bluuebunny/crossref_metadata_2025 huggingface dataset:
Single cell variations in expression of codominant alleles A and B on RBC of AB blood group individuals
Authors: Bajpai Anjali , Jonnalagadda Vidya , Sridevi Badanapuram , Mutthukotti Pathma , Jesudasan Rachel A
Published: October 2018

One of the key questions in biology is whether all cells of a “cell type” have more or less the same phenotype, especially with relation to non-imprinted autosomal loci. Recent studies point to differential allelic expression of autosomal genes being a prevalent phenomenon responsible to confer phenotypic variability at individual cell level. However, most studies have been carried out in actively transcribing cells. Here we display cellular mosaicism arising from differential allelic expression for the cell surface glycoprotein in the enucleated RBCs. We studied the expression of the A and B histo-blood group antigens encoded by the co-dominant alleles in individual RBCs using immunofluorescence. We assessed the relative levels of the co-dominant alleles IA and IB in 2512 RBC from 24 individuals with AB blood group using Cy3- and FITC- tagged antibodies. Quantification of individual fluorescence intensities from each cell and test of their normal distribution revealed that contrary to the general belief that all RBC in AB individuals express both antigens in comparable amounts, they segregated into 4 groups: showing normal distribution for both antigens, either antigen, and neither antigen; the deviation from normal distribution could not be correlated to maternal/paternal origin, thus appear to be stochastic. Surprisingly, very few people showed any correlation between the amounts of these two antigens on RBC. In fact, the ratio of antigen A to B in the entire set of samples spanned over 5 orders of magnitude. This variability in amount of the antigens A and/or B, combined with a lack of correlation between the amounts of these two antigens resulted in unique staining patterns for RBC, generating widespread mosaicism in the RBC population of AB blood group individuals.
Overlapping and unique neural circuits are activated during perceptual decision making and confidence
Authors: Yeon Jiwon , Shekhar Medha , Rahnev Dobromir
Published: October 2018

The period of making a perceptual decision is often followed by a period of confidence generation where one rates the likely accuracy of the initial decision. However, it remains unclear whether the same or different neural circuits are engaged during periods of perceptual decision making and confidence generation. To address this question, we conducted two functional MRI experiments in which we dissociated the periods related to perceptual decision making and confidence report by either separating their respective regressors or asking for confidence ratings only in the second half of the experiment. We found that perceptual decision making and confidence reports gave rise to activations in large and mostly overlapping brain circuits including frontal, parietal, posterior, and cingulate regions with the results being remarkably consistent across the two experiments. Further, the confidence report period activated a number of unique regions, whereas there was no evidence for the decision period activating unique regions not involved in the confidence period. We discuss the possible reasons for this overlap and explore their implications about theories of perceptual decision making and confidence generation.
Interactions of medial and lateral prefrontal cortex in hierarchical predictive coding
Authors: Alexander William H. , Womelsdorf Thilo
Published: October 2018

Cognitive control and decision-making relies on the interplay of medial and lateral prefrontal cortex (mPFC/LPFC), particularly for circumstances in which correct behavior requires integrating and selecting among multiple sources of interrelated information. While the interaction between mPFC and LPFC is generally acknowledged as a crucial circuit in adaptive behavior, the nature of this interaction remains open to debate, with various proposals suggesting complementary roles in (i) signaling the need for and implementing control, (ii) identifying and selecting appropriate behavioral policies from a candidate set, and (iii) constructing behavioral schemata for performance of structured tasks. Although these proposed roles capture salient aspects of conjoint mPFC/LPFC function, none are sufficiently well-specified to provide a detailed account of the continuous interaction of the two regions during ongoing behavior. A recent computational model of mPFC and LPFC, the Hierarchical Error Representation (HER) model, places the regions within the framework of hierarchical predictive coding, and suggests how they interact during behavioral periods preceding and following salient events. In this manuscript, we extend the HER model to incorporate real-time temporal dynamics and demonstrate how the extended model is able to capture single-unit neurophysiological, behavioral, and network effects previously reported in the literature. Our results add to the wide range of results that can be accounted for by the HER model, and provide further evidence for predictive coding as a unifying framework for understanding PFC function and organization.
Molecular neuroanatomy of anorexia nervosa
Authors: Howard Derek , Negraes Priscilla , Voineskos Aristotle N. , Kaplan Allan S. , Muotri Alysson , Duvvuri Vikas , French Leon
Published: October 2018

Anorexia nervosa is a complex eating disorder with genetic, metabolic, and psychosocial underpinnings. Using unbiased genome-wide methods, recent studies have associated a variety of genes with the disorder. We characterized these genes by projecting them into aggregated gene expression data from reference transcriptomic atlases of the prenatal and adult human brain. We found that genes from an induced stem cell study of anorexia nervosa are expressed at higher levels in the lateral parabrachial and the ventral tegmental areas. The adult expression enrichment of the lateral parabrachial is confirmed with genes from two independent genetic studies. In the fetal brain, enrichment of the ventral tegmental area is also observed for the six genes near the only common variant associated with the disorder (rs4622308). We also observed signals in the adult and fetal pontine raphe, but they were not observed when using the genes from the genetic studies. In addition to signals related to calcitonin gene-related peptide neurons and the tachykinin, we found more than the expected number of microglia marker genes within the gene sets. Using mouse transcriptomic data, we identified several anorexia nervosa associated genes that are differentially expressed during food deprivation. While these genes that respond to fasting are not enriched in the gene sets, we highlightRPS26which is proximal to rs4622308. We did not observe expression enrichment in the cingulate cortex or hypothalamus suggesting other targets for deep brain stimulation should be considered for severe cases. This work improves our understanding of the neurobiological causes of anorexia nervosa by suggesting disturbances in subcortical appetitive circuits.
Constrained airfoil optimization using the area-preserving free-form deformation
Authors: Leloudas Stavros N. , Strofylas Giorgos A. , Nikolos Ioannis K.
Published: October 2018

