Despite these achievements, imperial politics brought war to the region in the mid-eighteenth century, and saw most of the French inhabitants removed by force. Historical archaeology is helping to recover details of this early Canadian immigrant experience, but the task is complicated by a scholarly tradition dominated by romanticism and myth. This chapter surveys the development of historical archaeology in reference to the Acadians in Nova Scotia, noting how archaeology has helped reframe understandings of this colonial experience, and suggesting ways to carry the project further.
Hydroxychloroquine: balancing the need to maintain therapeutic levels with ocular safety: an update
Authors: Abdulaziz Nada , Shah Anjali R. , McCune William J.
Published: March 2018

Purpose of review

Antimalarial drugs including chloroquine, its less toxic quinolone-derivative hydroxychloroquine (HCQ), and quinacrine have become cornerstones in the treatment of autoimmune diseases including systemic lupus, rheumatoid arthritis, sarcoidosis, and Sjogren syndrome; cutaneous disorders, antiphospholipid syndrome, and have recently been employed at higher dioses in oncology. Benefits include anti-inflammatory effects, protection against thrombosis, and improved control of hyperglycemia and hyperlipidemia. In general, both the therapeutic advantages and the toxic effects of the drugs correlate with the dose and the duration of therapy. Here we summarize the current literature regarding the administration and the safety profile of HCQ in management of rheumatologic disease and focus on the most recent revised American Academy of Ophthalmology (AAO) guidelines for prevention and detection of hydroxychloroquine retinopathy to help guide therapeutic decision-making for patients.

Recent findings

The risk of antimalarial-induced retinal toxicity is better predicted by calculating the daily dosage based on 5 mg/kg total body weight rather than 6.5 mg/kg lean body weight and reducing dosage in patients with risk factors such as renal failure. The risk of retinal toxicity after 5 years is substantially increased even when these guidelines are followed; hence dose reduction is appropriate with long-term use. Newer techniques provide improved detection of early signs of retinal damage. These advances are reflected in the revised AAO guidelines 2016, which are in part based on the retrospective study by Melles and Marmor of HCQ toxicity.

The most important changes in practice guidelines include dose calculation based on total body weight, dose reduction after long-term use, and intensified screening with techniques including optical coherence tomography (OCT) after 5 years.
Residual Equinus After the Ponseti Method: An MRI-based 3-Dimensional Analysis
Authors: Mitchell Joseph , Bishop Aaron , Feng Yixuan , Farley Daniel , Hetzel Scott , Ploeg Heidi-Lynn , Nguyen Jie , Noonan Kenneth J.
Published: March 2018

Background:

Residual equinus deformity is present in up to 20% of clubfeet treated by the Ponseti method. These patients may require surgical release to restore dorsiflexion. Despite complete posterior release; persistent intraoperative equinus may be present and suggest concurrent joint incongruity. The purpose of this study was to characterize differences in ankle morphology in toddlers with residual equinus following the Ponseti method.

Methods:

Preoperative magnetic resonance imaging (MRI) data from 10 patients who underwent reconstruction (17 feet; 7 bilateral, 3 unilateral clubfeet) for persistent equinus were compared with 16 age-matched controls. Through reverse engineering software, MRI data were used to generate 3-dimensional (3D) models. Four talus-based measures were performed on both MRI data and 3D models—neck depth, neck angle, width, and length. Models were also used to calculate talus volume and arc of curvature (plafond and talar dome). Standard statistical analyses were performed.

Results:

Talus volumes, width, and length were less in clubfeet then in control feet. Although some measures were significant there was no mismatch with the ankle mortise dimensions or arc curvature that could account for any decrease in dorsiflexion. We found that from MRI measures the clubfoot neck depth was 2.3 versus 3.6 mm in controls (P<0.001) and from 3D modeling the clubfoot neck depth was 2.3 and 3.5 mm in controls (P=0.003). With 3D modeling talus clubfoot neck angle was 153.7 versus 140.4 degrees in controls (P=0.01). The clubfoot neck angle obtained from MRI measures were also different yet not significant [126.6 in clubfeet versus 122.5 degrees in controls (P=0.12)].

