bluuebunny/crossref_metadata_2025 huggingface dataset:
Collismycin A biosynthesis in Streptomyces sp. CS40 is regulated by iron levels through two pathway-specific regulators
Authors: Vior Natalia M. , Olano Carlos , García Ignacio , Méndez Carmen , Salas José A.
Published: December 2013

Two putative pathway-specific regulators have been identified in the collismycin A gene cluster: ClmR1, belonging to the TetR-family, and the LuxR-family transcriptional regulator ClmR2. Inactivation ofclmR1led to a moderate increase of collismycin A yields along with an early onset of its production, suggesting an inhibitory role for the product of this gene. Inactivation ofclmR2abolished collismycin A biosynthesis, whereas overexpression of ClmR2 led to a fourfold increase in production yields, indicating that ClmR2 is an activator of collismycin A biosynthesis. Expression analyses of the collismycin gene cluster in the wild-type strain and in ΔclmR1and ΔclmR2mutants confirmed the role proposed for both regulatory genes, revealing that ClmR2 positively controls the expression of most of the genes in the cluster and ClmR1 negatively regulates both its own expression and that ofclmR2. Additionally, production assays and further transcription analyses confirmed the existence of a higher regulatory level modulating collismycin A biosynthesis in response to iron concentrations in the culture medium. Thus, high iron levels inhibit collismycin A biosynthesis through the repression ofclmR2transcription. These results have allowed us to propose a regulatory model that integrates the effect of iron as the main environmental stimulus controlling collismycin A biosynthesis.
Bayesian inference of infectious disease transmission from whole genome sequence data
Authors: Didelot Xavier , Gardy Jennifer , Colijn Caroline
Published: December 2013

Genomics is increasingly being used to investigate disease outbreaks, but an important question remains unanswered – how well do genomic data capture known transmission events, particularly for pathogens with long carriage periods or large within-host population sizes? Here we present a novel Bayesian approach to reconstruct densely-sampled outbreaks from genomic data whilst considering within-host diversity. We infer a time-labelled phylogeny using BEAST, then infer a transmission network via a Monte-Carlo Markov Chain. We find that under a realistic model of within-host evolution, reconstructions of simulated outbreaks contain substantial uncertainty even when genomic data reflect a high substitution rate. Reconstruction of a real-world tuberculosis outbreak displayed similar uncertainty, although the correct source case and several clusters of epidemiologically linked cases were identified. We conclude that genomics cannot wholly replace traditional epidemiology, but that Bayesian reconstructions derived from sequence data may form a useful starting point for a genomic epidemiology investigation.
The ubiquitin-specific protease 14 (USP14) is a critical regulator of long-term memory formation
Authors: Jarome Timothy J. , Kwapis Janine L. , Hallengren Jada J. , Wilson Scott M. , Helmstetter Fred J.
Published: December 2013

Numerous studies have suggested a role for ubiquitin–proteasome-mediated protein degradation in learning-dependent synaptic plasticity; however, very little is known about how protein degradation is regulated at the level of the proteasome during memory formation. The ubiquitin-specific protease 14 (USP14) is a proteasomal deubiquitinating enzyme that is thought to regulate protein degradation in neurons; however, it is unknown if USP14 is involved in learning-dependent synaptic plasticity. We found that infusion of a USP14 inhibitor into the amygdala impaired long-term memory for a fear conditioning task, suggesting that USP14 is a critical regulator of long-term memory formation in the amygdala.
4,4-Difluoro-2,3;5,6-bis(tetramethylene)-4-bora-3a,4a-diaza-s-indacene (LD540)
Authors: Salorinne Kirsi , Tero Tiia-Riikka , Lahtinen Tanja
Published: December 2013

The title compound, C18H21BF2N2, is a lipophilic dye based on a BODIPY fluorophore backbone, which was developed for microscopic imaging of lipid droplets; the molecule has a planar BODIPY core [dihedral angle between the pyrrole rings = 2.3 (3)°] and two tetramethylene substituents at the 2,3- and 5,6-positions in a half-chair conformation. One of the tetramethylene substituents is disordered over two two sets of sites with site occupancies of 0.5. In the crystal, pairs of C—H...F interactions link the molecules into inversion dimers. Neighbouring dimers are linked by further C—H...F interactions, forming an infinite array. C—H...π and π–π [centroid–centroid distance = 4.360 (3) Å] interactions are observed between the BODIPY core and the tetramethylene substituents of neighbouring dimer pairs.
Managerial role in organizational CSR: empirical lessons from Ghana
Authors: Baba Abugre James
Published: December 2013

Purpose

–The purpose of this paper is to examine the managerial role in the practices of corporate social responsibility (CSR) in developing economies.

Design/methodology/approach

–The paper takes the form of an empirical analysis of employees' opinions based on a quantitative survey of 100 middle and senior level managers from four organisations chosen from relatively high impact industry sectors.

Findings

–Managerial role in the practice of CSR is limited and ineffective in Ghana. Difficulties of effective CSR implementation mainly stem from leadership weak spots in the form of mismanagement and corruption, lack of leadership commitment and unwillingness to allocate monies due for CSR activities. Organisations can do better in the practice of CSR if management's attitude to CSR, corruption, and work behaviors are positive.

Practical implications

–The paper provides valuable information on managerial activities with regards to organisational CSR, and how these can be improved.