Purpose

The purpose of this paper is the presentation of a technique to be integrated in a numerical airfoil optimization scheme, for the exact satisfaction of a strict equality cross-sectional area constraint.

Design/methodology/approach

An airfoil optimization framework is presented, based on Area-Preserving Free-Form Deformation (AP FFD) technique. A parallel metamodel-assisted differential evolution (DE) algorithm is used as an optimizer. In each generation of the DE algorithm, before the evaluation of the fitness function, AP FFD is applied to each candidate solution, via coupling a classic B-Spline-based FFD with an area correction step. The area correction step is achieved by solving a sub problem, which consists of computing and applying the minimum possible offset to each one of the free-to-move control points of the FFD lattice, subject to the area preservation constraint.

Findings

The proposed methodology is able to obtain better values of the objective function, compared to both a classic penalty function approach and a generic framework for handling constraints, which suggests the separation of constraints and objectives (separation-sub-swarm), without any loss of the convergence capabilities of the DE algorithm, while it also guarantees an exact area preservation. Due to the linearity of the area constraint in each axis, the extraction of an inexpensive closed-form solution to the sub problem is possible by using the method of Lagrange multipliers.

Practical implications

AP FFD can be easily incorporated into any 2D shape optimization/design process, as it is a time-saving and easy-to-implement repair algorithm, independent from the nature of the problem at hand.

Originality/value

The proposed methodology proved to be an efficient tool in facing airfoil design problems, enhancing the rigidity of the optimal airfoil by preserving its cross-sectional area to a predefined value.
The role of psychological screening for emergency service responders
Authors: Tehrani Noreen , Hesketh Ian
Published: October 2018

Purpose

The purpose of this paper is to examine the role that psychological screening and surveillance can take in improving the delivery of psychological support to emergency service responders (ESRs) at a time of increasing demands and complexity.

Design/methodology/approach

The study aims to present and discuss the use of psychological screening and surveillance of trauma exposed emergency service workers.

Findings

The evidence supports the use of psychological screening and surveillance using appropriate validated questionnaires and surveys.

Research limitations/implications

The findings suggest that emergency services should be using psychological screening and surveillance of ESRs in roles where there is high exposure to traumatic stress.

Originality/value

These findings will help emergency service organisations to recognise how psychological screening and surveillance can be used as part of a wider programme of well-being support. This approach can also help them meet their legal health and safety obligations to protect the psychological health and well-being of their ESRs.
Experiences of Karen refugees with traditional and western medicine in the USA
Authors: Wodniak Natalie R.
Published: October 2018

Purpose

The purpose of this paper is to further understand the medical experiences of Karen refugees who have been resettled to the USA. It examines the use of traditional medicine throughout the transition from Burma to the USA, as well as refugees’ experiences in the American healthcare system. This study aims to identify shortcomings in refugees’ access to preferred methods of healthcare.

Design/methodology/approach

Interviews were conducted with 39 Karen refugees in 3 US cities with large populations of refugees from Burma – Fort Wayne, Indiana; Amarillo, Texas; and Buffalo, New York. Participants were asked questions about their healthcare experiences in Burma and the USA, their use of traditional medicine in both countries and their satisfaction with medical care in the USA.

Findings

Nearly all interviewees reported using traditional medicine in Burma, but only six felt able to continue to use traditional methods in the USA. Most participants had positive experiences with healthcare in America, but 15 expressed dissatisfaction with obtaining health insurance and confusion over its coverage. Findings also indicate that refugees do not feel that traditional practices are accepted in the USA.

Research limitations/implications

Due to the language barrier, a phone interpreter was used for non-English-speaking participants, which may have affected proper understanding or clarity of answers.

Practical implications

This study brings to attention the need to improve refugee healthcare by encouraging traditional practices and assisting refugees with obtaining health insurance.

Originality/value

This paper identifies the importance of analyzing the accessibility of various forms of healthcare, including traditional medicine, to refugees in the USA.
Analysis of the impacts of entrepreneurship training on growth performance of firms
Authors: Efobi Uchenna , Orkoh Emmanuel
Published: October 2018

Purpose

Using quasi-experimental designs, the purpose of this paper is to study the effects of training entrepreneurs and such entrepreneurs going ahead to retrain its workers on the business high-growth performance.

Design/methodology/approach

This paper used a unique evaluation data from the National Business Plan Competition in Nigeria, organized by the Nigerian government in collaboration with the World Bank. The data was analyzed using the Propensity Score Matching technique and complemented with the Difference-in-Difference estimates.

