bluuebunny/crossref_metadata_2025 huggingface dataset:
Imatinib and pegylated IFN‐α2b discontinuation in first‐line chronic myeloid leukemia patients following a major molecular response
Authors: Koskenvesa Perttu , Kreutzman Anna , Rohon Peter , Pihlman Markus , Vakkila Emmi , Räsänen Anu , Vapaatalo Mirja , Remes Kari , Lundán Tuija , Hjorth‐Hansen Henrik , Vakkila Jukka , Simonsson Bengt , Mustjoki Satu , Porkka Kimmo
Published: December 2013

Objectives

Previous studies indicate that 40–50% of patients with chronic myeloid leukemia in prolonged complete molecular remission may discontinue imatinib therapy without imminent relapse. The combination of pegylated interferon‐alpha (Peg‐IFN‐α2b) and imatinib may increase the rate of successful discontinuation.

Methods

In this pilot study, we prospectively stopped imatinib from patients (n = 12) who had achieved major molecular response (MMR) after ≥12 months of treatment with either imatinib or imatinib+Peg‐IFN‐α2b. Molecular monitoring was carried out monthly for BCR‐ABL1. In addition, analyses of lymphocyte immunophenotype, function, and plasma cytokines were performed.

Results

In the monotherapy group, 5/6 patients lost MMR within 4 months. One patient remains to date in MR4.0 61 months after discontinuation. In the combination therapy group, 2/6 patients relapsed within 4 months while still receiving Peg‐IFN‐α2b. Four of six patients were able to discontinue both treatments, but three of these patients relapsed after 3 months. One patient is still in sustained MR4.0 at 58 months off all treatment. All relapsed patients re‐responded to imatinib. The two successfully discontinued patients had either an increased number of NK‐cells or functionally active T‐cells.

Conclusions

A higher frequency of relapsed patients in our study in comparison with other studies may be due to the shorter duration of imatinib treatment prior to discontinuation. However, in selected patients with an active immune system, even a short duration of TKI therapy (<2 yr) may allow for therapy discontinuation but this needs to be confirmed in larger prospective studies.
Frontal lobe seizures: From clinical semiology to localization
Authors: Bonini Francesca , McGonigal Aileen , Trébuchon Agnès , Gavaret Martine , Bartolomei Fabrice , Giusiano Bernard , Chauvel Patrick
Published: December 2013

Objective

Frontal lobe seizures are difficult to characterize according to semiologic and electrical features. We wished to establish whether different semiologic subgroups can be identified and whether these relate to anatomic organization.

Methods

We assessed all seizures from 54 patients with frontal lobe epilepsy that were explored with stereoelectroencephalography (SEEG) during presurgical evaluation. Semiologic features and concomitant intracerebralEEGchanges were documented and quantified. These variables were examined using Principal Component Analysis and Cluster Analysis, and semiologic features correlated with anatomic localization.

Results

Four main groups of patients were identified according to semiologic features, and correlated with specific patterns of anatomic seizure localization. Group 1 was characterized clinically by elementary motor signs and involved precentral and premotor regions. Group 2 was characterized by a combination of elementary motor signs and nonintegrated gestural motor behavior, and involved both premotor and prefrontal regions. Group 3 was characterized by integrated gestural motor behavior with distal stereotypies and involved anterior lateral and medial prefrontal regions. Group 4 was characterized by seizures with fearful behavior and involved the paralimbic system (ventromedial prefrontal cortex ± anterior temporal structures). The groups were organized along a rostrocaudal axis, representing bands within a spectrum rather than rigid categories. The more anterior the seizure organization, the more likely was the occurrence of integrated behavior during seizures. Distal stereotypies were associated with the most anterior prefrontal localizations, whereas proximal stereotypies occurred in more posterior prefrontal regions.

Significance

Meaningful categorization of frontal seizures in terms of semiology is possible and correlates with anatomic organization along a rostrocaudal axis, in keeping with current hypotheses of frontal lobe hierarchical organization. The proposed electroclinical categorization offers pointers as to the likely zone of organization of networks underlying semiologic production, thus aiding presurgical localization. Furthermore, analysis of ictal motor behavior in prefrontal seizures, including stereotypies, leads to deciphering the cortico‐subcortical networks that produce such behaviors.
A subset of genomic alterations detected in rolandic epilepsies contains candidate or known epilepsy genes including GRIN2A and PRRT2
Authors: Dimassi Sarra , Labalme Audrey , Lesca Gaetan , Rudolf Gabrielle , Bruneau Nadine , Hirsch Edouard , Arzimanoglou Alexis , Motte Jacques , de Saint Martin Anne , Boutry‐Kryza Nadia , Cloarec Robin , Benitto Afaf , Ameil Agnès , Edery Patrick , Ryvlin Philippe , De Bellescize Julitta , Szepetowski Pierre , Sanlaville Damien
Published: December 2013

Objectives

Rolandic epilepsies (REs) represent the most frequent epilepsy in childhood. Patients may experience cognitive, speech, language, reading, and behavioral issues. The genetic origin of REs has long been debated. The participation of rare copy number variations (CNVs) in the pathophysiology of various human epilepsies has been increasingly recognized. However, no systematic search for microdeletions or microduplications has been reported in RE so far.

Methods

Array comparative genomic hybridization (aCGH) and quantitative polymerase chain reaction (qPCR) were used to analyze the genomic status of a series of 47 unrelated RE patients who displayed various types of electroclinical manifestations.

