bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide analysis of cell-gene interactions
Authors: Cardinale S.
Published: March 2017

The study presents an analysis of how different cellular functions link cell size to the expression of synthetic genes inE. coli. The Size-Expression interaction was mapped with a two-gene genetic probe across 3800 single-gene deletion strains. Through regression analysis, expression-specific effects and gene-specific effects were derived from size effects and generic expression effects, respectively. The entire compendium of cell functions broadly mapped to four systems of distinct primary influence on the Size-Expression map. Specifically, membrane structural components primarily affected size, whereas protein and RNA stability primarily affected gene expression. In addition, major Size-Expression shifts showed no substantial gene-specific effects unless they were mediated by key components of the protein synthesis apparatus.

Subject Category:Synthetic Biology
Seasonal influenza circulation patterns and projections for 2017-2018
Authors: Bedford Trevor , Neher Richard A.
Published: March 2017

This is not meant as a comprehensive report of recent influenza evolution, but is instead intended as particular observations that may be of relevance. Please also note that observed patterns reflect the GISAID database and may not be entirely representative of underlying dynamics. All analyses are based on the nextflu pipeline [1] with continual updates posted tonextflu.org. We arrive at the following results:

H3N2

In H3N2, clade 3c2.a has continued to diversify genetically with complicated and rapid dynamics of different subclades. This diversification is not reflected in serological data that shows only minor to moderate antigenic evolution. Nevertheless, the highly parallel mutation patterns and the rapid rise and fall of clades suggests competitive dynamics of phenotypically distinct viruses.

H1N1pdm

Very few H1N1pdm viruses have been observed in recent months. The dominant clade continues to be 6b.1 and there is little amino acid sequence variation within HA. The only notable subclade that has been growing recently is the clade bearing HA1:R205K/S183P. This clade is dominated by North American viruses and we see no evidence that this clade has a particular competitive advantage.

B/Vic

Clade 1A has continued to dominate and mutation 117V has all but taken over the global population. The rise of this mutation was fairly gradual and we have no evidence that it is associated with antigenic change or other benefit to the virus.

B/Yam

Clade 3 has continued to dominate. Within clade 3, a clade with mutation HA1:251V is globally at frequency of about 80% throughout 2016. Within this clade, mutation 211R is at 25% frequency. In addition, a clade without prominent amino acid mutations has been rising throughout 2016.
Large-scale simultaneous measurement of epitopes and transcriptomes in single cells
Authors: Stoeckius Marlon , Hafemeister Christoph , Stephenson William , Houck-Loomis Brian , Chattopadhyay Pratip K. , Swerdlow Harold , Satija Rahul , Smibert Peter
Published: March 2017

Recent high-throughput single-cell sequencing approaches have been transformative for understanding complex cell populations, but are unable to provide additional phenotypic information, such as protein levels of cell-surface markers. Using oligonucleotide-labeled antibodies, we integrate measurements of cellular proteins and transcriptomes into an efficient, sequencing-based readout of single cells. This method is compatible with existing single-cell sequencing approaches and will readily scale as the throughput of these methods increase.
The Neural Basis of Motivational Influences on Cognitive Control
Authors: Parro Cameron , Dixon Matthew L , Christoff Kalina
Published: March 2017

Cognitive control mechanisms support the deliberate regulation of thought and behavior based on current goals. Recent work suggests that motivational incentives improve cognitive control, and has begun to elucidate the brain regions that may support this effect. Here, we conducted a quantitative meta-analysis of neuroimaging studies of motivated cognitive control using activation likelihood estimation (ALE) and Neurosynth in order to delineate the brain regions that are consistently activated across studies. The analysis included functional neuroimaging studies that investigated changes in brain activation during cognitive control tasks when reward incentives were present versus absent. The ALE analysis revealed consistent recruitment in regions associated with the frontoparietal control network including the inferior frontal sulcus (IFS) and intraparietal sulcus (IPS), as well as consistent recruitment in regions associated with the salience network including the anterior insula and anterior mid-cingulate cortex (aMCC). A large-scale exploratory meta-analysis using Neurosynth replicated the ALE results, and also identified the caudate nucleus, nucleus accumbens, medial thalamus, inferior frontal junction/premotor cortex (IFJ/PMC), and hippocampus. Finally, we conducted separate ALE analyses to compare recruitment during cue and target periods, which tap into proactive engagement of rule-outcome associations, and the mobilization of appropriate viscero-motor states to execute a response, respectively. We found that largely distinct sets of brain regions are recruited during cue and target periods. Altogether, these findings suggest that flexible interactions between frontoparietal, salience, and dopaminergic midbrain-striatal networks may allow control demands to be precisely tailored based on expected value.
Distinct projection patterns of different classes of layer 2 principal neurons in the olfactory cortex
Authors: Mazo Camille , Grimaud Julien , Murthy Venkatesh N. , Lau C. Geoffrey
Published: March 2017