Findings

The authors find from the estimation of this paper that those entrepreneurs who received standard evaluation training and goes ahead to retrain its workers experienced an expansion in the number of employees by two persons, an increase in innovation index by about 3 units. An increase in revenue is also observed, but this increase was not significant at the 1, 5 or 10 per cent levels.

Originality/value

This paper presents an interesting view point on how training within an entrepreneurial venture should be viewed as a ‘two sided coin’. This is such that training the entrepreneur is one side of the story, and the entrepreneur retraining its workers is another important side of the story.
Role of innovations in provision of competitiveness and innovational development of economy and overcoming of “underdevelopment whirlpools” in Russia and countries of Eastern Europe
Authors: Popkova Elena , Gornostaeva Zhanna , Tregulova Natalia
Published: October 2018

Purpose

The purpose of this paper is to determine the role of innovations in provision of competitiveness and innovational development of economy and overcoming of “underdevelopment whirlpools” in Russia and countries of Eastern Europe with the help of a special proprietary methodology.

Design/methodology/approach

The authors substantiate the concept and methodology of calculation of “underdevelopment whirlpools”, perform the analysis of development of “underdevelopment whirlpools” in Russia and countries of Eastern Europe and evaluate the influence of “underdevelopment whirlpools” on competitiveness of these countries’ economy.

Findings

The authors determine the perspectives of overcoming the “underdevelopment whirlpools” in Russia and countries of Eastern Europe and increasing their competitiveness with the help of innovation and develops practical recommendations for creation of innovational economy for the purpose of provision of high competitiveness and overcoming of “underdevelopment whirlpools” in Russia and countries of Eastern Europe and overcoming of strong and growing differentiation of the level of socio-economic development of their sub-systems.

Practical implications

Creation of innovational economy in Russia and countries of Eastern Europe is hindered by multiple obstacles (socio-economic and institutional), the success of overcoming of which determines the realization of a certain scenario of development of events.

Originality/value

The main conclusion is that creation of innovational economy can and should become a new vector of economic growth in Russia and countries of Eastern Europe and overcoming of strong and growing differentiation of the level of socio-economic development of their sub-systems.
Corporate social responsibility practices developed by Mexican family and non-family businesses
Authors: Esparza Aguilar José Luis
Published: October 2018

Purpose

The purpose of this paper is to identify the CSR practices developed by Mexican family and non-family MSMEs. The study also aims to compare the CSR practices carried out by family and non-family businesses in a country with an emergent economy.

Design/methodology/approach

The paper opted for an exploratory study using a sample of 384 businesses was selected in the southern state of Quintana Roo, Mexico, distributed in 245 family and 139 non-family businesses and a questionnaire was applied directly to the managers/owners.

Findings

The results show that family MSMEs develop CSR practices to a higher extent than non-family ones, mainly on environment and societal dimensions. In addition, CSR practices in family-owned enterprises develop to a higher extent when the manager/owner has more years of experience in the business, has a higher university education and the size of the business is larger.

Research limitations/implications

The study was developed exclusively with a MSMEs sample with a scope only on the southern part of Quintana Roo, Mexico; the shortage of business databases and the stratification of businesses based exclusively on the number of employees. This work presents information that contributes to the state of the art, broadening the existing literature related to CSR in businesses of a country with an emergent economy and an environment where the tourism and commercial sectors predominate.

Practical implications

This paper provides information to government institutions for the establishment of public policies targeted for an increase of CSR activities by businesses in the area. Manager and/or owners can understand the importance of implementing CSR activities within the business as a competitive strategy. It is also important for universities, professors/researchers and for all interested parties.

Originality/value

This paper provides theoretical and empirical evidence about CSR practices carried out among family and non-family MSMEs in an emergent economy.
The role of information technology in bridging the knowing-doing gap: an exploratory case study on knowledge application
Authors: Haamann Thilo , Basten Dirk
Published: October 2018

Purpose

Organisations that systematically manage their knowledge based on processes of creating, storing, transferring and applying knowledge are likely to achieve both performance improvements and competitive advantages. However, companies often succeed in the first three processes only, while neglecting knowledge application. The phenomenon of employees not relying on existing knowledge when solving specific problems is referred to as knowing-doing gap. While the existence of this gap is well acknowledged, the purpose of this study is to advance the understanding how respective barriers of knowledge application can be overcome, in particular concerning the role of information technology (IT).

Design/methodology/approach

This study applies a case study design, thereby relying on various data sources, such as interviews, documents, field notes, observations and demonstrations. The analysis follows established guidelines for thematic analysis.

Findings

An understanding of knowledge application as a three-step process is derived. The set of knowledge application barriers, identified practices to overcome the barriers and yielded themes that explain the role of IT in bridging the knowing-doing gap are complemented.

Research limitations/implications

The role of IT in bridging the knowing-doing gap and contributing to the general understanding of the knowing-doing gap by also considering practices concerning the people and process dimensions is illuminated. While IT plays a central role in applying knowledge, successfully overcoming the knowing-doing gap requires organisational practices at the people and processes dimensions that are aligned with the IT. The set of barriers of knowledge application at the individual, group and organisational levels is complemented.

Practical implications

The practices to bridge the knowing-doing gap at the intersection of the people, processes and technology dimensions are identified. Specifically, the role of IT in overcoming barriers to knowledge application is explored.

