Endocrinopathies in paediatric-onset neuromyelitis optica spectrum disorder with aquaporin 4 (AQP4) antibody.

PubMed

Hacohen, Yael; Messina, Silvia; Gan, Hoong-Wei; Wright, Sukhvir; Chandratre, Saleel; Leite, Maria Isabel; Fallon, Penny; Vincent, Angela; Ciccarelli, Olga; Wassmer, Evangeline; Lim, Ming; Palace, Jacqueline; Hemingway, Cheryl

2018-04-01

The involvement of the diencephalic regions in neuromyelitis optica spectrum disorder (NMOSD) may lead to endocrinopathies. In this study, we identified the following endocrinopathies in 60% (15/25) of young people with paediatric-onset aquaporin 4-Antibody (AQP4-Ab) NMOSD: morbid obesity ( n = 8), hyperinsulinaemia ( n = 5), hyperandrogenism ( n = 5), amenorrhoea ( n = 5), hyponatraemia ( n = 4), short stature ( n = 3) and central hypothyroidism ( n = 2) irrespective of hypothalamic lesions. Morbid obesity was seen in 88% (7/8) of children of Caribbean origin. As endocrinopathies were prevalent in the majority of paediatric-onset AQP4-Ab NMOSD, endocrine surveillance and in particular early aggressive weight management is required for patients with AQP4-Ab NMOSD.

Differential diagnosis of neuromyelitis optica spectrum disorders

PubMed Central

Kim, Sung-Min; Kim, Seong-Joon; Lee, Haeng Jin; Kuroda, Hiroshi; Palace, Jacqueline; Fujihara, Kazuo

2017-01-01

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disorder of the central nervous system (CNS) mostly manifesting as optic neuritis and/or myelitis, which are frequently recurrent/bilateral or longitudinally extensive, respectively. As the autoantibody to aquaporin-4 (AQP4-Ab) can mediate the pathogenesis of NMOSD, testing for the AQP4-Ab in serum of patients can play a crucial role in diagnosing NMOSD. Nevertheless, the differential diagnosis of NMOSD in clinical practice is often challenging despite the phenotypical and serological characteristics of the disease because: (1) diverse diseases with autoimmune, vascular, infectious, or neoplastic etiologies can mimic these phenotypes of NMOSD; (2) patients with NMOSD may only have limited clinical manifestations, especially in their early disease stages; (3) test results for AQP4-Ab can be affected by several factors such as assay methods, serologic status, disease stages, or types of treatment; (4) some patients with NMOSD do not have AQP4-Ab; and (5) test results for the AQP4-Ab may not be readily available for the acute management of patients. Despite some similarity in their phenotypes, these NMOSD and NMOSD-mimics are distinct from each other in their pathogenesis, prognosis, and most importantly treatment. Understanding the detailed clinical, serological, radiological, and prognostic differences of these diseases will improve the proper management as well as diagnosis of patients. PMID:28670343

Aquaporin 4 molecular mimicry and implications for neuromyelitis optica.

PubMed

Vaishnav, Radhika A; Liu, Ruolan; Chapman, Joab; Roberts, Andrew M; Ye, Hong; Rebolledo-Mendez, Jovan D; Tabira, Takeshi; Fitzpatrick, Alicia H; Achiron, Anat; Running, Mark P; Friedland, Robert P

2013-07-15

Neuromyelitis optica (NMO) is associated with antibodies to aquaporin 4 (AQP4). We hypothesized that antibodies to AQP4 can be triggered by exposure to environmental proteins. We compared human AQP4 to plant and bacterial proteins to investigate the occurrence of significantly similar structures and sequences. High similarity to a known epitope for NMO-IgG, AQP4(207-232), was observed for corn ZmTIP4-1. NMO and non-NMO sera were assessed for reactivity to AQP4(207-232) and the corn peptide. NMO patient serum showed reactivity to both peptides as well as to plant tissue. These findings warrant further investigation into the role of the environment in NMO etiology. Copyright © 2013 Elsevier B.V. All rights reserved.

Influence of female sex and fertile age on neuromyelitis optica spectrum disorders.

PubMed

Borisow, Nadja; Kleiter, Ingo; Gahlen, Anna; Fischer, Katrin; Wernecke, Klaus-Dieter; Pache, Florence; Ruprecht, Klemens; Havla, Joachim; Krumbholz, Markus; Kümpfel, Tania; Aktas, Orhan; Ringelstein, Marius; Geis, Christian; Kleinschnitz, Christoph; Berthele, Achim; Hemmer, Bernhard; Angstwurm, Klemens; Weissert, Robert; Stellmann, Jan-Patrick; Schuster, Simon; Stangel, Martin; Lauda, Florian; Tumani, Hayrettin; Mayer, Christoph; Zeltner, Lena; Ziemann, Ulf; Linker, Ralf A; Schwab, Matthias; Marziniak, Martin; Then Bergh, Florian; Hofstadt-van Oy, Ulrich; Neuhaus, Oliver; Winkelmann, Alexander; Marouf, Wael; Rückriem, Lioba; Faiss, Jürgen; Wildemann, Brigitte; Paul, Friedemann; Jarius, Sven; Trebst, Corinna; Hellwig, Kerstin

2017-07-01

Gender and age at onset are important epidemiological factors influencing prevalence, clinical presentation, and treatment response in autoimmune diseases. To evaluate the impact of female sex and fertile age on aquaporin-4-antibody (AQP4-ab) status, attack localization, and response to attack treatment in patients with neuromyelitis optica (NMO) and its spectrum disorders (neuromyelitis optica spectrum disorder (NMOSD)). Female-to-male ratios, diagnosis at last visit (NMO vs NMOSD), attack localization, attack treatment, and outcome were compared according to sex and age at disease or attack onset. A total of 186 NMO/SD patients (82% female) were included. In AQP4-ab-positive patients, female predominance was most pronounced during fertile age (female-to-male ratio 23:1). Female patients were more likely to be positive for AQP4-abs (92% vs 55%; p < 0.001). Interval between onset and diagnosis of NMO/SD was longer in women than in men (mean 54 vs 27 months; p = 0.023). In women, attacks occurring ⩽40 years of age were more likely to show complete remission ( p = 0.003) and better response to high-dose intravenous steroids ( p = 0.005) compared to woman at >40 years. Our data suggest an influence of sex and age on susceptibility to AQP4-ab-positive NMO/SD. Genetic and hormonal factors might contribute to pathophysiology of NMO/SD.

Spectrum of MRI brain lesion patterns in neuromyelitis optica spectrum disorder: a pictorial review.

PubMed

Wang, Kevin Yuqi; Chetta, Justin; Bains, Pavit; Balzer, Anthony; Lincoln, John; Uribe, Tomas; Lincoln, Christie M

2018-06-01

Neuromyelitis optica is a neurotropic autoimmune inflammatory disease of the central nervous system traditionally thought to exclusively involve the optic nerves and spinal cord. With the discovery of the disease-specific aquaporin-4 antibody and the increasing recognition of clinical and characteristic imaging patterns of brain involvement in what is now termed neuromyelitis optica spectrum disorder (NMOSD), MRI now plays a greater role in diagnosis of NMOSD based on the 2015 consensus criteria and in distinguishing it from other inflammatory disorders, particularly multiple sclerosis (MS). Several brain lesion patterns are highly suggestive of NMOSD, whereas others may serve as red flags. Specifically, long corticospinal lesions, hemispheric cerebral white matter lesions and periependymal lesions in the diencephalon, dorsal brainstem and white matter adjacent to lateral ventricles are typical of NMOSD. In contrast, juxtacortical, cortical, or lesions perpendicularly oriented to the surface of the lateral ventricle suggests MS as the diagnosis. Ultimately, a strong recognition of the spectrum of MRI brain findings in NMOSD is essential for accurate diagnosis, and particularly in differentiating from MS. This pictorial review highlights the spectrum of characteristic brain lesion patterns that may be seen in NMOSD and further delineates findings that may help distinguish it from MS.

Enhancing Brain Lesions during Acute Optic Neuritis and/or Longitudinally Extensive Transverse Myelitis May Portend a Higher Relapse Rate in Neuromyelitis Optica Spectrum Disorders.

PubMed

Orman, G; Wang, K Y; Pekcevik, Y; Thompson, C B; Mealy, M; Levy, M; Izbudak, I

2017-05-01

Neuromyelitis optica spectrum disorders are inflammatory demyelinating disorders with optic neuritis and/or longitudinally extensive transverse myelitis episodes. We now know that neuromyelitis optica spectrum disorders are associated with antibodies to aquaporin-4, which are highly concentrated on astrocytic end-feet at the blood-brain barrier. Immune-mediated disruption of the blood-brain barrier may manifest as contrast enhancement on brain MR imaging. We aimed to delineate the extent and frequency of contrast enhancement on brain MR imaging within 1 month of optic neuritis and/or longitudinally extensive transverse myelitis attacks and to correlate contrast enhancement with outcome measures. Brain MRIs of patients with neuromyelitis optica spectrum disorders were evaluated for patterns of contrast enhancement (periependymal, cloudlike, leptomeningeal, and so forth). The Fisher exact test was used to evaluate differences between the proportion of contrast enhancement in patients who were seropositive and seronegative for aquaporin-4 antibodies. The Mann-Whitney test was used to compare the annualized relapse rate and disease duration between patients with and without contrast enhancement and with and without seropositivity. Brain MRIs of 77 patients were evaluated; 59 patients (10 males, 49 females) were scanned within 1 month of optic neuritis and/or longitudinally extensive transverse myelitis attacks and were included in the analysis. Forty-eight patients were seropositive, 9 were seronegative, and 2 were not tested for aquaporin-4 antibodies. Having brain contrast enhancement of any type during an acute attack was significantly associated with higher annualized relapse rates ( P = .03) and marginally associated with shorter disease duration ( P = .05). Having periependymal contrast enhancement was significantly associated with higher annualized relapse rates ( P = .03). Brain MRIs of patients with neuromyelitis optica spectrum disorders with contrast

Paraneoplastic Neuromyelitis Optica Spectrum Disorder Associated With Metastatic Carcinoid Expressing Aquaporin-4

PubMed Central

Figueroa, Michelle; Guo, Yong; Tselis, Alexandros; Pittock, Sean J.; Lennon, Vanda A.; Lucchinetti, Claudia F.; Lisak, Robert P.

2014-01-01

IMPORTANCE Reports of neuromyelitis optica spectrum disorder (NMOSD) occurring in the setting of neoplasia suggest that aquaporin-4 autoimmunitymay in some cases have a paraneoplastic basis. OBSERVATIONS In this case report, we describe a patient with NMOSD whose test results were seropositive for aquaporin-4 IgG and who had a hepatic metastasis from a small-bowel neuroendocrine tumor. The tumor cells expressed aquaporin-4 immunoreactivity. She presented to the Neurology Department at Wayne State University with bilateral leg weakness, ascending paresthesias, and decreased sensation. CONCLUSIONS AND RELEVANCE This case extends the context of NMOSD as a paraneoplastic disorder. PMID:24733266

Evoked potentials are useful for diagnosis of neuromyelitis optica spectrum disorder.

PubMed

Ohnari, Keiko; Okada, Kazumasa; Takahashi, Toshiyuki; Mafune, Kosuke; Adachi, Hiroaki

2016-05-15

Neuromyelitis optica spectrum disorder (NMOSD) has been differentiated from relapsing-remitting multiple sclerosis (RRMS) by clinical, laboratory, and pathological findings, including the presence of the anti-aquaporin 4 antibody. Measurement of evoked potentials (EPs) is often used for the diagnosis of RRMS, although the possibility of applying EPs to the diagnosis of NMOSD has not been investigated in detail. Eighteen patients with NMOSD and 28 patients with RRMS were included in this study. The patients' neurological symptoms and signs were examined and their EPs were recorded. Characteristic findings were absence of visual evoked potentials and absence of motor evoked potentials in the lower extremities in patients with NMOSD, and a delay in these potentials in patients with RRMS. Most patients with NMOSD did not present abnormal subclinical EPs, whereas many patients with RRMS did. None of the patients with NMOSD showed abnormalities in auditory brainstem responses. NMOSD can be differentiated from RRMS by EP data obtained in the early stages of these diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Early and extensive spinal white matter involvement in neuromyelitis optica.

PubMed

Hayashida, Shotaro; Masaki, Katsuhisa; Yonekawa, Tomomi; Suzuki, Satoshi O; Hiwatashi, Akio; Matsushita, Takuya; Watanabe, Mitsuru; Yamasaki, Ryo; Suenaga, Toshihiko; Iwaki, Toru; Murai, Hiroyuki; Kira, Jun-Ichi

2017-05-01

Studies of longitudinally extensive spinal cord lesions (LESCLs) in neuromyelitis optica (NMO) have focused on gray matter, where the relevant antigen, aquaporin-4 (AQP4), is abundant. Because spinal white matter pathology in NMO is not well characterized, we aimed to clarify spinal white matter pathology of LESCLs in NMO. We analyzed 50 spinal cord lesions from eleven autopsied NMO/NMO spectrum disorder (NMOSD) cases. We also evaluated LESCLs with three or fewer spinal cord attacks by 3-tesla MRI in 15 AQP4 antibody-positive NMO/NMOSD patients and in 15 AQP4 antibody-negative multiple sclerosis (MS) patients. Pathological analysis revealed seven cases of AQP4 loss and four predominantly demyelinating cases. Forty-four lesions from AQP4 loss cases involved significantly more frequently posterior columns (PC) and lateral columns (LC) than anterior columns (AC) (59.1%, 63.6%, and 34.1%, respectively). The posterior horn (PH), central portion (CP), and anterior horn (AH) were similarly affected (38.6%, 36.4% and 31.8%, respectively). Isolated perivascular inflammatory lesions with selective loss of astrocyte endfoot proteins, AQP4 and connexin 43, were present only in white matter and were more frequent in PC and LC than in AC (22.7%, 29.5% and 2.3%, P corr  = 0.020, and P corr  = 0.004, respectively). MRI indicated LESCLs more frequently affected PC and LC than AC in anti-AQP4 antibody-seropositive NMO/NMOSD (86.7%, 60.0% and 20.0%, P corr  = 0.005, and P corr  = 0.043, respectively) and AQP4 antibody-seronegative MS patients (86.7%, 73.3% and 33.3%, P corr  = 0.063, and P corr  = 0.043, respectively). PH, CP and AH were involved in 93.3%, 86.7% and 73.3% of seropositive patients, respectively, and in 53.3%, 60.0% and 40.0% of seronegative patients, respectively. NMO frequently and extensively affects spinal white matter in addition to central gray matter, especially in PC and LC, where isolated perivascular lesions with astrocyte endfoot

Epidemiology of neuromyelitis optica in Latin America

PubMed Central

Alvarenga, MP; Schimidt, Sergio

2017-01-01

A major development over the past two decades was the recognition of recurrent neuromyelitis optica (NMO) as a particular central nervous system disorder different from multiple sclerosis (MS). Here we reviewed the epidemiology of NMO in Latin America (LATAM). A predominance of a mixed population is found in this region. Recurrent NMO in black women was described in the Caribbean Islands and in Rio de Janeiro. The prevalence of NMO in LATAM varied from 0.37/100,000 (Volta Redonda city) to 4.2/100,000 inhabitants (Caribbean Islands). NMO differs significantly from MS with respect to gender, ethnicity, morbidity and genetic susceptibility. An association of the HLA DRB1*03 alleles with NMO was described in the French Antilles, Ribeirão Preto, Rio de Janeiro and Mexico. It is not common to find familial forms of NMO. NMO represents 11.8% of all inflammatory idiopathic diseases in South America (SA). In SA, the highest frequency of NMO occurs in African Brazilian young women. The overall relative frequency of NMO among MS cases in this region was 14%, decreasing following a north-south gradient, which parallels the percentage of nonwhite people. PMID:28979797

Neuromyelitis optica: Application of computer diagnostics to historical case reports.

PubMed

Garcia Reitboeck, Pablo; Garrard, Peter; Peters, Timothy

2017-01-01

The retrospective diagnosis of illnesses by medical historians can often be difficult and prone to bias, although knowledge of the medical disorders of historical figures is key to the understanding of their behavior and reactions. The recent application of computer diagnostics to historical figures allows an objective differential diagnosis to be accomplished. Taking an example from clinical neurology, we analyzed the earliest reported cases of Devic's disease (neuromyelitis optica) that commonly affects the optic nerve and spinal cord and was previously often confused with multiple sclerosis. We conclude that in most identified cases the software concurred with the contemporary physicians' interpretation, but some claimed cases either had insufficient data to provide a diagnosis or other possible diagnoses were suggested that had not been considered. Computational methods may, therefore, help historians to diagnose the ailments of historical figures with greater objectivity.

Association of anti-aquaporin-4 antibody-positive neuromyelitis optica with myasthenia gravis.

PubMed

Uzawa, Akiyuki; Mori, Masahiro; Iwai, Yuhta; Kobayashi, Makoto; Hayakawa, Sei; Kawaguchi, Naoki; Kuwabara, Satoshi

2009-12-15

We describe 2 patients who developed anti-aquaporin-4 antibody-positive neuromyelitis optica (NMO) following the development of anti-acetylcholine receptor antibody-positive myasthenia gravis (MG). A literature review of 13 similar cases in addition to the present 2 cases of NMO with MG showed predominance among Asian women and frequent development of NMO following thymectomy for MG. Moreover, in one of our patients, serial assays of anti-aquaporin-4 antibody and anti-acetylcholine receptor antibody were performed. Accumulating evidence for the coexistence of NMO and MG suggests that a common immunopathogenesis of NMO and MG may exist, and the association of NMO with MG may be more frequent than hitherto believed.

Immunopathogenesis in Myasthenia Gravis and Neuromyelitis Optica

PubMed Central

Wang, Zhen; Yan, Yaping

2017-01-01

Myasthenia gravis (MG) and neuromyelitis optica (NMO) are autoimmune channelopathies of the peripheral neuromuscular junction (NMJ) and central nervous system (CNS) that are mainly mediated by humoral immunity against the acetylcholine receptor (AChR) and aquaporin-4 (AQP4), respectively. The diseases share some common features, including genetic predispositions, environmental factors, the breakdown of tolerance, the collaboration of T cells and B cells, imbalances in T helper 1 (Th1)/Th2/Th17/regulatory T cells, aberrant cytokine and antibody secretion, and complement system activation. However, some aspects of the immune mechanisms are unique. Both targets (AChR and AQP4) are expressed in the periphery and CNS, but MG mainly affects the NMJ in the periphery outside of CNS, whereas NMO preferentially involves the CNS. Inflammatory cells, including B cells and macrophages, often infiltrate the thymus but not the target—muscle in MG, whereas the infiltration of inflammatory cells, mainly polymorphonuclear leukocytes and macrophages, in NMO, is always observed in the target organ—the spinal cord. A review of the common and discrepant characteristics of these two autoimmune channelopathies may expand our understanding of the pathogenic mechanism of both disorders and assist in the development of proper treatments in the future. PMID:29312313

Aquaporin-4 antibody positive neuromyelitis optica spectrum disorder associated with esophageal cancer.

PubMed

Kon, Tomoya; Ueno, Tatsuya; Suzuki, Chieko; Nunomura, Jinichi; Igarashi, Shohei; Sato, Tsugumi; Tomiyama, Masahiko

2017-08-15

Autoimmune diseases are sometimes associated with neoplasms. A 70-year-old Japanese woman with myelitis, seropositive for aquaporin-4 (AQP4) antibody, was diagnosed with neuromyelitis optica spectrum disorder (NMOSD); thereafter an esophageal squamous cell carcinoma was identified. Immunohistochemically, her cancer was anti-AQP4 antibody negative. Her symptoms, imaging findings and AQP4 titer markedly improved with corticosteroid and anti-cancer therapies. Although AQP4 may be a paraneoplastic antigen, paraneoplastic syndrome could not be definitively diagnosed in this case. Nevertheless, this is the first report of an association between AQP4 antibody-seropositive NMOSD and esophageal cancer. The possibility of underlying malignancy should be considered in patients diagnosed with NMOSD. Copyright © 2017 Elsevier B.V. All rights reserved.

Seronegative Neuromyelitis Optica: A Case Report of a Hispanic Male

PubMed Central

Badri, Nabeel; Teleb, Mohamed; Syed, Saad; Wardi, Miraie; Porres-Aguilar, Mateo; Cruz-Flores, Salvador

2016-01-01

Abstract Neuromyelitis optica (NMO) is a rare disease, common in white females and rarely reported in Hispanic males. It is usually associated with recurrent demyelinating spectrum that is autoimmune in nature. The diagnosis is usually confirmed by antibody biomarkers; however, they can be negative and lead to more dilemma in diagnosis. Furthermore, the course of disease and prognosis are different in seronegative as compared to seropositive NMO. Treatment is similar in both subgroups with new approaches under investigation for seronegative NMO patients. We present an interesting case of a 37-year-old Hispanic male who presented with sudden onset of lower extremity weakness, numbness, blurry vision, and urinary retention. Magnetic resonance imaging (MRI) of the thoracic spine showed multiphasic demyelinating process involving the thoracic spinal cord. His brain MRI also revealed changes suggesting optic neuritis. The patient met the criteria for diagnosis of NMO by having optic neuritis and myelitis by imaging studies despite having negative aquaporin-4 antibodies (AQP4-Ab). His condition improved after plasma exchange. NMO can be difficult to distinguish from acute multiple sclerosis in the early stages of the disease. Having AQP4-Ab testing is important for diagnosis with imaging studies; however, negative antibody results cannot exclude the diagnosis, but rather group it in seronegative subtype. Ongoing studies and research suggest that seronegative NMO might have a different pathophysiology, manifestation, and prognosis. PMID:27403130

Chloride imbalance is involved in the pathogenesis of optic neuritis in neuromyelitis optica.

PubMed

Akaishi, Tetsuya; Takahashi, Toshiyuki; Himori, Noriko; Takeshita, Takayuki; Nakazawa, Toru; Aoki, Masashi; Nakashima, Ichiro

2018-07-15

Chloride imbalance between the serum and the cerebrospinal fluid (CSF) has been recently shown to exist in the acute phase of neuromyelitis optica (NMO). In this report, we studied the relation between the quotient of chloride (Q Cl ) and the severity of optic neuritis (ON) in NMO patients. There was a positive correlation (R = 0.67; p < 0.05) between Q Cl and the length of ON-lesion. The visual prognosis also showed a positive correlation with Q Cl in the acute phase (R = 0.58; p < 0.05). These results support the theory that chloride imbalance between serum and CSF may trigger the ON in NMO spectrum disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

New Insights into Neuromyelitis Optica

PubMed Central

Kim, Woojun; Kim, Su-Hyun

2011-01-01

Neuromyelitis optica (NMO) is an idiopathic inflammatory disorder of the central nervous system (CNS) that preferentially affects the optic nerves and spinal cord. In Asia, NMO has long been considered a subtype of multiple sclerosis (MS). However, recent clinical, pathological, immunological, and imaging studies have suggested that NMO is distinct from MS. This reconsideration of NMO was initially prompted by the discovery of a specific antibody for NMO (NMO-IgG) in 2004. NMO-IgG is an autoantibody that targets aquaporin-4 (AQP4), the most abundant water channel in the CNS; hence, it was named anti-AQP4 antibody. Since it demonstrated reasonable sensitivity and high specificity, anti-AQP4 antibody was incorporated into new diagnostic criteria for NMO.The spectrum of NMO is now known to be wider than was previously recognized and includes a proportion of patients with recurrent, isolated, longitudinally extensive myelitis or optic neuritis, and longitudinally extensive myelitis or optic neuritis associated with systemic autoimmune disease or with brain lesions typical of NMO. In this context, a new concept of "NMO spectrum disorders" was recently introduced. Furthermore, seropositivity for NMO-IgG predicts future relapses and is recognized as a prognostic marker for NMO spectrum disorders. Humoral immune mechanisms, including the activation of B-cells and the complement pathway, are considered to play important roles in NMO pathogenesis. This notion is supported by recent studies showing the potential pathogenic role of NMO-IgG as an initiator of NMO lesions. However, a demonstration of the involvement of NMO-IgG by the development of active immunization and passive transfer in animal models is still needed. This review focuses on the new concepts of NMO based on its pathophysiology and clinical characteristics. Potential management strategies for NMO in light of its pathomechanism are also discussed. PMID:22087205

Neuromyelitis optica immunoglobulin G in Chinese patients detected by immunofluorescence assay on a monkey brain substrate.

PubMed

Long, Youming; Hu, Xueqiang; Peng, Fuhua; Lu, Zhengqi; Wang, Yuge; Yang, Yu; Qiu, Wei

2012-01-01

Serum neuromyelitis optica immunoglobulin G (NMO-IgG) is used as a biomarker to differentiate between neuromyelitis optica (NMO) and multiple sclerosis (MS). However, the original assay is expensive and complex and shows low sensitivity. Here, we investigated the potential of NMO-IgG detection using an indirect immunofluorescence (IIF) assay on monkey brains. NMO-IgG seroprevalence was determined in 168 samples by an IIF assay on a monkey brain substrate. The data were compared with those from a standard mouse brain IIF assay using McNemar and kappa tests. Thirty-one of 50 (62%) NMO patients, 7 of 18 (38.9%) longitudinally extensive transverse myelitis patients, 6 of 57 (10.5%) MS patients, and 5 of 10 (50%) optic neuritis patients were seropositive for NMO-IgG. None of the acute partial transverse myelitis patients (n = 3) or healthy controls (n = 20) was positive. Thus, the sensitivity of the test was 62% for the patients with clinically definite NMO. The specificity was 89.5%, considering the 57 MS patients as the control group. The modified IIF assay on monkey brains and the standard IIF assay based on mouse brains were not significantly different (McNemar test; p = 1.000). The two assays were concordant in 39 seropositive samples and 100 seronegative samples (kappa test; kappa = 0.592, p < 0.0001). Although the modified IIF monkey brain assay was no better than the standard mouse brain IIF assay, we affirmed that NMO-IgG is a sensitive and specific biomarker to differentiate between NMO and MS. Copyright © 2011 S. Karger AG, Basel.

Neuromyelitis optica in pregnancy complicated by posterior reversible encephalopathy syndrome, eclampsia and fetal death.

PubMed

Igel, Catherine; Garretto, Diana; Robbins, Matthew S; Swerdlow, Michael; Judge, Nancy; Dayal, Ashlesha

2015-03-01

Neuromyelitis optica (NMO) is a demyelinating syndrome characterized by optic neuritis and acute myelitis with poor recovery and a progressive course. We report a poor outcome complicated by posterior reversible encephalopathy syndrome (PRES) and eclampsia and review available literature and current evidence for anticipation of adverse fetal and maternal effects. After a pregnancy complicated by multiple admissions for painful NMO exacerbations, a primiparous patient with seropositive NMO presented at 31 + 3/7 weeks with eclampsia, HELLP and subsequent fetal death. MRI confirmed PRES. NMO may be associated with eclampsia and leads to adverse maternal and fetal outcomes. Posited mechanisms include antibody-mediated placental damage and a heightened risk of eclampsia-associated PRES. Further characterization of the course of NMO and its relationship with pregnancy outcomes in larger series would be invaluable.

Neuromyelitis Optica in Pregnancy Complicated by Posterior Reversible Encephalopathy Syndrome, Eclampsia and Fetal Death

PubMed Central

Igel, Catherine; Garretto, Diana; Robbins, Matthew S; Swerdlow, Michael; Judge, Nancy; Dayal, Ashlesha

2015-01-01

Neuromyelitis optica (NMO) is a demyelinating syndrome characterized by optic neuritis and acute myelitis with poor recovery and a progressive course. We report a poor outcome complicated by posterior reversible encephalopathy syndrome (PRES) and eclampsia and review available literature and current evidence for anticipation of adverse fetal and maternal effects. After a pregnancy complicated by multiple admissions for painful NMO exacerbations, a primiparous patient with seropositive NMO presented at 31 + 3/7 weeks with eclampsia, HELLP and subsequent fetal death. MRI confirmed PRES. NMO may be associated with eclampsia and leads to adverse maternal and fetal outcomes. Posited mechanisms include antibody-mediated placental damage and a heightened risk of eclampsia-associated PRES. Further characterization of the course of NMO and its relationship with pregnancy outcomes in larger series would be invaluable. PMID:25584107

Autoimmune AQP4 channelopathies and neuromyelitis optica spectrum disorders.

PubMed

Hinson, Shannon R; Lennon, Vanda A; Pittock, Sean J

2016-01-01

Neuromyelitis optica (NMO) spectrum disorders (SD) represent an evolving group of central nervous system (CNS)-inflammatory autoimmune demyelinating diseases unified by a pathogenic autoantibody specific for the aquaporin-4 (AQP4) water channel. It was historically misdiagnosed as multiple sclerosis (MS), which lacks a distinguishing biomarker. The discovery of AQP4-IgG moved the focus of CNS demyelinating disease research from emphasis on the oligodendrocyte and myelin to the astrocyte. NMO is recognized today as a relapsing disease, extending beyond the optic nerves and spinal cord to include brain (especially in children) and skeletal muscle. Brain magnetic resonance imaging abnormalities, identifiable in 60% of patients at the second attack, are consistent with MS in 10% of cases. NMOSD-typical lesions (another 10%) occur in AQP4-enriched regions: circumventricular organs (causing intractable nausea and vomiting) and the diencephalon (causing sleep disorders, endocrinopathies, and syndrome of inappropriate antidiuresis). Advances in understanding the immunobiology of AQP4 autoimmunity have necessitated continuing revision of NMOSD clinical diagnostic criteria. Assays that selectively detect pathogenic AQP4-IgG targeting extracellular epitopes of AQP4 are promising prognostically. When referring to AQP4 autoimmunity, we suggest substituting the term "autoimmune aquaporin-4 channelopathy" for the term "NMO spectrum disorders." Randomized clinical trials are currently assessing the efficacy and safety of newer immunotherapies. Increasing therapeutic options based on understanding the molecular pathogenesis is anticipated to improve the outcome for patients with AQP4 channelopathy. © 2016 Elsevier B.V. All rights reserved.

High-risk syndrome for neuromyelitis optica: a descriptive and comparative study.

PubMed

Collongues, N; Marignier, R; Zéphir, H; Blanc, F; Vukusic, S; Outteryck, O; Fleury, M; Ruet, A; Borgel, F; Thouvenot, E; Moreau, T; Defer, G; Derache, N; Pelletier, J; Audoin, B; Debouverie, M; Labauge, P; Gout, O; Camu, W; Brassat, D; Brochet, B; Vermersch, P; Confavreux, C; de Seze, J

2011-06-01

Neuromyelitis optica (NMO) frequently begins with a monofocal episode of optic neuritis or myelitis. A concept named high-risk syndrome (HRS) for NMO has been proposed for patients with monofocal episodes and NMO-IgG antibodies. To describe HRS patients and compare them with NMO patients. We identified 30 patients with HRS: 18 with extensive myelitis (HRM) and 12 with optic neuritis (HRON), in a database pooling patients from 25 centres in France. Clinical, laboratory/magnetic resonance imaging (MRI) data and outcome were analysed and compared with a national cohort of 125 NMO patients extracted from the same database. Mean follow-up was 4.8 years. Mean age at onset was 42.8 years (range: 12.4-70) with a female:male ratio of 0.9. Asymptomatic lesions were report on visual evoked potentials in 4/8 tested HRM patients and on spinal cord MRI in 2/7 HRON patients. Three patients died, two owing to a cervical lesion. HRS and NMO patients had similar clinical/paraclinical data, except for a predominance of men in the HRS group and a later mean age at onset in the HRM subgroup. The description of HRS patients is compatible with a monofocal form of NMO. Asymptomatic lesions could be included in a new set of NMO diagnostic criteria.

Differentiation of Neuromyelitis Optica from Multiple Sclerosis on Spinal Magnetic Resonance Imaging

PubMed Central

Khan, Majid; Schlakman, Bruce; Penman, Alan; Gatlin, Joseph; Herndon, Robert

2012-01-01

In order to examine the accuracy of magnetic resonance imaging (MRI)–based diagnosis of neuromyelitis optica (NMO) versus multiple sclerosis (MS), we performed a retrospective, rater-blinded review of 29 cases of NMO and 30 cases of MS using the criteria of long (more than three vertebral levels), continuous lesions with a central cord location for NMO and more peripheral and patchy lesions for MS. Using these criteria, two raters were able to distinguish the two conditions with a good degree of confidence, particularly when the imaging was performed at the time of an acute cord attack. The sensitivity and specificity for diagnosis of NMO were 86.2% and 93.3%, respectively, for Rater A and 96.4% and 78.6%, respectively, for Rater B, with a kappa value of 0.72. Thus there are significant differences in lesion characteristics that allow the distinction on spinal cord imaging between MS and NMO with a moderately high degree of confidence. The location of the lesion as evident on MRI of the spine can be regarded as a distinguishing diagnostic feature between MS and NMO. PMID:24453753

Systematic review of the published data on the worldwide prevalence of John Cunningham virus in patients with multiple sclerosis and neuromyelitis optica.

PubMed

Paz, Sonia Patricia Castedo; Branco, Luciana; Pereira, Marina Alves de Camargo; Spessotto, Caroline; Fragoso, Yara Dadalti

2018-01-01

John Cunningham virus (JCV) is a polyoma virus that infects humans, mainly in childhood or adolescence, and presents no symptomatic manifestations. JCV can cause progressive multifocal leukoencephalopathy (PML) in immunosuppressed individuals, including those undergoing treatment for multiple sclerosis (MS) and neuromyelitis optica (NMO). PML is a severe and potentially fatal disease of the brain. The prevalence of JCV antibodies in human serum has been reported to be between 50.0 and 90.0%. The aim of the present study was to review worldwide data on populations of patients with MS and NMO in order to establish the rates of JCV seropositivity in these individuals. The present review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and used the following search terms: "JCV" OR "JC virus" AND "multiple sclerosis" OR "MS" OR "NMO" OR "neuromyelitis optica" AND "prevalence." These terms were searched for both in smaller and in larger clusters of words. The databases searched included PubMed, MEDLINE, SciELO, LILACS, Google Scholar, and Embase. After the initial selection, 18 papers were included in the review. These articles reported the prevalence of JCV antibodies in the serum of patients with MS or NMO living in 26 countries. The systematic review identified data on 29,319 patients with MS/NMO and found that 57.1% of them (16,730 individuals) were seropositive for the anti-JCV antibody (range, 40.0 to 69.0%). The median worldwide prevalence of JCV among adults with MS or NMO was found to be 57.1%.

Neuromyelitis optica: association with paroxysmal painful tonic spasms.

PubMed

Carnero Contentti, E; Leguizamón, F; Hryb, J P; Celso, J; Pace, J L Di; Ferrari, J; Knorre, E; Perassolo, M B

2016-10-01

Paroxysmal painful tonic spasms (PPTS) were initially described in multiple sclerosis (MS) but they are more frequent in neuromyelitis optica (NMO). The objective is to report their presence in a series of cases of NMO and NMO spectrum disorders (NMOSD), as well as to determine their frequency and clinical features. We conducted a retrospective assessment of medical histories of NMO/NMOSD patients treated in 2 hospitals in Buenos Aires (Hospital Durand and Hospital Álvarez) between 2009 and 2013. Out of 15 patients with NMOSD (7 with definite NMO and 8 with limited NMO), 4 presented PPTS (26.66%). PPTS frequency in the definite NMO group was 57.14% (4/7). Of the 9 patients with longitudinally extensive transverse myelitis (LETM), 44.44% (9/15) presented PPTS. Mean age was 35 years (range, 22-38 years) and all patients were women. Mean time between NMO diagnosis and PPTS onset was 7 months (range, 1-29 months) and mean time from last relapse of LETM was 30 days (range 23-40 days). LETM (75% cervicothoracic and 25% thoracic) was observed by magnetic resonance imaging (MRI) in all patients. Control over spasms and pain was achieved in all patients with carbamazepine (associated with gabapentin in one case). No favourable responses to pregabalin, gabapentin, or phenytoin were reported. PPTS are frequent in NMO. Mean time of PPTS onset is approximately one month after an LETM relapse, with extensive cervicothoracic lesions appearing on the MRI scan. They show an excellent response to carbamazepine but little or no response to pregabalin and gabapentin. Prospective studies with larger numbers of patients are necessary in order to confirm these results. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Acute-Onset Severe Occipital Neuralgia Associated With High Cervical Lesion in Patients With Neuromyelitis Optica Spectrum Disorder.

PubMed

Hayashi, Yuichi; Koumura, Akihiro; Yamada, Megumi; Kimura, Akio; Shibata, Toshirou; Inuzuka, Takashi

2017-07-01

To address occipital neuralgia in patients with neuromyelitis optica spectrum disorder (NMOSD). NMOSD is an inflammatory demyelinating disease that commonly presents with pain; however, headache symptoms have received little attention. We presented three cases of NMOSD in which the patients experienced acute-onset, severe, and steroid-responsive occipital neuralgia. All patients provided consent to use their demographic and imaging data retrospectively. In all three cases, MRI revealed a new high-intensity area in the cervical cord at the C1-C3 level of the spine, which was diminished in two of the three cases after corticosteroid pulse therapy. Our cases support the recognition of NMOSD as a cause of secondary headache. As patients with NMOSD experience severe occipital neuralgia, a relapse should be considered and a cervical MRI should be performed. © 2017 American Headache Society.

Thalamic Atrophy Contributes to Low Slow Wave Sleep in Neuromyelitis Optica Spectrum Disorder.

PubMed

Su, Lei; Han, Yujuan; Xue, Rong; Wood, Kristofer; Shi, Fu-Dong; Liu, Yaou; Fu, Ying

2016-12-01

Slow wave sleep abnormality has been reported in neuromyelitis optica spectrum disorder (NMOSD), but mechanism for such abnormality is unknown. To determine the structural defects in the brain that account for the decrease of slow wave sleep in NMOSD patients. Thirty-three NMOSD patients and 18 matched healthy controls (HC) were enrolled. Polysomnography was used to monitor slow wave sleep and three-dimensional T1-weighted MRIs were obtained to assess the alterations of grey matter volume. The percentage of deep slow wave sleep decreased in 93% NMOSD patients. Compared to HC, a reduction of grey matter volume was found in the bilateral thalamus of patients with a lower percentage of slow wave sleep (FWE corrected at cluster-level, p < 0.05, cluster size > 400 voxels). Furthermore, the right thalamic fraction was positively correlated with the decrease in the percentage of slow wave sleep in NMOSD patients (p < 0.05, FDR corrected, cluster size > 200 voxels). Our study identified that thalamic atrophy is associated with the decrease of slow wave sleep in NMOSD patients. Further studies should evaluate whether neurotransmitters or hormones which stem from thalamus are involved in the decrease of slow wave sleep.

A case of seropositive Neuromyelitis Optica in a paediatric patient with co-existing acute nephrotic syndrome.

PubMed

Volkman, Thomas; Hemingway, Cheryl

2017-11-01

Neuromyelitis optica (NMO) and NMO spectrum disorder (NMOSD) is a rare relapsing autoimmune disease of the central nervous system constituting less than 1% of demyelinating diseases (Jeffery and Buncic, 1996). It preferentially affects the optic nerves and spinal cord, with the brain parenchyma generally spared. Demyelinating lesions are characterised by longitudinally extensive transverse myelitis (LETM) and often longitudinally extensive optic neuritis. Following the discovery of a novel pathogenic antibody, Aquaporin 4 in 2004 (Lennon et al., 2004) this disease has been seen as a separate entity from Multiple Sclerosis (MS). We report the case of a severe AQP4 IgG case of NMO in a 10 year old child. This case unusually had a coexisting diagnosis of acute nephrotic syndrome which has only been reported once previously in the literature 2 . This article will examine some of the treatment challenges and the spectrum of co-existing autoimmune disease in NMOSD. Copyright © 2017. Published by Elsevier B.V.

Effectiveness of multi-disciplinary rehabilitation for patients with Neuromyelitis Optica

PubMed Central

Nechemia, Yael; Moreh, Elior; Weingarden, Harold; Bloch, Ayala; Givon, Uri; Vaknin-Dembinsky, Adi; Schwartz, Isabella; Meiner, Zeev

2016-01-01

Introduction Neuromyelitis optica (NMO), previously considered a subtype of multiple sclerosis (MS), is now known to be a unique disorder associated with autoantibodies against aquaporin-4. The rehabilitation protocols for MS have been applied to NMO, without specific measures of efficacy. Purpose The evaluation of the effectiveness of an MS type inpatient rehabilitation program for patients with NMO. Patient and Methods Retrospective chart reviews of 15 inpatients with NMO and 32 inpatients with MS. Clinical severity was assessed by the Expanded Disability Status Scale (EDSS), functional assessments were scored using the Functional Independence Measure (FIM), the Montebello Rehabilitation Factor Score (MRFS), and the Functional Ambulation Category (FAC). There was a higher percentage of women in the NMO group (87% vs 56% P = 0.003). The MS group had significantly more cognitive and communication deficits (P = 0.003 and P = 0.00001). No significant differences were found in admission FIM, EDSS and FAC scores. Results Both groups benefitted, however at discharge, the NMO group showed greater improvement in FIM scores (NMO admission 79 ± 24, discharge 98 ± 21; MS admission 80 ± 28, discharge 89 ± 28); and lower EDSS score (NMO from 7.2 ± 1.4 to 6.3 ± 1.4; MS from 7.4 ± 1.4 to 7 ± 1.5). Conclusions Inpatient multidisciplinary rehabilitation programs available for the patients with MS may be successfully implemented for patients with NMO. PMID:26446695

White Matter Atrophy and Cognitive Dysfunctions in Neuromyelitis Optica

PubMed Central

Blanc, Frederic; Noblet, Vincent; Jung, Barbara; Rousseau, François; Renard, Felix; Bourre, Bertrand; Longato, Nadine; Cremel, Nadjette; Di Bitonto, Laure; Kleitz, Catherine; Collongues, Nicolas; Foucher, Jack; Kremer, Stephane; Armspach, Jean-Paul; de Seze, Jerome

2012-01-01

Neuromyelitis optica (NMO) is an inflammatory disease of central nervous system characterized by optic neuritis and longitudinally extensive acute transverse myelitis. NMO patients have cognitive dysfunctions but other clinical symptoms of brain origin are rare. In the present study, we aimed to investigate cognitive functions and brain volume in NMO. The study population consisted of 28 patients with NMO and 28 healthy control subjects matched for age, sex and educational level. We applied a French translation of the Brief Repeatable Battery (BRB-N) to the NMO patients. Using SIENAx for global brain volume (Grey Matter, GM; White Matter, WM; and whole brain) and VBM for focal brain volume (GM and WM), NMO patients and controls were compared. Voxel-level correlations between diminished brain concentration and cognitive performance for each tests were performed. Focal and global brain volume of NMO patients with and without cognitive impairment were also compared. Fifteen NMO patients (54%) had cognitive impairment with memory, executive function, attention and speed of information processing deficits. Global and focal brain atrophy of WM but not Grey Matter (GM) was found in the NMO patients group. The focal WM atrophy included the optic chiasm, pons, cerebellum, the corpus callosum and parts of the frontal, temporal and parietal lobes, including superior longitudinal fascicle. Visual memory, verbal memory, speed of information processing, short-term memory and executive functions were correlated to focal WM volumes. The comparison of patients with, to patients without cognitive impairment showed a clear decrease of global and focal WM, including brainstem, corticospinal tracts, corpus callosum but also superior and inferior longitudinal fascicles. Cognitive impairment in NMO patients is correlated to the decreased of global and focal WM volume of the brain. Further studies are needed to better understand the precise origin of cognitive impairment in NMO patients

European Ancestry Predominates in Neuromyelitis Optica and Multiple Sclerosis Patients from Brazil

PubMed Central

Santos, Antônio Carlos; Lana-Peixoto, Marco Aurélio; Rocha, Cristiane Franklin; Brito, Maria Lucia; de Oliveira, Enedina Maria Lobato; Bichuetti, Denis Bernardi; Gabbai, Alberto Alan; Diniz, Denise Sisterolli; Kaimen-Maciel, Damacio Ramon; Comini-Frota, Elizabeth Regina; Vieira Wiezel, Claudia E.; Muniz, Yara Costa Netto; da Silva Costa, Roberta Martins; Mendes-Junior, Celso Teixeira; Donadi, Eduardo Antônio; Barreira, Amilton Antunes; Simões, Aguinaldo Luiz

2013-01-01

Background Neuromyelitis optica (NMO) is considered relatively more common in non-Whites, whereas multiple sclerosis (MS) presents a high prevalence rate, particularly in Whites from Western countries populations. However, no study has used ancestry informative markers (AIMs) to estimate the genetic ancestry contribution to NMO patients. Methods Twelve AIMs were selected based on the large allele frequency differences among European, African, and Amerindian populations, in order to investigate the genetic contribution of each ancestral group in 236 patients with MS and NMO, diagnosed using the McDonald and Wingerchuck criteria, respectively. All 128 MS patients were recruited at the Faculty of Medicine of Ribeirão Preto (MS-RP), Southeastern Brazil, as well as 108 healthy bone marrow donors considered as healthy controls. A total of 108 NMO patients were recruited from five Neurology centers from different Brazilian regions, including Ribeirão Preto (NMO-RP). Principal Findings European ancestry contribution was higher in MS-RP than in NMO-RP (78.5% vs. 68.7%) patients. In contrast, African ancestry estimates were higher in NMO-RP than in MS-RP (20.5% vs. 12.5%) patients. Moreover, principal component analyses showed that groups of NMO patients from different Brazilian regions were clustered close to the European ancestral population. Conclusions Our findings demonstrate that European genetic contribution predominates in NMO and MS patients from Brazil. PMID:23527051

IL2RA Allele Increases Risk of Neuromyelitis Optica in Southern Han Chinese.

PubMed

Dai, Yongqiang; Li, Jin; Zhong, Xiaonan; Wang, Yuge; Qiu, Wei; Lu, Zhengqi; Wu, Aimin; Bao, Jian; Peng, Fuhua; Hu, Xueqiang

2013-11-01

Neuromyelitis optica (NMO) and multiple sclerosis (MS) are chronic neuro-inflammatory diseases believed to arise from complex interactions between environmental and genetic factors. Recently, single nucleotide polymorphisms (SNPs) in interleukin (IL)-2 and -7 receptor alpha genes have been identified as novel susceptibility alleles for MS in genome-wide association studies. However, similar research on NMO is limited. We aimed to investigate the association of IL2RA SNPs rs2104286 and rs12722489 and IL7RA SNP rs6897932 with Southern Han Chinese NMO and MS patients. Frequencies of the three SNPs were examined in Southern Han Chinese mS cases (n=78), NMS cases (n=67) and controls (n=133) using sequencing-based typing. The rs2104286(G) frequency in the IL2RA gene was significantly higher in NMO patients than in controls (p(uncorr)=0.013, p(corr)=0.026, OR:1.942, 95%CI:1.146-3.291). The rs2104286 G allele in IL2RA is present at higher frequencies in NMO patients than in healthy controls within a Southern Han Chinese population. Les allèles IL2RA augmentent le risque de neuromyélite optique chez les Chinois Han du sud.