Results

Thirty rare CNVs were detected in 21 RE patients. Two CNVs were de novo, 12 were inherited, and 16 were of unknown inheritance. Each CNV was unique to one given patient, except for a 16p11.2 duplication found in two patients. The CNVs of highest interest comprised or disrupted strong candidate or confirmed genes for epileptic and other neurodevelopmental disorders, including BRWD3, GRIN2A, KCNC3, PRKCE, PRRT2, SHANK1, and TSPAN7.

Significance

Patients with REs showed rare microdeletions and microduplications with high frequency and heterogeneity. Whereas only a subset of all genomic alterations found here may actually participate in the phenotype, the novel de novo events as well as several inherited CNVs contain or disrupt genes, some of which are likely to influence the emergence, the presentation, or the comorbidity of RE. The future screening of cohorts of larger size will help in detecting more de novo or recurrent events and in appreciating the possible enrichment of specific CNVs in patients with RE.
Increased expression of the histamine H4 receptor following differentiation and mediation of the H4 receptor on interleukin‐8 mRNA expression in HaCaT keratinocytes
Authors: Suwa Eriko , Yamaura Katsunori , Sato Shiori , Ueno Koichi
Published: December 2013

Recent in vivo studies have demonstrated involvement of the histamine H4 receptor in pruritus and skin inflammation. We previously reported that an H4 receptor antagonist attenuated scratching behaviour and improved skin lesions in an experimental model of atopic dermatitis. We also reported the expression of the H4 receptor in human epidermal tissues. In this study, we investigated the expression of H4 receptor mRNA and the function of the receptor in a culture system that mimics in vivo inflammation on the HaCaT human keratinocyte cell line. Increased expression of the H4 receptor was observed in HaCaT cells following differentiation. Treatment of HaCaT cells with histamine and TNFα enhanced the mRNA expression of interleukin (IL)‐8. These increases in expression were significantly inhibited by the H4 receptor antagonist JNJ7777120. Our results indicate that IL‐8 mRNA expression might be enhanced by histamine and TNFα via H4 receptor stimulation in keratinocytes.
Genetically meaningful phenotypic subgroups in autism spectrum disorders
Authors: Veatch O. J. , Veenstra‐VanderWeele J. , Potter M. , Pericak‐Vance M. A. , Haines J. L.
Published: December 2013

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with strong evidence for genetic susceptibility. However, the effect sizes for implicated chromosomal loci are small, hard to replicate and current evidence does not explain the majority of the estimated heritability. Phenotypic heterogeneity could be one phenomenon complicating identification of genetic factors. We used data from the Autism Diagnostic Interview‐Revised, Autism Diagnostic Observation Schedule, Vineland Adaptive Behavior Scales, head circumferences, and ages at exams as classifying variables to identify more clinically similar subgroups of individuals with ASD. We identified two distinct subgroups of cases within the Autism Genetic Resource Exchange dataset, primarily defined by the overall severity of evaluated traits. In addition, there was significant familial clustering within subgroups (odds ratio, OR ≈ 1.38–1.42, P < 0.00001), and genotypes were more similar within subgroups compared to the unsubgrouped dataset (Fst = 0.17 ± 0.0.0009). These results suggest that the subgroups recapitulate genetic etiology. Using the same approach in an independent dataset from the Autism Genome Project, we similarly identified two distinct subgroups of cases and confirmed this severity‐based dichotomy. We also observed evidence for genetic contributions to subgroups identified in the replication dataset. Our results provide more effective methods of phenotype definition that should increase power to detect genetic factors influencing risk for ASD.
The pneumatic tube system does not affect complete blood count results; a validation study at a tertiary care hospital
Authors: Al‐Riyami A. Z. , Al‐Khabori M. , Al‐Hadhrami R. M. , Al‐Azwani I. S. , Davis H. M. , Al‐Farsi K. S. , Alkindi S. S. , Daar S. F.
Published: December 2013

Introduction

Effect of the pneumatic tube system (PTS) on sample quality is controversial. Herein we aim at evaluating the impact of sample transportation via the PTS on complete blood count (CBC) results.

Methods

Duplicate CBC samples from normal donors and anemic patients were sent in parallel to the laboratory for testing through the PTS and the courier (CO). We used scatter plots, Bland–Altman plots, correlation coefficient (r), and coefficient of determination for the validation.

Results

A total of 115 samples (donors: 59, patients: 56) were tested. There was excellent correlation between both methods for red blood cell parameters (r range = 0.9213–0.9958) and platelet count. White blood cell (WBC) count and differential count showed similar results (r range = 0.8605–0.9821) for all, with exception of basophils which showed modest correlation (r = 0.4827 for patients and 0.5758 for normal donors). Most of the differences in measurement of all CBC parameters were within the 95% confidence interval of the mean difference on Bland–Altman plots.

Conclusion

Modern PTS can be safely used for transporting CBC samples.
Examining patients' preferences for participation in clinical decision‐making: the experience in a Latin American chronic obstructive pulmonary disease and cancer outpatient population
Authors: Jordan P. , Quadrelli S. , Heres M. , Belli L. , Ruhl N. , Colt H.
Published: December 2013

Background and Aims

It is generally accepted that patients prefer to be told the truth by their physicians; however, the practice of partial truth‐telling is frequent with an existing ‘norm of nondisclosure.’ Our primary objective was to determine what patients wanted to be told about their illness, and whether there might be differences between patients with either cancer or advanced chronic obstructive pulmonary disease (COPD). A second objective was to determine how these patients envisioned their participation, or lack thereof, in the treatment decision‐making process.

