Interplay between edge states and simple bulk defects in graphene nanoribbons

We study the interplay between the edge states and a single impurity in a zigzag graphene nanoribbon. We use tight-binding exact diagonalization techniques, as well as density functional theory calculations to obtain the eigenvalue spectrum, the eigenfunctions, as well the dependence of the local density of states (LDOS) on energy and position. We note that roughly half of the unperturbed eigenstates in the spectrum of the finite-size ribbon hybridize with the impurity state, and the corresponding eigenvalues are shifted with respect to their unperturbed values. The maximum shift and hybridization occur for a state whose energy is inverse proportional to the impurity potential; this energy is that of the impurity peak in the DOS spectrum. We find that the interference between the impurity and the edge gives rise to peculiar modifications of the LDOS of the nanoribbon, in particular to oscillations of the edge LDOS. These effects depend on the size of the system, and decay with the distance between the edge and the impurity.Comment: 10 pages, 15 figures, revtex

Multiple Myeloma Treatment in Real-world Clinical Practice : Results of a Prospective, Multinational, Noninterventional Study

Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: M.M. has received personal fees from Janssen, Celgene, Amgen, Bristol-Myers Squibb, Sanofi, Novartis, and Takeda and grants from Janssen and Sanofi during the conduct of the study. E.T. has received grants from Janssen and personal fees from Janssen and Takeda during the conduct of the study, and grants from Amgen, Celgene/Genesis, personal fees from Amgen, Celgene/Genesis, Bristol-Myers Squibb, Novartis, and Glaxo-Smith Kline outside the submitted work. M.V.M. has received personal fees from Janssen, Celgene, Amgen, and Takeda outside the submitted work. M.C. reports honoraria from Janssen, outside the submitted work. M. B. reports grants from Janssen Cilag during the conduct of the study. M.D. has received honoraria for participation on advisory boards for Janssen, Celgene, Takeda, Amgen, and Novartis. H.S. has received honoraria from Janssen-Cilag, Celgene, Amgen, Bristol-Myers Squibb, Novartis, and Takeda outside the submitted work. V.P. reports personal fees from Janssen during the conduct of the study and grants, personal fees, and nonfinancial support from Amgen, grants and personal fees from Sanofi, and personal fees from Takeda outside the submitted work. W.W. has received personal fees and grants from Amgen, Celgene, Novartis, Roche, Takeda, Gilead, and Janssen and nonfinancial support from Roche outside the submitted work. J.S. reports grants and nonfinancial support from Janssen Pharmaceutical during the conduct of the study. V.L. reports funding from Janssen Global Services LLC during the conduct of the study and study support from Janssen-Cilag and Pharmion outside the submitted work. A.P. reports employment and shareholding of Janssen (Johnson & Johnson) during the conduct of the study. C.C. reports employment at Janssen-Cilag during the conduct of the study. C.F. reports employment at Janssen Research and Development during the conduct of the study. F.T.B. reports employment at Janssen-Cilag during the conduct of the study. The remaining authors have stated that they have no conflicts of interest. Publisher Copyright: © 2018 The AuthorsMultiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide. Conclusion: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits.publishersversionPeer reviewe

Exome Sequencing and the Management of Neurometabolic Disorders

BACKGROUND: Whole-exome sequencing has transformed gene discovery and diagnosis in rare diseases. Translation into disease-modifying treatments is challenging, particularly for intellectual developmental disorder. However, the exception is inborn errors of metabolism, since many of these disorders are responsive to therapy that targets pathophysiological features at the molecular or cellular level. METHODS: To uncover the genetic basis of potentially treatable inborn errors of metabolism, we combined deep clinical phenotyping (the comprehensive characterization of the discrete components of a patient's clinical and biochemical phenotype) with whole-exome sequencing analysis through a semiautomated bioinformatics pipeline in consecutively enrolled patients with intellectual developmental disorder and unexplained metabolic phenotypes. RESULTS: We performed whole-exome sequencing on samples obtained from 47 probands. Of these patients, 6 were excluded, including 1 who withdrew from the study. The remaining 41 probands had been born to predominantly nonconsanguineous parents of European descent. In 37 probands, we identified variants in 2 genes newly implicated in disease, 9 candidate genes, 22 known genes with newly identified phenotypes, and 9 genes with expected phenotypes; in most of the genes, the variants were classified as either pathogenic or probably pathogenic. Complex phenotypes of patients in five families were explained by coexisting monogenic conditions. We obtained a diagnosis in 28 of 41 probands (68%) who were evaluated. A test of a targeted intervention was performed in 18 patients (44%). CONCLUSIONS: Deep phenotyping and whole-exome sequencing in 41 probands with intellectual developmental disorder and unexplained metabolic abnormalities led to a diagnosis in 68%, the identification of 11 candidate genes newly implicated in neurometabolic disease, and a change in treatment beyond genetic counseling in 44%. (Funded by BC Children's Hospital Foundation and others.)

