bluuebunny/crossref_metadata_2025 huggingface dataset:
Forgiveness
Authors: Hughes Paul
Published: October 2016

There is by now an enormous, and growing, philosophical literature on forgiveness. Since at least Downie 1965 (cited under Forgiveness and Virtue), philosophers have produced articles, monographs, encyclopedia entries, and anthologized collections of essays on the conceptual, normative, phenomenological, and social-political nature of forgiveness. Much of this literature may be categorized as follows: General Overviews, Historical Sources, Emotions of Forgiveness, Acts of Forgiveness, Political Forgiveness, Self-Forgiveness, Feminist Approaches to Forgiveness, Forgiveness in Continental Philosophy, Forgiveness and Punishment, the Normative Status of Forgiveness, Third-Party Forgiveness, Paradoxes of Forgiveness, and God and Forgiveness. While no attempt has been made to canvass all the philosophical literature on the topic, and there is considerable overlap between the sections of this article, the following annotated citations aim to provide a guide to much of that literature.
Mitochondrial Haplogroups as a Risk Factor for Herpes Zoster
Authors: Levinson Rebecca T. , Hulgan Todd , Kalams Spyros A. , Fessel Joshua P. , Samuels David C.
Published: October 2016

Background.  Herpes zoster, or shingles, is a common, painful reactivation of latent varicella zoster virus infection. Understanding host factors that predispose to herpes zoster may permit development of more effective prevention strategies. Our objective was to examine mitochondrial haplogroups as a potential host factor related to herpes zoster incidence.

Methods.  Study participants were drawn from BioVU, a deoxyribonucleic acid (DNA) biobank connected to deidentified electronic medical records (EMRs) from Vanderbilt University Medical Center. Our study used 9691 Caucasian individuals with herpes zoster status determined by International Classification of Diseases, Ninth Revision codes 053–053.9. Cases and controls were matched on sex and date of birth within 5 years. Mitochondrial haplogroups were defined from mitochondrial DNA variants genotyped on the Illumina 660W or Illumina Infinium Human-Exome Beadchip. Sex and date of birth were extracted from the EMR.

Results.  European mitochondrial haplogroup H had a protective association with herpes zoster status (odds ratio [OR] = .82; 95% confidence interval [CI], .71–.94; P = .005), whereas haplogroup clade IWX was a risk factor for herpes zoster status (OR = 1.38; 95% CI, 1.07–1.77; P = .01).

Conclusions.  Mitochondrial haplogroup influences herpes zoster risk. Knowledge of a patient's mitochondrial haplogroup could allow for a precision approach to the management of herpes zoster risk through vaccination strategies and management of other modifiable risk factors.
Value and Clinical Impact of an Infectious Disease-Supervised Outpatient Parenteral Antibiotic Therapy Program
Authors: Petrak Russell M. , Skorodin Nathan C. , Fliegelman Robert M. , Hines David W. , Chundi Vishnu V. , Harting Brian P.
Published: October 2016

Background.  Outpatient parenteral antibiotic therapy (OPAT) is a safe and effective modality for treating serious infections. This study was undertaken to define the value of OPAT in a multicentered infectious disease (ID) private practice setting.

Methods.  Over a period of 32 months, 6120 patients were treated using 19 outpatient ID offices in 6 states. Analysis included patient demographics, indications of OPAT, diagnoses, therapeutic agent, duration of therapy, and site of therapy initiation. Outcomes were stratified by therapeutic success, clinical relapse, therapeutic complications, and hospitalizations after initiating therapy. Statistical analysis included an ordinal logistic regression analysis.

Results.  Forty-three percent of patients initiated therapy in an outpatient office, and 57% began therapy in a hospital. Most common diagnoses treated were bone and joint (32.2%), abscesses (18.8%), cellulitis (18.5%), and urinary tract infection (10.8%). Ninety-four percent of patients were successfully treated, and only 3% were hospitalized after beginning therapy. Most common cause of treatment failure was a relapse of primary infection (60%), progression of primary infection (21%), and therapeutic complication (19%).

Conclusions.  An ID-supervised OPAT program is safe, efficient, and clinically effective. By maximizing the delivery of outpatient care, OPAT provides a tangible value to hospitals, payers, and patients. This program is a distinctive competency available to ID physicians who offer this service to patients.
Toward Automated Cochlear Implant Fitting Procedures Based on Event-Related Potentials
Authors: Finke Mareike , Billinger Martin , Büchner Andreas
Published: October 2016

Objectives:

Cochlear implants (CIs) restore hearing to the profoundly deaf by direct electrical stimulation of the auditory nerve. To provide an optimal electrical stimulation pattern the CI must be individually fitted to each CI user. To date, CI fitting is primarily based on subjective feedback from the user. However, not all CI users are able to provide such feedback, for example, small children. This study explores the possibility of using the electroencephalogram (EEG) to objectively determine if CI users are able to hear differences in tones presented to them, which has potential applications in CI fitting or closed loop systems.

Design:

Deviant and standard stimuli were presented to 12 CI users in an active auditory oddball paradigm. The EEG was recorded in two sessions and classification of the EEG data was performed with shrinkage linear discriminant analysis. Also, the impact of CI artifact removal on classification performance and the possibility to reuse a trained classifier in future sessions were evaluated.