Originality/value

This thematic analysis yields a theoretical explanation for knowledge application as a three-step process and suggests practices to bridge the knowing-doing gap for each step. Furthermore, four major themes that explain the role of IT for this process in depth are derived.
Unintended consequences of special-needs law in Ireland and Sweden
Authors: Shine Thompson Mary , Svaerd Ann-Katrin Lena
Published: October 2018

Purpose

This paper aims to trace parallels in the unintended consequences of interpretations of special-needs law in Ireland and Sweden.

Design/methodology/approach

The paper is conceptual, based on Irish and Swedish legal reports, studies and national planning documents on supports for people with disabilities. It begins by discussing unintended consequences, and then analyses the Irish court decision in Sinnott v. Minister for Education (2001), which stated that the State’s obligation to provide for education for people with special education needs (SENs) ceases when they reach 18 years. It considers how economic considerations influenced that decision. The focus then diverts to Sweden’s human rights culture and the 1994 legislation, LSS (Sweden’s Act Concerning Support and Services for Persons with Certain Functional Impairments), which enshrines equality and support for people with disabilities, including personal assistance (PA). Cost-saving restrictions on PA allowances are discussed.

Findings

While the Irish State enacted a law on education rights following the Sinnott case the Education for Persons with Special Educational Needs Act (2004), or EPSEN (2004), it restricts those rights, and sections remain uncommenced. The case may have exhausted litigation as a remedy for people with SENs. In Sweden, austerity diluted the impact of LSS, leading to reduced entitlements and intrusions on privacy. It allowed legal discourse to dominate discussion. Families were negatively affected. In both countries, human rights may have suffered. Identifying which consequences of the legal actions were unintended, and which party did not intend them, can be problematic.

Practical implications

The paper concludes that the courts limited entitlement to the detriment of people with disabilities, and that caution must be exercised in having recourse to law courts in settling entitlements.

Originality/value

The paper is an original analysis of unintended consequences of legal interventions in special-needs policy. It illustrates difficulties in matching visions and systemic requirements in legal and the educational domains.
MiR‐101a ameliorates AngII‐mediated hypertensive nephropathy by blockade of TGFβ/Smad3 and NF‐κB signalling in a mouse model of hypertension
Authors: Ding Hong , Zhou Ying , Huang Haihua
Published: October 2018

Hypertensive nephropathy, clinically characterized by progressive renal fibrosis and inflammation, is a severe complication of hypertension. The objectives of this study were to investigate the roles of miR‐101a in relieving angiotensin II (Ang II)‐mediated hypertensive nephropathy and uncover the possible underlying mechanisms. A hypertensive mouse model was established via continuous 28‐day AngII infusion. Systolic blood pressure (SBP), ratio of urine albumin to creatinine, blood urea nitrogen (BUN), serum creatinine (Scr) and glomerular filtration rate (GFR) were evaluated. Dual luciferase reporter assay was used to explore the target of miR‐101a. mRNA levels of miR‐101a, TGFβRI, fibrotic markers (Collagen I and α‐SMA) and pro‐inflammatory cytokines (IL‐1β and TNF‐α) were determined by real‐time PCR. Protein levels of TGFβRI, Collagen I, α‐SMA, IL‐1β, TNF‐α, t‐p65, P‐p65, t‐Smad3, P‐Smad3, t‐IκBα and P‐IκBα were detected by western blot. MiR‐101a mimics significantly improved GFR and inhibited AngII‐induced increase in the ratio of urine albumin to creatinine, BUN and Scr. MiR‐101a mimics partially abolished AngII‐induced increase in the mRNA and protein level of fibrotic markers by targeting TGFβRI and inhibiting TGFβ/Smad3 pathway. Moreover, TGFβRI inhibitor galunisertib inhibited AngII‐mediated renal injury in mice with hypertensive nephropathy. Additionally, miR‐101a overexpression blocked AngII‐induced up‐regulation of pro‐inflammatory markers via suppressing NF‐κB pathway. MiR‐101a exhibited protective effects against hypertensive nephropathy via inhibiting TGFβ/Smad3 and NF‐κB signalling pathways.
When knowledgeable neighbors also share seedlings: diffusion of banana cultivation in Tanzania
Authors: Larsen Anna Folke
Published: October 2018

Networks have been found to increase adoption of technology by providing information about the new technology (e.g., Conley and Udry, 2010). However, little is known about provision of necessary inputs for adoption through networks. Using data from an intervention in Tanzania, I discuss how a farmer's network can also affect the adoption of improved banana cultivation by providing seedlings. A solidarity chain principle obliged project farmers to pass on improved seedlings to other farmers free of charge. I provide a theoretical framework to guide intuition for the empirical results and suggest an empirical distinction between information and input provision through networks. Empirically, I find support for network effects through provision of both information and inputs, jointly boosting the network effect on adoption: a farmer is 39 percentage points more likely to adopt banana cultivation if there is at least one banana grower in the farmer's network compared to none. In this setting, it is not possible to fully disentangle the input and information channel. While the findings suggest that a solidarity chain principle could be an interesting avenue to boost local diffusion of new technologies, more research is needed to unpack the causal impact and the interplay with existing input markets.
The steadily growing problem of lentigo maligna and lentigo maligna melanoma in Australia: Population‐based data on diagnosis and management
Authors: Guitera Pascale , Collgros Helena , Madronio Christine M , Goumas Christopher , Mann Graham J , Watts Caroline G , Pereira Amanda R , Armstrong Bruce K , Drummond Martin , Morton Rachael L , Scolyer Richard A , Menzies Scott W , Thompson John F , Cust Anne E
Published: October 2018

Background/Objectives

There are limited population‐based data documenting the incidence and management of lentigo maligna (LM) and invasive lentigo maligna melanoma (LMM). We report the data on occurrence and management of LM and LMM in an Australian population.