CFHR1-Modified Neural Stem Cells Ameliorated Brain Injury in a Mouse Model of Neuromyelitis Optica Spectrum Disorders.

PubMed

Shi, Kaibin; Wang, Zhen; Liu, Yuanchu; Gong, Ye; Fu, Ying; Li, Shaowu; Wood, Kristofer; Hao, Junwei; Zhang, Guang-Xian; Shi, Fu-Dong; Yan, Yaping

2016-11-01

A major hurdle for effective stem cell therapy is ongoing inflammation in the target organ. Reconditioning the lesion microenvironment may be an effective way to promote stem cell therapy. In this study, we showed that engineered neural stem cells (NSCs) with complement factor H-related protein 1, a complement inhibitor protein, can attenuate inflammatory infiltration and immune-mediated damage of astrocytes, an important pathogenic progress in patients with neuromyelitis optica spectrum disorders. Furthermore, we demonstrated that transplantation of the complement factor H-related protein 1-modified NSCs effectively blocked the complement activation cascade and inhibited formation of the membrane attack complex, thus contributing to the protection of endogenous and transplanted NSC-differentiated astrocytes. Therefore, manipulation of the lesion microenvironment contributes to a more effective cell replacement therapeutic strategy for autoimmune diseases of the CNS. Copyright © 2016 by The American Association of Immunologists, Inc.

Antibody response against HERV-W env surface peptides differentiates multiple sclerosis and neuromyelitis optica spectrum disorder.

PubMed

Arru, Giannina; Sechi, Elia; Mariotto, Sara; Farinazzo, Alessia; Mancinelli, Chiara; Alberti, Daniela; Ferrari, Sergio; Gajofatto, Alberto; Capra, Ruggero; Monaco, Salvatore; Deiana, Giovanni A; Caggiu, Elisa; Mameli, Giuseppe; Sechi, Leonardo A; Sechi, Gian Pietro

2017-01-01

A specific humoral immune response against HERV-W envelope surface (env-su) glycoprotein antigens has been reported in serum of patients with multiple sclerosis (MS). However, it has not been evaluated to date in patients with neuromyelitis optica spectrum disorder (NMOSD). The objective of this paper is to investigate whether antibody (Ab) response against HERV-W env-su antigenic peptides differs between NMOSD and MS. Serum samples were collected from 36 patients with NMOSD, 36 patients with MS and 36 healthy control individuals (HCs). An indirect ELISA was set up to detect specific Abs against HERV-W env-su peptides. Our data showed that two antigenic peptides, particularly HERV-Wenv 93-108 and HERV-Wenv 248-262, were statistically significantly present only in serum of MS compared to NMOSD and HCs. Thus, the specific humoral immune response against HERV-W env-su glycoprotein antigens found in MS is widely missing in NMOSD. Increased circulating serum levels of these HERV-W Abs may be suitable as additional biomarkers to better differentiate MS from NMOSD.

Sjögren syndrome and neuromyelitis optica spectrum disorder co-exist in a common autoimmune milieu.

PubMed

Carvalho, Diogo C; Tironi, Tauana S; Freitas, Denise S; Kleinpaul, Rodrigo; Talim, Natalia C; Lana-Peixoto, Marco A

2014-08-01

The relationship between Sjögren's syndrome (SS) and neuromyelitis optica spectrum disorder (NMOSD) is not completely understood. We report two patients with both conditions and review 47 other previously reported cases meeting currently accepted diagnostic criteria, from 17 articles extracted from PubMed. Out of 44 patients whose gender was informed, 42 were females. Mean age at onset of neurological manifestation was 36.2 years (10-74). Serum anti-AQP4-IgG was positive in 32 patients, borderline in 1, and negative in 4. Our Case 1 was seronegative for AQP4-IgG and had no non-organ-specific autoantibodies other than anti-SSB antibodies. Our Case 2 had serum anti-AQP4, anti-SSA/SSB, anti-thyreoglobulin and anti-acethylcholine-receptor antibodies, as well as clinical hypothyreoidism, but no evidence of myasthenia gravis. Our Cases and others, as previously reported in literature, with similar heterogeneous autoimmune response to aquaporin-4, suggest that SS and NMO co-exist in a common autoimmune milieu which is not dependent on aquaporin-4 autoimmunity.

Th17 Cells Pathways in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders: Pathophysiological and Therapeutic Implications

PubMed Central

Passos, Giordani Rodrigues Dos; Sato, Douglas Kazutoshi; Becker, Jefferson; Fujihara, Kazuo

2016-01-01

Several animal and human studies have implicated CD4+ T helper 17 (Th17) cells and their downstream pathways in the pathogenesis of central nervous system (CNS) autoimmunity in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), challenging the traditional Th1-Th2 paradigm. Th17 cells can efficiently cross the blood-brain barrier using alternate ways from Th1 cells, promote its disruption, and induce the activation of other inflammatory cells in the CNS. A number of environmental factors modulate the activity of Th17 pathways, so changes in the diet, exposure to infections, and other environmental factors can potentially change the risk of development of autoimmunity. Currently, new drugs targeting specific points of the Th17 pathways are already being tested in clinical trials and provide basis for the development of biomarkers to monitor disease activity. Herein, we review the key findings supporting the relevance of the Th17 pathways in the pathogenesis of MS and NMOSD, as well as their potential role as therapeutic targets in the treatment of immune-mediated CNS disorders. PMID:26941483

Long-term MRI findings in neuromyelitis optica: seropositive versus seronegative patients.

PubMed

Kıyat-Atamer, A; Ekizoğlu, E; Tüzün, E; Kürtüncü, M; Shugaiv, E; Akman-Demir, G; Eraksoy, M

2013-05-01

Neuromyelitis optica (NMO) is a severe demyelinating inflammatory disorder associated with serum antibodies against aquaporin 4 (AQP4-Ab). A significant number of patients with NMO remain seronegative over time. Long-term observational magnetic resonance imaging (MRI) studies of the CNS in patients with NMO are rare or of limited duration. The objective of this study is to determine long-term MRI characteristics of seropositive and seronegative patients, and assess possible overlap with multiple sclerosis (MS). Clinical and radiological characteristics of 28 patients with NMO at onset and of 17 patients after an average follow-up time of 9 years were recorded. Fifty percent of patients were seropositive for AQP4-Ab. Onset and final brain/spinal MRI scans were retrospectively analysed and compared. Significantly more patients in the seronegative group had brain lesions at onset. Spinal lesions of seropositive patients were longer and showed increased cord swelling at onset MRI scans. After the follow-up time the differences between both groups disappeared. Patients in the seropositive group tended to develop brain lesions over time. No patient fulfilled Barkhof's or McDonald's radiological criteria for MS at onset or over time. Brain MRI features show differences between seropositive and seronegative patients at time of onset in NMO, but differences between groups vanish over time. None of the AQP4-negative patients fulfill radiological MS criteria on a long-term basis, suggesting that seronegative NMO constitutes an independent entity. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

Gender effect on neuromyelitis optica spectrum disorder with aquaporin4-immunoglobulin G.

PubMed

Kim, Sung-Min; Waters, Patrick; Woodhall, Mark; Kim, Yoo-Jin; Kim, Jin-Ah; Cheon, So Young; Lee, Sehoon; Jo, Seong Rae; Kim, Dong Gun; Jung, Kyeong Cheon; Lee, Kwang-Woo; Sung, Jung-Joon; Park, Kyung Seok

2017-07-01

Neuromyelitis optica spectrum disorder with aquaporin4-immunoglobulin G (NMOSD-AQP4) is an inflammatory disease characterised by a high female predominance. However, the effect of gender in patients with NMOSD-AQP4 has not been fully evaluated. The aim of this study was to determine the effect of gender in clinical manifestations and prognosis of patients with NMOSD-AQP4. The demographics, clinical and radiological characteristics, pattern reversal visual evoked potential (VEP) test results, and prognosis of 102 patients (18 males) with NMOSD-AQP4 were assessed. Male patients had a higher age at onset (48.7 vs 41 years, p = 0.037) and less optic neuritis as the onset attack (17% vs 44%, p = 0.026), higher tendency to manifest as isolated myelitis over the follow-up period (67% vs 28%, p = 0.005), fewer optic neuritis attacks per year (0.08 vs 0.27, p < 0.001), and shorter relative P100 latency on VEP testing (97.1% vs 108.3%, p = 0.001). Moreover, male gender was significantly associated with the absence of optic neuritis attacks over the follow-up period independent of their age of onset. In NMOSD-AQP4 patients, gender impacts on disease onset age and site of attack. This may be an important clue in identifying NMOSD-AQP4 patients with limited manifestations as well as in predicting their clinical courses.

Pregnancy in neuromyelitis optica spectrum disorder: A multicenter study from South China.

PubMed

Huang, Yanlu; Wang, Yuge; Zhou, Yifan; Huang, Qiao; Sun, Xiaobo; Chen, Chen; Fang, Ling; Long, Youming; Yang, Hui; Wang, Honghao; Li, Caixia; Lu, Zhengqi; Hu, Xueqiang; Kermode, Allan G; Qiu, Wei

2017-01-15

This study aimed to assess the effect of pregnancy on the course of neuromyelitis optica spectrum disorder (NMOSD), and the effect of this disease on pregnancy outcomes. Consecutive patients with NMOSD were recruited between September 2015 and April 2016 at an outpatient clinic from four referral institutes in South China. Demographic, clinical, and pregnancy data were retrieved by questionnaires to analyze the association between NMOSD and pregnancy, as well as the potential risk factors for relapse. Among 249 patients with NMOSD, 55 had pregnancy-related attacks. The annual relapse rate in the first (3.20±6.82) and second (3.25±3.32) 3-month postpartum periods was marginally higher than that before pregnancy (1.44±0.92, p=0.682) and during pregnancy (1.23±1.32, p=0.758). The Kurtzke Expanded Disability Status Scale score increased from 1.55±0.38 before pregnancy to 2.88±2.14 at postpartum (p<0.001). NMOSD significantly increased the premature birth rate in patients after disease onset (8.33%) compared with before disease onset (1.95%, p=0.025). Multivariate analysis showed that negative anti-aquaporin-4 IgG, concomitance with autoimmune diseases/antibodies, and no treatment in remission were risk factors of recurrence. Our study shows a significant association between pregnancy and NMOSD in the Chinese population. Larger scale prospective studies are warranted in the future. Copyright © 2016 Elsevier B.V. All rights reserved.

Neuromyelitis optica IgG stimulates an immunological response in rat astrocyte cultures.

PubMed

Howe, Charles L; Kaptzan, Tatiana; Magaña, Setty M; Ayers-Ringler, Jennifer R; LaFrance-Corey, Reghann G; Lucchinetti, Claudia F

2014-05-01

Neuromyelitis optica (NMO) is a primary astrocyte disease associated with central nervous system inflammation, demyelination, and tissue injury. Brain lesions are frequently observed in regions enriched in expression of the aquaporin-4 (AQP4) water channel, an antigenic target of the NMO IgG serologic marker. Based on observations of disease reversibility and careful characterization of NMO lesion development, we propose that the NMO IgG may induce a dynamic immunological response in astrocytes. Using primary rat astrocyte-enriched cultures and treatment with NMO patient-derived serum or purified IgG, we observed a robust pattern of gene expression changes consistent with the induction of a reactive and inflammatory phenotype in astrocytes. The reactive astrocyte factor lipocalin-2 and a broad spectrum of chemokines, cytokines, and stress response factors were induced by either NMO patient serum or purified IgG. Treatment with IgG from healthy controls had no effect. The effect is disease-specific, as serum from patients with relapsing-remitting multiple sclerosis, Sjögren's, or systemic lupus erythematosus did not induce a response in the cultures. We hypothesize that binding of the NMO IgG to AQP4 induces a cellular response that results in transcriptional and translational events within the astrocyte that are consistent with a reactive and inflammatory phenotype. Strategies aimed at reducing the inflammatory response of astrocytes may short circuit an amplification loop associated with NMO lesion development. Copyright © 2014 Wiley Periodicals, Inc.

Abnormal brain function in neuromyelitis optica: A fMRI investigation of mPASAT.

PubMed

Wang, Fei; Liu, Yaou; Li, Jianjun; Sondag, Matthew; Law, Meng; Zee, Chi-Shing; Dong, Huiqing; Li, Kuncheng

2017-10-01

Cognitive impairment with the Neuromyelitis Optica (NMO) patients is debated. The present study is to study patterns of brain activation in NMO patients during a pair of task-related fMRI. We studied 20 patients with NMO and 20 control subjects matched for age, gender, education and handedness. All patients with NMO met the 2006 Wingerchuk diagnostic criteria. The fMRI paradigm included an auditory attention monitoring task and a modified version of the Paced Auditory Serial Addition Task (mPASAT). Both tasks were temporally and spatially balanced, with the exception of task difficulty. In mPASAT, Activation regions in control subjects included bilateral superior temporal gyri (BA22), left inferior frontal gyrus (BA45), bilateral inferior parietal lobule (BA7), left cingulate gyrus (BA32), left insula (BA13), and cerebellum. Activation regions in NMO patients included bilateral superior temporal gyri (BA22), left inferior frontal gyrus (BA9), right cingulate gyrus (BA32), right inferior parietal gyrus (BA40), left insula (BA13) and cerebellum. Some dispersed cognition related regions are greater in the patients. The present study showed altered cerebral activation during mPASAT in patients with NMO relative to healthy controls. These results are speculated to provide further evidence for brain plasticity in patients with NMO. Copyright © 2017 Elsevier B.V. All rights reserved.

Diagnosis and management of Neuromyelitis Optica Spectrum Disorder (NMOSD) in Iran: A consensus guideline and recommendations.

PubMed

Sahraian, Mohammad Ali; Moghadasi, Abdorreza Naser; Azimi, Amir Reza; Asgari, Nasrin; H Akhoundi, Fahimeh; Abolfazli, Roya; Alaie, Shekoofeh; Ashtari, Fereshteh; Ayromlou, Hormoz; Baghbanian, Seyed Mohammad; Moghadam, Nahid Beladi; Fatehi, Farzad; Foroughipour, Mohsen; Langroodi, Hamidreza Ghalyanchi; Majdinasab, Nastaran; Nickseresht, Alireza; Nourian, Abbas; Shaygannejad, Vahid; Torabi, Hamid Reza

2017-11-01

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a relapsing neuro inflammatory disease of the central nervous system that typically presents with optic neuritis or myelitis and may cause severe disability. The diagnostic criteria have been updated and several immunosuppressive agents have been demonstrated to prevent acute exacerbations. As the disease rarely develops in a progressive course, management of acute attacks and proper prevention of exacerbations may change the long term out-come and prevent future disability. Consensus recommendations and guidelines will help the physicians to improve their practice and unify the treatment approaches in different communities. In order to develop a national consensus and recommendations for the diagnosis and management of NMOSD in Iran, a group of neurologists with long term experience in management of NMOSD were gathered to develop this consensus based on available national and international data. The primary draft was prepared and discussed to suggest the most appropriate treatment for these patients. We propose strategies for early diagnosis and treatment for prevention of relapses and minimizing consequences of attacks as a primary therapeutic goal. Attacks are currently treated with intravenous corticosteroids and, in refractory cases, with plasma exchange. All participants agreed on preventive treatment with currently available immunosuppressive agents such as azothioprin, rituximab and mycofenolate mofetil based on previous positive data in NMOSD in order to reduce attack frequency. The current consensus reviews the previous data and provides the clinicians with practical recommendations and advices for the diagnosis and management of NMOSD based on scientific data and clinical experience. Copyright © 2017 Elsevier B.V. All rights reserved.

A case of neuromyelitis optica spectrum disorder (NMOSD) with Sjögren's syndrome manifested only brain involvement by preceding parotitis.

PubMed

Furukawa, Takahiro; Matsui, Naoko; Tanaka, Keiko; Izumi, Yuishin; Kaji, Ryuji

2017-02-25

A 33 year-old woman presented with intentional incontinence, motor aphasia, supranuclear gaze palsy, and spasticity after parotitis. Brain magnetic resonance images (MRI) showed abnormal signaling in long corticospinal tract involving internal capsules and cerebral peduncles, middle cerebellar peduncle, and frontal subcortical white matter lesions. She had a long history of dry eye and mouth. Immunoserological study showed that she was positive for anti-SS-A, aquaporin 4 (AQP4), and AQP5 antibodies. She clinically showed not only Sjögren's syndrome but also neuromyelitis optica spectrum disorder (NMOSD) without optic neuritis or myelitis. She responded to steroid followed by plasma exchange dramatically. Thereafter, the relapse of brain lesion was once detected while tapering of steroid, but her symptoms have been stable for several years after administration of immunosuppressant. This case suggested that salivary gland inflammation might be associated with the pathogenesis of NMOSD.

Imbalance in multiple sclerosis and neuromyelitis optica: association with deep sensation disturbance.

PubMed

Demura, Yutaka; Kinoshita, Masako; Fukuda, Osamu; Nose, Shouzou; Nakano, Hitoshi; Juzu, Akira; Murase, Nagako; Yamamoto, Kenji

2016-12-01

Abnormality in balance is one of the most important causes of gait disturbance which has a direct impact to disability and medical cost in multiple sclerosis (MS) and neuromyelitis optica (NMO). However, characteristics of imbalance in these two diseases have not been fully elucidated. The aim of this study was to evaluate the degree and features of imbalance using stabilography, the degree of deep sensation disturbance using tibial nerve somatosensory evoked potentials (SEP), and their association with clinical impairment, in patients with MS and NMO. Seven NMO patients and seven MS patients with balance disturbance were examined. The relationship among stabilography measurements representing the degree and features of imbalance, height-adjusted P38 peak latency of SEP, and neurological functional disability, were analyzed. Stabilography evaluation showed a significantly severer degree of imbalance in NMO than in MS. Romberg quotient of the patients with brainstem lesions was significantly larger than those without them. In all patients, length of excursion per second significantly correlated positively with anterio-posterior-axis power spectra at intermediate frequency band. In all patients and in NMO, P38 peak latency adjusted by height significantly correlated positively with anterio-posterior-axis power spectra at intermediate frequency band. These findings suggest that the degree of imbalance of MS and NMO possibly correlate with deep sensation disturbance, which could be evaluated by anterio-posterior-axis power spectra at intermediate frequency band by stabilography. Severer imbalance in NMO than MS may be associated with the severe longitudinally extensive spinal cord lesions.

Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin-4 channelopathies: a decade later

PubMed Central

Pittock, Sean J.; Lucchinetti, Claudia F.

2015-01-01

The discovery of AQP4-IgG (a pathogenic antibody that targets the astrocytic water channel aquaporin-4) as the first sensitive and specific biomarker for any inflammatory central nervous system demyelinating disease, has shifted emphasis from the oligodendrocyte and myelin to the astrocyte as a central immunopathogenic player. Neuromyelitis optica (NMO) spectrum disorders (SD) represent an evolving spectrum of IDDs extending beyond the optic nerves and spinal cord to include the brain (especially in children) and, rarely, muscle. NMOSD typical brain lesions are located in areas that highly express the target antigen, AQP4, including the circumventricular organs (accounting for intractable nausea and vomiting) and the diencephalon (accounting for sleep disorders, endocrinopathies, and syndrome of inappropriate antidiuresis). Magnetic resonance imaging (MRI) brain abnormalities fulfill Barkoff criteria for multiple sclerosis in up to 10% of patients. As the spectrum broadens, the importance of highly specific assays that detect pathogenic AQP4-IgG targeting extracellular epitopes of AQP4 cannot be overemphasized. The rapid evolution of our understanding of the immunobiology of AQP4 autoimmunity necessitates continuing revision of NMOSD diagnostic criteria. Here, we describe scientific advances that have occurred since the discovery of NMO-IgG in 2004 and review novel targeted immunotherapies. We also suggest that NMOSDs should now be considered under the umbrella term autoimmune aquaporin-4 channelopathy. PMID:26096370

Rituximab monitoring and redosing in pediatric neuromyelitis optica spectrum disorder

PubMed Central

Nosadini, Margherita; Alper, Gulay; Riney, Catherine J.; Benson, Leslie A.; Mohammad, Shekeeb S.; Ramanathan, Sudarshini; Nolan, Melinda; Appleton, Richard; Leventer, Richard J.; Deiva, Kumaran; Brilot, Fabienne; Gorman, Mark P.; Waldman, Amy T.; Banwell, Brenda

2016-01-01

Objective: To study rituximab in pediatric neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD) and the relationship between rituximab, B cell repopulation, and relapses in order to improve rituximab monitoring and redosing. Methods: Multicenter retrospective study of 16 children with NMO/NMOSD receiving ≥2 rituximab courses. According to CD19 counts, events during rituximab were categorized as “repopulation,” “depletion,” or “depletion failure” relapses (repopulation threshold CD19 ≥10 × 106 cells/L). Results: The 16 patients (14 girls; mean age 9.6 years, range 1.8–15.3) had a mean of 6.1 events (range 1–11) during a mean follow-up of 6.1 years (range 1.6–13.6) and received a total of 76 rituximab courses (mean 4.7, range 2–9) in 42.6-year cohort treatment. Before rituximab, 62.5% had received azathioprine, mycophenolate mofetil, or cyclophosphamide. Mean time from rituximab to last documented B cell depletion and first repopulation was 4.5 and 6.8 months, respectively, with large interpatient variability. Earliest repopulations occurred with the lowest doses. Significant reduction between pre- and post-rituximab annualized relapse rate (ARR) was observed (p = 0.003). During rituximab, 6 patients were relapse-free, although 21 relapses occurred in 10 patients, including 13 “repopulation,” 3 “depletion,” and 4 “depletion failure” relapses. Of the 13 “repopulation” relapses, 4 had CD19 10–50 × 106 cells/L, 10 had inadequate monitoring (≤1 CD19 in the 4 months before relapses), and 5 had delayed redosing after repopulation detection. Conclusion: Rituximab is effective in relapse prevention, but B cell repopulation creates a risk of relapse. Redosing before B cell repopulation could reduce the relapse risk further. Classification of evidence: This study provides Class IV evidence that rituximab significantly reduces ARR in pediatric NMO/NMOSD. This study also demonstrates a relationship between B cell repopulation

Differentiating neuromyelitis optica from other causes of longitudinally extensive transverse myelitis on spinal magnetic resonance imaging

PubMed Central

Pekcevik, Yeliz; Mitchell, Charles H; Mealy, Maureen A; Orman, Gunes; Lee, In H; Newsome, Scott D; Thompson, Carol B; Pardo, Carlos A; Calabresi, Peter A; Levy, Michael; Izbudak, Izlem

2016-01-01

Background Although spinal magnetic resonance imaging (MRI) findings of neuromyelitis optica (NMO) have been described, there is limited data available that help differentiate NMO from other causes of longitudinally extensive transverse myelitis (LETM). Objective To investigate the spinal MRI findings of LETM that help differentiate NMO at the acute stage from multiple sclerosis (MS) and other causes of LETM. Methods We enrolled 94 patients with LETM into our study. Bright spotty lesions (BSL), the lesion distribution and location were evaluated on axial T2-weighted images. Brainstem extension, cord expansion, T1 darkness and lesion enhancement were noted. We also reviewed the brain MRI of the patients during LETM. Results Patients with NMO had a greater amount of BSL and T1 dark lesions (p < 0.001 and 0.003, respectively). The lesions in NMO patients were more likely to involve greater than one-half of the spinal cord’s cross-sectional area; to enhance and be centrally-located, or both centrally- and peripherally-located in the cord. Of the 62 available brain MRIs, 14 of the 27 whom were NMO patients had findings that may be specific to NMO. Conclusions Certain spinal cord MRI features are more commonly seen in NMO patients and so obtaining brain MRI during LETM may support diagnosis. PMID:26209588

Frequency of brain MRI abnormalities in neuromyelitis optica spectrum disorder at presentation: A cohort of Latin American patients.

PubMed

Carnero Contentti, Edgar; Daccach Marques, Vanessa; Soto de Castillo, Ibis; Tkachuk, Veronica; Antunes Barreira, Amilton; Armas, Elizabeth; Chiganer, Edson; de Aquino Cruz, Camila; Di Pace, José Luis; Hryb, Javier Pablo; Lavigne Moreira, Carolina; Lessa, Carmen; Molina, Omaira; Perassolo, Monica; Soto, Arnoldo; Caride, Alejandro

2018-01-01

Brain magnetic resonance imaging (BMRI) lesions were classically not reported in neuromyelitis optica (NMO). However, BMRI lesions are not uncommon in NMO spectrum disorder (NMOSD) patients. To report BMRI characteristic abnormalities (location and configuration) in NMOSD patients at presentation. Medical records and BMRI characteristics of 79 patients with NMOSD (during the first documented attack) in Argentina, Brazil and Venezuela were reviewed retrospectively. BMRI abnormalities were observed in 81.02% of NMOSD patients at presentation. Forty-two patients (53.1%) showed typical-NMOSD abnormalities. We found BMRI abnormalities at presentation in the brainstem/cerebellum (n = 26; 32.9%), optic chiasm (n = 16; 20.2%), area postrema (n = 13; 16.4%), thalamus/hypothalamus (n = 11; 13.9%), corpus callosum (n = 11; 13.9%), periependymal-third ventricle (n = 9; 11.3%), corticospinal tract (n = 7; 8.8%), hemispheric white matter (n = 1; 1.2%) and nonspecific areas (n = 49; 62.03%). Asymptomatic BMRI lesions were more common. The frequency of brain MRI abnormalities did not differ between patients who were positive and negative for aquaporin 4 antibodies at presentation. Typical brain MRI abnormalities are frequent in NMOSD at disease onset. Copyright © 2017 Elsevier B.V. All rights reserved.

Only Follow-Up of Memory B Cells Helps Monitor Rituximab Administration to Patients with Neuromyelitis Optica Spectrum Disorders.

PubMed

Lebrun, Christine; Cohen, Mikael; Rosenthal-Allieri, Maria Alessandra; Bresch, Saskia; Benzaken, Sylvia; Marignier, Romain; Seitz-Polski, Barbara; Ticchioni, Michel

2018-06-07

Neuromyelitis optica spectrum disorders (NMOSD) are identified as a spectrum of inflammatory demyelinating disorders involving the brain, spinal cord and optic nerves. These disorders require early diagnosis and highly active immunosuppressive treatment. Rituximab (RTX) has demonstrated efficacy in limiting relapse in NMOSD when using several administration schedules. We questioned if the CD19+ CD27+ memory B cell count was a more reliable marker to monitor RTX administration than the RTX plasma level and CD19+ B cell count. We analyzed 125 blood samples from 17 NMOSD patients treated with RTX and also measured the level of anti-aquaporine-4 antibodies (anti-AQP-4 Abs), human anti-chimeric antibodies to the murine fragment of RTX (HACA-RTX Abs), and the RTX concentration. The mean follow-up time of the cohort was 7.4 (2-16) years. All patients improved with a mean EDSS going from 4 (1-8.5) to 2.7 (1-5.5). The mean interval between RTX infusions was 9.6 months with identification of prolonged responders. Total CD19+ B cell detection with the routine technique did not correlate to re-emergence of CD19+ CD27+ memory B cells. The RTX residual concentration did not correlate with the CD19+ CD27+ memory B cell count or with anti-RTX antibody production. In contrast to total CD19+ cell, detected with the routine technique, CD19+ CD27+ memory B cells are a reliable marker for biological relapse and allow a decrease in the frequency of infusions.

Patterns of Antibody Binding to Aquaporin-4 Isoforms in Neuromyelitis Optica

PubMed Central

Mader, Simone; Lutterotti, Andreas; Di Pauli, Franziska; Kuenz, Bettina; Schanda, Kathrin; Aboul-Enein, Fahmy; Khalil, Michael; Storch, Maria K.; Jarius, Sven; Kristoferitsch, Wolfgang; Berger, Thomas; Reindl, Markus

2010-01-01

Background Neuromyelitis optica (NMO), a severe demyelinating disease, represents itself with optic neuritis and longitudinally extensive transverse myelitis. Serum NMO-IgG autoantibodies (Abs), a specific finding in NMO patients, target the water channel protein aquaporin-4 (AQP4), which is expressed as a long (M-1) or a short (M-23) isoform. Methodology/Principal Findings The aim of this study was to analyze serum samples from patients with NMO and controls for the presence and epitope specificity of IgG and IgM anti-AQP4 Abs using an immunofluorescence assay with HEK293 cells expressing M-1 or M-23 human AQP4. We included 56 patients with definite NMO (n = 30) and high risk NMO (n = 26), 101 patients with multiple sclerosis, 27 patients with clinically isolated syndromes (CIS), 30 patients with systemic lupus erythematosus (SLE) or Sjögren's syndrome, 29 patients with other neurological diseases and 47 healthy controls. Serum anti-AQP4 M-23 IgG Abs were specifically detected in 29 NMO patients, 17 patients with high risk NMO and two patients with myelitis due to demyelination (CIS) and SLE. In contrast, IgM anti-AQP4 Abs were not only found in some NMO and high risk patients, but also in controls. The sensitivity of the M-23 AQP4 IgG assay was 97% for NMO and 65% for high risk NMO, with a specificity of 100% compared to the controls. Sensitivity with M-1 AQP4 transfected cells was lower for NMO (70%) and high risk NMO (39%). The conformational epitopes of M-23 AQP4 are the primary targets of NMO-IgG Abs, whereas M-1 AQP4 Abs are developed with increasing disease duration and number of relapses. Conclusions Our results confirm M-23 AQP4-IgG Abs as reliable biomarkers in patients with NMO and high risk syndromes. M-1 and M-23 AQP4-IgG Abs are significantly associated with a higher number of relapses and longer disease duration. PMID:20463974

Cognitive performance of neuromyelitis optica patients: comparison with multiple sclerosis.

PubMed

Vanotti, Sandra; Cores, Evangelina Valeria; Eizaguirre, Barbara; Melamud, Luciana; Rey, Raúl; Villa, Andrés

2013-06-01

The aim of the present research was to investigate cognitive pattern of patients with neuromyelitis optica (NMO) and to compare it with multiple sclerosis (MS) patients' performance. Fourteen NMO, 14 relapsing remitting multiple sclerosis (RRMS), and 14 healthy control patients participated in the investigation. Neuropsychological functions were evaluated with the Brief Repeatable Neuropsychological Battery for MS; Symbol Digit Modalities Test; Digit Span; and Semantic Fluency. Fifty-seven percent of NMO patients and 42.85% of the MS ones had abnormal performance in at least two cognitive tests. The NMO Group showed abnormal performance in verbal fluency, verbal and visual memories, with greater attention deficits. NMO patients outperformed healthy control in the paced auditory serial addition test (PASAT). However, no difference was found between NMO and RRMS patients. The NMO Group showed more dysfunction in attention and verbal fluencies than in verbal and visual memories. When compared with the MS patients, a similar dysfunction pattern was found. O objetivo da presente pesquisa foi investigar o padrão cognitivo de pacientes com neuromielite óptica (NMO) e compará-lo com o desempenho de pacientes com esclerose múltipla (EM). Métodos: Quatorze pacientes com NMO, 14 com esclerose múltipla recorrente remitente (EMRR) e 14 participantes do Controle saudáveis participaram da presente investigação. As funções neuropsicológicas foram avaliadas com a Bateria Breve de Testes Neuropsicológicos de Rao, Teste Símbolo Digit e a Fluência Semântica. Resultados: Cinquenta e sete por cento dos pacientes com NMO e 42,85% daqueles com EM apresentaram desempenho anormal em pelo menos dois testes cognitivos. O Grupo NMO apresentarou desempenho anormal na fluência verbal e nas memórias visual e verbal, com maiores déficits de atenção. Pacientes com NMO superaram os controles saudáveis em PASAT. No entanto, não foi encontrada diferença entre os pacientes com

Quantitative Susceptibility Mapping Indicates a Disturbed Brain Iron Homeostasis in Neuromyelitis Optica - A Pilot Study.

PubMed

Doring, Thomas Martin; Granado, Vanessa; Rueda, Fernanda; Deistung, Andreas; Reichenbach, Juergen R; Tukamoto, Gustavo; Gasparetto, Emerson Leandro; Schweser, Ferdinand

2016-01-01

Dysregulation of brain iron homeostasis is a hallmark of many neurodegenerative diseases and can be associated with oxidative stress. The objective of this study was to investigate brain iron in patients with Neuromyelitis Optica (NMO) using quantitative susceptibility mapping (QSM), a quantitative iron-sensitive MRI technique. 12 clinically confirmed NMO patients (6 female and 6 male; age 35.4y±14.2y) and 12 age- and sex-matched healthy controls (7 female and 5 male; age 33.9±11.3y) underwent MRI of the brain at 3 Tesla. Quantitative maps of the effective transverse relaxation rate (R2*) and magnetic susceptibility were calculated and a blinded ROI-based group comparison analysis was performed. Normality of the data and differences between patients and controls were tested by Kolmogorov-Smirnov and t-test, respectively. Correlation with age was studied using Spearman's rank correlation and an ANCOVA-like analysis. Magnetic susceptibility values were decreased in the red nucleus (p<0.01; d>0.95; between -15 and -22 ppb depending on reference region) with a trend toward increasing differences with age. R2* revealed significantly decreased relaxation in the optic radiations of five of the 12 patients (p<0.0001; -3.136±0.567 s-1). Decreased relaxation in the optic radiation is indicative for demyelination, which is in line with previous findings. Decreased magnetic susceptibility in the red nucleus is indicative for a lower brain iron concentration, a chemical redistribution of iron into less magnetic forms, or both. Further investigations are necessary to elucidate the pathological cause or consequence of this finding.

Development of a patient-centred conceptual framework of health-related quality of life in neuromyelitis optica: a qualitative study.

PubMed

Methley, Abigail M; Mutch, Kerry; Moore, Perry; Jacob, Anu

2017-02-01

Neuromyelitis optica (NMO) is an auto-immune disease that can cause severe visual and mobility impairments. Research on health-related quality of life (HRQoL) in NMO is scarce, limiting knowledge on factors influencing HRQoL and support needs. This study provides the first qualitative exploration of HRQoL in NMO, conducted to provide a conceptual framework for the development of an NMO patient-reported outcome measure. Fifteen people with NMO (aged 18-74; 11 women, 4 men) participated in semi-structured interviews; data were analysed using constant comparative analysis. HRQoL in NMO is a multifaceted concept incorporating highly subjective perceptions of normality and meaning. Four major themes were identified: impact of physical symptoms on daily living, utilizing support to achieve independence, expectations for life and meaningful roles in life and purpose. Themes highlighted the importance of perceived normality, and its relationship to attaining life goals comparable to peers, as underpinning evaluations of HRQoL. Many people with severe disability reported a high HRQoL, suggesting the inappropriateness of assuming a negative HRQoL on the basis of an individual's neurological impairment. These findings further the conceptual understanding of HRQoL in NMO, informing patient-care approaches and the development of an NMO-specific patient-reported outcome measure. © 2015 The Authors. Health Expectation published by John Wiley & Sons Ltd.

Short-segment transverse myelitis lesions in a cohort of Latin American patients with neuromyelitis optica spectrum disorders.

PubMed

Carnero Contentti, Edgar; Daccach Marques, Vanessa; Soto de Castillo, Ibis; Tkachuk, Verónica; Antunes Barreira, Amilton; Armas, Elizabeth; Chiganer, Edson; de Aquino Cruz, Camila; Di Pace, José Luis; Hryb, Javier Pablo; Lavigne Moreira, Carolina; Lessa, Carmen; Molina, Omaira; Perassolo, Mónica; Soto, Arnoldo; Caride, Alejandro

2018-05-22

Multicenter retrospective study. The aim was to determine the frequency and magnetic resonance imaging (MRI) features of short-segment transverse myelitis (STM) in patients with neuromyelitis optica spectrum disorders (NMOSD) during a myelitis attack. Latin American diagnostic centres (Neuroimmunology Unit). A multicenter study from Argentina, Brazil and Venezuela was performed. Seventy-six patients with NMOSD were included. We analyzed 346 attacks and reviewed spinal cord MRIs performed within 30 days from spinal attack onset. Sagittal and axial characteristics on cervical and thoracic MRI (1.5 tesla) were observed. Demographics, clinical, serological, and disability data were collected. Among the 76 patients with NMOSD, isolated STM was observed in 8% (n = 6), multisegmental lesions (longitudinally extensive transverse myelitis (LETM) + STM) in 28% (n = 21; 13 had at least one STM), LETM in 42% (n = 32), and normal spinal MRI in 22% (n = 17). However, isolated STM was increased by 10% in patients with NMOSD with spinal lesions (6 out of 59) with mean attacks of 2.5 (±0.83) and last follow-up expanded disability status scale (EDSS) of 3.1 (±2.63). Positive aquaporin 4 antibodies (AQP4-ab) were found in 50%. Upper-cervical lesion was most frequently observed (5 out of 6). Myelitis was preceded by ON in all isolated patients with STM. Only one had a positive gadolinium lesion and none of these had asymptomatic spinal cord lesion. Isolated STM does not exclude NMOSD diagnosis. Therefore, APQ4-ab testing could be useful during a myelitis attack with STM.

Longitudinally extensive transverse myelitis in neuromyelitis optica: a prospective study of 13 Caucasian patients and literature review.

PubMed

Bălaşa, Rodica; Maier, Smaranda; Bajko, Zoltan; Motataianu, Anca; Crişan, Alexandra; Bălaşa, Adrian

2015-12-01

Neuromyelitis optica (NMO) is a homogenous disease that can be diagnosed by an association of clinical, neuroimaging and serological aspects. We analysed our 4 years NMO series with longitudinally extensive transverse myelitis (LETM) during the disease course. We included consecutive adult Caucasian patients who were diagnosed with definite NMO, or cases of NMO-IgG seropositive LETM considered as limited forms of NMO. Patients included were negative for other diseases (autoimmune, infectious, etc.). We report the Expanded Disability Status Scale (EDSS), brain and spine MRI, CSF, NMO-IgG, treatment, motor and visual outcome. Thirteen cases fulfilled the inclusion criteria, and the mean follow-up period was 3.74 ± 1.8 years. The initial motor deficit was severe with the mean value of motor functional parameter of 4.46 ± 1 and improved at discharge to 2.53 ± 1.4 (p < 0.001). With treatment, the outcome after LETM attack was good in 10 patients, with a significant improvement of the EDSS mainly upon motor deficit, while visual function had a very slight amelioration. The CSF analysis was normal in 8 cases; spinal MRI showed evidence of LETM in all patients while brain MRI was normal in 7. NMO-IgG is a biomarker for NMO that is of diagnostic value in cases of isolated LETM. LETM has a better outcome than ON in NMO Caucasians. Spinal MRI is essential for NMO diagnosis in the presence of LETM and the absence of multiple brain MRI lesions. Maintenance immunosuppressive therapy reduces the frequency of attacks.

Comparative brain stem lesions on MRI of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis.

PubMed

Lu, Zhengqi; Zhang, Bingjun; Qiu, Wei; Kang, Zhuang; Shen, Liping; Long, Youming; Huang, Junqi; Hu, Xueqiang

2011-01-01

Brain stem lesions are common in patients with acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), and multiple sclerosis (MS). To investigate comparative brain stem lesions on magnetic resonance imaging (MRI) among adult patients with ADEM, NMO, and MS. Sixty-five adult patients with ADEM (n = 17), NMO (n = 23), and MS (n = 25) who had brain stem lesions on MRI were enrolled. Morphological features of brain stem lesions among these diseases were assessed. Patients with ADEM had a higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%, P<0.001) and MS (94.1% vs. 40.0%, P<0.001); patients with NMO had a lower frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001) and ADEM (34.8% vs. 70.6%, P = 0.025); and patients with NMO had a higher frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs. 35.3%, P<0.001) and MS (91.3% vs. 36.0%, P<0.001). On the axial section of the brain stem, the majority (82.4%) of patients with ADEM showed lesions on the ventral part; the brain stem lesions in patients with NMO were typically located in the dorsal part (91.3%); and lesions in patients with MS were found in both the ventral (44.0%) and dorsal (56.0%) parts. The lesions in patients with ADEM (100%) and NMO (91.3%) had poorly defined margins, while lesions of patients with MS (76.0%) had well defined margins. Brain stem lesions in patients with ADEM were usually bilateral and symmetrical (82.4%), while lesions in patients with NMO (87.0%) and MS (92.0%) were asymmetrical or unilateral. Brain stem lesions showed various morphological features among adult patients with ADEM, NMO, and MS. The different lesion locations may be helpful in distinguishing these diseases.

Comparative Brain Stem Lesions on MRI of Acute Disseminated Encephalomyelitis, Neuromyelitis Optica, and Multiple Sclerosis

PubMed Central

Kang, Zhuang; Shen, Liping; Long, Youming; Huang, Junqi; Hu, Xueqiang

2011-01-01

Background Brain stem lesions are common in patients with acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), and multiple sclerosis (MS). Objectives To investigate comparative brain stem lesions on magnetic resonance imaging (MRI) among adult patients with ADEM, NMO, and MS. Methods Sixty-five adult patients with ADEM (n = 17), NMO (n = 23), and MS (n = 25) who had brain stem lesions on MRI were enrolled. Morphological features of brain stem lesions among these diseases were assessed. Results Patients with ADEM had a higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%, P<0.001) and MS (94.1% vs. 40.0%, P<0.001); patients with NMO had a lower frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001) and ADEM (34.8% vs. 70.6%, P = 0.025); and patients with NMO had a higher frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs. 35.3%, P<0.001) and MS (91.3% vs. 36.0%, P<0.001). On the axial section of the brain stem, the majority (82.4%) of patients with ADEM showed lesions on the ventral part; the brain stem lesions in patients with NMO were typically located in the dorsal part (91.3%); and lesions in patients with MS were found in both the ventral (44.0%) and dorsal (56.0%) parts. The lesions in patients with ADEM (100%) and NMO (91.3%) had poorly defined margins, while lesions of patients with MS (76.0%) had well defined margins. Brain stem lesions in patients with ADEM were usually bilateral and symmetrical (82.4%), while lesions in patients with NMO (87.0%) and MS (92.0%) were asymmetrical or unilateral. Conclusions Brain stem lesions showed various morphological features among adult patients with ADEM, NMO, and MS. The different lesion locations may be helpful in distinguishing these diseases. PMID:21853047

Prevalence of neuromyelitis optica spectrum disorder in the multi-ethnic Penang Island, Malaysia, and a review of worldwide prevalence.

PubMed

Hor, Jyh Yung; Lim, Thien Thien; Chia, Yuen Kang; Ching, Yee Ming; Cheah, Chun Fai; Tan, Kenny; Chow, Han Bing; Arip, Masita; Eow, Gaik Bee; Easaw, P E Samuel; Leite, M Isabel

2018-01-01

Neuromyelitis optica spectrum disorder (NMOSD) occurs worldwide in all ethnicities. Recently, population-based studies have shown that NMOSD is more common among non-White populations. There is scarce data about NMOSD prevalence in South East Asian populations. (1) A population-based study was undertaken to estimate NMOSD prevalence in the multi-ethnic Penang Island, Malaysia, comprising Chinese, Malays, and Indians. Medical records of NMOSD patients followed up at the Penang General Hospital (the neurology referral centre in Penang Island) were reviewed. The 2015 diagnostic criteria of the International Panel for NMO Diagnosis were used for case ascertainment. (2) A review of population-based prevalence studies of NMOSD worldwide was carried out. PubMed and conference proceedings were searched for such studies. Of the 28 NMOSD patients, 14 were residents of Penang Island on prevalence day [13 (93%) Chinese and one (7%) Malay]. All 14 patients were females and aquaporin 4 seropositive. The prevalence of NMOSD in Penang Island was 1.99/100,000 population; according to ethnicities, the prevalence in Chinese was significantly higher than in Malays (3.31/100,000 vs 0.43/100,000, respectively, p = 0.0195). Based on our and other population-based studies, among Asians, East Asian origin populations (Chinese and Japanese) appear to have higher NMOSD prevalence than other Asian ethnic groups. Worldwide, Blacks seem to have the highest NMOSD prevalence. More studies in different geographical regions and ethnic groups will be useful to further inform about potential factors in NMOSD pathogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

Analysis of brain and spinal cord lesions to occult brain damage in seropositive and seronegative neuromyelitis optica.

PubMed

Sun, Jie; Sun, Xianting; Zhang, Ningnannan; Wang, Qiuhui; Cai, Huanhuan; Qi, Yuan; Li, Ting; Qin, Wen; Yu, Chunshui

2017-09-01

According to aquaporin-4 antibody (AQP4-Ab), neuromyelitis optica (NMO) can be divided into seropositive and seronegative subgroups. The purpose of this study was to a) compare the distribution of spinal cord and brain magnetic resonance imaging (MRI) lesions between seropositive and seronegative NMO patients; b) explore occult brain damage in seropositive and seronegative NMO patients; and c) explore the contribution of visible lesions to occult grey and white matter damage in seropositive and seronegative NMO patients. Twenty-two AQP4-Ab seropositive and 14 seronegative NMO patients and 30 healthy controls were included in the study. Two neuroradiologists independently measured the brain lesion volume (BLV) and the length of spinal cord lesion (LSCL) and recorded the region of brain lesions. The normal-appearing grey matter volume (NAGM-GMV) and white matter fractional anisotropy (NAWM-FA) were calculated for each subject to evaluate occult brain damage. The seropositive patients displayed more extensive damage in the spinal cord than the seronegative patients, and the seronegative group had a higher proportion of patients with brainstem lesions (28.57%) than the seropositive group (4.55%, P=0.064). Both NMO subgroups exhibited reduced NAGM-GMV and NAWM-FA compared with the healthy controls. NAGM-GMV was negatively correlated with LSCL in the seropositive group (r s =-0.444, P=0.044) and with BLV in the seronegative group (r s =-0.768, P=0.002). NAWM-FA was also negatively correlated with BLV in the seropositive group (r s =-0.682, P<0.001). Our findings suggest that the occult brain damage in these two NMO subgroups may be due to different mechanisms, which need to be further clarified. Copyright © 2017 Elsevier B.V. All rights reserved.