Results:

Overall, classification performance was above chance level for all participants although performance varied considerably between participants. Also, artifacts were successfully removed from the EEG without impairing classification performance. Finally, reuse of the classifier causes only a small loss in classification performance.

Conclusions:

Our data provide first evidence that EEG can be automatically classified on single-trial basis in CI users. Despite the slightly poorer classification performance over sessions, classifier and CI artifact correction appear stable over successive sessions. Thus, classifier and artifact correction weights can be reused without repeating the set-up procedure in every session, which makes the technique easier applicable. With our present data, we can show successful classification of event-related cortical potential patterns in CI users. In the future, this has the potential to objectify and automate parts of CI fitting procedures.
Giant Cell Tumor of Cervical Spine Presenting as Acute Asphyxia
Authors: Kumar Rajendra , Meis Jeanne M. , Amini Behrang , McEnery Kevin W. , Madewell John E. , Rhines Laurence D. , Benjamin Robert S.
Published: October 2016

Study Design.

Case report and literature review.

Objective.

To describe treatment of a unique case of acute airway obstruction by a large C7 giant cell tumor (GCT) with preoperative denosumab followed by surgical resection, and review the literature on this rare entity.

Summary of Background Data.

Standard treatment for GCTs includes surgical resection or curettage and packing. Large lesions in the spine may require preoperative therapy with denosumab, a human monoclonal antibody to RANKL, to facilitate surgery. It is highly unusual for GCT arising in cervical spine to present with acute asphyxia (requiring tracheostomy).

Methods.

We report a patient with large C7 GCT that caused tracheal compression with almost complete airway obstruction requiring emergency intubation.

Results.

The tumor responded to subcutaneously administered denosumab with marked decrease in size and relief of symptoms. Increased tumor mineralization in response to therapy facilitated subsequent successful surgical tumor resection. The patient remains symptom-free 2 years after surgery without tumor recurrence.

Conclusion.

Denosumab can shrink the size of large GCTs, providing symptom relief before surgery and facilitate tumor resection.

Level of Evidence:5
On mitochondrial metabolism in tumor biology
Authors: Shoshan Maria
Published: October 2016

Purpose of review

To provide examples of mitochondria-specific metabolic events that influence tumor cell biology, and of metabolism-related mitochondrial biomarkers and therapeutic targets in cancer cells.

Recent findings

Cancer cell mitochondria are rewired to optimally serve the cancer cell under various conditions of cellular stress. The nonexhaustive list of mitochondrial alterations that support cancer cell proliferation, survival, and/or progression includes upregulation of oxidative metabolism and use of alternative substrates, oncometabolites, increased superoxide production, mutated mitochondrial DNA, and altered mitochondrial morphology and dynamics. Potential therapeutic targets include fatty acid oxidation, voltage-dependent anion channel-1, the pyruvate dehydrogenase complex, and Complex I.

Some phenotypical traits, for example, chemoresistance and metastasis, are likely regulated by a fine-tuned balance between several metabolic processes and events that are upregulated in parallel and are also dependent on microenvironmental cues. Many metabolism-related mitochondrial biomarkers show prognostic value, but the biological interpretation of the data may be confounded by the overall metabolic status and context. Understanding metabolic regulation of stemness is important for targeting cancer stem cells. Therapeutic targeting of cancer cell mitochondria remains experimental but promising, and more predictive markers will be needed for metabolism-based treatments and personalized medicine.
The Effect of Timing on Breast Reconstruction Outcomes in Diabetic Women
Authors: Major Melanie , Devulapalli Chris , Bello Ricardo J. , Baltodano Pablo A. , Reinhardt Myrna Eliann , Manahan Michele A. , Cooney Carisa M. , Rosson Gedge D.
Published: October 2016

Background:

This study examines the effect of timing (immediate vs delayed) on postoperative morbidity in diabetic women undergoing breast reconstruction after mastectomy.

Methods:

We reviewed the National Surgical Quality Improvement Program (NSQIP) databases from 2005 to 2012 for all diabetic women undergoing breast reconstruction. Multivariable logistic regression was used to estimate the risk of 30-day overall complications in the immediate versus delayed cohorts. Additionally, we retrospectively reviewed outcomes for all Johns Hopkins Hospital diabetic patients undergoing breast reconstruction from 2005 to 2014.

Results:

In the NSQIP, 1,408 diabetic women underwent breast reconstruction: 958 (68%) immediate and 450 (32%) delayed. In the immediate group, 10.75% of patients developed a 30-day overall complication, compared with 7.78% of patients in the delayed group. On multivariable analysis, the odds of developing 30-day overall complications were significantly higher (adjusted odds ratio = 1.68; P = 0.033) for the immediate compared with the delayed cohort. In the Johns Hopkins Hospital cohort, 114 reconstructions were performed in 52 diabetic women: 59 (51.8%) immediate and 55 (47.2%) delayed. On long-term follow-up (median = 16.5 months), 41.0% of immediate reconstructions developed a surgical complication compared with 27.8% of delayed reconstructions. Deep infections (P = 0.026), seroma formation (P = 0.003), reconstruction failure (P = 0.001), and reoperation rates (P = 0.001) were significantly increased in the immediate cohort.