Processing of olfactory information in the anterior piriform cortex (APC) is widely thought to be non-topographic due to distributed projections from the olfactory bulb (OB). Layer 2 principal neurons in the APC can be divided into 2 subtypes: semilunar (SL) and superficial pyramidal (SP) cells. Although it is known that SL and SP cells receive differential inputs from the OB, little is known about their projection pattern to downstream structures, such as the posterior piriform cortex (PPC). Here we examined feedforward and feedback axonal projections of SL and SP cells using a combination of mouse genetics, and retrograde labeling. Retrograde tracing from the OB or PPC showed that the APC projects to these higher and lower brain regions mainly through layer 2b cells, while dual-labeling revealed a sizeable fraction of cells extending collaterals to both target regions. Furthermore, a transgenic mouse line specifically labeling SL cells showed that they send profuse axonal projections to olfactory cortical areas, but not to the OB. These findings support a model in which information flow from SL to SP cells and back to the OB forms a hierarchical feedback circuit whereas the two cell types process recurrent and feedforward information in a parallel manner.
Cooperative nucleotide binding in Hsp90 and the underlying mechanisms
Authors: Wortmann Philipp , Goötz Markus , Hugel Thorsten
Published: March 2017

The function of the molecular chaperone Hsp90 depends on large conformational changes, rearrangement of local motifs, as well as the binding and hydrolysis of ATP. The complexity of the Hsp90 system impedes the detailed investigation of their interplay using standard methods. By the application of three-color single molecule FRET to Hsp90 and a reporter nucleotide, we directly observe cooperativity between the two nucleotide binding pockets in the protein dimer. Through allocating the microscopic states and extracting their kinetics, we identify the mechanisms underlying the cooperativity. Surprisingly, nucleotide binding affects several state transitions, which demonstrates the complexity of cooperativity in protein systems. The co-chaperone Aha1, known to accelerate Hsp90's ATPase activity, adds another layer of complexity by affecting transitions in a nucleotide-dependent and -independent manner.
Redetermination of the crystal structure of dimethylbis[2,4-pentanedionato(1−)-κ2O2,O4]tin(IV)
Authors: Reuter Hans , Reichelt Martin
Published: March 2017

The redetermination of the title compound, [Sn(CH3)2(C5H7O2)2] or SnMe2(acac)2, from CCD data recorded at 100 K basically confirms the previous study based on integrated film data recorded at room temperature [Miller & Schlemper (1972).Inorg. Chem.12, 677–681], but reveals a remarkable shrinkage of theaaxis [7.12 (1) > 6.7694 (4) Å]. The molecule belongs to point groupCiwith the SnIVatom on a centre of inversion. The SnIVatom shows a slightly distorted octahedral coordination sphere with the methyl groups intranspositions and a Sn—C bond length of 2.115 (2) Å which may serve as a standard value for an Sn—CH3bond of an octahedrally coordinated SnIVatom. The Sn—O bonds involving the two carbonyl groups of the acetylacetonate ligand are of equal length [2.180 (1) and 2.183 (1) Å], as are the C=O [1.273 (1) and 1.274 (1) Å] and C—C bond lengths [1.393 (2) and 1.400 (2) Å]. The acetylacetonate ligand deviates considerably from planarity, with a dihedral angle of 5.57 (9)° between the least-squares planes of the two acetone moieties. The four O atoms of the two symmetry-related acetylacetonate ligands are arranged in a nearly quadratic rectangle. Weak C—H...O interactions consolidate the crystal packing.
Visualising “junkies” and “meth heads” – a visual analysis of the persistent negative reputation of heroin and meth users
Authors: Scheibe Lisa
Published: March 2017

Purpose

The purpose of this paper is to explore the persistent negative reputation of two particular types of drug users, the so-called heroin junkie and the meth head. The visual portrayal of both kinds of users in the media has been consistent in the last decades. Inspired by films and anti-drug campaigns, stereotypical ideas about heroin and meth users dominate the visual portrayals. Existing research has already shown that this standardised picture is not applicable uniformly. Nevertheless, the important role of the visual element for constituting beliefs about drug use and users is lacking in the current drug research. Therefore, this work focusses on the visual element of the drug discourse.

Design/methodology/approach

On the basis of the British movieTrainspotting, and the two American campaigns Faces of Meth and Montana Meth Project the visual representation of heroin and meth users is discussed. With the help of a visual discourse analysis this research discloses the particularities of every image.

Findings

The current visual portrayal of heroin and meth users stigmatises them as deviant and unhealthy. This single-sided perspective labels all users, without acknowledging different patterns of use. Counterexamples obtained through existing research do not support this uniformly applied stereotypical representation. The persistent negative reputation mediates inaccurate knowledge about drug use, with harmful consequences for the users, and harm-reduction work.

Originality/value

Drug research has not been focussing enough on the visual element of the drug discourse. This research intends to close the existing gap and emphasise the possible harmful consequences produced by such visuality.
The effects of a lean transition on process times, patients and employees
Authors: Simons Pascale , Backes Huub , Bergs Jochen , Emans Davy , Johannesma Madelon , Jacobs Maria , Marneffe Wim , Vandijck Dominique
Published: March 2017

Purpose

Treatment delays must be avoided, especially in oncology, to assure sustainable high-quality health care and increase the odds of survival. The purpose of this paper is to hypothesize that waiting times would decrease and patients and employees would benefit, when specific lean interventions are incorporated in an organizational improvement approach.

Design/methodology/approach

In 2013, 15 lean interventions were initiated to improve flow in a single radiotherapy institute. Process/waiting times, patient satisfaction, safety, employee satisfaction, and absenteeism were evaluated using a mixed methods methodology (2010-2014). Data from databases, surveys, and interviews were analyzed by time series analysis, χ2, multi-level regression, and t-tests.