Iron and Non-iron Related Characteristics of Multiple Sclerosis and Neuromyelitis Optica Lesions at 7T MRI

PubMed Central

Chawla, Sanjeev; Kister, Ilya; Wuerfel, Jens; Brisset, Jean-Christophe; Liu, Saifeng; Sinnecker, Tim; Dusek, Petr; Haacke, E. Mark; Paul, Friedemann; Ge, Yulin

2016-01-01

Background and Purpose To investigate the potential of ultra-high field MR imaging to distinguish multiple sclerosis (MS) from neuromyelitis optica (NMO) and to characterize tissue injury associated with iron pathology within lesions. Methods Twenty-one MS and 21 NMO patients underwent 7T high-resolution 2D-gradient-echo (GRE-T2*) and 3D-susceptibility weighted imaging (SWI). An in-house developed algorithm was used to reconstruct quantitative susceptibility mapping (QSM) from SWI. Lesions were classified as ‘iron laden’ if they demonstrated hypointensity on GRE-T2*- weighted images and/or SWI, and hyperintensity on QSM. Lesions were considered ‘non-iron laden’ if they were hyperintense on GRE-T2* and isointense or hyperintense on QSM. Results Of 21 MS patients, 19 (90.5%) demonstrated atleast one QSM-hyperintense lesion and 11/21 (52.4%) patients harbored iron-laden lesions. No QSM-hyperintense or iron-laden lesions were observed in any of the NMO patients. Iron-laden and non iron-laden lesions could each be further characterized into two distinct patterns based on lesion signal and morphology on GRE-T2*/SWI and QSM. In MS, the majority of lesions (n=262, 75.9% of all lesions) were hyperintense on GRE-T2* and isointense on QSM (Pattern A), while a small minority (n=26, 7.5% of all lesions) were hyperintense on both GRE-T2* and QSM (Pattern B). Iron laden lesions (n=57, 16.5% of all lesions) were further classified as ‘nodular’ (n=22, 6.4%, Pattern C) or ‘ring-like’ (n=35, 10.1%, Pattern D). Conclusions Ultra-high field MRI may be useful in distinguishing MS from NMO. Different patterns related to iron and non-iron pathology may provide in vivo insights into pathophysiology of lesions in MS. PMID:27012298

Marked central nervous system pathology in CD59 knockout rats following passive transfer of Neuromyelitis optica immunoglobulin G.

PubMed

Yao, Xiaoming; Verkman, Alan S

2017-02-17

Neuromyelitis optica spectrum disorders (herein called NMO) is an inflammatory demyelinating disease of the central nervous system in which pathogenesis involves complement-dependent cytotoxicity (CDC) produced by immunoglobulin G autoantibodies targeting aquaporin-4 (AQP4-IgG) on astrocytes. We reported evidence previously, using CD59 -/- mice, that the membrane-associated complement inhibitor CD59 modulates CDC in NMO (Zhang and Verkman, J. Autoimmun. 53:67-77, 2014). Motivated by the observation that rats, unlike mice, have human-like complement activity, here we generated CD59 -/- rats to investigate the role of CD59 in NMO and to create NMO pathology by passive transfer of AQP4-IgG under conditions in which minimal pathology is produced in normal rats. CD59 -/- rats generated by CRISPR/Cas9 technology showed no overt phenotype at baseline except for mild hemolysis. CDC assays in astrocyte cultures and cerebellar slices from CD59 -/- rats showed much greater sensitivity to AQP4-IgG and complement than those from CD59 +/+ rats. Intracerebral administration of AQP4-IgG in CD59 -/- rats produced marked NMO pathology, with astrocytopathy, inflammation, deposition of activated complement, and demyelination, whereas identically treated CD59 +/+ rats showed minimal pathology. A single, intracisternal injection of AQP4-IgG in CD59 -/- rats produced hindlimb paralysis by 3 days, with inflammation and deposition of activated complement in spinal cord, optic nerves and brain periventricular and surface matter, with most marked astrocyte injury in cervical spinal cord. These results implicate an important role of CD59 in modulating NMO pathology in rats and demonstrate amplification of AQP4-IgG-induced NMO disease with CD59 knockout.

Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders

PubMed Central

2011-01-01

Background Serum autoantibodies against the water channel aquaporin-4 (AQP4) are important diagnostic biomarkers and pathogenic factors for neuromyelitis optica (NMO). However, AQP4-IgG are absent in 5-40% of all NMO patients and the target of the autoimmune response in these patients is unknown. Since recent studies indicate that autoimmune responses to myelin oligodendrocyte glycoprotein (MOG) can induce an NMO-like disease in experimental animal models, we speculate that MOG might be an autoantigen in AQP4-IgG seronegative NMO. Although high-titer autoantibodies to human native MOG were mainly detected in a subgroup of pediatric acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS) patients, their role in NMO and High-risk NMO (HR-NMO; recurrent optic neuritis-rON or longitudinally extensive transverse myelitis-LETM) remains unresolved. Results We analyzed patients with definite NMO (n = 45), HR-NMO (n = 53), ADEM (n = 33), clinically isolated syndromes presenting with myelitis or optic neuritis (CIS, n = 32), MS (n = 71) and controls (n = 101; 24 other neurological diseases-OND, 27 systemic lupus erythematosus-SLE and 50 healthy subjects) for serum IgG to MOG and AQP4. Furthermore, we investigated whether these antibodies can mediate complement dependent cytotoxicity (CDC). AQP4-IgG was found in patients with NMO (n = 43, 96%), HR-NMO (n = 32, 60%) and in one CIS patient (3%), but was absent in ADEM, MS and controls. High-titer MOG-IgG was found in patients with ADEM (n = 14, 42%), NMO (n = 3, 7%), HR-NMO (n = 7, 13%, 5 rON and 2 LETM), CIS (n = 2, 6%), MS (n = 2, 3%) and controls (n = 3, 3%, two SLE and one OND). Two of the three MOG-IgG positive NMO patients and all seven MOG-IgG positive HR-NMO patients were negative for AQP4-IgG. Thus, MOG-IgG were found in both AQP4-IgG seronegative NMO patients and seven of 21 (33%) AQP4-IgG negative HR-NMO patients. Antibodies to MOG and AQP4 were predominantly of the IgG1 subtype, and were able to

Astrocytic autoantibody of neuromyelitis optica (NMO-IgG) binds to aquaporin-4 extracellular loops, monomers, tetramers and high order arrays

PubMed Central

Iorio, Raffaele; Fryer, James P.; Hinson, Shannon R.; Fallier-Becker, Petra; Wolburg, Hartwig; Pittock, Sean J.; Lennon, Vanda A.

2012-01-01

The principal central nervous system (CNS) water channel, aquaporin-4 (AQP4), is confined to astrocytic and ependymal membranes and is the target of a pathogenic autoantibody, neuromyelitis optica (NMO)-IgG. This disease-specific autoantibody unifies a spectrum of relapsing CNS autoimmune inflammatory disorders of which NMO exemplifies the classic phenotype. Multiple sclerosis and other immune-mediated demyelinating disorders of the CNS lack a distinctive biomarker. Two AQP4 isoforms, M1 and M23, exist as homotetrameric and heterotetrameric intramembranous particles (IMPs). Orthogonal arrays of predominantly M23 particles (OAPs) are an ultrastructural characteristic of astrocytic membranes. We used high-titered serum from 32 AQP4-IgG-seropositive patients and 85 controls to investigate the nature and molecular location of AQP4 epitopes that bind NMO-IgG, and the influence of supramolecular structure. NMO-IgG bound to denatured AQP4 monomers (68% of cases), to native tetramers and high order arrays (90% of cases), and to AQP4 in live cell membranes (100% of cases). Disease-specific epitopes reside in extracellular loop C more than in loops A or E. IgG binding to intracellular epitopes lacks disease specificity. These observations predict greater disease specificity and sensitivity for tissue-based and cell-based serological assays employing “native” AQP4 than assays employing denatured AQP4 and fragments. NMO-IgG binds most avidly to plasma membrane surface AQP4 epitopes formed by loop interactions within tetramers and by intermolecular interactions within high order structures. The relative abundance and localization of AQP4 high order arrays in distinct CNS regions may explain the variability in clinical phenotype of NMO spectrum disorders. PMID:22906356

Validation of the Modified Fatigue Impact Scale and the relationships among fatigue, pain and serum interleukin-6 levels in patients with neuromyelitis optica spectrum disorder.

PubMed

Masuda, Hiroki; Mori, Masahiro; Uzawa, Akiyuki; Uchida, Tomohiko; Ohtani, Ryohei; Kobayashi, Shigeo; Kuwabara, Satoshi

2018-02-15

Fatigue and pain are disabling symptoms in patients with neuromyelitis optica spectrum disorder (NMOSD). The Modified Fatigue Impact Scale (MFIS) has not yet been validated in patients with NMOSD, and anti-interleukin-6 (IL-6) receptor antibody was reported to decrease pain and fatigue in patients with NMOSD. The aim of this study was to validate MFIS and to investigate the relationships among fatigue, pain and serum IL-6 levels in patients with NMOSD. MFIS and the Multidimensional Fatigue Inventory (MFI), an established scale for fatigue, were administered to patients with NMOSD and age- and sex-matched healthy controls (HCs). The Pain Effects Scale score and serum IL-6 levels were also measured in patients with NMOSD. Correlations among clinical characteristics, laboratory data and each score were investigated. To validate MFIS in patients with NMOSD, MFIS was administered twice within 4days from the first administration. Fifty-one patients answered the first MFIS, and 26 patients answered the second MFIS. There was no difference between the first and second MFIS scores. Patients with NMOSD had higher MFIS and MFI scores than HCs. No correlations were observed between serum IL-6 levels and either score. MFIS was validated in patients with NMOSD. Serum IL-6 levels may not be involved in the pathogenesis of fatigue and pain in patients with NMOSD. Copyright © 2017 Elsevier B.V. All rights reserved.

Inhibitor(s) of the classical complement pathway in mouse serum limit the utility of mice as experimental models of neuromyelitis optica.

PubMed

Ratelade, Julien; Verkman, A S

2014-11-01

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system in which anti-aquaporin-4 (AQP4) autoantibodies (AQP4-IgG) cause damage to astrocytes by complement-dependent cytotoxicity (CDC). Various approaches have been attempted to produce NMO lesions in rodents, some involving genetically modified mice with altered immune cell function. Here, we found that mouse serum strongly inhibits complement from multiple species, preventing AQP4-IgG-dependent CDC. Effects of mouse serum on complement activation were tested in CDC assays in which AQP4-expressing cells were incubated with AQP4-IgG and complement from different species. Biochemical assays and mass spectrometry were used to characterize complement inhibitor(s) in mouse serum. Sera from different strains of mice produced almost no AQP4-IgG-dependent CDC compared with human, rat and guinea pig sera. Remarkably, addition of mouse serum prevented AQP4-IgG-dependent CDC caused by human, rat or guinea pig serum, with 50% inhibition at <5% mouse serum. Hemolysis assays indicated that the inhibitor(s) in mouse serum target the classical and not the alternative complement pathway. We found that the complement inhibitor(s) in mouse serum were contained in a serum fraction purified with protein-A resin; however, the inhibitor was not IgG as determined using serum from IgG-deficient mice. Mass spectrometry on the protein A-purified fraction produced several inhibitor candidates. The low intrinsic complement activity of mouse serum and the presence of complement inhibitor(s) limit the utility of mouse models to study disorders, such as NMO, involving the classical complement pathway. Copyright © 2014 Elsevier Ltd. All rights reserved.

Role of the H-bond between L53 and T56 for Aquaporin-4 epitope in Neuromyelitis Optica.

PubMed

Pisani, Francesco; Simone, Laura; Gargano, Concetta Domenica; De Bellis, Manuela; Cibelli, Antonio; Mola, Maria Grazia; Catacchio, Giacomo; Frigeri, Antonio; Svelto, Maria; Nicchia, Grazia Paola

2017-03-01

Aquaporin-4 (AQP4) is the CNS water channel organized into well-ordered protein aggregates called Orthogonal Arrays of Particles (OAPs). Neuromyelitis Optica (NMO) is an autoimmune disease caused by anti-OAP autoantibodies (AQP4-IgG). Molecular Dynamics (MD) simulations have identified an H-bond between L53 and T56 as the key for AQP4 epitope and therefore of potential interest for drug design in NMO field. In the present study, we have experimentally tested this MD-prediction using the classic mutagenesis approach. We substituted T56 with V56 and tested this mutant for AQP4 aggregates and AQP4-IgG binding. gSTED super-resolution microscopy showed that the mutation does not affect AQP4 aggregate dimension; immunofluorescence and cytofluorimetric analysis demonstrated its unaltered AQP4-IgG binding, therefore invalidating the MD-prediction. We later investigated whether AQP4, expressed in Sf9 insect and HEK-293F cells, is able to correctly aggregate before and after the purification steps usually applied to obtain AQP4 crystal. The results demonstrated that AQP4-IgG recognizes AQP4 expressed in Sf9 and HEK-293F cells by immunofluorescence even though BN-PAGE analysis showed that AQP4 forms smaller aggregates when expressed in insect cells compared to mammalian cell lines. Notably, after AQP4 purification, from both insect and HEK-293F cells, no aggregates are detectable by BN-PAGE and AQP4-IgG binding is impaired in sandwich ELISA assays. All together these results indicate that 1) the MD prediction under analysis is not supported by experimental data and 2) the procedure to obtain AQP4 crystals might affect its native architecture and, as a consequence, MD simulations. In conclusion, given the complex nature of the AQP4 epitope, MD might not be the suitable for molecular medicine advances in NMO. Copyright © 2016. Published by Elsevier B.V.

Cognitive impairment in neuromyelitis optica spectrum disorders: A comparison of the Wechsler Adult Intelligence Scale-III and the Wechsler Memory Scale Revised with the Rao Brief Repeatable Neuropsychological Battery.

PubMed

Fujimori, Juichi; Nakashima, Ichiro; Baba, Toru; Meguro, Yuko; Ogawa, Ryo; Fujihara, Kazuo

2017-12-01

Approximately 55% of patients with neuromyelitis optica spectrum disorder (NMOSD) show cognitive impairment as evaluated using the Rao Brief Repeatable Neuropsychological Battery (BRBN), but this frequency appears to be higher than the frequency of specific brain lesions in NMOSD. We studied whether cognitive impairment could be observed in NMOSD patients with no or minor non-specific brain lesions. We evaluated cognitive function in 12 NMOSD and 14 MS patients using the Wechsler Adult Intelligence Scale-III (WAIS-III), the Wechsler Memory Scale-Revised (WMS-R), and the BRBN. We judged as cognitively impaired patients whose scores were below the average by 2 standard deviations or greater in 2 or more cognitive domains. Cognitive impairment was observed in 5 MS patients (35.7%) and in the only NMOSD patient (8.3%) with symptomatic brain lesions, but not in the other NMOSD patients who had no or minor non-specific brain lesions. Meanwhile, 5 NMOSD (41.7%) and 4 MS (28.6%) patients who had normal cognition according to the WAIS-III and WMS-R were assessed as cognitively impaired by the BRBN (which is not standardized for age). Cognitive function in NMOSD patients with no or mild non-specific brain lesions was preserved according to the WAIS-III and WMS-R.

Importance of Regular and Maintenance Therapy Adherence in Neuromyelitis Optica (NMO): Lessons from a Repeating Relapse Case

PubMed Central

Miao, Jing; Aboagye, Doreen E.; Chulpayev, Boris; Liu, Lin; Ishkanian, Gary; Kolanuvada, Bangaruraju; Alaie, Dariush; Petrillo, Richard L.

2018-01-01

Patient: Female, 58 Final Diagnosis: NMO Symptoms: New-onset right leg weakness and pain Medication: — Clinical Procedure: Progressive and recurring Specialty: Neurology Objective: Rare disease Background: Neuromyelitis optica (NMO) is a rare demyelinating disease of the central nervous system; NMO predominantly affects the spinal cord and optic nerves. The diagnosis is based on history, clinical presentation, seropositive NMO-IgG antibody, and notably, exclusion of other diseases. Despite the absence of definitive therapeutic strategies for NMO, methylprednisolone pulse therapy and plasma exchange are used for acute phase treatment, while immunosuppressive agent(s) are recommended to prevent relapses and improve prognosis. Here, we report a repeating relapse NMO case due to lack of regular and maintenance therapy. Case Report: A 58-year-old female with chronic NMO presented with a three-day history of new-onset right leg weakness and pain. The patient was diagnosed with NMO three years ago and presented with her fourth attacks. During her initial diagnosis, she was initiated on steroids. One year later, she developed the first relapse and was treated with steroids and rituximab, leading to 1.5-year remission. After the second relapse, steroids and rituximab was still given as maintenance therapy, but was not followed. Thus, the third relapse occurred in five months. During this hospitalization, she received initially high-dose solumedrol (1 g daily for five days) in addition to gabapentin 100 mg (gradually increased to 300 mg) three times a day for muscle spasms. Due to worsening of paresthesia and hemiparesis, it was decided to place her on plasma exchange treatment. After two plasma exchanges, the patient’s condition was improved and she regained strength in her lower extremity. She completed five more cycles of plasma exchange, and was then discharged on steroid therapy (prednisone 20 mg daily for 10 days then taper) as maintenance therapy and with follow

[Proportion and significance of CD1d(hi)CD5⁺CD19⁺ regulatory B cell in peripheral blood of patients with neuromyelitis optica].

PubMed

Yang, Fen; Huang, Dehui; Cheng, Chen; Wu, Weiping

2015-03-01

To detect the proportion of CD1d(hi)CD5⁺CD19⁺ regulatory B cells (Bregs) in peripheral blood of the patients with neuromyelitis optica (NMO), and explore whether CD1d(hi)CD5⁺CD19⁺ Bregs can play a role as a biomarker in the diagnosis of NMO versus multiple sclerosis (MS). Flow cytometry was performed to detect the proportion of CD1d(hi)CD5⁺CD19⁺ Bregs in peripheral blood from 44 cases of NMO, 38 cases of MS, and 30 healthy controls. The serum level of aquaporin-4 antibody (AQP4-Ab) of patients with NMO was detected by indirect immunofluorescence assay. The proportion of CD1d(hi)CD5⁺CD19⁺ Bregs in CD19⁺ B cells and lymphocytes was significantly lower in NMO group than in MS and control groups; however, there was no significant difference between MS group and control group. The proportion of CD1d(hi)CD5⁺CD19⁺ Bregs in CD19⁺ B cells and lymphocytes was lower in AQP4-Ab-positive NMO patients than in AQP4-Ab-negative NMO patients, and the difference was statistically significant. CD1d(hi)CD5⁺CD19⁺ Bregs may be a biomarker in the differential diagnosis of NMO versus MS.

Large-Scale in-House Cell-Based Assay for Evaluating the Serostatus in Patients with Neuromyelitis Optica Spectrum Disorder Based on New Diagnostic Criteria.

PubMed

Kim, Yeseul; Kim, Gayoung; Kong, Byung Soo; Lee, Ji Eun; Oh, Yu Mi; Hyun, Jae Won; Kim, Su Hyun; Joung, AeRan; Kim, Byoung Joon; Choi, Kyungho; Kim, Ho Jin

2017-04-01

The detection of aquaporin 4-IgG (AQP4-IgG) is now a critical diagnostic criterion for neuromyelitis optica spectrum disorder (NMOSD). To evaluate the serostatus of NMOSD patients based on the 2015 new diagnostic criteria using a new in-house cell-based assay (CBA). We generated a stable cell line using internal ribosome entry site-containing bicistronic vectors, which allow the simultaneous expression of two proteins (AQP4 and green fluorescent protein) separately from the same RNA transcript. We performed in-house CBA using serum from 386 patients: 178 NMOSD patients diagnosed according to the new diagnostic criteria without AQP4-IgG, 63 high risk NMOSD patients presenting 1 of the 6 core clinical characteristics of NMOSD but not fulfilling dissemination in space, and 145 patients with other neurological diseases, including 66 with multiple sclerosis. The serostatus of 111 definite and high risk NMOSD patients were also tested using a commercial CBA kit with identical serum to evaluate the correlation between the 2 methods. All assays were performed by two independent and blinded investigators. Our in-house assay yielded a specificity of 100% and sensitivities of 80% (142 of 178) and 76% (48 of 63) when detecting definite- and high risk NMOSD patients, respectively. The comparison with the commercial CBA kit revealed a correlation for 102 of the 111 patients: no correlation was present in 7 patients who were seronegative using the commercial method but seropositive using the in-house method, and in 2 patients who were seropositive using the commercial method but seronegative using the in-house method. These results demonstrate that our in-house CBA is a highly specific and sensitive method for detecting AQP4-IgG in NMOSD patients. Copyright © 2017 Korean Neurological Association

Comparative study of quality of life, anxiety, depression, and fatigue among patients with neuromyelitis optica spectrum disorder and multiple sclerosis: The first report from Iran.

PubMed

Barzegar, Mahdi; Badihian, Shervin; Mirmosayyeb, Omid; Ashtari, Fereshteh; Jamadi, Maryam; Emami, Shohreh; Jahani, Leila; Safavi, Armaghan; Shaygannejad, Vahid

2018-05-01

Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are associated with reduced Health Related Quality of Life (HRQOL). To the best of our knowledge, change of HRQOL in patients with NMOSD has not been yet measure in Iran. The objective of this study was to assess HRQOL in NMOSD and MS patients and identify related factors METHODS: A cross sectional study of 41 patients with NMOSD and 136 age and sex-match MS patients was performed. A series of questionnaires including Persian validated questionnaires on HRQOL (SF-36), fatigue (MFIS), depression (BDI-II), anxiety (HAM-A) and sleep quality (PSQI) were record. All demographic variables, socioeconomic status and clinical data were also obtained. Student's T test and Mann-Whitney U test used to compare variables between groups and multivariate regression analysis applied to assay predictor factors. The mean scores of mental (MCS) and physical (PCS) components of QOL were statistically lower in patients with NMOSD compare with MS patients (β = -4.49, P = 0.004; β = -3.52, P = 0.015). Multivariate analysis indicated fatigue, depression and anxiety were independent, significant predictor of MCS (β = -0.229, P = 0.002; β = -0.229, P = 0.002; β = -0.258, P = 0.020 respectively). However, PCS was significantly predicted by fatigue (β = -0.258 P < 0.001), solely. These findings indicate NMOSD patients have lower HRQOL in compare to patients with MS. Also, screening and treatment of fatigue as the most important predictor for HRQOL is necessary. Copyright © 2018. Published by Elsevier B.V.

Neuromyelitis Optica

MedlinePlus

... from cell to cell. NMO is different from multiple sclerosis (MS). Attacks are usually more severe in NMO ... from cell to cell. NMO is different from multiple sclerosis (MS). Attacks are usually more severe in NMO ...

Increased occurrence of anti-AQP4 seropositivity and unique HLA Class II associations with neuromyelitis optica (NMO), among Muslim Arabs in Israel.

PubMed

Brill, Livnat; Mandel, Micha; Karussis, Dimitrios; Petrou, Panayiota; Miller, Keren; Ben-Hur, Tamir; Karni, Arnon; Paltiel, Ora; Israel, Shoshana; Vaknin-Dembinsky, Adi

2016-04-15

Previous studies have revealed different human leukocyte antigen (HLA) associations in multiple sclerosis (MS) and neuromyelitis optica (NMO), further discriminating these two demyelinating pathological conditions. In worldwide analyses, NMO and opticospinal MS are represented at higher proportions among demyelinating conditions in African, East-Asian and Latin American populations. There are currently no data regarding the prevalence of NMO in Middle East Muslims. The population in Israel is diverse in many ways, and includes subpopulations, based on religion and ethnicity; some exhibit genetic homogeneity. In Israel, the incidence of MS is lower in the Muslim population than the Jewish population and Muslims carry different allele frequency distribution of HLA haplotypes. To evaluate the occurrence of anti-AQP4 seropositivity in the Israeli Muslim population among patients with central nervous system (CNS) demyelinating conditions; and to identify the HLA DR and DQ profiles of Muslim Arab Israeli patients with NMO spectrum of diseases (NMOSD). The prevalence of anti-AQP4 seropositivity was analyzed in 342 samples, obtained from patients with various CNS demyelinating conditions and in a validation set of 310 samples. HLA class II alleles (HLA-DRB1 and DQB1) were examined in DNA samples from 35 Israeli Muslim Arabs NMO patients and compared to available data from 74 Israeli Muslim controls. Our data reveal a significantly increased prevalence of anti-AQP4 seropositivity, indicative of NMOSD, in Muslim Arab Israeli patients with initial diagnosis of a CNS demyelinating syndrome. In this population, there was a positive association with the HLA-DRB1*04:04 and HLA-DRB1*10:01 alleles (p=0.03), and a strong negative association with the HLA-DRB1*07 and HLA-DQB1*02:02 alleles (p=0.003, p=0.002). Our findings indicate a possibly increased prevalence of NMOSD in Muslim Arabs in Israel with distinct (positive and negative) HLA associations. Further studies in patients with

Optic Neuropathy Associated with Primary Sjögren's Syndrome: A Case Series.

PubMed

Bak, Eunoo; Yang, Hee Kyung; Hwang, Jeong-Min

2017-04-01

To determine the diverse clinical features of optic neuropathy associated with primary Sjögren's syndrome in Korean patients. Five women with acute and/or chronic optic neuropathy who were diagnosed as primary Sjögren's syndrome were retrospectively evaluated. Primary Sjögren's syndrome was diagnosed by signs and symptoms of keratoconjunctivitis sicca, positive serum anti-Ro/SSA and/or anti-La/SSB antibodies, and/or minor salivary gland biopsy. All patients underwent a complete ophthalmologic examination. Among the five patients diagnosed as optic neuropathy related to primary Sjögren's syndrome, four patients had bilateral optic neuropathy and one patient was unilateral. The clinical course was chronic in three patients and one of them showed acute exacerbation and was finally diagnosed with neuromyelitis optica spectrum disorder. The other two patients presented as acute optic neuritis and one was diagnosed with neuromyelitis optica spectrum disorder. Sicca symptoms were present in four patients, but only two patients reported these symptoms before the onset of optic neuropathy. Patients showed minimal response to systemic corticosteroids or steroid dependence, requiring plasmapheresis in the acute phase and immunosuppressive agents for maintenance therapy. Optic neuropathy associated with primary Sjögren's syndrome may show variable clinical courses, including acute optic neuritis, insidious progression of chronic optic atrophy, or in the context of neuromyelitis optica spectrum disorders. Optic neuropathy may be the initial manifestation of primary Sjögren's syndrome without apparent sicca symptoms, which makes the diagnosis often difficult. The presence of specific antibodies including anti-Ro/SSA, anti-La/SSB, and anti-aquaporin-4 antibodies are supportive for the diagnosis and treatment in atypical cases of optic neuropathy.

Review of the novelties from the 31st ECTRIMS Congress, 2015, presented at the 8th Post-ECTRIMS meeting.

PubMed

Fernandez, O; Rodriguez-Antiguedad, A; Olascoaga, J; Oreja-Guevara, C; Prieto, J M; Mendibe-Bilbao, M M; Garcia-Merino, J A; Ramio-Torrenta, Ll; Ginestal, R; Meca-Lallana, J E; Romero-Pinel, L; Munoz, D; Saiz, A; Calles-Hernandez, M C; Izquierdo, G; Villar, L M; Oliva-Nacarino, P; Arnal-Garcia, C; Comabella, M; Brieva, Ll; Arroyo, R; Montalban, X

2016-06-16

Renowned national specialists in multiple sclerosis (MS) met, for the eighth year in a row, to give details of the latest novelties presented at the last ECTRIMS Congress 2015, which are included in this review. One of the highlights at this Congress was the new classification of the phenotypes of MS. Both the diagnostic criteria of the neuromyelitis optica spectrum and the problems involved in the differential diagnosis derived from the lack of definition of the radiological spectrum were reviewed. The microbiota comes to the fore as a possible factor determining the disease, together with extrinsic factors such as tobacco, salt ingestion or vitamin D deficiency. Advances made in immunomodulation are driving the progress being made in the treatment of MS. Ocrelizumab is the first treatment with positive results in the primarily progressive forms and tocilizumab, a drug product for rheumatoid arthritis, stands out as a potential candidate for the treatment of neuromyelitis optica. Certain antibiotics and vitamins could also play a role in the treatment of MS. In this edition of the Congress special attention was paid to personalised therapy. To date, 11 drugs have been approved for use in Europe. There is a need for therapeutic algorithms that help us to choose the best treatment for each patient. Likewise, we need to be able to identify, in the early stages of the disease, the risk of developing disability, so as to be able to design therapeutic strategies. To do so, molecular biomarkers and other predictive tools are required. The problems that still exist in software technology in magnetic resonance hinder its application in daily clinical practice.

Hypothalamic demyelination causing panhypopituitarism.

PubMed

Dixon-Douglas, Julia; Burgess, John; Dreyer, Michael

2018-05-01

Hypothalamic involvement in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) is rare and endocrinopathies involving the hypothalamic-pituitary axis in patients with demyelinating conditions have rarely been reported. We present two cases of MS/NMOSD with associated hypothalamic-pituitary involvement and subsequent hypopituitarism, including the first report of a patient with hypothalamic demyelination causing panhypopituitarism. Differential diagnoses, including alemtuzumab-related and primary pituitary pathology are discussed. © 2018 Royal Australasian College of Physicians.

Hydroxycholesterol Levels in the Serum and Cerebrospinal Fluid of Patients with Neuromyelitis Optica Revealed by LC-Ag+CIS/MS/MS and LC-ESI/MS/MS with Picolinic Derivatization: Increased Levels and Association with Disability during Acute Attack

PubMed Central

Park, Ki Duk; Park, Kyung Seok; Lee, Kwang-Woo; Kim, Sung-Min; Lee, Jaeick

2016-01-01

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS). Hydroxycholesterols (OHCs), metabolites of CNS cholesterol, are involved in diverse cellular responses to inflammation and demyelination, and may also be involved in the pathogenesis of NMO. We aimed to develop a sensitive and reliable method for the quantitative analysis of three major OHCs (24S-, 25-, and 27-OHCs), and to evaluate their concentration in the cerebrospinal fluid (CSF) and serum of patients with NMO. The levels of the three OHCs in the serum and CSF were measured using liquid chromatography-silver ion coordination ionspray tandem mass spectrometry and liquid chromatography-electrospray ionization tandem mass spectrometry with picolinyl ester derivatization, respectively. The linear range was 5–250 ng/mL for 24S- and 27-OHC, and 0.5–25 ng/mL for 25-OHC in serum, and was 0.1–5 ng/mL for 24S- and 27-OHC, and 0.03–1 ng/mL for 25-OHC in CSF. Precision and accuracy were 0.5%–14.7% and 92.5%–109.7%, respectively, in serum, and were 0.8%–7.7% and 94.5%–119.2%, respectively, in CSF. Extraction recovery was 82.7%–90.7% in serum and 68.4%–105.0% in CSF. When analyzed in 26 NMO patients and 23 control patients, the 25-OHC (0.54 ± 0.96 ng/mL vs. 0.09 ± 0.04 ng/mL, p = 0.032) and 27-OHC (2.68 ± 3.18 ng/mL vs. 0.68 ± 0.25 ng/mL, p = 0.005) were increased in the CSF from NMO patients. When we measured the OHCCSF index that controls the effects of blood–brain barrier disruption on the level of OHC in the CSF, the 27-OHCCSF index was associated with disability (0.723; 95% confidence interval (CI)– 0.181, 0.620; p = 0.002), while the 24-OHCCSF index (0.518; 95% CI– 1.070, 38.121; p = 0.040) and 25-OHCCSF index (0.677; 95% CI– 4.313, 18.532; p = 0.004) were associated with the number of white blood cells in the CSF of NMO patients. Our results imply that OHCs in the CNS could play a role in the pathogenesis of NMO. PMID:27942009

[Myelitis as a differential diagnosis of spinal cord tumors].

PubMed

Vermersch, P; Outteryck, O; Ferriby, D; Zéphir, H

2017-11-01

Myelitis is common, related to multiple aetiologies and constitute in some cases a differential diagnosis for spinal cord tumors. Our objective was to review the clinical and paraclinical aspects of the main aetiologies of myelitis. These aetiologies will be reviewed based on data not only from the scientific literature but also from our personal experience reported in different cohorts of patients. Multiple sclerosis is the main cause of partial myelitis in young adults. Neuromyelitis optica is now a well-known specific entity frequently revealed by a transverse myelitis. The diagnosis is based on specific criteria, including the presence of anti-NMO antibodies. In our cohorts, approximately 12 % of the patients admitted for an acute or subacute myelitis were related to infections, mainly of a viral origin. Patients with myelitis must be screened for systemic diseases. As for neuromyelitis optica, patients with myelitis related to a systemic disease should be treated in emergency. Acute myelitis is sometimes the first symptom of a systemic lupus or of a sarcoidosis. Sjögren syndrome can mimic myelitis related to primary progressive multiple sclerosis. Spinal cord imaging contributes greatly to defining the myelitis. In most cases, a routine clinical and paraclinical examination and the follow-up of the patients can contribute to establishing the aetiology of a myelitis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Estudo de propriedades estruturais e opticas de multicamadas epitaxiais emissoras de luz baseadas em InGaN/GaN

NASA Astrophysics Data System (ADS)

Pereira, Sergio Manuel de Sousa

Esta tese apresenta os resultados de uma investigacao experimental em filmes epitaxiais emissores de luz baseados em InxGa1-xN. O InxGa1-xN e uma liga semicondutora ternaria do grupo III-N muito utilizada como camada activa numa gama de dispositivos optoelectronicos em desenvolvimento, incluindo diodos emissores de luz (LEDs) e diodos laser (LDs), para operacao na regiao do visivel e ultravioleta do espectro electromagnetico. Neste estudo, caracterizam-se as propriedade opticas e estruturais de camadas simples e pocos quânticos multiplos (Multiple Quantum Wells, MQWs) de InxGa1-xN/GaN, com enfase nas suas propriedades fisicas fundamentais. O objectivo central do trabalho prende-se com a compreensao mais profunda dos processos fisicos que estao por tras das suas propriedades opticas, preenchendo o fosso existente entre aplicacoes tecnologicas e o conhecimento cientifico. Nomeadamente, a tese aborda os problemas da medicao da fraccao de InN (x) em multicamadas ultrafinas sujeitas a tensoes, a influencia da composicao e das tensoes microscopicas nas propriedades opticas e estruturais. A questao relativa a segregacao de fases em multicamadas de InxGa1-xN/GaN e tambem discutida a luz dos resultados obtidos. A metodologia seguida assenta na integracao de resultados obtidos por tecnicas complementares atraves de uma analise sistematica e multidisciplinar. Esta abordagem passa pela combinacao de: 1) Crescimento de amostras por deposicao epitaxial em fase de vapor organometalico (MOVPE) com caracteristicas especificas de forma a tentar isolar parâmetros estruturais, tais como espessura e composicao; 2) Caracterizacao nanoestrutural por microscopia de forca atomica (AFM), microscopica electronica de varrimento (SEM), difraccao de raios-X e retro-dispersao de Rutherford (RBS); 3) Caracterizacao optica a escalas complementares por: espectroscopia de absorcao optica (OA), fotoluminescencia (PL), catodoluminescencia (CL) e microscopia confocal (CM) com analise espectral. Com

Patient-reported outcome measure for neuromyelitis optica: pretesting of preliminary instrument and protocol for further development in accordance with international guidelines.

PubMed

Moore, P; Jackson, C; Mutch, K; Methley, A; Pollard, C; Hamid, S; Jacob, A

2016-09-30

This study outlines the development of a patient-reported outcome measure (PROM), an instrument to obtain self-reported health status for neuromyeltis optica (NMO), a disabling neurological condition. Development was conducted in accordance with international guidance for PROMs including systematic review of existing literature, item generation guided by qualitative interviews, health-related quality of life conceptual framework and clinical expert panel and cognitive interviews with NMO patients. Participants were identified through a national NMO clinic in a tertiary NHS neurosciences service. 15 individuals with NMO participated in cognitive interviews requiring review and ranking of proposed PROM items and qualitative feedback on content, layout and response options. Participants endorsed the draft instrument as reflecting their experience of the condition and as being easy to understand. Rating and ranking of item relevance and importance reduced the draft instrument from 106 to 48 items. Participant feedback on overlapping items eliminated a further 2 items and resulted in a preliminary instrument of 46 items. As a direct result of participant feedback ordering of the 10 domains was revised, a 4 option Likert scale was employed and a 4-week recall period for impact of symptoms was selected. A 46-item instrument developed in accordance with international PROM development guidelines through literature review, developed by subject matter experts and refined through pretesting examining content validity provides a preliminary measure for assessing patient-report of health status in NMO. Further evaluation is proposed including sensitivity to clinical change, and international contributions to evaluating the measure are encouraged. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Pure spinal multiple sclerosis: A possible novel entity within the multiple sclerosis disease spectrum.

PubMed

Schee, Jie Ping; Viswanathan, Shanthi

2018-05-01

We identified five female patients retrospectively with relapsing short-segment partial myelitis whose clinical and paraclinical features were suggestive of cord involvement of multiple sclerosis (MS)-type albeit not rigidly fulfilling the 2017 McDonald criteria. Notably, these patients had not developed any typical MS-like brain lesions despite repeated neuroimaging assessments over years. Comprehensive work-up for differential diagnoses of MS and other causes of transverse myelitis particularly neuromyelitis optica spectrum disorders had been consistently negative on longitudinal follow-up. Thus, we postulate a possible entity of pure spinal MS which may represent a novel forme fruste within the MS disease spectrum.

Autoantibody-induced internalization of CNS AQP4 water channel and EAAT2 glutamate transporter requires astrocytic Fc receptor.

PubMed

Hinson, Shannon R; Clift, Ian C; Luo, Ningling; Kryzer, Thomas J; Lennon, Vanda A

2017-05-23

Aquaporin-4 (AQP4) water channel-specific IgG distinguishes neuromyelitis optica (NMO) from multiple sclerosis and causes characteristic immunopathology in which central nervous system (CNS) demyelination is secondary. Early events initiating the pathophysiological outcomes of IgG binding to astrocytic AQP4 are poorly understood. CNS lesions reflect events documented in vitro following IgG interaction with AQP4: AQP4 internalization, attenuated glutamate uptake, intramyelinic edema, interleukin-6 release, complement activation, inflammatory cell recruitment, and demyelination. Here, we demonstrate that AQP4 internalization requires AQP4-bound IgG to engage an astrocytic Fcγ receptor (FcγR). IgG-lacking Fc redistributes AQP4 within the plasma membrane and induces interleukin-6 release. However, AQP4 endocytosis requires an activating FcγR's gamma subunit and involves astrocytic membrane loss of an inhibitory FcγR, CD32B. Interaction of the IgG-AQP4 complex with FcγRs triggers coendocytosis of the excitatory amino acid transporter 2 (EAAT2). Requirement of FcγR engagement for internalization of two astrocytic membrane proteins critical to CNS homeostasis identifies a complement-independent, upstream target for potential early therapeutic intervention in NMO.

Autoantibody-induced internalization of CNS AQP4 water channel and EAAT2 glutamate transporter requires astrocytic Fc receptor

PubMed Central

Hinson, Shannon R.; Clift, Ian C.; Luo, Ningling; Kryzer, Thomas J.; Lennon, Vanda A.

2017-01-01

Aquaporin-4 (AQP4) water channel-specific IgG distinguishes neuromyelitis optica (NMO) from multiple sclerosis and causes characteristic immunopathology in which central nervous system (CNS) demyelination is secondary. Early events initiating the pathophysiological outcomes of IgG binding to astrocytic AQP4 are poorly understood. CNS lesions reflect events documented in vitro following IgG interaction with AQP4: AQP4 internalization, attenuated glutamate uptake, intramyelinic edema, interleukin-6 release, complement activation, inflammatory cell recruitment, and demyelination. Here, we demonstrate that AQP4 internalization requires AQP4-bound IgG to engage an astrocytic Fcγ receptor (FcγR). IgG-lacking Fc redistributes AQP4 within the plasma membrane and induces interleukin-6 release. However, AQP4 endocytosis requires an activating FcγR’s gamma subunit and involves astrocytic membrane loss of an inhibitory FcγR, CD32B. Interaction of the IgG–AQP4 complex with FcγRs triggers coendocytosis of the excitatory amino acid transporter 2 (EAAT2). Requirement of FcγR engagement for internalization of two astrocytic membrane proteins critical to CNS homeostasis identifies a complement-independent, upstream target for potential early therapeutic intervention in NMO. PMID:28461494

Multiple Sclerosis in Malaysia: Demographics, Clinical Features, and Neuroimaging Characteristics

PubMed Central

Viswanathan, S.; Rose, N.; Masita, A.; Dhaliwal, J. S.; Puvanarajah, S. D.; Rafia, M. H.; Muda, S.

2013-01-01

Background. Multiple sclerosis (MS) is an uncommon disease in multiracial Malaysia. Diagnosing patients with idiopathic inflammatory demyelinating diseases has been greatly aided by the evolution in diagnostic criterion, the identification of new biomarkers, and improved accessibility to neuroimaging in the country. Objectives. To investigate the spectrum of multiple sclerosis in Malaysia. Methods. Retrospective analysis with longitudinal follow-up of patients referred to a single tertiary medical center with neurology services in Malaysia. Results. Out of 245 patients with idiopathic inflammatory demyelinating disease, 104 patients had multiple sclerosis. Female to male ratio was 5 : 1. Mean age at onset was 28.6 ± 9.9 years. The Malays were the predominant racial group affected followed by the Chinese, Indians, and other indigenous groups. Subgroup analysis revealed more Chinese having neuromyelitis optica and its spectrum disorders rather than multiple sclerosis. Positive family history was reported in 5%. Optic neuritis and myelitis were the commonest presentations at onset of disease, and relapsing remitting course was the commonest disease pattern observed. Oligoclonal band positivity was 57.6%. At disease onset, 61.5% and 66.4% fulfilled the 2005 and 2010 McDonald's criteria for dissemination in space. Mean cord lesion length was 1.86 ± 1.65 vertebral segments in the relapsing remitting group as opposed to 6.25 ± 5.18 vertebral segments in patients with neuromyelitis optica and its spectrum disorders. Conclusion. The spectrum of multiple sclerosis in Malaysia has changed over the years. Further advancement in diagnostic criteria will no doubt continue to contribute to the evolution of this disease here. PMID:24455266

Care of an undocumented immigrant

PubMed Central

Beresford, H. Richard

2014-01-01

Summary This commentary addresses the care of an undocumented immigrant with neuromyelitis optica in the context of a state law designed to deny state-funded medical services to individuals whose presence in the United States is unlawful. It considers specific circumstances in which the law would permit or require medical care for undocumented persons in state medical facilities, including a duty to “stabilize” an “emergency medical condition” and the provision of care necessary to “protect life or safety.” It also addresses dilemmas clinicians may experience when faced with an apparent tension between their professional ethical obligations and legal rules aimed at enforcing immigration policies. PMID:29443225

Ethical considerations when counseling patients about stem cell tourism.

PubMed

Tsou, Amy

2015-02-01

Worldwide, many clinics market stem-cell based interventions often touted as effective for many diseases including spinal cord injury, multiple sclerosis (MS), and other neurodegenerative diseases. These clinics and their expensive, unproven treatments continue to fuel the practice of stem cell tourism. Given concerns about patient exploitation and safety, how should the physician engage a patient who wants to pursue such treatments? This article presents the case of a patient with neuromyelitis optica interested in pursuing expensive stem cell injections abroad. This article describes stem cell tourism along with some of the ethical issues physicians should consider, while also providing practical resources that physicians may employ to educate and engage patients in making an informed decision.

NMOSD triggered by yellow fever vaccination - An unusual clinical presentation with segmental painful erythema.

PubMed

Schöberl, F; Csanadi, E; Eren, O; Dieterich, M; Kümpfel, T

2017-01-01

Neuromyelitis Optica Spectrum Disorder (NMOSD) is an immune-mediated disease of the central nervous system with the presence of aquaporin 4-antibodies (AQP4-abs) in most cases. We describe a patient who developed NMOSD after a yellow fever vaccination. He presented to us with an unusual painful erythema Th7-9 triggered by touch in the respective skin area due to a cervical spinal cord lesion affecting the dorsolateral parts of C6/7. To our knowledge, this is the first case of NMOSD with such a clinical presentation expanding the clinical spectrum of NMOSD. It is important to be aware of that a yellow fever vaccination can trigger NMOSD. Copyright © 2016 Elsevier B.V. All rights reserved.

Biomarkers in the evolution of multiple sclerosis.

PubMed

Berger, Thomas

2017-11-01

Nonimaging biomarkers can be applied in differential diagnosis, evaluation of disease progression and therapy monitoring of multiple sclerosis (MS). Presence of oligoclonal IgG bands in cerebrospinal fluid is a diagnostic element and a negative predictor of MS evolution. AQP4 antibodies are pathogenic and diagnostic for neuromyelitis optica spectrum disorder. Antibodies to myelin oligodendrocyte glycoprotein develop in about 50% of predominantly pediatric patients with acute disseminated encephalomyelitis, but their possible role in pathogenesis is unknown. Currently, there are no individualized biomarkers suitable to track disease progression. Neutralizing antibodies against IFN-β, natalizumab and daclizumab arise with variable frequency and reduce treatment efficacy. The anti-John Cunningham virus antibody index has potential as a biomarker for risk of progressive multifocal leukoencephalopathy.

Clinical features and sera anti-aquaporin 4 antibody positivity in patients with demyelinating disorders of the central nervous system from Tianjin, China.

PubMed

Yang, Chun-Sheng; Zhang, Da-Qi; Wang, Jing-Hua; Jin, Wei-Na; Li, Min-Shu; Liu, Jie; Zhang, Cun-Jin; Li, Ting; Shi, Fu-Dong; Yang, Li

2014-01-01

To investigate the clinical characteristics and sera anti-aquaporin 4 (AQP4) antibody positivity in patients with inflammatory demyelinating disorders (IDDs) of the central nervous system (CNS) in Tianjin, China. We retrospectively evaluated 234 patients with IDDs including neuromyelitis optica (NMO), recurrent optic neuritis (rON), longitudinally extensive transverse myelitis (LETM), clinically isolated syndrome (CIS), and multiple sclerosis (MS) groups. Sera from 217 patients were determined for AQP4-Ab. The clinical characteristics and sera anti-AQP4 positivity were compared. The IDDS comprised 63 MS, 51 NMO, 56 LETM, 10 rON, and 54 CIS. Compared with MS, NMO had a higher frequency of occurrence in women, intractable hiccup and nausea (IHN), medullospinal lesion, longitudinally extensive spinal cord lesions (LESCL) and bilateral ON, disease onset at a later age, and worsening residual disability. AQP4-Ab-positive rates were 84.1% and 69% in NMO and NMO spectrum disorders (NMOSD), respectively, whereas it was undetectable in all of the MS sera samples. We comprehensively contrast the distinct clinical features of MS, NMO, and NMOSD in our center. A sensitive AQP4-Ab assay is necessary for the early diagnosis of NMOSD in our patients. Neither medullospinal lesion nor IHN is unique in NMO. © 2013 John Wiley & Sons Ltd.

Opportunistic infections of the retina in patients with aquaporin-4 antibody disease.