Conclusions:

Among diabetics seeking breast reconstruction, delaying the reconstructive surgery from the mastectomy is associated with decreased postoperative morbidity. It also appears that the 30-day postoperative time point available in the NSQIP does not fully reflect the magnitude of the long-term complications these diabetic patients will develop.
Building trust: The influence of mentoring behaviors on perceptions of health care managers’ trustworthiness
Authors: Fleig-Palmer Michelle M. , Rathert Cheryl , Porter Tracy H.
Published: October 2016

Background:

In health care organizations, trust is critical for effective workplace relationships that ensure patient-centered outcomes. Although research has focused on trust in the relationship between patients and clinicians, less is known about what influences workers to trust their managers. An understanding is needed of the specific behaviors that influence health care workers’ evaluations of their managers’ trustworthiness. Mentoring research focuses on the developmental assistance that a more experienced worker provides to a less experienced worker. Building upon Kram’s (1988) seminal research on mentoring functions, we argue that health care managers can build trust by providing informational (career-related) and interpersonal (psychosocial) support.

Purpose:

The aim of the study was to investigate the influence of health care managers’ informational and interpersonal mentoring behaviors on workers’ perceptions of their managers’ trustworthiness and the mediating role of trustworthiness on trust in the managers.

Methodology/Approach:

Surveys were completed during work hours by 315 health care workers at an acute care hospital and associated clinics in the Midwest.

Findings:

Results showed that managers’ mentoring behaviors influenced worker perceptions of their managers’ trustworthiness, in terms of ability, integrity, and benevolence. Ability partially mediated the relationship between informational mentoring and trust in managers, whereas integrity and benevolence partially mediated the relationship between interpersonal mentoring and trust in managers.

Practice Implications:

Health care managers can actively build trust through mentoring behaviors that inspire positive assessments of managers’ ability, integrity, and benevolence.
Successful Integrative Medicine Assessment and Treatment of Chronic Pain Associated With Breast Surgery
Authors: Chung Myung Kyu , LaRiccia Patrick J.
Published: October 2016

Presented is the first reported case series of chronic neck and back pain associated with breast scars from breast surgery and successfully treated with an integrative medicine assessment and treatment approach, which included the assessment technique of autonomic response testing and the scar therapy technique of neural therapy. Implications for nursing practice are discussed.
Centers for Disease Control and Prevention 2015 Human Papillomavirus Vaccine Recommendations for Sexually Assaulted Patients: A Review and Update
Authors: Scannell Meredith
Published: October 2016

Individuals who have been sexually assaulted are at risk for contracting human papillomavirus (HPV), the most common sexually transmitted infection. One of the best methods in protecting against contracting the HPV is to receive the HPV vaccine. To date, national sexual assault protocols and guidelines do not include information on HPV vaccination. The current 2015 Centers for Disease Control and Prevention has updated their recommendations for sexually assaulted patients to now receive the HPV vaccine. This article reviews information on HPV, HPV vaccines, and specific considerations for patients who have been sexually assaulted.
Dipeptidyl Peptidase-4, Wound Healing, Scarring, and Fibrosis
Authors: Hu Michael S. , Longaker Michael T.
Published: October 2016

Scarring and fibrosis are an enormous public health concern, resulting in excessive morbidity and mortality in addition to countless lost health care dollars. Recent advances in cell and developmental biology promise a better understanding of scarring and fibrosis and may translate to new clinical therapies.
Venous Thromboembolism: A Comparison of Chronic Spinal Cord Injury and General Surgery Patients in a Metropolitan Veterans Affairs Hospital
Authors: Moore Ryan M. , Rimler Jonathan , Smith Brian R. , Wirth Garrett A. , Paydar Keyianoosh Z.
Published: October 2016

Background:

Venous thromboembolic events result in significant morbidity, mortality, and costly therapeutic interventions. As medical resource allocation strategies are becoming more pervasive, appropriate risk stratification and prophylactic regimens are essential. Previous studies have shown a decreased incidence of perioperative venous thromboembolism in the chronic spinal cord injury population. The question remains of whether chronic spinal cord injury is protective against venous thromboembolism.

Methods:

A retrospective review of all cases involving chronic spinal cord injury patients who underwent plastic and reconstructive surgery operations (n = 424) and general surgery patients (n = 777) with a primary outcome of deep venous thrombosis or pulmonary embolism within 90 days of surgery was performed.

Results:

The incidence of postoperative deep venous thrombosis in the control and spinal cord injury groups was 1.7 percent and 0.2 percent, respectively (p = 0.027). However, such significance was not observed with regard to postoperative pulmonary embolism incidence (p = 0.070). Collectively, the incidence of postoperative venous thromboembolism—specifically, deep venous thrombosis or pulmonary embolism—was significantly greater in the general surgery population (p = 0.014). A nearly 10-fold increased risk of venous thromboembolism was seen among the control group (1.9 percent versus 0.2 percent) despite administration of optimal prophylaxis.

