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International audience; INTRODUCTION:Diagnostic relevance of plasma amyloid β (Aβ) for Alzheimer's disease (AD) process yields conflicting results. The objective of the study was to assess plasma levels of Aβ42 and Aβ40 in amnestic mild cognitive impairment (MCI), nonamnestic MCI, and AD patients and to investigate relationships between peripheral and central biomarkers.METHODS:One thousand forty participants (417 amnestic MCI, 122 nonamnestic MCI, and 501 AD) from the Biomarker of AmyLoïd pepTide and AlZheimer's diseAse Risk multicenter prospective study with cognition, plasma, cerebrospinal fluid (CSF), and magnetic resonance imaging assessments were included.RESULTS:Plasma Aβ1-42 and Aβ1-40 were lower in AD (36.9 [11.7] and 263 [80] pg/mL) than in amnestic MCI (38.2 [11.9] and 269 [68] pg/mL) than in nonamnestic MCI (39.7 [10.5] and 272 [52] pg/mL), respectively (P = .01 for overall difference between groups for Aβ1-42 and P = .04 for Aβ1-40). Globally, plasma Aβ1-42 correlated with age, Mini-Mental State Examination, and APOE ε4 allele. Plasma Aβ1-42 correlated with all CSF biomarkers in MCI but only with CSF Aβ42 in AD.DISCUSSION:Plasma Aβ was associated with cognitive status and CSF biomarkers, suggesting the interest of plasma amyloid biomarkers for diagnosis purpose.Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Background Homeostatic turnover of the extracellular matrix conditions the structure and function of the healthy lung. In lung transplantation, long-term management remains limited by chronic lung allograft dysfunction, an umbrella term used for a heterogeneous entity ultimately associated with pathological airway and/or parenchyma remodeling. Objective This study assessed whether the local cross-talk between the pulmonary microbiota and host cells is a key determinant in the control of lower airway remodeling posttransplantation. Methods Microbiota DNA and host total RNA were isolated from 189 bronchoalveolar lavages obtained from 116 patients post lung transplantation. Expression of a set of 11 genes encoding either matrix components or factors involved in matrix synthesis or degradation (anabolic and catabolic remodeling, respectively) was quantified by real-time quantitative PCR. Microbiota composition was characterized using 16S ribosomal RNA gene sequencing and culture. Results We identified 4 host gene expression profiles, among which catabolic remodeling, associated with high expression of metallopeptidase-7, -9, and -12, diverged from anabolic remodeling linked to maximal thrombospondin and platelet-derived growth factor D expression. While catabolic remodeling aligned with a microbiota dominated by proinflammatory bacteria (eg, Staphylococcus, Pseudomonas, and Corynebacterium), anabolic remodeling was linked to typical members of the healthy steady state (eg, Prevotella, Streptococcus, and Veillonella). Mechanistic assays provided direct evidence that these bacteria can impact host macrophage-fibroblast activation and matrix deposition. Conclusions Host-microbes interplay potentially determines remodeling activities in the transplanted lung, highlighting new therapeutic opportunities to ultimately improve long-term lung transplant outcome., Graphical abstract

In 2009, the G20 embarked on an ambitious financial regulatory reform agenda to address the fault lines that caused the global financial crisis. Although the global benefits are expected to outweigh the overall costs, these reforms could produce cross-border adverse spillover effects to individual emerging markets and developing economies that are not required to implement the reforms themselves, but are affected by their implementation elsewhere. To improve the evidence base on such potential adverse impacts, the World Bank has undertaken qualitative surveys of senior officials at regulatory agencies, local banks, and global banks that are active in seven emerging markets and developing economies. While important caveats prevent the formulation of definitive conclusions, the survey finds that banks and regulators routinely have different perspectives on the impacts. Most banks claim adverse effects on financial products, services, and markets; regulators broadly expect the effects to be positive over the longer term, but some recognize they may be negative during the transition phase. Regulators tend to agree that the (potential for) spillover impacts demand stronger home-host coordination, impose a higher supervisory burden, and require a stronger role for the international community to monitor and evaluate the impacts. The findings also emphasize the need for regulatory consistency within and between jurisdictions to ensure a level playing field. Taken together, more work remains to better understand the nature of these spillover effects, how they shape the provision of commercial financing to meet developmental objectives, and what action can be taken to mitigate any adverse impacts.

