bluuebunny/crossref_metadata_2025 huggingface dataset:
stAIcalc: tRNA adaptation index calculator based on species-specific weights
Authors: Sabi Renana , Volvovitch Daniel Renana , Tuller Tamir
Published: October 2016

The tRNA Adaptation Index (tAI) is a tRNA-centric measure of translation efficiency which includes weights that take into account the efficiencies of the different wobble interactions. To enable the calculation of the index based on a species-specific inference of these weights, we created the stAIcalc. The calculator includes optimized tAI weights for 100 species from the three domains of life along with a standalone software package that optimizes the weights for new organisms. The tAI with the optimized weights should enable performing large scale studies in disciplines such as molecular evolution, genomics, systems biology and synthetic biology.

Availability and Implementation

The calculator is publicly available at http://www.cs.tau.ac.il/∼tamirtul/stAIcalc/stAIcalc.html
King and Colony in Pierre Corneille’s
Le Cid
Authors: True Micah
Published: October 2016

Pierre Corneille’s tragicomedy
Le Cid
has often been interpreted as the story of medieval Castile’s transition from feudalism to a strong monarchy, a story that clearly resonates with France’s own domestic political concerns under Louis XIII. This article focuses instead on Castile’s external political engagements in the play, and how they reflect France’s efforts to establish colonies during the seventeenth century. It is argued here that reading
Le Cid
alongside France’s record of colonization in North America allows the play to be understood not only as an exploration of a fraught moment in French domestic politics, but also as a reflection of the kingdom’s efforts to maintain and expand control over foreign lands. Several aspects of
Le Cid
— Rodrigue’s duel with Don Gomès and the events surrounding it, Castile’s conflict with the Moors, and King Don Fernand’s mostly ineffective efforts to maintain order — appear on close inspection to have implications for affairs external as much as internal, a feature of Corneille’s tragicomedy that distinguishes it from the Spanish play that inspired it. More broadly, this article shows how accounting for France’s colonization of the New World may help cast the famously insular French seventeenth century in a new and revealing light.
Climate sensitivity and the rate of ocean acidification: future impacts, and implications for experimental design
Authors: Humphreys Matthew P.
Published: October 2016

The global mean surface temperature and partial pressure of carbon dioxide (CO2) are increasing both in the atmosphere and ocean. Oceanic CO2 uptake causes a decline in pH called ocean acidification (OA), which also alters other biologically important carbonate system variables such as carbonate mineral saturation states. Here, we discuss how a “temperature buffering” effect chemically links the rates of warming and OA at a more fundamental level than is often appreciated, meaning that seawater warming could mitigate some of the adverse biological impacts of OA. In a global mean sense, the rate of warming relative to the CO2 increase can be quantified by the climate sensitivity (CS), the exact value of which is uncertain. It may initially appear that a greater CS would therefore reduce the negative influence of OA. However, the dependence of the rate of CO2 increase on the CS could enhance, nullify or even reverse the temperature buffering effect, depending upon the future trajectory of anthropogenic CO2 emissions. Regional deviations from the global mean seawater temperature and CO2 uptake trends could modulate local responses to OA. For example, mitigation of OA impacts through temperature buffering could be particularly effective in the Arctic Ocean, where the surface seawater warming rate is greater than the global mean, and the aqueous CO2 concentration might increase more slowly than elsewhere. Some carbonate system variables are more strongly affected than others, highlighting the need to develop a mechanistic understanding of precisely which variables are important to each biogeochemical process. Temperature buffering of the marine carbonate system should be taken into account when designing experiments to determine marine species and ecosystem responses to warming and OA, in order that their results accurately reflect future conditions, and therefore can generate realistic predictions when applied to Earth system models.
An informatics-based approach to reducing heart failure all-cause readmissions: the Stanford heart failure dashboard
Authors: Banerjee Dipanjan , Thompson Christine , Kell Charlene , Shetty Rajesh , Vetteth Yohan , Grossman Helene , DiBiase Aria , Fowler Michael
Published: October 2016

Background: Reduction of 30-day all-cause readmissions for heart failure (HF) has become an important quality-of-care metric for health care systems. Many hospitals have implemented quality improvement programs designed to reduce 30-day all-cause readmissions for HF. Electronic medical record (EMR)-based measures have been employed to aid in these efforts, but their use has been largely adjunctive to, rather than integrated with, the overall effort.

Objectives: We hypothesized that a comprehensive EMR-based approach utilizing an HF dashboard in addition to an established HF readmission reduction program would further reduce 30-day all-cause index hospital readmission rates for HF.

Methods: After establishing a quality improvement program to reduce 30-day HF readmission rates, we instituted EMR-based measures designed to improve cohort identification, intervention tracking, and readmission analysis, the latter 2 supported by an electronic HF dashboard. Our primary outcome measure was the 30-day index hospital readmission rate for HF, with secondary measures including the accuracy of identification of patients with HF and the percentage of patients receiving interventions designed to reduce all-cause readmissions for HF.

Results: The HF dashboard facilitated improved penetration of our interventions and reduced readmission rates by allowing the clinical team to easily identify cohorts with high readmission rates and/or low intervention rates. We significantly reduced 30-day index hospital all-cause HF readmission rates from 18.2% at baseline to 14% after implementation of our quality improvement program (P = .045). Implementation of our EMR-based approach further significantly reduced 30-day index hospital readmission rates for HF to 10.1% (P for trend = .0001). Daily time to screen patients decreased from 1 hour to 15 minutes, accuracy of cohort identification improved from 83% to 94.6% (P = .0001), and the percentage of patients receiving our interventions, such as patient education, also improved significantly from 22% to 100% over time (P < .0001).