Conclusions:

This study demonstrates a profoundly low incidence of venous thromboembolism among chronic spinal cord injury patients compared with general surgery patients. Future efforts to elucidate how chronic spinal cord injury confers a protective mechanism may potentially influence the evolution of venous thromboembolism prevention guidelines, and spark the development of alternative prophylactic agents or customized application of prevention efforts.
Wall structure and material properties cause viscous damping of swimbladder sounds in the oyster toadfishOpsanus tau
Authors: Fine Michael L. , King Terrence L. , Ali Heba , Sidker Nehan , Cameron Timothy M.
Published: October 2016

Despite rapid damping, fish swimbladders have been modelled as underwater resonant bubbles. Recent data suggest that swimbladders of sound-producing fishes use a forced rather than a resonant response to produce sound. The reason for this discrepancy has not been formally addressed, and we demonstrate, for the first time, that the structure of the swimbladder wall will affect vibratory behaviour. Using the oyster toadfishOpsanus tau, we find regional differences in bladder thickness, directionality of collagen layers (anisotropic bladder wall structure), material properties that differ between circular and longitudinal directions (stress, strain and Young's modulus), high water content (80%) of the bladder wall and a 300-fold increase in the modulus of dried tissue. Therefore, the swimbladder wall is a viscoelastic structure that serves to damp vibrations and impart directionality, preventing the expression of resonance.
Thyroid hormone modulates offspring sex ratio in a turtle with temperature-dependent sex determination
Authors: Sun Bao-Jun , Li Teng , Mu Yi , McGlashan Jessica K. , Georges Arthur , Shine Richard , Du Wei-Guo
Published: October 2016

The adaptive significance of temperature-dependent sex determination (TSD) has attracted a great deal of research, but the underlying mechanisms by which temperature determines the sex of a developing embryo remain poorly understood. Here, we manipulated the level of a thyroid hormone (TH), triiodothyronine (T3), during embryonic development (by adding excess T3to the eggs of the red-eared slider turtleTrachemys scripta, a reptile with TSD), to test two competing hypotheses on the proximate basis for TSD: thedevelopmental rate hypothesisversus thehormone hypothesis. Exogenous TH accelerated embryonic heart rate (and hence metabolic rate), developmental rate, and rates of early post-hatching growth. More importantly, hyperthyroid conditions depressed expression ofCyp19a1(the gene encoding for aromatase) and levels of oestradiol, and induced more male offspring. This result is contrary to the direction of sex-ratio shift predicted by thedevelopmental rate hypothesis, but consistent with that predicted by thehormone hypothesis. Our results suggest an important role for THs in regulating sex steroid hormones, and therefore, in affecting gonadal sex differentiation in TSD reptiles. Our study has implications for the conservation of TSD reptiles in the context of global change because environmental contaminants may disrupt the activity of THs, and thereby affect offspring sex in TSD reptiles.
High evolutionary constraints limited adaptive responses to past climate changes in toad skulls
Authors: Simon Monique Nouailhetas , Machado Fabio Andrade , Marroig Gabriel
Published: October 2016

Interactions among traits that build a complex structure may be represented as genetic covariation and correlation. Genetic correlations may act as constraints, deflecting the evolutionary response from the direction of natural selection. We investigated the relative importance of drift, selection, and constraints in driving skull divergence in a group of related toad species. The distributional range of these species encompasses very distinct habitats with important climatic differences and the species are primarily distinguished by differences in their skulls. Some parts of the toad skull, such as the snout, may have functional relevance in reproductive ecology, detecting water cues. Thus, we hypothesized that the species skull divergence was driven by natural selection associated with climatic variation. However, given that all species present high correlations among skull traits, our second prediction was of high constraints deflecting the response to selection. We first extracted the main morphological direction that is expected to be subjected to selection by using within- and between-species covariance matrices. We then used evolutionary regressions to investigate whether divergence along this direction is explained by climatic variation between species. We also used quantitative genetics models to test for a role of random drift versus natural selection in skull divergence and to reconstruct selection gradients along species phylogeny. Climatic variables explained high proportions of between-species variation in the most selected axis. However, most evolutionary responses were not in the direction of selection, but aligned with the direction of allometric size, the dimension of highest phenotypic variance in the ancestral population. We conclude that toad species have responded to selection related to climate in their skulls, yet high evolutionary constraints dominated species divergence and may limit species responses to future climate change.
Whole genome analysis of Yersinia ruckeri isolated over 27 years in Australia and New Zealand reveals geographical endemism over multiple lineages and recent evolution under host selection
Authors: Barnes Andrew C. , Delamare-Deboutteville Jerome , Gudkovs Nicholas , Brosnahan Cara , Morrison Richard , Carson Jeremy
Published: October 2016