PubMed

George, Jithin S; Leite, Maria Isabel; Kitley, Joanna L; Jones, Nicola; Cortes, Nicholas; Donati, Matthew; Matthews, Bethan Non; Calladine, Daniel; Hillier, Charles; Yusuf, Imran H; Munneke, Robert; Patel, Chetan K; Palace, Jacqueline A; Elston, John S

2014-11-01

Patients with neuromyelitis optica who have aquaporin-4 antibodies are being identified and receiving immunosuppressant treatment earlier and more aggressively as a result of increasing awareness of the importance of preventing relapses responsible for the high morbidity and mortality associated with the disease. To our knowledge, opportunistic retinal infection in patients with aquaporin-4 antibodies who are receiving immunosuppressants has not been reported to date. We describe 2 patients with aquaporin-4 antibodies who were receiving conventional doses of first-line immunosuppressive therapy. Both patients presented with vision loss that was initially thought to be optic neuritis attacks. The subsequent diagnoses were ocular toxoplasmosis and cytomegalovirus retinitis. Retinal opportunistic infections can occur in patients with aquaporin-4 antibodies who are receiving relatively low levels of immunosuppression, may mimic optic neuritis, and are a potentially reversible cause of vision loss when treated promptly.

Aquaporins: important but elusive drug targets

PubMed Central

Verkman, Alan S.; Anderson, Marc O.; Papadopoulos, Marios C.

2014-01-01

The aquaporins (AQPs) are a family of small, integral membrane proteins that facilitate water transport across the plasma membranes of cells in response to osmotic gradients. Data from knockout mice support the involvement of AQPs in epithelial fluid secretion, cell migration, brain oedema and adipocyte metabolism, which suggests that modulation of AQP function or expression could have therapeutic potential in oedema, cancer, obesity, brain injury, glaucoma and several other conditions. Moreover, loss-of-function mutations in human AQPs cause congenital cataracts (AQP0) and nephrogenic diabetes insipidus (AQP2), and autoantibodies against AQP4 cause the autoimmune demyelinating disease neuromyelitis optica. Although some potential AQP modulators have been identified, challenges associated with the development of better modulators include the druggability of the target and the suitability of the assay methods used to identify modulators. PMID:24625825

Catálogo de Radio-Fuentes Opticas con Astrolabio Fotoeléctrico PAII

NASA Astrophysics Data System (ADS)

Manrique, W. T.; Podestá, R. C.; Alonso, E.; Actis, E. V.; Pacheco, A. M.; Bustos, G.; Lizhi, L.; Zezhi, W.; Fanmiao, Z.; Hongqi, W.; Perdomo, R.

Usando los datos observados en San Juan con el Astrolabio Fotoeléctrico PAII desde Febrero de 1992 hasta Marzo de 1997, se ha realizado el Catálogo de Radio-Fuentes Opticas de San Juan conteniendo 69 estrellas. Las observaciones de las posiciones de las radio-fuentes están realizadas para la época y equinoccio J2000,0 y en un sistema cercano al del FK5. Las precisiones medias son ± 2,2 ms y ± 0,"035 en ascensión recta y declinación respectivamente. Las magnitudes de las estrellas son desde 0,9 a 10,7 . Las declinaciones son desde --2,5 grados a --60 grados. La época media es 1995,1. Se muestran también los resultados comparados con el Catálogo Hiparcos.

New biological agents in the treatment of multiple sclerosis.

PubMed

Buc, M

2018-01-01

Multiple sclerosis (MS) is an inflammatory disease induced by autoimmune processes. Their understanding has resulted in an introduction of biological agents to its treatment. Interferon beta and glatiramer acetate have been in clinical practice for more than 20 years. Nowadays, novel biologics, which target molecules involved in immunopathological processes more specifically have entered the scene. They are represented by monoclonal antibodies binding to molecules VLA4 (natalizumab), CD20 (ocrelizumab), CD52 (alemtuzumab) or alpha subunit of IL-2 receptor (daclizumab) or by small molecules such as those modulating the receptors involved in regulation of lymphocyte migration (fingolimod, ozanimod) or in induction of lymphopenia by apoptosis (dimethyl fumarate, cladribine). In the article, we shortly describe their efficacies, adverse reactions and perspectives of a future development in MS biologics. A treatment of neuromyelitis optica by monoclonal antibodies (rituximab, aquaporumab) is given too (Tab. 1, Fig. 2, Ref. 71).

The usefulness of immunotherapy in pediatric neurodegenerative disorders: A systematic review of literature data.

PubMed

Vitaliti, Giovanna; Tabatabaie, Omidreza; Matin, Nassim; Ledda, Caterina; Pavone, Piero; Lubrano, Riccardo; Serra, Agostino; Di Mauro, Paola; Cocuzza, Salvatore; Falsaperla, Raffaele

2015-01-01

Immunotherapeutic strategies to treat neurodegenerative disorders have inspired the scientific community. The aim of our review is to address the translational aspects of neuroimmunology to describe the efficacy of immunotherapy in the treatment of pediatric neurodegenerative disorders. In the studies we analyzed IVIG were found to be efficient in the treatment of post-streptococcal neurodegenerative disorders, even if in PANDAS, plasma-exchange (PE) showed a higher efficiency. IVIG were also successfully used in ADEM and Guillan-Barré syndrome. In Sydenham Chorea the use of methylprednisolone was found in most cases as efficient as IVIG, while in Tourette's Syndrome, Colecoxib was successfully used in one patient. Pediatric Multiple Sclerosis seems to respond better to immunosuppressant agents (Mitoxantrone, Cyclophosphamide, Natalizumab), as well as Neuromyelitis optica (Rituximab, Mycofenolate). The importance of this review relies in the attempt to draw standardized guidelines for immunotherapy in pediatric neurodegeneratve disorders.

The usefulness of immunotherapy in pediatric neurodegenerative disorders: A systematic review of literature data

PubMed Central

Vitaliti, Giovanna; Tabatabaie, Omidreza; Matin, Nassim; Ledda, Caterina; Pavone, Piero; Lubrano, Riccardo; Serra, Agostino; Di Mauro, Paola; Cocuzza, Salvatore; Falsaperla, Raffaele

2015-01-01

Immunotherapeutic strategies to treat neurodegenerative disorders have inspired the scientific community. The aim of our review is to address the translational aspects of neuroimmunology to describe the efficacy of immunotherapy in the treatment of pediatric neurodegenerative disorders. In the studies we analyzed IVIG were found to be efficient in the treatment of post-streptococcal neurodegenerative disorders, even if in PANDAS, plasma-exchange (PE) showed a higher efficiency. IVIG were also successfully used in ADEM and Guillan-Barré syndrome. In Sydenham Chorea the use of methylprednisolone was found in most cases as efficient as IVIG, while in Tourette's Syndrome, Colecoxib was successfully used in one patient. Pediatric Multiple Sclerosis seems to respond better to immunosuppressant agents (Mitoxantrone, Cyclophosphamide, Natalizumab), as well as Neuromyelitis optica (Rituximab, Mycofenolate). The importance of this review relies in the attempt to draw standardized guidelines for immunotherapy in pediatric neurodegeneratve disorders PMID:26266339

Optic neuromyelitis syndrome in Brazilian patients

PubMed Central

Papais-Alvarenga, R; Miranda-Santos, C; Puccioni-Sohler, M; de Almeida, A M V; Oliveira, S; De Oliveira, C A B.; Alvarenga, H; Poser, C

2002-01-01

Objectives: To report the clinical features and outcome of 24 Brazilian patients with optic neuromyelitis syndrome (ONM); discuss the underlying pathological events associated with the ONM syndrome; review the nosological situation of ONM in the group of inflammatory and demyelinating diseases of the central nervous system. Patients and Methods: Patients with ONM treated at the Hospital da Lagoa, Rio de Janeiro were studied. Demographic, clinical, magnetic resonance imaging, cerebrospinal fluid, and pathological data were analysed. Results: The study consisted of 20 women, four men of whom 10 were white and 14 Afro-Brazilians. Clinical course was recurrent in 22 cases and monophasic in two. Neurological manifestations at inclusion were: sensory impairment (66%), bilateral (41.6%) or unilateral blindness (20.8%), paraplegia or quadriplegia (37.5%). The EDSS was moderate/severe in 70.8%. The underlying pathological events were respectively pulmonary tuberculosis and upper respiratory infection in the two monophasic cases; in the 22 recurrent ONM patients: pulmonary tuberculosis (3), neurocysticercosis (1), polyarteritis nodosa (1), antinuclear antibody and rheumatoid factor (1), antiphospholipid antibody primary syndrome (1), diabetes mellitus (1), hypothyroidism (1), and amenorrhea-galactorrhea (4). Normal cerebrospinal fluid was found in 52% and an inflammatory profile in 48%. Only four recurrent ONM white patients had brain and spinal cord magnetic resonance imaging and cerebrospinal fluid findings compatible with the diagnosis of multiple sclerosis. Large lesions were seen in 62% of spinal magnetic resonance images. Six of 12 recurrent ONM Afro-Brazilian died. There were no statistical differences in the demographic data of the two ethnic groups. Afro-Brazilians were significantly more severely impaired and had a higher mortality rate than the white patients. Conclusion: These cases were classified as follows: two monophasic acute disseminated encephalomyelitis

Management of disease-modifying treatments in neurological autoimmune diseases of the central nervous system.

PubMed

Salmen, A; Gold, R; Chan, A

2014-05-01

The therapeutic armamentarium for autoimmune diseases of the central nervous system, specifically multiple sclerosis and neuromyelitis optica, is steadily increasing, with a large spectrum of immunomodulatory and immunosuppressive agents targeting different mechanisms of the immune system. However, increasingly efficacious treatment options also entail higher potential for severe adverse drug reactions. Especially in cases failing first-line treatment, thorough evaluation of the risk-benefit profile of treatment alternatives is necessary. This argues for the need of algorithms to identify patients more likely to benefit from a specific treatment. Moreover, paradigms to stratify the risk for severe adverse drug reactions need to be established. In addition to clinical/paraclinical measures, biomarkers may aid in individualized risk-benefit assessment. A recent example is the routine testing for anti-John Cunningham virus antibodies in natalizumab-treated multiple sclerosis patients to assess the risk for the development of progressive multi-focal leucoencephalopathy. Refined algorithms for individualized risk assessment may also facilitate early initiation of induction treatment schemes in patient groups with high disease activity rather than classical escalation concepts. In this review, we will discuss approaches for individiualized risk-benefit assessment both for newly introduced agents as well as medications with established side-effect profiles. In addition to clinical parameters, we will also focus on biomarkers that may assist in patient selection. © 2013 British Society for Immunology.

Aquaporins in Clinical Medicine

PubMed Central

Verkman, A.S.

2012-01-01

The aquaporins are a family of membrane water channels, some of which also transport glycerol. They are involved in a wide range of physiological functions (including water/salt homeostasis, exocrine fluid secretion, and epidermal hydration) and human diseases (including glaucoma, cancer, epilepsy, and obesity). At the cellular level, aquaporin-mediated osmotic water transport across cell plasma membranes facilitates transepithelial fluid transport, cell migration, and neuroexcitation; aquaporin-mediated glycerol transport regulates cell proliferation, adipocyte metabolism, and epidermal water retention. Genetic diseases caused by loss-of-function mutations in aquaporins include nephrogenic diabetes insipidus and congenital cataracts. The neuroinflammatory demyelinating disease neuromyelitis optica is marked by pathogenic autoantibodies against astrocyte water channel aquaporin-4. There remain broad opportunities for the development of aquaporin-based diagnostics and therapeutics. Disease-relevant aquaporin polymorphisms are beginning to be explored. There is great promise in the development of small-molecule aquaporin modulators for therapy of some types of refractory edema, brain swelling, neuroinflammation, glaucoma, epilepsy, cancer, pain, and obesity. PMID:22248325

[Roles of Aquaporins in Brain Disorders].

PubMed

Yasui, Masato

2015-06-01

Aquaporin (AQP) is a water channel protein that is expressed in the cell membranes. AQPs are related to several kinds of human diseases such as cataract. In the mammalian central nervous system (CNS), AQP4 is specifically expressed in the astrocyte membranes lining the perivascular and periventricular structures. AQP4 plays a role in the development of brain edema associated with certain brain disorders. Neuromyelitis optica (NMO) is a demyelinating disorder, and patients with NMO develop autoimmune antibodies against AQP4 in their serum. Therefore, AQP4 is involved in NMO pathogenesis. A new concept referred to as "glymphatic pathway" has been recently proposed to explain the lymphatic system in the CNS. Dysfunction of the "glymphatic pathway" may cause several neurodegenerative diseases and mood disorders. Importantly, AQP4 may play a role in the "glymphatic pathway". Further investigation of AQP4 in CNS disorders is necessary, and a new drug against AQP4 is expected.

The profile of patients followed at the Neuroimmunology Clinic at UNIFESP: 20 years analysis.

PubMed

Bichuetti, Denis Bernardi; Falcão, Alessandra Billi; Boulos, Fernanda de Castro; Morais, Marilia Mamprim de; Lotti, Claudia Beatriz de Campos; Fragomeni, Manuela de Oliveira; Campos, Maria Fernanda; Souza, Nilton Amorim de; Oliveira, Enedina Maria Lobato

2015-04-01

To describe the clinical activities at the Neuroimmunology Clinic of the Universidade Federal de São Paulo (UNIFESP) from 1994 to 2013. The final diagnosis of all patients that attended the center was reviewed and established upon specific guidelines for each disease. The number of total appointments and extra clinical activities (reports and prescriptions) were also analyzed, as are part of routine activities. 1,599 patients attended the Clinic from 1994 to 2013: 816 with multiple sclerosis (MS), 172 with clinical isolated syndromes, 178 with neuromyelitis optica (NMO), 216 with other demyelinating disease, 20 with metabolic disorder, 42 with a vascular disease and 155 with other or undetermined diagnosis. A mean 219 outpatient visits and 65 extra clinical activities were performed monthly. We identified that 15% of patients seen have NMO. As patients with NMO have a more severe disease than MS, this data may be important for planning local health care policies.

Anti-aquaporin-4 autoantibodies in systemic lupus erythematosus persist for years and induce astrocytic cytotoxicity but not CNS disease.

PubMed

Alexopoulos, Harry; Kampylafka, Eleni I; Fouka, Penelope; Tatouli, Ioanna; Akrivou, Sofia; Politis, Panagiotis K; Moutsopoulos, Haralampos M; Tzioufas, Athanasios G; Dalakas, Marinos C

2015-12-15

Anti-aquaporin-4 autoantibodies are specific for the neuromyelitis optica spectrum disorders (NMOSD) and they have also been described in patients with systemic lupus erythematosus (SLE) with neurological signs consistent with NMOSD. Our objective was to test for the presence and pathogenicity of anti-AQP4 antibodies in SLE patients without neurological disease. Sera from 89 non-CNS-SLE patients were screened for anti-AQP4 autoantibodies. Two of the 89 patients were positive. Archived samples dating back 11 years were also positive. A brain and spinal cord MRI did not reveal any NMOSD-compatible lesions. An in vitro cytotoxicity assay showed that either sera or purified IgG from these patients induced a complement-mediated damage in cultured astrocytes comparable to antibodies obtained from typical NMO patients. We conclude that AQP4-antibodies can be present in SLE patients and persist for many years, without concurrent clinical or radiological NMOSD signs. It is unclear why the anti-AQP4 antibodies did not induce CNS disease. Copyright © 2015 Elsevier B.V. All rights reserved.

A case of anti aquapolin-4 antibody positive myelitis with hyperhidrosis, following herpes zoster.

PubMed

Suda, Machiko; Tsutsumiuchi, Michiko; Uesaka, Yoshikazu; Hayashi, Nobukazu

2017-01-31

We report an acute myelitis in a 53-year-old woman that occurred in 7 days after the diagnosis of Th5-6 herpes zoster. Clinical examination revealed hyperhidrosis of left side of her face, neck, arm and upper chest. She also had muscle weakness of her left leg and sensory impairment for light touch and temperature in her chest and legs. Spinal cord MRI demonstrated a longitudinal T 2 -hyperintense lesion extending from Th1 to 7. In the axial imaging, the lesion dominantly located in the left side gray matter. Hyperhidrosis, weakness and sensory impairment were improved after intravenous therapy with acyclovir and methylprednisolone. VZV (varicella zoster virus) IgG index of the cerebrospinal fluid was high and serological anti aquaporin-4 antibodies were positive at the time of the admission. This case had both characteristics of VZV myelitis and neuromyelitis optica spectrum disorder. Myelitis relapsed 19 months after the first attack. We believe that sympathetic hyper reactivity due to thoracic spinal cord lesion was responsible for the hyperhidrosis in our patient.

Rare inflammatory diseases of the white matter and mimics of multiple sclerosis and related disorders.

PubMed

Tardieu, Marc; Deiva, Kumaran

2013-12-01

The spectra of white matter neuroinflammatory diseases and pathological processes inducing inflammatory lesions in the white matter of the central nervous system are wider in children than in adults. The definitions of multiple sclerosis (MS) and of the related clinically isolated syndromes (CIS) and acute disseminated encephalomyelitis (ADEM) have been recently revised leading to a new consensus definition. However, other entities with similarities to these diseases may also develop with monophasic or relapsing white matter inflammation. These conditions include congenital immunogenetic diseases (such as hemophagocytic lymphohistiocytosis), vasculitis, and autoantibody-mediated encephalopathies (Hashimoto encephalopathy, encephalitis with anti-N-methyl-D-aspartate receptor antibodies and neuromyelitis optica). Moreover, infectious diseases, such as Lyme disease, tumors (oligodendroglioma and lymphoma), and even genetic or metabolic diseases should also be considered if the clinical course of the disease does not follow the typical pattern for ADEM or MS. This short review describes these different entities and provides information for the differential diagnosis of inflammatory diseases of the white matter. Georg Thieme Verlag KG Stuttgart · New York.

[Nosology and etiologies of acute longitudinally extensive transverse myelitis].

PubMed

Collongues, N; Papeix, C; Zéphir, H; Audoin, B; Cotton, F; Durand-Dubief, F; Vukusic, S; Brassat, D; Laplaud, D; Marignier, R

2014-01-01

Acute transverse myelitis had many names and definitions, based primarily on clinical criteria. The role of MRI in the exploration of myelitis has increased recently after the individualization of neuromyelitis optica (NMO) in 2004. This approach has enabled clarification of the diagnostic and prognostic value of acute longitudinally extensive transverse myelitis (LETM), defined by an extensive T2 lesion affecting three vertebral segments in the sagittal plane. The limitations of this definition, the multiplicity of terms used to characterize it as well as the large number of etiologies associated with it led our group of experts to clarify its etiology and nosology. We conducted a national survey on this subject in order to propose a new definition of LETM. Additional first- and second-intention examinations were determined according to the clinical context. Infectious/para-infectious, inflammatory or paraneoplastic causes can thus be identified. To determine within a short time the cause of LETM is essential, since most of its causes are severe and require urgent treatment. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Eosinophils in Autoimmune Diseases

PubMed Central

Diny, Nicola L.; Rose, Noel R.; Čiháková, Daniela

2017-01-01

Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs. PMID:28496445

Meningitis determined by oligosymptomatic dengue virus type 3 infection: report of a case.

PubMed

Soares, C N; Cabral-Castro, M J; Peralta, J M; Freitas, M R G; Puccioni-Sohler, M

2010-02-01

Dengue infection is a mosquito-borne disease caused by a flavivirus, and is recognized in over 100 countries with 2.5 billion people living in areas of risk. Neurological manifestations such as encephalitis, myelitis, Guillain-Barré syndrome, cranial nerve palsies, neuromyelitis optica, and encephalomyelitis have been recognized as clinical consequences of dengue infection. Meningitis is a rare complication. We report the case of a 24-year-old woman who presented with fever, headache, and nuchal rigidity without the typical symptoms of dengue infection. Cerebrospinal fluid analysis showed lymphocytic pleocytosis with a normal glucose value and negative bacterial and fungal cultures. The etiology of meningitis was confirmed by positive dengue PCR in the serum. This case report highlights dengue infection as a potential cause of meningitis in endemic areas. Also, meningitis can be the first manifestation of the infection. Dengue should be investigated even in the absence of a typical picture of the infection. Copyright 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Channelopathies.

PubMed

Kim, June-Bum

2014-01-01

Channelopathies are a heterogeneous group of disorders resulting from the dysfunction of ion channels located in the membranes of all cells and many cellular organelles. These include diseases of the nervous system (e.g., generalized epilepsy with febrile seizures plus, familial hemiplegic migraine, episodic ataxia, and hyperkalemic and hypokalemic periodic paralysis), the cardiovascular system (e.g., long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia), the respiratory system (e.g., cystic fibrosis), the endocrine system (e.g., neonatal diabetes mellitus, familial hyperinsulinemic hypoglycemia, thyrotoxic hypokalemic periodic paralysis, and familial hyperaldosteronism), the urinary system (e.g., Bartter syndrome, nephrogenic diabetes insipidus, autosomal-dominant polycystic kidney disease, and hypomagnesemia with secondary hypocalcemia), and the immune system (e.g., myasthenia gravis, neuromyelitis optica, Isaac syndrome, and anti-NMDA [N-methyl-D-aspartate] receptor encephalitis). The field of channelopathies is expanding rapidly, as is the utility of molecular-genetic and electrophysiological studies. This review provides a brief overview and update of channelopathies, with a focus on recent advances in the pathophysiological mechanisms that may help clinicians better understand, diagnose, and develop treatments for these diseases.

Recurrent longitudinal extensive transverse myelitis in a neuro-Behçet syndrome treated with infliximab.

PubMed

Uygunoğlu, Uğur; Pasha, Maarya; Saip, Sabahattin; Siva, Aksel

2015-01-01

Spinal cord involvement is not common, but can be seen in neuro-Behçet's syndrome (NBS). The major site of involvement is the cervical spinal cord with the myelitis-like inflammatory lesions continuing more than two segments, and extending to the brainstem. A 30-year-old male patient who has been followed with a diagnosis of Behçet's syndrome admitted to our neurology department clinically and radiologically suggestive of recurrent and extensive longitudinal myelitis. His anti-aquaporine antibody was negative. Because of insufficient effect of azathioprine, cyclophosphamide, and corticosteroids, infliximab was started. His clinical and radiological status is stationary for 3 years under infliximab treatment. Myelitis such as that occurring in our patient may have a similar presentation like neuromyelitis optica (NMO), which should therefore be included in differential diagnosis. Myelitis observed in both NMO and NBS shows spinal cord lesions longer than three or more vertebrae. Anti-aquaporine antibody must be evaluated in all patients presenting with longitudinal myelitis. Anti-tumor necrosis factor agent infliximab might be an alternative treatment in severe form of NBS such as myelitis. In our case, successful treatment of recurrent and extensive longitudinal transverse myelitis in NBS with infliximab was demonstrated.

[Neuro-ophthalmology: the eye as a window to the brain].

PubMed

Kesler, Anat

2013-02-01

Neuro-ophthalmology focuses on the diagnosis and treatment of visual disorders related to the neurological system rather than the globe itself. Being a subspecialty of both neurology and ophthalmology, it requires specialized training and expertise in diseases of the eye, brain, nerves and muscles. Commonly encountered pathologies in neuro-ophthalmology include: optic neuropathies (such as optic neuritis and ischemic optic neuropathy), visual field loss (transient, constant, unexplained), transient visual loss, unspecified visual disturbances, diplopia, abnormal eye movements, thyroid eye disease, myasthenia gravis, anisocoria, and eyelid abnormalities. The current issue of "Harefuah" is dedicated to contemporary knowledge in neuro-opthalmology, and spans from studies of neuromyelitis optica (NMO), ischemic optic neuropathies, and optic neuropathies induced by phosphodiesterase inhibitors, to the management of sight-threatening carotid-cavernous fistulas, and more. These studies emphasize the importance of an interdisciplinary treatment team consisting of a neuro-ophthalmologist, a neuro-radiologist, and sometimes, even a neuro-surgeon. Such an approach may prove to be beneficial to the patient, by optimizing follow-up and treatment decisions. This issue emphasizes how a correct and timely diagnosis is of paramount significance in patients with neuro-ophthalmological disorders.

Anti-MOG antibody-positive ADEM following infectious mononucleosis due to a primary EBV infection: a case report.

PubMed

Nakamura, Yoshitsugu; Nakajima, Hideto; Tani, Hiroki; Hosokawa, Takafumi; Ishida, Shimon; Kimura, Fumiharu; Kaneko, Kimihiko; Takahashi, Toshiyuki; Nakashima, Ichiro

2017-04-19

Anti-Myelin oligodendrocyte glycoprotein (MOG) antibodies are detected in various demyelinating diseases, such as pediatric acute disseminated encephalomyelitis (ADEM), recurrent optic neuritis, and aquaporin-4 antibody-seronegative neuromyelitis optica spectrum disorder. We present a patient who developed anti-MOG antibody-positive ADEM following infectious mononucleosis (IM) due to Epstein-Barr virus (EBV) infection. A 36-year-old healthy man developed paresthesia of bilateral lower extremities and urinary retention 8 days after the onset of IM due to primary EBV infection. The MRI revealed the lesions in the cervical spinal cord, the conus medullaris, and the internal capsule. An examination of the cerebrospinal fluid revealed pleocytosis. Cell-based immunoassays revealed positivity for anti-MOG antibody with a titer of 1:1024 and negativity for anti-aquaporin-4 antibody. His symptoms quickly improved after steroid pulse therapy followed by oral betamethasone. Anti-MOG antibody titer at the 6-month follow-up was negative. This case suggests that primary EBV infection would trigger anti-MOG antibody-positive ADEM. Adult ADEM patients can be positive for anti-MOG antibody, the titers of which correlate well with the neurological symptoms.

Autoimmune encephalopathies

PubMed Central

Leypoldt, Frank; Armangue, Thaís; Dalmau, Josep

2014-01-01

Over the last 10 years the continual discovery of novel forms of encephalitis associated with antibodies to cell-surface or synaptic proteins has changed the paradigms for diagnosing and treating disorders that were previously unknown or mischaracterized. We review here the process of discovery, the symptoms, and the target antigens of twelve autoimmune encephatilic disorders, grouped by syndromes and approached from a clinical perspective. Anti-NMDAR encephalitis, several subtypes of limbic encephalitis, stiff-person spectrum disorders, and other autoimmune encephalitides that result in psychosis, seizures, or abnormal movements are described in detail. We include a novel encephalopathy with prominent sleep dysfunction that provides an intriguing link between chronic neurodegeneration and cell-surface autoimmunity (IgLON5). Some of the caveats of limited serum testing are outlined. In addition, we review the underlying cellular and synaptic mechanisms that for some disorders confirm the antibody pathogenicity. The multidisciplinary impact of autoimmune encephalitis has been expanded recently by the discovery that herpes simplex encephalitis is a robust trigger of synaptic autoimmunity, and that some patients may develop overlapping syndromes, including anti-NMDAR encephalitis and neuromyelitis optica or other demyelinating diseases. PMID:25315420

Channelopathies

PubMed Central

Kim, June-Bum

2014-01-01

Channelopathies are a heterogeneous group of disorders resulting from the dysfunction of ion channels located in the membranes of all cells and many cellular organelles. These include diseases of the nervous system (e.g., generalized epilepsy with febrile seizures plus, familial hemiplegic migraine, episodic ataxia, and hyperkalemic and hypokalemic periodic paralysis), the cardiovascular system (e.g., long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia), the respiratory system (e.g., cystic fibrosis), the endocrine system (e.g., neonatal diabetes mellitus, familial hyperinsulinemic hypoglycemia, thyrotoxic hypokalemic periodic paralysis, and familial hyperaldosteronism), the urinary system (e.g., Bartter syndrome, nephrogenic diabetes insipidus, autosomal-dominant polycystic kidney disease, and hypomagnesemia with secondary hypocalcemia), and the immune system (e.g., myasthenia gravis, neuromyelitis optica, Isaac syndrome, and anti-NMDA [N-methyl-D-aspartate] receptor encephalitis). The field of channelopathies is expanding rapidly, as is the utility of molecular-genetic and electrophysiological studies. This review provides a brief overview and update of channelopathies, with a focus on recent advances in the pathophysiological mechanisms that may help clinicians better understand, diagnose, and develop treatments for these diseases. PMID:24578711

Pattern Recognition of the Multiple Sclerosis Syndrome

PubMed Central

Stewart, Renee; Healey, Kathleen M.

2017-01-01

During recent decades, the autoimmune disease neuromyelitis optica spectrum disorder (NMOSD), once broadly classified under the umbrella of multiple sclerosis (MS), has been extended to include autoimmune inflammatory conditions of the central nervous system (CNS), which are now diagnosable with serum serological tests. These antibody-mediated inflammatory diseases of the CNS share a clinical presentation to MS. A number of practical learning points emerge in this review, which is geared toward the pattern recognition of optic neuritis, transverse myelitis, brainstem/cerebellar and hemispheric tumefactive demyelinating lesion (TDL)-associated MS, aquaporin-4-antibody and myelin oligodendrocyte glycoprotein (MOG)-antibody NMOSD, overlap syndrome, and some yet-to-be-defined/classified demyelinating disease, all unspecifically labeled under MS syndrome. The goal of this review is to increase clinicians’ awareness of the clinical nuances of the autoimmune conditions for MS and NMSOD, and to highlight highly suggestive patterns of clinical, paraclinical or imaging presentations in order to improve differentiation. With overlay in clinical manifestations between MS and NMOSD, magnetic resonance imaging (MRI) of the brain, orbits and spinal cord, serology, and most importantly, high index of suspicion based on pattern recognition, will help lead to the final diagnosis. PMID:29064441

New developments in the treatment of optic neuritis

PubMed Central

Jenkins, Thomas M; Toosy, Ahmed T

2010-01-01

Acute optic neuritis (ON) has various etiologies. The most common presentation is inflammatory, demyelinating, idiopathic, or “typical” ON, which may be associated with multiple sclerosis. This must be differentiated from “atypical” causes of ON, which differ in their clinical presentation, natural history, management, and prognosis. Clinical “red flags” for an atypical cause of ON include absent or persistent pain, exudates and hemorrhages on fundoscopy, very severe, bilateral, or progressive visual loss, and failure to recover. In typical ON, steroids shorten the duration of the attack, but do not influence visual outcome. This is in contrast to atypical ON associated with conditions such as sarcoidosis and neuromyelitis optica, which require aggressive immunosuppression and sometimes plasma exchange. The visual prognosis of typical ON is generally good. The prognosis in atypical ON is more variable. New developments aimed at designing better treatments for patients who fail to recover are discussed, focusing on recent research elucidating mechanisms of damage and recovery in ON. Future therapeutic directions may include enhancing repair processes, such as remyelination or adaptive neuroplasticity, or alternative methods of immunomodulation. Pilot studies investigating the safety and proof-of-principle of stem cell treatment are currently underway. PMID:28539768

Distinct brain imaging characteristics of autoantibody-mediated CNS conditions and multiple sclerosis.

PubMed

Jurynczyk, Maciej; Geraldes, Ruth; Probert, Fay; Woodhall, Mark R; Waters, Patrick; Tackley, George; DeLuca, Gabriele; Chandratre, Saleel; Leite, Maria I; Vincent, Angela; Palace, Jacqueline

2017-03-01

Brain imaging characteristics of MOG antibody disease are largely unknown and it is unclear whether they differ from those of multiple sclerosis and AQP4 antibody disease. The aim of this study was to identify brain imaging discriminators between those three inflammatory central nervous system diseases in adults and children to support diagnostic decisions, drive antibody testing and generate disease mechanism hypotheses. Clinical brain scans of 83 patients with brain lesions (67 in the training and 16 in the validation cohort, 65 adults and 18 children) with MOG antibody (n = 26), AQP4 antibody disease (n = 26) and multiple sclerosis (n = 31) recruited from Oxford neuromyelitis optica and multiple sclerosis clinical services were retrospectively and anonymously scored on a set of 29 predefined magnetic resonance imaging features by two independent raters. Principal component analysis was used to perform an overview of patients without a priori knowledge of the diagnosis. Orthogonal partial least squares discriminant analysis was used to build models separating diagnostic groups and identify best classifiers, which were then tested on an independent cohort set. Adults and children with MOG antibody disease frequently had fluffy brainstem lesions, often located in pons and/or adjacent to fourth ventricle. Children across all conditions showed more frequent bilateral, large, brainstem and deep grey matter lesions. MOG antibody disease spontaneously separated from multiple sclerosis but overlapped with AQP4 antibody disease. Multiple sclerosis was discriminated from MOG antibody disease and from AQP4 antibody disease with high predictive values, while MOG antibody disease could not be accurately discriminated from AQP4 antibody disease. Best classifiers between MOG antibody disease and multiple sclerosis were similar in adults and children, and included ovoid lesions adjacent to the body of lateral ventricles, Dawson's fingers, T1 hypointense lesions (multiple

Fiber-optic components for optical communicatios and sensing =

NASA Astrophysics Data System (ADS)

Marques, Carlos Alberto Ferreira

Nos ultimos anos, a Optoelectronica tem sido estabelecida como um campo de investigacao capaz de conduzir a novas solucoes tecnologicas. As conquistas abundantes no campo da optica e lasers, bem como em comunicacoes opticas tem sido de grande importancia e desencadearam uma serie de inovacoes. Entre o grande numero de componentes opticos existentes, os componentes baseados em fibra optica sao principalmente relevantes devido a sua simplicidade e a elevada de transporte de dados da fibra optica. Neste trabalho foi focado um destes componentes opticos: as redes de difraccao em fibra optica, as quais tem propriedades opticas de processamento unicas. Esta classe de componentes opticos e extremamente atraente para o desenvolvimento de dispositivos de comunicacoes opticas e sensores. O trabalho comecou com uma analise teorica aplicada a redes em fibra e foram focados os metodos de fabricacao de redes em fibra mais utilizados. A inscricao de redes em fibra tambem foi abordado neste trabalho, onde um sistema de inscricao automatizada foi implementada para a fibra optica de silica, e os resultados experimentais mostraram uma boa aproximacao ao estudo de simulacao. Tambem foi desenvolvido um sistema de inscricao de redes de Bragg em fibra optica de plastico. Foi apresentado um estudo detalhado da modulacao acustico-optica em redes em fibra optica de silica e de plastico. Por meio de uma analise detalhada dos modos de excitacao mecanica aplicadas ao modulador acustico-optico, destacou-se que dois modos predominantes de excitacao acustica pode ser estabelecidos na fibra optica, dependendo da frequencia acustica aplicada. Atraves dessa caracterizacao, foi possivel desenvolver novas aplicacoes para comunicacoes opticas. Estudos e implementacao de diferentes dispositivos baseados em redes em fibra foram realizados, usando o efeito acustico-optico e o processo de regeneracao em fibra optica para varias aplicacoes tais como rapido multiplexador optico add-drop, atraso de grupo

Helicobacter pylori and autoimmune disease: Cause or bystander

PubMed Central

Smyk, Daniel S; Koutsoumpas, Andreas L; Mytilinaiou, Maria G; Rigopoulou, Eirini I; Sakkas, Lazaros I; Bogdanos, Dimitrios P

2014-01-01

Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and a major risk factor for gastric cancer. This pathogen has also been considered a potential trigger of gastric autoimmunity, and in particular of autoimmune gastritis. However, a considerable number of reports have attempted to link H. pylori infection with the development of extra-gastrointestinal autoimmune disorders, affecting organs not immediately relevant to the stomach. This review discusses the current evidence in support or against the role of H. pylori as a potential trigger of autoimmune rheumatic and skin diseases, as well as organ specific autoimmune diseases. We discuss epidemiological, serological, immunological and experimental evidence associating this pathogen with autoimmune diseases. Although over one hundred autoimmune diseases have been investigated in relation to H. pylori, we discuss a select number of papers with a larger literature base, and include Sjögrens syndrome, rheumatoid arthritis, systemic lupus erythematosus, vasculitides, autoimmune skin conditions, idiopathic thrombocytopenic purpura, autoimmune thyroid disease, multiple sclerosis, neuromyelitis optica and autoimmune liver diseases. Specific mention is given to those studies reporting an association of anti-H. pylori antibodies with the presence of autoimmune disease-specific clinical parameters, as well as those failing to find such associations. We also provide helpful hints for future research. PMID:24574735

Recurrent longitudinal extensive transverse myelitis in a neuro-Behçet syndrome treated with infliximab

PubMed Central

Uygunoğlu, Uğur; Pasha, Maarya; Saip, Sabahattin; Siva, Aksel

2015-01-01

Background Spinal cord involvement is not common, but can be seen in neuro-Behçet's syndrome (NBS). The major site of involvement is the cervical spinal cord with the myelitis-like inflammatory lesions continuing more than two segments, and extending to the brainstem. Case A 30-year-old male patient who has been followed with a diagnosis of Behçet's syndrome admitted to our neurology department clinically and radiologically suggestive of recurrent and extensive longitudinal myelitis. His anti-aquaporine antibody was negative. Because of insufficient effect of azathioprine, cyclophosphamide, and corticosteroids, infliximab was started. His clinical and radiological status is stationary for 3 years under infliximab treatment. Discussion Myelitis such as that occurring in our patient may have a similar presentation like neuromyelitis optica (NMO), which should therefore be included in differential diagnosis. Myelitis observed in both NMO and NBS shows spinal cord lesions longer than three or more vertebrae. Anti-aquaporine antibody must be evaluated in all patients presenting with longitudinal myelitis. Anti-tumor necrosis factor agent infliximab might be an alternative treatment in severe form of NBS such as myelitis. Conclusion In our case, successful treatment of recurrent and extensive longitudinal transverse myelitis in NBS with infliximab was demonstrated. PMID:24673549

High Spatial Resolution Imaging Mass Spectrometry of Human Optic Nerve Lipids and Proteins

NASA Astrophysics Data System (ADS)

Anderson, David M. G.; Spraggins, Jeffrey M.; Rose, Kristie L.; Schey, Kevin L.

2015-06-01

The human optic nerve carries signals from the retina to the visual cortex of the brain. Each optic nerve is comprised of approximately one million nerve fibers that are organized into bundles of 800-1200 fibers surrounded by connective tissue and supportive glial cells. Damage to the optic nerve contributes to a number of blinding diseases including: glaucoma, neuromyelitis optica, optic neuritis, and neurofibromatosis; however, the molecular mechanisms of optic nerve damage and death are incompletely understood. Herein we present high spatial resolution MALDI imaging mass spectrometry (IMS) analysis of lipids and proteins to define the molecular anatomy of the human optic nerve. The localization of a number of lipids was observed in discrete anatomical regions corresponding to myelinated and unmyelinated nerve regions as well as to supporting connective tissue, glial cells, and blood vessels. A protein fragment from vimentin, a known intermediate filament marker for astrocytes, was observed surrounding nerved fiber bundles in the lamina cribrosa region. S100B was also found in supporting glial cell regions in the prelaminar region, and the hemoglobin alpha subunit was observed in blood vessel areas. The molecular anatomy of the optic nerve defined by MALDI IMS provides a firm foundation to study biochemical changes in blinding human diseases.

The contemporary spectrum of multiple sclerosis misdiagnosis: A multicenter study.

PubMed

Solomon, Andrew J; Bourdette, Dennis N; Cross, Anne H; Applebee, Angela; Skidd, Philip M; Howard, Diantha B; Spain, Rebecca I; Cameron, Michelle H; Kim, Edward; Mass, Michele K; Yadav, Vijayshree; Whitham, Ruth H; Longbrake, Erin E; Naismith, Robert T; Wu, Gregory F; Parks, Becky J; Wingerchuk, Dean M; Rabin, Brian L; Toledano, Michel; Tobin, W Oliver; Kantarci, Orhun H; Carter, Jonathan L; Keegan, B Mark; Weinshenker, Brian G

2016-09-27

To characterize patients misdiagnosed with multiple sclerosis (MS). Neurologists at 4 academic MS centers submitted data on patients determined to have been misdiagnosed with MS. Of 110 misdiagnosed patients, 51 (46%) were classified as "definite" and 59 (54%) "probable" misdiagnoses according to study definitions. Alternate diagnoses included migraine alone or in combination with other diagnoses 24 (22%), fibromyalgia 16 (15%), nonspecific or nonlocalizing neurologic symptoms with abnormal MRI 13 (12%), conversion or psychogenic disorders 12 (11%), and neuromyelitis optica spectrum disorder 7 (6%). Duration of misdiagnosis was 10 years or longer in 36 (33%) and an earlier opportunity to make a correct diagnosis was identified for 79 patients (72%). Seventy-seven (70%) received disease-modifying therapy and 34 (31%) experienced unnecessary morbidity because of misdiagnosis. Four (4%) participated in a research study of an MS therapy. Leading factors contributing to misdiagnosis were consideration of symptoms atypical for demyelinating disease, lack of corroborative objective evidence of a CNS lesion as satisfying criteria for MS attacks, and overreliance on MRI abnormalities in patients with nonspecific neurologic symptoms. Misdiagnosis of MS leads to unnecessary and potentially harmful risks to patients. Misinterpretation and misapplication of MS clinical and radiographic diagnostic criteria are important contemporary contributors to misdiagnosis. © 2016 American Academy of Neurology.

Comparison of 6-mercaptopurine with 6-thioguanine for the analysis of thiopurine S-methyltransferase activity in human erythrocyte by LC-MS/MS.

PubMed

Mei, Shenghui; Li, Xindi; Gong, Xiaoqing; Zhang, Xiaoyi; Li, Xingang; Yang, Li; Zhu, Leting; Zhou, Heng; Liu, Yonghong; Zhou, Anna; Zhang, Xinghu; Zhao, Zhigang

2017-09-01

Thiopurines (TPDs) are first-line drugs in treating neuromyelitis optica spectrum disorders (NMOSD). Evaluation of thiopurine S-methyltransferase activity (TPMT), a major determinant of TPD toxicity, before TPD treatment using 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) as substrate was suggested. However, the equivalent of the two substrates in TPMT activity evaluation was unknown, and an alternative substrate was required in TPMT activity evaluation in patients who were already taking 6-MP or 6-TG. Before evaluating the agreement of 6-MP and 6-TG in TPMT activity measurement in patients with NMOSD, the affinity of the two substrates for the active center of TPMT should be established. A computer-based simulation indicated that 6-MP and 6-TG had similar affinities for the two active sites of TPMT. According to the guidelines, an LC-MS/MS method was developed and validated to evaluate the TPMT activity in human erythrocyte hemolysate using 6-MP or 6-TG as substrates via 1 h incubation at 37°C. The method was applied in 81 patients with NMOSD. Evaluated by Bland-Altman plot, 6-methylmercaptopurine and 6-methylthioguanine represented TPMT activities were in agreement with each other. Further studies are warranted to confirm the results. Copyright © 2017 John Wiley & Sons, Ltd.

Disturbed Glucose Metabolism in Rat Neurons Exposed to Cerebrospinal Fluid Obtained from Multiple Sclerosis Subjects

PubMed Central

Mathur, Deepali; María-Lafuente, Eva; Ureña-Peralta, Juan R.; Sorribes, Lucas; Hernández, Alberto; Casanova, Bonaventura; López-Rodas, Gerardo; Coret-Ferrer, Francisco; Burgal-Marti, Maria

2017-01-01

Axonal damage is widely accepted as a major cause of permanent functional disability in Multiple Sclerosis (MS). In relapsing-remitting MS, there is a possibility of remyelination by myelin producing cells and restoration of neurological function. The purpose of this study was to delineate the pathophysiological mechanisms underpinning axonal injury through hitherto unknown factors present in cerebrospinal fluid (CSF) that may regulate axonal damage, remyelinate the axon and make functional recovery possible. We employed primary cultures of rat unmyelinated cerebellar granule neurons and treated them with CSF obtained from MS and Neuromyelitis optica (NMO) patients. We performed microarray gene expression profiling to study changes in gene expression in treated neurons as compared to controls. Additionally, we determined the influence of gene-gene interaction upon the whole metabolic network in our experimental conditions using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) program. Our findings revealed the downregulated expression of genes involved in glucose metabolism in MS-derived CSF-treated neurons and upregulated expression of genes in NMO-derived CSF-treated neurons. We conclude that factors in the CSF of these patients caused a perturbation in metabolic gene(s) expression and suggest that MS appears to be linked with metabolic deformity. PMID:29267205

Viruses and Multiple Sclerosis

PubMed Central

Owens, Gregory P.; Gilden, Don; Burgoon, Mark P.; Yu, Xiaoli; Bennett, Jeffrey L.

2012-01-01

Multiple sclerosis (MS) is a chronic demyelinating disorder of unknown etiology, possibly caused by a virus or virus-triggered immunopathology. The virus might reactivate after years of latency and lyse oligodendrocytes, as in progressive multifocal leukoencephalopathy, or initiate immunopathological demyelination, as in animals infected with Theiler’s murine encephalomyelitis virus or coronaviruses. The argument for a viral cause of MS is supported by epidemiological analyses and studies of MS in identical twins, indicating that disease is acquired. However, the most important evidence is the presence of bands of oligoclonal IgG (OCBs) in MS brain and CSF that persist throughout the lifetime of the patient. OCBs are found almost exclusively in infectious CNS disorders, and antigenic targets of OCBs represent the agent that causes disease. Here, the authors review past attempts to identify an infectious agent in MS brain cells and discuss the promise of using recombinant antibodies generated from clonally expanded plasma cells in brain and CSF to identify disease-relevant antigens. They show how this strategy has been used successfully to analyze antigen specificity in subacute sclerosing panencephalitis, a chronic encephalitis caused by measles virus, and in neuromyelitis optica, a chronic autoimmune demyelinating disease produced by antibodies directed against the aquaporin-4 water channel. PMID:22130640

Evaluation of aquaporin-4 antibody assays

PubMed Central

Waters, Patrick J.; Pittock, Sean J.; Bennett, Jeffrey L.; Jarius, Sven; Weinshenker, Brian G.; Wingerchuk, Dean M.

2015-01-01

Aquaporin-4 (AQP4) is a water channel protein that is most highly, but not exclusively, expressed in the central nervous system. In 2005 AQP4 was shown to be the antigenic target of neuromyelitis optica-immunoglobulin G (NMO-IgG, or AQP4-IgG), an antibody found specifically in patients with NMO and in formes frustes of NMO, such as longitudinally extensive transverse myelitis (LETM) or optic neuritis (ON). This discovery facilitated the clinical, pathological, and radiological distinction of NMO and the spectrum of NMO-related disorders from classical multiple sclerosis. In addition to its use as a diagnostic tool, AQP4-IgG predicts a high risk of relapse in patients with a clinically isolated syndrome of either LETM or ON. As disability in NMO is attack-related, early diagnosis and treatment are predicted to have a major effect on long-term disability. Thus, the importance of sensitive and specific assays to detect AQP4-IgG cannot be overstated. Both academic institutions and commercial companies have developed assays to identify AQP4-IgG in patients’ sera or cerebrospinal fluid. Both AQP4 isoforms from different species have been used as the antigenic target in the form of frozen tissue sections in indirect immunofluorescence assays, partially purified protein for fluorescence immunoprecipitation assay, radioimmunoprecipita-tion assay or enzyme-linked immunosorbent assay, or transfected into cells for cell based assays or flow cytometry. We carried out a systematic review of the literature reporting different methodologies used to identify AQP4-IgG, examine whether longitudinal AQP4-IgG titers predict relapses in seropositive patients, and attempt to establish a reasonable timeframe for retesting negative serum samples. PMID:27840658

Demyelinating diseases in Asia.