Conclusions: In an institution with a quality improvement program already in place to reduce 30-day readmission rates for HF, an EMR-based approach further significantly reduced 30-day index hospital readmission rates.
Simulating the onset of grazing envelope evolution of binary stars
Authors: Shiber Sagiv , Kashi Amit , Soker Noam
Published: October 2016

We present the first three-dimensional gas-dynamical simulations of the grazing envelope evolution (GEE) of stars, with the goal of exploring the basic flow properties and the role of jets at the onset of the GEE. In the simulated runs, a secondary main-sequence star grazes the envelope of the primary asymptotic giant branch (AGB) star. The orbit is circular at the radius of the AGB primary star on its equator. We inject two opposite jets perpendicular to the equatorial plane from the location of the secondary star, and follow the evolution for several orbital periods. We explore the flow pattern by which the jets eject the outskirts of the AGB envelope. After one orbit, the jets start to interact with gas ejected in previous orbits and inflate hot low-density bubbles.
The Case against Forced Methadone Detox in the US Prisons
Authors: D’Hotman Daniel , Pugh Jonathan , Douglas Thomas
Published: October 2016

Methadone maintenance therapy is a cost-effective, evidence-based treatment for heroin dependence. In the USA, a majority of heroin-dependent offenders are forced to detox from methadone when incarcerated. Recent research published in The Lancet has demonstrated the negative health and economic outcomes associated with such policies (Rich, J. D., McKenzie, M., Larney, S., Wong, J. B., Tran, L., Clarke, J. et al. (2015). Methadone Continuation Versus Forced Withdrawal on Incarceration in a Combined US Prison and Jail: A Randomised, Open Label Trial. The Lancet, 386, 350–359). This novel evidence raises questions as to the justification for current policies of forced detox in American prisons. Opponents of methadone provision in prisons might offer arguments from retributivism, resource allocation and curative effectiveness to justify their position. This article contends that these arguments do not stand up to ethical scrutiny. In light of this, we hold that American policymakers should reform criminal justice policies to allow the initiation and continuation of methadone treatment in correctional settings. This would be consistent with both international recommendations and the example set by a number of other Western countries.
Psychosocial Influences on Exercise-Induced Hypoalgesia
Authors: Brellenthin Angelique G. , Crombie Kevin M. , Cook Dane B. , Sehgal Nalini , Koltyn Kelli F.
Published: October 2016

Objective. The purpose of this study was to examine psychosocial influences on exercise-induced hypoalgesia (EIH).

Design. Randomized controlled trial.

Setting. Clinical research unit in a hospital.

Subjects. Fifty-eight healthy men and women (mean age = 21 ± 3 years) participated in this study.

Methods. Participants were first asked to complete a series of baseline demographic and psychological questionnaires including the Pain Catastrophizing Scale, the Fear of Pain Questionnaire, and the Family Environment Scale. Following this, they were familiarized with both temporal summation of heat pain and pressure pain testing protocols. During their next session, participants completed the Profile of Mood States, rated the intensity of heat pulses, and indicated their pressure pain thresholds and ratings before and after three minutes of submaximal, isometric exercise. Situational catastrophizing was assessed at the end of the experimental session.

Results. Results indicated that experimental pain sensitivity was significantly reduced after exercise (P < 0.05). Men and women did not differ on any of the measured psychosocial variables (P > 0.05). Positive family environments predicted attenuated pain sensitivity and greater EIH, whereas negative and chronic pain-present family environments predicted worse pain and EIH outcomes. Situational catastrophizing and negative mood state also predicted worse pain and EIH outcomes and were additionally associated with increased ratings of perceived exertion and muscle pain during exercise.

Conclusions. This study provides preliminary evidence that psychosocial variables, such as the family environment and mood states, can affect both pain sensitivity and the ability to modulate pain through exercise-induced hypoalgesia.
Thinking, Fast and Slow? Some Field Experiments to Reduce Crime and Dropout in Chicago*
Authors: Heller Sara B. , Shah Anuj K. , Guryan Jonathan , Ludwig Jens , Mullainathan Sendhil , Pollack Harold A.
Published: October 2016

We present the results of three large-scale randomized controlled trials (RCTs) carried out in Chicago, testing interventions to reduce crime and dropout by changing the decision making of economically disadvantaged youth. We study a program called Becoming a Man (BAM), developed by the nonprofit Youth Guidance, in two RCTs implemented in 2009–2010 and 2013–2015. In the two studies participation in the program reduced total arrests during the intervention period by 28–35%, reduced violent-crime arrests by 45–50%, improved school engagement, and in the first study where we have follow-up data, increased graduation rates by 12–19%. The third RCT tested a program with partially overlapping components carried out in the Cook County Juvenile Temporary Detention Center (JTDC), which reduced readmission rates to the facility by 21%. These large behavioral responses combined with modest program costs imply benefit-cost ratios for these interventions from 5-to-1 up to 30-to-1 or more. Our data on mechanisms are not ideal, but we find no positive evidence that these effects are due to changes in emotional intelligence or social skills, self-control or “grit,” or a generic mentoring effect. We find suggestive support for the hypothesis that the programs work by helping youth slow down and reflect on whether their automatic thoughts and behaviors are well suited to the situation they are in, or whether the situation could be construed differently.
Get to know “low T”
Authors: Pickett Kim Anne
Published: October 2016