In 2009, the G20 embarked on an ambitious financial regulatory reform agenda to address the fault lines that caused the global financial crisis. Although the global benefits are expected to outweigh the overall costs, these reforms could produce cross-border adverse spillover effects to individual emerging markets and developing economies that are not required to implement the reforms themselves, but are affected by their implementation elsewhere. To improve the evidence base on such potential adverse impacts, the World Bank has undertaken qualitative surveys of senior officials at regulatory agencies, local banks, and global banks that are active in seven emerging markets and developing economies. While important caveats prevent the formulation of definitive conclusions, the survey finds that banks and regulators routinely have different perspectives on the impacts. Most banks claim adverse effects on financial products, services, and markets; regulators broadly expect the effects to be positive over the longer term, but some recognize they may be negative during the transition phase. Regulators tend to agree that the (potential for) spillover impacts demand stronger home-host coordination, impose a higher supervisory burden, and require a stronger role for the international community to monitor and evaluate the impacts. The findings also emphasize the need for regulatory consistency within and between jurisdictions to ensure a level playing field. Taken together, more work remains to better understand the nature of these spillover effects, how they shape the provision of commercial financing to meet developmental objectives, and what action can be taken to mitigate any adverse impacts.

Fragile X Syndrome (FXS) is caused by a deficiency in Fragile X Mental Retardation Protein (FMRP) leading to global sensorial abnormalities, among which visual defects represent a critical part. These visual defects are associated with cerebral neuron immaturity especially in the primary visual cortex. However, we recently demonstrated that retinas of adult Fmr1−/y mice, the FXS murine model, present molecular, cellular and functional alterations. However, no data are currently available on the evolution pattern of such defects. As retinal stimulation through Eye Opening (EO) is a crucial signal for the cerebral visual system maturation, we questioned the precocity of molecular and functional retinal phenotype. To answer this question, we studied the retinal molecular phenotype of Fmr1−/y mice before EO until adult age and the consequences of the retinal loss of Fmrp on retinal function in young and adult mice. We showed that retinal molecular defects are present before EO and remain stable at adult age, leading to electrophysiological impairments without any underlying structural changes. We underlined that loss of Fmrp leads to a wide range of defects in the retina, settled even before EO. Our work demonstrates a critical role of the sensorial dysfunction in the Fmr1−/y mice overall phenotype, and provides evidence that altered peripheral perception is a component of the sensory processing defect in FXS conditions.

In 2015, the International Society for Heart and Lung Transplantation (ISHLT) published a consensus document for the selection of lung transplant candidates. In the absence of recent French recommendations, this guideline is useful in order to send lung transplant candidates to the transplantation centers and to list them for lung transplantation at the right time.The main indications for lung transplantation in adults are COPD and emphysema, idiopathic pulmonary fibrosis and interstitial diseases, cystic fibrosis and pulmonary arterial hypertension (PAH). The specific indications for each underlying disease as well as the general contraindications have been reviewed in 2015 by the ISHLT. For cystic fibrosis, the main factors are forced expiratory volume in one second, 6-MWD, PAH and clinical deterioration characterized by increased frequency of exacerbations; for emphysema progressive disease, the BODE score, hypercapnia and FEV1; for PAH progressive disease or the need of specific intravenous therapy and NYHA classification. Finally, the diagnosis of fibrosing interstitial lung disease is usually a sufficient indication for lung transplantation assessment.These new recommendations, close to French practices, help clinicians to find the right time for referral of patients to transplantation centers. This is crucial for the prognosis of lung transplantation.