Conclusions:

In comparison to age-matched feet; we have noted a decrease in talar neck depth and an obtuse talar neck angle in clubfeet treated in the manner of Ponseti. This may result in anterior ankle impingement and be the cause of residual equinus despite posterior release. In these procedures, the surgeon should recognize this possibility when the amount of dorsiflexion is less than expected.

Level of Evidence:

Level III—case control study.
Probiotics in digestive, emotional, and pain-related disorders
Authors: Roman Pablo , Abalo Raquel , Marco Eva M. , Cardona Diana
Published: March 2018

In recent years, interest in the relationship between gut microbiota and disease states has grown considerably. Indeed, several strategies have been employed to modify the microbiome through the administration of different diets, by the administration of antibiotics or probiotics, or even by transplantation of feces. In the present manuscript, we focus specifically on the potential application of probiotics, which seem to be a safe strategy, in the management of digestive, pain, and emotional disorders. We present evidence from animal models and human studies, notwithstanding that translation to clinic still deserves further investigation. The microbiome influences gut functions as well as neurological activity by a variety of mechanisms, which are also discussed. The design and performance of larger trials is urgently needed to verify whether these new strategies might be useful not only for the treatment of disorders affecting the gastrointestinal tract but also in the management of emotional and pain disorders not directly related to the gut.
Outcomes of Descemet Membrane Endothelial Keratoplasty in Eyes With a Previous Descemet Stripping Automated Endothelial Keratoplasty Graft
Authors: Sorkin Nir , Showail Mahmood , Einan-Lifshitz Adi , Boutin Tanguy , Borovik Armand , Kreimei Mohammad , Rosenblatt Amir , Chan Clara C. , Rootman David S.
Published: March 2018

Purpose:

To analyze the outcomes of Descemet membrane endothelial keratoplasty (DMEK) in eyes with previous Descemet stripping automated endothelial keratoplasty (DSAEK).

Methods:

This retrospective interventional case series included 26 eyes (26 patients) that underwent DMEK to replace a previous DSAEK graft with at least 6 months of follow-up. The outcome measures were indications for surgery, best spectacle-corrected visual acuity (BSCVA), endothelial cell density, rebubbling rate, rejection, and failure.

Results:

Patient age was 71.9 ± 12.6 years. The average follow-up time after DMEK was 15.1 ± 10.6 months. Indications for DMEK were DSAEK graft failure (69%) and a DSAEK suboptimal visual outcome (31%). BSCVA of the entire cohort (n = 26) improved from 1.33 ± 0.78 logMAR preoperatively to 1.04 ± 0.78 and 1.06 ± 0.89 logMAR at 6 months postoperatively and at the last follow-up, respectively (P = 0.019 and P = 0.033). BSCVA among eyes without visual comorbidities (n = 13) improved from 0.84 ± 0.50 logMAR preoperatively to 0.55 ± 0.47 and 0.51 ± 0.49 logMAR at 6 months postoperatively and at final follow-up, respectively (P = 0.023 for both). Of these eyes, 84.6% had improvement in BSCVA at 6 months postoperatively and at last follow-up. In the subgroup of 8 eyes with DMEK for suboptimal visual outcomes after DSAEK, BSCVA improved from 0.81 ± 0.44 to 0.52 ± 0.35 logMAR at final follow-up (P = 0.024). When excluding eyes with visual comorbidities, BSCVA of this subgroup (n = 5) improved from 0.54 ± 0.32 to 0.36 ± 0.25 logMAR at final follow-up (P = 0.038). BSCVA of this subgroup at 6 months postoperatively was not significantly different from preoperative BSCVA, when including visual comorbidities (n = 8, 0.75 ± 0.60 logMAR, P = 0.79) and when excluding visual comorbidities (n = 5, 0.40 ± 0.28 logMAR, P = 0.621). Endothelial cell density decreased from 2753 ± 307 cells/mm2 to 1659 ± 655 cells/mm2 6 months after surgery (39.7% loss, P = 0.005). Three eyes (11.5%) required rebubbling, and 5 eyes (19.2%) had secondary graft failure at 2 to 20 months.