Originality/value

–Empirical literature on CSR in developing countries is limited. This paper identifies the roles that management and organisational leadership can play in the practice of CSR in developing countries. The paper proposes a universal approach which aims to address the need for adequate and effective enforcement of CSR.
Application of new optimal homotopy perturbation and Adomian decomposition methods to the MHD non-Newtonian fluid flow over a stretching sheet
Authors: Khan Yasir , Latifizadeh Habibolla
Published: December 2013

Purpose

– The purpose of this paper is to introduce a new modified version of the homotopy perturbation method (NMHPM) and Adomian decomposition method (ADM) for solving the nonlinear ordinary differential equation arising in MHD non-Newtonian fluid flow over a linear stretching sheet.

Design/methodology/approach

– The governing equation is solved analytically by applying a newly developed optimal homotopy perturbation approach and ADM. This optimal approach contains convergence-control parameter and is computationally rather efficient. The results of numerical example are presented and only a few terms are required to obtain accurate solutions.

Findings

– A new modified optimal and ADM methods accelerate the rapid convergence of the series solution. These methods dramatically reduce the size of work. The obtained series solution is combined with the diagonal Padé approximants to handle the boundary condition at infinity. Results derived from these methods are shown graphically and in tabulated forms to study the efficiency and accuracy.

Practical implications

– Non-Newtonian flow processes play a key role in many types of polymer engineering operations. The formulation of mathematical model for these processes can be based on the equations of non-Newtonian fluid mechanics. The flow of an electrically conducting fluid in the presence of a magnetic field is of importance in various areas of technology and engineering such as MHD power generation, MHD flow meters, MHD pumps, etc. It is generally admitted that a number of astronomical bodies (e.g. the sun, Earth, Jupiter, Magnetic stars, Pulsars) posses fluid interiors and (or least surface) magnetic fields.

Originality/value

– The present results are original and new for the MHD non-Newtonian fluid flow over a linear stretching sheet. The results attained in this paper confirm the idea that NMHPM and ADM are powerful mathematical tools and that can be applied to a large class of linear and nonlinear problems arising in different fields of science and engineering.
Modifying the Black-Scholes-Merton model to calculate the cost of employee stock options
Authors: D. Finnerty John
Published: December 2013

Purpose

– More than 80 percent of S&P 500 firms that issue ESOs use the Black-Scholes-Merton (BSM) model and substitute the estimated average term for the contractual expiration to calculate ESO expense. This simplification systematically overprices ESOs, which worsens as the stock's volatility increases. The purpose of this paper is to present a modification of the BSM model to explicitly incorporate the rates of forfeiture pre- and post-vesting and the rate of early exercise.

Design/methodology/approach

– The paper demonstrates the model's usefulness by employing historical exercise and forfeiture data for 127 separate ESO grants and 1.31 billion ESOs to calculate the exercise and forfeiture parameters and value ESOs for nine firms.

Findings

– The modified BSM model is just as accurate but easier to use than the more computationally intensive utility maximization and trinomial lattice models, and it avoids the ASC 718 BSM model's overpricing bias.

Originality/value

– If firms prefer the BSM model over more mathematically elegant alternatives, they should at least use a BSM model that is free of overpricing bias.
Learning over tea! Studying in informal learning spaces
Authors: Hunter Jonathan , Cox Andrew
Published: December 2013

Purpose

– The purpose of this paper is to offer an exploratory investigation of students' use of informal learning spaces for their studies at the University of Sheffield. Previous research has mainly focused on formal learning spaces such as libraries and lecture theatres, but there is an increasing recognition of the value of informal learning spaces such as coffee bars.

Design/methodology/approach

– Questionnaires, observations and interviews were the sources of data for the study. The research approach particularly looked at how students used informal learning spaces and what their perceptions of the spaces were.

Findings

– Analysis showed that students found that the background atmosphere greatly influenced their choice of study location and that technological devices were only used sparingly. Students adapted their study habits to fit the learning spaces that they liked.

Originality/value

– Although, attention is often paid to the furniture and colour schemes in libraries, this article makes librarians consider the importance of all sensual stimuli in making libraries warm, friendly and homely spaces. The “Model of Zengagement” was developed to show how stimuli from the background atmosphere influences' students' study experience.
In vitro effects of cilostazol, a phosphodiesterase 3A inhibitor, on mouse oocyte maturation and morphology
Authors: Taiyeb Ahmed M , Dees William L , Ridha‐Albarzanchi Mundhir T , Sayes Christie M , Kraemer Duane C
Published: December 2013

Inhibition of phosphodiesterase 3A (PDE3A) in oocytes has been reported to arrest oocyte maturation and to increase intra‐oocyte cyclic adenosine monophosphate levels. Although many PDE3A inhibitors have been found to arrest oocyte maturation in different species, including humans, the most commonly prescribed PDE3A inhibitor named cilostazol (CLZ) has not yet been fully evaluated in reproduction.

The present study was designed to investigate the potential inhibitory effects of CLZ on oocyte maturation and morphology in vitro. Antral oocytes were recovered from hyperstimulated mice and allocated to 10 different CLZ concentrations (0.00–67.66 μmol/L). Oocytes were then assessed after 24 and 48 h of incubation for maturation and morphology.