Introduction: Birt-Hogg-Dube syndrome (BHDS) is a rare inherited autosomal dominant disorder characterized by cutaneous fibrofolliculomas, renal tumors, multiple pulmonary cysts and spontaneous pneumothoraces. BHDS is caused by mutations in the tumor suppressor gene FLCN coding for folliculin. Only limited data on lung function in BHDS are available, and whether lung function declines over time as in other cystic lung diseases is unknown. Aims: To assess lung function at baseline and over time in BHDS. Methods: We retrospectively studied lung function parameters from 30 patients with BHDS at baseline and during disease course, and looked for correlations with age, gender and smoking history. Results: Mean±SD age at baseline was 42±14 yr, 60% were males, 43% were smokers and 90% had pulmonary cysts at HRCT. Baseline FEV1 and FVC (n=30) were 95±13 and 100±14 %pred respectively, and FEV1/FVC ratio was 80±6%. TLC (n=21) was 98±15 %pred, RV (n=21) was 111±30 %pred, DLCO (n=18) was 86±16 %pred, KCO (n=19) was 96±20 %pred, and PaO2 (n=8) was 88±11 mmHg. FEV1, FVC and FEV1/FVC at 1, 2 and 3 years follow-up (n= 12, 9 and 6 respectively) were not significantly different from baseline. FEV1/FVC tended to decrease with age at baseline (p=0.05) and over time (p=0.02). In smokers, FEV1 was 9% lower at baseline (p=0.08) and over time (p=0.013) as compared to non-smokers. FVC significantly increased with age at baseline (p=0.007) and over time (p=0.002). Other parameters at baseline and over time were not correlated with age, gender and smoking history. Conclusions: These data suggest that cystic lung disease in BHDS does not affect respiratory function at baseline, and that no deterioration occurs over a follow-up period of 3 years.

Introduction Les recommandations pour la prescription des traitements inhales chez les patients BPCO reposent principalement sur les symptomes et sur l’histoire des exacerbations. Nous avons voulu analyser en vraie-vie l’evolution longitudinale de la prescription, et en particulier observer les patients pour qui la prescription est renforcee, et ceux pour qui elle est diminuee. Methodes Sept cent soixante-quinze patients pour lesquels l’observatoire Colibri-BPCO permet un suivi entre 12 et 24 mois ont ete analyses selon l’evolution de leur charge therapeutique. La charge therapeutique a ete definie en cinq categories mixant les bronchodilatateurs (BD) s2 agonistes (s2), anticholinergiques (AC) et corticoides inhales (CI) de longue duree d’action. Nous avons regarde dans un premier temps l’evolution globale de la repartition des charges therapeutiques, et dans un deuxieme temps nous avons observe si le traitement initial etait maintenu, renforce ou diminue. Resultats Voir Fig. 1 . Conclusion Globalement, on observe plutot une tendance a l’augmentation de la charge therapeutique au-dela d’une annee. Par ailleurs, il apparait que le nombre de patients traites par une double bronchodilatation Anticholinergiques + s2 tend a augmenter, alors qu’a l’inverse l’association s2 + CI semble diminuer. Une analyse detaillee precisera plus finement les caracteristiques des patients concernes par ces changements et si le changement de traitement repond a une logique previsible.

Running through the varied roles principals must play are two threads: leadership and management. (Author/IRT)

The author presents predictions concerning the major trends of education in the 1980's. He discusses financial matters, the relationships between the interests of society and those of educators, and the relationship of education to society. This paper was presented at a European conference on mathematics education in the 1980's. (SD)