Findings

Median waiting/process times improved from 20.2 days in 2012 to 16.3 days in 2014 (p<0.001). The percentage of palliative patients for which waiting times had exceeded Dutch national norms (ten days) improved from 35 (six months in 2012: pre-intervention) to 16 percent (six months in 2013-2014: post-intervention; p<0.01), and the percentage exceeding national objectives (seven days) from 22 to 17 percent (p=0.44). For curative patients, exceeding of norms (28 days) improved from 17 (2012) to 8 percent (2013-2014: p=0.05), and for the objectives (21 days) from 18 to 10 percent (p<0.01). Reported safety incidents decreased 47 percent from 2009 to 2014, whereas safety culture, awareness, and intention to solve problems improved. Employee satisfaction improved slightly, and absenteeism decreased from 4.6 (2010) to 2.7 percent (2014; p<0.001).

Originality/value

Combining specific lean interventions with an organizational improvement approach improved waiting times, patient safety, employee satisfaction, and absenteeism on the short term. Continuing evaluation of effects should study the improvements sustainability.
Observational skills: eye-openers for innovation
Authors: Gilmore James
Published: March 2017

Purpose

Observational tools offer the means to introduce new techniques into an organization, to skill individuals in new and different ways of seeing innovation possibilities.

Design/methodology/approach

The Six Looking Glasses method is a tool designed to improve observational skills, using a distinct set of “lenses.” The tool offers a set of perspectives for making insights about the operating environment, which employed repeatedly can enhance observational skills.

Findings

A key lesson to be learned from these three pivotal points in Starbucks’ history is: recognize that observation is the fountainhead from which any and all innovation takes place.

Practical implications

Much talk of innovation, with too little skilled observation, usually remains just talk.””

Originality/value

All strategy and leadership depends on seeing the world as it truly is and imagining its most opportune possibilities and its serious risks. To innovate in this operating environment – its broader culture, its immediate business circumstances and those within its own company – requires the very best observational skills. The Six Looking Glasses provide a good start toward fulfilling that need.
Topics in histopathology of sweat gland and sebaceous neoplasms
Authors: Ansai Shin‐ichi
Published: March 2017

This article reviews several topics regarding sweat gland and sebaceous neoplasms. First, the clinicopathological characteristics of poroid neoplasms are summarized. It was recently reported that one‐fourth of poroid neoplasms are composite tumors and one‐fourth are apocrine type lesions. Recent progress in the immunohistochemical diagnosis of sweat gland neoplasms is also reviewed. CD117 can help to distinguish sweat gland or sebaceous tumors from other non‐Merkel cell epithelial tumors of the skin. For immunohistochemical differential diagnosis between sweat gland carcinoma (SGC) other than primary cutanesous apocrine carcinoma and skin metastasis of breast carcinoma (SMBC), a panel of antibodies may be useful, including p63 (SGC+, SMBC−), CK5/6 (SGC+, SMBC−), podoplanin (SGC+, SMBC−) and mammaglobin (SGC−, SMBC+). Comparison of antibodies used for immunohistochemical diagnosis of sebaceous carcinoma (SC) suggests that adipophilin has the highest sensitivity and specificity. Some authors have found that immunostaining for survivin, androgen receptor and ZEB2/SIP1 has prognostic value for ocular SC, but not extraocular SC. In situ SC is rare, especially extraocular SC, but there have been several recent reports that actinic keratosis and Bowen's disease are the source of invasive SC. Finally, based on recent reports, classification of sebaceous neoplasms into three categories is proposed, which are sebaceoma (a benign neoplasm with well‐defined architecture and no atypia), borderline sebaceous neoplasm (low‐grade SC; an intermediate tumor with well‐defined architecture and nuclear atypia) and SC (a malignant tumor with invasive growth and evident nuclear atypia).
What is new in the histogenesis of granulomatous skin diseases?
Authors: Asai Jun
Published: March 2017

A granuloma is a form of inflammation, which predominantly consists of macrophages. It typically develops when the immune system attempts to enclose substances that are usually insoluble and cannot be eliminated to prevent the spread of these substances to the other body compartments. According to the source of the substances, granulomatous diseases can be divided into two groups: infectious and non‐infectious. The mechanisms of infectious granuloma formation have been widely investigated because of its easy reproducibility in experimental models, both in vivo and in vitro. On the contrary, mechanisms of non‐infectious granuloma formation have not been well investigated because of the difficulty to reproduce this formation in experimental models. In this article, we review our recent understanding of the histogenesis and pathogenesis of granuloma formation, confirmed from studies of infectious granulomas, and we present potential hypotheses of the histogenesis and pathogenesis of non‐infectious granulomas based on clinical investigations.
Advances in histopathological diagnosis of keratoacanthoma
Authors: Takai Toshihiro
Published: March 2017

Keratoacanthoma is a common epithelial lesion, but its nature is controversial. Although a distinct crateriform appearance is a hallmark of keratoacanthoma, other benign or malignant skin lesions may show a similar architecture. Moreover, as lesions diagnosed as conventional keratoacanthoma may show malignant behavior, some authors consider keratoacanthoma to be a variant of squamous cell carcinoma, whereas others consider it as a distinct self‐resolving squamous proliferative lesion. The controversy seems to originate from the diverse behavior of keratoacanthoma‐like epithelial lesions. However, a reproducible histopathological classification criterion has been recently proposed in the diagnosis of keratoacanthoma‐like epithelial lesions, and its validity is supported by several reports that deal with the natural course or molecular aspects of these lesions. This article attempts to provide a comprehensive review on recent insights and advances in the histopathological diagnosis of keratoacanthoma or related lesions, as well as summary of related published works.
Nail neoplasms
Authors: Park Ji‐Hye , Lee Dong‐Youn , Kim Noori
Published: March 2017