Conclusions:

DMEK is effective for replacing previous DSAEK not only for graft failure but also for suboptimal visual outcomes.
Orbital Radiotherapy Combined With Corticosteroid Treatment for Thyroid Eye Disease-Compressive Optic Neuropathy
Authors: Gold Katherine G. , Scofield Stacy , Isaacson Steven R. , Stewart Michael W. , Kazim Michael
Published: March 2018

Purpose:

To evaluate the effectiveness of orbital radiotherapy (ORT) in the treatment of thyroid eye disease (TED)–compressive optic neuropathy.

Methods:

A retrospective review of patients with corticosteroid-responsive compressive optic neuropathy due to TED treated with ORT. Study was conducted in compliance with Health Insurance Portability and Accountability Act. One hundred four patients (163 orbits) with a mean age of 61.7 years met inclusion criteria. Seventy-four percent (77/104) were female, and 32.7% (34/104) were current or previous smokers. A total absorbed dose of 2000 cGy fractionated in 10 treatment doses over the course of 2 weeks was administered to the retroocular tissues according to a standard protocol. The primary end point was failure of ORT, defined as persistent optic neuropathy following completion of radiotherapy that mandated urgent orbital decompression surgery.

Results:

Ninety-eight of 104 (94%) patients or 152 of 163 (93.3%) orbits did not require orbital decompression surgery during the acute phase. Patients who responded successfully to ORT had similar improvements in visual acuity, color vision, Humphrey threshold visual field testing, and afferent pupillary defects compared with patients who failed ORT and underwent urgent decompression surgery. Only 36.7% of successfully treated patients ultimately underwent elective surgery, including orbital decompression, strabismus, or eyelid surgery, during the inactive phase of TED.

Conclusions:

The data from this study, the largest retrospective review reported to date, supports the use of ORT in eyes with corticosteroid-responsive TED–compressive optic neuropathy. ORT may favorably alter the natural history of active-phase TED by preventing recurrent compressive optic neuropathy after withdrawal of corticosteroids.
Clinical presentation, assessment, and management of inducible laryngeal obstruction
Authors: Haines Jemma , Hull James H. , Fowler Stephen J.
Published: March 2018

Purpose of review

Many aspects of inducible laryngeal obstruction (ILO) are still poorly understood. However, in recent years there have been advances made and an international consensus has achieved a standardized taxonomy. This review will synthesize recent research; specifically, relating to clinical presentation, assessment, and therapeutic interventions.

Recent findings

The evidence base is growing but still limited for ILO and mostly comprises retrospective reviews, case studies, and anecdotal reports. The proposed relationship between ILO and other manifestations of laryngeal dysfunction via laryngeal hypersensitivity and hyperresponsiveness warrants further investigation. Progress has been made with guidelines published on laryngoscopy reporting procedures and validated symptom questionnaires produced for clinical use, although diagnostic algorithms are yet to be established. Emerging conservative and surgical interventions show promise, although as yet there are no randomized controlled trials investigating treatment efficacy.

The field is in an embryonic state and key research priorities, acknowledged in the current literature, need to be addressed to positively impact patient care.
Anal Malignant Melanoma Manifesting Hepatic Metastases Shown on FDG PET/CT
Authors: Zou Sijuan , Cheng Zhaoting , Song Shuang , Kuang Dong , Zhu Xiaohua
Published: March 2018

Multiple hepatic metastases are uncommon as initial presentation of primary anal malignant melanoma. We report FDG PET/CT findings of pathology-proven hepatic metastases from anal malignant melanoma of unknown origin in a 43-year-old woman whose initial presentation was worsening abdominal pain.
Trade-off between fertility and predation risk drives a geometric sequence in the pattern of group sizes in baboons
Authors: Dunbar R. I. M. , MacCarron Padraig , Robertson Cole
Published: March 2018