The pressures of an expanding population and an increasingly complex technology will increase the demand for education in the next ten or fifteen years. On examining the figures available for expense per pupil for teachers and for instructional materials, it seems as if the education industry is overstaffed and underequipped. In the future there will be changes in the organization of schools, and in the patterns of learning and teaching. A combination of large group instruction with small group discussion and experimentation would seem to be the pattern of the future. If the instructional materials industry can produce more varied and effective software, some of the presently idle equipment may be used, especially in the individualization of instruction. Teachers will have to examine and rethink how they are providing educative experiences for children. They will have to be ready to consider new approaches and new media; and they will have to be trained to use them. The role of the National Council for Educational Technology will be in teacher training; identification, classification, and assessment of instructional materials; and coordination of instructional material development. (JY)

Schools and colleges should arrange for the participation of all members of staff in decisionmaking about the choice of resources, in the management of these resources, and in the consideration of innovative ideas. (Author)

Purpose – The purpose of this paper is two-fold: first, to bring into sharper focus the role of organisational performance management both for “exploring the future to deliver better outcomes” and “learning from the past to improve the future”; and second, to introduce the control tower approach to optimising complex service delivery performance, explaining how this approach is derived from a unique combination of lean thinking and connected performance. Design/methodology/approach – This is a practitioner paper based on extensive practical experience. Findings – While the tools and techniques of “exploring the future to deliver better outcomes” may be less common than those for “learning from the past to improve the future”, they offer significant benefits, particularly in complex service delivery situations. Research limitations/implications – It has not, so far, been possible to find organisations willing and able to participate in a quasi-controlled experiment to explore how organisations which implement the control tower approach actually perform in relation to others that do not. However, the authors hope this paper will help move thinking forward in the field of complex service delivery, and perhaps inform future academic research. Practical implications – The control tower approach offers significant opportunities to improve service delivery performance, not just within healthcare but across all sectors where service delivery is complex and important. Social implications – The improvement of complex service delivery performance offers huge social benefits for all stakeholders, including customers, providers (and their staff) and society as a whole, notably through improved outcomes and efficiency. Originality/value – Although the value of “learning from the past to improve the future” in organisational performance management terms is widely understood, the value of “exploring the future to deliver better outcomes” is much less well known. Hence, this paper highlights a perspective of real practical significance.

Background Lung transplantation is hampered by some complications, particularly acute rejection and chronic lung allograft dysfunction (CLAD), the latter including bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS) with fibrotic process. RAS therapeutic strategy is not clearly defined, but several cases reported the use of antifibrotic agents, indicated in idiopathic pulmonary fibrosis (IPF), to treat RAS, such as pirfenidone. 1 Purpose In this case report we relate the use of nintedanib, a new antifibrotic agent, for RAS treatment in a lung transplanted patient. Material and methods Case report Results A 71-year-old-man received a right lung transplant in 2009 because of IPF. In 2010, BOS stage 0-p was found, evolving to stage 1 in 2011 and leading to the introduction of montelukast and azithromycin, and extracorporeal photopheresis. Despite these therapies, the forced expiratory volume 1 (FEV1) per cent predicted decreased to 43% and dyspnoea worsened, suggesting evolution of BOS towards RAS, whose prognosis is worse. Oxygen therapy was introduced in January 2016 (1.5 L/min during exercise). In February 2016, CT showed IPF large lesions in the left lung and worse RAS fibrotic lesions in the right lung. A multidisciplinary team decided to start nintedanib 150 mg twice a day. The patient’s immunosuppressive therapies (tacrolimus and everolimus) were monitored every 15 days because of potential cytochrome 3A4 induction of nintedanib. During nintedanib treatment, oxygen debit was 1 L/min during exercise and FEV1% predicted was 47%, suggesting clinical improvement. Nintedanib was stopped in August 2016 because of persistence of digestive intolerance. Conclusion Our clinical case suggests a potential clinical benefit of nintedanib in the treatment of RAS. To our knowledge, this is the first case reporting the use of nintedanib, a tyrosine kinase inhibitor targeting platelet derived growth factor receptors and fibroblast growth factor receptor, to treat RAS. Further studies have to be conducted to assess the place of antifibrotic agents in RAS therapeutic management. References and/or acknowledgements 1. Vos R, Verleden SE, Ruttens D, et al. Pirfenidone: A potential new therapy for restrictive allograft syndrome? Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg 2013;13:3035–40. No conflict of interest