Consumer-targeted therapy has heightened awareness of male hypogonadism, which may lead to more of your patients asking for testosterone replacement.
Sexually inappropriate behavior in patients with dementia
Authors: Murphy Kathryn
Published: October 2016

Sexual disinhibition is one of the most challenging and stressful symptoms of dementia. We give you tips to help you intervene effectively.
How to take a sexual health history
Authors: Pessagno Richard A.
Published: October 2016

Assessing your patients' sexual well-being can be tough. Here's what you need to be comfortable with.
The influence of mother-daughter connectedness on sexual activity
Authors: Tyson Teresa
Published: October 2016

What are African American female adolescents' and young adults' perceptions of their mothers' role in their decision to initiate sexual intercourse?
Capsule Endoscopy Crohn’s Disease Activity Index (CECDAIic or Niv Score) for the Small Bowel and Colon
Authors: Niv Yaron , Gal Eyal , Gabovitz Violeta , Hershkovitz Marcela , Lichtenstein Lev , Avni Irit
Published: October 2016

Background and the Study Aim:

Crohn’s disease (CD) is a chronic inflammatory disorder defined as a transmural inflammation of the bowel wall, affecting the small and large intestine. The Capsule Endoscopy Crohn’s Disease Activity Index (CECDAI or Niv score) was devised to measure mucosal disease activity. We extended the Niv score to the colon and have a comprehensive view of the whole intestine.

Methods:

We evaluated 3 parameters of intestinal pathology: A, Inflammation; B, Extent of disease; C, Presence of strictures. The scoring formula is as follows: CEDCAIic=(A1×B1+C1)+(A2×B2+C2)+(A3×B3+C3)+(A4×B4+C4) (1=proximal small bowel, 2=distal small bowel, 3=right colon, 4=left colon).

Results:

The median CECDAIic score was 15.5 (range, 0 to 42), and the mean±SD score was 17.2±11.5. The CECDAIic scores per patient were similar among the 5 observers. Kendall’s coefficient of concordance was high and significant for almost all the parameters examined except for strictures in the proximal small bowel and distal colon. Nevertheless, the coefficients for the small bowel and for the whole intestine were high, 0.85 and 0.77,P<0.0001, respectively.

Conclusions:

We established a new score, the CECDAIic of the small-bowel and colonic CD. We offer this easy, user-friendly score for use in randomized controlled trials and in the clinical follow-up of CD patients.
Role of YAP-1 in Thyroid Tumor Progression and Outcome
Authors: Ugolini Clara , Borrelli Nicla , Niccoli Cristina , Elisei Rossella , Viola David , Vitti Paolo , Miccoli Paolo , Basolo Fulvio
Published: October 2016

Context:

Yes-associated protein-1 (YAP-1) is a player of the Hippo pathway and is involved in regulating cell proliferation. YAP-1 is overexpressed in papillary and anaplastic thyroid cancers. However, a correlation between YAP-1 expression and outcome in thyroid carcinoma has not been conclusively demonstrated.

Objective:

This study was designed to clarify whether YAP-1 may be considered a marker of worse prognosis and outcome in thyroid cancer.

Design:

A large series of cases of thyroid cancer with a long follow-up were investigated for YAP-1 expression.

Setting:

The study was carried out in the Pathology section of a referral Italian center for Endocrine Surgery and Endocrinology.

Patients or Other Participants:

The study included a consecutive series of 105 patients who underwent thyroidectomy from 1985 to 1992. The mean follow-up was 15 years. For all patients, clinicopathologic features were considered. All patients completed the study.

The study also included a consecutive series of 52 patients who underwent thyroidectomy from 2012 to 2013 in order to analyze more deeply the correlation of YAP-1expression with BRAF mutation.

Intervention:

The 105 thyroid tumors were immunohistochemically investigated for YAP-1 expression.

Outcome Measures:

We expected a correlation between YAP-1 expression and worse prognosis.

Results:

Among 105 tumors, 77 scored positive for YAP-1 expression, of which 68 papillary thyroid carcinomas and 9 anaplastic thyroid carcinomas were YAP-1 positive. The correlation of YAP-1 expression with clinicopathologic characteristics was significant for the absence of a tumoral capsule, gender, and extrathyroid invasion.

Interestingly, significant correlations were found between YAP-1 and both persistence of disease and death from carcinoma.