Methods

Subjects were eligible for this prospective study if they were attending the oncology or pulmonary outpatient consultation services at the British Hospital or the Sanatorio Güemes Private Hospital in Buenos Aires, Argentina between June 2009 and May 2010.

Results

Ninety‐nine patients were recruited. Forty‐four had a diagnosis of COPD, and 55 patients had cancer. Seventeen of the patients expected their health to improve in the future, but a significantly higher proportion of patients with malignant disorders expected to get better in the near future as compared with those with COPD (98.2% vs 62.8%, P < 0.001). Most study participants expressed a desire to receive all the information available about their condition. A majority of the participants expressed a preference for making treatment decisions in collaboration with their physician (40.4%)

Conclusions

While they considered the role of their families relevant and wanted information to be shared so that family members might participate in decision‐making, they did not want their families to have a right to withhold information, make final decisions.
Selective informality: The self‐limiting growth choices of small businesses in South Africa
Authors: BISCHOFF Christine , WOOD Geoffrey
Published: December 2013

Based on in‐depth interviews, this study explores the reasons why many South African small businesses abide by some aspects of labour law, but not others: they generally comply with legislated labour regulations, but less so with regulations set by the statutory industry‐level Bargaining Councils. Such selective engagement with the system is attributed to employer hostility to unions in the context of post‐apartheid industrial relations. Since a larger workforce attracts closer scrutiny by the Councils, small firms are reluctant to expand, relying on outsourcing to increase production. The very size of the firm is thus a pliable concept, positioned between formal and informal norms.
Uruguay's “single tax” social protection scheme for the self‐employed
Authors: AMARANTE Veronica , PERAZZO Ivone
Published: December 2013

Extending social security coverage to self‐employed workers is a major challenge in Latin America. In 2007, Uruguay eased the rules applying to its “single tax” social security scheme for microenterprises, as a result of which a considerable number of self‐employed workers were able to join. The authors analyse the characteristics and employment conditions of these workers between 2000 and 2010, look at how social security coverage increased as a result of the amended single tax scheme, and assess the scheme's potential for incorporating greater numbers of workers.
Informal employment in developed and developing economies: Perspectives and policy responses
Authors: WILLIAMS Colin C. , LANSKY Mark A.
Published: December 2013

The aim of this introductory article is to provide a critical overview of how informality has been defined and measured, together with selected findings on its extent and character, and a summary of competing views regarding its role in contemporary economies and how it can be tackled. The outcome is a set of conceptual frameworks for understanding both the burgeoning literature on informal employment and how each of the perspectives presented in this Special Issue contributes to the advancement of knowledge on this subject so as to set the scene for the articles that follow.
Minimum wage coverage and compliance in developing countries
Authors: RANI Uma , BELSER Patrick , OELZ Martin , RANJBAR Setareh
Published: December 2013

Using household and labour force survey data from 11 developing countries, the authors calculate rates of minimum wage compliance for formal/informal employees covered by current legislation and assess the average “depth” of violations. Though compliance is negatively related to the ratio of minimum to median wages, countries with a national minimum wage set at a meaningful level typically achieve higher compliance rates than countries with occupational or industry‐specific minimum wage systems. However, better compliance – especially for women, ethnic groups, and unskilled and informal workers – also depends on contextualized yet comprehensive minimum wage policies combining union/employer involvement, awareness‐raising and credible enforcement.
Triage: an investigation of the process and potential vulnerabilities
Authors: Hitchcock Maree , Gillespie Brigid , Crilly Julia , Chaboyer Wendy
Published: December 2013

Aim

To explore and describe the triage process in the Emergency Department to identify problems and potential vulnerabilities that may affect the triage process.

Background

Triage is the first step in the patient journey in the Emergency Department and is often the front line in reducing the potential for errors and mistakes.

Design

A fieldwork study to provide an in‐depth appreciation and understanding of the triage process.

Methods

Fieldwork included unstructured observer‐only observation, field notes, informal and formal interviews that were conducted over the months of June, July and August 2012. Over 170 hours of observation were performed covering day, evening and night shifts, 7 days of the week. Sixty episodes of triage were observed; 31 informal interviews and 14 formal interviews were completed. Thematic analysis was used.

Findings

Three themes were identified from the analysis of the data and included: ‘negotiating patient flow and care delivery through the Emergency Department’; ‘interdisciplinary team communicating and collaborating to provide appropriate and safe care to patients’; and ‘varying levels of competence of the triage nurse’. In these themes, vulnerabilities and problems described included over and under triage, extended time to triage assessment, triage errors, multiple patients arriving simultaneously, emergency department and hospital overcrowding.