Nail neoplasms include all tumors occurring in the nail or periungual apparatus tissue. While some nail tumors can be similar to tumors located on the skin, others are unique. Both benign and malignant lesions can affect the nail apparatus. In particular, early malignant tumors like melanoma and squamous cell carcinoma can present similarly to onychomycosis or benign melanonychia and frequently missed by clinicians. Therefore, physicians should be aware of nail structures and the characteristics of nail tumors. Our review covers the normal nail structure and the most common nail tumors from benign to malignant.
Immunoglobulin G4‐related disease and its skin manifestations
Authors: Takayama Ryoko , Ueno Takashi , Saeki Hidehisa
Published: March 2017

Immunoglobulin G4‐related disease (IgG4‐RD) is a systemic inflammatory condition characterized by tissue infiltration with IgG4+plasma cells and an elevated serum IgG4 level. It usually occurs in middle‐aged or older patients, with male predominance, and can involve multiple organs synchronously or metachronously. Patients with IgG4‐RDgenerally respond to steroid therapy. IgG4‐related skin lesions are typically erythematous and itchy plaques, subcutaneous nodules, or papules like prurigo nodularis located on the head and neck areas. Histologically, lymphoplasmacytic infiltrates with abundant IgG4+ plasma cells are seen in the dermis and/or subcutaneous tissue. The skin condition of IgG4‐RDdoes not necessarily exhibit infiltration of IgG4+plasma cells, which is a prerequisite for IgG4‐related skin disease, but such skin lesions without infiltration by IgG4+plasma cells can be included in the skin manifestations of IgG4‐RD.
Granular cell differentiation: A review of the published work
Authors: Cardis Michael A. , Ni Jonathan , Bhawan Jag
Published: March 2017

Since the initial description of the granular cell tumor in 1926, numerous other neoplasms, both benign and malignant, have been described to exhibit granular cell change. In most cases, diagnosis remains straightforward via recognition of retained histopathological morphology of the archetypal tumor, despite the presence of focal granular appearance. However, tumors with granular cell differentiation can present a diagnostic challenge either by mimicking alternative diagnoses, or by failing to exhibit architectural clues of the primary entity, thus requiring an immunohistochemical work‐up. In light of this, it is important to be aware of the various entities that have been reported to exhibit granular cell morphology. In this review such tumors are discussed along with pertinent clinical and histopathological features.
Treatment patterns of postherpetic neuralgia patients before and after the launch of pregabalin and its effect on medical costs: Analysis of Japanese claims data provided by Japan Medical Data Center
Authors: Honda Mariko , Murata Tatsunori , Ebata Nozomi , Fujii Koichi , Ogawa Setsuro
Published: March 2017

Except for neurotrophin, no drug had an indication for postherpetic neuralgia (PHN) in Japan prior to pregabalin approval. This approval might have changed PHN treatment patterns. This study aimed to compare PHN treatment patterns and medical costs between patients who started treatment before and after pregabalin approval. Japanese claims data were used to identify patients aged 18 years or more with PHN, postherpetic trigeminal neuralgia or postherpetic polyneuropathy who were initiated on their first PHN‐associated prescription through May 2010 (before approval) or from June 2010 (after approval). From these claims, 6‐month treatment patterns from first prescription were compared for the periods before and after approval. These patterns included pain‐related medications and the frequency of pain‐relief procedures. All‐cause and pain‐related medical costs were also compared for these periods. The number of PHN patients who were initiated on treatment before and after approval were 107 (mean age, 47.4 ± 13.0 years) and 505 (45.9 ± 13.0), respectively. Post‐approval, significant reductions were observed for prescription of non‐steroidal anti‐inflammatory drugs, tricyclic antidepressants and neurotrophin relative to before approval. Excluding pregabalin acquisition costs, mean costs per patient for medications associated with PHN for 6 months from the first prescription were significantly lower after approval, ¥2882 vs ¥4185. Total medical costs were similar in both periods. Approval of pregabalin appeared to result in a treatment paradigm toward use of an approved therapy with demonstrated efficacy.
Making ‘Critical Performativity’ Concrete: Sumantra Ghoshal and Linkages between the Mainstream and the Critical
Authors: Edwards Paul K.
Published: March 2017

Critical performativity (CP) advocates direct engagement with managerial practice to promote social change while being subversive of a focus on efficiency. Its critique of efficiency needs to be reconsidered: there can be a common real interest in efficiency, and addressing efficiency does not entail an uncritical acceptance of a managerial agenda. Taking this step allows CP to engage with more conventional views. Two kinds of such views can be distinguished, the unitarist, which stresses common interests, and the pluralist, which allows for diverging interests. The work of the mainstream scholar Sumantra Ghoshal illustrates an effort to move beyond unitarism towards a more pluralist position. He developed a ‘good theory of management’ that aimed to address efficiency, but also the quality of jobs. Appraisal of this theory from the perspective of real interests points to limitations, but also ways in which it can be given a critical edge. The result is an analysis that advances that strand of CP that seeks to make specific interventions in concrete organizational practice.
Taking Abortion Rights Seriously: Whole Woman's Health v Hellerstedt
Authors: Greasley Kate
Published: March 2017