International audience; La bronchopneumopathie chronique obstructive (BPCO) est une maladie fréquente que l’on peut prévenir et traiter, qui est caractérisée par des symptômes respiratoires persistants et un trouble ventilatoire obstructif dû à des lésions des voies aériennes (bronchite chronique et/ou du tissu alvéolaire (emphysème), en général en relation avec une exposition significative à des particules ou à des gaz toxiques, selon la définition mise à jour par les recommandations internationales [...]

BACKGROUND: Total Lung Lavage (TLL) is considered as standard of care in Pulmonary Alveolar Proteinosis (PAP). Yet, new therapies have emerged in the treatment of PAP and therefore there is a real need to evaluate the efficacy of TTL in this rare disease. OBJECTIVES: The aim of this study was to assess the efficacy of TTL in patients with PAP. METHODS : We have included 33 patients who underwent TTL from 11 centers, members of the French-Speaking Endoscopy Group (GELF) for analysis. Data collection concerned patient9s and disease characteristics, pulmonary function tests (PFTs) before and after the procedure, and technical informations on the procedure. RESULTS: Patients with respiratory insufficiancy at presentation were 22 (68.75%). All patients underwent lung lavage by general anesthesia and selective lung ventilation, except one who underwent flexible bronchoscopy. We noted differences in the technique as 12 (36.36%) patients had percussion during the procedure and only 7(21.2%) underwent two-lungs lavage during one anesthesia. A median of 16.8 L were used to performed TLL (1.0L to 40L). Complications occured in 11 (33.3%) patients and 18(56.25%) of them relapsed in a median period of 16.9 months. No significant changes were found in all PFTs parameters studied, in exception to PaO2 which was after the procedure higher of 6.375 mmHg (p=0.0213 ; [95%CI: 1.03-11.7]) in comparison to before. CONCLUSION: Although the technique of TLL has a variability in its application, due probably to patient9s condition, it improves significantly patients9 short-term respiratory condition, by improving PaO2. However, long-term effect needs to be confirmed, as many of our patients relapsed.

International audience; ObjectiveAbdominal tuberculosis is a rare disease. The clinical and radiological manifestations are non-specific and the diagnosis is difficult. Our objective was to describe the characteristics and treatment of patients presenting with abdominal tuberculosis in a low-incidence country.Patients and methodsWe reviewed the clinical, diagnostic, treatment, and outcome features of patients presenting with abdominal tuberculosis diagnosed by bacteriological and/or histological results and managed in five French university hospitals from January 2000 to December 2009.ResultsWe included 21 patients. The mean diagnostic delay was 13 months. Twelve patients (57%) came from a low-incidence area and only two had a known immunosuppressed condition. Eighteen patients (86%) presented with abdominal symptoms. The main organs involved were the peritoneum (n = 14, 66%), the mesenteric lymph nodes (n = 13, 62%), and the bowel (n = 7, 33%). Sixteen patients (76%) underwent surgery, including two in an emergency setting. Seventeen patients (81%) received six months or more of anti-tuberculosis treatment. Finally, 16 patients (76%) had a positive outcome.ConclusionNew diagnostic procedures, and especially molecular biology, may help diagnose unusual clinical presentations of tuberculosis. Invasive procedures are frequently necessary to obtain samples but also for the treatment of digestive involvement.; ObjectifsLa tuberculose abdominale est rare, le tableau clinico-radiologique aspécifique et le diagnostic difficile. Notre objectif était de décrire les caractéristiques et la prise en charge thérapeutique de patients présentant une tuberculose abdominale dans un pays où la prévalence de cette infection est faible.Patients et méthodesNous avons recueilli les données cliniques, diagnostiques, thérapeutiques et le suivi des patients atteints de tuberculose abdominale, diagnostiquée sur des arguments bactériologiques et/ou anatomopathologiques, et pris en charge dans cinq hôpitaux universitaires français de janvier 2000 à décembre 2009.RésultatsVingt et un patients ont été inclus. Le délai diagnostique moyen était de 13 mois. Douze patients (57 %) étaient originaires d’une zone de faible prévalence de la tuberculose et seulement deux patients étaient immunodéprimés. Dix-huit patients (86 %) présentaient des symptômes abdominaux. Les principaux organes atteints étaient le péritoine (n = 14, 66 %), les ganglions mésentériques (n = 13, 62 %) et le tube digestif (n = 7, 33 %). Une intervention chirurgicale a été nécessaire chez 16 patients (76 %), en urgence pour deux d’entre eux. Dix-sept patients (81 %) ont reçu au moins six mois de quadri-thérapie antituberculeuse. Au final, 16 patients (76 %) présentaient une évolution favorable.ConclusionLes nouvelles techniques diagnostiques, notamment la biologie moléculaire, peuvent être utiles pour le diagnostic des formes cliniques inhabituelles de tuberculose. Des explorations invasives sont souvent nécessaires pour obtenir des prélèvements, mais aussi pour la prise en charge thérapeutique de l’atteinte digestive.