Conclusion

Findings suggest that vulnerabilities in the triage process may cause disruptions to patient flow and compromise care, thus potentially impacting nurses' ability to provide safe and effective care.
Efficacy and Safety of Nighttime Dosing of Antihypertensives: Review of the Literature and Design of a Pragmatic Clinical Trial
Authors: Carter Barry L. , Chrischilles Elizabeth A. , Rosenthal Gary , Gryzlak Brian M. , Eisenstein Eric L. , Vander Weg Mark W.
Published: December 2013

Blood pressure exhibits circadian variability, and nighttime blood pressure is one of the best predictors of cardiovascular (CV) events. Adults with hypertension who lack a nighttime dipping pattern are at particularly high risk. Several studies have found that bedtime dosing of antihypertensive agents reduces sleep blood pressure and improves the dipping pattern in nondippers. One small study and 2 substudies of diabetes and chronic kidney disease suggest that bedtime dosing of ≥1 antihypertensives significantly reduced CV events. A Cochrane review of 5 studies found no difference in adverse events between morning and evening dosing. However, several evaluations in ophthalmology have found that nocturnal arterial hypotension precipitated ocular vascular disorders such as ischemic optic neuropathy. Some authors have suggested that additional studies of nighttime dosing of antihypertensive agents that evaluate CV events need to be conducted. The authors describe a randomized controlled pragmatic trial that is being planned at the University of Iowa and Duke University. Patients with hypertension and other comorbid conditions will be randomized to either continue morning dosing of all antihypertensive agents or to switch their nondiuretic medications to bedtime dosing. Patients will be followed for 36 to 42 months. This study will determine whether nighttime dosing reduces CV risk when compared with traditional morning dosing of antihypertensive agents.
KCNQ1 rs2237892 C→T gene polymorphism and type 2 diabetes mellitus in the Asian population: a meta‐analysis of 15,736 patients
Authors: Li Yan‐yan , Wang Xiang‐ming , Lu Xin‐zheng
Published: December 2013

The KCNQ1 rs2237892 C→T gene polymorphism is reportedly associated with T2DM susceptibility, but various studies show conflicting results. To explore this association in the Asian population, a meta‐analysis of 15,736 patients from 10 individual studies was performed. The pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were evaluated using random‐effect or fixed‐effect models. A significant relationship between the KCNQ1 rs2237892 C→T gene polymorphism and T2DM was observed in the Asian population under the allelic (OR, 1.350; 95% CI, 1.240–1.480; P < 0.00001), recessive (OR: 0.650; 95% CI: 0.570–0.730; P < 0.00001), dominant (OR: 1.450; 95% CI: 1.286–1.634; P < 0.00001), and additive (OR: 1.346; 95% CI: 1.275–1.422; P < 0.00001) genetic models. In the subgroup analysis by race, a significant association was found in Chinese, Korean and Malaysia population, but not in Indian population. KCNQ1 rs2237892 C→T gene polymorphism was found to be significantly associated with increased T2DM risk in the Asian population, except Indian population. The C allele of the KCNQ1 rs2237892 C→T gene polymorphism may confer susceptibility to T2DM.
Identification of Transposable Element Markers for a Rust (Puccinia arachidis Speg.) Resistance Gene in Cultivated Peanut
Authors: Mondal Suvendu , Hande Poonam , Badigannavar Anand M.
Published: December 2013

Peanut rust (Puccinia arachidis Speg.) affects pod yield and quality up to an extent of 10–50%. Efforts have been made on transferring the rust resistance gene to cultivated peanut species through interspecific hybridization. But, in most of the cases, it failed due to linkage drag of undesirable plant and pod features. Identification of tightly linked molecular markers will help to identify the desirable recombinants more efficiently. A recombinant inbred line population comprising 164 lines was developed from a cross between a rust‐resistant parent VG 9514 and a rust susceptible parent TAG 24. Using a modified bulk segregant analysis, 243 transposable element (TE) primer pairs were screened for putative linkage with rust resistance. Of the 243, 40 TE primer pairs were found polymorphic between parents and two transposable element markers, and TE 360 and TE 498 were found associated with rust resistance gene. Based on genetic mapping, TE 360 was found linked to the rust resistance gene at 4.5 cM distance. Identification of such markers could be applied for marker‐assisted selection of rust resistance plants in peanut.
Post‐paracentesis circulatory derangements are related to monocyte activation
Authors: Carl Daniel E. , Ghosh Siddharta , Cheng Jianfeng , Gehr Todd W. B. , Stravitz R. Todd , Sanyal Arun
Published: December 2013

Background & Aims

Post‐paracentesis circulatory dysfunction is associated with development of hepatorenal syndrome and increased mortality. The impact of large volume paracentesis (LVP) on the 24‐h blood pressure (BP) profile is unknown, and the relationship to Na+‐retentive and pro‐inflammatory cytokines also remains unknown. The aims of this study were to (i) define the effects of LVP with albumin administration on 24‐h BP profiles, and (ii) relate changes in BP over time to changes in Na+‐retentive hormones, clinical factors and inflammatory cytokines.

Methods

Ten patients undergoing LVP had 24‐h ambulatory BP monitoring performed pre‐ and post‐paracentesis. Markers of the innate immune system, bacterial translocation and Na+‐retentive hormones were drawn pre‐ and post‐LVP.

Results

Mean arterial pressure (MAP) dropped in nine of the 10 patients in the 24 h following a paracentesis compared to 24 h preceding the procedure (mean drop of 5.5 mmHg, P < 0.005). A mixed effects model was used to define time‐covariate interactions in predicting changes in BP profile. Monocyte chemotactic protein‐1 (MCP1) was associated with Δsystolic BP (β = −0.011, P < 0.05), Δdiastolic BP (β = −0.012, P < 0.05) and ΔMAP (β = −0.012, P < 0.05). Plasma renin activity was also significantly associated with Δsystolic BP (β = −0.21, P < 0.05). Renal function was also significantly reduced following LVP.