MULTI DISABLE PEOPLE NEEDS' PROFILE - A COMPREHENSIVE APPROACH

Persons with multi disabilities are individuals of all ages who require extensive ongoing support in more than one major life activity to participate in integrated community settings. The study intented to identify the physical, educational, social and emotional needs of the multi disable people in an attempt to gain a better understanding of the factors influencing their life. A questionnaire with 80 items distributed on 4 domains, interviewing a wide spectrum of physical, educational, social and emotional needs of the persons with multi disabilities was used. The sample consisted of 43 multi disable children and youth, 24 males and 19 females, from four special education centers in Bahrain managing persons with different types of disabilities- motor, blindness and intellectual. Three centers had similar pattern with the social domain on the first rank, followed by educational, physical and emotional domains. More than half of the sample, 53.5% (23 cases) was in high need to be trained for daily care and independent skills. A high percentage of the persons were in need for speech therapy, 51.3% (22 cases). The medical follow up was the highest physical need for 48.8% persons, followed by hospitalization marked by 44.2% persons. Requirment of special educational tools was the highest on the educational domain needs. The society should take care of these domains-physical, social, emotional and educational, separately and in interaction, in order to offer a fundamental environment that can allow people with multi disabilities to do the best regarding their capabilities

Fulminant Neonatal Liver Failure in MPV 17-Related Mitochondrial DNA Depletion Syndrome

Mitochondrial depletion syndromes are well established causes of liver failure in infants. Hepatocerebral variant related to MPV17 gene defect is characterized by infantile onset of progressive liver failure, developmental delay, neurological manifestations, lactic acidosis, hypoglycemia, and mtDNA depletion in liver tissue. We report a hepatocerebral variant of mitochondrial DNA depletion syndrome in a neonate who presented with septic shock picture, hypoglycemia, jaundice, hypotonia, and rotatory nystagmus. Family history was significant for consanguinity and a brother who died at the age of 4 months. Investigations showed mild liver function derangement contrasting with severe coagulopathy, hyperlactatemia, and generalized aminoaciduria. The brain MRI was normal. Next generation sequencing (NGS) panel identified a MPV17 gene missense homozygous pathogenic variant. The infant expired at the age of 2 weeks with refractory ascites. This case illustrates a challenging diagnosis causing liver failure and death in neonatal period. Genetic testing of mitochondrial DNA depletion syndromes should be a part of liver failure workup in addition to other treatable disorders presenting with encephalo-hepatopathy in infancy

Effects of topiramate on pregnancy outcome in rats

Background: Anti-epileptics taken during pregnancy might lead to low birth-weight and birth defects which could be associated with neonatal morbidity and mortality. Objective: To evaluate the effects of maternal exposure to therapeutic doses of topiramate on the growth of 20-day rat fetuses. Design: An Experimental Animal Study. Setting: Teratology Laboratory, Anatomy Department, College of Medicine and Medical Sciences, Arabian Gulf University, Bahrain. Method: Three groups of Sprague-Dawley pregnant rats were used in the experiment: control, Topiramate 50mg/Kg BW and Topiramate 100 mg/Kg BW. Topiramate was administered by intragastric intubation from day 6 through day 19 of gestation. Cesarean section was performed on day 20. Resorption was calculated, placental weight and umbilical cord length were measured. Fetuses were collected to assess their growth parameters: fetal weight (FW), biparietal diameter (BPD), crown-rump length (CRL) and head length (HL). Ponderal index and CRL/HL ratio were calculated to indicate the type of growth restriction. Result: The Topiramate treated groups showed an insignificant increase in the rate of resorption, a significant decrease in umbilical cord length, placental weight and highly significant reduction in fetal growth parameters. No significant changes were noticed in fetal growth parameters between Topiramate groups. A positive correlation was found between FW and UCL, PW, CRL, HL and BPD in all examined groups. Ponderal index and CRL/HL ratio indicate symmetrical growth restriction of the fetuses in both treated Topiramate groups. Conclusion: The doses of Topiramate, which were given to pregnant rats were equivalent to the human therapeutic range; the drug led to symmetrical fetal gross restriction with few abnormal fetuses and placentae. Topiramate attributed effects were not dose related. The drug should be taken with caution during pregnancy.Scopu

A novel bi-allelic loss-of-function mutation in STIM1 expands the phenotype of STIM1-related diseases

International audienceSTIM1, the stromal interaction molecule 1, is the key protein for maintaining calciumconcentration in the endoplasmic reticulum by triggering the Store Operated CalciumEntry (SOCE). Bi-allelic mutations in STIM1 gene are responsible for a loss-offunctionin patients affected with a CRAC channelopathy syndrome in which severecombined immunodeficiency syndrome (SCID-like), autoimmunity, ectodermal dysplasiaand muscle hypotonia are combined. Here, we studied two siblings from a consanguineousSyrian family, presenting with muscle weakness, hyperlaxity, elastic skin,tooth abnormalities, dysmorphic facies, hypoplastic patellae and history of respiratoryinfections. Using exome sequencing, we have identified a new homozygous frameshiftmutation in STIM1: c.685delT [p.(Phe229Leufs*12)], leading to a complete lossof STIM1 protein. In this study, we describe an unusual phenotype linked to STIM1mutations, combining clinical signs usually observed in different STIM1-related diseases.In particular, we confirmed that the complete loss of STIM1 function is notalways associated with severe immune disorders. Altogether, our results broaden thespectrum of phenotypes associated with mutations in STIM1 and opens new perspectiveson the pathological mechanisms associated with a defect in the proteins constitutingthe SOCE complex

Friedel oscillations: Decoding the hidden physics

AbstractWe show that the impurity-induced Friedel oscillations allow one to probe in an unexpected and quite remarkable manner the electronic properties of two-dimensional systems such as graphene or high-temperature superconductors. In particular, we show that by studying these oscillations, one can get access not only to the constant-energy maps, but also to more hidden information such as the chiral properties of Dirac electrons in graphene, which cannot be observed directly by other methods. For graphene, this hidden information is revealed by comparing the theoretical predictions with scanning tunneling microscopy experimental measurements of the local density of states