Group-living offers both benefits (protection against predators, access to resources) and costs (increased ecological competition, the impact of group size on fertility). Here, we use cluster analysis to detect natural patternings in a comprehensive sample of baboon groups, and identify a geometric sequence with peaks at approximately 20, 40, 80 and 160. We suggest (i) that these form a set of demographic oscillators that set habitat-specific limits to group size and (ii) that the oscillator arises from a trade-off between female fertility and predation risk.
We need to talk about reliability: Making better use of test-retest studies for study design and interpretation
Authors: Matheson Granville J.
Published: March 2018

Positron emission tomography (PET), along with many other fields of clinical research, is both timeconsuming and expensive, and recruitable patients can be scarce. These constraints limit the possibility of large-sample experimental designs, and often lead to statistically underpowered studies. This problem is exacerbated by the use of outcome measures whose accuracy is sometimes insufficient to answer the scientific questions posed. Reliability is usually assessed in validation studies using healthy participants, however these results are often not easily applicable to clinical studies examining different populations. I present a new method and tools for using summary statistics from previously published test-retest studies to approximate the reliability of outcomes in new samples. In this way, the feasibility of a new study can be assessed during planning stages, and before collecting any new data. An R package called relfeas also accompanies this article for performing these calculations. In summary, these methods and tools will allow researchers to avoid performing costly studies which are, by virtue of their design, unlikely to yield informative conclusions.
Knomics-Biota - a system for exploratory analysis of human gut microbiota data
Authors: Popenko Anna , Tyakht Alexander , Vasilyev Anatoly , Altukhov Ilya , Efimova Daria , Odintsova Vera , Klimenko Natalya , Loshkarev Robert , Pashkova Maria , Elizarova Anna , Voroshilova Viktoriya , Slavskii Sergei , Pekov Yury , Filipova Ekaterina , Shashkova Tatyana , Levin Evgenii , Alexeev Dmitry
Published: March 2018

Metagenomic surveys of human microbiota are becoming increasingly widespread in academic research as well as in food and pharmaceutical industries and clinical context. Intuitive tools for exploration of experimental data are of high interest to researchers. Knomics-Biota is a Web-based resource for exploratory analysis of human gut metagenomes. Users can generate analytical reports that correspond to common experimental schemes (like case-control study or paired comparison). Statistical analysis and visualizations of microbiota composition are provided in association with the external factors and in the context of thousands of publicly available datasets.

Availability and Implementation

The Web-service is available at https://biota.knomics.ru.

Contact

anna.popenko@knomics.ru or a.tyakht@gmail.com.

Supplementary information

Supplementary figures are available at Bioinformatics online.
Latent-Based Imputation of Laboratory Measures from Electronic Health Records: Case for Complex Diseases
Authors: Abedi V. , Shivakumar M.K. , Lu P. , Hontecillas R. , Leber A. , Ahuja M. , Ulloa A.E. , Shellenberger M.J. , Bassaganya-Riera J.
Published: March 2018

Imputation is a key step in Electronic Health Records-mining as it can significantly affect the conclusions derived from the downstream analysis. There are three main categories that explain the missingness in clinical settings–incompleteness, inconsistency, and inaccuracy–and these can capture a variety of situations: the patient did not seek treatment, the health care provider did not enter the information, etc. We used EHR data from patients diagnosed with Inflammatory Bowel Disease from Geisinger Health System to design a novel imputation that focuses on a complex phenotype. Our approach is based on latent-based analysis integrated with clustering to group patients based on their comorbidities before imputation. IBD is a chronic illness of unclear etiology and without a complete cure. We have taken advantage of the complexity of IBD to pre-process the EHR data of 10,498 IBD patients and show that imputation can be improved using shared latent comorbidities. The R code and sample simulated input data will be available at a future time.
Genome-wide association study meta-analysis of the Alcohol Use Disorder Identification Test (AUDIT) in two population-based cohorts (N=141,932)
Authors: Sanchez-Roige Sandra , Palmer Abraham A. , Fontanillas Pierre , Elson Sarah L. ,   The 23andMe Research Team,   Substance Use Disorder Working Group of the Psychiatric Genomics Consortium, Adams Mark J. , Howard David M. , Edenberg Howard J. , Davies Gail , Crist Richard C. , Deary Ian J. , McIntosh Andrew M. , Clarke Toni-Kim
Published: March 2018