Conclusions

Systolic, diastolic and MAP decreased over 24 h after LVP compared to the 24 h pre‐LVP. This drop is related to increases in MCP‐1 after LVP. Increased MCP‐1, a marker of monocyte activation, was strongly related to changes in BP.
The importance of genomic novelty in social evolution
Authors: Sumner Seirian
Published: December 2013

Insect societies dominate the natural world: They mould landscapes, sculpt habitats, pollinate plants, sow seeds and control pests. The secret to their success lies in the evolution of queen (reproductive) and worker (provisioner and carer) castes (Oster & Wilson ). A major problem in evolutionary biology is explaining the evolution of insect castes, particularly the workers (Darwin ). Next‐generation sequencing technologies now make it possible to understand how genomic material is born, lost and reorganized in the evolution of alternative phenotypes. Such analyses are revealing a general role for novel (e.g. taxonomically restricted) genes in phenotypic innovations across the animal kingdom (Chen et al. 2013). In this issue of molecular ecology, Feldmeyer et al. (2014) provide overwhelming evidence for the importance of novel genes in caste evolution in an ant. Feldmeyer et al.'s study is important and exciting because it cements the role of genomic novelty, as well as conservation, firmly into the molecular jigsaw of social evolution. Evolution is eclectic in its exploitation of both old and new genomic material to generate replicated phenotypic innovations across the tree of life.
Identification of a broad family of lipid A late acyltransferases with non‐canonical substrate specificity
Authors: Rubin Erica J. , O'Brien John P. , Ivanov Petko L. , Brodbelt Jennifer S. , Trent M. Stephen
Published: December 2013

Most Gram‐negative organisms produce lipopolysaccharide (LPS), a complex macromolecule anchored to the bacterial membrane by the lipid A moiety. Lipid A is synthesized via the Raetz pathway, a conserved nine‐step enzymatic process first characterized in Escherichia coli. The Epsilonproteobacterium Helicobacter pylori uses the Raetz pathway to synthesize lipid A; however, only eight of nine enzymes in the pathway have been identified in this organism. Here, we identify the missing acyltransferase, Jhp0255, which transfers a secondary acyl chain to the 3′‐linked primary acyl chain of lipid A, an activity similar to that of E. coli LpxM. This enzyme, reannotated as LpxJ due to limited sequence similarity with LpxM, catalyses addition of a C12:0 or C14:0 acyl chain to the 3′‐linked primary acyl chain of lipid A, complementing an E. coli LpxM mutant. Enzymatic assays demonstrate that LpxJ and homologues in Campylobacter jejuni and Wolinella succinogenes can act before the 2′ secondary acyltransferase, LpxL, as well as the 3‐deoxy‐d‐manno‐octulosonic acid (Kdo) transferase, KdtA. Ultimately, LpxJ is one member of a large class of acyltransferases found in a diverse range of organisms that lack an E. coli LpxM homologue, suggesting that LpxJ participates in lipid A biosynthesis in place of an LpxM homologue.
CqsA–CqsS quorum‐sensing signal‐receptor specificity in Photobacterium angustum
Authors: Ke Xiaobo , Miller Laura C. , Ng Wai‐Leung , Bassler Bonnie L.
Published: December 2013

Quorum sensing (QS) is a process of bacterial cell–cell communication that relies on the production, detection and population‐wide response to extracellular signal molecules called autoinducers. The QS system commonly found in vibrios and photobacteria consists of the CqsA synthase/CqsS receptor pair. Vibrio cholerae CqsA/S synthesizes and detects (S)‐3‐hydroxytridecan‐4‐one (C10‐CAI‐1), whereas Vibrio harveyi produces and detects a distinct but similar molecule, (Z)‐3‐aminoundec‐2‐en‐4‐one (Ea‐C8‐CAI‐1). To understand the signalling properties of the larger family of CqsA–CqsS pairs, here, we characterize the Photobacterium angustum CqsA/S system. Many photobacterial cqsA genes harbour a conserved frameshift mutation that abolishes CAI‐1 production. By contrast, their cqsS genes are intact. Correcting the P. angustum cqsA reading frame restores production of a mixture of CAI‐1 moieties, including C8‐CAI‐1, C10‐CAI‐1, Ea‐C8‐CAI‐1 and Ea‐C10‐CAI‐1. This signal production profile matches the P. angustum CqsS receptor ligand‐detection capability. The receptor exhibits a preference for molecules with 10‐carbon tails, and the CqsS Ser168 residue governs this preference. P. angustum can overcome the cqsA frameshift to produce CAI‐1 under particular limiting growth conditions presumably through a ribosome slippage mechanism. Thus, we propose that P. angustum uses CAI‐1 signalling for adaptation to stressful environments.
Complications in pediatric scoliosis surgery
Authors: Sullivan Daniel J. , Primhak Robert A. , Bevan Cliff , Breakwell Lee M. , Humphreys Nigel
Published: December 2013

Background

Scoliosis surgery in childhood is associated with a range of postoperative complications that may require admission to the pediatric intensive care unit (PICU) or high‐dependency unit (HDU).

Aim

The aim of this study was to identify preoperative factors associated with PICU and HDU admissions after corrective surgery and devise a scoring system that could be used by clinicians to predict the level of dependency required postoperatively.