Some of the evaluated CLZ concentrations (1.06–4.23 μmol/L) were made similar to those observed in human clinical trials. CLZ arrested oocyte maturation at the germinal vesicle (GV) stage at concentrations as low as 1.06 μmol/L (P < 0.0001). A selective degenerative impact of CLZ targeting arrested oocytes at the GV stage was observed during 24 h of incubation (r = −0.781, P < 0.0001). This was not the case with non‐arrested oocytes (r = −0.082, P = 0.64). Such degenerative impact was dose‐dependent (P < 0.0001), suggesting a role for cyclic adenosine monophosphate in this degenerative process. The degenerated oocytes were of distorted oolema or fragmented cytoplasm.

Based on the experiments, it is concluded that CLZ can inhibit oocyte maturation in vitro, at concentrations similar to those observed in humans taking CLZ, and under such conditions the prolonged maintenance of oocytes at the GV stage is harmful.
Monte Carlo simulation analysis of ceftobiprole, dalbavancin, daptomycin, tigecycline, linezolid and vancomycin pharmacodynamics against intensive care unit‐isolated methicillin‐resistant Staphylococcus aureus
Authors: Salem Ahmed Hamed , Zhanel George G , Ibrahim Safaa A , Noreddin Ayman M
Published: December 2013

The aim of the present study was to compare the potential of ceftobiprole, dalbavancin, daptomycin, tigecycline, linezolid and vancomycin to achieve their requisite pharmacokinetic/pharmacodynamic (PK/PD) targets against methicillin‐resistant Staphylococcus aureus isolates collected from intensive care unit (ICU) settings.

Monte Carlo simulations were carried out to simulate the PK/PD indices of the investigated antimicrobials. The probability of target attainment (PTA) was estimated at minimum inhibitory concentration values ranging from 0.03 to 32 μg/mL to define the PK/PD susceptibility breakpoints. The cumulative fraction of response (CFR) was computed using minimum inhibitory concentration data from the Canadian National Intensive Care Unit study.

Analysis of the simulation results suggested the breakpoints of 4 μg/mL for ceftobiprole (500 mg/2 h t.i.d.), 0.25 μg/mL for dalbavancin (1000 mg), 0.12 μg/mL for daptomycin (4 mg/kg q.d. and 6 mg/kg q.d.) and tigecycline (50 mg b.i.d.), and 2 μg/mL for linezolid (600 mg b.i.d.) and vancomycin (1 g b.i.d. and 1.5 g b.i.d.). The estimated CFR were 100, 100, 70.6, 88.8, 96.5, 82.4, 89.4, and 98.3% for ceftobiprole, dalbavancin, daptomycin (4 mg/kg/day), daptomycin (6 mg/kg/day), linezolid, tigecycline, vancomycin (1 g b.i.d.) and vancomycin (1.5 g b.i.d.), respectively.

In conclusion, ceftobiprole and dalbavancin have the highest probability of achieving their requisite PK/PD targets against methicillin‐resistant Staphylococcus aureus isolated from ICU settings. The susceptibility predictions suggested a reduction of the vancomycin breakpoint to 1 μg/mL.
Rapid recovery in sub‐optimal readers in Wales through a self‐paced computer‐based reading programme
Authors: Reed Phil , Hughes Antony , Phillips Gordon
Published: December 2013

Basic literacy skills underlie much future adult functioning, and are targeted in children through a variety of means. Children with identified special needs in reading were exposed to a self‐paced computer‐based reading programme that focused on improving phonetic ability. Exposure was limited to three, 40‐minute sessions a week, for 10 weeks. The children were assessed in terms of their reading, spelling and mathematics abilities before the programme commenced, and immediately after the programme terminated. The programme improved reading and spelling by about eight months, but had no impact on mathematics. The results suggest that brief exposure to a self‐paced phonetic computer‐based teaching programme had some benefits for the sample.
Houses of Experiment: Modern Housing and the Will to Laboratorization
Authors: Strebel Ignaz , Jacobs Jane M.
Published: December 2013

This article adds historical and geographical specificity to the link between city building and laboratorization processes. It does so by way of the example of housing in mid‐twentieth‐centuryBritain. Housing provision at this time saw an intensification of the relationship between architectural design and science by way of the emergent field of building science as well as new social‐science studies of householder satisfaction. The article focuses on two examples of these housing sciences, tracing their role in the production ofBritish modern housing. The first example focuses on a set of experiments conducted on ventilation and heating atBritain's Building Research Station. The second example examines the social science of a post‐occupancy study of multi‐storey flats inGlasgow. The article argues that mid‐twentieth‐century housing construction and provision was structured in and through a laboratory logic that had a complex geography and temporality. In the sciences of housing conducted during this period there is a conflation and hybridization of the space of the laboratory, the site of the house and the action of the experiment.
Feeling like a State: Design Guidelines and the Legibility of ‘Urban Experience’ in Singapore
Authors: Lee Kah‐Wee
Published: December 2013