Conclusions:

The data show an association of YAP-1 expression with worse clinicopathologic features of thyroid tumors that seem to have a specific impact on outcome.
A Comparative Immunohistochemical Study of Epithelial Membrane Antigen and NHERF1/EBP50 in the Diagnosis of Ependymomas
Authors: Nambirajan Aruna , Sharma Mehar C. , Rajeshwari Madhu , Kakkar Aanchal , Suri Vaishali , Sarkar Chitra
Published: October 2016

Ependymomas are gliomas that recapitulate normal ependymal cells. The epithelial membrane antigen (EMA) shows “dot-like” and “ring-like” staining patterns, highlighting “microlumens” or intracytoplasmic rosettes, a pathognomonic ultrastructural feature. NHERF1/EBP50, an adaptor protein localized at the apical plasma membrane of human epithelia, has been found to localize to these microlumens. We aimed to analyze the staining patterns of EMA and EBP50 in ependymomas and other tumors, and thereby compare their diagnostic utility. Sixty-three ependymomas of different grades and 44 nonependymal tumors (meningiomas, 5; pilocytic astrocytoma, 2; paraganglioma, 2; neurocytoma, 4; pituitary adenoma, 3; papillary tumor of pineal region, 3; oligodendroglioma, 4; choroid plexus papilloma, 3; medulloblastoma, 2; schwannoma, 2; cellular hemangioblastoma, 2; subependymal giant cell astrocytoma, 1; glioblastoma multiforme, 8; diffuse astrocytoma, 1; anaplastic astrocytoma, 1; and pilomyxoid astrocytoma, 1) were included. Ring-like positivity was 100% specific for ependymomas, but showed a poor sensitivity (EMA, 29%; EBP50, 37%). Dot EMA positivity was more sensitive in grade III ependymomas (100%), whereas dot EBP50 positivity was more sensitive in grade I subependymomas (80%) and myxopapillary ependymomas (40%). Among grade II ependymomas, EBP50 labeled a significantly higher number of dots and rings, which may be of value in small biopsies. Focal dot positivity for EMA and EBP50 in glioblastoma multiforme and meningioma contributed to the lowered specificity (EMA, 84%; EBP50, 80%). Myxopapillary ependymomas (60%), choroid plexus papillomas (66%), and papillary tumors of pineal region (100%) showed membranous staining with EBP50. Although EPB50 appears to be a better diagnostic marker for grade I/II ependymomas, we recommend a combined panel of EMA and EBP50 for grade III ependymomas to compensate for the reduced sensitivity of EBP50 in this subgroup.
Immunohistochemical Expression of Antitissue Transglutaminase 2 in Tissue Injuries: An Interpretation Beyond Celiac Disease
Authors: Das Prasenjit , Rawat Ramakant , Verma Anil K. , Singh Geetika , Vallonthaiel Archana G. , Yadav Rajni , Gahlot Gaurav P.S. , Dinda Amit K. , Ahuja Vineet , Datta Gupta Siddhartha , Agarwal Sanjay K. , Makharia Govind K.
Published: October 2016

Tissue transglutaminase 2 enzyme plays a diverse role in intracellular and extracellular functioning. Aberrant expression of anti-TG2 antibody has recently been proposed for extraintestinal identification of celiac disease (CeD), but its utility is questionable. To examine whether anti-TG2 immunohistochemical (IHC) staining can be of diagnostic value in identifying extraintestinal involvement in CeD, tissue blocks of patients with IgA nephropathies (IgAN), minimal change disease, membranous glomerulonephritis, membrano-proliferative glomerulonephritis, normal kidney, intestinal biopsies from CeD, tropical sprue, nonspecific duodenitis, and inflammatory bowel disease; liver biopsies from patients with chronic hepatitis B and C, acute liver failure (ALF), and CeD-associated liver diseases were retrieved and subjected to IHC staining for anti-tissue transglutaminase 2 enzyme. H-score was calculated by multiplying the area of positivity and stain intensity. Anti-TG2 stain H-scores were almost similar in IgAN and non-IgANs (H-score 6.31±3 vs. 7.03±2.7); however, H-scores in both of these groups were significantly higher than in normal renal parenchyma (1.6±1.5). Only 6.2% patients with IgAN with anti-TG2 immunostain positivity showed a positive anti-tTG antibody serology and villous abnormalities, suggestive of CeD. Intestinal biopsies from patients with CeD, tropical sprue, nonspecific duodenitis, and inflammatory bowel disease also showed high anti-TG2 H-scores, with no statistically significant differences. Liver biopsies from patients with both ALF, as well as chronic liver diseases showed high anti-TG2 H-scores; with highest stain expression in ALF. In conclusion, IHC expression of anti-TG2 stain correlates with both acute and chronic tissue injuries, irrespective of etiology and organ involvement. It is not a reliable marker for diagnosis of CeD.
Assessment of EGFR and ERBB2 (HER2) in Gastric and Gastroesophageal Carcinomas: EGFR Amplification is Associated With a Worse Prognosis in Early Stage and Well to Moderately Differentiated Carcinoma
Authors: Liao Jia-Bin , Lee Huai-Pao , Fu Hsiao-Ting , Lee Herng-Sheng
Published: October 2016