Methods

A retrospective case note review was carried out in 90 patients who underwent corrective scoliosis surgery at Sheffield Children's Hospital (SCH) between January 2008 and October 2010. Predictors of PICU and HDU requirement postoperatively were identified and a simple scoring system created using multiple logistic regression and receiver operator characteristic (ROC).

Results

There was a statistically significant difference in the preoperative parameters (pulmonary function, Cobb angle, and number of vertebrae fused) of those patients who required PICU or HDU care compared with those who did not. The area under the receiver operator characteristic curve for the final scoring system was 0.95 for PICU admission and 0.87 for HDU admission at the optimal cut‐off point, demonstrating good diagnostic accuracy.

Conclusions

The authors have identified a significant relationship between preoperative variables and the levels of dependency required postoperatively and have proposed a scoring system which can be used to aid decision‐making involving bed planning for patients after corrective scoliosis surgery. However, this work is based on the clinical course of a single set of patients who had surgery in a single tertiary center and has not been tested on patients from other centers.
Effect of meropenem with or without immunoglobulin as second‐line therapy for pediatric febrile neutropenia
Authors: Kobayashi Ryoji , Suzuki Daisuke , Sano Hirozumi , Kishimoto Kenji , Yasuda Kazue , Kobayashi Kunihiko
Published: December 2013

Background

Meropenem (MEPM) is widely used for treatment of febrile neutropenia. There have been many reports on MEPM for pediatric febrile neutropenia showing success rates of approximately 50–75%. Although i.v. immunoglobulin (IVIG) is widely used for treatment of infection with antibiotics, there has been no report on the efficacy of IVIG for pediatric febrile neutropenia. This prospective randomized study was therefore carried out to clarify the usefulness of MEPM with or without IVIG as second line‐therapy for pediatric febrile neutropenia.

Methods

A total of 61 pediatric patients with 146 episodes were judged to have failure of first‐line therapy (August 2008–April 2010: cefozopran vs cefepime; April 2010–April 2012: cefepime vs piperacillin/tazobactam) for febrile neutropenia, and were randomized to MEPM and MEPM + IVIG groups.

Results

MEPM with or without IVIG as second‐line therapy was effective in 68.1% of a total of 144 episodes. Success rates in the MEPM and MEPM + IVIG groups were 66.3% and 70.5%, respectively. Furthermore, success rates for patients with IgG <500 mg/dL were 62.5% in the MEPM group and 81.3% in the MEPM + IVIG group. This result, however, was not statistically significant, possibly because of the small sample size.

Conclusions

MEPM is effective and safe for second‐line treatment of febrile episodes in neutropenic pediatric patients. Moreover, IVIG is effective for patients with low serum IgG.
Plant biology in space: recent accomplishments and recommendations for future research
Authors: Ruyters G. , Braun M.
Published: December 2013

Gravity has shaped the evolution of life since its origin. However, experiments in the absence of this overriding force, necessary to precisely analyse its role, e.g. for growth, development, and orientation of plants and single cells, only became possible with the advent of spaceflight. Consequently, this research has been supported especially by space agencies around the world for decades, mainly for two reasons: first, to enable fundamental research on gravity perception and transduction during growth and development of plants; and second, to successfully grow plants under microgravity conditions with the goal of establishing a bioregenerative life support system providing oxygen and food for astronauts in long‐term exploratory missions. For the second time, the International Space Life Sciences Working Group (ISLSWG), comprised of space agencies with substantial life sciences programmes in the world, organised a workshop on plant biology research in space. The present contribution summarises the outcome of this workshop. In the first part, an analysis is undertaken, if and how the recommendations of the first workshop held in Bad Honnef, Germany, in 1996 have been implemented. A chapter summarising major scientific breakthroughs obtained in the last 15 years from plant research in space concludes this first part. In the second part, recommendations for future research in plant biology in space are put together that have been elaborated in the various discussion sessions during the workshop, as well as provided in written statements from the session chairs. The present paper clearly shows that plant biology in space has contributed significantly to progress in plant gravity perception, transduction and responses – processes also relevant for general plant biology, including agricultural aspects. In addition, the interplay between light and gravity effects has increasingly received attention. It also became evident that plants will play a major role as components of bioregenerative life support and energy systems that are necessary to complement physico‐chemical systems in upcoming long‐term exploratory missions. In order to achieve major progress in the future, however, standardised experimental conditions and more advanced analytical tools, such as state‐of‐the‐art onboard analysis, are required.
Low induction of non‐photochemical quenching and high photochemical efficiency in the annual desert plant Anastatica hierochuntica
Authors: Eppel Amir , Shaked Ruth , Eshel Gil , Barak Simon , Rachmilevitch Shimon
Published: December 2013