Yersinia ruckeri is a salmonid pathogen with widespread distribution in cool-temperate waters including Australia and New Zealand, two isolated environments with recently developed salmonid farming industries. Phylogenetic comparison of 58 isolates from Australia, New Zealand, USA, Chile, Finland and China based on non-recombinant core genome SNPs revealed multiple deep-branching lineages, with a most recent common ancestor estimated at 18 500 years BP (12 355–24 757 95% HPD) and evidence of Australasian endemism. Evolution within the Tasmanian Atlantic salmon serotype O1b lineage has been slow, with 63 SNPs describing the variance over 27 years. Isolates from the prevailing lineage are poorly/non-motile compared to a lineage pre-vaccination, introduced in 1997, which is highly motile but has not been isolated since from epizootics. A non-motile phenotype has arisen independently in Tasmania compared to Europe and USA through a frameshift in fliI, encoding the ATPase of the flagella cluster. We report for the first time lipopolysaccharide O-antigen serotype O2 isolates in Tasmania. This phenotype results from deletion of the O-antigen cluster and consequent loss of high-molecular-weight O-antigen. This phenomenon has occurred independently on three occasions on three continents (Australasia, North America and Asia) as O2 isolates from the USA, China and Tasmania share the O-antigen deletion but occupy distant lineages. Despite the European and North American origins of the Australasian salmonid stocks, the lineages of Y. ruckeri in Australia and New Zealand are distinct from those of the northern hemisphere, suggesting they are pre-existing ancient strains that have emerged and evolved with the introduction of susceptible hosts following European colonization.
Alternating dynamics of segregation and integration in human brain functional networks during working-memory task
Authors: Zippo Antonio G. , Della Rosa Pasquale A. , Castiglioni Isabella , Biella Gabriele E. M.
Published: October 2016

Brain functional networks show high variability in short time windows but mechanisms governing these transient dynamics still remain unknown. In this work we studied the temporal evolution of functional brain networks involved in a working memory task while recording high-density electroencephalography in human normal subjects. We found that functional brain networks showed an initial phase characterized by an increase of the functional segregation index followed by a second phase where the functional segregation fell down and the functional integration prevailed. Notably, wrong trials were associated with different sequences of the segregation-integration profile and measures of network centrality and modularity were able to catch crucial aspects of the oscillatory network dynamics. Additionally, computational investigations further supported the experimental results. The brain functional organization may respond to the information processing demand of a working memory task following a 2-step atomic scheme wherein segregation and integration alternately dominate the functional configurations.
Methods for detecting co-mutated pathways in cancer samples to inform treatment selection
Authors: Jiang Tingting , Shaham Uri , Parisi Fabio , Halaban Ruth , Safonov Anton , Kluger Harriet , Weissman Sherman , Chang Joseph , Kluger Yuval
Published: October 2016

Tumor genomes evolve through a selection of mutations. These mutations may complement each other to promote tumorigenesis. To better understand the functional interactions of different processes in cancer, we studied mutation data of a set of tumors and identified significantly co-mutated pathways. Fisher’s exact test is a standard approach that can be used to assess the significance of the joint dysregulation of pathways pairs across a patient population. We developed a robust test to identify co-occurrence using DNA mutations, which overcomes deficiencies of the Fisher’s exact test by taking into account the large variability in overall mutation load and sequencing depth. Applying our method to a study of six common cancer types, we identify enrichment of co-mutated signal transduction pathways such as IP3 synthesis and PI3K and pairs of co-mutated pathways involving other processes such as immunity and development. We observed enrichment of clonal co-mutation of the proteasome and apoptosis pathways in colorectal cancer, which suggests potential mechanisms for immune evasion.
Neuronal responses support a role for orbitofrontal cortex in cognitive set reconfiguration
Authors: Sleezer Brianna J. , Loconte Giuliana , Castagno Meghan D. , Hayden Benjamin Y.
Published: October 2016

We are often faced with the need to abandon no-longer beneficial rules and adopt new ones. This process, known as cognitive set reconfiguration, is a hallmark of executive control. Although cognitive functions like reconfiguration are most often associated with dorsal prefrontal structures, recent evidence suggests that the orbitofrontal cortex (OFC) may play an important role as well. We recorded activity of OFC neurons while rhesus macaques performed a version of the Wisconsin Card Sorting Task that involved a trial-and-error stage. OFC neurons demonstrated two types of switch-related activity, an early (switch-away) signal and a late (switch-to) signal, when the new task set was established. We also found a pattern ofmatch modulation: a significant change in activity for the stimulus that matched the current rule (and would therefore be selected). These results extend our understanding of the executive functions of the OFC. They also allow us to directly compare OFC with complementary datasets we previously collected in ventral (VS) and dorsal (DS) striatum. Although both effects are observed in all three areas, the timing of responses aligns OFC more closely with DS than with VS.
A Computational Model of Perceptual and Mnemonic Deficits in Medial Temporal Lobe Amnesia
Authors: Sadil Patrick S. , Cowell Rosemary A.
Published: October 2016