This article examines how ‘urban experience’ is objectified and transformed into something that is legible to the state and its experts. It conceptualizes design guidelines as a political technology where bodies of expert knowledge, emplaced in a planning bureaucracy, shape the way the built environment is produced and experienced. Using Singapore as an example of a centralized planning bureaucracy, I analyze how lighting, public art and advertisement signs are targeted to produce a total environment with normative narratives. This article makes two contributions. First, it unpacks the processes that translate different modes of legibility in an attempt to make ‘experience’ legible for planners. The political efficacy of guidelines and pre‐established bureaucratic boundaries means that planners can only intervene through a series of combinations, mediations and approximations. Thus, legibility proceeds in a way that is akin to ‘feeling around’. Second, it foregrounds the ‘middle layer of urban governance’ that is often ignored in the discipline. Guidelines represent one coordinate in a system of political technologies that is concerned with producing the norm, that substrate of urban production mechanized through a series of repetitions, gradations and classifications.
An Update on the Clinical Development of Proprotein Convertase Subtilisin Kexin 9 Inhibitors, Novel Therapeutic Agents for Lowering Low‐Density Lipoprotein Cholesterol
Authors: Ling Hua , Burns Tammy L. , Hilleman Daniel E.
Published: December 2013

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an essential role in the degradation of low‐density lipoprotein C (LDL‐C) receptors, and PCSK9 inhibitors have recently emerged as a potential treatment option to reduce LDL‐C. Our paper reviewed the current available Phase II clinical trials of PCSK9 inhibitors for the treatment of dyslipidemia. A second objective of this review was to evaluate the potential clinical role of PCSK9 inhibitors in the management of dyslipidemia. Studies evaluating the efficacy and safety of any PCSK9 inhibitors in patients with dyslipidemia were included. The monoclonal antibodies REGN727/SAR236553 and AMG145 have the most published clinical data. Seven phase II trials were retrieved that evaluated the efficacy and safety of REGN727/SAR236553 or AMG145 in patients with either hypercholesterolemia or heterozygous familial hypercholesterolemia (HeFH). These two agents significantly decreased LDL‐C levels either as monotherapy or in combination with other lipid‐lowering agents. REGN727/SAR236553 and AMG145 have been well tolerated. The ongoing phase III trials of these two agents are summarized. REGN727/SAR236553 and AMG145 have demonstrated the potential to further decrease LDL‐C levels when added to conventional lipid‐lowering therapy. Morbidity and mortality data are required to define their roles in clinical practice.
P44, the ‘longevity‐assurance’ isoform of P53, regulates tau phosphorylation and is activated in an age‐dependent fashion
Authors: Pehar Mariana , Ko Mi Hee , Li Mi , Scrable Heidi , Puglielli Luigi
Published: December 2013

p44 is a short isoform of p53 with ‘longevity‐assurance’ activity. Overexpression of p44 in the mouse (p44+/+ transgenic mice) causes a progeroid phenotype that mimics an accelerated form of aging. The phenotype includes abnormal phosphorylation of the microtubule‐binding protein tau, synaptic deficits, and cognitive decline. Genetic engineering demonstrated that the phosphorylation status of tau acts upstream of the synaptic deficits. Here, we provide evidence that p44 promotes the phosphorylation of tau in the mouse. Specifically, we show that p44 binds to the promoter of tau kinases Dyrk1A, GSK3β, Cdk5, p35, and p39 and activates their transcription. The upregulation of the above kinases is followed by increased phosphorylation of tau. Finally, we show that p44 is preferentially found in the nucleus and that its levels increase with age in the mouse brain. Taken together, these results suggest that an imbalance in the p53:p44 ratio might be involved with the altered tau metabolism that characterizes aging.
Variation in the coding and 3′ untranslated regions of the porcine prolactin receptor short form modifies protein expression and function
Authors: Trott Josephine F. , Freking Bradley A. , Hovey Russell C.
Published: December 2013

The actions of prolactin (PRL) are mediated by both long (LF) and short isoforms (SF) of the PRL receptor (PRLR). Here, we report on a genetic and functional analysis of the porcine PRLR (pPRLR) SF. Three single nucleotide polymorphisms (SNPs) within exon 11 of the pPRLR‐SF give rise to four amino acid haplotypes of the intracellular domain. We identified the dimorphic insertion of a short interspersed repetitive DNA element (PRE‐1) along with 32 SNPs and four other insertion/deletion sites within the 3′ untranslated region (UTR) of pPRLR‐SF. The PRE‐1 element reduced protein translation in vitro by 75%, whereas the combination of 10 SNPs and one insertion/deletion decreased translation by 50%. Full‐length cDNAs for all four haplotypes of pPRLR‐SF were cloned behind the elongation factor 1‐alpha promoter and functionally analyzed in vitro. None of the haplotypes could initiate transcription from the ß‐casein promoter, whereas all four were dominant negatives against PRL‐activation of the pPRLR‐LF. Two of the haplotypes completely inhibited pPRLR‐LF activity at a four‐fold excess, whereas the others required a six‐fold excess to impart the same effect. The ligand binding affinities of the pPRLR‐SF haplotypes did not differ. Expression of the pPRLR‐SF increased linearly during gestation in the endometrium and was hormonally regulated in a tissue‐specific manner in the mammary glands and uterus. In conclusion, we identified a PRE‐1 and other SNPs in the pPRLR‐SF 3′ UTR that reduce protein expression and four haplotypes of the pPRLR‐SF that suppress pPRLR‐LF signaling and may differentially impact the phenotypic effects of PRL in vivo.
Structural transformation and smallholder agriculture: an information‐theoretic analysis of the Nicaraguan case
Authors: Henderson Heath
Published: December 2013