Alcohol use disorders (AUD) are common conditions that have enormous social and economic consequences. We obtained quantitative measures using the Alcohol Use Disorder Identification Test (AUDIT) from two population-based cohorts of European ancestry: UK Biobank (UKB; N=121,604) and 23andMe (N=20,328) and performed a genome-wide association study (GWAS) meta-analysis. We also performed GWAS for AUDIT items 1-3, which focus on consumption (AUDIT-C), and for items 4-10, which focus on the problematic consequences of drinking (AUDIT-P). The GWAS meta-analysis of AUDIT total score identified 10 associated risk loci. Novel associations localized to genes including JCAD and SLC39A13; we also replicated previously identified signals in the genes ADH1B, ADH1C, KLB, and GCKR. The dimensions of AUDIT showed positive genetic correlations with alcohol consumption (rg=0.76-0.92) and Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) alcohol dependence (rg=0.33-0.63). AUDIT-P and AUDIT-C showed significantly different patterns of association across a number of traits, including psychiatric disorders. AUDIT-P was positively genetically correlated with schizophrenia (rg=0.22, p=3.0×10−10), major depressive disorder (rg=0.26, p=5.6×10−3), and attention-deficit/hyperactivity disorder (ADHD; rg=0.23, p=1.1×10−5), whereas AUDIT-C was negatively genetically correlated with major depressive disorder (rg=−0.24, p=3.7×10−3) and ADHD (rg=−0.10, p=1.8×10−2). We also used the AUDIT data in the UKB to identify thresholds for dichotomizing AUDIT total score that optimize genetic correlations with DSM-IV alcohol dependence. Coding individuals with AUDIT total score of ≤4 as controls and ≥12 as cases produced a high genetic correlation with DSM-IV alcohol dependence (rg=0.82, p=3.2×10−6) while retaining most subjects. We conclude that AUDIT scores ascertained in population-based cohorts can be used to explore the genetic basis of both alcohol consumption and AUD.
Inflammatory bowel disease microbiotas alter gut CD4 T-cell homeostasis and drive colitis in mice
Authors: Britton Graham J. , Contijoch Eduardo J. , Mogno Ilaria , Vennaro Olivia H. , Llewellyn Sean R. , Ng Ruby , Li Zhihua , Mortha Arthur , Merad Miriam , Das Anuk , Gevers Dirk , McGovern Dermot P.B. , Singh Namita , Braun Jonathan , Jacobs Jonathan P. , Clemente Jose C. , Grinspan Ari , Sands Bruce E. , Colombel Jean-Frederic , Dubinsky Marla C. , Faith Jeremiah J.
Published: March 2018

To examine the functional contribution of Inflammatory Bowel Disease (IBD) microbes to immune homeostasis and colitis, we colonized unchallenged and colitis-susceptible germ-free mice with over twenty human intestinal microbiotas from healthy and IBD donors. Compared to healthy microbiotas, IBD microbiotas led to expanded RORγt+Th17 cells and reduced RORγt+Treg in the gut of unchallenged gnotobiotic mice and increased disease severity in colitis-susceptible mice. The proportions of RORγt+Th17 and RORγt+Treg induced by each microbiota were highly predictive of the human disease status and strongly correlated with disease severity in colitis-susceptible mice colonized with the same human microbiotas. The transmittable functional potential of IBD microbes suggests a mechanism for a microbial contribution to IBD pathogenesis and a potential route for its treatment and prevention.
A Russian validation study of the Coma Recovery Scale-Revised (CRS-R)
Authors: Mochalova Elizaveta G. , Legostaeva Liudmila A. , Zimin Alexey A. , Sergeev Dmitry V. , Domashenko Maxim A. , Samorukov Vladislav Y. , Yusupova Dzhamilya G. , Ryabinkina Julia V. , Suponeva Natalia A. , Piradov Michael A. , Bodien Yelena. G. , Giacino Joseph T.
Published: March 2018

Introduction: The aim of the present study was to validate a Russian adaptation of the Coma Recovery Scale–Revised (CRS-R).