Damage to the Medial Temporal Lobe (MTL) has long been known to impair declarative memory and recent evidence suggests that it also impairs visual perception. A theory termed the representational-hierarchical account explains such impairments by assuming that MTL stores conjunctive representations of items and events, and that individuals with MTL damage must rely upon representations of simple visual features in posterior visual cortex, which are inadequate to support memory and perception under certain circumstances. One recent study of visual discrimination behavior revealed a surprising anti-perceptual learning effect in MTL-damaged individuals: with exposure to a set of visual stimuli, discrimination performance worsened rather than improved (Barense et al., 2012). We extend the representational-hierarchical account to explain this paradox by assuming that difficult visual discriminations are performed by comparing the relative ‘representational tunedness’ – or familiarity – of the to-be-discriminated items. Exposure to a set of highly similar stimuli entails repeated presentation of simple visual features, eventually rendering all feature representations maximally, and thus equally, familiar ― hence, they are inutile for solving the task. Discrimination performance in patients with MTL lesions is therefore impaired by stimulus exposure. Because the unique conjunctions represented in MTL do not occur repeatedly, healthy individuals are shielded from this perceptual interference. We simulate this mechanism with a neural network previously used to explain recognition memory, thereby providing a model that accounts for both mnemonic and perceptual deficits caused by MTL damage with a unified architecture and mechanism.
Robust mixture modeling reveals category-free selectivity in reward region neuronal ensembles
Authors: Blanchard Tommy C. , Piantadosi Steven T. , Hayden Benjamin Y.
Published: October 2016

Classification of neurons into clusters based on their response properties is an important tool for gaining insight into neural computations. However, it remains unclear to what extent neurons fall naturally into discrete functional categories. We developed a Bayesian method that models the tuning properties of neural populations as a mixture of multiple types of task-relevant response patterns. We applied this method to data from several cortical and striatal regions in economic choice tasks. In all cases, neurons fell into only two clusters: one mixed-selectivity cluster containing all task-sensitive cells and another of no selectivity (i.e. pure noise) cells. The single cluster of task-sensitive cells argues against robust categorical tuning in these areas. The no selectivity cells were unanticipated; their identification allows for improved measurement of ensemble effects. Our findings provide a valuable tool for analysis of neural data and place strong constraints on neurocomputational models of choice and control.
Inference of multiple-wave population admixture by modeling decay of linkage disequilibrium with polynomial functions
Authors: Zhou Ying , Yuan Kai , Yu Yaoliang , Ni Xumin , Xie Pengtao , Xing Eric P , Xu Shuhua
Published: October 2016

To infer the histories of population admixture, one important challenge with methods based on the admixture linkage disequilibrium (ALD) is to get rid of the effect of source LD (SLD) which is directly inherited from source populations. In previous methods, only the decay curve of weighted LD between pairs of sites whose genetic distance were larger than a certain starting distance was fitted by single or multiple exponential functions, for the inference of recent single- or multiple-wave of admixture. However, the effect of SLD has not been well defined and no tool has been developed to estimate the effect of SLD on weighted LD decay. In this study, we defined the SLD in the formularized weighted LD statistic under the two-way admixture model, and proposed polynomial spectrum (p-spectrum) to study the weighted SLD and weighted LD. We also found reference populations could be used to reduce the SLD in weighted LD statistic. We further developed a method, iMAAPs, to inferMultiple-waveAdmixture by fittingALD usingPolynomialspectrum. We evaluated the performance of iMAAPs under various admixture models in simulated data and applied iMAAPs into analysis of genome-wide single nucleotide polymorphism data from the Human Genome Diversity Project (HGDP) and the HapMap Project. We showed that iMAAPs is a considerable improvement over other current methods and further facilitates the inference of the histories of complex population admixtures.
High-risk human papillomavirus in oral cavity squamous cell carcinoma
Authors: Palve Vinayak , Bagwan Jamir , Krishnan Neeraja M , Pareek Manisha , Chandola Udita , Suresh Amritha , Siddappa Gangotri , James Bonney L , Kekatpure Vikram , Kuriakose Moni Abraham , Panda Binay
Published: October 2016

Purpose

The prevalence of human papillomavirus (HPV) in oral cavity squamous cell carcinoma (OSCC) varies significantly based on assay sensitivity and patient geography. Accurate detection is essential to understand the role of HPV in disease prognosis and management of patients with OSCC.

Methods

We generated and integrated data from multiple analytes (HPV DNA, HPV RNA, and p16), assays (immunohistochemistry, PCR, qPCR and digital PCR) and molecular changes (somatic mutations and DNA methylation) from 153 OSCC patients to correlate p16 expression, HPV DNA, and HPV RNA with HPV incidence and patient survival.

Results

High prevalence (33-58%) of HPV16/18 DNA did not correlate with the presence of transcriptionally active viral genomes (15%) in tumors. Eighteen percent of the tumors were p16 positive. and only 6% were both HPV DNA and RNA positive. Most tumors with relatively high-copy HPV DNA, and/or HPV RNA, but not with HPV DNA alone (irrespective of copy number), were wild-type forTP53andCASP8genes. In our study, p16 protein, HPV DNA and HPV RNA, either alone or in combinations, did not correlate with patient survival. Nine HPV-associated genes stratified the virus +ve from the –ve tumor group with high confidence (p<0.008) when HPV DNA copy number and/or HPV RNA were considered to define HPV positivity and not HPV DNA alone irrespective of their copy number (p< 0.2).