Methods

Prospective collection of incidence and clinician‐reported management of melanoma in situ (MIS; n = 450, capped) and localised invasive melanoma (n = 3251) notified to the New South Wales Cancer Registry over 12‐months in 2006–2007.

Results

The estimated annual incidence of all MIS was 27.0 per 100 000 (LM 12.2, non‐LM MIS 5.9 and unclassified MIS 9.0). Patients with LM or LMM were on average approximately 10 years older than those with other melanoma subtypes (P < 0.001). The head and neck was the location of 59% of LM, 44% of LMM and <20% of other melanoma subtypes (P < 0.001). The majority of LM and LMM were treated only by specialists. Diagnostic partial biopsies were more frequent for LM and LMM than for other melanoma subtypes, and primary care physicians were more likely than specialists to do a punch partial biopsy than a shave biopsy. The reported median definitive excision margin for LM was 5.0 mm compared with 7.2 mm for non‐LM MIS (P = 0.001).

Conclusions

In this Australian population, LM was twice as frequent as other types of MIS. Improved strategies for diagnosis and management are required.
Kete pikau: A basket of knowledge – ‘guidelines from back home’
Authors: Koroheke‐Rogers Marara , Blattner Katharina
Published: October 2018

From the perspective of one rural New Zealand Māori community involved in a health service research study, this article describes ‘Te Tomokanga’ – an established local Māori model of engagement. This model served as an essential guide for researchers coming into the community and at the same time, enabled the community to take ownership of the research process. This may have applicability to research in rural Indigenous communities elsewhere.
Maternal paracetamol intake and fetal ductus arteriosus constriction or closure: a case series analysis
Authors: Allegaert Karel , Mian Paola , Lapillonne Alexandre , van den Anker John N.
Published: October 2018

Recent case reports describe an association between maternal paracetamol intake and fetal ductus arteriosus constriction or closure. To put these cases into perspective and explore causality, a structured literature search was conducted. The World Health Organization Uppsala Monitoring Centre (WHO–UMC) causality tool was applied to the cases retrieved. The search resulted in 12 papers with 25 case descriptions, of which one case was classified as unlikely, nine as possible, 11 as probable and four as certain. Consequently, we concluded that a causal relationship between maternal paracetamol intake and fetal ductus arteriosus constriction or closure is likely. These findings suggest that pharmacovigilance studies on paracetamol safety during pregnancy are warranted to quantify the event and put the current findings into clinical perspective. Although analgesia during pregnancy and during the peripartum period is of obvious relevance, alternative analgesics such as opioids or other nonsteroidal anti‐inflammatory drugs also have side effects.
Long‐term cost comparison between surgical and medical therapy for benign prostatic hyperplasia: a study using hospital billing data
Authors: Ahn Hyun Soo , Kim Se Joong , Choi Jong Bo , Choo Seol Ho , Shim Kang Hee , Kim Sun Il
Published: October 2018

Objectives

To analyse actual long‐term medical treatment of benign prostatic hyperplasia (BPH) and compare the incurred cost with that of patients with BPH who underwent early surgery.

Patients and methods

Patients who were first diagnosed with BPH from 1 January 2008 to 31 December 2010 were identified using the Clinical Data Warehouse. Hospital billing data generated by the electronic hospital management system were collected until December 2015. For outpatient care, only procedures, materials and drugs directly related to the management of BPH were selected for the analysis. For inpatient care, all procedures, materials and drugs ordered on dates with continuity with BPH surgery date were included. The primary endpoint of the study was the total treatment‐related direct costs of patients undergoing a long‐term curative medical therapy for BPH (Group 1), which was arbitrarily defined as any medical therapy including a 5α‐reductase inhibitor with a minimum medication possession ratio of 0.5 during ≥5 consecutive years, or ≥1 year until BPH surgery due to medical therapy failure. In all, 70 patients who underwent BPH surgery at <1 year of initial visit served as controls (Group 2).

Results

Amongst 137 patients in the Group 1, four patients underwent BPH surgery at a median of 57.8 months after the initial visit (2.9%). At a median follow‐up of 76 months, the mean total treatment cost was significantly higher in Group 1 than in Group 2 ($3987 vs $3036 [USA dollars], P < 0.001). Similarly, the mean ‘out‐of‐pocket’ cost was significantly higher in Group 1 than in Group 2 ($1742 vs $1436, P = 0.005). When a linear increment of annual BPH treatment cost is assumed for Group 1 and all costs are assumed to be produced within the first year for Group 2, the total and out‐of‐pocket costs became equal at the end of the fifth year of medical treatment. For both total and out‐of‐pocket costs, medication‐related costs occupied the largest proportion, exceeding half of the costs.