Introduction Les recommandations pour la prescription des traitements inhales ont evolue a la suite de l’etude FLAME (mai 2016), qui a montre le benefice d’une double bronchodilatation de longue duree pour reduire la dyspnee et la frequence des exacerbations. Grâce a l’observatoire Colibri-BPCO qui collecte les donnees de 4300 patients depuis 2012, nous avons voulu analyser l’impact eventuel des resultats de cette etude sur les prescriptions de traitements inhales observees en vraie-vie. Methodes Au total, 3007 patients remplissant des criteres d’exhaustivite minimaux (sexe, âge, IMC, tabagisme, VEMS, CVF, traitement, exacerbations, comorbidites) ont ete selectionnes, puis separes en 2 groupes : 2190 (73 %) inclus avant mai 2016, et 817 (27 %) inclus apres juin 2016. Nous avons ensuite compare la charge therapeutique prescrite dans ces groupes. La charge therapeutique a ete definie en 5 categories mixant les bronchodilatateurs (BDI) s2 agonistes (s2), anticholinergiques (AC) et corticoides inhales (CI) de courte (court) et longue duree d’action (long). A : non-traite ou BDI court seul B : 1 BDI long (s 2 ou AC) C : 2 BDI long (s 2 et AC) D : 1 BDI long + CI E : 2 BDI long + CI. Resultats Repartition des charges therapeutiques avant/apres FLAME : Tableau 1 . Les populations avant/apres FLAME sont identiques pour l’âge, l’IMC, la qualite de vie (CAT) et les comorbidites. En revanche, le recrutement des patients apres FLAME comprend legerement plus de GOLD I (24 % vs 18 %), moins de patients dyspneiques (MRC ≥ 2 a 50 % vs 57 %) et moins de patients exacerbateurs (29 % vs 33 %). Chez les patients peu severes (GOLD I et MRC Conclusion Trois evolutions significatives sont observees dans la prescription des traitements inhales apres l’etude FLAME : (1) Une augmentation de la charge therapeutique A (non-traite ou BDI court seul), en particulier chez les patients GOLD I non-dyspneiques, indiquant que le recours aux traitements inhales est moins systematique chez ces patients peu severes ; (2) une augmentation significative de la charge therapeutique C (bitherapie AC + s2). Cette augmentation est certainement imputable aux conclusions de l’etude FLAME ; (3) une reduction importante des charges therapeutiques D (s2 + CI) et surtout E (s2 + AC + CI) ce qui montre que le recours aux corticoides inhales a diminue, conformement aux recommandations.