Conclusions

In OSCC, the presence of both HPV RNA and p16 are rare. HPV DNA alone is not an accurate measure of HPV positivity and therefore not informative. Moreover, HPV DNA, RNA or p16 don’t correlate with outcome.
Cooperation not competition: bihemispheric tDCS and fMRI show role for ipsilateral hemisphere in motor learning
Authors: Waters Sheena , Wiestler Tobias , Diedrichsen Jörn
Published: October 2016

What is the role of ipsilateral motor and pre-motor areas in motor learning? One view supposes that ipsilateral activity suppresses contralateral motor cortex, and thus needs to be inhibited to improve motor learning. Alternatively, the ipsilateral motor cortex may play an active role in the control and learning of unilateral hand movements. We approached this question by applying double-blind bihemispheric transcranial direct current stimulation (tDCS) over both contralateral and ipsilateral motor cortex in a between-group design during four days of unimanual explicit sequence training. Independently of whether the anode was placed over contralateral or ipsilateral motor cortex, bihemispheric stimulation yielded substantial performance gains relative to unihemispheric or sham stimulation. This performance advantage appeared to be supported by plastic changes in both hemispheres: First, we found that behavioral advantages generalized strongly to the untrained hand, suggesting that tDCS strengthened effector-independent representations. Secondly, functional imaging during speed-matched execution of trained sequences conducted 48 h after training revealed sustained, polarity-independent increases in activity in both motor cortices relative to the sham group. These results suggest a cooperative rather than competitive interaction of the two motor cortices during skill learning and suggest that bihemispheric brain stimulation during unimanual skill learning may be beneficial, because it harnesses plasticity in the ipsilateral hemisphere.

Significance statement

Many neurorehabilitation approaches are based on the idea that is beneficial to boost excitability in the contralateral hemisphere while attenuating that of the ipsilateral cortex to reduce interhemispheric inhibition. We observed that bihemispheric tDCS with the excitatory anode either over contralateral or ipsilateral motor cortex facilitated motor learning nearly twice as strongly as unihemispheric tDCS. These increases in motor learning were accompanied by increases in fMRI activation in both motor cortices that outlasted the stimulation period, as well as increased generalization to the untrained hand. Collectively, our findings suggest a cooperative—rather than competitive—role of the hemispheres and imply that it is most beneficial to harness plasticity in both hemispheres in neurorehabilitation of motor deficits.
Distinct oscillatory frequencies underlie excitability of human occipital and parietal cortex
Authors: Samaha Jason , Gosseries Olivia , Postle Bradley R.
Published: October 2016

Magnetic stimulation (TMS) of human occipital and posterior parietal cortex can give rise to visual sensations called phosphenes, but neural correlates of phosphene perception preceding and succeeding stimulation of both areas are unknown. Using near-threshold TMS with concurrent electroencephalography (EEG) recordings, we uncover oscillatory brain dynamics that covary, on single trials, with the perception of phosphenes following occipital and parietal TMS. Prestimulus power and phase predominantly in the alpha-band (8-13 Hz) predicted occipital TMS phosphenes, whereas higher frequency beta-band (13-20 Hz) power (but not phase) predicted parietal TMS phosphenes. TMSevokedresponses related to phosphene perception were similar across stimulation sites and were characterized by an early (200 ms) posterior negativity and a later (>300 ms) parietal positivity in the time domain and an increase in low-frequency (~5-7 Hz) power followed by a broadband decrease in alpha/beta power in the time-frequency domain. These correlates of phosphene perception closely resemble known electrophysiological correlates of conscious perception using near-threshold visual stimuli and speak to the possible early onset of visual consciousness. The differential pattern of prestimulus predictors of phosphene perception suggest that distinct frequencies reflect cortical excitability within different cortical regions, and that the alpha-band rhythm, long thought of as a general index of cortical inhibition, may not reflect excitability of posterior parietal cortex.

Significance statement

Alpha-band oscillations are thought to reflect cortical excitability and are therefor suggested to play an important role in gating information transmission across cortex. We directly probe cortical excitability in human occipital and parietal cortex and observed that whereas alpha-band dynamics indeed reflect excitability of occipital areas, beta-band activity was most predictive of parietal cortex excitability. Differences in the state of cortical excitability predicted perceptual outcomes, which were manifest in both early and late patterns of evoked activity, shedding light on the neural correlates of consciousness. Our findings prompt revision of the notion that alpha activity reflects inhibition across all of cortex and suggests instead that excitability in different regions is reflected in distinct frequency bands.
Lattice dynamics and elasticity of SrCO3
Authors: Nguyen-Thanh Tra , Bosak Alexei , Bauer Johannes D. , Luchitskaia Rita , Refson Keith , Milman Victor , Winkler Bjoern
Published: October 2016

The lattice dynamics and elasticity of synthetic SrCO3 have been investigated by a combination of ab initio lattice dynamics calculations, microcalorimetry, Raman spectroscopy, X-ray thermal diffuse scattering and high-resolution inelastic X-ray scattering. The results of density functional based calculations were in all cases in good agreement with experiment. For the spectroscopic investigations, peak positions and intensities are well reproduced by the density functional theory model. Experimentally determined intensity distributions in thermal diffuse scattering maps differ from the theoretical distribution only in the (HK0) plane, a fact that is attributed to stacking disorder. As the model is accurate and reliable, the complete elastic stiffness tensor is predicted and, on the basis of these results, the anisotropy of the sound velocities is discussed, also in relation to the anisotropy in other carbonate systems.
Structural characterization of the thermostableBradyrhizobium japonicumD-sorbitol dehydrogenase
Authors: Fredslund Folmer , Otten Harm , Gemperlein Sabrina , Poulsen Jens-Christian N. , Carius Yvonne , Kohring Gert-Wieland , Lo Leggio Leila
Published: October 2016