Conclusions

We suggest patient counselling at the beginning of BPH treatment should include the likelihood that the cumulative out‐of‐pocket cost at 5 years of continuous medication will exceed that of early surgery. Our cost study using hospital billing data extractable from the electronic hospital management system may be a good model for cost studies that could provide valuable information to health providers and payers.
Oxidative stress and inflammation in a spectrum of epileptogenic cortical malformations: molecular insights into their interdependence
Authors: Arena Andrea , Zimmer Till S. , van Scheppingen Jackelien , Korotkov Anatoly , Anink Jasper J. , Mühlebner Angelika , Jansen Floor E. , van Hecke Wim , Spliet Wim G. , van Rijen Peter C. , Vezzani Annamaria , Baayen Johannes C. , Idema Sander , Iyer Anand M. , Perluigi Marzia , Mills James D. , van Vliet Erwin A. , Aronica Eleonora
Published: October 2018

Oxidative stress (OS) occurs in brains of patients with epilepsy and coincides with brain inflammation, and both phenomena contribute to seizure generation in animal models. We investigated whether expression of OS and brain inflammation markers co‐occurred also in resected brain tissue of patients with epileptogenic cortical malformations: hemimegalencephaly (HME), focal cortical dysplasia (FCD) and cortical tubers in tuberous sclerosis complex (TSC). Moreover, we studied molecular mechanisms linking OS and inflammation in an in vitro model of neuronal function. Untangling interdependency and underlying molecular mechanisms might pose new therapeutic strategies for treating patients with drug‐resistant epilepsy of different etiologies. Immunohistochemistry was performed for specific OS markers xCT and iNOS and brain inflammation markers TLR4, COX‐2 and NF‐κB in cortical tissue derived from patients with HME, FCD IIa, IIb and TSC. Additionally, we studied gene expression of these markers using the human neuronal cell line SH‐SY5Y in which OS was induced using H2O2. OS markers were higher in dysmorphic neurons and balloon/giant cells in cortex of patients with FCD IIb or TSC. Expression of OS markers was positively correlated to expression of brain inflammation markers. In vitro, 100 µM, but not 50 µM, of H2O2 increased expression of TLR4, IL‐1β and COX‐2. We found that NF‐κB signaling was activated only upon stimulation with 100 µM H2O2 leading to upregulation of TLR4 signaling and IL‐1β. The NF‐κB inhibitor TPCA‐1 completely reversed this effect. Our results show that OS positively correlates with neuroinflammation and is particularly evident in brain tissue of patients with FCD IIb and TSC. In vitro, NF‐κB is involved in the switch to an inflammatory state after OS. We propose that the extent of OS can predict the neuroinflammatory state of the brain. Additionally, antioxidant treatments may prevent the switch to inflammation in neurons thus targeting multiple epileptogenic processes at once.
Molecular pharmacology of GPCRs
Authors: Langmead Christopher J , Summers Roger J
Published: October 2018

Linked Articles

This article is part of a themed section on Molecular Pharmacology of GPCRs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.21/issuetoc
Accuracy of grading pancreatic neuroendocrine neoplasms with Ki‐67 index in fine‐needle aspiration cellblock material
Authors: Grosse Claudia , Noack Petar , Silye Rene
Published: October 2018

Objective

The aim of this study was to assess the preoperative tumour grade of pancreatic neuroendocrine neoplasms (panNENs) by determining the Ki‐67 index in endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) material and to correlate the preoperative tumour grade with the postoperative tumour grade in surgical specimens.

Methods

We performed a retrospective review of the institutional pathology database over a 10‐year period (2007‐2017) to identify all cases of panNENs with corresponding preoperative EUS‐FNA cytological material and surgical specimens. Fifteen cases with adequate EUS‐FNA material (more than 400 tumour cells on cellblock) were identified. The cytological and histological samples were graded based on the mitotic rate and the Ki‐67 index in accordance with the 2017 World Health Organisation grading system for panNENs. The tumour grades determined on EUS‐FNA cellblock material were compared with the histological tumour grades.

Results

Mean age at diagnosis was 64.8 ± 12.7 years (range, 38‐85 years). The grading scores assigned to the cytological and histological samples were concordant in all 15 (100%) cases. Of those, two (13%) cases were scored as grade 1, nine (60%) cases as grade 2 and four (27%) cases as grade 3 tumours.

Conclusion

Our study shows that tumour grade in patients with PanNENs can be reliably determined by assessing the Ki‐67 index in EUS‐FNA specimens based on the 2017 World Health Organisation classification and grading system.
Deferasirox in children with transfusion‐dependent thalassemia or sickle cell anemia: A large cohort real‐life experience from Turkey (REACH‐THEM)
Authors: Antmen Bulent , Karakaş Zeynep , Yeşilipek Mehmet Akif , Küpesiz Osman Alphan , Şaşmaz İlgen , Uygun Vedat , Kurtoğlu Erdal , Oktay Gonul , Aydogan Gonul , Akın Mehmet , Salcioglu Zafer , Vergin Canan , Kazancı Elif Güler , Ünal Selma , Çalışkan Ümran , Aral Yusuf Ziya , Türkkan Emine , Meral Güneş Adalet , Tunç Bahattin , Gümrük Fatma , Ayhan Aylin Canbolat , Söker Murat , Koç Ahmet , Oymak Yeşim , Ertem Mehmet , Timur Çetin , Yıldırmak Yıldız , İrken Gülersu , Apak Hilmi , Biner Betül , Eren Tuğba Gürleyen , Işık Balcı Yasemin , Koçak Ülker , Karasu Gülsün , Akkaynak Diyar , Patıroğlu Türkan
Published: October 2018

Objectives

To evaluate the long‐term efficacy and safety of deferasirox therapy in a large observational cohort of children with transfusion‐dependent thalassemia (TDT) and sickle cell anemia (SCA) in Turkey.