PubMed

Ochi, Hirofumi; Fujihara, Kazuo

2016-06-01

The present review aims to discuss the recent advances in inflammatory demyelinating diseases of the central nervous system in Asia. Prevalence of multiple sclerosis (MS) in Asia is lower than that in Western countries, although it has been increasing recently. Meanwhile, there seems to be no major difference in neuromyelitis optica (NMO) prevalence in various regions or ethnicities. Thus, the ratios of NMO/NMO spectrum disorder (NMOSD) to MS are higher in Asia as compared with Western countries, indicating that the differential diagnosis between NMO/NMOSD and MS is a major challenge in Asia. Although the detection of aquaporin-4 (AQP4)-antibody is critical in distinguishing NMO/NMOSD from MS, some patients with NMO/NMOSD phenotype are seronegative for AQP4-antibody, and a fraction of those patients possess autoantibody against myelin oligodendrocyte glycoprotein. The clinical profile of Asian MS seems to be essentially similar to that in Western MS after careful exclusion of NMO/NMOSD, although some unique genetic and/or environmental factors may modify the disease in Asians. MS prevalence has been low but is increasing in Asia. In contrast, NMO/NMOSD prevalence seems relatively constant in the world. Asian MS is not fundamentally different from Western MS, but some genetic and/or environmental differences may cause some features unique to Asian patients.

[Pathomechanism of Autoantibody Production in the Nervous System Diseases].

PubMed

Shimizu, Fumitaka; Kanda, Takashi

2018-04-01

Antibodies to different brain and peripheral nerve proteins have recently been found to be associated with several different autoimmune diseases. They can bind to either neuronal or non-neuronal antigens and may have a pathogenic role by themselves or in synergy with other inflammatory mediators after penetrating the blood-brain barrier or the blood-nerve barrier. In this review, we will describe the association with the impairment of immune tolerance, innate immunity, and autoantibody production of myasthenia gravis (MG), systemic lupus erythematosus (SLE), and Guillain-Barré syndrome (GBS). Impairment of central tolerance, which is characterized by the repertoire selection of immature T-lymphocytes in the thymus, is seen in patients with MG who are positive for anti-Ach R antibodies. Impairment of peripheral tolerance due to activation of autoreactive T-cells and suppression of regulatory T-cells is seen in SLE. In addition, molecular mimicry between the lipooligosaccharides of Campylobacter jejuni and gangliosides of the peripheral nerves results in the production of anti-gangliosides antibodies in GBS. Next, we will describe the antibody-mediated pathology in neuromyelitis optica and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. The binding of anti-aquaporin-4 antibodies or anti-NMDAR antibodies to their respective targets initiates target internalization and complement- or antibody-dependent cellular cytotoxicity of the target cells. Further understanding of antibody-mediated pathology may suggest novel therapeutic strategies.

Enhanced accumulation of Kir4.1 protein, but not mRNA, in a murine model of cuprizone-induced demyelination.

PubMed

Nakajima, Mitsunari; Kawamura, Takuya; Tokui, Ryuji; Furuta, Kohei; Sugino, Mami; Nakanishi, Masayuki; Okuyama, Satoshi; Furukawa, Yoshiko

2013-11-06

Two channel proteins, inwardly rectifying potassium channel 4.1 (Kir4.1) and water channel aquaporin-4 (AQP4), were recently identified as targets of an autoantibody response in patients with multiple sclerosis and neuromyelitis optica, respectively. In the present study, we examined the expression patterns of Kir4.1 and AQP4 in a mouse model of demyelination induced by cuprizone, a copper chelator. Demyelination was confirmed by immunohistochemistry using an anti-proteolipid protein antibody in various brain regions, including the corpus callosum, of cuprizone-fed mice. Activation of microglial and astroglial cells was also confirmed by immunohistochemistry, using an anti-ionized calcium binding adapter molecule and a glial fibrillary acidic protein antibody. Western blot analysis revealed the induction of Kir4.1 protein, but not AQP4, in the cortex of cuprizone-fed mice. Immunohistochemical analysis confirmed the Kir4.1 protein induction in microvessels of the cerebral cortex. Real-time polymerase chain reaction analysis revealed that mRNA levels of Kir4.1 and AQP4 in the cortex did not change during cuprizone administration. These findings suggest that enhanced accumulation of Kir4.1 protein in the brain with an inflammatory condition facilitates the autoantibody formation against Kir4.1 in patients with multiple sclerosis. © 2013 Published by Elsevier B.V.

Baseline demographics, clinical features, and treatment protocols of 240 patients with optic neuropathy: experiences from a neuro-ophthalmological clinic in the Aegean region of Turkey.

PubMed

Karti, Omer; Karti, Dilek Top; Kilic, İlay Hilal; Gokcay, Figen; Celebisoy, Nese

2017-12-19

To analyze the demographic patterns, clinical characteristics, and treatment protocols of optic neuropathies. The hospital data of patients with optic neuropathy admitted to the Department of Neuro-ophthalmology in a tertiary referral center in Turkey between January 2010 to January 2017 were retrospectively analyzed. Demographic patterns, clinical features, treatment protocols, and the natural disease courses were assessed. The total number of patients with optic neuropathy seen over this period was 240, which consist of 43 with idiopathic optic neuritis (17.9%), 40 with multiple sclerosis-related optic neuritis (16.7%), 12 with chronic relapsing inflammatory optic neuritis (5.0%), 12 with atypical optic neuritis (5.0%), 11 with neuromyelitis optica spectrum disorders-related optic neuritis (4.6%), 90 with non-arteritic ischemic optic neuropathy (37.5%), 4 with arteritic ischemic optic neuropathy (1.7%), 10 with traumatic optic neuropathy (4.1%), 6 with compressive optic neuropathy (2.5%), and 12 with mitochondrial optic neuropathy [9 with toxic optic neuropathy (3.7%) and 3 with Leber's hereditary optic neuropathy (1.2%)]. There were 101 males (42%) and 139 females (58%). The mean age was 43.34 ± 15.86 years. This study reported the demographics, clinical characteristics, and treatment protocols of optic neuropathies in a neuro-ophthalmology specialty clinic at a tertiary referral center in Turkey during the past decade. The data may be useful in assessing the global status of optic neuropathies.

The binding property of a monoclonal antibody against the extracellular domains of aquaporin-4 directs aquaporin-4 toward endocytosis.

PubMed

Huang, Ping; Takai, Yoshiki; Kusano-Arai, Osamu; Ramadhanti, Julia; Iwanari, Hiroko; Miyauchi, Takayuki; Sakihama, Toshiko; Han, Jing-Yan; Aoki, Masashi; Hamakubo, Takao; Fujihara, Kazuo; Yasui, Masato; Abe, Yoichiro

2016-09-01

Neuromyelitis optica (NMO), an autoimmune disease of the central nervous system, is characterized by an autoantibody called NMO-IgG that recognizes the extracellular domains (ECDs) of aquaporin-4 (AQP4). In this study, monoclonal antibodies (mAbs) against the ECDs of mouse AQP4 were established by a baculovirus display method. Two types of mAb were obtained: one (E5415A) recognized both M1 and M23 isoforms, and the other (E5415B) almost exclusively recognized the square-array-formable M23 isoform. While E5415A enhanced endocytosis of both M1 and M23, followed by degradation in cells expressing AQP4, including astrocytes, E5415B did so to a much lesser degree, as determined by live imaging using fluorescence-labeled antibodies and by Western blotting of lysate of cells treated with these mAbs. E5415A promoted cluster formation of AQP4 on the cell surface prior to endocytosis as determined by immunofluorescent microscopic observation of bound mAbs to astrocytes as well as by Blue native PAGE analysis of AQP4 in the cells treated with the mAbs. These observations clearly indicate that an anti-AQP4-ECDs antibody possessing an ability to form a large cluster of AQP4 by cross-linking two or more tetramers outside the AQP4 arrays enhances endocytosis and the subsequent lysosomal degradation of AQP4.

Evaluation of idiopathic transverse myelitis revealing specific myelopathy diagnoses.

PubMed

Zalewski, Nicholas L; Flanagan, Eoin P; Keegan, B Mark

2018-01-09

To evaluate specific myelopathy diagnoses made in patients with suspected idiopathic transverse myelitis (ITM). A total of 226 patients 18 years and older were referred to Mayo Clinic Neurology for suspected ITM from December 1, 2010, to December 31, 2015. Electronic medical records were reviewed for detailed clinical presentation and course, laboratory and electrophysiologic investigations, and neuroimaging to determine the etiology. Current diagnostic criteria for ITM and alternative myelopathy diagnoses were applied. All cases where any discrepancy was suspected from the final reported clinical diagnosis were reviewed by each author and a consensus final diagnosis was made. The diagnostic criteria for ITM were met in 41 of 226 patients (18.1%). In 158 patients (69.9%), an alternative specific myelopathy diagnosis was made: multiple sclerosis or clinically isolated syndrome, 75; vascular myelopathy, 41; neurosarcoidosis, 12; neuromyelitis optica spectrum disorder, 12; myelin oligodendrocyte glycoprotein myelopathy, 5; neoplastic, 4; compressive, 3; nutritional, 3; infectious, 2; and other, 2. A myelopathy was not confirmed in 27 patients. Time from symptom onset to final clinical diagnosis in patients without ITM was a median of 9 months (range 0-288). Fifty-five patients (24%) required treatment changes according to their final clinical diagnosis. The majority of patients with suspected ITM have an alternative specific myelopathy diagnosis. A presumptive diagnosis of ITM can lead to premature diagnostic conclusions affecting patient treatment. Copyright © 2017 American Academy of Neurology.

Segmentation of microcystic macular edema in Cirrus OCT scans with an exploratory longitudinal study

NASA Astrophysics Data System (ADS)

Swingle, Emily K.; Lang, Andrew; Carass, Aaron; Al-Louzi, Omar; Saidha, Shiv; Prince, Jerry L.; Calabresi, Peter A.

2015-03-01

Microcystic macular edema (MME) is a term used to describe pseudocystic spaces in the inner nuclear layer (INL) of the human retina. It has been noted in multiple sclerosis (MS) as well as a variety of other diseases. The processes that lead to MME formation and their change over time have yet to be explained sufficiently. The low rate at which MME occurs within such diverse patient groups makes the identification and consistent quantification of this pathology important for developing patient-specific prognoses. MME is observed in optical coherence tomography (OCT) scans of the retina as changes in light reflectivity in a pattern suggestive of fluid accumulations called pseudocysts. Pseudocysts can be readily identified in higher signal-to-noise ratio (SNR) images, however pseudocysts can be indistinguishable from noise in lower SNR scans. In this work, we expand upon our earlier MME identification methods on Spectralis OCT scans to handle lower quality Cirrus OCT scans. Our approach uses a random forest classifier, trained on manual segmentation of ten subjects, to automatically detect MME. The algorithm has a true positive rate for MME identification of 0.95 and a Dice score of 0.79. We include a preliminary longitudinal study of three patients over four to five years to explore the longitudinal changes of MME. The patients with relapsing-remitting MS and neuromyelitis optica appear to have dynamic pseudocyst volumes, while the MME volume appears stable in the one patient with primary progressive MS.

A case of MOG antibody-positive bilateral optic neuritis and meningoganglionitis following a genital herpes simplex virus infection.

PubMed

Nakamura, Masataka; Iwasaki, Yuko; Takahashi, Toshiyuki; Kaneko, Kimihiko; Nakashima, Ichiro; Kunieda, Takenobu; Kaneko, Satoshi; Kusaka, Hirofumi

2017-10-01

Myelin oligodendrocyte glycoprotein (MOG) antibody-positive optic neuritis (ON) and myelitis are recognized as important differential diagnosis of aquaporin-4 (AQP4) antibody-positive neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD). Similar to NMO/NMOSD associated with AQP4 antibodies, preceding infections have been reported in patients with MOG antibody-positive ON. This is the first report of bilateral ON following a herpes simplex virus (HSV) infection associated with a positive MOG antibody. A 41-year-old man who initially presented with genital herpes developed allodynia in the Th2-Th5 and Th8-L2 areas, urinary retention, and painful visual loss in the left eye. Ophthalmological evaluation and brain magnetic resonance imaging (MRI) revealed bilateral ON. A spinal MRI showed leptomeningeal enhancement from the thoracic to lumbar vertebrae and abnormal enhancement of the L3 to S3 dorsal root ganglia without a change in intramedullary signals. Following treatment with acyclovir and steroid pulse, he fully recovered. Serum anti-AQP4 antibodies were negative, but anti-MOG antibodies were positive. Finally, he was diagnosed with MOG antibody-positive bilateral ON and meningoganglionitis following an HSV infection. Our case supports a relationship between anti-MOG antibodies and ON triggered by an HSV infection. Clinicians should thus consider testing for MOG antibodies in patients with post-infectious neurological symptoms due to an HSV infection. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical characteristics of optic neuritis in Hong Kong population: 10-year review.

PubMed

Choy, Bonnie Nga Kwan; Ng, Alex Lap Ki; Lai, Jimmy Shiu Ming

2018-04-01

To review the clinical course of adult patients with acute optic neuritis over 10 years in Hong Kong, and the results were compared with other studies among Asian and Caucasian patients. This study retrospectively analysed the clinical features of 38 adult patients (51 eyes) presented with optic neuritis in a Hong Kong hospital over 10 years (2001-2010). Optic neuritis had a female predominance (68%). The mean age of presentation was 40 years old. Disc swelling (39%) was more common compared to the optic neuritis treatment trial (ONTT). The recovery time ranged from no recovery to 5 years, with a mean of 6.0 months. However, vision continued to deteriorate despite initial improvement in 45% of patients. Only 11.8% of the eyes attained final visual acuity (VA) of 1.0 or better, while 31.4% had VA 0.1 or worse. Multiple sclerosis or neuromyelitis optica only occurred in 10.4% of patients. Three of our patients who did not receive any treatment showed faster recovery than the average. Optic neuritis in Hong Kong is mostly a clinically isolated syndrome. Our patients presented at a later age and showed a worse visual outcome. Corticosteroid according to ONTT protocol remained our mainstay of treatment although it did not benefit our patients as much as ONTT study. More work on the long-term prognosis and treatment strategies is worthwhile among Chinese optic neuritis patients.

A nationwide survey of pediatric acquired demyelinating syndromes in Japan

PubMed Central

Yamaguchi, Y.; Kira, R.; Ishizaki, Y.; Sakai, Y.; Sanefuji, M.; Ichiyama, T.; Oka, A.; Kishi, T.; Kimura, S.; Kubota, M.; Takanashi, J.; Takahashi, Y.; Tamai, H.; Natsume, J.; Hamano, S.; Hirabayashi, S.; Maegaki, Y.; Mizuguchi, M.; Minagawa, K.; Yoshikawa, H.; Kira, J.; Kusunoki, S.; Hara, T.

2016-01-01

Objective: To investigate the clinical and epidemiologic features of pediatric acquired demyelinating syndromes (ADS) of the CNS in Japan. Methods: We conducted a nationwide survey and collected clinical data on children with ADS aged 15 years or younger, who visited hospitals between 2005 and 2007. Results: Among 977 hospitals enrolled, 723 (74.0%) responded to our inquiries and reported a total of 439 patients as follows: 244 with acute disseminated encephalomyelitis (ADEM), 117 with multiple sclerosis (MS), 14 with neuromyelitis optica (NMO), and 64 with other ADS. We collected and analyzed detailed data from 204 cases, including those with ADEM (66), MS (58), and NMO (10). We observed the following: (1) the estimated annual incidence rate of pediatric ADEM in Japan was 0.40 per 100,000 children (95% confidence interval [CI], 0.34–0.46), with the lowest prevalence in the north; (2) the estimated prevalence rate of MS was 0.69 per 100,000 children (95% CI, 0.58–0.80), with the lowest prevalence in the south; (3) NMO in Japan was rare, with an estimated prevalence of 0.06 per 100,000 children (95% CI, 0.04–0.08); and (4) the sex ratio and mean age at onset varied by ADS type, and (5) male/female ratios correlated with ages at onset in each ADS group. Conclusions: Our results clarify the characteristic clinical features of pediatric ADS in the Japanese population. PMID:27742816

Microcystic macular oedema in optic neuropathy: case series and literature review.

PubMed

Kessel, Line; Hamann, Steffen; Wegener, Marianne; Tong, Jessica; Fraser, Clare L

2018-05-25

Cavitations in the inner nuclear layer associated with severe optic atrophy and loss of retinal ganglion cells have clinically been termed microcystic macular oedema (MME). We describe a case series of MME in patients of all ages but predominantly younger patients with a wide range of optic atrophies ranging from acute onset optic disc drusen associated ischemic optic neuropathy to slowly progressive disease as glaucoma. There were no physical distinctions between MME in different causes of optic atrophy suggesting a common causative mechanism. We reviewed the literature on MME and it appears that MME is associated with more severe visual loss, and is more common in hereditary optic neuropathies and neuro-myelitis optica spectrum disease rather than in patients with optic atrophy secondary to multiple sclerosis and glaucoma. Three main causative mechanisms have been proposed, including increased vitreal traction on the macular as the ganglion cells are lost. Others have suggested that trans-synaptic loss of cells in the inner nuclear layer causes formation of empty spaces or cavities. Finally, some have hypothesized a disturbance in the fluid homeostasis of the inner retina as Müller cells are lost or their function is impaired. There are no known treatments of MME. In conclusion, MME seems to be a marker of severe optic nerve atrophy irrespective of the underlying cause. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Measurement of soluble CD59 in CSF in demyelinating disease: Evidence for an intrathecal source of soluble CD59.

PubMed

Zelek, Wioleta M; Watkins, Lewis M; Howell, Owain W; Evans, Rhian; Loveless, Sam; Robertson, Neil P; Beenes, Marijke; Willems, Loek; Brandwijk, Ricardo; Morgan, B Paul

2018-02-01

CD59, a broadly expressed glycosylphosphatidylinositol-anchored protein, is the principal cell inhibitor of complement membrane attack on cells. In the demyelinating disorders, multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), elevated complement protein levels, including soluble CD59 (sCD59), were reported in cerebrospinal fluid (CSF). We compared sCD59 levels in CSF and matched plasma in controls and patients with MS, NMOSD and clinically isolated syndrome (CIS) and investigated the source of CSF sCD59 and whether it was microparticle associated. sCD59 was quantified using enzyme-linked immunosorbent assay (ELISA; Hycult; HK374-02). Patient and control CSF was subjected to western blotting to characterise anti-CD59-reactive materials. CD59 was localised by immunostaining and in situ hybridisation. CSF sCD59 levels were double those in plasma (CSF, 30.2 ng/mL; plasma, 16.3 ng/mL). Plasma but not CSF sCD59 levels differentiated MS from NMOSD, MS from CIS and NMOSD/CIS from controls. Elimination of microparticles confirmed that CSF sCD59 was not membrane anchored. CSF levels of sCD59 are not a biomarker of demyelinating diseases. High levels of sCD59 in CSF relative to plasma suggest an intrathecal source; CD59 expression in brain parenchyma was low, but expression was strong on choroid plexus (CP) epithelium, immediately adjacent the CSF, suggesting that this is the likely source.

Different patterns of longitudinal brain and spinal cord changes and their associations with disability progression in NMO and MS.

PubMed

Liu, Yaou; Duan, Yunyun; Huang, Jing; Ren, Zhuoqiong; Liu, Zheng; Dong, Huiqing; Weiler, Florian; Hahn, Horst K; Shi, Fu-Dong; Butzkueven, Helmut; Barkhof, Frederik; Li, Kuncheng

2018-01-01

To investigate the longitudinal spinal cord and brain changes in neuromyelitis optica (NMO) and multiple sclerosis (MS) and their associations with disability progression. We recruited 28 NMO, 22 MS, and 20 healthy controls (HC), who underwent both spinal cord and brain MRI at baseline. Twenty-five NMO and 20 MS completed 1-year follow-up. Baseline spinal cord and brain lesion loads, mean upper cervical cord area (MUCCA), brain, and thalamus volume and their changes during a 1-year follow-up were measured and compared between groups. All the measurements were also compared between progressive and non-progressive groups in NMO and MS. MUCCA decreased significantly during the 1-year follow-up in NMO not in MS. Percentage brain volume changes (PBVC) and thalamus volume changes in MS were significantly higher than NMO. MUCCA changes were significantly different between progressive and non-progressive groups in NMO, while baseline brain lesion volume and PBVC were associated with disability progression in MS. MUCCA changes during 1-year follow-up showed association with clinical disability in NMO. Spinal cord atrophy changes were associated with disability progression in NMO, while baseline brain lesion load and whole brain atrophy changes were related to disability progression in MS. • Spinal cord atrophy progression was observed in NMO. • Spinal cord atrophy changes were associated with disability progression in NMO. • Brain lesion and atrophy were related to disability progression in MS.

Clinical outcomes and predictive factors related to good outcomes in plasma exchange in severe attack of NMOSD and long extensive transverse myelitis: Case series and review of the literature.

PubMed

Aungsumart, Saharat; Apiwattanakul, Metha

2017-04-01

To investigate the predictive factors associated with good outcomes of plasma exchange in severe attacks through neuromyelitis optica spectrum disorder (NMOSD) and long extensive transverse myelitis (LETM). In addition, to review the literature of predictive factors associated with the good outcomes of plasma exchange in central nervous system inflammatory demyelinating diseases (CNS IDDs). Retrospective study in 27 episodes of severe acute attacks myelitis and optic neuritis in 24 patients, including 20 patients with NMOSD seropositive, 1 patient with NMOSD seronegative and 3 patients with LETM. Plasma exchange was performed, reflecting poor responses to high-dose intravenous methylprednisolone (IVMP) therapy. The outcomes of the present study were the functional outcome improvements at 6 months after plasma exchange. The predictive factors of good outcomes after plasma exchange were determined in this cohort, and additional factors reported in the literature were reviewed. Plasma exchange was performed in 16 spinal cord attacks and 11 attacks of optic neuritis. Twenty patients were female (83%). The median age of the patients at the time of plasma exchange was 41 years old. The median disease duration was 0.6 years. The AQP4-IgG status was positive in 20 patients (83%). Plasma exchange following IVMP therapy led to a significant improvement in 81% of the cases after 6 months of follow up. A baseline Expanded Disability Status Scale (EDSS) score ≤6 before the attack was associated with significant improvement at 6 months (p=0.02, OR 58.33, 95%CI 1.92-1770). In addition, we reviewed the evidence for factors associated with good outcomes of plasma exchange in CNS IDDs, classified according to pre-plasma exchange, post-plasma exchange, and radiological features. Plasma exchange following IVMP therapy is effective as a treatment for patients experiencing a severe attack of NMOSD or LETM. The factors associated with good outcomes after plasma exchange in CNS IDDs are

Changes of Colonic Bacterial Composition in Parkinson's Disease and Other Neurodegenerative Diseases.

PubMed

Gerhardt, Sara; Mohajeri, M Hasan

2018-06-01

In recent years evidence has emerged that neurodegenerative diseases (NDs) are strongly associated with the microbiome composition in the gut. Parkinson's disease (PD) is the most intensively studied neurodegenerative disease in this context. In this review, we performed a systematic evaluation of the published literature comparing changes in colonic microbiome in PD to the ones observed in other NDs including Alzheimer's disease (AD), multiple system atrophy (MSA), multiple sclerosis (MS), neuromyelitis optica (NMO) and amyotrophic lateral sclerosis (ALS). To enhance the comparability of different studies, only human case-control studies were included. Several studies showed an increase of Lactobacillus , Bifidobacterium , Verrucomicrobiaceae and Akkermansia in PD. A decrease of Faecalibacterium spp., Coprococcus spp., Blautia spp., Prevotella spp. and Prevotellaceae was observed in PD. On a low taxonomic resolution, like the phylum level, the changes are not disease-specific and are inconsistent. However, on a higher taxonomic resolution like genus or species level, a minor overlap was observed between PD and MSA, both alpha synucleinopathies. We show that standardization of sample collection and analysis is necessary for ensuring the reproducibility and comparability of data. We also provide evidence that assessing the microbiota composition at high taxonomic resolution reveals changes in relative abundance that may be specific to or characteristic of one disease or disease group, and might evolve discriminative power. The interactions between bacterial species and strains and the co-abundances must be investigated before assumptions about the effects of specific bacteria on the host can be made with certainty.

Computer-based diagnosis of illness in historical persons.

PubMed

Peters, T J

2013-01-01

Retrospective diagnosis of illness in historical figures is a popular but somewhat unreliable pastime due to the lack of detailed information and reliable reports about clinical features and disease progression. Modern computer-based diagnostic programmes have been used to supplement historical documents and accounts, offering new and more objective approaches to the retrospective investigations of the medical conditions of historical persons. In the case of King George III, modern technology has been used to strengthen the findings of previous reports rejecting the popular diagnosis of variegate porphyria in the King, his grandson Augustus d'Esté and his antecedent King James VI and I. Alternative diagnoses based on these programmes are indicated. The Operational Criteria in Studies of Psychotic Illness (OPCRIT) programme and the Young mania scale have been applied to the features described for George III and suggest a diagnosis of bipolar disorder. The neuro-diagnostic programme SimulConsult was applied to Augustus d'Esté and suggests a diagnosis of neuromyelitis optica rather than acute porphyria with secondarily multiple sclerosis, as proposed by others. James VI and I's complex medical history and the clinical features of his behavioural traits were also subjected to SimulConsult analysis; acute porphyria was rejected and the unexpected diagnosis of attenuated (mild) Lesch-Nyhan disease offered. A brief review of these approaches along with full reference listings to the methodology including validation are provided. Textual analysis of the written and verbal outputs of historical figures indicate possible future developments in the diagnosis of medical disorders in historical figures.

HYPOCRETIN/OREXIN AND NARCOLEPSY NEW BASIC AND CLINICAL INSIGHTS

PubMed Central

NISHINO, Seiji; OKURO, Masashi; KOTORII, Nozomu; ANEGAWA, Emiko; ISHIMARU, Yuji; MATSUMURA, Mari; KANBAYASHI, Takashi

2009-01-01

Narcolepsy is a chronic sleep disorder, characterized by excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, and sleep paralysis. Both sporadic (95%) and familial (5%) forms of narcolepsy exist in humans. The major pathophysiology of human narcolepsy has been recently discovered based on the discovery of narcolepsy genes in animals; the genes involved in the pathology of the hypocretin/orexin ligand and its receptor. Mutations in hypocretin-related genes are rare in humans, but hypocretin-ligand deficiency is found in a large majority of narcolepsy with cataplexy. Hypocretin ligand deficiency in human narcolepsy is likely due to the postnatal cell death of hypocretin neurons. Although tight association between human leukocyte antigen (HLA) association and human narcolepsy with cataplexy suggests an involvement of autoimmune mechanisms, this has not yet been proven. Hypocretin deficiency is also found in symptomatic cases of narcolepsy and EDS with various neurological conditions, including immune-mediated neurological disorders, such as Guillain-Barre syndrome, MA2-positive paraneoplastic syndrome and neuromyelitis optica (NMO) related disorder. These findings likely have significant clinical relevance and for understanding the mechanisms of hypocretin cell death and choice of treatment option. These series of discoveries in humans lead to the establishment of the new diagnostic test of narcolepsy (i.e. low cerebrospinal fluid [CSF] hypocretin-1 levels for narcolepsy with cataplexy and narcolepsy due to medical condition). Since a large majority of human narcolepsy patients are ligand deficient, hypocretin replacement therapy may be a promising new therapeutic option, and animal experiments using gene therapy and cell transplantations are in progress. PMID:19555382

Optic neuritis: Observation and experience at a tertiary care hospital in Qassim region, Saudi Arabia

PubMed Central

Alamgir, Mohammad Jawad; Ali, Syed Abrar; Hamdy, Nermin Aly; Khan, Moin Zafar; Mohammad, Elgamri E

2017-01-01

Objectives: Optic neuritis (ON) can occur in isolation or association with multiple sclerosis (MS) or neuromyelitis optica. ON, is seen more commonly in Caucasians and interaction is found to exist between ethnic origin and the latitude at which the patient grows up. At present limited information is available about the profile of ON in Saudi patients. We aimed to analyze the records of ON patients, in regard to their presentation, natural history, treatment outcome, and risk and association with MS. Whether, ON in Saudi patients behaves differently from the Western and Asian patients? Methods: In this retrospective observational study; we retrieved the data from the medical records of the patients with ON, who attended the ophthalmology and neurology services of King Fahad Specialist Hospital Buraidah, Al Qassim, Saudi Arabia, from period 2006 to 2012. Results: We recorded data of 60 patients of ON; 38 females (63.3%) and 22 males (36.7%). Color vision was affected in 66.7% of cases. Vision in the affected eye was 20/200 or worse in 74.97 % of our cases. Magnetic resonance imaging (MRI) brain revealed multiple lesions in 55% of cases; most of them developed MS on follow-up. Only 48.3% of patients had received systemic steroids. Vision improved in 85% of our cases. Conclusion: Most of our patients had idiopathic ON, and almost 85% had good visual recovery, in this regard our study is comparable with such studies done in other Asian countries. On the other hand, 55% of our patients had multiple MRI brain lesions, a high risk and association of MS, almost similar to the Western Europe and North American ON patients. PMID:29114192

Optic neuritis: Observation and experience at a tertiary care hospital in Qassim region, Saudi Arabia.

PubMed

Alamgir, Mohammad Jawad; Ali, Syed Abrar; Hamdy, Nermin Aly; Khan, Moin Zafar; Mohammad, Elgamri E

2017-01-01

Optic neuritis (ON) can occur in isolation or association with multiple sclerosis (MS) or neuromyelitis optica. ON, is seen more commonly in Caucasians and interaction is found to exist between ethnic origin and the latitude at which the patient grows up. At present limited information is available about the profile of ON in Saudi patients. We aimed to analyze the records of ON patients, in regard to their presentation, natural history, treatment outcome, and risk and association with MS. Whether, ON in Saudi patients behaves differently from the Western and Asian patients? In this retrospective observational study; we retrieved the data from the medical records of the patients with ON, who attended the ophthalmology and neurology services of King Fahad Specialist Hospital Buraidah, Al Qassim, Saudi Arabia, from period 2006 to 2012. We recorded data of 60 patients of ON; 38 females (63.3%) and 22 males (36.7%). Color vision was affected in 66.7% of cases. Vision in the affected eye was 20/200 or worse in 74.97 % of our cases. Magnetic resonance imaging (MRI) brain revealed multiple lesions in 55% of cases; most of them developed MS on follow-up. Only 48.3% of patients had received systemic steroids. Vision improved in 85% of our cases. Most of our patients had idiopathic ON, and almost 85% had good visual recovery, in this regard our study is comparable with such studies done in other Asian countries. On the other hand, 55% of our patients had multiple MRI brain lesions, a high risk and association of MS, almost similar to the Western Europe and North American ON patients.

Aquaporin-4 antibody titration in NMO patients treated with rituximab: A retrospective study.

PubMed

Valentino, Paola; Marnetto, Fabiana; Granieri, Letizia; Capobianco, Marco; Bertolotto, Antonio

2017-03-01

We undertook an observational retrospective study to investigate the usefulness of aquaporin-4 (AQP4) antibodies (Ab) titration in the management of patients with neuromyelitis optica (NMO) treated with rituximab (RTX) by studying (1) the correlation between AQP4-Ab titer and disease activity, (2) the influence of RTX on antibody levels, and (3) the association between AQP4-Ab levels and responsiveness to RTX. A cell-based assay was used for AQP4-Ab titration in 322 serum samples from 7 patients with NMO treated with RTX (median follow-up 65 months), according to a treatment-to-target approach. Serum samples were collected every month following standardized procedures. (1) In group analysis, AQP4-Ab titers correlated with the disease activity, showing higher titers during and preceding relapses than during remission. However, in individual analysis, an increase in AQP4-Ab titers and CD19+ B cells did not always precede a relapse. (2) A reduction of AQP4-Ab titers in the short-term and long-term period was observed during RTX treatment. (3) Reduction of AQP4-Ab titers was observed in responder patients both 3 months after RTX infusion and in the long-term follow-up. In one nonresponder patient, AQP4-Ab levels never decreased during the treatment period. Titration of AQP4-Abs could be useful in the clinical management of patients with NMO treated with RTX: titration before each reinfusion and 3 months after each reinfusion may provide information about responsiveness to RTX. Although a relationship among AQP4-Ab levels, disease activity, and response to RTX was observed, the usefulness of AQP4-Ab titration to predict relapses is limited.

Paediatric acquired demyelinating syndromes: incidence, clinical and magnetic resonance imaging features.

PubMed

Absoud, Michael; Lim, Ming J; Chong, Wui K; De Goede, Christian G; Foster, Katharine; Gunny, Roxana; Hemingway, Cheryl; Jardine, Philip E; Kneen, Rachel; Likeman, Marcus; Nischal, Ken K; Pike, Michael G; Sibtain, Naomi A; Whitehouse, William P; Cummins, Carole; Wassmer, Evangeline

2013-01-01

Changing trends in multiple sclerosis (MS) epidemiology may first be apparent in the childhood population affected with first onset acquired demyelinating syndromes (ADSs). We aimed to determine the incidence, clinical, investigative and magnetic resonance imaging (MRI) features of childhood central nervous system ADSs in the British Isles for the first time. We conducted a population active surveillance study. All paediatricians, and ophthalmologists (n = 4095) were sent monthly reporting cards (September 2009-September 2010). International Paediatric MS Study Group 2007 definitions and McDonald 2010 MS imaging criteria were used for acute disseminated encephalomyelitis (ADEM), clinically isolated syndrome (CIS) and neuromyelitis optica (NMO). Clinicians completed a standard questionnaire and provided an MRI copy for review. Card return rates were 90%, with information available for 200/222 positive notifications (90%). After exclusion of cases, 125 remained (age range 1.3-15.9), with CIS in 66.4%, ADEM in 32.0% and NMO in 1.6%. The female-to-male ratio in children older than 10 years (n = 63) was 1.52:1 (p = 0.045). The incidence of first onset ADS in children aged 1-15 years old was 9.83 per million children per year (95% confidence interval [CI] 8.18-11.71). A trend towards higher incidence rates of ADS in children of South Asian and Black ethnicity was observed compared with White children. Importantly, a number of MRI characteristics distinguished ADEM from CIS cases. Of CIS cases with contrast imaging, 26% fulfilled McDonald 2010 MS diagnostic criteria. We report the highest surveillance incidence rates of childhood ADS. Paediatric MS diagnosis at first ADS presentation has implications for clinical practice and clinical trial design.

Evidence-based guideline: clinical evaluation and treatment of transverse myelitis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

PubMed

Scott, T F; Frohman, E M; De Seze, J; Gronseth, G S; Weinshenker, B G

2011-12-13

To assess the evidence for diagnostic tests and therapies for transverse myelitis (TM) and make evidence-based recommendations. A review of the published literature from 1966 to March 2009 was performed, with evidence-based classification of relevant articles. Level B recommendations: neuromyelitis optica (NMO)-immunoglobulin G (IgG) antibodies should be considered useful to determine TM cause in patients presenting with clinical acute complete transverse myelitis (ACTM) features. The presence of NMO-IgG antibodies (aquaporin-4-specific antibodies) should be considered useful in determining increased TM recurrence risk. Level C recommendations: in suspected TM, distinction between ACTM or acute partial transverse myelitis may be considered useful to determine TM etiology and risk for relapse (more common with APTM). Age and gender may be considered useful to determine etiology in patients presenting with TM syndrome, with spinal infarcts seen more often in older patients and more female than male patients having TM due to multiple sclerosis (MS). Brain MRI characteristics consistent with those of MS may be considered useful to predict conversion to MS after a first partial TM episode. Longer spinal lesions extending over >3 vertebral segments may be considered useful in determining NMO vs MS. CSF examination for cells and oligoclonal bands may be considered useful to determine the cause of the TM syndrome. Plasma exchange may be considered in patients with TM who fail to improve after corticosteroid treatment. Rituximab may be considered in patients with TM due to NMO to decrease the number of relapses. Level U recommendations: there is insufficient evidence to support or refute the efficacy of other TM therapies or the usefulness of ethnicity to determine the cause of a subacute myelopathy.

Pain in patients with transverse myelitis and its relationship to aquaporin 4 antibody status.

PubMed

Kong, Yazhuo; Okoruwa, Helen; Revis, Jon; Tackley, George; Leite, Maria Isabel; Lee, Michael; Tracey, Irene; Palace, Jacqueline

2016-09-15

Pain in transverse myelitis has been poorly studied. The aim of the study was to investigate the relationship between transverse myelitis related pain and disability, quality of life, anxiety and depression, cognitive-affective states in neuromyelitis optica (NMO) patients and aquaporin4 antibody status (AQP4-Ab +ve as positive and AQP4-Ab -ve as negative). Transverse myelitis patients (44 in total; 29 AQP4-Ab +ve and 15 AQP4-Ab -ve) completed questionnaires including Pain Severity Index (PSI), Pain Catastrophising Scale (PCS), Hospital Anxiety and Depression Scale (HADS), Short Form-36 quality of life (SF-36 QOL). Clinical details such as disability, gender, age and spinal cord lesion type (short or long lesion) were noted. Correlation and multiple linear regression tests were performed using these clinical scores. Pain was found to be correlated strongly with quality of life in both groups but only correlated with disability in the AQP4-Ab +ve group. PCS, HADS and EDMUS were found to be highly correlated with pain severity using partial correlation, however, a stronger relationship between pain severity and PCS was found in the AQP4-Ab -ve group. Multiple regression analysis showed that pain severity was the most important factor for quality of life but not disability or anxiety and depression symptoms in the whole patient group. We confirm that pain is an important symptom of transverse myelitis and has more influence on quality of life than disability despite health services being predominantly focused on the latter. There may be different factors associated with pain between AQP4-Ab +ve and -ve patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Association between demyelinating disease and autoimmune rheumatic disease in a pediatric population.

PubMed

Amorim, Ana Luiza M; Cabral, Nadia C; Osaku, Fabiane M; Len, Claudio A; Oliveira, Enedina M L; Terreri, Maria Teresa

Multiple sclerosis (MS) and neuromyelitis optica (NMO) are demyelinating diseases of the central nervous system. Autoimmunity in patients with demyelinating disease and in their families has been broadly investigated and discussed. Recent studies show a higher incidence of rheumatic autoimmune diseases among adult patients with MS or NMO and their families, but there are no studies in the pediatric population. To evaluate an association of MS and NMO with autoimmune rheumatic diseases in pediatric patients. 22 patients younger than 21 years old with MS or NMO diagnosed before the age of 18 years were evaluated regarding epidemiological data, clinical presentation, association with autoimmune diseases, family history of autoimmune diseases, laboratory findings, imaging studies and presence of auto-antibodies. Among the patients studied, there was a prevalence of females (68.1%). The mean age of symptoms onset was 8 years and 9 months and the mean current age was 16 years and 4 months. Two patients (9%) had a history of associated autoimmune rheumatic disease: one case of juvenile dermatomyositis in a patient with NMO and another of systemic lupus erythematosus in a patient with MS. Three patients (13%) had a family history of autoimmunity in first-degree relatives. Antinuclear antibody was found positive in 80% of patients with NMO and 52% of patients with MS. About 15% of antinuclear antibody-positive patients were diagnosed with rheumatologic autoimmune diseases. Among patients with demyelinating diseases diagnosed in childhood included in this study there was a high frequency of antinuclear antibody positivity but a lower association with rheumatologic autoimmune diseases than that observed in studies conducted in adults. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

Study of the Generation of Intense Pulsed Electron Beams Using Glow Discharges

DTIC Science & Technology

1988-02-01

de Investigaciones Opticas, Rep. Argentina. (2) On leave from PROFET (UNCPBA) Programa de Fisica Experimental Tandil, Rep. Argentina. (3) Edwards... de Investigaciones Opticas, (CIC-BA) Rep. Argentina. Section III-D. Measurements of the plasma density andB. T. Szapiro is on leave from Programa de ...discussed. The radial profiles Szapiro was supported by a fellowship from the Universidad Nacional de show the presence of a high-current-density

Aquaporin-4 in brain and spinal cord oedema.

PubMed

Saadoun, S; Papadopoulos, M C

2010-07-28

Brain oedema is a major clinical problem produced by CNS diseases (e.g. stroke, brain tumour, brain abscess) and systemic diseases that secondarily affect the CNS (e.g. hyponatraemia, liver failure). The swollen brain is compressed against the surrounding dura and skull, which causes the intracranial pressure to rise, leading to brain ischaemia, herniation, and ultimately death. A water channel protein, aquaporin-4 (AQP4), is found in astrocyte foot processes (blood-brain border), the glia limitans (subarachnoid cerebrospinal fluid-brain border) and ependyma (ventricular cerebrospinal fluid-brain border). Experiments using mice lacking AQP4 or alpha syntrophin (which secondarily downregulate AQP4) showed that AQP4 facilitates oedema formation in diseases causing cytotoxic (cell swelling) oedema such as cerebral ischaemia, hyponatraemia and meningitis. In contrast, AQP4 facilitates oedema elimination in diseases causing vasogenic (vessel leak) oedema and therefore AQP4 deletion aggravates brain oedema produced by brain tumour and brain abscess. AQP4 is also important in spinal cord oedema. AQP4 deletion was associated with less cord oedema and improved outcome after compression spinal cord injury in mice. Here we consider the possible routes of oedema formation and elimination in the injured cord and speculate about the role of AQP4. Finally we discuss the role of AQP4 in neuromyelitis optica (NMO), an inflammatory demyelinating disease that produces oedema in the spinal cord and optic nerves. NMO patients have circulating AQP4 IgG autoantibody, which is now used for diagnosing NMO. We speculate how NMO-IgG might produce CNS inflammation, demyelination and oedema. Since AQP4 plays a key role in the pathogenesis of CNS oedema, we conclude that AQP4 inhibitors and activators may reduce CNS oedema in many diseases. Copyright (c) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Challenges in randomized controlled trials and emerging multiple sclerosis therapeutics.

PubMed

Huang, DeRen

2015-12-01

The remarkable global development of disease-modifying therapies (DMTs) specific for multiple sclerosis (MS) has significantly reduced the frequency of relapse, slowed the progression of disability, and improved the quality of life in patients with MS. With increasing numbers of approved DMTs, neurologists in North America and Europe are able to present multiple treatment options to their patients to achieve a better therapeutic outcome, and in many cases, no evidence of disease activity. MS patients have improved accessibility to various DMTs at no or minimal out-of-pocket cost. The ethical guidelines defined by the Edinburgh revision of the Declaration of Helsinki strongly discourage the use of placebo control groups in modern MS clinical trials. The use of an active comparator control group increases the number of participants in each group that is essential to achieve statistical significance, thus further increasing the difficulty of completing randomized controlled trials (RCTs) for the development of new MS therapies. There is evidence of a high prevalence of MS and a large number of patients in Asia. The belief of the existence of Asian types of MS that are distinct from Western types, and regulatory policies are among the reasons why DMTs are limited in most Asian countries. Lack of access to approved DMTs provides a good opportunity for clinical trials that are designed for the development of new MS therapies. Recently, data from RCTs have demonstrated excellent recruitment of participants and the completion of multi-nation and single-nation MS trials within this region. Recent studies using the McDonald MS diagnostic criteria carefully excluded patients with neuromyelitis optica (NMO) and NMO spectrum disorder, and demonstrated that patients with MS in Asia have clinical characteristics and treatment responses similar to those in Western countries.

Challenging AQP4 druggability for NMO-IgG antibody binding using molecular dynamics and molecular interaction fields.

PubMed

Mangiatordi, Giuseppe Felice; Alberga, Domenico; Siragusa, Lydia; Goracci, Laura; Lattanzi, Gianluca; Nicolotti, Orazio

2015-07-01

Neuromyelitis optica (NMO) is a multiple sclerosis-like immunopathology disease affecting optic nerves and the spinal cord. Its pathological hallmark is the deposition of a typical immunoglobulin, called NMO-IgG, against the water channel Aquaporin-4 (AQP4). Preventing NMO-IgG binding would represent a valuable molecular strategy for a focused NMO therapy. The recent observation that aspartate in position 69 (D69) is determinant for the formation of NMO-IgG epitopes prompted us to carry out intensive Molecular Dynamics (MD) studies on a number of single-point AQP4 mutants. Here, we report a domino effect originating from the point mutation at position 69: we find that the side chain of T62 is reoriented far from its expected position leaning on the lumen of the pore. More importantly, the strength of the H-bond interaction between L53 and T56, at the basis of the loop A, is substantially weakened. These events represent important pieces of a clear-cut mechanistic rationale behind the failure of the NMO-IgG binding, while the water channel function as well as the propensity to aggregate into OAPs remains unaltered. The molecular interaction fields (MIF)-based analysis of cavities complemented MD findings indicating a putative binding site comprising the same residues determining epitope reorganization. In this respect, docking studies unveiled an intriguing perspective to address the future design of small drug-like compounds against NMO. In agreement with recent experimental observations, the present study is the first computational attempt to elucidate NMO-IgG binding at the molecular level, as well as a first effort toward a less elusive AQP4 druggability. Copyright © 2015 Elsevier B.V. All rights reserved.

Aquaporin-4 antibodies in patients treated with natalizumab for suspected MS

PubMed Central

Gahlen, Anna; Trampe, Anne-Kathrin; Haupeltshofer, Steffen; Ringelstein, Marius; Aktas, Orhan; Berthele, Achim; Wildemann, Brigitte; Gold, Ralf; Jarius, Sven

2017-01-01

Objective: To evaluate (1) the frequency of aquaporin-4 antibody (AQP4-ab)-seropositive cases among patients treated with natalizumab (NAT) and previously diagnosed with MS (MSNAT) in a nationwide cohort, (2) the clinical course of NAT-treated AQP4-ab–seropositive neuromyelitis optica spectrum disorder (NMOSD) patients (NMONAT), (3) AQP4-ab titers in NMONAT and AQP4-ab–seropositive NMOSD treated with other immunotherapies (NMOIT), and (4) immune mechanisms influencing disease activity in NMONAT. Methods: MSNAT serum samples were retrospectively screened with a cell-based assay for AQP4-IgG and titers determined by ELISA. The annualized relapse rate (ARR) and disability progression were assessed. Serum levels of proinflammatory cytokines (interleukin [IL]-1β, IL-4, IL-6, IL-8, IL-10, IL-17, IL-21, and interferon [IFN]-γ) and the chemokine CXCL-10 of NMONAT patients identified in this (n = 4) and a previous study (n = 5) were measured by cytometric bead array and ELISA. Results: Of the 1,183 MSNAT patients (851 female, median 9 NAT infusions), only 4 (0.33%; 3 female, 1 male) had AQP4-IgG. Of these, 2 fulfilled the 2006 NMO criteria and all met the 2015 NMOSD criteria. The ARR was higher in NMONAT vs MSNAT (p = 0.0182). All 4 NMONAT patients had relapses and 2 had an increase of disability. AQP4-ab titers were higher in NMONAT (n = 9) vs NMOIT (n = 13; p = 0.0059). IL-8, IL-1β, and IFN-γ serum levels were significantly higher, and CXCL-10 was significantly lower in NMONAT vs NMOIT. Conclusions: Misdiagnosis of NMOSD with MS is rare. NAT was not able to control disease activity in NMONAT patients, who had higher serum levels of AQP4-IgG and proinflammatory cytokines than patients with NMOSD treated with other immunotherapies. PMID:28642888

Diagnostic algorithm for relapsing acquired demyelinating syndromes in children.