Subjects and methods: We evaluated 58 patients diagnosed with chronic disorders of consciousness (>4 weeks post-injury, DOC) of various etiology and two patients in a locked-in state at different time points in their post-comatose recovery. We tested sensitivity for changes over 1 week, reliability, as well as criterion validity and diagnostic sensitivity of the Russian adaptation of the CRS-R in comparison with the Russian adaptations of Full Outline of UnResponsiveness Score (FOUR), and Glasgow Coma Scale (GCS).

Results: We obtained good sensitivity for changes in neurological status over one week (p<0.0001) and good test-retest reliability (r=1, p<0.0001) of the CRS-R. Inter-rater reliability for the CRS-R total score (κ=0.99, p<0.001) and subscale scores was good. We showed high internal consistency (α=0.87 and 0.89 for the first and second visit respectively). We also showed good criterion validity between two other standardized behavioral scales (moderate correlation with GCS, r=0.597 and high correlation with FOUR Score, r=0.900). CRS-R also demonstrated a significantly higher sensitivity in differential diagnosis of DOC, as compared to GCS, and FOUR Score (p<0.001).

Conclusion: The results show that the Russian version of the CRS-R is a valid and sensitive tool for the evaluation of severely brain damaged patients with chronic DOC which can be used for differential diagnosis and for the assessment of dynamic recovery.
Endogenous protection from ischemic brain injury by preconditioned monocytes
Authors: Garcia-Bonilla Lidia , Brea David , Benakis Corinne , Lane Diane , Murphy Michelle , Moore Jamie , Racchumi Gianfranco , Jiang Xinran , Iadecola Costantino , Anrather Josef
Published: March 2018

Exposure to low dose lipopolysaccharide prior to cerebral ischemia is neuroprotective in stroke models, a phenomenon termed preconditioning. While it is well established that lipopolysaccharide-preconditioning induces central and peripheral immune responses, the cellular mechanisms modulating ischemic injury remain unclear. Here, we investigated the role of immune cells in the brain protection afforded by preconditioning and we tested whether monocytes may be reprogrammed byex vivolipopolysaccharide exposure thus modulating the inflammatory injury after cerebral ischemia in male mice. We found that systemic injection of low-dose lipopolysaccharide induces a distinct subclass of CD115+Ly6Chimonocytes that protect the brain after transient middle cerebral artery occlusion in mice. Remarkably, adoptive transfer of monocytes isolated from preconditioned mice into naïve mice 7 hours after transient middle cerebral artery occlusion reduced brain injury. Gene expression and functional studies showed that IL-10, iNOS and CCR2 in monocytes are essential for the neuroprotection. This protective activity was elicited even if mouse or human monocytes were exposedex vivoto lipopolysaccharide and then injected into male mice after stroke. Cell tracking studies showed that protective monocytes are mobilized from the spleen and reach brain and meninges, wherein they suppressed post-ischemic inflammation and neutrophils influx into the brain parenchyma. Our findings unveil a previously unrecognized subpopulation of splenic monocytes capable to protect the brain with an extended therapeutic window, and provide the rationale for cell therapies based on the delivery of autologous or allogeneic protective monocytes into patients with ischemic stroke.