Bradyrhizobium japonicumsorbitol dehydrogenase is NADH-dependent and is active at elevated temperatures. The best substrate is D-glucitol (a synonym for D-sorbitol), although L-glucitol is also accepted, giving it particular potential in industrial applications. Crystallization led to a hexagonal crystal form, with crystals diffracting to 2.9 Å resolution. In attempts to phase the data, a molecular-replacement solution based upon PDB entry 4nbu (33% identical in sequence to the target) was found. The solution contained one molecule in the asymmetric unit, but a tetramer similar to that found in other short-chain dehydrogenases, including the search model, could be reconstructed by applying crystallographic symmetry operations. The active site contains electron density consistent with D-glucitol and phosphate, but there was not clear evidence for the binding of NADH. In a search for the features that determine the thermostability of the enzyme, theTmfor the orthologue fromRhodobacter sphaeroides, for which the structure was already known, was also determined, and this enzyme proved to be considerably less thermostable. A continuous β-sheet is formed between two monomers in the tetramer of theB. japonicumenzyme, a feature not generally shared by short-chain dehydrogenases, and which may contribute to thermostability, as may an increased Pro/Gly ratio.
Being a guest – perspectives of an extended hospitality approach
Authors: Pechlaner Harald , Nordhorn Christian , Poppe Xenia
Published: October 2016

Purpose

This paper aims to deduce and present an extended hospitality approach. In developed countries, hospitality is increasingly linked to tourism; in times of migration and increased refugee flows, the accompanying social, economic and political determining factors play a more prominent role, necessitating a new view of hospitality. This study aims to extend the domain of tourism in hospitality by including aspects related to asylum seekers and to combine it with topics regarding welcome culture, service quality and relational quality. The paper explores the question concerning whether, and in which ways, the various sectors may learn from each other.

Design/methodology/approach

To expand this new research area and to take the exploratory nature of the research aim into consideration, a qualitative approach was chosen. Fourteen qualitative interviews with experts from the tourism and industry sectors and organizations linked with asylum seekers were conducted; the interviewees were chosen by purposeful sampling, according to knowledge and diversity criteria. GABEK was used as a qualitative research strategy, which involves theories of a phenomenological and linguistic nature. This method allows for a more holistic approach to the complex nature of the topic through the collection of perceptions resulting from open qualitative interviews and a keyword-based analysis.

Findings

The paper presents a model for an extended hospitality approach, as hospitality should not be limited to its connection with tourism matters. Refugees as well as tourists rely on the friendliness and the welcoming nature (hereafter: “welcome culture”) of a host country. The tourism industry can stand to improve its unconditional hospitality toward refugees — the comprehension and understanding of different cultures and values is an important aspect of welcoming new arrivals in the local surroundings, be they tourists, migrants or refugees.

Research limitations/implications

As stated above, a qualitative research approach was chosen with the intent to open the research field toward an extended hospitality approach. Therefore, future research must focus on testing the results for application in a more general context. The study was also limited insofar as the conduction of research took place in Bavaria alone.

Practical implications

As stated above, a qualitative research approach was chosen with the intent to open the research field toward an extended hospitality approach. Therefore, future research must focus on testing the results for application in a more general context. The study was also limited insofar as the conduction of research took place in Bavaria alone.

Originality/value

This paper combines different access points to hospitality in a new form.
Connecting curriculum, capabilities and careers
Authors: Thomas Ian , Depasquale James
Published: October 2016

Purpose

The reported research aims to examine the extent to which sustainability capabilities have been delivered by a specific example of Education for Sustainability (EfS) and Education for Sustainable Development (ESD), and how important the capabilities have been in the workplace.

Design/methodology/approach

Students who participated in an undergraduate internationally based research project were electronically surveyed. Questions sought responses related to demographics, the relevance of five “sustainability competencies” to the participant’s employment, the degree to which the five competencies had been developed within the students’ project and capabilities participants felt were important to their careers.

Findings

Clearly supported was the relevance of all five sustainability competencies, especially that of “interpersonal competence”.

Practical implications

A problem-based learning (PBL) design guided the students’ project and the findings indicate that these designs can be effective in delivering the five capabilities discussed. Interpersonal capability appears to be strongly developed, probably because PBL typically involves teamwork, often across disciplines. Nonetheless, those running these PBL-based subjects could note that careful design may be needed to ensure the development of systems thinking, anticipatory and normative capabilities. Also, the five competencies provide a reasonably good guide for what is important in the workplace and for designing learning experiences.

Originality/value

Clarification of competencies valued in the workplace provides guidance for the design of higher education curricular so that graduates become effective sustainability professionals.