In Whole Woman's Health v Hellerstedt the Supreme Court of the United States passed down its most important decision on abortion for just under a decade. By a majority of 5‐3, the Court ruled that two provisions in a Texas law regulating abortion on grounds of women's health were constitutionally invalid, placing a ‘substantial obstacle’ in the way of women seeking to exercise their right to abortion. This comment delineates the key ways in which the Court's application of the standard of constitutional review under Planned Parenthood v Casey (1992) to the Texas provisions marks a landmark development for the protection of the constitutional right to abortion established in Roe v Wade, not the least by making clear that state abortion regulations which cite ‘women's health’ justifications should not pass constitutional review where those justifications lack a credible factual basis.
Analysis of the preferential mechanisms of denaturation of whey protein variants as a function of temperature and pH for the development of an optical sensor
Authors: Taterka Heather , Castillo Manuel
Published: March 2017

A pH‐ and temperature‐dependent study was conducted using reconstituted low‐heat skim milk at pH 6.3, 6.7 and 7.1 heated for 10 min at 80 and 90 °C to evaluate the relationship between bound and aggregate whey protein and optical light backscatter response. Significant correlations were found between casein micelle particle size and bound whey protein, and light backscatter correlations existed with both bound and aggregate whey protein, thus optical light backscatter may be useful to determine both whey protein attachment to the casein micelle and the formation of whey protein aggregates.
Meaningful Use and Hospital Performance on Post‐Acute Utilization Indicators
Authors: Brice Yanick N. , Joynt Karen E. , Tompkins Christopher P. , Ritter Grant A.
Published: March 2017

Objectives

To examine trends in hospital post‐acute utilization indicators and to determine whether improvement in these indicators is associated with attesting to meaningful use (MU).

Data Sources

Medicare claims‐based, repeated measures on 30‐day hospital‐wide all‐cause readmission and emergency department (ED) utilization rates for 160 short‐stay hospitals (2009–2012); Medicare EHR Incentive Program Payments files (2011–2012); and other hospital and market data.

Study Design

Interrupted time series with concurrent comparison group.

Principal Findings

Propensity score‐weighted multilevel models for change demonstrate that 30‐day readmission rates (unadjusted) fell from 13.4 percent in 2009 to 12.1 percent in 2012. Similarly, 30‐day ED utilization declined from 18.9 percent to 17.3 percent during the same period. However, MU and non‐MU hospitals were indistinguishable vis‐à‐vis performance. Controlling for hospital and market characteristics, MU was unrelated to 30‐day readmission. In contrast, 30‐day ED utilization deteriorated.

Conclusions

Hospitals with MU Stage 1 designation did not show significantly higher improvement on post‐acute utilization compared to their counterparts without. To achieve gains in quality and safety, potentially associated with EHRs, and to advance care coordination and patient engagement, the regulators should strengthen accountability by linking comprehensive, outcomes‐based performance measures to specific MU objectives.
Sex and age discrepancy of HbA1c and fetal hemoglobin determined by HPLC in a large Chinese Han population
Authors: Hu Jihong , Gao Jun , Li Jianbo
Published: March 2017

Background

It is accepted that HbA1c is an effective indicator to evaluate glycemic control. Fetal hemoglobin (HbF) is seldom measured because traditional detection is inconvenient. In this regard, there may be an advantage in using HPLC autoanalysis of HbA1c as a surrogate method for HbF detection. The aim of the present study was to explore the distribution of HbA1c and HbF in a large Chinese Han population.

Methods

In all, 70 553 blood samples were collected between January 2012 and June 2016. Study subjects were inpatients undergoing routine medical care and were divided into four groups based on age: Group A, 20–39 years; Group B, 40–59 years; Group C, 60–79 years; and Group D, ≥80 years. Blood HbA1c and HbF concentrations were measured by HPLC using a Tosho Bioscience (Tokyo, Japan) G8 analyzer.

Results

There was a positive association between HbA1c and age, and a negative association between HbF and age. The concentration range of HbF was narrow and HbF concentrations were significantly higher in females than males, regardless of age (median 0.7% vs 0.6%, respectively; P < 0.0001). There was a low degree of correlation between HbF and HbA1c (r = 0.181, P < 0.0001). Although median HbA1c levels were higher in male than female subjects aged 20–59 years (5.5% vs 5.4%, respectively, in Group A; 5.9% vs 5.8%, respectively in Group B), in the 60–79 years group, HbA1c levels were lower in males than females (6.1% vs 6.2%, respectively; P < 0.0001).

Conclusions

The data suggest that sex and age should be considered in clinical interpretation of HbA1c.
A review of implantable cardioverter defibrillator failures during radiation therapy in three Sydney hospitals
Authors: Hudson Felicity J , Ryan Elaine A
Published: March 2017

Introduction

In recent years, using radiation energies greater than 10 MV in patients with implantable cardioverter defibrillators (ICDs) has been contra‐indicated due to the risk of a power on reset (POR) occurring. The ICD is often greater than 30 cm from the treatment field and subject to scatter radiation only. The aim of this study was to use recent patient cases to verify published failure rates and treatment recommendations.

Method

Five patients with ICDs who experienced a device malfunction during radiation therapy treatments were identified in three Sydney hospitals between 2008 and 2012. The types of treatments delivered during these events were assessed. Further assessment of all ICD patients at one Sydney hospital during this time was carried out to assess the rate of ICD failure during high energy treatments using 18 MV.

Results

All ICDs that suffered malfunctions were exposed to scatter radiation only. All were exposed to partial or exclusive irradiation using 18 MV photons. Accumulated doses to the ICDs were estimated to be well below accepted dose limits found in literature. One centre reported a 22.2% rate of POR during exposure to 18 MV radiation therapy during this time frame.