Methods

This was a multicenter, prospective cohort study including TDT and SCA patients aged 2‐18 years with iron overload (≥100 mL/kg of pRBC or a serum ferritin [SF] level >1000 μg/L) receiving deferasirox. Patients were followed for up to 3 years according to standard practice.

Results

A total of 439 patients were evaluated (415 [94.5%] TDT, 143 [32.6%] between 2 and 6 years). Serum ferritin levels consistently and significantly decreased across 3 years of deferasirox therapy from a median of 1775.5 to 1250.5 μg/L (P < 0.001). Serum ferritin decreases were noted in TDT (1804.9 to 1241 μg/L), SCA (1655.5 to 1260 μg/L), and across age groups of 2‐6 years (1971.5 to 1499 μg/L), 7‐12 years (1688.5 to 1159.8 μg/L), and 13‐18 years (1496.5 to 1107 μg/L). Serum ferritin decreases were also noted for all deferasirox dose groups but only significant in patients with doses ≥30 mg/kg/d (n = 120, −579.6 median reduction, P < 0.001). Only 9 (2%) patients had adverse events suspected to be related to deferasirox. Serum creatinine slightly increased but remained within the normal range.

Conclusions

Deferasirox has long‐term efficacy and safety in children with TDT and SCA, although higher doses (≥30 mg/kg/d) may be required to achieve iron balance.
Biochemical characterization of the minimal domains of an iterative eukaryotic polyketide synthase
Authors: Sabatini Martin , Comba Santiago , Altabe Silvia , Recio‐Balsells Alejandro I. , Labadie Guillermo R. , Takano Eriko , Gramajo Hugo , Arabolaza Ana
Published: October 2018

Iterative type I polyketide synthases (PKS) are megaenzymes essential to the biosynthesis of an enormously diverse array of bioactive natural products. Each PKS contains minimally three functional domains, β‐ketosynthase (KS), acyltransferase (AT), and acyl carrier protein (ACP), and a subset of reducing domains such as ketoreductase (KR), dehydratase (DH), and enoylreductase (ER). The substrate selection, condensation reactions, and β‐keto processing of the polyketide growing chain are highly controlled in a programmed manner. However, the structural features and mechanistic rules that orchestrate the iterative cycles, processing domains functionality, and chain termination in this kind of megaenzymes are often poorly understood. Here, we present a biochemical and functional characterization of the KS and the AT domains of a PKS from the mallard duck Anas platyrhynchos (ApPKS). ApPKS belongs to an animal PKS family phylogenetically more related to bacterial PKS than to metazoan fatty acid synthases. Through the dissection of the ApPKS enzyme into mono‐ to didomain fragments and its reconstitution in vitro, we determined its substrate specificity toward different starters and extender units. ApPKS AT domain can effectively transfer acetyl‐CoA and malonyl‐CoA to the ApPKS ACP stand‐alone domain. Furthermore, the KS and KR domains, in the presence of Escherichia coli ACP, acetyl‐CoA, and malonyl‐CoA, showed the ability to catalyze the chain elongation and the β‐keto reduction steps necessary to yield a 3‐hydroxybutyryl‐ACP derivate. These results provide new insights into the catalytic efficiency and specificity of this uncharacterized family of PKSs.
Hsa_circ_101280 promotes hepatocellular carcinoma by regulating miR‐375/JAK2
Authors: Cao Shuang , Wang Guohua , Wang Jia , Li Cheng , Zhang Le
Published: October 2018

In this study, we sought to predict the effects of a certain circular RNA (circRNA), hsa_circ_101280 (also known as hsa_circ_0100929 and hsa_circ_SLAIN1), on hepatocellular carcinoma (HCC) cells and to determine the potential mechanism. After screening differentially expressed circRNAs in HCC tissues through Gene Expression Omnibus data analysis, hsa_circ_101280 was found to be highly expressed, and its high expression was verified in HCC cell lines with qRT‐PCR along with the low expression of its downstream miRNA miR‐375. Colony formation and flow cytometry assays showed that both hsa_circ_101280 silencing and miR‐375 overexpression restrained proliferation and promoted apoptosis in HCC cells. JAK2 was identified as a downstream mRNA target of miR‐375 by RNA pull‐down and dual‐luciferase reporter gene assays, its expression in HCC cell lines were positively regulated by hsa_circ_101280 and negatively by miR‐375 expression. Furthermore, the silencing of hsa_circ_101280 significantly inhibited the growth of HCC xenografts in nude mice, with the downregulated expression of JAK2. Overall, both the in vitro and in vivo studies revealed that hsa_circ_101280 largely facilitated the tumorigenesis of HCC, characterized by the promoted proliferation and suppressed apoptosis of HCC cells, by sponging miR‐375 and upregulating JAK2.
Assessment of serious infections in pemphigus and pemphigoid by a national registry
Authors: Maglie R. , Hertl M.
Published: October 2018