International audience; The 2q37 locus is one of the most commonly deleted subtelomeric regions. Such a deletion has been identified in >100 patients by telomeric fluorescence in situ hybridization (FISH) analysis and, less frequently, by array-based comparative genomic hybridization (array-CGH). A recognizable ‘2q37-deletion syndrome’ or Albright’s hereditary osteodystrophy-like syndrome has been previously described. To better map the deletion and further refine this deletional syndrome, we formed a collaboration with the Association of French Language Cytogeneticists to collect 14 new intellectually deficient patients with a distal or interstitial 2q37 deletion characterized by FISH and array-CGH. Patients exhibited facial dysmorphism (13/14) and brachydactyly (10/14), associated with behavioural problems, autism or autism spectrum disorders of varying severity and overweight or obesity. The deletions in these 14 new patients measured from 2.6 to 8.8 Mb. Although the major role of HDAC4 has been demonstrated, the phenotypic involvement of several other genes in the deleted regions is unknown. We further refined the genotype–phenotype correlation for the 2q37 deletion. To do this, we examined the smallest overlapping deleted region for candidate genes for skeletal malformations (facial dysmorphism and brachydactyly), overweight, behavioural problems and seizures, using clinical data, a review of the literature, and the Manteia database. Among the candidate genes identified, we focus on the roles of PRLH, PER2, TWIST2, CAPN10, KIF1A, FARP2, D2HGDH and PDCD1.

Resume Nous presentons un cas de diagnostic antenatal de trisomie 21 compliquee de leucemie. Le diagnostic a ete evoque devant la decouverte d’une hepatosplenomegalie isolee lors de l’echographie du troisieme trimestre. L’hepatosplenomegalie peut suggerer un syndrome myelodysplasique. Une revue de la litterature de huit cas de diagnostic antenatal et de 14 cas de diagnostic a la naissance est presentee.

Setting targets is normal in most organisations. Alan Meekings, Steve Briault and Andy Neely think such a practice can cause more harm than good. They offer a better way. © 2010 London Business School.

Gene localization was determined by linkage analysis in a large French family with X-linked mental retardation (MRX). Seven living affected males were clinically studied and the clinical picture was characterized by moderate to severe mental handicap with poor secondary speech acquisition. Seizures, slight microcephaly, simian crease, anteverted pinnae, and macroorchidism were observed in some patients only. Linkage analysis revealed no recombination between the MRX gene and two loci: DXS255 at Xp11.22 (Zmax = 3.31 at theta = 0.00) and PGKP1 at Xq11.2-q12 (Zmax = 3.08 at theta = 0.00). One recombination was observed between the gene and the two loci DXS164 at Xp21.2 and DXS441 at Xq13.3, respectively. These results suggested gene localization in the pericentromeric region of the X chromosome, and the LOD scores justified assignment of the symbol MRX14 to this family.

Recognition of bacterial lipopolysaccharide (LPS) by the innate immune system involves at least three receptor molecules: CD14, TLR4 and MD-2. Additional receptor components such as heat shock proteins, chemokine receptor 4 (CXCR4), or CD55 have been suggested to be part of this activation cluster; possibly acting as additional LPS transfer molecules. Our group has previously identified CXCR4 as a component of the "LPS-sensing apparatus". In this study we aimed to elucidate the role that CXCR4 plays in innate immune responses to LPS. Here we demonstrate that CXCR4 transfection results in responsiveness to LPS. Fluorescence correlation spectroscopy experiments further showed that LPS directly interacts with CXCR4. Our data suggest that CXCR4 is not only involved in LPS binding but is also responsible for triggering signalling, especially mitogen-activated protein kinases in response to LPS. Finally, co-clustering of CXCR4 with other LPS receptors seems to be crucial for LPS signalling, thus suggesting that CXCR4 is a functional part of the multimeric LPS "sensing apparatus".

The article discusses various reports published within the issue, including one by John Seddon and Simon Caulkin on the connection between systems thinking and lean production and another by Matthew Hind and John Koenigsberger on action learning projects in a software company.