In light of continued debate regarding the capacity of small‐scale agricultural producers to compete amidst globalization and/or liberalization, we examine recent trends in the distribution and use of agricultural landholdings in developing nations via refined exploration of the Nicaraguan case. With nationally‐representative, Living Standards Measurement Survey‐type data for the years 1998, 2001, and 2005, we employ Markov chain methods within an information‐theoretic framework in an attempt to advance the analysis of structural transformation in developing countries beyond the examination of trends in mean farm sizes or Gini coefficients, approaches ill‐suited to the detection of the apparent complexities of structural change. Further, while Markov chain analysis has witnessed relatively widespread application in the investigation of structural transformation in developed nations, we offer a novel methodological extension by allowing for the simultaneous exploration of structural transformation across multiple dimensions–namely, structural change in both the distribution and use of agricultural landholdings—as well as the incorporation of microlevel determinants of farm size and land use change. The results of the inquiry, above all, suggest that Nicaragua's agricultural and livestock sector is characterized by a definitive persistence of smallholders. While a moderate tendency toward bifurcation in the distribution of landholdings would appear to obscure any immediate relationship between operational landholdings and land productivity, we contend that such trends are, in fact, consistent with the often observed inverse farm size‐productivity relationship.
Association between nonsteroidal anti‐inflammatory drug use and brain tumour risk: a meta‐analysis
Authors: Liu Yanqiong , Lu Yu , Wang Jian , Xie Li , Li Taijie , He Yu , Peng Qiliu , Qin Xue , Li Shan
Published: December 2013

Aims

Several epidemiological studies have evaluated the association between nonsteroidal anti‐inflammatory drugs (NSAIDs) and brain tumour risk. However, results from these studies have been inconsistent. The aim of this detailed meta‐analysis is to review and summarize the evidence on this association.

Methods

A comprehensive search for articles published up to September 2013 was performed. Studies evaluating the association between exposure to NSAIDs and risk of brain tumours were included. Random‐effects meta‐analytical models were used to calculate the relative risk (RR) and corresponding 95% confidence intervals (CIs). Sensitivity analyses, Galbraith plots and subgroup analyses were also performed.

Results

Ten studies (six case–control studies, three cohort studies and one randomized controlled trial), published between 2003 and 2013, were included in this analysis. Compared with non‐use, overall use of NSAIDs was not statistically significantly associated with brain tumour risk based on the random‐effects models (RR = 1.01; 95% CI = 0.89, 1.15). No differences were observed when analyses were stratified by gender and brain tumour subtype. Specific analysis for aspirin and non‐aspirin NSAIDs yielded similar results. However, a slightly increased risk of brain tumour in NSAID users was observed in cohort studies (RR = 1.32; 95% CI = 1.06, 1.64; P = 0.014). Furthermore, our analysis did not show a significant association between frequency and dose of aspirin use and brain tumour risk.

Conclusions

Use of NSAIDs (aspirin and non‐aspirin NSAIDs) does not appear to be associated with brain tumour risk, but larger studies are needed to substantiate this relationship.
Baby‐Friendly Hospital Practices and Birth Costs
Authors: Allen Jessica A , Longenecker Holly B , Perrine Cria G , Scanlon Kelley S
Published: December 2013

Background

Hospital practices supportive of breastfeeding can improve breastfeeding rates. There are limited data available on how improved hospital practices are associated with hospital costs. We describe the association between the number of breastfeeding supportive practices a hospital has in place and the cost of an uncomplicated birth.

Methods

Data from hospitals in 20 states that participated in the 2007 Maternity Practices in Infant Nutrition and Care (mPINC) survey and Healthcare Cost and Utilization Project's (HCUP) State Inpatient Databases (SID) were merged to calculate the average median hospital cost of uncomplicated vaginal and cesarean section births by number of ideal practices from the Ten Steps to Successful Breastfeeding. Linear regression analyses were conducted to estimate change in birth cost for each additional ideal practice in place.

Results

Sixty‐one percent of hospitals had ideal practice on 3–5 of the 10 steps, whereas 29 percent of hospitals had ideal practice on 6–8. Adjusted analyses of uncomplicated births revealed a higher but nonsignificant increase in any of the birth categories (all births, $19; vaginal, $15; cesarean section, $39) with each additional breastfeeding supportive maternity care practice in place.

Conclusions

Our results revealed that the number of breastfeeding supportive practices a hospital has in place is not significantly associated with higher birth costs. Concern for higher birth costs should not be a barrier for improving maternity care practices that support women who choose to breastfeed.
Safety and efficacy of 90Yttrium‐Ibritumomab‐Tiuxetan for untreated follicular lymphoma patients. An Italian cooperative study
Authors: Ibatici Adalberto , Pica Gian Matteo , Nati Sandro , Vitolo Umberto , Botto Barbara , Ciochetto Chiara , Petrini Mario , Galimberti Sara , Ciabatti Elena , Orciuolo Enrico , Zinzani Pier Luigi , Cascavilla Nicola , Guolo Fabio , Fraternali Orcioni Giulio , Carella Angelo M.
Published: December 2013