PubMed

Hacohen, Yael; Mankad, Kshitij; Chong, W K; Barkhof, Frederik; Vincent, Angela; Lim, Ming; Wassmer, Evangeline; Ciccarelli, Olga; Hemingway, Cheryl

2017-07-18

To establish whether children with relapsing acquired demyelinating syndromes (RDS) and myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) show distinctive clinical and radiologic features and to generate a diagnostic algorithm for the main RDS for clinical use. A panel reviewed the clinical characteristics, MOG-Ab and aquaporin-4 (AQP4) Ab, intrathecal oligoclonal bands, and Epstein-Barr virus serology results of 110 children with RDS. A neuroradiologist blinded to the diagnosis scored the MRI scans. Clinical, radiologic, and serologic tests results were compared. The findings showed that 56.4% of children were diagnosed with multiple sclerosis (MS), 25.4% with neuromyelitis optica spectrum disorder (NMOSD), 12.7% with multiphasic disseminated encephalomyelitis (MDEM), and 5.5% with relapsing optic neuritis (RON). Blinded analysis defined baseline MRI as typical of MS in 93.5% of children with MS. Acute disseminated encephalomyelitis presentation was seen only in the non-MS group. Of NMOSD cases, 30.7% were AQP4-Ab positive. MOG-Ab were found in 83.3% of AQP4-Ab-negative NMOSD, 100% of MDEM, and 33.3% of RON. Children with MOG-Ab were younger, were less likely to present with area postrema syndrome, and had lower disability, longer time to relapse, and more cerebellar peduncle lesions than children with AQP4-Ab NMOSD. A diagnostic algorithm applicable to any episode of CNS demyelination leads to 4 main phenotypes: MS, AQP4-Ab NMOSD, MOG-Ab-associated disease, and antibody-negative RDS. Children with MS and AQP4-Ab NMOSD showed features typical of adult cases. Because MOG-Ab-positive children showed notable and distinctive clinical and MRI features, they were grouped into a unified phenotype (MOG-Ab-associated disease), included in a new diagnostic algorithm. © 2017 American Academy of Neurology.

Molecular mimicry as a mechanism for food immune reactivities and autoimmunity.

PubMed

Vojdani, Aristo

2015-01-01

The mucosal immune system is constantly exposed to challenges from the antigenic substances found in food and released from the body's own microbial flora. The body's normal tolerance to friendly antigenic substances can be disrupted by a number of factors, such as disease, injury, shock, trauma, surgery, drugs, blood transfusion, environmental triggers, etc. When this disruption happens, the ingestion of foods containing antigenic substances that have compositions similar to those of the body's autoantigens can result in the production of antibodies that react not only against the food antigens but also the body's own tissues. This response is known as food autoimmune reactivity. Between 7% and 10% of the world's population suffers from some form of autoimmune disease. Each patient's antibodies, both immunoglobulin A (IgA) + immunoglobulin M (IgM) in the saliva and immunoglobulin G (IgG) and IgA in the blood must be examined to give a complete picture of food immune reactivity. A host of health problems and autoimmune disorders have increasingly become associated with some of the most commonly consumed foods in the world, such as wheat and milk. Many of these problems can be traced to molecular mimicry. The peptide sequences of foods such as milk and wheat are similar to those of human molecules, such as myelin oligodendrocyte glycoprotein, human islet cell tissue, and human aquaporin 4 (AQP4). This similarity can result in cross-reactivity that leads to food autoimmunity and even autoimmune disorders, such as multiple sclerosis (MS), celiac disease (CD), and neuromyelitis optica. Further research is needed to determine what other foods have dangerous sequence similarities to human tissues and what methods are available to test for the autoantibodies resulting from these molecular, mimicry-induced misfires of the immune system. The identification and removal of corresponding food triggers can then be used as the basis of therapy.

Life-threatening hypokalemia following rapid correction of respiratory acidosis.

PubMed

Hammond, Kendra; You, David; Collins, Eileen G; Leehey, David J; Laghi, Franco

2013-01-01

A 56-year-old woman with a history of paraplegia and chronic pain due to neuromyelitis optica (Devic's syndrome) was admitted to a spinal cord injury unit for management of a sacral decubitus ulcer. During the hospitalization, she required emergency transfer to the intensive care unit (ICU) because of progressive deterioration of respiratory muscle function, severe respiratory acidosis, obtundation and hypotension. Upon transfer to the ICU, arterial blood gas revealed severe acute-on-chronic respiratory acidosis (pH 7.00, PCO2 120 mm Hg, PO2 211 mm Hg). The patient was immediately intubated and mechanically ventilated. Intravenous fluid boluses of normal saline (10.5 L in about 24 h) and vasopressors were started with rapid correction of hypotension. In addition, she was given hydrocortisone. Within 40 min of initiation of mechanical ventilation, there was improvement in acute respiratory acidosis. Sixteen hours later, however, the patient developed life-threatening hypokalemia (K(+) of 2.1 mEq/L) and hypomagnesemia (Mg of 1.4 mg/dL). Despite aggressive potassium supplementation, hypokalemia continued to worsen over the next several hours (K(+) of 1.7 mEq/L). Urine studies revealed renal potassium wasting. We reason that the recalcitrant life-threatening hypokalemia was caused by several mechanisms including total body potassium depletion (chronic respiratory acidosis), a shift of potassium from the extracellular to intracellular space (rapid correction of respiratory acidosis with mechanical ventilation), increased sodium delivery to the distal nephron (normal saline resuscitation), hyperaldosteronism (secondary to hypotension plus administration of hydrocortisone) and hypomagnesemia. We conclude that rapid correction of respiratory acidosis, especially in the setting of hypotension, can lead to life-threatening hypokalemia. Serum potassium levels must be monitored closely in these patients, as failure to do so can lead to potentially lethal consequences

The intrinsic pathogenic role of autoantibodies to aquaporin 4 mediating spinal cord disease in a rat passive-transfer model

PubMed Central

Geis, Christian; Ritter, Christian; Ruschil, Christoph; Weishaupt, Andreas; Grünewald, Benedikt; Stoll, Guido; Holmoy, Trygve; Misu, Tatsuro; Fujihara, Kazuo; Hemmer, Bernhard; Stadelmann, Christine; Bennett, Jeffrey L.; Sommer, Claudia; Toyka, Klaus V.

2015-01-01

Neuromyelitis optica (NMO) is causally linked to autoantibodies (ABs) against aquaporin 4 (AQP4). Here, we focused on the pathogenic effects exclusively mediated by human ABs to AQP4 in vivo. We performed cell-free intrathecal (i.th.) passive transfer experiments in Lewis rats using purified patient NMO immunoglobulin G (IgG) and various recombinant human anti-AQP4 IgG-ABs via implanted i.th. catheters. Repetitive application of patient NMO IgG fractions and of recombinant human anti-AQP4 ABs induced signs of spinal cord disease. Magnetic resonance imaging (MRI) revealed longitudinal spinal cord lesions at the site of application of anti-AQP4 IgG. Somatosensory evoked potential amplitudes were reduced in symptomatic animals corroborating the observed functional impairment. Spinal cord histology showed specific IgG deposition in the grey and white matter in the affected areas. We did not find inflammatory cell infiltration nor activation of complement in spinal cord areas of immunoglobulin deposition. Moreover, destructive lesions showing axon or myelin damage and loss of astrocytes and oligodendrocytes were all absent. Immunoreactivity to AQP4 and to the excitatory amino acid transporter 2 (EAAT2) was markedly reduced whereas immunoreactivity to the astrocytic marker glial fibrillary acid protein (GFAP) was preserved. The expression of the NMDA-receptor NR1 subunit was down-regulated in areas of IgG deposition possibly induced by sustained glutamatergic overexcitation. Disease signs and histopathology were reversible within weeks after stopping injections. We conclude that in vivo application of ABs directed at AQP 4 can induce a reversible spinal cord disease in recipient rats by inducing distinct histopathological abnormalities. These findings may be the experimental correlate of “penumbra-like” lesions recently reported in NMO patients adjacent to effector-mediated tissue damage. PMID:25542977

The intrinsic pathogenic role of autoantibodies to aquaporin 4 mediating spinal cord disease in a rat passive-transfer model.

PubMed

Geis, Christian; Ritter, Christian; Ruschil, Christoph; Weishaupt, Andreas; Grünewald, Benedikt; Stoll, Guido; Holmoy, Trygve; Misu, Tatsuro; Fujihara, Kazuo; Hemmer, Bernhard; Stadelmann, Christine; Bennett, Jeffrey L; Sommer, Claudia; Toyka, Klaus V

2015-03-01

Neuromyelitis optica (NMO) is causally linked to autoantibodies (ABs) against aquaporin 4 (AQP4). Here, we focused on the pathogenic effects exclusively mediated by human ABs to AQP4 in vivo. We performed cell-free intrathecal (i.th.) passive transfer experiments in Lewis rats using purified patient NMO immunoglobulin G (IgG) and various recombinant human anti-AQP4 IgG-ABs via implanted i.th. catheters. Repetitive application of patient NMO IgG fractions and of recombinant human anti-AQP4 ABs induced signs of spinal cord disease. Magnetic resonance imaging (MRI) revealed longitudinal spinal cord lesions at the site of application of anti-AQP4 IgG. Somatosensory evoked potential amplitudes were reduced in symptomatic animals corroborating the observed functional impairment. Spinal cord histology showed specific IgG deposition in the grey and white matter in the affected areas. We did not find inflammatory cell infiltration nor activation of complement in spinal cord areas of immunoglobulin deposition. Moreover, destructive lesions showing axon or myelin damage and loss of astrocytes and oligodendrocytes were all absent. Immunoreactivity to AQP4 and to the excitatory amino acid transporter 2 (EAAT2) was markedly reduced whereas immunoreactivity to the astrocytic marker glial fibrillary acid protein (GFAP) was preserved. The expression of the NMDA-receptor NR1 subunit was downregulated in areas of IgG deposition possibly induced by sustained glutamatergic overexcitation. Disease signs and histopathology were reversible within weeks after stopping injections. We conclude that in vivo application of ABs directed at AQP 4 can induce a reversible spinal cord disease in recipient rats by inducing distinct histopathological abnormalities. These findings may be the experimental correlate of "penumbra-like" lesions recently reported in NMO patients adjacent to effector-mediated tissue damage. Copyright © 2014 Elsevier Inc. All rights reserved.

CSF free light chain identification of demyelinating disease: comparison with oligoclonal banding and other CSF indexes.

PubMed

Gurtner, Kari M; Shosha, Eslam; Bryant, Sandra C; Andreguetto, Bruna D; Murray, David L; Pittock, Sean J; Willrich, Maria Alice V

2018-02-19

Cerebrospinal fluid (CSF) used in immunoglobulin gamma (IgG) index testing and oligoclonal bands (OCBs) are common laboratory tests used in the diagnosis of multiple sclerosis. The measurement of CSF free light chains (FLC) could pose as an alternative to the labor-intensive isoelectric-focusing (IEF) gels used for OCBs. A total of 325 residual paired CSF and serum specimens were obtained after physician-ordered OCB IEF testing. CSF kappa (cKFLC) and lambda FLC (cLFLC), albumin and total IgG were measured. Calculations were performed based on combinations of analytes: CSF sum of kappa and lambda ([cKFLC+cLFLC]), kappa-index (K-index) ([cKFLC/sKFLC]/[CSF albumin/serum albumin]), kappa intrathecal fraction (KFLCIF) {([cKFLC/sKFLC]-[0.9358×CSF albumin/serum albumin]^[0.6687×sKFLC]/cKFLC)} and IgG-index ([CSF IgG/CSF albumin]/[serum IgG/serum albumin]). Patients were categorized as: demyelination (n=67), autoimmunity (n=53), non-inflammatory (n=50), inflammation (n=38), degeneration (n=28), peripheral neuropathy (n=24), infection (n=13), cancer (n=11), neuromyelitis optica (n=10) and others (n=31). cKFLC measurement used alone at a cutoff of 0.0611 mg/dL showed >90% agreement to OCBs, similar or better performance than all other calculations, reducing the number of analytes and variables. When cases of demyelinating disease were reviewed, cKFLC measurements showed 86% clinical sensitivity/77% specificity. cKFLC alone demonstrates comparable performance to OCBs along with increased sensitivity for demyelinating diseases. Replacing OCB with cKFLC would alleviate the need for serum and CSF IgG and albumin and calculated conversions. cKFLC can overcome challenges associated with performance, interpretation, and cost of traditional OCBs, reducing costs and maintaining sensitivity and specificity supporting MS diagnosis.

Analysis of prognostic factors associated with longitudinally extensive transverse myelitis.

PubMed

Sepúlveda, María; Blanco, Yolanda; Rovira, Alex; Rio, Jordi; Mendibe, Mar; Llufriu, Sara; Gabilondo, Iñigo; Villoslada, Pablo; Castilló, Joaquin; Corral, Juan; Ayuso, Teresa; Iñiguez, Cristina; Santos, Sonia; Guijarro, Cristina; Ramió-Torrentà, Lluis; Sempere, Angel P; Olascoaga, Javier; Graus, Francesc; Montalban, Xavier; Saiz, Albert

2013-05-01

The aim of this study is to report the clinical profile and outcome of longitudinally extensive transverse myelitis (LETM). We prospectively studied adult patients who presented with LETM from January 2008 to December 2011. Information on demographic, clinical course, magnetic resonance imaging (MRI) and outcome was collected. HLA-DRB1 genotype was compared with those of 225 normal controls and patients with MS (228) and neuromyelitis optica (NMO) (22). In total, 23 patients (16 female) with a median age of 44.5 years (range: 20-77 years) were included. Most (74%) had moderate-severe disability at nadir (48% non-ambulatory), normal/non-multiple sclerosis (MS) brain MRI (96%) and a median MRI cord lesion of 5 vertebral segments (range: 3-19). Laboratory analysis showed cerebrospinal fluid pleocytosis (45%), NMO-IgG (9%), antinuclear antibodies (70%), and genotype HLA-DRB1*13 (57%). The frequency of DRB1*13 genotype was higher compared with controls (p=0.002), MS (p=0.001) and NMO (p=0.003) patients. After a median follow-up of 32 months, one patient converted to MS, two had relapsing LETM with NMO-IgG, and 20 remained as idiopathic with recurrences in four (20%). Twelve (52%) patients recovered with minimal disability (Expanded Disability Status Scale (EDSS) ≤2.5) and three (13%) remained wheelchair dependent. Disability at nadir was associated with the final outcome and extension of the spinal cord lesion with risk of recurrence. Recurrence was not associated with worse outcome. Inflammatory LETM is mostly idiopathic with a good outcome. It includes a relatively homogenous group of patients with an overrepresentation of the HLA-DRB1*13 genotype. EDSS at nadir is a predictor of the final outcome and extension of the myelitis of the recurrence risk.

Trident sign trumps Aquaporin-4-IgG ELISA in diagnostic value in a case of longitudinally extensive transverse myelitis.

PubMed

Jolliffe, Evan A; Keegan, B Mark; Flanagan, Eoin P

2018-04-21

Longitudinally-extensive T2-hyperintense spinal cord lesions (≥3 vertebral segments) are associated with neuromyelitis optical spectrum disorder but occur with other disorders including spinal cord sarcoidosis. When linear dorsal subpial enhancement is accompanied by central cord/canal enhancement the axial post-gadolinium sequences may reveal a "trident" pattern that has previously been shown to be strongly suggestive of spinal cord sarcoidosis. We report a case in which the patient was initially diagnosed with neuromyelitis optical spectrum disorder, but where the "trident" sign ultimately led to the correct diagnosis of spinal cord sarcoidosis. Copyright © 2018. Published by Elsevier B.V.

Screening prostate cancer using a portable near infrared scanning imaging unit with an optical fiber-based rectal probe

NASA Astrophysics Data System (ADS)

Pu, Yang; Wang, Wubao; Tang, Guichen; Budansky, Yury; Sharonov, Mikhail; Xu, Min; Achilefu, Samuel; Eastham, James A.; Alfano, Robert R.

2012-01-01

A portable near infrared scanning polarization imaging unit with an optical fiber-based rectal probe, namely Photonic Finger, was designed and developed o locate the 3D position of abnormal prostate site inside normal prostate tissue. An inverse algorithm, Optical Tomography using Independent Component Analysis (OPTICA) was improved particularly to unmix the signal from targets (cancerous tissue) embedded in a turbid medium (normal tissue) in the backscattering imaging geometry. Photonic Finger combined with OPTICA was tested to characterize different target(s) inside different tissue medium, including cancerous prostate tissue embedded by large piece of normal tissue.

Optica aperture synthesis

NASA Astrophysics Data System (ADS)

van der Avoort, Casper

2006-05-01

Optical long baseline stellar interferometry is an observational technique in astronomy that already exists for over a century, but is truly blooming during the last decades. The undoubted value of stellar interferometry as a technique to measure stellar parameters beyond the classical resolution limit is more and more spreading to the regime of synthesis imaging. With optical aperture synthesis imaging, the measurement of parameters is extended to the reconstruction of high resolution stellar images. A number of optical telescope arrays for synthesis imaging are operational on Earth, while space-based telescope arrays are being designed. For all imaging arrays, the combination of the light collected by the telescopes in the array can be performed in a number of ways. In this thesis, methods are introduced to model these methods of beam combination and compare their effectiveness in the generation of data to be used to reconstruct the image of a stellar object. One of these methods of beam combination is to be applied in a future space telescope. The European Space Agency is developing a mission that can valuably be extended with an imaging beam combiner. This mission is labeled Darwin, as its main goal is to provide information on the origin of life. The primary objective is the detection of planets around nearby stars - called exoplanets- and more precisely, Earth-like exoplanets. This detection is based on a signal, rather than an image. With an imaging mode, designed as described in this thesis, Darwin can make images of, for example, the planetary system to which the detected exoplanet belongs or, as another example, of the dust disk around a star out of which planets form. Such images will greatly contribute to the understanding of the formation of our own planetary system and of how and when life became possible on Earth. The comparison of beam combination methods for interferometric imaging occupies most of the pages of this thesis. Additional chapters will treat related subjects, being experimental work on beam combination optics, a description of a novel formalism for aberration retrieval and experimental work on nulling interferometry. The Chapters on interferometric imaging are organized in such a way that not only the physical principles behind a stellar interferometer are clear, but these chapters also form a basis for the method of analysis applied to the interferometers - -or rather beam combination methods- under consideration. The imaging process in a stellar interferometer will be treated as the inversion of a linear system of equations. The definition of interferometric imaging in this thesis can be stated to be the reconstruction of a luminosity distribution function on the sky, that is, in angular measure, larger than the angular diffraction limited spot size -or Point-Spread Function (PSF)- of a single telescope in the array and that contains, again in angular measure, spatial structure that is much smaller than the PSF of a single telescope. This reconstruction has to be based on knowledge of the dimensions of the telescope array and the detector. The detector collects intensity data that is formed by observation of the polychromatic luminosity distribution on the sky and is deteriorated by the quantum-nature of light and an imperfect electronic detection process. Therefore, the imaging study presented in this thesis can be regarded to be a study on the signal characteristics of various interferometers while imaging a polychromatic wide-field stellar source. The collection of beam combination methods under consideration consists of four types. Among these are two well-known types, having either co-axially combined beams as in the Michelson-Morley experiment to demonstrate the existence of ether, or beams that follow optical paths as if an aperture mask were placed in front of a telescope, making the beams combine in the focus of that telescope, as suggested by Fizeau. For separated apertures rather than an aperture mask, these optical paths are stated to be homothetic. In short, these two types will be addressed as the Michelson or the Homothetic type. The other two types are addressed as Densified and Staircase. The first one is short for densified pupil imaging, an imaging technique very similar to the Homothetic type, be it that the natural course of light after the aperture mask is altered. However, the combination of the beams of light is again in focus. The Staircase method is an alternative to the co-axial Michelson method and lends its name from the fact that a staircase-shaped mirror is placed in an intermediate focal plane after each telescope in the array, before combining the beams of light co-axially. This addition allows stellar imaging as with the Michelson type, with the advantage of covering a large field-of-view. The details of these methods will intensively be discussed in this thesis, but the introduction of them at this point allows a short list of results, found by comparing them for equal imaging tasks. Homothetic imagers are best suited for covering a wide field-of-view, considering the information content of the interferometric signals these arrays produce. The large number of detectors does not seem to limit the imaging performance in the presence of noise, due to the high ratio of coherent versus incoherent information in the detector signal. The imaging efficiency of a Michelson type array is also high, although -considering only polychromatic wide-field imaging tasks- the ratio of coherent versus incoherent information in the detected signals is very low. This results in very large observation times needed to produce images comparable to those obtained with a Homothetic array. A detailed presentation of the characteristics of the detected signals in a co-axial Michelson array reveal that such signals, obtained by polychromatic observation of extended sources, have fringe envelope functions that do not allow Fourier-spectroscopy to obtain high-resolution spectroscopic information about such a source. For the Densified case, it is found that this method can indeed provide an interferometric PSF that is more favorable than a homothetic PSF, but only for narrow-angle observations. For polychromatic wide-field observations, the Densified-PSF is field-dependent, for which the image reconstruction process can account. Wide-field imaging using the favorable properties of the Densified-PSF can be performed, by using special settings of the delay or optical path length difference between interferometer arms and including observations with several settings of delay in the observation data. The Staircase method is the second best method for the imaging task under consideration. The discontinuous nature of the staircase-shaped mirrors does not give rise to a discontinuous reconstructed luminosity distribution or non-uniformly covered spatial frequencies. The intrinsic efficiency of the interferometric signal in this type of interferometer is worse than that of the other co-axial method, although the ratio of coherent versus incoherent signal in the data -the length of the fringe packet in one intensity trace-e- is nearly ultimate. The inefficiency is overwhelmingly compensated for by the very short observation time needed. Besides numerical studies of interferometer arrays, one interferometric imager was also studied experimentally. A homothetic imager was built, comprising three telescopes with fully separated beam relay optics. The pointing direction, the location and the optical path length of two of the three beams are electronically controllable. The beams can be focused together to interfere, via a beam combiner consisting of curved surfaces. This set-up allows to measure the required accuracies at which certain optical elements have to be positioned. Moreover, this set-up demonstrates that without knowledge of the initial pointing directions, locations and optical path lengths of the beams, the situation of homothesis can be attained, solely based on information from the focal plane of the set-up. Further experiments show that the approximation of exact homothesis is limited by the optical quality of the beam combiner optics. Parallel to the experiments on homothesis, a study was performed to evaluate the use of the Extended Nijboer-Zernike (ENZ) formalism for analysis of multiple aperture optical systems. It is envisaged that an aberration retrieval algorithm, provided with the common focus of a homothetic array, can be used to detect misalignment of or even aberrations in the sub-apertures of the sparse synthetic aperture. The ENZ formalism is a powerful tool to describe the focal intensity profile in an optical imaging system, imaging a monochromatic point source through a pupil that is allowed to have a certain transmission profile and phase aberration function over the pupil. Moreover, the formalism allows calculation of intensity profiles outside the best-focus plane. With the intensity information of several through-focus planes, enough information is available to reconstruct the pupil function from it. The formalism is described, including the reconstruction algorithm. Although very good results are obtained for general pupil functions, the results for synthetic pupil functions are not very promising. The detailed description of the ENZ-aberration retrieval reveals the origin of the breakdown of the retrieval process. Finally, a description of experiments on nulling interferometry is given, starting with the presentation of an experimental set-up for three-beam nulling. A novel strategy for polychromatic nulling is treated here, with the goal of relieving the tight phase constraint on the spectra in the individual beams. This theoretically allows broad band-nulling with a high rejection ratio without using achromatic phase shifters. The disappointing results led to an investigation of the spectra of the individual beams. The origin of the unsatisfactory level of the rejection ratio is found in the spectral unbalance of the beams. Before branching off, the beams have an equal spectrum. Then, the encounter of different optical elements with individually applied coatings, the control of beam-power per beam and finally the beam coupling into a single-mode fiber, apparently alter the spectra in such a way that the theoretically achievable level of the rejection ratio cannot be reached. The research described in this thesis provides onsets for research in several areas of interest related to aperture synthesis and guidelines concerning the design of synthetic telescopes for imaging. As such, this research contributes to the improvement of instrumentation for observational astronomy, in particular for stellar interferometry. While nulling interferometry is the detection technique that allows a space telescope array such as ESA-Darwin to identify exoplanets, optical aperture synthesis imaging is the technique that can make images of the planetary systems to which these exoplanets belong. Moreover, many objects can be observed that represent earlier versions of our planetary system, our Sun and even our galaxy, the Milky Way. Observing these objects might answer questions about the origins of the Earth itself and the life on it.

Protocol for a multicentre randomiSed controlled TRial of IntraVEnous immunoglobulin versus standard therapy for the treatment of transverse myelitis in adults and children (STRIVE)

PubMed Central

Absoud, M; Gadian, J; Hellier, J; Brex, P A; Ciccarelli, O; Giovannoni, G; Kelly, J; McCrone, P; Murphy, C; Palace, J; Pickles, A; Pike, M; Robertson, N; Jacob, A; Lim, M

2015-01-01

Introduction Transverse myelitis (TM) is an immune-mediated disorder of the spinal cord which causes motor and sensory disturbance and limited recovery in 50% of patients. Standard treatment is steroids, and patients with more severe disease appear to respond to plasma exchange (PLEX). Intravenous immunoglobulin (IVIG) has also been used as an adjunct to steroids, but evidence is lacking. We propose the first randomised control trial in adults and children, to determine the benefit of additional treatment with IVIG. Methods and analysis 170 adults and children aged over 1 year with acute first episode TM or neuromyelitis optica (with myelitis) will be recruited over a 2.5-year period and followed up for 12 months. Participants randomised to the control arm will receive standard therapy of intravenous methylprednisolone (IVMP). The intervention arm will receive the above standard therapy, plus additional IVIG. Primary outcome will be a 2-point improvement on the American Spinal Injury Association (ASIA) Impairment scale at 6 months postrandomisation by blinded assessors. Additional secondary and tertiary outcome measures will be collected: ASIA motor and sensory scales, Kurtzke expanded disability status scale, International Spinal Cord Injury (SCI) Bladder/Bowel Data Set, Client Services Receipt Index, Pediatric Quality of Life Inventory, EQ-5D, SCI Pain and SCI Quality of Life Data Sets. Biological samples will be biobanked for future studies. After 6-months' follow-up of the first 52 recruited patients futility analysis will be carried out. Health economics analysis will be performed to calculate cost-effectiveness. After 6 months’ recruitment futility analysis will be performed. Ethics and dissemination Research Ethics Committee Approval was obtained: 14/SC/1329. Current protocol: v3.0 (15/01/2015). Study findings will be published in peer-reviewed journals. Trial registration numbers This study is registered with EudraCT (REF: 2014

Differential diagnosis of multiple sclerosis.

PubMed

Fadil, Halim; Kelley, Roger E; Gonzalez-Toledo, Eduardo

2007-01-01

There are a number of illnesses that can mimic multiple sclerosis (MS). This pretty much includes any pathological process that can reflect injury to the central nervous system either in a transient or progressive basis. Typically, MS presents itself in individuals in their teens up to their late 30s. On occasion, however, one can see MS present in patients in their 60s. However, in retrospect, many of these patients might have had subtle manifestations of MS in their younger years. Visual obscuration or visual loss can be a manifestation of retinal ischemia, retinal migraine, or optic neuritis which might or might not evolve into a clinical picture compatible with MS. Cranial neuropathy, long tract signs, sensory disturbance, and/or gait ataxia can be related to a number of different processes such as illicit drug use, neurosarcoidosis, neuro-Behcet's disease, neuroborreliosis, HIV-related disease, neurosyphilis, vascular occlusive disease including vasculitis, connective tissue disorders, acute disseminated encephalomyelitis (ADEM), idiopathic transverse myelitis, neuromyelitis optica (NMO), or tropical spastic paraparesis. In addition, a constellation of symptoms, with questionable objective findings, along with normal MRI imaging, normal CSF results, and normal evoked response testing, when indicated, might identify a conversion disorder or possibly malingering. There are now established criteria for the diagnosis of MS, but initial presentations can be less than "textbook" in nature. With the advent of immunomodulating therapy, it has become more important to diagnose MS more effectively earlier on in the course of the illness. Prior to specific therapy for MS, astute clinicians did not necessarily move with alacrity to establish the diagnosis in patients with subtle or transient manifestations. This was in recognition of the fact that little could be offered to alter the course of the illness and a number of patients might never experience further problems if

High resolution retinal scanning reveals regional structural differences between MS and NMOSD optic neuritis regardless of antibody status.

PubMed

Bertsch-Gout, Marcel; Loeb, Richard; Finch, Ashley K; Javed, Adil; Bernard, Jacqueline

2018-01-15

There is a need for biomarkers that can classify optic neuritis (ON) attacks as belonging to either neuromyelitis optica spectrum disorder with optic neuritis (NMOSD-ON) or relapsing remitting multiple sclerosis with optic neuritis (MS-ON). This study uses spectral domain optical coherence tomography (SD-OCT) data to perform a preliminary contrast between NMOSD-ON and MS-ON by analyzing peripapillary retinal nerve fiber layer and intra-macular layer patterns of injury. In this cross-sectional study, we used SD-OCT to obtain peripapillary retinal nerve fiber layer and intra-macular layer data for 26 NMOSD-ON, 25 MS-ON, and 26 healthy control (HC) age-matched eyes. Additionally, sub-comparisons compared 11 NMOSD-ON eyes that were seronegative for IgG antibodies against aquaporin 4 (NMOSD-ON (-)) and 16 NMOSD-ON eyes that were seropositive (NMOSD-ON (+)) to age-matched MS-ON eyes. Layer thicknesses were assessed using an automated algorithm and were then statistically compared using generalized estimating equations to account for inter-eye correlations. Selective thinning was found in the pRNFL, mRNFL, and GCL in NMOSD-ON compared to MS-ON. Thinning in the pRNFL nasal sector was found to persist in both NMOSD-ON (-) (P=0.017) and NMOSD-ON (+) (P=0.021) compared to MS-ON. Thinning in the mRNFL temporal sector was found to persist in NMOSD-ON (+) compared to MS-ON. Diffuse thinning was found in the pRNFL, mRNFL, GCL and IPL in NMOSD-ON compared to HC, and while diffuse thinning was also found in the GCL and IPL in MS-ON compared to HC, selective thinning was found in the pRNFL and mRNFL. The nasal region of the pRNFL may be capable of distinguishing between NMOSD-ON and MS-ON regardless of antibody status. Additionally, NMOSD-ON may cause more profound nasal axonal and inferior arcuate neuronal degeneration compared to MS-ON. Copyright © 2017 Elsevier B.V. All rights reserved.

Metabolomics reveals distinct, antibody-independent, molecular signatures of MS, AQP4-antibody and MOG-antibody disease.

PubMed

Jurynczyk, Maciej; Probert, Fay; Yeo, Tianrong; Tackley, George; Claridge, Tim D W; Cavey, Ana; Woodhall, Mark R; Arora, Siddharth; Winkler, Torsten; Schiffer, Eric; Vincent, Angela; DeLuca, Gabriele; Sibson, Nicola R; Isabel Leite, M; Waters, Patrick; Anthony, Daniel C; Palace, Jacqueline

2017-12-06

The overlapping clinical features of relapsing remitting multiple sclerosis (RRMS), aquaporin-4 (AQP4)-antibody (Ab) neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-Ab disease mean that detection of disease specific serum antibodies is the gold standard in diagnostics. However, antibody levels are not prognostic and may become undetectable after treatment or during remission. Therefore, there is still a need to discover antibody-independent biomarkers. We sought to discover whether plasma metabolic profiling could provide biomarkers of these three diseases and explore if the metabolic differences are independent of antibody titre. Plasma samples from 108 patients (34 RRMS, 54 AQP4-Ab NMOSD, and 20 MOG-Ab disease) were analysed by nuclear magnetic resonance spectroscopy followed by lipoprotein profiling. Orthogonal partial-least squares discriminatory analysis (OPLS-DA) was used to identify significant differences in the plasma metabolite concentrations and produce models (mathematical algorithms) capable of identifying these diseases. In all instances, the models were highly discriminatory, with a distinct metabolite pattern identified for each disease. In addition, OPLS-DA identified AQP4-Ab NMOSD patient samples with low/undetectable antibody levels with an accuracy of 92%. The AQP4-Ab NMOSD metabolic profile was characterised by decreased levels of scyllo-inositol and small high density lipoprotein particles along with an increase in large low density lipoprotein particles relative to both RRMS and MOG-Ab disease. RRMS plasma exhibited increased histidine and glucose, along with decreased lactate, alanine, and large high density lipoproteins while MOG-Ab disease plasma was defined by increases in formate and leucine coupled with decreased myo-inositol. Despite overlap in clinical measures in these three diseases, the distinct plasma metabolic patterns support their distinct serological profiles and confirm that these

CONFERENCE NOTE: CETO—Centro de Ciências e Tecnologias Opticas, Trends in Optical Fibre Metrology and Standards

NASA Astrophysics Data System (ADS)

1994-01-01

requirements of the new generation of analogue and digital fibre optical systems, which require sophisticated measurement techniques employing complex instruments unique to optical measurements. The school will foster and enhance the interaction between material, devices, systems, and standards-oriented R&D communities, as well as between engineers concerned with design and manufacturers of systems and instrumentation. Topics Review of optical fibre communication technology and systems Measurement techniques for fibre characterization: Reliability and traceability Reference fibres and calibration artefacts Ribbon fibres Mechanical and environmental testing Fibre reliability Polarimetric measurements Passive components characterization: Splices and connectors Couplers, splitters, taps and WDMs Optical fibres and isolators WDM technologies and applications: WDM technologies Tunable optical filters Fibre amplifiers and sources: Performances and characterization Design and standards Nonlinear effects Subsystem design and standards: Design and fabrication techniques Performance degradation and reliability Evaluation of costs/performance/technology Sensors IR - optical fibres Plastic fibres Instrumentation Registration Participation free of charge for postgraduate students, with some grants available for travel and lodging expenses. All correspondence should be addressed to: Secretariat, Trends in Optical Fibre Metrology and Standards, a/c Prof. Olivério D D Soares, Centro de Ciências e Tecnologias Opticas, Lab. Fisica - Faculdade de Ciências, Praça Gomes Teixeira, P-4000 Porto, Portugal. Tel: 351-2-310290, 351-2-2001648; Fax: 351-2-319267.

PREFACE: International Conference on Control and Synchronization of Dynamical Systems (CSDS-2005)

NASA Astrophysics Data System (ADS)

Pisarchik, Alexander N.

2005-01-01

This volume of Journal of Physics: Conference Series contains selected articles by the participants at the International Conference on Control and Synchronization of Dynamical Systems (CSDS-2005) organized by Centro de Investigaciones en Optica (CIO) in cooperation with the Society for Industrial and Applied Mathematics (SIAM), which was held in Leon, Guanajuato, Mexico on 4-7 October 2005. CSDS-2005 featured the latest research in nonlinear dynamics concentrating on the theory of control and synchronization of complex systems and its applications in different areas of science and engineering, including optics, electronics, mechanics, chemistry, medicine, economy, communication, etc. The conference brought together leading researchers, both theoreticians and experimentalists, from different fields of science and provided an excellent opportunity for sharing ideas and problems among specialists in controlling dynamical systems and synchronization. The meeting served a dual purpose: to expose the scientific community to the cutting edge of forefront research done by leaders in this area from as many as 25 countries and to attract the attention of Mexican researchers to this field of science. These proceedings are intended to be a record of this conference and to serve as a reference for future research which the conference hopes to have initiated. After the pioneering work on controlling chaos of E Ott, C Grebogi and J Yorke appeared in Physical Review Letters in 1990, the number of works on this topic grew tremendously. Our extensive bibliographic search among 110 peer reviewed journals yielded more than 1500 papers on controlling chaos and more than 2500 on synchronization of chaotic systems published during the last decade. The numbers of publications are still at their peaks that began to saturate, in 1998 and 2003, respectively. It is my pleasure to acknowledge the contribution of the program and organizing committees, the funding agencies and cooperating

The spectral sensitivity of the human short-wavelength sensitive cones derived from thresholds and color matches.

PubMed

Stockman, A; Sharpe, L T; Fach, C

1999-08-01

We used two methods to estimate short-wave (S) cone spectral sensitivity. Firstly, we measured S-cone thresholds centrally and peripherally in five trichromats, and in three blue-cone monochromats, who lack functioning middle-wave (M) and long-wave (L) cones. Secondly, we analyzed standard color-matching data. Both methods yielded equivalent results, on the basis of which we propose new S-cone spectral sensitivity functions. At short and middle-wavelengths, our measurements are consistent with the color matching data of Stiles and Burch (1955, Optica Acta, 2, 168-181; 1959, Optica Acta, 6, 1-26), and other psychophysically measured functions, such as pi 3 (Stiles, 1953, Coloquio sobre problemas opticos de la vision, 1, 65-103). At longer wavelengths, S-cone sensitivity has previously been over-estimated.

The optical properties of smoke-protective devices.

DOT National Transportation Integrated Search

1978-10-01

Optical properties of 13 smoke-protective devices were determined. The devices tested comprised 8 goggles and 5 fullface oxygen masks (3 rigid one-piece masks and 2 flexible hoods). Those properties evaluated were: (i) light transmission, (ii) optica...

CSF cytokine profile in MOG-IgG+ neurological disease is similar to AQP4-IgG+ NMOSD but distinct from MS: a cross-sectional study and potential therapeutic implications.

PubMed

Kaneko, Kimihiko; Sato, Douglas Kazutoshi; Nakashima, Ichiro; Ogawa, Ryo; Akaishi, Tetsuya; Takai, Yoshiki; Nishiyama, Shuhei; Takahashi, Toshiyuki; Misu, Tatsuro; Kuroda, Hiroshi; Tanaka, Satoru; Nomura, Kyoichi; Hashimoto, Yuji; Callegaro, Dagoberto; Steinman, Lawrence; Fujihara, Kazuo; Aoki, Masashi

2018-06-06

To evaluate cerebrospinal fluid (CSF) cytokine profiles in myelin oligodendrocyte glycoprotein IgG-positive (MOG-IgG+) disease in adult and paediatric patients. In this cross-sectional study, we measured 27 cytokines in the CSF of MOG-IgG+ disease in acute phase before treatment (n=29). The data were directly compared with those in aquaporin-4 antibody-positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD) (n=20), multiple sclerosis (MS) (n=20) and non-inflammatory controls (n=14). In MOG-IgG+ disease, there was no female preponderance and the ages were younger (mean 18 years, range 3-68; 15 were below 18 years) relative to AQP4-IgG+ NMOSD (41, 15-77) and MS (34, 17-48). CSF cell counts were higher and oligoclonal IgG bands were mostly negative in MOG-IgG+ disease and AQP4-IgG+ NMOSD compared with MS. MOG-IgG+ disease had significantly elevated levels of interleukin (IL)-6, IL-8, granulocyte-colony stimulating factor and granulocyte macrophage-colony stimulating factor, interferon-γ, IL-10, IL-1 receptor antagonist, monocyte chemotactic protein-1 and macrophage inflammatory protein-1α as compared with MS. No cytokine in MOG-IgG+ disease was significantly different from AQP4-IgG+ NMOSD. Moreover many elevated cytokines were correlated with each other in MOG-IgG+ disease and AQP4-IgG+ NMOSD but not in MS. No difference in the data was seen between adult and paediatric MOG-IgG+ cases. The CSF cytokine profile in the acute phase of MOG-IgG+ disease is characterised by coordinated upregulation of T helper 17 (Th17) and other cytokines including some Th1-related and regulatory T cells-related ones in adults and children, which is similar to AQP4-IgG+ NMOSD but clearly different from MS. The results suggest that as with AQP4-IgG+ NMOSD, some disease-modifying drugs for MS may be ineffective in MOG-IgG+ disease while they may provide potential therapeutic targets. © Article author(s) (or their employer(s) unless otherwise stated in the text of the

Antibodies to myelin oligodendrocyte glycoprotein in idiopathic optic neuritis.

PubMed

Nakajima, Hideki; Motomura, Masakatsu; Tanaka, Keiko; Fujikawa, Azusa; Nakata, Ruka; Maeda, Yasuhiro; Shima, Tomoaki; Mukaino, Akihiro; Yoshimura, Shunsuke; Miyazaki, Teiichiro; Shiraishi, Hirokazu; Kawakami, Atsushi; Tsujino, Akira

2015-04-02

To investigate the differences of clinical features, cerebrospinal fluid (CSF), MRI findings and response to steroid therapies between patients with optic neuritis (ON) who have myelin oligodendrocyte glycoprotein (MOG) antibodies and those who have seronegative ON. We recruited participants in the department of neurology and ophthalmology in our hospital in Japan. We retrospectively evaluated the clinical features and response to steroid therapies of patients with ON. Sera from patients were tested for antibodies to MOG and aquaporin-4 (AQP4) with a cell-based assay. Between April 2009 and March 2014, we enrolled serial 57 patients with ON (27 males, 30 females; age range 16-84 years) who ophthalmologists had diagnosed as having or suspected to have ON with acute visual impairment and declined critical flicker frequency, abnormal findings of brain MRI, optical coherence tomography and fluorescein fundus angiography at their onset or recurrence. We excluded those patients who fulfilled the diagnostic criteria of neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD), MS McDonald's criteria, and so on. Finally we defined 29 patients with idiopathic ON (14 males, 15 females, age range 16-84 years). 27.6% (8/29) were positive for MOG antibodies and 3.4% (1/29) were positive for AQP4. Among the eight patients with MOG antibodies, five had optic pain (p=0.001) and three had prodromal infection (p=0.179). Three of the eight MOG-positive patients showed significantly high CSF levels of myelin basic protein (p=0.021) and none were positive for oligoclonal band in CSF. On MRIs, seven MOG-positive patients showed high signal intensity on optic nerve, three had a cerebral lesion and one had a spinal cord lesion. Seven of the eight MOG-positive patients had a good response to steroid therapy. Although not proving primary pathogenicity of anti-MOG antibodies, the present results indicate that the measurement of MOG antibodies is useful in diagnosing and treating ON

A Single Amino Acid Substitution Prevents Recognition of a Dominant Human Aquaporin-4 Determinant in the Context of HLA-DRB1*03:01 by a Murine TCR

PubMed Central

Arellano, Benjamine; Hussain, Rehana; Miller-Little, William A.; Herndon, Emily; Lambracht-Washington, Doris; Eagar, Todd N.; Lewis, Robert; Healey, Don; Vernino, Steven; Greenberg, Benjamin M.; Stüve, Olaf

2016-01-01

Background Aquaporin 4 (AQP4) is considered a putative autoantigen in patients with Neuromyelitis optica (NMO), an autoinflammatory disorder of the central nervous system (CNS). HLA haplotype analyses of patients with NMO suggest a positive association with HLA-DRB1* 03:01. We previously showed that the human (h) AQP4 peptide 281–300 is the dominant immunogenic determinant of hAQP4 in the context of HLA-DRB1*03:01. This immunogenic peptide stimulates a strong Th1 and Th17 immune response. AQP4281-300-specific encephalitogenic CD4+ T cells should initiate CNS inflammation that results in a clinical phenotype in HLA-DRB1*03:01 transgenic mice. Methods Controlled study with humanized experimental animals. HLA-DRB1*03:01 transgenic mice were immunized with hAQP4281-300, or whole-length hAQP4 protein emulsified in complete Freund’s adjuvant. Humoral immune responses to both antigens were assessed longitudinally. In vivo T cell frequencies were assessed by tetramer staining. Mice were followed clinically, and the anterior visual pathway was tested by pupillometry. CNS tissue was examined histologically post-mortem. Flow cytometry was utilized for MHC binding assays and to immunophenotype T cells, and T cell frequencies were determined by ELISpot assay. Results Immunization with hAQP4281-300 resulted in an in vivo expansion of antigen-specific CD4+ T cells, and an immunoglobulin isotype switch. HLA-DRB1*03:01 TG mice actively immunized with hAQP4281-300, or with whole-length hAQP4 protein were resistant to developing a neurological disease that resembles NMO. Experimental mice show no histological evidence of CNS inflammation, nor change in pupillary responses. Subsequent analysis reveals that a single amino acid substitution from aspartic acid in hAQP4 to glutamic acid in murine (m)AQP4 at position 290 prevents the recognition of hAQP4281-300 by the murine T cell receptor (TCR). Conclusion Induction of a CNS inflammatory autoimmune disorder by active immunization of

Frequency of Aquaporin-4 Immunoglobulin G in Longitudinally Extensive Transverse Myelitis With Antiphospholipid Antibodies.