Conclusions

Where possible, radiation therapy using energies greater than 10 MV should be avoided for ICD patients. While the use of these energies carries a risk of failure, it must be weighed against potential benefit to the patient requiring treatment if no alternatives are available. Stringent monitoring of these patients, including regular cardiac device checks and ECG monitoring is recommended if treatment is to proceed with energies greater than 10 MV.
Fly Fishing as Religion: Literature as a Form of Public Consciousness
Authors: Fife Wayne
Published: March 2017

Focusing on the question of how to be in the world, ontological religion often comes in forms that look very little like our standard expectations for religious institutions. Intuitive, experiential, and often taking a mystical bent, this direct kind of religious practice nevertheless needs guideposts for its participants. The literature of fly fishing serves as one such guidepost, offering a forum for a kind of spiritual public consciousness that can be drawn upon at will by those who seek it. This article explores the parallels between fly fishing, its literature, and the kinds of spiritual statements that are regularly found among religious practitioners who are most concerned with questions about how to live. I am arguing here that fly fishing literature forms an implicit repository for a religious form of consciousness and a religious way of being in the world.
Conceptual Systems Theory: A Neglected Perspective for the Anthropology of Consciousness
Authors: Laughlin Charles D.
Published: March 2017

As anthropology becomes more interested in consciousness and its numerous states, and with a slowly increasing appeal to neuroscience for insights and explanations of consciousness, there is an understandable interest in the components of consciousness and how they combine into alternative states in different sociocultural settings. One of those components should be the complexity of information processing producing the knowing aspect of consciousness. The author introduces an approach to this aspect in the form of conceptual systems theory (CST), a neo‐Piagetian model of cognitive development, which has been used to good effect to explain information processing in social situations but heretofore neglected by anthropologists. The neuroanthropological underpinnings of CST are discussed, as is the range of potential applications to ethnological and ethnographic problems.
Fatalism, the Self, Intentionality, and Signs of Ill Portent in Quintana Roo, Mexico
Authors: Callahan Robey
Published: March 2017

Severe illnesses and sudden deaths are all too common occurrences in the lives of the Maya of the Yucatán Peninsula, so it is perhaps no surprise that, as a people, they tend to be rather fatalistic. Maya fatalism finds one of its most prominent expressions in the tamax chi'—a type of omen that speaks of impending suffering, usually of a terminal nature, for a member of one's close family. In terms of components and mechanics, however, a tamax chi' is actually something more than a mere kin‐doom sign; it forms part of a hybrid, if somewhat limited, cultural self, one of whose key functions seems to be helping people cope. Through recourse to Goffman () speaker roles and Danziger's (2013) hearer roles and through analysis of data derived from years of research in the region, I also demonstrate its relevance to more general understandings of self and intentionality.
Assessment of continuous pain in newborns admitted to NICUs in 18 European countries
Authors: Anand Kanwaljeet J. S. , Eriksson Mats , Boyle Elaine M. , Avila‐Alvarez Alejandro , Andersen Randi Dovland , Sarafidis Kosmas , Polkki Tarja , Matos Cristina , Lago Paola , Papadouri Thalia , Attard‐Montalto Simon , Ilmoja Mari‐Liis , Simons Sinno , Tameliene Rasa , van Overmeire Bart , Berger Angelika , Dobrzanska Anna , Schroth Michael , Bergqvist Lena , Courtois Emilie , Rousseau Jessica , Carbajal Ricardo ,   the EUROPAIN survey working group of the NeoOpioid Consortium
Published: March 2017

Aim

Continuous pain occurs routinely, even after invasive procedures, or inflammation and surgery, but clinical practices associated with assessments of continuous pain remain unknown.

Methods

A prospective cohort study in 243 neonatal intensive care units (NICUs) from 18 European countries recorded the frequency of pain assessments, use of mechanical ventilation, sedation, analgesia or neuromuscular blockade for each neonate for up to 28 days after NICU admission.

Results

Only 2113 of 6648 (31.8%) of neonates received assessments of continuous pain, occurring variably among tracheal ventilation (TrV, 46.0%), noninvasive ventilation (NiV, 35.0%) and no ventilation (NoV, 20.1%) groups (p < 0.001). Daily assessments for continuous pain occurred in only 10.4% of all neonates (TrV: 14.0%, NiV: 10.7%, NoV: 7.6%; p < 0.001). More frequent assessments of continuous pain occurred in NICUs with pain guidelines, nursing champions and surgical admissions (all p < 0.01), and for newborns <32 weeks gestational age, those requiring ventilation, or opioids, sedatives‐hypnotics, general anaesthetics (O–SH–GA) (all p < 0.001), or surgery (p = 0.028). Use of O–SH–GA drugs increased the odds for pain assessment in the TrV (OR:1.60, p < 0.001) and NiV groups (OR:1.40, p < 0.001).