Non‐photochemical quenching (NPQ) plays a major role in photoprotection. Anastatica hierochuntica is an annual desert plant found in hot deserts. We compared A. hierochuntica to three other different species: Arabidopsis thaliana, Eutrema salsugineum and Helianthus annuus, which have different NPQ and photosynthetic capacities. Anastatica hierochuntica plants had very different induction kinetics of NPQ and, to a lesser extent, of photosystem II electron transport rate (PSII ETR), in comparison to all other plants species in the experiments. The major components of the unusual photosynthetic and photoprotective response in A. hierochuntica were: (1) Low NPQ at the beginning of the light period, at various light intensities and CO2 concentrations. The described low NPQ cannot be explained by low leaf absorbance or by low energy distribution to PSII, but was related to the de‐epoxidation state of xanthophylls. (2) Relatively high PSII ETR at various CO2 concentrations in correlation with low NPQ. PSII ETR responded positively to the increase of CO2 concentrations. At low CO2 concentrations PSII ETR was mostly O2 dependent. At moderate and high CO2 concentrations the high PSII ETR in A. hierochuntica was accompanied by relatively high CO2 assimilation rates. We suggest that A. hierochuntica have an uncommon NPQ and PSII ETR response. These responses in A. hierochuntica might represent an adaptation to the short growing season of an annual desert plant.
Flood Hazard and Flood Risk Assessment Using a Time Series of Satellite Images: A Case Study in Namibia
Authors: Skakun Sergii , Kussul Nataliia , Shelestov Andrii , Kussul Olga
Published: December 2013

In this article, the use of time series of satellite imagery to flood hazard mapping and flood risk assessment is presented. Flooded areas are extracted from satellite images for the flood‐prone territory, and a maximum flood extent image for each flood event is produced. These maps are further fused to determine relative frequency of inundation (RFI). The study shows that RFI values and relative water depth exhibit the same probabilistic distribution, which is confirmed by Kolmogorov‐Smirnov test. The produced RFI map can be used as a flood hazard map, especially in cases when flood modeling is complicated by lack of available data and high uncertainties. The derived RFI map is further used for flood risk assessment. Efficiency of the presented approach is demonstrated for the Katima Mulilo region (Namibia). A time series of Landsat‐5/7 satellite images acquired from 1989 to 2012 is processed to derive RFI map using the presented approach. The following direct damage categories are considered in the study for flood risk assessment: dwelling units, roads, health facilities, and schools. The produced flood risk map shows that the risk is distributed uniformly all over the region. The cities and villages with the highest risk are identified. The proposed approach has minimum data requirements, and RFI maps can be generated rapidly to assist rescuers and decisionmakers in case of emergencies. On the other hand, limitations include: strong dependence on the available data sets, and limitations in simulations with extrapolated water depth values.
Inter‐subject variability of muscle synergies during bench press in power lifters and untrained individuals
Authors: Kristiansen M. , Madeleine P. , Hansen E. A. , Samani A.
Published: December 2013

The purpose of the study was to elucidate the role of expertise on muscle synergies involved in bench press. Ten expert power lifters (EXP) and nine untrained participants (UNT) completed three sets of eight repetitions at 60% of three repetition maximum in bench press. Muscle synergies were extracted from surface electromyography data of 21 bench press cycles using non‐negative matrix factorization algorithm. The synergy activation coefficient represents the relative contribution of the muscle synergy to the overall muscle activity pattern, while the muscle synergy vector represents the relative weighting of each muscle within each synergy. Describing more than 90% of the variability, two muscle synergies reflected the eccentric and concentric phase. The cross‐correlations (ρmax) for synergy activation coefficient 2 (concentric phase) were 0.83 [0.71;0.88] and 0.59 [0.49;0.77] [Median ρmax (25th;75th percentile)] (P = 0.001) in UNT and EXP, respectively. Median correlation coefficient (ρ) for muscle synergy vector 2 was 0.15 [−0.08;0.46] and 0.48 [0.02;0.70] (P = 0.03) in UNT and EXP, respectively. Thus, EXP showed larger inter‐subject variability than UNT in the synergy activation coefficient during the concentric phase, while the muscle synergy vectors were less variable in EXP. This points at the importance of a specialized neural strategy in elite bench press performance.
Superiority of preemptive donor lymphocyte infusion based on minimal residual disease in acute leukemia patients after allogeneic hematopoietic stem cell transplantation
Authors: Tan Yamin , Du Kaili , Luo Yi , Shi Jimin , Cao Ling , Zheng Yanlong , Zheng Gaofeng , Zhao Yanmin , Ye Xiujing , Cai Zhen , Huang He
Published: December 2013

Background

Donor lymphocyte infusion (DLI) was used as salvage therapy in leukemia relapse after allogeneic hematopoietic stem cell transplantation (allo‐HSCT), but existing results on DLI administration to acute leukemia patients were disappointing. Although increasing minimal residual disease (MRD) after HSCT had been proven to be highly indicative of posttransplant relapse, preemptive DLI (pDLI) based on MRD has not been well evaluated.

Study Design and Methods

We retrospectively analyzed 70 acute leukemia patients after allo‐HSCT in our center between January 2005 and December 2010. Sixteen patients received pDLIs based on increasing MRD results (pDLI group), and 11 relapsed patients received therapeutic DLIs with or without chemotherapy (tDLI group). Donor lymphocytes were collected from the original donors without stimulation and infused without further manipulation. The median mononuclear cell doses and CD3+ cell doses were 1.49 × 108 and 5.51 × 107/kg. Forty‐three patients who did not receive pDLI therapy after detecting increasing MRD (no pDLI group) were also included as a comparison.

Results

The response rate was 100% in the pDLI group, whereas it was 63.6% in the tDLI group (p = 0.019). Survival outcomes were superior in the pDLI group compared with the tDLI group (χ2 = 14.624, p = 0.000); estimated overall survival (OS) at 1 year was 93.8% with pDLI and 27.3% with tDLI. The incidence of overall acute graft‐versus‐host disease (aGVHD) and Grade III to IV aGVHD was higher in the pDLI group but with no significance. Patients in the “no pDLI” group showed an inferior prognosis with 1‐year OS at 65.1% (95% confidence interval, 50.8%‐79.4%).