Significance Statement

Inflammation is a key component of the pathophysiology of the brain in stroke, a leading cause of death and disability with limited therapeutic options. Here, we investigate endogenous mechanisms of protection against cerebral ischemia. Using LPS preconditioning as an approach to induce ischemic tolerance in mice, we found the generation of neuroprotective monocytes within the spleen from where they traffic to the brain and meninges suppressing post-ischemic inflammation. Importantly, systemic LPS preconditioning can be mimicked by adoptive transfer ofin vitro-preconditioned mouse or human monocytes at translational relevant time points after stroke. This model of neuroprotection may facilitate clinical efforts to increase the efficacy of bone marrow mononuclear cell treatments in acute neurological diseases such as cerebral ischemia.
Near-Infrared Spectroscopy for metabolite quantification and species identification
Authors: Aw WC , Ballard JWO
Published: March 2018

The aim of the study was to investigate the accuracy of near-infrared spectroscopy (NIRS) in determining triglyceride level and species of wild caught Drosophila. NIRS is a remote sensing method that uses the near-infrared region of the electromagnetic spectrum. It detects the absorption of light by molecular bonds and can be used with live insects. We employ the chemometric approach to combine spectra and reference data from a known sample to produce a multivariate calibration model. Once the calibration model was developed, we used an independent set to validate the accuracy of the calibration model. The optimized calibration model for triglyceride quantification yielded an accuracy of 73%. Simultaneously, we used NIRS to discriminate two species of Drosophila. Flies from independent sets were correctly classified into D. melanogaster and D. simulans with accuracy higher than 80%. Finally, we show that the biological interpretations derived from reference data and the NIRS predictions do not differ. These results suggest that NIRS has the potential to be used as a high throughput screening method to assess a live individual insect’s triglyceride level and taxonomic status.
Comparison of different methods for average anatomical templates creation: do we really gain anything from a diffeomorphic framework?
Authors: Fonov Vladimir S. , Collins D. Louis
Published: March 2018

In the field of computation anatomy, the diffeomorphic framework is widely used to perform analysis of human brain anatomy in both healthy and diseased populations. While useful for analysis, the framework imposes certain implementation constraints that do not necessarily result in improved accuracy of inter-subject co-registration in case of average anatomical template (AAT) construction – a common technique used in large population studies. In this work, we evaluated several state-of-the-art non-diffeomorphic and diffeomorphic non-linear registration frameworks in terms of their ability to build AATs. While all methods generated well behaved transforms, we found that the diffeomorphic framework does not automatically guarantee an increase of accuracy in average anatomical template construction.
Focal optogenetic suppression in macaque area MT biases direction discrimination and choice confidence, but only transiently
Authors: Fetsch Christopher R. , Odean Naomi N. , Jeurissen Danique , El-Shamayleh Yasmine , Horwitz Gregory D. , Shadlen Michael N.
Published: March 2018

Insights from causal manipulations of brain activity depend on targeting the spatial and temporal scale most relevant for behavior. Using a sensitive perceptual decision task in monkeys, we examined the effects of randomly-interleaved, rapid, reversible inactivation on a spatial scale previously achieved only with electrical microstimulation. Inactivating neurons in area MT with consistent direction tuning produced systematic effects on choice and confidence. Behavioral effects were attenuated over the course of each session, suggesting compensatory adjustments in the downstream readout of MT over tens of minutes. Compensation also occurred on a sub-second time scale: behavior was largely unaffected on trials with visual stimuli (and concurrent suppression) longer than ∼350ms. These trends were similar for choice and confidence, consistent with the idea of a common mechanism underlying both measures. The findings demonstrate the utility of hyperpolarizing opsins for linking neural population activity at fine spatial and temporal scales to cognitive functions in primates.
Excitability regulation in the dorsomedial prefrontal cortex during sustained instructed fear responses: a TMS-EEG study
Authors: Gonzalez-Escamilla Gabriel , Chirumamilla Venkata C. , Meyer Benjamin , Bonertz Tamara , von Grothus Sarah , Vogt Johannes , Stroh Albrecht , Tüscher Oliver , Kalisch Raffael , Muthuraman Muthuraman , Groppa Sergiu
Published: March 2018

Background

Threat detection is essential for protecting individuals from precarious situations. Early studies suggested a network of amygdala, limbic regions and dorsomedial prefrontal cortex (dmPFC) involved in fear processing. Excitability regulation in the dmPFC might be crucial for physiological fear processing, while an abnormal excitability pattern could lead to mental illness. Non-invasive paradigms to measure excitability regulation during fear processing in humans are missing.