90Yttrium (90Y)‐Ibritumomab‐Tiuxetan combines the targeting advantage of a monoclonal antibody with the radiosensitivity of Follicular Lymphoma (FL). Previous studies showed that 90Y‐IT is safe and effective in relapsed/refractory indolent FL, irrespective of prior treatment with rituximab. This multicentre trial aimed to evaluate the safety and the efficacy of “upfront” single‐agent (90Y)‐Ibritumomab‐Tiuxetan in advanced‐stage FL. The primary objective was the incidence of responses in terms of complete (CR) and partial remission (PR). Fifty patients with stage II “bulky”, III or IV FL received a single treatment course with (90Y)‐Ibritumomab‐Tiuxetan as initial therapy. The median age was 60 years. Bone marrow involvement (<25%) was observed in 24 patients (48%) and 7 (14%) had an elevated lactate dehydrogenase level. The overall response (ORR) and CR rates were 94% and 86%, respectively with a median follow‐up of 38·8 months. The median progression‐free survival (PFS) was not reached, whereas the 3‐year estimated PFS and overall survival (OS) rate was 63·4% and 90%, respectively. Grade 3/4 neutropenia and thrombocytopenia occurred in 30% and 26% of patients respectively; none experienced grade 3/4 non‐haematological toxicity. No cases of secondary haematological malignancies were observed. (90Y)‐Ibritumomab‐Tiuxetan was demonstrated to be highly effective and safe as first‐line treatment for advanced‐stage FL.
Interindividual variability in social insects – proximate causes and ultimate consequences
Authors: Jeanson Raphaël , Weidenmüller Anja
Published: December 2013

Individuals within social groups often show consistent differences in behaviour across time and context. Such interindividual differences and the evolutionary challenge they present have recently generated considerable interest. Social insects provide some of the most familiar and spectacular examples of social groups with large interindividual differences. Investigating these within‐group differences has a long research tradition, and behavioural variability among the workers of a colony is increasingly regarded as fundamental for a key feature of social insects: division of labour. The goal of this review is to illustrate what we know about both the proximate mechanisms underlying behavioural variability among the workers of a colony and its ultimate consequences; and to highlight the many open questions in this research field. We begin by reviewing the literature on mechanisms that potentially introduce, maintain, and adjust the behavioural differentiation among workers. We highlight the fact that so far, most studies have focused on behavioural variability based on genetic variability, provided by e.g. multiple mating of the queen, while other mechanisms that may be responsible for the behavioural differentiation among workers have been largely neglected. These include maturational, nutritional and environmental influences. We further discuss how feedback provided by the social environment and learning and experience of adult workers provides potent and little‐explored sources of differentiation. In a second part, we address what is known about the potential benefits and costs of increased behavioural variability within the workers of a colony. We argue that all studies documenting a benefit of variability so far have done so by manipulating genetic variability, and that a direct test of the effect of behavioural variability on colony productivity has yet to be provided. We emphasize that the costs associated with interindividual variability have been largely overlooked, and that a better knowledge of the cost/benefit balance of behavioural variability is crucial for our understanding of the evolution of the mechanisms underlying the social organization of insect societies. We conclude by highlighting what we believe to be promising but little‐explored avenues for future research on how within‐colony variability has evolved and is maintained. We emphasize the need for comparative studies and point out that, so far, most studies on interindividual variability have focused on variability in individual response thresholds, while the significance of variability in other parameters of individual response, such as probability and intensity of the response, has been largely overlooked. We propose that these parameters have important consequences for the colony response. Much more research is needed to understand if and how interindividual variability is modulated in order to benefit division of labour, homeostasis and ultimately colony fitness in social insects.
Mesenchymal‐transitioned cancer cells instigate the invasion of epithelial cancer cells through secretion of WNT3 and WNT5B
Authors: Kato Shinichiro , Hayakawa Yoshihiro , Sakurai Hiroaki , Saiki Ikuo , Yokoyama Satoru
Published: December 2013

Although the heterogeneities of epithelial and mesenchymal‐transitioned cancer cells are often observed within the tumor microenvironment, the biological significance of the interaction between epithelial cancer cells and mesenchymal‐transitioned cancer cells is not yet understood. In this study, we show that the mesenchymal‐transitioned cancer cells instigate the invasive ability and metastatic potential of the neighboring epithelial cancer cells in vitro and in vivo. We identify WNT3 and WNT5B as critical factors secreted from Transforming growth factor‐induced mesenchymal cancer cells for instigating the epithelial cancer cell invasion along with the induction of secondary EMT phenotype. These results shed light on the significance of cancer heterogeneity and the interaction between epithelial and mesenchymal‐transitioned cancer cells within the tumor microenvironment in promoting metastatic disease through the WNT‐dependent mechanism.
764. PINUS AMAMIANA
Authors: Ohba Hideaki
Published: December 2013

Pinus amamiana Koidz., an endangered pine from Yakushima and Tanegashima, is illustrated and described. Threats to its survival are discussed.
773. GINKGO BILOBA – Connections with people and art across a thousand years
Authors: Crane Peter R. , Nagata Toshiyuki , Murata Jin , Ohi‐Toma Tetsuo , DuVal Ashley , Nesbitt Mark , Jarvis Charles
Published: December 2013

We review the representation of Ginkgo biloba L., a quintessentially Chinese plant, in the art of those Western botanists who first encountered it in China and Japan. We also show how several later representations of Ginkgo, in both the West and the East, were inspired and made possible by specimens of Ginkgo in cultivation.
Cardiovascular disease risk factors in the South Asian population living in Kuwait: a cross‐sectional study
Authors: Elkum N. , Al‐Arouj M. , Sharifi M. , Behbehani K. , Bennakhi A.
Published: December 2013

Background

High rates of diabetes and cardiovascular disease have been reported in South Asian immigrants in many countries. However, the prevalence and characteristics of cardiovascular disease risk factors among a South Asian population living in Kuwait have not yet been investigated. This study was therefore designed to estimate the prevalence of cardiovascular disease risk factors and determine whether they are independently associated with diabetes in such a population.