Epidermal growth factor receptor 1 (EGFR) and erb-b2 receptor tyrosine kinase 2 (ERBB2/HER2) are frequently dysregulated in human cancers. We analyzed EGFR and ERBB2 status in 105 gastric and gastroesophageal junction carcinoma and their clinicopathologic features. For EGFR, 92 (88%) tumors were scored as 0, 2 (2%) as 1+, 7 (7%) as 2+, and 4 (3%) as 3+ by immunohistochemistry (IHC) and 4 (4%) tumors showed EGFR amplification by fluorescence in situ hybridization (FISH). For ERBB2, 90 (86%) tumors were scored as 0, 4 (4%) as 1+, 6 (6%) as 2+, and 5 (5%) as 3+ by IHC and 12 (12%) showed ERBB2 amplification by FISH. The concordance rate between IHC and FISH of EGFR was 98.1% (P<0.001) and of ERBB2 was 93.3% (P<0.001). Most tumors with ERBB2 amplification were tubular adenocarcinoma (N=11, P=0.02) and Lauren intestinal type (N=12, P=0.016). There was no statistically significant difference between EGFR amplification and tumor classification. EGFR amplification had significant impact on overall survival in certain subgroups: early stages (stages I and II) (P<0.001), well to moderately differentiated tumors (P=0.001), and fewer regional lymph node metastasis (pN1) (P=0.001). ERBB2 status had little predictive value on overall survival. In conclusion, this study showed ERBB2 amplification was significantly observed in tubular adenocarcinoma and Lauren intestinal-type carcinoma. The IHC scoring criteria for ERBB2 can be applied to EGFR. EGFR amplification had associated with poor prognosis in early, well to moderately differentiated carcinoma.
Child Passenger Restraint System Misuse in Rural Versus Urban Children
Authors: Hafner John W. , Kok Stephanie J. , Wang Huaping , Wren Dale L. , Aitken Mary E. , Miller Beverly K. , Anderson Byron L. , Monroe Kathy W.
Published: October 2016

Objectives

Motor vehicle crashes are the leading cause of childhood fatality, making use of properly installed child passenger restraint system (CRS) a public health priority. Motor vehicle crashes in rural environments are associated with increased injuries and fatalities, and overall CRS use tends to be lower compared with urban populations. However, it remains unclear if proper installation of car seats is lower in a rural population compared with a similar matched urban population.

Methods

A multisite (Alabama, Arkansas, Illinois), observational, case-control study was performed using data from community child passenger safety checkup events in rural (economically and population-controlled) and urban locations. Data were matched to the primary child assessed in a vehicle, and stratified by age, site, and year with urban unscheduled CRS check data. All CRS checks were performed using nationally certified CRS technicians who used the best practice standards of the American Academy of Pediatrics and collected subject demographics, car seat misuse patterns, and interventions using identical definitions.

Results

Four hundred eighty-four CRS checks (242 rural and 242 urban) involving 603 total children from 3 states (Alabama, 43 [7%]; Arkansas, 442 [73%]; Illinois, 118 [20%]) were examined; of which, 86% had at least 1 documented CRS misuse. Child passenger restraint system misuse was more common in rural than urban locations (90.5% vs 82.6%; P = 0.01). Child passenger restraint system misuse was more common in rural children aged 4 to 8 years (90.3% vs 80.6%; P = 0.02).

Conclusions

In this multisite study, rural location was associated with higher CRS misuse. Child passenger restraint system education and resources that target rural populations specifically appear to be justified.
Grill-Related Injuries in Children Treated in US Emergency Departments, 1990–2009
Authors: Ortega Henry W. , Vander Velden Heidi , Smith Gary A.
Published: October 2016

Objective

The aim of the study was to describe grill-related injuries in pediatric patients seeking emergency treatment.

Methods

Data from the National Electronic Injury Surveillance System from 1990 through 2009 were investigated. Sample weights were used to calculate national estimates. United States Census Bureau data were used to calculate injury rates per 100,000 individuals. Linear regression and computation of relative risks (RRs) with 95% confidence intervals (CIs) were performed.

Results

An estimated 308,560 children were treated in US emergency departments for grill-related injuries during the study period, with an average of 15,428 cases per year. The rate of injuries increased by 32.3% during the study period. Males (62.8%) and children aged 11 to 18 years (55.8%) sustained the largest number of injuries. Children younger than 5 years were more likely to injure the head and neck (RR, 1.26 [95% CI, 1.21–1.33]), be injured by impact with a grill (RR, 1.97 [95% CI, 1.88–2.07]), and sustain burns (RR, 1.39 [95% CI, 1.35–1.45]) when compared with other age groups. Children aged 11 to 18 years were more likely to experience a fracture or dislocation (RR, 2.07 [95% CI, 1.58–2.72]) and more likely to sustain a grill-related injury while the grill was not in use (RR, 7.95 [95% CI, 6.25–10.12]).

Conclusions

The rate of grill-related injuries among children is increasing, which underscores the need for increased prevention efforts. Prevention strategies should address measures such as lighting a grill and grill location in addition to burn prevention.
‘Bodily precision’: a predictive coding account of individual differences in interoceptive accuracy
Authors: Ainley Vivien , Apps Matthew A. J. , Fotopoulou Aikaterini , Tsakiris Manos
Published: October 2016

Individuals differ in their awareness of afferent information from within their bodies, which is typically assessed by a heartbeat perception measure of ‘interoceptive accuracy’ (IAcc). Neural and behavioural correlates of this trait have been investigated, but a theoretical explanation has yet to be presented. Building on recent models that describe interoception within the free energy/predictive coding framework, this paper applies similar principles to IAcc, proposing that individual differences in IAcc depend on ‘precision’ in interoceptive systems, i.e. the relative weight accorded to ‘prior’ representations and ‘prediction errors’ (that part of incoming interoceptive sensation not accounted for by priors), at various levels within the cortical hierarchy and between modalities. Attention has the effect of optimizing precision both within and between sensory modalities. Our central assumption is that people with high IAcc are able, with attention, to prioritize interoception over other sensory modalities and can thus adjust the relative precision of their interoceptive priors and prediction errors, where appropriate, given their personal history. This characterization explains key findings within the interoception literature; links results previously seen as unrelated or contradictory; and may have important implications for understanding cognitive, behavioural and psychopathological consequences of both high and low interoceptive awareness.