Conclusion

Assessments of continuous pain occurred in less than one‐third of NICU admissions and daily in only 10% of neonates. NICU clinical practices should consider including routine assessments of continuous pain in newborns.
Editorial: ONO‐2952 in irritable bowel syndrome with diarrhoea – authors’ reply
Authors: Whitehead W. E. , Duffy K. , Sharpe J. , Nabata T. , Bruce M.
Published: March 2017

Linked Content

This article should be linked to Nee and Lembo, and W. E. Whitehead et al papers. To view these articles visit https://doi.org/10.1111/apt.13920 and https://doi.org/10.1111/apt.13839.
Letter: changes in FIB‐4 cut‐off points for viral hepatitis – authors’ reply
Authors: Surana P. , Takyar V. , Koh C.
Published: March 2017

Linked Content

This article is linked to Kayadibi and Takyar et al papers. To view these articles visit https://doi.org/10.1111/apt.13956 and https://doi.org/10.1111/apt.13834.
Editorial: metabolic adaptation of colonic microbiota to galactooligosaccharides – good news for prebiotics in irritable bowel syndrome?
Authors: Staudacher H. M. , Cox S. R.
Published: March 2017

Linked Content

This article is linked to Mego et al and Manichanh and Accarino papers. To view this article visit https://doi.org/10.1111/apt.13931.
Bayesian Population Finding with Biomarkers in a Randomized Clinical Trial
Authors: Morita Satoshi , Müller Peter
Published: March 2017

The identification of good predictive biomarkers allows investigators to optimize the target population for a new treatment. We propose a novel utility-based Bayesian population finding (BaPoFi) method to analyze data from a randomized clinical trial with the aim of finding a sensitive patient population. Our approach is based on casting the population finding process as a formal decision problem together with a flexible probability model, Bayesian additive regression trees (BART), to summarize observed data. The proposed method evaluates enhanced treatment effects in patient subpopulations based on counter-factual modeling of responses to new treatment and control for each patient. In extensive simulation studies, we examine the operating characteristics of the proposed method. We compare with a Bayesian regression-based method that implements shrinkage estimates of subgroup-specific treatment effects. For illustration, we apply the proposed method to data from a randomized clinical trial.
Might Corporate Social Responsibility Hollow Out Support for Public Assistance in Europe?
Authors: Burgoon Brian , Fransen Luc
Published: March 2017

This article explores whether private regulatory activity to promote labour and social standards might hollow out traditional public regulations to provide welfare and labour protection at home and abroad. Such exploration has hitherto been frustrated by empirical limitations of measures of private regulatory activity and its implications for public regulation. The present article extends those limits by focusing on how new measures of labour‐related private regulation affect attitudes in 27 European polities towards welfare redistribution and for foreign assistance. Our analysis suggests that private‐regulatory CSR promoting labour and social standards may directly and indirectly diminish public support for domestic welfare redistribution, but appears to have little effect on support for foreign aid. We see, hence, possible crowding‐out only with respect to domestic, not international, assistance.
The anti‐hepatic fibrosis effects of dihydrotanshinone I are mediated by disrupting the yes‐associated protein and transcriptional enhancer factor D2 complex and stimulating autophagy
Authors: Ge Maoxu , Liu Hong , Zhang Yixuan , Li Naren , Zhao Shuangshuang , Zhao Wuli , Zhen Yongzhan , Yu Jianzhong , He Hongwei , Shao Rong‐guang
Published: March 2017

Background and Purpose

Dihydrotanshinone I (DHI), a lipophilic component of traditional Chinese medicine Salvia miltiorrhiza Bunge, has various therapeutic effects. We investigated the anti‐fibrotic effect of DHI and its underlying mechanisms in vitro and in vivo.

Experimental Approach

Rats subjected to bile duct ligation (BDL) were treated with DHI (25 mg·kg−1·day−1, i.p.) for 14 days. Serum biochemical and liver tissue morphological analyses were performed. The human hepatic stellate cell line LX‐2 served as a liver fibrosis model in vitro. Liver fibrogenic genes, yes‐associated protein (YAP) downstream genes and autophagy markers were examined using western blot and real‐time PCR analyses. Similar analyses were done in rat primary hepatic stellate cells (pHSCs). Autophagy flux was assessed by immunofluorescence.

Key Results

In BDL rats, DHI administration attenuated liver necrosis, bile duct proliferation and collagen accumulation and reduced the expression of genes associated with fibrogenesis, including Tgfb1, Mmp‐2, Acta2 and Col1a1. DHI (1, 5, 10 μmol·L−1) time‐ and dose‐dependently suppressed the protein level of COL1A1, TGFβ1 and α‐SMA in LX‐2 cells and rat pHSCs. Furthermore, DHI blocked the nuclear translocation of YAP, which inhibited the YAP/TEAD2 interaction and its downstream fibrogenic genes, connective tissue growth factor, SOX4 and survivin. This stimulated autophagic flux and accelerated the degradation of liver collagen.

Conclusions and Implications

DHI exerts anti‐fibrotic effects in BDL rats, LX‐2 cells and rat pHSCs by inhibiting the YAP and TEAD2 complex and stimulating autophagy. These findings indicate that DHI may be a potential therapeutic for the treatment of liver fibrosis.
Randomized phase II study of nab‐paclitaxel as first‐line chemotherapy in patients with HER2‐negative metastatic breast cancer
Authors: Tamura Kenji , Inoue Kenichi , Masuda Norikazu , Takao Shintaro , Kashiwaba Masahiro , Tokuda Yutaka , Iwata Hiroji , Yamamoto Naohito , Aogi Kenjiro , Saeki Toshiaki , Nakayama Takahiro , Sato Nobuaki , Toyama Tatsuya , Ishida Takanori , Arioka Hitoshi , Saito Mitsue , Ohno Shinji , Yamauchi Hideko , Yamada Kimito , Watanabe Junichiro , Ishiguro Hiroshi , Fujiwara Yasuhiro
Published: March 2017