Methods

A population‐based cross‐sectional study was conducted on 1094 South Asians (781 men and 313 women), mainly Indian and Pakistani (≥ 18 years of age), of whom 75.1% were Indians. Interviews were carried out, during which socio‐demographic and anthropometric data were collected, followed by a physical examination and collection of fasting blood samples for laboratory investigations. Diabetes was defined by fasting plasma glucose ≥ 7 mmol/l, or being on treatment, and/or self‐reported previously diagnosed Type 2 diabetes.

Results

The prevalence of diabetes was 21.1%, with 3.4% of that percentage of people being newly diagnosed. Using BMI measurements, 24.0% of those who participated in the study were obese and 46.1% were overweight. Dyslipidaemia was found in 77.6% and hypertension in 44.8%. Advancing age (≥ 40 years), male gender, high LDL, high total cholesterol, hypertension and positive family history of diabetes were significantly associated with increased risk of diabetes.

Conclusion

Our study shows that the prevalence of cardiovascular disease risk factors in South Asian expatriates in Kuwait exceeds prevalence rates reported in their homeland and other countries. This may suggest the added stress of environmental factors on the development of cardiovascular disease risk factors in such populations. Specialized prevention programmes targeting such high‐risk ethnic populations are paramount and need to be implemented.
Pre‐hospital delay in patients with diabetic foot problems: influencing factors and subsequent quality of care
Authors: Yan J. , Liu Y. , Zhou B. , Sun M.
Published: December 2013

Aims

To assess pre‐hospital patient delay and its associated variables in patients with diabetic foot problems.

Methods

We classified 270 patients with diabetic foot problems retrospectively based on the distribution of pre‐hospital delay. Clinical, demographic and socio‐economic data were collected. Logistic regression analysis was performed to examine independent associations with patient delay.

Results

The median pre‐hospital delay time was 46.49 days. Patients reported short (≤ 1 week; 77 patients, 28.5%), moderate (> 1 week and ≤ 1 month; 106 patients, 39.3%) and long delays (> 1 month; 87 patients, 32.2%). In a univariate analysis, nine variables were associated with a longer delay (P < 0.05): (1) no previous ulcer; (2) no health insurance; (3) poor housing conditions; (4) low income level; (5) low educational level; (6) infrequent foot inspection; (7) few follow‐up medical visits; (8) absence of diabetic foot education; (9) lack of knowledge of foot lesion warning signals. A multivariate analysis showed that absence of diabetic foot education (odds ratio 2.70, 95% CI1.03–7.06,P = 0.043) and lack of knowledge of foot lesion warning signals (odds ratio 2.14, 95% CI1.16–3.94,P = 0.015) were independent predictors of long patient delay. Long delay increased the risk of amputation (odds ratio 2.22, 95% CI1.36–3.64,P = 0.002) and mortality (odds ratio 2.69, 95% CI1.35–5.33,P = 0.005).

Conclusions

A number of factors were involved in pre‐hospital delay among patients with diabetic foot problems and contributed to poor outcomes. We recommend developing a community intervention programme that targets at‐risk communities to encourage earlier multidisciplinary team assessment to reduce disparities and improve foot outcomes in patients with diabetes.
RD Lawrence Lecture 2013 Stratified approaches to the management of diabetes
Authors: Pearson E.
Published: December 2013

A stratified approach to medicine aims to identify subgroups of patients who should be managed differently from others. Diabetes is a condition that offers considerable potential for stratification, in areas of drug response, complication risk and rate of progression amongst others. Approaches to stratification can be simple, using clinical phenotyping, or more complex involving genomic and other ‘–omic’ technologies. In this review, I will highlight the utility of measuring endogenous insulin production to aid in diagnosis and appropriate treatment; outline key advances in monogenic diabetes where determining genetic aetiology can result in dramatic changes in treatment, and describe the developments in the field of pharmacogenetics in Type 2 diabetes.
Defining Characteristics of Early Adopters of Multimodality Cardiovascular Imaging
Authors: Velez Michael R. , Auseon Alex J.
Published: December 2013

Background

The prototype for the cardiovascular imager has evolved to necessitate some degree of competency in multimodality imaging (MMI)—defined as expertise in at least 2 of the 4 modalities (echocardiography [ECHO], nuclear cardiology [NUC], cardiovascular computed tomography [CCT], and magnetic resonance [CMR]). Uncertainty exists about the effects of this change.

Methods

Information detailing the current totals of board‐certified practitioners in MMI was collected and organized into groups of 1, 2, and 3 modalities. A randomized stratified sample of names was obtained to identify a representative 10% of each group. Those names were cross‐referenced online with information from state medical boards, faculty rosters of academic medical centers, and physician tracking Websites.