PubMed

Guerra, Hilda; Pittock, Sean J; Moder, Kevin G; Fryer, James P; Gadoth, Avi; Flanagan, Eoin P

2018-04-11

Antiphospholipid (aPL) antibodies have historically been postulated to cause a poorly understood inflammatory myelitis. Neuromyelitis optica spectrum disorder (NMOSD) causes an inflammatory longitudinally extensive transverse myelitis (LETM). In 2004, aquaporin-4 immunoglobulin G (AQP4-IgG) was first reported as a highly specific (>99%) serum diagnostic biomarker of NMOSD, distinguishing it from other disorders (eg, multiple sclerosis). We sought to assess the frequency of AQP4-IgG (and thus NMOSD diagnosis) in LETM with aPL antibodies. We searched Mayo Clinic records (from January 1, 1996, through December 31, 2014) for patients with (1) LETM and (2) aPL or β 2 -glycoprotein I antibodies and (3) a serum sample available. AQP4-IgG was evaluated in the 24 included patients and in 20 controls with aPL antibodies but without myelitis. Seropositivity for AQP4-IgG was confirmed in 11 of 24 patients with LETM (46%), confirming an AQP4-IgG-seropositive NMOSD diagnosis rather than aPL-associated LETM. Six of 11 AQP4-IgG-seropositive patients (54%) were initially diagnosed as having aPL/lupus-associated myelitis. Recurrent LETM was exclusive to AQP4-IgG-seropositive patients (P=.003). Alternative diagnoses assigned to the remaining 13 AQP4-IgG-seronegative patients included idiopathic transverse myelitis (n=5), seronegative NMOSD (n=2), spinal cord infarct attributed to aPL antibodies (n=2), spinal cord sarcoidosis (n=1), varicella-zoster virus myelitis (n=1), postinfectious myelitis (n=1), and multiple sclerosis (n=1). All 20 controls were seronegative for AQP4-IgG. Clotting disorders occurred in 36% of patients (4 of 11) with LETM with both aPL antibodies and AQP4-IgG. AQP4-IgG should be tested in all patients with LETM and aPL antibodies because AQP4-IgG-seropositive NMOSD accounts for almost half of all cases. Clotting disorders are common in patients with LETM with dual positivity for AQP4-IgG and aPL antibodies. Copyright © 2018 Mayo Foundation for Medical Education

Early College, Early Success: Early College High School Initiative Impact Study

ERIC Educational Resources Information Center

Berger, Andrea; Turk-Bicakci, Lori; Garet, Michael; Song, Mengli; Knudson, Joel; Haxton, Clarisse; Zeiser, Kristina; Hoshen, Gur; Ford, Jennifer; Stephan, Jennifer; Keating, Kaeli; Cassidy, Lauren

2013-01-01

In 2002, the Bill & Melinda Gates Foundation launched the Early College High School Initiative (ECHSI) with the primary goal of increasing the opportunity for underserved students to earn a postsecondary credential. To achieve this goal, Early Colleges provide underserved students with exposure to, and support in, college while they are in…

Early Diagnosis and Early Intervention in Cerebral Palsy

PubMed Central

Hadders-Algra, Mijna

2014-01-01

This paper reviews the opportunities and challenges for early diagnosis and early intervention in cerebral palsy (CP). CP describes a group of disorders of the development of movement and posture, causing activity limitation that is attributed to disturbances that occurred in the fetal or infant brain. Therefore, the paper starts with a summary of relevant information from developmental neuroscience. Most lesions underlying CP occur in the second half of gestation, when developmental activity in the brain reaches its summit. Variations in timing of the damage not only result in different lesions but also in different neuroplastic reactions and different associated neuropathologies. This turns CP into a heterogeneous entity. This may mean that the best early diagnostics and the best intervention methods may differ for various subgroups of children with CP. Next, the paper addresses possibilities for early diagnosis. It discusses the predictive value of neuromotor and neurological exams, neuroimaging techniques, and neurophysiological assessments. Prediction is best when complementary techniques are used in longitudinal series. Possibilities for early prediction of CP differ for infants admitted to neonatal intensive care and other infants. In the former group, best prediction is achieved with the combination of neuroimaging and the assessment of general movements, in the latter group, best prediction is based on carefully documented milestones and neurological assessment. The last part reviews early intervention in infants developing CP. Most knowledge on early intervention is based on studies in high-risk infants without CP. In these infants, early intervention programs promote cognitive development until preschool age; motor development profits less. The few studies on early intervention in infants developing CP suggest that programs that stimulate all aspects of infant development by means of family coaching are most promising. More research is urgently needed

Early Childhood Systems: Transforming Early Learning

ERIC Educational Resources Information Center

Kagan, Sharon Lynn, Ed.; Kauertz, Kristie, Ed.

2012-01-01

In this seminal volume, leading authorities strategize about how to create early childhood systems that transcend politics and economics to serve the needs of all young children. The authors offer different interpretations of the nature of early childhood systems, discuss the elements necessary to support their development, and examine how…

Energy-resolved attosecond interferometric photoemission from Ag(111) and Au(111) surfaces

NASA Astrophysics Data System (ADS)

Ambrosio, M. J.; Thumm, U.

2018-04-01

Photoelectron emission from solid surfaces induced by attosecond pulse trains into the electric field of delayed phase-coherent infrared (IR) pulses allows the surface-specific observation of energy-resolved electronic phase accumulations and photoemission delays. We quantum-mechanically modeled interferometric photoemission spectra from the (111) surfaces of Au and Ag, including background contributions from secondary electrons and direct emission by the IR pulse, and adjusted parameters of our model to energy-resolved photoelectron spectra recently measured at a synchrotron light source by Roth et al. [J. Electron Spectrosc. 224, 84 (2018), 10.1016/j.elspec.2017.05.008]. Our calculated spectra and photoelectron phase shifts are in fair agreement with the experimental data of Locher et al. [Optica 2, 405 (2015), 10.1364/OPTICA.2.000405]. Our model's not reproducing the measured energy-dependent oscillations of the Ag(111) photoemission phases may be interpreted as evidence for subtle band-structure effects on the final-state photoelectron-surface interaction not accounted for in our simulation.

Early Intervention.

ERIC Educational Resources Information Center

Nathanson, Jeanne H., Ed.

1992-01-01

This theme issue focuses on early intervention. The four articles presented on this theme are: (1) "Deaf Infants, Hearing Mothers: A Research Report" (Kathryn P. Meadow-Orlans, and others), reporting findings on effects of auditory loss on early development; (2) "Maintaining Involvement of Inner City Families in Early Intervention Programs through…

Infusing Early Childhood Mental Health into Early Intervention Services

ERIC Educational Resources Information Center

Grabert, John C.

2009-01-01

This article describes the process of enhancing early childhood mental health awareness and skills in non-mental health staff. The author describes a pilot training model, conducted the U.S. Army's Early Intervention Services, that involved: (a) increasing early childhood mental health knowledge through reflective readings, (b) enhancing…

Early Literacy and Early Numeracy: The Value of Including Early Literacy Skills in the Prediction of Numeracy Development

ERIC Educational Resources Information Center

Purpura, David J.; Hume, Laura E.; Sims, Darcey M.; Lonigan, Cristopher J.

2011-01-01

The purpose of this study was to examine whether early literacy skills uniquely predict early numeracy skills development. During the first year of the study, 69 3- to 5-year-old preschoolers were assessed on the Preschool Early Numeracy Skills (PENS) test and the Test of Preschool Early Literacy Skills (TOPEL). Participants were assessed again a…

Brachytherapy in early prostate cancer--early experience.

PubMed

Jose, B O; Bailen, J L; Albrink, F H; Steinbock, G S; Cornett, M S; Benson, D C; Schmied, W K; Medley, R N; Spanos, W J; Paris, K J; Koerner, P D; Gatenby, R A; Wilson, D L; Meyer, R

1999-01-01

Use of brachytherapy with radioactive seeds in the management of early prostate cancer is commonly used in the United States. The early experience has been reported from the prostate treatment centers in Seattle for the last 10 years. In this manuscript we are reporting our early experience of 150 radioactive seed implantations in early stage prostate cancer using either Iodine 125 or Palladium 103 seeds. The average age of the patient is 66 years and the median Gleason score is 5.4 with a median PSA of 6. A brief description of the evolution of the treatment of prostate cancer as well as the preparation for the seed implantation using the volume study with ultrasound of the prostate, pubic arch study using CT scan of the pelvis and the complete planning using the treatment planning computers are discussed. We also have described the current technique which is used in our experience based on the Seattle guidelines. We plan a follow-up report with the results of the studies with longer follow-up.

Peripatetic and Euclidean theories of the visual ray.

PubMed

Jones, A

1994-01-01

The visual ray of Euclid's Optica is endowed with properties that reveal the concept to be an abstraction of a specific physical account of vision. The evolution of a physical theory of vision compatible with the Euclidean model can be traced in Peripatetic writings of the late fourth and third centuries B.C.

Central Nervous System Idiopathic Inflammatory Demyelinating Disorders in South Americans: A Descriptive, Multicenter, Cross-Sectional Study.

PubMed

Papais-Alvarenga, Regina Maria; Vasconcelos, Claudia Cristina Ferreira; Carra, Adriana; de Castillo, Ibis Soto; Florentin, Sara; Diaz de Bedoya, Fernando Hamuy; Mandler, Raul; de Siervi, Luiza Campanella; Pimentel, Maria Lúcia Vellutini; Alvarenga, Marina Papais; Alvarenga, Marcos Papais; Grzesiuk, Anderson Kuntz; Gama Pereira, Ana Beatriz Calmon; Gomes Neto, Antonio Pereira; Velasquez, Carolina; Soublette, Carlos; Fleitas, Cynthia Veronica; Diniz, Denise Sisteroli; Armas, Elizabeth; Batista, Elizabeth; Hernandez, Freda; Pereira, Fernanda Ferreira Chaves da Costa; Siqueira, Heloise Helena; Cabeça, Hideraldo; Sanchez, Jose; Brooks, Joseph Bruno Bidin; Gonçalves, Marcus Vinicius; Barroso, Maria Cristina Del Negro; Ravelo, Maria Elena; Castillo, Maria Carlota; Ferreira, Maria Lúcia Brito; Rocha, Maria Sheila Guimarães; Parolin, Monica Koncke Fiuza; Molina, Omaira; Marinho, Patricia Beatriz Christino; Christo, Paulo Pereira; Brant de Souza, Renata; Pessanha Neto, Silvio; Camargo, Solange Maria das Graças; Machado, Suzana Costa; Neri, Vanderson Carvalho; Fragoso, Yara Dadalti; Alvarenga, Helcio; Thuler, Luiz Claudio Santos

2015-01-01

The idiopathic inflammatory demyelinating disease (IIDD) spectrum has been investigated among different populations, and the results have indicated a low relative frequency of neuromyelitis optica (NMO) among multiple sclerosis (MS) cases in whites (1.2%-1.5%), increasing in Mestizos (8%) and Africans (15.4%-27.5%) living in areas of low MS prevalence. South America (SA) was colonized by Europeans from the Iberian Peninsula, and their miscegenation with natives and Africans slaves resulted in significant racial mixing. The current study analyzed the IIDD spectrum in SA after accounting for the ethnic heterogeneity of its population. A cross-sectional multicenter study was performed. Only individuals followed in 2011 with a confirmed diagnosis of IIDD using new diagnostic criteria were considered eligible. Patients' demographic, clinical and laboratory data were collected. In all, 1,917 individuals from 22 MS centers were included (73.7% female, 63.0% white, 28.0% African, 7.0% Mestizo, and 0.2% Asian). The main disease categories and their associated frequencies were MS (76.9%), NMO (11.8%), other NMO syndromes (6.5%), CIS (3.5%), ADEM (1.0%), and acute encephalopathy (0.4%). Females predominated in all main categories. The white ethnicity also predominated, except in NMO. Except in ADEM, the disease onset occurred between 20 and 39 years old, early onset in 8.2% of all cases, and late onset occurred in 8.9%. The long-term morbidity after a mean disease time of 9.28±7.7 years was characterized by mild disability in all categories except in NMO, which was scored as moderate. Disease time among those with MS was positively correlated with the expanded disability status scale (EDSS) score (r=0.374; p=<0.001). This correlation was not observed in people with NMO or those with other NMO spectrum disorders (NMOSDs). Among patients with NMO, 83.2% showed a relapsing-remitting course, and 16.8% showed a monophasic course. The NMO-IgG antibody tested using indirect

Central Nervous System Idiopathic Inflammatory Demyelinating Disorders in South Americans: A Descriptive, Multicenter, Cross-Sectional Study

PubMed Central

Papais-Alvarenga, Regina Maria; Vasconcelos, Claudia Cristina Ferreira; Carra, Adriana; de Castillo, Ibis Soto; Florentin, Sara; Diaz de Bedoya, Fernando Hamuy; Mandler, Raul; de Siervi, Luiza Campanella; Pimentel, Maria Lúcia Vellutini; Alvarenga, Marina Papais; Papais Alvarenga, Marcos; Grzesiuk, Anderson Kuntz; Gama Pereira, Ana Beatriz Calmon; Gomes Neto, Antonio Pereira; Velasquez, Carolina; Soublette, Carlos; Fleitas, Cynthia Veronica; Diniz, Denise Sisteroli; Armas, Elizabeth; Batista, Elizabeth; Hernandez, Freda; Pereira, Fernanda Ferreira Chaves da Costa; Siqueira, Heloise Helena; Cabeça, Hideraldo; Sanchez, Jose; Brooks, Joseph Bruno Bidin; Gonçalves, Marcus Vinicius; Barroso, Maria Cristina Del Negro; Ravelo, Maria Elena; Castillo, Maria Carlota; Ferreira, Maria Lúcia Brito; Rocha, Maria Sheila Guimarães; Parolin, Monica Koncke Fiuza; Molina, Omaira; Marinho, Patricia Beatriz Christino; Christo, Paulo Pereira; Brant de Souza, Renata; Pessanha Neto, Silvio; Camargo, Solange Maria das Graças; Machado, Suzana Costa; Neri, Vanderson Carvalho; Fragoso, Yara Dadalti; Alvarenga, Helcio; Thuler, Luiz Claudio Santos

2015-01-01

The idiopathic inflammatory demyelinating disease (IIDD) spectrum has been investigated among different populations, and the results have indicated a low relative frequency of neuromyelitis optica (NMO) among multiple sclerosis (MS) cases in whites (1.2%-1.5%), increasing in Mestizos (8%) and Africans (15.4%-27.5%) living in areas of low MS prevalence. South America (SA) was colonized by Europeans from the Iberian Peninsula, and their miscegenation with natives and Africans slaves resulted in significant racial mixing. The current study analyzed the IIDD spectrum in SA after accounting for the ethnic heterogeneity of its population. A cross-sectional multicenter study was performed. Only individuals followed in 2011 with a confirmed diagnosis of IIDD using new diagnostic criteria were considered eligible. Patients’ demographic, clinical and laboratory data were collected. In all, 1,917 individuals from 22 MS centers were included (73.7% female, 63.0% white, 28.0% African, 7.0% Mestizo, and 0.2% Asian). The main disease categories and their associated frequencies were MS (76.9%), NMO (11.8%), other NMO syndromes (6.5%), CIS (3.5%), ADEM (1.0%), and acute encephalopathy (0.4%). Females predominated in all main categories. The white ethnicity also predominated, except in NMO. Except in ADEM, the disease onset occurred between 20 and 39 years old, early onset in 8.2% of all cases, and late onset occurred in 8.9%. The long-term morbidity after a mean disease time of 9.28±7.7 years was characterized by mild disability in all categories except in NMO, which was scored as moderate. Disease time among those with MS was positively correlated with the expanded disability status scale (EDSS) score (r=0.374; p=<0.001). This correlation was not observed in people with NMO or those with other NMO spectrum disorders (NMOSDs). Among patients with NMO, 83.2% showed a relapsing-remitting course, and 16.8% showed a monophasic course. The NMO-IgG antibody tested using indirect

Early literacy and early numeracy: the value of including early literacy skills in the prediction of numeracy development.

PubMed

Purpura, David J; Hume, Laura E; Sims, Darcey M; Lonigan, Christopher J

2011-12-01

The purpose of this study was to examine whether early literacy skills uniquely predict early numeracy skills development. During the first year of the study, 69 3- to 5-year-old preschoolers were assessed on the Preschool Early Numeracy Skills (PENS) test and the Test of Preschool Early Literacy Skills (TOPEL). Participants were assessed again a year later on the PENS test and on the Applied Problems and Calculation subtests of the Woodcock-Johnson III Tests of Achievement. Three mixed effect regressions were conducted using Time 2 PENS, Applied Problems, and Calculation as the dependent variables. Print Knowledge and Vocabulary accounted for unique variance in the prediction of Time 2 numeracy scores. Phonological Awareness did not uniquely predict any of the mathematics domains. The findings of this study identify an important link between early literacy and early numeracy development. Copyright © 2011 Elsevier Inc. All rights reserved.

Early Childhood Special Education and Early Intervention Personnel Preparation Standards of the Division for Early Childhood: Field Validation

ERIC Educational Resources Information Center

Cochran, Deborah C.; Gallagher, Peggy A.; Stayton, Vicki D.; Dinnebeil, Laurie A.; Lifter, Karin; Chandler, Lynette K.; Christensen, Kimberly A.

2012-01-01

Results of the field validation survey of the revised initial and new advanced Council for Exceptional Children (CEC) Division for Early Childhood (DEC) early childhood special education (ECSE)/early intervention (EI) personnel standards are presented. Personnel standards are used as part of educational accountability systems and in teacher…

Early Attachment Relationships and the Early Childhood Curriculum

ERIC Educational Resources Information Center

Cortazar, Alejandra; Herreros, Francisca

2010-01-01

This article explores the relationship between attachment theory and the early childhood curriculum. During the first years of life children develop early attachment relationships with their primary caregivers. These attachment relationships, either secure or insecure, will shape children's socio-emotional development. In the USA, the predominant…

Classification of shiga toxin-producing escherichia coli (STEC) serotypes with hyperspectral microscope imagery

USDA-ARS?s Scientific Manuscript database

Non-O157:H7 Shiga toxin-producing Escherichia coli (STEC) strains such as O26, O45, O103, O111, O121 and O145 are recognized as serious outbreak to cause human illness due to their toxicity. Since a conventional microbiological method for cell counting is laborious and time-consuming process, optica...

Early Years Practitioners' Views on Early Personal, Social and Emotional Development

ERIC Educational Resources Information Center

Aubrey, Carol; Ward, Karen

2013-01-01

Current policy guidance stresses the need for early identification of obstacles to learning and appropriate intervention. New standards for learning (Early Years Foundation Stage) place personal, social and emotional development (PSED) as central to learning and development. This paper reports a survey and follow-up interviews with early years…

Seizures and Encephalitis in Myelin Oligodendrocyte Glycoprotein IgG Disease vs Aquaporin 4 IgG Disease.

PubMed

Hamid, Shahd H M; Whittam, Dan; Saviour, Mariyam; Alorainy, Amal; Mutch, Kerry; Linaker, Samantha; Solomon, Tom; Bhojak, Maneesh; Woodhall, Mark; Waters, Patrick; Appleton, Richard; Duddy, Martin; Jacob, Anu

2018-01-01

Antibodies to myelin oligodendrocyte glycoprotein IgG (MOG-IgG) are increasingly detected in patients with non-multiple sclerosis-related demyelination, some of whom manifest a neuromyelitis optica (NMO) phenotype. Cortical involvement, encephalopathy, and seizures are rare in aquaporin 4 antibody (AQP4-IgG)-related NMO in the white European population. However, the authors encountered several patients with seizures associated with MOG-IgG disease. To compare incidence of seizures and encephalitis-like presentation, or both between AQP4-IgG-positive and MOG-IgG-positive patients. Retrospective case series of all patients who were seropositive for MOG-IgG (n = 34) and the last 100 patients with AQP4-IgG disease (NMO spectrum disorder) seen in the NMO service between January 2013 and December 2016, and analysis was completed January 4, 2017. All patients were seen in a tertiary neurological center, The Walton Centre NHS Foundation Trust in Liverpool, England. The difference in seizure frequency between the AQP4-IgG-positive and MOG-IgG-positive patient groups was determined. Thirty-four patients with MOG-IgG disease (20 female) with a median age at analysis of 30.5 years (interquartile range [IQR], 15-69 years), and 100 AQP4-IgG-positive patients (86 female) with a median age at analysis of 54 years (IQR, 12-91 years) were studied. Most patients were of white race. Five of the 34 patients with MOG-IgG (14.7%) had seizures compared with 1 patient with AQP4-IgG (2-sided P < .008, Fisher test). On magnetic resonance imaging, all 5 MOG-IgG-positive patients had inflammatory cortical brain lesions associated with the seizures. In 3 of the 5 MOG-IgG-positive patients, seizures occurred as part of the index event. Four of the 5 presented with encephalopathy and seizures, and disease relapsed in all 5 patients. Four of these patients were receiving immunosuppressant medication at last follow-up, and 3 continued to take antiepileptic medication. In contrast, the only

Early menarche, nulliparity and the risk for premature and early natural menopause.

PubMed

Mishra, Gita D; Pandeya, Nirmala; Dobson, Annette J; Chung, Hsin-Fang; Anderson, Debra; Kuh, Diana; Sandin, Sven; Giles, Graham G; Bruinsma, Fiona; Hayashi, Kunihiko; Lee, Jung Su; Mizunuma, Hideki; Cade, Janet E; Burley, Victoria; Greenwood, Darren C; Goodman, Alissa; Simonsen, Mette Kildevæld; Adami, Hans-Olov; Demakakos, Panayotes; Weiderpass, Elisabete

2017-03-01

Are parity and the timing of menarche associated with premature and early natural menopause? Early menarche (≤11 years) is a risk factor for both premature menopause (final menstrual period, FMP <40 years) and early menopause (FMP 40-44 years), a risk that is amplified for nulliparous women. Women with either premature or early menopause face an increased risk of chronic conditions in later life and of early death. Findings from some studies suggest that early menarche and nulliparity are associated with early menopause, however overall the evidence is mixed. Much of the evidence for a direct relationship is hampered by a lack of comparability across studies, failure to adjust for confounding factors and inadequate statistical power. This pooled study comprises 51 450 postmenopausal women from nine observational studies in the UK, Scandinavia, Australia and Japan that contribute to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Age at menarche (categorized as ≤11, 12, 13, 14 and 15 or more years) and parity (categorized as no children, one child and two or more children) were exposures of interest. Age at FMP was confirmed by at least 12 months of cessation of menses where this was not the result of an intervention (such as surgical menopause due to bilateral oophorectomy or hysterectomy) and categorized as premature menopause (FMP before age 40), early menopause (FMP 40-44 years), 45-49 years, 50-51 years, 52-53 years and 54 or more years. We used multivariate multinomial logistic regression models to estimate relative risk ratio (RRR) and 95% CI for associations between menarche, parity and age at FMP adjusting for within-study correlation. The median age at FMP was 50 years (interquartile range 48-53 years), with 2% of the women experiencing premature menopause and 7.6% early menopause. Women with early menarche (≤11 years, compared with 12-13 years) were at higher risk of premature

Recent Coverage of Early Childhood Education Approaches in Open Access Early Childhood Journals

ERIC Educational Resources Information Center

Keskin, Burhanettin

2016-01-01

A content analysis of the coverage of the major approaches to early childhood education in the early childhood research journals, published between 2010 and 2014, that are early childhood research oriented and have free online access were investigated. Among 21 journals in early childhood education, two journals were selected for the content…

Early Educational Intervention, Early Cumulative Risk, and the Early Home Environment as Predictors of Young Adult Outcomes within a High-Risk Sample

ERIC Educational Resources Information Center

Pungello, Elizabeth P.; Kainz, Kirsten; Burchinal, Margaret; Wasik, Barbara H.; Sparling, Joseph J.; Ramey, Craig T.; Campbell, Frances A.

2010-01-01

The extent to which early educational intervention, early cumulative risk, and the early home environment were associated with young adult outcomes was investigated in a sample of 139 young adults (age 21) from high-risk families enrolled in randomized trials of early intervention. Positive effects of treatment were found for education attainment,…

[In-patient (early) rehabilitation].

PubMed

Wallesch, Claus-W; Lautenschläger, Sindy

2017-04-01

It is difficult to develop the financing and hospital provision of interventions for early rehabilitation within the diagnosis-related group (DRG) system. In addition to a range of partially rehabilitative complex interventions, the system recognizes three main forms of early rehabilitative interventions: geriatric, neurological/neurosurgical, and interdisciplinary and others. In this article, the appropriate definitions and cost-effectiveness of these procedures are analyzed and compared. The early rehabilitative interventions are characterized by constant cooperation in the therapeutic team, especially neurological early rehabilitation through the incorporation of nursing as a therapeutic profession. Whereas geriatric and neurological early rehabilitation are reflected in the DRG system, the former provided in many general hospitals and the latter mainly in specialized institutions, interdisciplinary early rehabilitation has only occasionally been represented in the DRG system so far. If all acute in-patients who require early rehabilitation should receive such an intervention, an additional fee must be implemented for this this interdisciplinary service.

African ancestry, early life exposures, and respiratory morbidity in early childhood.

PubMed

Kumar, R; Tsai, H-J; Hong, X; Gignoux, C; Pearson, C; Ortiz, K; Fu, M; Pongracic, J A; Burchard, E G; Bauchner, H; Wang, X

2012-02-01

Racial disparities persist in early childhood wheezing and cannot be completely explained by known risk factors. To evaluate the associations of genetic ancestry and self-identified race with early childhood recurrent wheezing, accounting for socio-economic status (SES) and early life exposures. We studied 1034 children in an urban, multi-racial, prospective birth cohort. Multivariate logistic regression was used to evaluate the association of genetic ancestry as opposed to self-identified race with recurrent wheezing (>3 episodes). Sequential models accounted for demographic, socio-economic factors and early life risk factors. Genetic ancestry, estimated using 150 ancestry informative markers, was expressed in deciles. Approximately 6.1% of subjects (mean age 3.1 years) experienced recurrent wheezing. After accounting for SES and demographic factors, African ancestry (OR: 1.16, 95% CI: 1.02-1.31) was significantly associated with recurrent wheezing. By self-reported race, hispanic subjects had a borderline decrease in risk of wheeze compared with African Americans (OR: 0.44, 95% CI: 0.19-1.00), whereas white subjects (OR: 0.46, 95% CI: 0.14-1.57) did not have. After further adjustment for known confounders and early life exposures, both African (OR: 1.19, 95% CI: 1.05-1.34) and European ancestry (OR: 0.84, 95% CI: 0.74-0.94) retained a significant association with recurrent wheezing, as compared with self-identified race (OR(whites) : 0.31, 95% CI: 0.09-1.14; OR(hispanic) : 0.47, 95% CI: 0.20-1.08). There were no significant interactions between ancestry and early life factors on recurrent wheezing. In contrast to self-identified race, African ancestry remained a significant, independent predictor of early childhood wheezing after accounting for early life and other known risk factors associated with lung function changes and asthma. Genetic ancestry may be a powerful way to evaluate wheezing disparities and a proxy for differentially distributed genetic and

African ancestry, early life exposures, and respiratory morbidity in early childhood

PubMed Central

Kumar, R.; Tsai, H.-J.; Hong, X.; Gignoux, C.; Pearson, C.; Ortiz, K.; Fu, M.; Pongracic, J. A.; Burchard, E. G.; Bauchner, H.; Wang, X.

2012-01-01

Summary Background Racial disparities persist in early childhood wheezing and cannot be completely explained by known risk factors. Objective To evaluate the associations of genetic ancestry and self-identified race with early childhood recurrent wheezing, accounting for socio-economic status (SES) and early life exposures. Methods We studied 1034 children in an urban, multi-racial, prospective birth cohort. Multivariate logistic regression was used to evaluate the association of genetic ancestry as opposed to self-identified race with recurrent wheezing (>3 episodes). Sequential models accounted for demographic, socio-economic factors and early life risk factors. Genetic ancestry, estimated using 150 ancestry informative markers, was expressed in deciles. Results Approximately 6.1% of subjects (mean age 3.1 years) experienced recurrent wheezing. After accounting for SES and demographic factors, African ancestry (OR: 1.16, 95% CI: 1.02–1.31) was significantly associated with recurrent wheezing. By self-reported race, hispanic subjects had a borderline decrease in risk of wheeze compared with African Americans (OR: 0.44, 95% CI: 0.19–1.00), whereas white subjects (OR: 0.46, 95% CI: 0.14–1.57) did not have. After further adjustment for known confounders and early life exposures, both African (OR: 1.19, 95% CI: 1.05–1.34) and European ancestry (OR: 0.84, 95% CI: 0.74–0.94) retained a significant association with recurrent wheezing, as compared with self-identified race (ORwhites: 0.31, 95% CI: 0.09–1.14; ORhispanic: 0.47, 95% CI: 0.20–1.08). There were no significant interactions between ancestry and early life factors on recurrent wheezing. Conclusions and Clinical Relevance In contrast to self-identified race, African ancestry remained a significant, independent predictor of early childhood wheezing after accounting for early life and other known risk factors associated with lung function changes and asthma. Genetic ancestry may be a powerful way to

A Study of the Relationship between Early Childhood Program Attributes and Early Childhood Reading Achievement

ERIC Educational Resources Information Center

Washington, Novella M.

2012-01-01

This quantitative correlational study focuses on the relationship between early childhood program attributes and early childhood reading success. Data will be gathered from early childhood sites with grades prekindergarten through second grade in which early childhood program attributes exist and early childhood reading is measured by the…

Early Childhood Diplomacy: Policy Planning for Early Childhood Development

ERIC Educational Resources Information Center

Vargas-Barón, Emily; Diehl, Kristel

2018-01-01

Children who are well nurtured, appropriately cared for, and provided with positive learning opportunities in their early years have a better chance of becoming healthy and productive citizens of nations and of the world. This article reviews the art and science of policy planning for early childhood development (ECD) from a diplomacy perspective.…

Dynamical Imaging using Spatial Nonlinearity

DTIC Science & Technology

2014-01-29

643. [5] R. Heintzmann, C. Cremer , Lateral modulated excitation microscopy: Improvement of resolution by using a diffraction grating, Proceedings...by stochastic optical reconstruction microscopy (STORM), Nat Methods, 3 ( 2006 ) 793-795. [14] E. Betzig, G.H. Patterson, R. Sougrat, O.W. Lindwasser...Science, 313 ( 2006 ) 1642-1645. [15] W. Lukosz, M. Marchand, Optischen Abbildung Unter Überschreitung der Beugungsbedingten Auflösungsgrenze, Optica

Gregory [Gregorie], James (1638-75)

NASA Astrophysics Data System (ADS)

Murdin, P.

2000-11-01

Scottish mathematician and optician, born in Aberdeen. Gregory described in Optica Promota a design (which he never realized) for the first practical reflecting telescope in which a perforated primary concave parabolic mirror converges the light to the focus of a concave ellipsoidal secondary mirror. The light is reflected back to the ellipsoid's second focus behind the main mirror. A real image ...

Overview of Play: Its Uses and Importance in Early Intervention/Early Childhood Special Education

ERIC Educational Resources Information Center

Lifter, Karin; Foster-Sanda, Suzanne; Arzamarski, Caley; Briesch, Jacquelyn; McClure, Ellen

2011-01-01

Play is a natural activity of early childhood, which has great relevance to the fields of early intervention, early childhood special education, and early childhood education. Within these fields, ongoing tensions persist in how play is described and used. These tensions compromise activities of assessment, intervention, and curriculum development…

Early Number Skills Gains and Mathematics Achievement: Intervening to Establish Successful Early Mathematics Trajectories

ERIC Educational Resources Information Center

Shanley, Lina; Clarke, Ben; Doabler, Christian T.; Kurtz-Nelson, Evangeline; Fien, Hank

2017-01-01

Early number skills, comprised of both informal and formal skills, are associated with later mathematics achievement. Thus, the development of foundational early number skills is an important aspect of early mathematics instruction. This study explored relations between early number skills gains and mathematics achievement for students at risk for…

Individual differences in early adolescents' latent trait cortisol (LTC): Relation to early adversity.

PubMed

Stroud, Catherine B; Chen, Frances R; Doane, Leah D; Granger, Douglas A

2016-09-01

Substantial evidence suggests that youth who experience early adversity exhibit alterations in hypothalamic pituitary adrenal (HPA) axis functioning, thereby increasing risk for negative health outcomes. However, few studies have explored whether early adversity alters enduring trait indicators of HPA axis activity. Using objective contextual stress interviews with adolescents and their mothers to assess early adversity, we examined the cumulative impact of nine types of early adversity on early adolescents girls' latent trait cortisol (LTC). Adolescents (n = 122; M age = 12.39 years) provided salivary cortisol samples three times a day (waking, 30 min post-waking, and bedtime) over 3 days. Latent state-trait modeling indicated that the waking and 30 min post-waking samples contributed to a LTC factor. Moreover, greater early adversity was associated with a lower LTC level. Implications of LTC for future research examining the impact of early adversity on HPA axis functioning are discussed. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58:700-713, 2016. © 2016 Wiley Periodicals, Inc.

Reframing Early Childhood Leadership

ERIC Educational Resources Information Center

Stamopoulos, Elizabeth

2012-01-01

Rapid changes in Australian education have intensified the role of early childhood leaders and led to unprecedented challenges. The Australian Curriculum (ACARA, 2011), mandated Australian "National Quality Framework" (NQF) for Early Childhood Education & Care (DEEWR, 2010b) and the "National Early Years Learning Framework"…

Earth's early biosphere

NASA Technical Reports Server (NTRS)

Des Marais, D. J.

1998-01-01

Understanding our own early biosphere is essential to our search for life elsewhere, because life arose on Earth very early and rocky planets shared similar early histories. The biosphere arose before 3.8 Ga ago, was exclusively unicellular and was dominated by hyperthermophiles that utilized chemical sources of energy and employed a range of metabolic pathways for CO2 assimilation. Photosynthesis also arose very early. Oxygenic photosynthesis arose later but still prior to 2.7 Ga. The transition toward the modern global environment was paced by a decline in volcanic and hydrothermal activity. These developments allowed atmospheric O2 levels to increase. The O2 increase created new niches for aerobic life, most notably the more advanced Eukarya that eventually spawned the megascopic fauna and flora of our modern biosphere.

Value-Added Early Learning

ERIC Educational Resources Information Center

Dichter, Harriet

2011-01-01

Elected state leaders often prioritize economic prosperity and competitiveness, which provides an important opportunity too rarely taken for investing in early education. In 2003, Pennsylvania recognized the connection between early education and the economy, and smartly embraced early learning as part of its economic prosperity and…

Abnormal early cleavage events predict early embryo demise: sperm oxidative stress and early abnormal cleavage.

PubMed

Burruel, Victoria; Klooster, Katie; Barker, Christopher M; Pera, Renee Reijo; Meyers, Stuart

2014-10-13

Human embryos resulting from abnormal early cleavage can result in aneuploidy and failure to develop normally to the blastocyst stage. The nature of paternal influence on early embryo development has not been directly demonstrated although many studies have suggested effects from spermatozoal chromatin packaging, DNA damage, centriolar and mitotic spindle integrity, and plasma membrane integrity. The goal of this study was to determine whether early developmental events were affected by oxidative damage to the fertilizing sperm. Survival analysis was used to compare patterns of blastocyst formation based on P2 duration. Kaplan-Meier survival curves demonstrate that relatively few embryos with short (<1 hr) P2 times reached blastocysts, and the two curves diverged beginning on day 4, with nearly all of the embryos with longer P2 times reaching blastocysts by day 6 (p < .01). We determined that duration of the 2nd to 3rd mitoses were sensitive periods in the presence of spermatozoal oxidative stress. Embryos that displayed either too long or too short cytokineses demonstrated an increased failure to reach blastocyst stage and therefore survive for further development. Although paternal-derived gene expression occurs later in development, this study suggests a specific role in early mitosis that is highly influenced by paternal factors.

Early College Entrance in Australia

ERIC Educational Resources Information Center

Jung, Jae Yup; Young, Marie; Gross, Miraca U. M.

2015-01-01

Early college entry is an educational intervention that is being increasingly used in Australia. Following a review of the current Australian literature on early college entry, an overview is provided of the characteristics of, and the procedures associated with, one formal Australian early college entry program (the Early Admission for…

The link between early onset drinking and early onset alcohol-impaired driving in young males.

PubMed

Zhang, Lening; Wieczorek, William F; Welte, John W

2014-05-01

Young drivers represent a disproportionate number of the individuals involved in alcohol-impaired driving. Although there is a known association between drinking and alcohol-impaired driving in young drivers, the link between early onset drinking and early onset alcohol-impaired driving has not been explored. The present study aimed to assess this link along with potentially confounding factors. The assessment used a proportional hazards model with data collected from the Buffalo Longitudinal Study of Young Men, a population-based sample of 625 males at aged 16-19. Controlling for the effects of potentially relevant confounds, the early onset of drinking was the most influential factor in predicting the early onset of alcohol-impaired driving. Race and the early onset of other forms of delinquency also played a significant role in the early onset of alcohol-impaired driving. Preventing an early start of drinking among adolescents may be the most critical factor to address in preventing an early start of alcohol-impaired driving.

Cognitive Development in Early Readers.

ERIC Educational Resources Information Center

Briggs, Chari; Elkind, David

Some studies of early readers are discussed. It is pointed out that study of early readers has relevance for practical and theoretical issues in psychology and education. Of interest in this document are the following questions: (1) Are there any special talents or traits distinguishing early from non-early readers? (2) Do children who read early…

Special Session on Adaptive Optics in Russia and China. Volume 23

DTIC Science & Technology

1995-01-01

Fisica Aplicada. Universidad de Cantabria. 39005. SANTANDER. SPAIN. Tel: 42-201445. Fax: 42-201402. 1.- INTRODUCTION To estimate the centroid of a light...Lia M. Zerbino ##, Eduardo Aguirre +, Anibal P. Laquidara ++ and Mario-Garavaglia ft. Centro de Investigaciones Opticas (CIOp) CC 124 Correo Central...Professor at Universidad Nacional dt La Plata and CONICET Engiuneer. C (lOp belongs to Consejo Nacional de Investigaciones Cientificas y Ticnicas (CONICET

THE LINK BETWEEN EARLY ONSET DRINKING AND EARLY ONSET ALCOHOL-IMPAIRED DRIVING IN YOUNG MALES

PubMed Central

Zhang, Lening; Wieczorek, William F.; Welte, John W.

2014-01-01

Background Young drivers represent a disproportionate number of the individuals involved in alcohol-impaired driving. Although there is a known association between drinking and alcohol-impaired driving in young drivers, the link between early onset drinking and early onset alcohol-impaired driving has not been explored. Objectives The present study aimed to assess this link along with potentially confounding factors. Methods The assessment used a proportional hazards model with data collected from the Buffalo Longitudinal Study of Young Men, a population based sample of 625 males at ages of 16–19 years old. Results Controlling for the effects of potentially relevant confounds, the early onset of drinking was the most influential factor in predicting the early onset of alcohol-impaired driving. Race and the early onset of other forms of delinquency also played a significant role in the early onset of alcohol-impaired driving. Conclusion Preventing an early start of drinking among adolescents may be the most critical factor to address in preventing an early start of alcohol-impaired driving. PMID:24766089

Famines in Africa: is early warning early enough?

PubMed Central

Kim, Jeeyon Janet; Guha-Sapir, Debarati

2012-01-01

Following the second Sahelian famine in 1984–1985, major investments were made to establish Early Warning Systems. These systems help to ensure that timely warnings and vulnerability information are available to decision makers to anticipate and avert food crises. In the recent crisis in the Horn of Africa, alarming levels of acute malnutrition were documented from March 2010, and by August 2010, an impending food crisis was forecast. Despite these measures, the situation remained unrecognised, and further deteriorated causing malnutrition levels to grow in severity and scope. By the time the United Nations officially declared famine on 20 July 2011, and the humanitarian community sluggishly went into response mode, levels of malnutrition and mortality exceeded catastrophic levels. At this time, an estimated 11 million people were in desperate and immediate need for food. With warnings of food crises in the Sahel, South Sudan, and forecast of the drought returning to the Horn, there is an immediate need to institutionalize change in the health response during humanitarian emergencies. Early warning systems are only effective if they trigger an early response. PMID:22745628

Famines in Africa: is early warning early enough?

PubMed

Kim, Jeeyon Janet; Guha-Sapir, Debarati

2012-01-01

Following the second Sahelian famine in 1984-1985, major investments were made to establish Early Warning Systems. These systems help to ensure that timely warnings and vulnerability information are available to decision makers to anticipate and avert food crises. In the recent crisis in the Horn of Africa, alarming levels of acute malnutrition were documented from March 2010, and by August 2010, an impending food crisis was forecast. Despite these measures, the situation remained unrecognised, and further deteriorated causing malnutrition levels to grow in severity and scope. By the time the United Nations officially declared famine on 20 July 2011, and the humanitarian community sluggishly went into response mode, levels of malnutrition and mortality exceeded catastrophic levels. At this time, an estimated 11 million people were in desperate and immediate need for food. With warnings of food crises in the Sahel, South Sudan, and forecast of the drought returning to the Horn, there is an immediate need to institutionalize change in the health response during humanitarian emergencies. Early warning systems are only effective if they trigger an early response.

Employment and educational outcomes in early intervention programmes for early psychosis: a systematic review.

PubMed

Bond, G R; Drake, R E; Luciano, A

2015-10-01

Young adults with early psychosis want to pursue normal roles - education and employment. This paper summarises the empirical literature on the effectiveness of early intervention programmes for employment and education outcomes. We conducted a systematic review of employment/education outcomes for early intervention programmes, distinguishing three programme types: (1) those providing supported employment, (2) those providing unspecified vocational services and (3) those without vocational services. We summarised findings for 28 studies. Eleven studies evaluated early intervention programmes providing supported employment. In eight studies that reported employment outcomes separately from education outcomes, the employment rate during follow-up for supported employment patients was 49%, compared with 29% for patients receiving usual services. The two groups did not differ on enrolment in education. In four controlled studies, meta-analysis showed that the employment rate for supported employment participants was significantly higher than for control participants, odds ratio = 3.66 [1.93-6.93], p < 0.0001. Five studies (four descriptive and one quasi-experimental) of early intervention programmes evaluating unspecified vocational services were inconclusive. Twelve studies of early intervention programmes without vocational services were methodologically heterogeneous, using diverse methods for evaluating vocational/educational outcomes and precluding a satisfactory meta-analytic synthesis. Among studies with comparison groups, 7 of 11 (64%) reported significant vocational/education outcomes favouring early intervention over usual services. In early intervention programmes, supported employment moderately increases employment rates but not rates of enrolment in education. These improvements are in addition to the modest effects early programmes alone have on vocational/educational outcomes compared with usual services.

The Association between Early Conduct Problems and Early Marijuana Use in College Students

ERIC Educational Resources Information Center

Falls, Benjamin J.; Wish, Eric D.; Garnier, Laura M.; Caldeira, Kimberly M.; O'Grady, Kevin E.; Vincent, Kathryn B.; Arria, Amelia M.

2011-01-01

Early conduct problems have been linked to early marijuana use in adolescence. The present study examines this association in a sample of 1,076 college students that was divided into three groups: (1) early marijuana users (began marijuana use prior to age 15; N = 126), (2) late marijuana users (began marijuana use at or after age 15; N = 607),…

A multicentre randomiSed controlled TRial of IntraVEnous immunoglobulin compared with standard therapy for the treatment of transverse myelitis in adults and children (STRIVE).

PubMed

Absoud, Michael; Brex, Peter; Ciccarelli, Olga; Diribe, Onyinye; Giovannoni, Gavin; Hellier, Jennifer; Howe, Rosemary; Holland, Rachel; Kelly, Joanna; McCrone, Paul; Murphy, Caroline; Palace, Jackie; Pickles, Andrew; Pike, Michael; Robertson, Neil; Jacob, Anu; Lim, Ming

2017-05-01

Transverse myelitis (TM) is an immune-mediated disorder of the spinal cord that affects adults and children and that causes motor, sensory and autonomic dysfunction. There is a prolonged recovery phase, which may continue for many years. Neuromyelitis optica (NMO) is an uncommon relapsing inflammatory central nervous system condition in which TM can be the first presenting symptom. As TM and NMO affect many patients in the prime of their working life, the disorder can impose a significant demand on health resources. There are currently no robust controlled trials in children or adults to inform the optimal treatment of TM. However, treatment with intravenous immunoglobulin (IVIG) is being effectively used in the management of a range of neurological conditions. Although other interventions such as plasma exchange (PLEX) in addition to intravenous (IV) methylprednisolone therapy can be beneficial in TM, PLEX is costly and technically challenging to deliver in the acute setting. IVIG is more readily accessible and less costly. To evaluate whether additional and early treatment with IVIG is of extra benefit in TM compared with standard therapy with IV steroids. A multicentre, single-blind, parallel-group randomised controlled trial of IVIG compared with standard therapy for the treatment of TM in adults and children. Patients aged ≥ 1 year diagnosed with either acute first-onset TM or first presentation of NMO. Target recruitment was 170 participants (85 participants per arm). Participants were randomised 1 : 1 to treatment with IV methylprednisolone only or treatment with IV methylprednisolone plus 2 g/kg of IVIG in divided doses within 5 days of the first commencement of steroid therapy. Primary outcome measure - American Spinal Injury Association (ASIA) Impairment Scale at 6 months post randomisation, with a good outcome defined by a two-grade change. Secondary and tertiary outcome measures - ASIA motor and sensory scales, Expanded Disability Status Scale

Early Childhood Education.

ERIC Educational Resources Information Center

Elkind, David

In five sections, this paper explores dimensions of early childhood education: schooling generally construed as nonparental instruction in knowledge, values, and skills. Section 1 looks at some of the factors which have contributed to the rapid growth of early childhood education in modern times. Section 2 briefly highlights the contributions of…

Early Pregnancy Loss

MedlinePlus

... known pregnancies. What causes early pregnancy loss? About one half of cases of early pregnancy loss are caused by a ... do not show any signs of an infection, one option is to wait and let the ... may take longer in some cases. Another option is to take medication that helps ...

Early Retirement Payoff

ERIC Educational Resources Information Center

Fitzpatrick, Maria D.; Lovenheim, Michael F.

2014-01-01

As public budgets have grown tighter over the past decade, states and school districts have sought ways to control the growth of spending. One increasingly common strategy employed to rein in costs is to offer experienced teachers with high salaries financial incentives to retire early. Although early retirement incentive (ERI) programs have been…

Rethinking Early Education

ERIC Educational Resources Information Center

Celeste, Eric

2017-01-01

The National Association for the Education of Young Children (NAEYC) says in its current policy paper that, for high-quality early education to exist outside of tiny islands across the country, the following must be addressed: (1) teacher preparation; (2) ongoing professional learning; and (3) disparity in early education teacher pay. To achieve…

Biological aspects of early osteoarthritis.

PubMed

Madry, Henning; Luyten, Frank P; Facchini, Andrea

2012-03-01

Early OA primarily affects articular cartilage and involves the entire joint, including the subchondral bone, synovial membrane, menisci and periarticular structures. The aim of this review is to highlight the molecular basis and histopathological features of early OA. Selective review of literature. Risk factors for developing early OA include, but are not limited to, a genetic predisposition, mechanical factors such as axial malalignment, and aging. In early OA, the articular cartilage surface is progressively becoming discontinuous, showing fibrillation and vertical fissures that extend not deeper than into the mid-zone of the articular cartilage, reflective of OARSI grades 1.0-3.0. Early changes in the subchondral bone comprise a progressive increase in subchondral plate and subarticular spongiosa thickness. Early OA affects not only the articular cartilage and the subchondral bone but also other structures of the joint, such as the menisci, the synovial membrane, the joint capsule, ligaments, muscles and the infrapatellar fat pad. Genetic markers or marker combinations may become useful in the future to identify early OA and patients at risk. The high socioeconomic impact of OA suggests that a better insight into the mechanisms of early OA may be a key to develop more targeted reconstructive therapies at this first stage of the disease. Systematic review, Level II.