Weekly administration of nanoparticle albumin‐bound paclitaxel (nab‐paclitaxel) has been shown to be a safe and effective treatment for metastatic breast cancer (MBC) in clinical studies. We conducted a multicenter, randomized, open‐label phase II study to compare the efficacy and safety of weekly nab‐paclitaxel and docetaxel in Japanese patients with human epidermal growth factor receptor 2‐negative MBC. The primary endpoint was progression‐free survival (PFS). Patients were randomized to receive nab‐paclitaxel (150 mg/m2 nab‐paclitaxel once per week for 3 of 4 weeks; n = 100) or docetaxel (75 mg/m2 docetaxel every 3 weeks; n = 100). The median PFS by independent radiologist assessment was 9.8 months (90% confidence interval [CI]: 8.5–11.2) for nab‐paclitaxel and 11.2 months (90% CI: 8.4–13.8) for docetaxel (hazard ratio: 1.25, P = 0.363), and the median overall survival was 42.4 months and 34.0 months, respectively. The overall response rate was 56.1% for nab‐paclitaxel and 52.5% for docetaxel. Adverse events in both treatment arms were similar to previous reports. Neutropenia was the most common adverse event in both arms, with 35.0% of patients in the nab‐paclitaxel arm and 89.0% in the docetaxel arm experiencing grade 4 neutropenia. Grade 3 peripheral sensory neuropathy occurred in 22.0% of patients in the nab‐paclitaxel and 5.0% in the docetaxel arm. In this study, although weekly nab‐paclitaxel 150 mg/m2 did not show superiority in PFS compared with docetaxel, efficacy outcomes were similar in patients treated with weekly nab‐paclitaxel and docetaxel.
Interferon-α coincides with suppressed levels of pentraxin-3 (PTX3) in systemic lupus erythematosus and regulates leucocyte PTX3 in vitro
Authors: Wirestam L , Enocsson H , Skogh T , Eloranta M L , Rönnblom L , Sjöwall C , Wetterö J
Published: March 2017

Dysfunctional elimination of cell debris, and the role of opsonins such as pentraxins, is of interest regarding systemic lupus erythematosus (SLE) pathogenesis. Interferon (IFN)-α is typically elevated during SLE flares, and inhibits hepatocyte production of the pentraxin ‘C-reactive protein’ (CRP), partly explaining the poor correlation between CRP levels and SLE disease activity. The extrahepatically produced ‘pentraxin 3’ (PTX3) shares waste disposal functions with CRP, but has not been studied extensively in SLE. We analysed serum PTX3 in SLE, and assessed its interference with IFN-α in vitro. Serum samples from 243 patients with SLE and 100 blood donors were analysed regarding PTX3. Patient sera were analysed for IFN-α, and genotyped for three PTX3 single nucleotide polymorphisms reported previously to associate with PTX3 levels. Stimulated PTX3 release was assessed in the presence or absence of IFN-α in blood donor neutrophils and peripheral blood mononuclear cells (PBMC). Serum PTX3 was 44% lower in patients with SLE compared to blood donors (P < 0·0001) and correlated with leucocyte variables. Patients with undetectable IFN-α had 29% higher median PTX3 level than patients with detectable IFN-α (P = 0·01). PTX3 production by PBMC was inhibited by IFN-α, whereas neutrophil degranulation of PTX3 was increased. No differences in PTX3 levels were observed between the SNPs. In conclusion, median serum PTX3 is lower in SLE (especially when IFN-α is detectable) compared to blood donors. In addition to its potential consumption during waste disposal, it is plausible that IFN-α also attenuates PTX3 by inhibiting synthesis by PBMC and/or exhausting PTX3 storage in neutrophil granules.
Human limbal neurospheres prevent photoreceptor cell death in a rat model of retinal degeneration
Authors: McLenachan Samuel , Zhang Dan , Hao Erwei , Zhang Ling , Chen Shang‐Chih , Chen Fred K
Published: March 2017

Background

The culture of retinal progenitors from an accessible adult stem cell source such as the limbus could provide a useful autologous source of retinal cell therapies. The human corneoscleral limbus contains multipotent stem cells that can be cultured as floating neurospheres. Previous work in rodents has demonstrated neuronal and photoreceptor differentiation from limbal neurosphere cultures. Here, this study has examined undifferentiated cultured adult human limbal neurospheres as donor cells for retinal cell therapies by transplantation into a rat model of retinal degeneration.

Methods

Gene expression in limbal neurospheres was examined by immunostaining and western blot. Human limbal neurospheres were transplanted into the subretinal space of Royal College of Surgeon's rats. Rats were monitored by optical coherence tomography for 6 weeks then processed for retinal histology.

Results

Human limbal neurospheres expressed the neural lineage markers, Nestin, sex determining region box‐2 and N‐cadherin, and the retinal transcription factors microphthalmia‐associated transcription factor, sex determining region box‐2 and orthodentical homeobox‐2. Human limbal neurospheres could be cultured to express NeuN, neurofilament and rhodopsin. Rats receiving saline or no injection underwent complete degeneration of the retinal outer nuclear layer after 3 weeks. In contrast, rats injected with human limbal neurospheres or retinal pigment epithelial cells maintained the outer nuclear layer for up to 6 weeks. Gene expression in transplanted limbal neurospheres was inconsistent with the production of mature retinal pigment epithelial or photoreceptor cells.

Conclusions

Human limbal neurospheres represent an accessible source of autologous donor cells for the treatment of retinal diseases.