This article is part of the themed issue ‘Interoception beyond homeostasis: affect, cognition and mental health’.
Is the cardiac monitoring function related to the self in both the default network and right anterior insula?
Authors: Babo-Rebelo Mariana , Wolpert Nicolai , Adam Claude , Hasboun Dominique , Tallon-Baudry Catherine
Published: October 2016

The self has been proposed to be rooted in the neural monitoring of internal bodily signals and might thus involve interoceptive areas, notably the right anterior insula (rAI). However, studies on the self consistently showed the involvement of midline default network (DN) nodes, without referring to visceral monitoring. Here, we investigate this apparent discrepancy. We previously showed that neural responses to heartbeats in the DN encode two different self-dimensions, the agentive ‘I’ and the introspective ‘Me’, in a whole-brain analysis of magnetoencephalography (MEG) data. Here, we confirm and anatomically refine this result with intracranial recordings (intracranial electroencephalography, iEEG). In two patients, we show a parametric modulation of neural responses to heartbeats by the self-relatedness of thoughts, at the single trial level. A region-of-interest analysis of the insula reveals that MEG responses to heartbeats in the rAI encode the ‘I’ self-dimension. The effect in rAI was weaker than in the DN and was replicated in iEEG data in one patient out of two. We propose that a common mechanism, the neural monitoring of cardiac signals, underlies the self in both the DN and rAI. This might reconcile studies on the self highlighting the DN, with studies on interoception focusing on the insula.

This article is part of the themed issue ‘Interoception beyond homeostasis: affect, cognition and mental health’.
Active interoceptive inference and the emotional brain
Authors: Seth Anil K. , Friston Karl J.
Published: October 2016

We review a recent shift in conceptions of interoception and its relationship to hierarchical inference in the brain. The notion of interoceptive inference means that bodily states are regulated by autonomic reflexes that are enslaved by descending predictions from deep generative models of our internal and external milieu. This re-conceptualization illuminates several issues in cognitive and clinical neuroscience with implications for experiences of selfhood and emotion. We first contextualize interoception in terms of active (Bayesian) inference in the brain, highlighting its enactivist (embodied) aspects. We then consider the key role of uncertainty or precision and how this might translate into neuromodulation. We next examine the implications for understanding the functional anatomy of the emotional brain, surveying recent observations on agranular cortex. Finally, we turn to theoretical issues, namely, the role of interoception in shaping a sense of embodied self and feelings. We will draw links between physiological homoeostasis and allostasis, early cybernetic ideas of predictive control and hierarchical generative models in predictive processing. The explanatory scope of interoceptive inference ranges from explanations for autism and depression, through to consciousness. We offer a brief survey of these exciting developments.

This article is part of the themed issue ‘Interoception beyond homeostasis: affect, cognition and mental health’.
Affective touch and attachment style modulate pain: a laser-evoked potentials study
Authors: Krahé Charlotte , Drabek Marianne M. , Paloyelis Yannis , Fotopoulou Aikaterini
Published: October 2016

Affective touch and cutaneous pain are two sub-modalities of interoception with contrasting affective qualities (pleasantness/unpleasantness) and social meanings (care/harm), yet their direct relationship has not been investigated. In 50 women, taking into account individual attachment styles, we assessed the role of affective touch and particularly the contribution of the C tactile (CT) system in subjective and electrophysiological responses to noxious skin stimulation, namely N1 and N2-P2 laser-evoked potentials. When pleasant, slow (versus fast) velocity touch was administered to the (non-CT-containing) palm of the hand, higher attachment anxiety predicted increased subjective pain ratings, in the same direction as changes in N2 amplitude. By contrast, when pleasant touch was administered to CT-containing skin of the arm, higher attachment anxiety predicted attenuated N1 and N2 amplitudes. Higher attachment avoidance predicted opposite results. Thus, CT-based affective touch can modulate pain in early and late processing stages (N1 and N2 components), with the direction of effects depending on attachment style. Affective touch not involving the CT system seems to affect predominately the conscious perception of pain, possibly reflecting socio-cognitive factors further up the neurocognitive hierarchy. Affective touch may thus convey information about available social resources and gate pain responses depending on individual expectations of social support.

This article is part of the themed issue ‘Interoception beyond homeostasis: affect, cognition and mental health’.
Differentiating attention styles and regulatory aspects of self-reported interoceptive sensibility
Authors: Mehling Wolf
Published: October 2016

Based on prior research, multiple discriminable dimensions of interoception have been defined: awareness, accuracy and sensibility. Some investigators defined
interoceptive awareness
as metacognitive awareness of interoceptive accuracy, assessed as correspondence between subjective confidence in and objective accuracy of one's heartbeat detection. However, metacognitive awareness has been understood quite differently: ‘a cognitive set in which negative thoughts/feelings are experienced as mental events, rather than as the self’ or as ‘error awareness’.
Interoceptive sensibility
, defined as self-reported interoception, distinguishes self-reported interoception from objective
interoceptive accuracy
, but does not differentiate between anxiety-driven and mindful attention styles towards interoceptive cues, a distinction of key clinical importance: one attention style is associated with somatization and anxiety disorders; the other has been viewed as healthy, adaptive, resilience-enhancing. The self-report Multidimensional Assessment of Interoceptive Awareness was developed to differentiate these attention styles. It has been translated into 16 languages and applied in cross-sectional and longitudinal studies. Findings from these applications suggest that differentiating interoceptive sensibility according to attention style and regulatory aspects (i) provides insights into the psychology of interoceptive awareness, (ii) differentiates between clinically maladaptive and beneficial interoceptive attention, and (iii) helps elucidate therapeutic approaches that claim to provide health benefits by training mindful styles of bodily awareness.