Results

There are a total of 2209 board‐certified MMI practitioners (2 modalities = 1885, 3 modalities = 324) and 6450 single‐modality imagers in the United States. Of those sampled, 98.9% were cardiologists, 31.3% were at academic medical centers and mean time from medical school graduation was 17.75 years. MMI practitioners were more likely to have graduated from medical school more recently (P < 0.0001) and to be trained cardiologists (P = 0.003) than those who practice in a single modality. There was a nonsignificant trend toward MMI being practiced more commonly in an academic setting (P = 0.38).

Conclusion

Board‐certified specialists in MMI tend to be younger cardiologists than those engaged in single‐modality cardiac imaging. There are few advanced (3 modality) MMI practitioners in the United States.
Primary Cardiac Lymphoma Presenting as an Atypical Type of Hypertrophic Cardiomyopathy
Authors: Kim Dong‐Hyeok , Kim Yong‐Hyun , Song Woo‐Hyuk , Ahn Jeong‐Cheon
Published: December 2013

Primary cardiac lymphoma (PCL) is a very rare malignancy although cardiac involvement with the disseminated disease is not uncommon. We present a case of a 43‐year‐old man with PCL that initially presented as marked thickening of all cardiac walls and was mistakenly diagnosed as an atypical type of hypertrophic cardiomyopathy. The diagnosis of PCL was made with a delay of 9 months after the initial presentation, when atypical lymphocytes staining positive for CD79a and CD20 were demonstrated in the rapidly growing mediastinal and neck mass. Anthracycline‐based chemotherapy and anti‐CD20 immunotherapy resulted in a remarkable reduction in cardiac wall thickness and mediastinal mass. The first lesson to be learnt from this case is that PCL can present as a diffuse infiltrative disease without a mass. The second lesson is that prompt exploratory thoracotomy should not be delayed when the diagnosis is elusive.
Assessment of Two‐Component Ventricular Septum: Functional Differences in Systolic Deformation and Rotation Assessed by Speckle Tracking Imaging
Authors: Hayabuchi Yasunobu , Sakata Miho , Kagami Shoji
Published: December 2013

Background

The purpose of this study was to elucidate functional differences in the right and left components of the ventricular septum (Rt and Lt, respectively).

Methods

Strain, strain rate, rotation, and rotation rate profile curves of Rt and Lt were obtained using speckle tracking echocardiography in 38 normal children and adolescents.

Results

The echogenic bright line serving as the boundary separating Rt from Lt was consistently visible in the middle of the ventricular septum. There was no significant difference in peak strain or peak strain rate during systole between Rt and Lt. However, the time interval from the onset of QRS‐wave to peak strain and peak strain rate were significantly lower in Lt than in Rt in terms of radial and circumferential deformation (P < 0.005, all), whereas there was no significant difference in longitudinal deformation in the time to peak strain or peak strain rate between Rt and Lt. Lt showed counterclockwise rotation, whereas Rt showed clockwise rotation (10.4 ± 2.9° vs. –10.2 ± 2.6°, P < 0.0001). Time to peak rotation was significantly lower in Lt than in Rt (201.7 ± 32.7 msec vs. 370.4 ± 31.2 msec, P < 0.0001).

Conclusion

Morphologically and functionally the ventricular septum is a two‐component structure. Evaluation of deformation and rotation of the 2 components would help in evaluating septal performance.
Prognostic value of culprit site neutrophils in acute coronary syndrome
Authors: Distelmaier Klaus , Winter Max‐Paul , Dragschitz Florian , Redwan Bassam , Mangold Andreas , Gleiss Andreas , Perkmann Thomas , Maurer Gerald , Adlbrecht Christopher , Lang Irene M.
Published: December 2013

Background

Recent data suggest that acute coronary syndromes (ACS) and acute myocardial infarction (AMI) are characterized by an inflammatory subset of thrombosis. We have previously described the accumulation of neutrophils at the coronary culprit lesion site. In this work, we assessed the prognostic value of culprit site (CS) neutrophil accumulation on long‐term mortality in patients with AMI.

Materials and methods

In this prospective study, 417 AMI patients were enrolled after thrombectomy during primary percutaneous coronary intervention. The optimal cut‐off for CS neutrophil accumulation for predicting 4‐year all‐cause mortality was calculated using time‐dependent receiver operator characteristic curve analyses.

Results

The median follow‐up time was 39 months interquartile range (IQR 21·4–54·6 months) corresponding to 1217 patient years of follow‐up. The cut‐off for CS neutrophil accumulation (difference between culprit neutrophil counts and systemic neutrophil counts) was 0·25 Giga/l. CS neutrophil accumulation occurred in 195 patients (47%) and was independently associated with mortality (hazard ratio 1·88 (95%CI 1·02–3·41, P = 0·043)). In patients with CS neutrophil accumulation, 1‐year mortality (10·8% vs. 7·2%) and 4‐year mortality (19·8% vs. 10·4%) were markedly increased compared with patients without local neutrophil accumulation. Concordance index for CS neutrophil accumulation and mortality was 0·64 (95% CI 0·51–0·77; P = 0·035). Patients with CS neutrophil accumulation had significantly more often nonobstructive lesions compared with patients without neutrophil accumulation (32·6% vs. 22·4%; P = 0·024).

Conclusions

Neutrophil accumulation at the coronary culprit lesion site is a strong and independent predictor of mortality in patients with ACS/AMI.