Methods

We adapted an experimental approach of excitability characterization using electroencephalography (EEG) recordings and transcranial magnetic stimulation (TMS) over the dmPFC during an instructed fear paradigm to dynamically dissect its role in fear processing. Event-related (ERP) and TMS-evoked potentials (TEP) were analyzed to trace dmPFC excitability in healthy young volunteers (n = 40, age = 27.6 ± 5.7 years, 22 females). Moreover, we linked the excitability regulation patterns to individual structural MRI-derived properties of gray matter microstructural integrity of the fear network.

Results

An increased cortical excitability was demonstrated in the threat (T) condition in comparison to no-threat (NT) as showed by increased amplitude of evoked potentials. Furthermore, TMS over the dmPFC induced markedly increased evoked responses during T condition in relation to NT. Moreover, we found that the structural integrity of the dmPFC and the amygdala predict excitability regulation patterns as measured by ERP and TEP during fear processing.

Conclusions

We describe the dynamic range of excitability regulation in dmPFC during fear processing. The applied paradigm can be used to non-invasively track response abnormalities to threat stimuli in healthy subjects or patients with mental disorders.
Farmers’ responses to the changes in Hungarian agricultural insurance system
Authors: Zubor-Nemes Anna , Fogarasi József , Molnár András , Kemény Gábor
Published: March 2018

Purpose

The purpose of this paper is to investigate the role of crop insurance among Hungarian crop farmers and the responses to the introduction of the two-scheme risk management system. Specifically, first, it examines the economic and environmental factors affecting the willingness of farmers to contract crop insurance. Second, it reveals the relationship between having crop insurance and technical efficiency of crop producing farms.

Design/methodology/approach

Probit models of panel data are applied to explore the factors of insurance decisions. The relationship between efficiency and insurance is investigated with two-stage data envelopment analysis (DEA) model with double bootstrap using panel data for the 2001 to 2014 period.

Findings

The results of Probit model estimations show that the education, the size, the indebtedness of crop producing farms and the new two-scheme risk management system are in positive correlation, while the concentration of farming activity are in negative correlation with the crop insurance contracting. The estimations of two-stage DEA model reveal that crop producing farms with an agricultural insurance contract are more efficient than the farmers without using this risk management tool.

Originality/value

Empirical investigation of the influencing factors of agricultural insurance demand in Hungary and the examination of the relationship between insurance and technical efficiency may contribute to the development of Hungarian risk management system.
Gender diversity in the board, women’s leadership and business performance
Authors: Moreno-Gómez Jorge , Lafuente Esteban , Vaillant Yancy
Published: March 2018

Purpose

This paper aims to investigate how gender diversity in top management – i.e. boardroom and top management positions – affects business performance among Colombian public businesses.

Design/methodology/approach

Building on the upper echelon theory which emphasizes that gender in an important characteristic that influences top management’s decision-making, panel data models are used on a sample of 54 Colombian public businesses for the period 2008-2015 to test the proposed hypotheses relating to gender diversity and subsequent business performance.

Findings

The results support that gender diversity is positively associated with subsequent business performance. More concretely, the relationship between gender diversity at the top of the corporate hierarchy – in the present case, as CEO and in the top management team – and subsequent performance becomes more evident when performance is linked to business operations (ROA), whereas the positive effect of women’s representation in the boardroom and subsequent performance is significant when performance is measured via shareholder-oriented metrics (ROE).

Originality/value

Few studies have addressed the role of gender diversity on performance in developing economies. This study contributes to better understand how gender diversity affects performance in contexts where women are underrepresented in the top management, and where the appointment of women directors or managers is not driven by regulatory pressures.