Conclusion

Our results demonstrated the efficacy and safety of pDLI and suggested that pDLI based on MRD monitoring was superior in acute leukemia patients with potential progression compared with salvage DLI administrated in overt relapse.
Innate collateral segments are predominantly present in the subendocardium without preferential connectivity within the left ventricular wall
Authors: van Horssen Pepijn , Siebes Maria , Spaan Jos A. E. , Hoefer Imo E. , van den Wijngaard Jeroen P. H. M.
Published: December 2013

Key points

Innate collateral arteries provide the biophysical substrate for arteriogenesis. Their distribution and morphology predestine tissue areas salvageable by collateral flow.

Fluorescent episcopic cryomicrotome imaging resulted in a three‐dimensional representation of the coronary network, in which collateral segments were automatically identified.

Innate collateral segments are predominantly present in the subendocardium without preferential connectivity within the left ventricular wall of the dog heart and are preferentially oriented perpendicular to the long axis of the heart in the outer layers and parallel to this axis at the subendocardium.

These results suggest that collateral segments are maintained without local hypoxia but because of heterogeneity in pressure gradients in the arterial tree.

The high density and long‐axis orientation of collateral arteries in the subendocardial region provide the substrate for arterial plexus formation and indicate the need for three‐dimensional perfusion assessment in clinical perfusion imaging.

Functional collateral vessels often stem from outward remodelling of pre‐existing connections between perfusion territories. Knowledge of the distribution and morphology of innate collateral connections may help in identifying myocardial areas with protection against risk for ischaemia. The coronary network of six healthy canine hearts was investigated with an imaging cryomicrotome. Innate collateral connections ranged from 286 to 1015 μm in diameter. Left ventricular collateral density (number per gram of tissue) was about five in the subendocardium vs. 2.5 in the mid‐myocardium (P < 0.01) and 1.3 in the epicardium (P < 0.01). Subendocardial collateral connections were oriented parallel to the long axis of the heart. For the major coronary arteries, five times more intracoronary than intercoronary connections were found, while their median diameter and interquartile range were not significantly different, at 96.1 (16.9) vs. 94.7 (18.9) μm. Collateral vessels connecting crowns from sister branches from a stem are denoted intercrown connections and those within crowns intracrown connections. The number of intercrown connections was related to the mean tissue weight of the crowns (y = 0.73x − 0.33, r2 = 0.85, P < 0.0001). This relation was likewise found to describe intercoronary connections. The median collateral diameter and length were independent of the tissue volumes bridged. We conclude that connectivity and morphology of the innate collateral network are distributed with no preference for intra‐ or intercrown connections, independent of stem diameter, including epicardial arteries. This renders all sites of the myocardium equally protected in case of coronary artery disease. The orientation of subendocardial collateral vessels indicates the longitudinal direction of subendocardial collateral flow.
Following the ontogeny of retinal waves: pan‐retinal recordings of population dynamics in the neonatal mouse
Authors: Maccione Alessandro , Hennig Matthias H. , Gandolfo Mauro , Muthmann Oliver , van Coppenhagen James , Eglen Stephen J. , Berdondini Luca , Sernagor Evelyne
Published: December 2013

Key points

Novel pan‐retinal recordings of mouse retinal waves were obtained at near cellular resolution using a large‐scale, high‐density array of 4096 electrodes to investigate changes in wave spatiotemporal properties from postnatal day 2 to eye opening.

Early cholinergic waves are large, slow and random, with low cellular recruitment.

A developmental shift in GABAA signalling from depolarizing to hyperpolarizing influences the dynamics of cholinergic waves.

Glutamatergic waves that occur just before eye opening are focused, faster, denser, non‐random and repetitive.

These results provide a new, deeper understanding of developmental changes in retinal spontaneous activity patterns, which will help researchers in the investigation of the role of early retinal activity during wiring of the visual system.

The immature retina generates spontaneous waves of spiking activity that sweep across the ganglion cell layer during a limited period of development before the onset of visual experience. The spatiotemporal patterns encoded in the waves are believed to be instructive for the wiring of functional connections throughout the visual system. However, the ontogeny of retinal waves is still poorly documented as a result of the relatively low resolution of conventional recording techniques. Here, we characterize the spatiotemporal features of mouse retinal waves from birth until eye opening in unprecedented detail using a large‐scale, dense, 4096‐channel multielectrode array that allowed us to record from the entire neonatal retina at near cellular resolution. We found that early cholinergic waves propagate with random trajectories over large areas with low ganglion cell recruitment. They become slower, smaller and denser when GABAA signalling matures, as occurs beyond postnatal day (P) 7. Glutamatergic influences dominate from P10, coinciding with profound changes in activity dynamics. At this time, waves cease to be random and begin to show repetitive trajectories confined to a few localized hotspots. These hotspots gradually tile the retina with time, and disappear after eye opening. Our observations demonstrate that retinal waves undergo major spatiotemporal changes during ontogeny. Our results support the hypotheses that cholinergic waves guide the refinement of retinal targets and that glutamatergic waves may also support the wiring of retinal receptive fields.