Linked article: This is a commentary on Z. Ren et al., pp. 1768–1776 in this issue. To view this article visit https://doi.org/10.1111/jdv.14961
Effects of glufosinate‐ammonium herbicide and pod sealant on spider Pardosa agrestis
Authors: Niedobová Jana , Krištofová Lucie , Michalko Radek , Hula Vladimír , Kýnický Jindřich , Brtnický Martin
Published: October 2018

Herbicides based upon glufosinate‐ammonium (GLA) are among the world's most widely used. They also are applied on the most prominent oil crops as desiccants in combination with pod sealants to prevent pod shatter and seed loss close to harvest. Even though these crops occupy a significant part of the world's agroecosystems, the effects of GLA herbicides on non‐target arthropods, and in particular natural enemies of pests, have been studied very rarely, and such effects of pod sealants have never been studied. We studied in our laboratory mortality as well as prey capture efficiency of the common GLA herbicide and desiccant Basta 15®, pod sealant Arrest®, and a mixture of both on the wolf spider Pardosa agrestis. We found that Basta 15® and the mixture had lethal effect on spiders. We also found significant, short‐term effect on predatory activity of spiders after all treatments. Basta 15® significantly influenced the amount of captured prey also in the long term. This is the first study showing lethal effect on spiders of the herbicide and herbicide plus pod sealant mixture. This is also the first study examining the effects of pod sealant on the mortality and predatory activity of a pest antagonist. More studies regarding the effects of agricultural chemical mixes are needed to uncover their effects on beneficial organisms existing within agroecosystems.
Development and Validation of a Fall Prevention Knowledge Test
Authors: Dykes Patricia C. , Bogaisky Michael , Carter Eileen J. , Duckworth Megan , Hurley Ann C. , Jackson Emily M. , Khasnabish Srijesa , Lindros Mary Ellen , Lipsitz Stuart R. , Scanlan Maureen , Yu Shao P. , Bates David W. , Adelman Jason S.
Published: October 2018

Falls are a serious, persistent problem in hospitals. Ensuring that all hospital staff have adequate knowledge of how to prevent falls is the first step in prevention. We identified validated fall prevention knowledge tests (FPKTs) and planned to conduct a systematic literature review. When the review identified a lack of FPKTs, we developed and evaluated a FPKT, confirmed its conceptual framework, identified the content domain, drafted test items, devised the format, selected items for empirical examination, and conducted a psychometric evaluation. We randomly divided a 209‐subject data set into test and validation samples to make item reduction decisions and examine reliability and validity. The typical respondent was a white, 42‐year old female nurse with a bachelor's degree and 7 years' experience. Subjects were confident in their ability to prevent falls, rating themselves an 8 on a self‐efficacy scale of 1 (not at all) to 10 (very). The 11‐item FPKT scale (range 0–11) attained a tetrachoric coefficient of 0.73, confirming initial reliability. FPKT mean scores obtained before and after fall prevention education improved from 5.1 ± 1.8 to 6.6 ± 1.7. Statistically significant differences (paired t‐test = 12.4, p < .001) confirmed validity. A robust way to assess nurses' knowledge of fall prevention is needed to inform effective educational programs. Addressing gaps in validated FPKTs provides an opportunity to inform and evaluate effective fall prevention programs. J Am Geriatr Soc 67:133–138, 2019.
"We Take Care of Patients, but We Don't Advocate for Them": Advance Care Planning in Prison or Jail
Authors: Ekaireb Rachel , Ahalt Cyrus , Sudore Rebecca , Metzger Lia , Williams Brie
Published: October 2018

Objectives

To investigate correctional healthcare providers’ knowledge of and experience with advance care planning (ACP), their perspectives on barriers to ACP in correctional settings, and how to overcome those barriers.

Design

Qualitative.

Setting

Four prisons in 2 states and 1 large city jail in a third state.

Participants

Correctional healthcare providers (e.g., physicians, nurses, social workers; N=24).

Results

Participants demonstrated low baseline ACP knowledge; 85% reported familiarity with ACP, but only 42% provided accurate definitions. Fundamental misconceptions included the belief that providers provided ACP without soliciting inmate input. Multiple ACP barriers were identified, many of which are unique to prison and jail facilities, including provider uncertainty about the legal validity of ACP documents in prison or jail, inmate mistrust of the correctional healthcare system, inmates’ isolation from family and friends, and institutional policies that restrict use of ACP. Clinicians’ suggestions for overcoming those barriers included ACP training for clinicians, creating psychosocial support opportunities for inmates, revising policies that limit ACP, and systematically integrating ACP into healthcare practice.

Conclusion

Despite an increasing number of older and seriously ill individuals in prisons and jails, many correctional healthcare providers lack knowledge about ACP. In addition to ACP barriers found in the community, there are unique barriers to ACP in prisons and jails. Future research and policy innovation are needed to develop clinical training programs and identify ACP implementation strategies for use in correctional settings. J Am Geriatr Soc 66:2382–2388, 2018.