This article is part of the themed issue ‘Interoception beyond homeostasis: affect, cognition and mental health’.
Interoceptive dimensions across cardiac and respiratory axes
Authors: Garfinkel Sarah N. , Manassei Miranda F. , Hamilton-Fletcher Giles , In den Bosch Yvo , Critchley Hugo D. , Engels Miriam
Published: October 2016

Interoception refers to the sensing of signals concerning the internal state of the body. Individual differences in interoceptive sensitivity are proposed to account for differences in affective processing, including the expression of anxiety. The majority of investigations of interoceptive accuracy focus on cardiac signals, typically using heartbeat detection tests and self-report measures. Consequently, little is known about how different organ-specific axes of interoception relate to each other or to symptoms of anxiety. Here, we compare interoception for cardiac and respiratory signals. We demonstrate a dissociation between cardiac and respiratory measures of interoceptive accuracy (i.e. task performance), yet a positive relationship between cardiac and respiratory measures of interoceptive awareness (i.e. metacognitive insight into own interoceptive ability). Neither interoceptive accuracy nor metacognitive awareness for cardiac and respiratory measures was related to touch acuity, an exteroceptive sense. Specific measures of interoception were found to be predictive of anxiety symptoms. Poor respiratory accuracy was associated with heightened anxiety score, while good metacognitive awareness for cardiac interoception was associated with reduced anxiety. These findings highlight that detection accuracies across different sensory modalities are dissociable and future work can better delineate their relationship to affective and cognitive constructs.

This article is part of the themed issue ‘Interoception beyond homeostasis: affect, cognition and mental health’.
Towards a psychophysics of interoceptive processes: the measurement of heartbeat detection
Authors: Brener Jasper , Ring Christopher
Published: October 2016

It is difficult to collect objective evidence of interoception. Unlike exteroception, the effective stimuli for interoception are often unknown, and even when identifiable, they are difficult to control experimentally. Furthermore, direct stimulation of the interoceptors is seldom appropriate in human experimentation. Hence, non-invasive behavioural measures of accuracy in heartbeat detection have frequently been adopted to index interoceptive sensitivity. However, there has been little standardization and the two most popular methods for assessing heartbeat detection, heartbeat tracking and two alternative forced choice methods, appear to be biased and of questionable validity. These issues do not arise with other methods that are based on classical psychophysics and that enable subjects to indicate when during the cardiac cycle their heartbeat sensations occur. Not only are these classical methods highly reliable, but they also provide continuous unbiased measures of the temporal locations of heartbeat sensations and the precision with which these sensations are detected.

This article is part of the themed issue ‘Interoception beyond homeostasis: affect, cognition and mental health’.
How the heart speaks to the brain: neural activity during cardiorespiratory interoceptive stimulation
Authors: Hassanpour Mahlega S. , Yan Lirong , Wang Danny J. J. , Lapidus Rachel C. , Arevian Armen C. , Simmons W. Kyle , Feusner Jamie D. , Khalsa Sahib S.
Published: October 2016

Prominent theories emphasize key roles for the insular cortex in the central representation of interoceptive sensations, but how this brain region responds dynamically to changes in interoceptive state remains incompletely understood. Here, we systematically modulated cardiorespiratory sensations in humans using bolus infusions of isoproterenol, a rapidly acting peripheral beta-adrenergic agonist similar to adrenaline. To identify central neural processes underlying these parametrically modulated interoceptive states, we used pharmacological functional magnetic resonance imaging (phMRI) to simultaneously measure blood-oxygenation-level dependent (BOLD) and arterial spin labelling (ASL) signals in healthy participants. Isoproterenol infusions induced dose-dependent increases in heart rate and cardiorespiratory interoception, with all participants endorsing increased sensations at the highest dose. These reports were accompanied by increased BOLD and ASL activation of the right insular cortex at the highest dose. Different responses across insula subregions were also observed. During anticipation, insula activation increased in more anterior regions. During stimulation, activation increased in the mid-dorsal and posterior insula on the right, but decreased in the same regions on the left. This study demonstrates the feasibility of phMRI for assessing brain activation during adrenergic interoceptive stimulation, and provides further evidence supporting a dynamic role for the insula in representing changes in cardiorespiratory states.

This article is part of the themed issue ‘Interoception beyond homeostasis: affect, cognition and mental health’.
Connecting myelin-related and synaptic dysfunction in schizophrenia with SNP-rich gene expression hubs
Authors: Hegyi Hedi
Published: October 2016

The recent availability of several genome-wide data sets such as genome-wide mapping of SNP-rich regions and differentially methylated genes in schizophrenic individuals and gene expression data in all brain compartments across the span of human life prompted us to integrate these datasets to gain a better insight into the underlying gene networks driving this enigmatic disease.

We summed up the differentially methylated “expression neighbors” (i.e. genes with positively or negatively correlating expression values) of genes that fall into one of 108 distinct schizophrenia-associated genetic loci with high number of SNPs in schizophrenic patients derived from a large cohort of pooled sequencing experiments. Surprisingly, the number of expression neighbors (with a Pearson correlation of R>=0.8 or R<=−0.7) of the genes falling into the 108 genomic regions were about35 timeshigher for the positively correlating genes and32 timeshigher for the negatively correlating ones than for the rest of the ~16000 genes outside these loci. While the genes in the 108 loci have relatively little known impact in schizophrenia, using this approach we identified many more known schizophrenia-related important genes with a high degree of connectedness to other genes and high scores of differentially methylated probes for their expression neighbors (such as MBP, MOBP, GRIA1, COMT, SYNGR1, MAP2 and DGCR6), validating our approach.

The analysis revealed that the most positively correlating as well as the most negatively correlating genes affect synapse-related genes the most, offering an explanation and a unified view into the root cause of schizophrenia.
Histone Hyperacetylation in Maize in Response to Treatment with HC-Toxin or Infection by the Filamentous Fungus Cochliobolus carbonum
Authors: Ransom R. F. , Walton J. D.
Published: October 2016

HC-toxin, the host-selective toxin produced by the filamentous fungus Cochliobolus carbonum, inhibits maize (Zea mays L.) histone deacetylases (HDs) in vitro. Here we show that HDs are also inhibited by HC-toxin in vivo, as demonstrated by the accumulation of hyperacetylated forms of the core (nucleosomal) histones H3.1, H3.2, H3.3, and H4 in both maize embryos and tissue cultures. Hyperacetylation of H4 and all isoforms of H3 in tissue cultures of inbred Pr (genotype hm/hm) occurred at 10 ng/mL (23 nM). The effect was host-selective; acetylation of histones in the near isogenic inbred Pr1 (genotype Hm/Hm) did not occur in tissue cultures or embryos treated with 0.2 [mu]g/mL or 10 [mu]g/mL HC-toxin, respectively. Hyperacetylation of histone H4 in embryos of Pr1 began to occur at 50 [mu]g/mL. HC-toxin, and 200 [mu]g/mL HC-toxin caused equal hyperacetylation in Pr and Pr1 embryos. Hyperacetylated core histones, especially of the isoforms of histone H3, accumulated in leaves of inbred Pr, but not Pr1, after infection by toxin-producing strains of C. carbonum. Accumulation of hyperacetylated histones began at 24 h after inoculation, before the development of visible disease symptoms. Hyperacetylation of H2A or H2B histones were not detected in any of the studies. The results are consistent with HD being a primary site of action of HC-toxin.
Characterization of Thylakoid-Derived Lipid-Protein Particles Bearing the Large Subunit of Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase
Authors: Smith M. D. , Ghosh S. , Dumbroff E. B. , Thompson J. E.
Published: October 2016

Lipid-protein particles bearing the 55-kD ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) (EC 4.1.1.39) large subunit (RLSU) and no detectable corresponding Rubisco small subunit (RSSU) were isolated from the stroma of intact chloroplasts by flotation centrifugation. Stromal RLSU-bearing particles appear to originate from thylakoids because they can also be generated in vitro by illumination of isolated thylakoids. Their formation in vitro is largely heat denaturable and is facilitated by light or ATP. RLSU-containing lipid-protein particles range from 0.05 to 0.10 [mu]m in radius, contain the same fatty acids as thylakoids, but have a 10- to 15-fold higher free-to-esterified fatty acid ratio than thylakoids. RLSU-bearing lipid-protein particles with no detectable RSSU were also immunopurified from the populations of both stromal lipid-protein particles and those generated in vitro from illuminated thylakoids. Protease shaving indicated that the RLSU is embedded in the lipid-protein particles and that there is also a protease-protected RLSU in thylakoids. These observations collectively indicate that the RLSU associated with thylakoids is released into the stroma by light-facilitated blebbing of lipid-protein particles. The release of RLSU-containing particles may in turn be coordinated with the assembly of Rubisco holoenzyme because chaperonin 60 is also associated with lipid-protein particles isolated from stroma.
Treatment of Grape Berries, a Nonclimacteric Fruit with a Synthetic Auxin, Retards Ripening and Alters the Expression of Developmentally Regulated Genes
Authors: Davies C. , Boss P. K. , Robinson S. P.
Published: October 2016

Treatment of grape (Vitis vinifera L.) berries with the synthetic auxin-like compound benzothiazole-2-oxyacetic acid (BTOA) caused a delay in the onset of ripening of approximately 2 weeks. This was manifested as a retardation of the increases in berry weight, color, deformability, and hexose concentration. BTOA treatment also delayed by 2 weeks the increase in abscisic acid level that normally accompanies ripening and altered the expression of a number of developmentally regulated genes. A putative vacuolar invertase, which is normally expressed from berry set until ripening and turned off after ripening commences, remained expressed throughout development in BTOA-treated grape berries. This elevated expression resulted in increased levels of invertase activity. In contrast, the up-regulation of four other genes normally switched on at the time of ripening was delayed in BTOA-treated fruit. These included chalcone synthase and UDP-glucose-flavonoid 3-O-glucosyl transferase, both of which are involved in anthocyanin synthesis, a chitinase, and a ripening-related gene of an unknown function. These observations support the view that auxins (perhaps in conjunction with abscisic acid) may have a role in the control of grape berry ripening by affecting the expression of genes involved in the ripening process.