Eco-Early Childhood Education: A New Paradigm of Early Childhood Education in South Korea

ERIC Educational Resources Information Center

Kim, Eunju; Lim, Jaetack

2007-01-01

In the early 1990s, university faculty members, early childhood educators, and preschool teachers in South Korea created a new paradigm for education. Eco-early childhood education uses an ecological point of view to reform existing child-centered education. This perspective proposes moving from child- to life-centered, individual- to…

Course of Disinhibited Social Engagement Disorder From Early Childhood to Early Adolescence.

PubMed

Guyon-Harris, Katherine L; Humphreys, Kathryn L; Fox, Nathan A; Nelson, Charles A; Zeanah, Charles H

2018-05-01

Disinhibited social engagement disorder (DSED) is poorly understood beyond early childhood. The course of DSED signs in a sample of children who experienced severe, early deprivation from early childhood to early adolescence was examined using variable-centered (linear mixed modeling) and person-centered (growth mixture modeling) approaches. The study included 124 children with a history of institutional care from a randomized controlled trial of foster care as an alternative to institutional care and 69 community comparison children matched by age and sex. DSED signs were assessed at baseline (mean age 22 months), 30, 42, and 54 months of age, and 8 and 12 years of age using a validated caregiver report of disturbed attachment behavior. Variable-centered analyses based on intent-to-treat groups indicated that signs of DSED decreased sharply for children randomized to foster care and decreased slightly but remained high for children randomized to care as usual. Person-centered analyses showed 4 profiles (i.e., elevated, persistent modest, early decreasing, and minimal). Elevated and persistent modest courses were associated with greater placement disruptions (F 3,99  = 4.29, p = .007, partial eta-squared [η 2 ] = 0.12), older age at placement into foster care (F 3,56  = 3.41, p < .05, partial η 2  = 0.16), and more time in institutional care (F 3,115  = 11.91, p < .001, partial η 2  = 0.24) compared with decreasing and minimal courses. Early and sustained placement into families after deprivation is associated with minimal or decreasing signs of DSED across development. Shortening the amount of time children spend in institutions and preserving placements could help decrease signs of DSED into early adolescence in previously institutionalized children. Copyright © 2018 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Leadership Competencies in U.S. Early Intervention/Early Childhood Special Education Service Systems: A National Survey

ERIC Educational Resources Information Center

Bruns, Deborah A.; LaRocco, Diana J.; Sharp, Olga L.; Sopko, Kim Moherek

2017-01-01

In 2015, the Division for Early Childhood of the Council for Exceptional Children released a position statement on leadership in early intervention and early childhood special education (EI/ECSE). Division for Early Childhood emphasized the importance of developing and supporting high-quality leadership within and across all levels of EI/ECSE…

Early Numeracy Assessment: The Development of the Preschool Early Numeracy Scales

ERIC Educational Resources Information Center

Purpura, David J.; Lonigan, Christopher J.

2015-01-01

Research Findings: The focus of this study was to construct and validate 12 brief early numeracy assessment tasks that measure the skills and concepts identified as key to early mathematics development by the National Council of Teachers of Mathematics (2006) and the National Mathematics Advisory Panel (2008)-as well as critical developmental…

Timing of Orphanhood, Early Sexual Debut, and Early Marriage in Four Sub-Saharan African Countries

PubMed Central

Chae, Sophia

2014-01-01

According to a growing body of literature, some orphans are at heightened risk of early sexual debut and early marriage. This study examines a rarely explored aspect of orphanhood: the timing and type of parental death and their relationship to these outcomes. The study also explores whether education mediates orphans’ risk of early sexual initiation and early marriage. The data are drawn from the 2004 National Survey of Adolescents, which includes interviews with 12–19-year-old adolescents in Burkina Faso, Ghana, Malawi, and Uganda. Results from discrete-time event history analysis indicate that female double orphans, regardless of timing of orphanhood, have greater odds of early sexual debut than do nonorphans. Education explains little of their increased risk. In contrast, male orphans of any type reveal no increased vulnerability to early sexual debut. Uganda is the only country where female orphans, specifically double orphans and those who are paternal orphans before age 10, have greater odds of early marriage, with education accounting for a small portion of the risk. PMID:23719999

Early Childhood Predictors of Low-Income Boys’ Pathways to Antisocial Behavior in Childhood, Adolescence, and Early Adulthood

PubMed Central

Shaw, Daniel S.; Gilliam, Mary

2016-01-01

Guided by a bridging model of pathways leading to low-income boys’ early-starting and persistent trajectories of antisocial behavior, the current paper reviews evidence supporting the model from early childhood through early adulthood. Using primarily a cohort of 310 low-income boys of families recruited from WIC centers in a large metropolitan area followed from infancy to early adulthood, and smaller cohorts of boys and girls followed through early childhood, we provide evidence supporting the critical role of parenting, maternal depression, and other proximal family risk factors in early childhood that are prospectively linked to trajectories of parent-reported conduct problems in early and middle childhood, youth-reported antisocial behavior during adolescence and early adulthood, as well as court-reported violent offending in adolescence. The findings are discussed in terms of the need to identify at-risk boys in early childhood and methods and platforms for engaging families in health care settings not previously used to implement preventive mental health services. PMID:28026042

Early cosmology constrained

NASA Astrophysics Data System (ADS)

Verde, Licia; Bellini, Emilio; Pigozzo, Cassio; Heavens, Alan F.; Jimenez, Raul

2017-04-01

We investigate our knowledge of early universe cosmology by exploring how much additional energy density can be placed in different components beyond those in the ΛCDM model. To do this we use a method to separate early- and late-universe information enclosed in observational data, thus markedly reducing the model-dependency of the conclusions. We find that the 95% credibility regions for extra energy components of the early universe at recombination are: non-accelerating additional fluid density parameter ΩMR < 0.006 and extra radiation parameterised as extra effective neutrino species 2.3 < Neff < 3.2 when imposing flatness. Our constraints thus show that even when analyzing the data in this largely model-independent way, the possibility of hiding extra energy components beyond ΛCDM in the early universe is seriously constrained by current observations. We also find that the standard ruler, the sound horizon at radiation drag, can be well determined in a way that does not depend on late-time Universe assumptions, but depends strongly on early-time physics and in particular on additional components that behave like radiation. We find that the standard ruler length determined in this way is rs = 147.4 ± 0.7 Mpc if the radiation and neutrino components are standard, but the uncertainty increases by an order of magnitude when non-standard dark radiation components are allowed, to rs = 150 ± 5 Mpc.

Early cosmology constrained

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verde, Licia; Jimenez, Raul; Bellini, Emilio

We investigate our knowledge of early universe cosmology by exploring how much additional energy density can be placed in different components beyond those in the ΛCDM model. To do this we use a method to separate early- and late-universe information enclosed in observational data, thus markedly reducing the model-dependency of the conclusions. We find that the 95% credibility regions for extra energy components of the early universe at recombination are: non-accelerating additional fluid density parameter Ω{sub MR} < 0.006 and extra radiation parameterised as extra effective neutrino species 2.3 < N {sub eff} < 3.2 when imposing flatness. Our constraintsmore » thus show that even when analyzing the data in this largely model-independent way, the possibility of hiding extra energy components beyond ΛCDM in the early universe is seriously constrained by current observations. We also find that the standard ruler, the sound horizon at radiation drag, can be well determined in a way that does not depend on late-time Universe assumptions, but depends strongly on early-time physics and in particular on additional components that behave like radiation. We find that the standard ruler length determined in this way is r {sub s} = 147.4 ± 0.7 Mpc if the radiation and neutrino components are standard, but the uncertainty increases by an order of magnitude when non-standard dark radiation components are allowed, to r {sub s} = 150 ± 5 Mpc.« less

Early Practicum Experiences: Preservice Early Childhood Students' Perceptions and Sense of Efficacy

ERIC Educational Resources Information Center

Van Schagen Johnson, Amy; La Paro, Karen M.; Crosby, Danielle A.

2017-01-01

The current study explored early practicum experiences (those occurring before student teaching) in an early childhood birth to kindergarten teacher education program. Undergraduates enrolled in practicum courses completed questionnaires about their overall practicum experience including: socio-emotional components (their perceived fit with their…

Redefining early gastric cancer.

PubMed

Barreto, Savio G; Windsor, John A

2016-01-01

The problem is that current definitions of early gastric cancer allow the inclusion of regional lymph node metastases. The increasing use of endoscopic submucosal dissection to treat early gastric cancer is a concern because regional lymph nodes are not addressed. The aim of the study was thus to critically evaluate current evidence with regard to tumour-specific factors associated with lymph node metastases in "early gastric cancer" to develop a more precise definition and improve clinical management. A systematic and comprehensive search of major reference databases (MEDLINE, EMBASE, PubMed and the Cochrane Library) was undertaken using a combination of text words "early gastric cancer", "lymph node metastasis", "factors", "endoscopy", "surgery", "lymphadenectomy" "mucosa", "submucosa", "lymphovascular invasion", "differentiated", "undifferentiated" and "ulcer". All available publications that described tumour-related factors associated with lymph node metastases in early gastric cancer were included. The initial search yielded 1494 studies, of which 42 studies were included in the final analysis. Over time, the definition of early gastric cancer has broadened and the indications for endoscopic treatment have widened. The mean frequency of lymph node metastases increased on the basis of depth of infiltration (mucosa 6% vs. submucosa 28%), presence of lymphovascular invasion (absence 9% vs. presence 53%), tumour differentiation (differentiated 13% vs. undifferentiated 34%) and macroscopic type (elevated 13% vs. flat 26%) and tumour diameter (≤2 cm 8% vs. >2 cm 25%). There is a need to re-examine the diagnosis and staging of early gastric cancer to ensure that patients with one or more identifiable risk factor for lymph node metastases are not denied appropriate chemotherapy and surgical resection.

Early psychosis workforce development: Core competencies for mental health professionals working in the early psychosis field.

PubMed

Osman, Helen; Jorm, Anthony F; Killackey, Eoin; Francey, Shona; Mulcahy, Dianne

2017-08-09

The aim of this study was to identify the core competencies required of mental health professionals working in the early psychosis field, which could function as an evidence-based tool to support the early psychosis workforce and in turn assist early psychosis service implementation and strengthen early psychosis model fidelity. The Delphi method was used to establish expert consensus on the core competencies. In the first stage, a systematic literature search was conducted to generate competency items. In the second stage, a panel consisting of expert early psychosis clinicians from around the world was formed. Panel members then rated each of the competency items on how essential they are to the clinical practice of all early psychosis clinicians. In total, 1023 pieces of literature including textbooks, journal articles and grey literature were reviewed. A final 542 competency items were identified for inclusion in the questionnaire. A total of 63 early psychosis experts participated in 3 rating rounds. Of the 542 competency items, 242 were endorsed as the required core competencies. There were 29 competency items that were endorsed by 62 or more experts, and these may be considered the foundational competencies for early psychosis practice. The study generated a set of core competencies that provide a common language for early psychosis clinicians across professional disciplines and country of practice, and potentially are a useful professional resource to support early psychosis workforce development and service reform. © 2017 John Wiley & Sons Australia, Ltd.

Early childhood predictors of early onset of smoking: a birth prospective study.

PubMed

Hayatbakhsh, Reza; Mamun, Abdullah A; Williams, Gail M; O'Callaghan, Michael J; Najman, Jake M

2013-10-01

Early onset of smoking is associated with subsequent abuse of other substances and development of negative health outcomes. This study aimed to examine early life predictors of onset of smoking in an Australian young cohort. Data were from the Mater Hospital and University of Queensland Study of Pregnancy (MUSP), a population-based prospective birth cohort study (1981-2012). The present study is based on a cohort of 3714 young adults who self-reported smoking status and age of onset of smoking at the 21-year follow-up. Of these, data were available for 3039 on early childhood factors collected between the baseline and 14-year follow-up of the study. Of 3714 young adults, 49.6% (49.9% males and 49.3% females) reported having ever smoked cigarettes. For those who had ever smoked, mean and median ages at first smoke were 15.5 and 16.0years, respectively. In multivariate Cox proportional hazard analysis mother's education, change in maternal marital status, maternal cigarette smoking and alcohol consumption, maternal depression and child externalizing when the child was 5years statistically significantly predicted early onset of smoking. The data suggest that individuals exposed to personal and environmental risk factors during the early stage of childhood are at increased risk of initiation to cigarette smoking at an earlier age. Identification of the pathways of association between these early life factors and initiation to cigarette smoking may help reduce risk of tobacco smoking in adolescents and its adverse consequences. Copyright © 2013 Elsevier Ltd. All rights reserved.

Beyond Developmentalism? Early Childhood Teachers' Understandings of Multiage Grouping in Early Childhood Education and Care

ERIC Educational Resources Information Center

Edwards, Susan; Blaise, Mindy; Hammer, Marie

2009-01-01

Postdevelopmental perspectives in early childhood education and care increasingly reference alternative ways of understanding learning, growth and development in early learning. Drawing on these ideas, this paper examines research findings which focused on early childhood teachers' understandings of multiage grouping. The findings suggested that…

Early Educational Intervention, Early Cumulative Risk, and the Early Home Environment as Predictors of Young Adult Outcomes Within a High-Risk Sample

PubMed Central

Pungello, Elizabeth P.; Kainz, Kirsten; Burchinal, Margaret; Wasik, Barbara H.; Sparling, Joseph J.; Ramey, Craig T.; Campbell, Frances A.

2009-01-01

The extent to which early educational intervention, early cumulative risk, and the early home environment were associated with young adult outcomes was investigated in a sample of 139 young adults (age 21) from high-risk families enrolled in randomized trials of early intervention. Positive effects of treatment were found for education attainment, attending college, and skilled employment; negative effects of risk were found for education attainment, graduating high school, being employed and avoiding teen parenthood. The home mediated the effects of risk for graduating high school, but not being employed or teen parenthood. Evidence for moderated mediation was found for educational attainment; the home mediated the association between risk and educational attainment for the control group, but not the treated group. PMID:20331676

Evaluation of Young Children for Early Intervention and Early Childhood Special Education.

ERIC Educational Resources Information Center

Allen, Diana

This technical assistance document provides guidelines for child assessment and eligibility determination for early intervention and early childhood special education programs in Oregon. An overview of the assessment process explains screening, eligibility evaluation, and assessment for the Individual Family Service Plan (IFSP). Legal requirements…

EARLY CHILDHOOD PREDICTORS OF LOW-INCOME BOYS' PATHWAYS TO ANTISOCIAL BEHAVIOR IN CHILDHOOD, ADOLESCENCE, AND EARLY ADULTHOOD.

PubMed

Shaw, Daniel S; Gilliam, Mary

2017-01-01

Guided by a bridging model of pathways leading to low-income boys' early starting and persistent trajectories of antisocial behavior, the current article reviews evidence supporting the model from early childhood through early adulthood. Using primarily a cohort of 310 low-income boys of families recruited from Women, Infants, and Children Nutrition Supplement centers in a large metropolitan area followed from infancy to early adulthood and a smaller cohort of boys and girls followed through early childhood, we provide evidence supporting the critical role of parenting, maternal depression, and other proximal family risk factors in early childhood that are prospectively linked to trajectories of parent-reported conduct problems in early and middle childhood, youth-reported antisocial behavior during adolescence and early adulthood, and court-reported violent offending in adolescence. The findings are discussed in terms of the need to identify at-risk boys in early childhood and methods and platforms for engaging families in healthcare settings not previously used to implement preventive mental health services. © 2016 Michigan Association for Infant Mental Health.

Early Reading and Concrete Operations.

ERIC Educational Resources Information Center

Polk, Cindy L. Howes; Goldstein, David

1980-01-01

Indicated that early readers are more likely to be advanced in cognitive development than are nonearly-reading peers. After one year of formal reading instruction, early readers maintained their advantage in reading achievement. Measures of concrete operations were found to predict reading achievement for early and nonearly readers. (Author/DB)

The Effectiveness of Early Intervention.

ERIC Educational Resources Information Center

Guralnick, Michael J., Ed.

This book reviews research on the effectiveness of early intervention for children with disabilities or who are at risk. Program factors for children at risk and with disabilities, the effects of early intervention on different types of disabilities, and the outcomes of early intervention are explored. Chapters include: "Second-Generation Research…

Early Rockets

NASA Image and Video Library

2004-04-15

During the 19th century, rocket enthusiasts and inventors began to appear in almost every country. Some people thought these early rocket pioneers were geniuses, and others thought they were crazy. Claude Ruggieri, an Italian living in Paris, apparently rocketed small animals into space as early as 1806. The payloads were recovered by parachute. As depicted here by artist Larry Toschik, French authorities were not always impressed with rocket research. They halted Ruggieri's plans to launch a small boy using a rocket cluster. (Reproduced from a drawing by Larry Toschik and presented here courtesy of the artist and Motorola Inc.)

Individual differences in early adolescents' latent trait cortisol: Interaction of early adversity and 5-HTTLPR.

PubMed

Chen, Frances R; Stroud, Catherine B; Vrshek-Schallhorn, Suzanne; Doane, Leah D; Granger, Douglas A

2017-10-01

The present study aimed to examine the interaction of 5-HTTLPR and early adversity on trait-like levels of cortisol. A community sample of 117 early adolescent girls (M age=12.39years) provided DNA samples for 5-HTTLPR genotyping, and saliva samples for assessing cortisol 3 times a day (waking, 30min post-waking, and bedtime) over a three-day period. Latent trait cortisol (LTC) was modeled using the first 2 samples of each day. Early adversity was assessed with objective contextual stress interviews with adolescents and their mothers. A significant 5-HTTLPR×early adversity interaction indicated that greater early adversity was associated with lower LTC levels, but only among individuals with either L/L or S/L genotype. Findings suggest that serotonergic genetic variation may influence the impact of early adversity on individual differences in HPA-axis regulation. Future research should explore whether this interaction contributes to the development of psychopathology through HPA axis functioning. Copyright © 2017 Elsevier B.V. All rights reserved.

Clarifying Parent-Child Reciprocities during Early Childhood: The Early Childhood Coercion Model

ERIC Educational Resources Information Center

Scaramella, Laura V.; Leve, Leslie D.

2004-01-01

Consistent with existing theory, the quality of parent-child interactions during early childhood affects children's social relationships and behavioral adjustment during middle childhood and adolescence. Harsh parenting and a propensity toward emotional overarousal interact very early in life to affect risk for later conduct problems. Less…

Risk of early surgery for Crohn's disease: implications for early treatment strategies.

PubMed

Sands, Bruce E; Arsenault, Joanne E; Rosen, Michael J; Alsahli, Mazen; Bailen, Laurence; Banks, Peter; Bensen, Steven; Bousvaros, Athos; Cave, David; Cooley, Jeffrey S; Cooper, Herbert L; Edwards, Susan T; Farrell, Richard J; Griffin, Michael J; Hay, David W; John, Alex; Lidofsky, Sheldon; Olans, Lori B; Peppercorn, Mark A; Rothstein, Richard I; Roy, Michael A; Saletta, Michael J; Shah, Samir A; Warner, Andrew S; Wolf, Jacqueline L; Vecchio, James; Winter, Harland S; Zawacki, John K

2003-12-01

In this study we aimed to define the rate of early surgery for Crohn's disease and to identify risk factors associated with early surgery as a basis for subsequent studies of early intervention in Crohn's disease. We assembled a retrospective cohort of patients with Crohn's disease diagnosed between 1991 and 1997 and followed for at least 3 yr, who were identified in 16 community and referral-based practices in New England. Chart review was performed for each patient. Details of baseline demographic and disease features were recorded. Surgical history including date of surgery, indication, and procedure were also noted. Risk factors for early surgery (defined as major surgery for Crohn's disease within 3 yr of diagnosis, exclusive of major surgery at time of diagnosis) were identified by univariate analysis. Multiple logistic regression was used to identify independent risk factors. Of 345 eligible patients, 69 (20.1%) required surgery within 3 yr of diagnosis, excluding the 14 patients (4.1%) who had major surgery at the time of diagnosis. Overall, the interval between diagnosis and surgery was short; one half of all patients who required surgery underwent operation within 6 months of diagnosis. Risk factors identified by univariate analysis as significantly associated with early surgery included the following: smoking; disease of small bowel without colonic involvement; nausea and vomiting or abdominal pain on presentation; neutrophil count; and steroid use in the first 6 months. Disease localized to the colon only, blood in the stool, use of 5-aminosalicylate, and lymphocyte count were inversely associated with risk of early surgery. Logistic regression confirmed independent associations with smoking as a positive risk factor and involvement of colon without small bowel as a negative risk factor for early surgery. The rate of surgery is high in the first 3 yr after diagnosis of Crohn's disease, particularly in the first 6 months. These results suggest that

Implementing Obstetric Early Warning Systems.

PubMed

Friedman, Alexander M; Campbell, Mary L; Kline, Carolyn R; Wiesner, Suzanne; D'Alton, Mary E; Shields, Laurence E

2018-04-01

Severe maternal morbidity and mortality are often preventable and obstetric early warning systems that alert care providers of potential impending critical illness may improve maternal safety. While literature on outcomes and test characteristics of maternal early warning systems is evolving, there is limited guidance on implementation. Given current interest in early warning systems and their potential role in care, the 2017 Society for Maternal-Fetal Medicine (SMFM) Annual Meeting dedicated a session to exploring early warning implementation across a wide range of hospital settings. This manuscript reports on key points from this session. While implementation experiences varied based on factors specific to individual sites, common themes relevant to all hospitals presenting were identified. Successful implementation of early warnings systems requires administrative and leadership support, dedication of resources, improved coordination between nurses, providers, and ancillary staff, optimization of information technology, effective education, evaluation of and change in hospital culture and practices, and support in provider decision-making. Evolving data on outcomes on early warning systems suggest that maternal risk may be reduced. To effectively reduce maternal, risk early warning systems that capture deterioration from a broad range of conditions may be required in addition to bundles tailored to specific conditions such as hemorrhage, thromboembolism, and hypertension.

Early Childhood Workforce Index, 2016

ERIC Educational Resources Information Center

Whitebook, Marcy; McLean, Caitlin; Austin, Lea J. E.

2016-01-01

The State of the Early Childhood Workforce (SECW) Initiative is a groundbreaking multi-year project to shine a steady spotlight on the nation's early childhood workforce. The SECW Initiative is designed to challenge entrenched ideas and policies that maintain an inequitable and inadequate status quo for early educators and for the children and…

Early Attrition among Suicidal Clients

ERIC Educational Resources Information Center

Surgenor, P. W. G.; Meehan, V.; Moore, A.

2016-01-01

The study aimed to identify the level of suicidal ideation in early attrition clients and their reasons for the early termination of their therapy. The cross-sectional design involved early attrition clients (C[subscript A]) who withdrew from therapy before their second session (n = 61), and continuing clients who (C[subscript C]) progressed…

Early Childhood Special Music Education

ERIC Educational Resources Information Center

Darrow, Alice-Ann

2011-01-01

The process of early intervention is a critical component of Early Childhood Special Music Education. Early intervention is the process of providing services, education, and support to young children who have disabilities or to children who are at-risk of developing needs that may affect their physical, cognitive, or emotional development. The…

Indicators of Access to Early Childhood Services in the Mississippi Delta. Rural Early Childhood Report No. 5

ERIC Educational Resources Information Center

Shores, Elizabeth F.; Barbaro, Erin; Barbaro, Michael C.; Flenner, Michelle; Bell, Lynn

2007-01-01

The Early Childhood Atlas facilitates spatial analysis in early childhood services research for the promotion of greater quality and accessibility of early care and education. The Atlas team collects and geocodes federal, state and nongovernmental datasets about early childhood services, integrating selected data elements into its online mapmaking…

Precursors of Adolescent Substance Use from Early Childhood and Early Adolescence: Testing a Developmental Cascade Model

PubMed Central

Sitnick, Stephanie; Shaw, Daniel S.; Hyde, Luke

2013-01-01

This study examined developmentally-salient risk and protective factors of adolescent substance use assessed during early childhood and early adolescence using a sample of 310 low-income boys. Child problem behavior and proximal family risk and protective factors (i.e., parenting, maternal depression) during early childhood, as well as child and family factors and peer deviant behavior during adolescence were explored as potential precursors to later substance use during adolescence using structural equation modeling. Results revealed that early childhood risk and protective factors (i.e., child externalizing problems, mothers’ depressive symptomatology, and nurturant parenting) were indirectly related to substance use at the age of 17 via risk and protective factors during early and middle adolescence (i.e., parental knowledge and externalizing problems). The implications of these findings for early prevention and intervention are discussed. PMID:24029248

Contemporary Perspectives on Early Childhood Curriculum. Contemporary Perspectives in Early Childhood Education.

ERIC Educational Resources Information Center

Saracho, Olivia N. Ed.; Spodek, Bernard, Ed.

Noting that the curriculum in early childhood education is dramatically different from that at other levels of education, this volume seeks to clarify some of the issues related to early childhood curriculum development and its bases in both personal knowledge and knowledge from the different disciplines to achieve a "balanced curriculum."…

The Effect of Early Marriages and Early Childbearing on Women's Nutritional Status in India.

PubMed

Goli, Srinivas; Rammohan, Anu; Singh, Deepti

2015-08-01

The consequences of early childbearing on the growth and nutritional status of women in India has not been quantified in previous studies. Our study aimed to fill this gap by analysing the association between early marriage and early childbearing on nutritional status of Indian women, with a focus on Bihar and Andhra Pradesh, the two states accounting for the highest proportion of women marrying and giving first birth before 18 years of age. Our findings revealed that a substantial number of women were married before 18 years and thereby exposed to early pregnancy. Furthermore, a significantly higher proportion of women in the 'thin' category were married before 18 years, both in the Indian sample (33 %, p < 0.001) and in the selected states, Andhra Pradesh (31 %, p < 0.001) and Bihar (43 %, p < 0.001), compared to those women married at higher ages. Similarly, across all our samples women whose first birth was before age 18 years also had a significantly higher probability of being in the 'thin' category across all our samples. This pattern was also observed for associations between early childbirth and anemia levels. We conclude that the net effect of the early age at marriage and age at first birth on nutritional status is significant. Our results underline the need for preventing early marriages and the consequent high adolescent pregnancies in India, particularly in high prevalence states. This will help to improve nutritional status and health care utilisation among women, thereby, prevent maternal and child mortality and thus, achieve the MDGs 4-5.

[Transverse myelitis associated with toxocariasis and the importance of locally produced antibodies for diagnosis].

PubMed

Ural, Serap; Özer, Behiye; Gelal, Fazıl; Dirim Erdoğan, Derya; Sezak, Nurbanu; Balık, Recep; Demirdal, Tuna; Korkmaz, Metin

2016-07-01

Toxocariasis caused by Toxocara canis or less frequently by T.catis is a common parasitic infection worldwide. Clinical spectrum in humans can vary from asymptomatic infection to serious organ disfunction depending on the load of parasite, migration target of the larva and the inflammatory response of the host. Transverse myelitis (TM) due to toxocariasis is an uncommon illness identified mainly as case reports in literature. In this report, a case of TM who was diagnosed as neurotoxocariasis by serological findings has been presented. A 44-year-old male patient complained with backache was diagnosed as TM in a medical center in which he has admitted two years ago, and treated with pregabalin and nonsteroidal drugs for six months. Because of the progression of the lesions he readmitted to another center and treated with high dose steroid therapy for three months. After six months of follow up, improvement has been achieved, however, since his symptoms reccurred in the following year he was admitted to our hospital. Magnetic resonance imaging (MRI) examination revealed a TM in a lower segment of spinal cord. He was suffering with weakness and numbness in the left lower extremity. There was no history of rural life or contact with cats or dogs in his anamnesis. Physical examination revealed normal cranial nerve functions, sensory and motor functions. There has been no pathological reflexes, and deep tendon reflexes were also normal. Laboratory findings yielded normal hemogram and biochemical tests, negative PPD and parasitological examination of stool were negative for cysts and ova. Viral hepatitis markers, anti-HIV, toxoplasma-IgM, CMV-IgM, rubella-IgM, EBV-VCA-IgM, VDRL, Brucella tube agglutination, echinococcus antibody, autoantibody tests and neuromyelitis optica test were negative. Examination of CSF showed 20 cells/mm3 (mononuclear cells), 45 mg/dl protein and normal levels of glucose and chlorine. In both serum and CSF samples of the patient Toxocara

High normal blood pressure in early pregnancy also contribute to early onset preeclampsia and severe preeclampsia.

PubMed

He, Dian; Wu, Shaowen; Zhao, Haiping; Zheng, Zihe; Zhang, Weiyuan

2017-11-27

This study was to evaluate effects of high normal blood pressure (HNBP) in early pregnancy on total preeclampsia, early preeclampsia, and severe preeclampsia. We conducted a multicenter, national representative retrospective cohort study. HNBP was defined as systolic blood pressure between 130 and 140 mmHg or diastolic blood pressure between 85 and 90 mmHg. We used multivariable logistic regression to examine the associations of HNBP and the risks of above three types of preeclampsia. We included 58 054 women who were normotensive and nulliparous in early pregnancy. 4 809 (8.3%) fulfilled the definition of having HNBP, 16 682 (28.7%) were in normal blood pressure group, and 36 563 (63.0%) were in optimal blood pressure group. The incidence rates of total preeclampsia, early preeclampsia, and severe preeclampsia were 2.1% (1 217), 0.8% (491), and 1.4% (814), respectively. Compared to having optimal blood pressure, women with HNBP had significantly higher odds of total preeclampsia (odds ratio (OR) = 4.028, 95% confidence interval (CI) 3.377, 4.804), severe preeclampsia (OR = 3.542, 95% CI 2.851, 4.400), and early preeclampsia (OR = 8.163, 95% CI 6.219, 10.715). Our restricted cubic spline results supported the dose-response relationship between continuous blood pressure and the odds ratio of three types of preeclampsia. The fraction of early preeclampsia associated with prehypertension was 58.6%, which was higher than those of total preeclampsia (42.2%) or severe preeclampsia (40.5%). Women in early pregnancy with HNBP more likely develop total preeclampsia, early preeclampsia and severe preeclampsia, compared to those with optimal blood pressure. HNBP contribute more to early preeclampsia than severe preeclampsia. Our study provided robust epidemiological evidences for monitoring HNBP in early pregnancy to reduce the risks of preeclampsia.

Rethinking Early Childhood Education

ERIC Educational Resources Information Center

Pelo, Ann, Ed.

2008-01-01

"Rethinking Early Childhood Education" is alive with the conviction that teaching young children involves values and vision. This anthology collects inspiring stories about social justice teaching with young children. Included here is outstanding writing from childcare teachers, early-grade public school teachers, scholars, and parents.…

Early Head Start: Research Findings. Early Childhood Highlights. Volume 1, Issue 2

ERIC Educational Resources Information Center

Child Trends, 2010

2010-01-01

Early Head Start is a federally funded community-based program for low-income families with infants and toddlers and for low-income pregnant women. Created in 1995, Early Head Start strives to promote healthy prenatal outcomes for pregnant women, to enhance the development of children ages birth to three, and to promote healthy family functioning.…

Zucchi, Niccolo (1586-1670)

NASA Astrophysics Data System (ADS)

Murdin, P.

2000-11-01

Born in Parma, Italy, became a Jesuit, and in 1608, or perhaps 1616, used a lens to observe the image produced by a concave mirror, the first reflecting telescope. He described it in a book Optica Philosophica, in 1652. He was the first to observe the spots on Jupiter, in 1630. In about 1640, he is reported to have examined spots on Mars, as discovered by Fontana, but this must be regarded skepti...

Enhanced Backscattering from Rough Surfaces

DTIC Science & Technology

1991-10-18

experimental results M. Nieto-Vesperinas and J. A. Sinchez-Gfi Insuituto de Optica. Consejo Superior de Investigaciones Cientificas, c/Serrono 1221. Madrid...2A7, UK I Division de Fisica Aplicada, CICESE, Apdo. Postal 2732 Ensenada, Baja California, Mexico Instituto de Optics, CSIC, Serrano 121, Madrid 2806...extracted as a de - is less than two for the copolarized case because of the scriptive parameter of the curves, and the variation of contribution of single

Early Intervention Services for Early-Phase Psychosis - Centre for integrative psychiatry in Psychiatric Hospital "Sveti Ivan", Croatia.

PubMed

Matić, Katarina; Gereš, Natko; Gerlach, Josefina; Prskalo-Čule, Diana; Zadravec Vrbanc, Tihana; Lovretić, Vanja; Librenjak, Dina; Vuk Pisk, Sandra; Ivezić, Ena; Šimunović Filipčić, Ivona; Jeleč, Vjekoslav; Filipčić, Igor

2018-06-01

There is a growing body of evidence suggesting that early and effective management in the critical early years of schizophrenia can improve long-term outcomes. The objective of this study was to evaluate time to relapse of the patients with early-phase psychosis treated in the Centre for integrative psychiatry (CIP). We performed a retrospective cohort study on the sample of 373 early-phase psychosis patients admitted to Psychiatric Hospital "Sveti Ivan", Zagreb Croatia: from January 1, 2015 to December 31, 2017. The primary outcome was time to relapse. Patients who were admitted to group psychotherapeutic program after the end of acute treatment had 70% lower hazard for relapse (HR=0.30; 95% CI 0.16-0.58). Patients who were included first in the psychotherapeutic program and then treated and controlled in the daily hospital had 74% lower hazard for relapse (HR=0.26; 95% CI 0.10-0.67). In early-phase psychosis, integrative early intervention service has relevant beneficial effects compare to treatment as usual. These results justified the implementation of multimodal early intervention services in treatment of patients with early-phase psychosis.

The Influence of the Early Retirement Process on Satisfaction with Early Retirement and Psychological Well-Being

ERIC Educational Resources Information Center

Potocnik, Kristina; Tordera, Nuria; Peiro, Jose Maria

2010-01-01

The present study explores the influence of the early retirement process on adjustment to early retirement, taking into account the roles of individual characteristics and social context in this process. We proposed a systematic model integrating perceived ability to continue working, organizational pressures toward early retirement and group…

Early osteoarthritis of the knee.

PubMed

Madry, Henning; Kon, Elizaveta; Condello, Vincenzo; Peretti, Giuseppe M; Steinwachs, Matthias; Seil, Romain; Berruto, Massimo; Engebretsen, Lars; Filardo, Giuseppe; Angele, Peter

2016-06-01

There is an increasing awareness on the importance in identifying early phases of the degenerative processes in knee osteoarthritis (OA), the crucial period of the disease when there might still be the possibility to initiate treatments preventing its progression. Early OA may show a diffuse and ill-defined involvement, but also originate in the cartilage surrounding a focal lesion, thus necessitating a separate assessment of these two entities. Early OA can be considered to include a maximal involvement of 50 % of the cartilage thickness based on the macroscopic ICRS classification, reflecting an OARSI grade 4. The purpose of this paper was to provide an updated review of the current status of the diagnosis and definition of early knee OA, including the clinical, radiographical, histological, MRI, and arthroscopic definitions and biomarkers. Based on current evidence, practical classification criteria are presented. As new insights and technologies become available, they will further evolve to better define and treat early knee OA.

Growth hormone and early treatment.

PubMed

Antoniazzi, F; Cavarzere, P; Gaudino, R

2015-06-01

Growth hormone (GH) treatment is approved by the US Food and Drug Administration (FDA) not only for GH deficiency (GHD) but also for other childhood growth disorders with growth failure and/or short stature. GHD is the most frequent endocrine disorder presenting with short stature in childhood. During neonatal period, metabolic effects due to congenital GHD require a prompt replacement therapy to avoid possible life-threatening complications. In childhood and adolescence, growth impairment is the most evident effect of GHD and early treatment has the aim of restore normal growth and to reach normal adult height. We reassume in this review the conditions causing GHD and the diagnostic challenge to reach an early diagnosis, and an early treatment, necessary to obtain the best results. Finally, we summarize results obtained in clinical studies about pediatric patients with GHD treated at an early age, in which a marked early catch-up growth and a normalization of adult height were obtained.

Preventive child health care findings on early childhood predict peer-group social status in early adolescence.

PubMed

Jaspers, Merlijne; de Winter, Andrea F; Veenstra, René; Ormel, Johan; Verhulst, Frank C; Reijneveld, Sijmen A

2012-12-01

A disputed social status among peers puts children and adolescents at risk for developing a wide range of problems, such as being bullied. However, there is a lack of knowledge about which early predictors could be used to identify (young) adolescents at risk for a disputed social status. The aim of this study was to assess whether preventive child health care (PCH) findings on early childhood predict neglected and rejected status in early adolescence in a large longitudinal community-based sample. Data came from 898 participants who participated in TRAILS, a longitudinal study. Information on early childhood factors was extracted from the charts of routine PCH visits registered between infancy and age of 4 years. To assess social status, peer nominations were used at age of 10-12 years. Multinomial logistic regression showed that children who had a low birth weight, motor problems, and sleep problems; children of parents with a low educational level (odds ratios [ORs] between 1.71 and 2.90); and those with fewer attention hyperactivity problems (ORs = .43) were more likely to have a neglected status in early adolescence. Boys, children of parents with a low educational level, and children with early externalizing problems were more likely to have a rejected status in early adolescence (ORs between 1.69 and 2.56). PCH findings on early childhood-on motor and social development-are predictive of a neglected and a rejected status in early adolescence. PCH is a good setting to monitor risk factors that predict the social status of young adolescents. Copyright © 2012 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Early Intervention in Bipolar Disorder.

PubMed

Vieta, Eduard; Salagre, Estela; Grande, Iria; Carvalho, André F; Fernandes, Brisa S; Berk, Michael; Birmaher, Boris; Tohen, Mauricio; Suppes, Trisha

2018-05-01

Bipolar disorder is a recurrent disorder that affects more than 1% of the world population and usually has its onset during youth. Its chronic course is associated with high rates of morbidity and mortality, making bipolar disorder one of the main causes of disability among young and working-age people. The implementation of early intervention strategies may help to change the outcome of the illness and avert potentially irreversible harm to patients with bipolar disorder, as early phases may be more responsive to treatment and may need less aggressive therapies. Early intervention in bipolar disorder is gaining momentum. Current evidence emerging from longitudinal studies indicates that parental early-onset bipolar disorder is the most consistent risk factor for bipolar disorder. Longitudinal studies also indicate that a full-blown manic episode is often preceded by a variety of prodromal symptoms, particularly subsyndromal manic symptoms, therefore supporting the existence of an at-risk state in bipolar disorder that could be targeted through early intervention. There are also identifiable risk factors that influence the course of bipolar disorder, some of them potentially modifiable. Valid biomarkers or diagnosis tools to help clinicians identify individuals at high risk of conversion to bipolar disorder are still lacking, although there are some promising early results. Pending more solid evidence on the best treatment strategy in early phases of bipolar disorder, physicians should carefully weigh the risks and benefits of each intervention. Further studies will provide the evidence needed to finish shaping the concept of early intervention. AJP AT 175 Remembering Our Past As We Envision Our Future April 1925: Interpretations of Manic-Depressive Phases Earl Bond and G.E. Partridge reviewed a number of patients with manic-depressive illness in search of a unifying endo-psychic conflict. They concluded that understanding either phase of illness was "elusive" and

Waterford Early Reading Program.

ERIC Educational Resources Information Center

Education Commission of the States, Denver, CO.

This paper provides an overview of the Waterford Early Reading Program (WERP), which is designed to shift teaching and learning away from remediation and failure to prevention, early achievement, and sustained growth for every student. WERP includes three levels of instruction: emergent, beginning, and fluent readers. It targets pre-K through…

Children's early helping in action: Piagetian developmental theory and early prosocial behavior.

PubMed

Hammond, Stuart I

2014-01-01

After a brief overview of recent research on early helping, outlining some central problems, and issues, this paper examines children's early helping through the lens of Piagetian moral and developmental theory, drawing on Piaget's "Moral Judgment of the Child" (Piaget, 1932/1997), "Play, Dreams, and Imitation in Childhood" (Piaget, 1945/1951), and the "Grasp of Consciousness" (Piaget, 1976). Piaget refers to a level of moral development in action that precedes heteronomous and autonomous moral reasoning. This action level allows children to begin to interact with people and objects. In his later work, Piaget explores the gradual construction of understanding from this activity level. Taken together, these elements of Piagetian theory provide a promising conceptual framework for understanding the development of early helping.

Early Childhood Educators' Perceived and Actual Metalinguistic Knowledge, Beliefs and Enacted Practice about Teaching Early Reading

ERIC Educational Resources Information Center

Hammond, Lorraine

2015-01-01

Results of influential reports on early literacy have drawn attention to the need for early childhood educators to take up a more explicit, teacher-directed approach to beginning reading. Positive classroom results however are in part dependent upon teacher knowledge and this study investigated the relationship between early childhood educators'…

Early presentation of primary glioblastoma.

PubMed

Faguer, R; Tanguy, J-Y; Rousseau, A; Clavreul, A; Menei, P

2014-08-01

Clinical and neuroimaging findings of glioblastomas (GBM) at an early stage have rarely been described and those tumors are most probably under-diagnosed. Furthermore, their genetic alterations, to our knowledge, have never been previously reported. We report the clinical as well as neuroimaging findings of four early cases of patients with GBM. In our series, early stage GBM occurred at a mean age of 57 years. All patients had seizures as their first symptom. In all early stages, MRI showed a hyperintense signal on T2-weighted sequences and an enhancement on GdE-T1WI sequences. A hyperintense signal on diffusion sequences with a low ADC value was also found. These early observed occurrences of GBM developed rapidly and presented the MRI characteristics of classic GBM within a few weeks. The GBM size was multiplied by 32 in one month. Immunohistochemical analysis indicated the de novo nature of these tumors, i.e. absence of mutant IDH1 R132H protein expression, which is a diagnostic marker of low-grade diffuse glioma and secondary GBM. A better knowledge of early GBM presentation would allow a more suitable management of the patients and may improve their prognosis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Sharing Books with Babies: Promoting Early Literacy in Early Care and Education. [Videotape].

ERIC Educational Resources Information Center

Boston Medical Center, MA. Doc4Kids Project.

Suggesting that very young children spend every waking minute getting ready for kindergarten, this videotape for caregivers and early childhood teachers shows how to support early literacy skill development by sharing stories, relationships, and books with infants, toddlers, and preschoolers in care and education settings. The 25-minute videotape…

Emotional Self-Regulation, Peer Rejection, and Antisocial Behavior: Developmental Associations from Early Childhood to Early Adolescence

ERIC Educational Resources Information Center

Trentacosta, Christopher J.; Shaw, Daniel S.

2009-01-01

This study examined relations among emotional self-regulation, peer rejection, and antisocial behavior in a sample of 122 boys from low-income families who participated in a summer camp and were followed longitudinally from early childhood to early adolescence. Emotional self-regulation strategies were coded in early childhood from a waiting task,…

The At Risk Child: Early Identification, Intervention, and Evaluation of Early Childhood Strategies.

ERIC Educational Resources Information Center

Lennon, Joan M.

A review of literature was conducted in order to: (1) determine whether factors placing the young child at risk for school failure can be identified; (2) determine whether early family interventions and early childhood programs are effective; and (3) identify policy implications. Findings are summarized, and recommendations are offered. Research…

Taiwanese Early Childhood Educators' Professional Development

ERIC Educational Resources Information Center

Hsu, Ching-Yun

2008-01-01

This study was designed based on a qualitative paradigm to explore the professional development of Taiwanese early childhood educators. The method of phenomenology was employed. The main research question addressed was "How do early childhood educators construe their professional development experience?" Seven Taiwanese early childhood…

Resilience in mathematics after early brain injury: The roles of parental input and early plasticity.

PubMed

Glenn, Dana E; Demir-Lira, Özlem Ece; Gibson, Dominic J; Congdon, Eliza L; Levine, Susan C

2018-04-01

Children with early focal unilateral brain injury show remarkable plasticity in language development. However, little is known about how early brain injury influences mathematical learning. Here, we examine early number understanding, comparing cardinal number knowledge of typically developing children (TD) and children with pre- and perinatal lesions (BI) between 42 and 50 months of age. We also examine how this knowledge relates to the number words children hear from their primary caregivers early in life. We find that children with BI, are, on average, slightly behind TD children in both cardinal number knowledge and later mathematical performance, and show slightly slower learning rates than TD children in cardinal number knowledge during the preschool years. We also find that parents' "number talk" to their toddlers predicts later mathematical ability for both TD children and children with BI. These findings suggest a relatively optimistic story in which neural plasticity is at play in children's mathematical development following early brain injury. Further, the effects of early number input suggest that intervening to enrich the number talk that children with BI hear during the preschool years could narrow the math achievement gap. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

23 CFR 710.501 - Early acquisition.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Early acquisition. 710.501 Section 710.501 Highways... REAL ESTATE Property Acquisition Alternatives § 710.501 Early acquisition. (a) Real property... so based on program or project considerations. The State may undertake early acquisition for corridor...

23 CFR 710.501 - Early acquisition.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 23 Highways 1 2011-04-01 2011-04-01 false Early acquisition. 710.501 Section 710.501 Highways... REAL ESTATE Property Acquisition Alternatives § 710.501 Early acquisition. (a) Real property... so based on program or project considerations. The State may undertake early acquisition for corridor...

Treatment of early Parkinson's disease.

PubMed

Pahwa, Rajesh; Lyons, Kelly E

2014-08-01

This review summarizes currently available treatment options and treatment strategies, investigational treatments, and the importance of exercise for early Parkinson's disease. The available treatment options for early Parkinson's disease have changed little in the past decade and include carbidopa/levodopa, dopamine agonists, and monoamine oxidase type B (MAO-B) inhibitors. However, we discuss changes in treatment strategies, including dosing and the use of combination therapy used in an attempt to reduce or delay the appearance of motor complications and other adverse events. We will also review several investigational treatments that have shown promise for the treatment of early Parkinson's disease, including a new extended release formulation of carbidopa/levodopa (IPX066), safinamide which inhibits MAO-B, dopamine uptake and glutamate and pardoprunox which is a 5HT-1A agonist and a partial dopamine agonist. Finally, we discuss recent studies focusing on exercise as an important component in the management of early Parkinson's disease. Advances in the management of early Parkinson's disease include evolving treatment strategies, new investigational treatments, and earlier implementation of various forms of exercise.

Early Life Exposures and Cancer

Cancer.gov

Early-life events and exposures have important consequences for cancer development later in life, however, epidemiological studies of early-life factors and cancer development later in life have had significant methodological challenges.

Natural course of early COPD.

PubMed

Rhee, Chin Kook; Kim, Kyungjoo; Yoon, Hyoung Kyu; Kim, Jee-Ae; Kim, Sang Hyun; Lee, Sang Haak; Park, Yong Bum; Jung, Ki-Suck; Yoo, Kwang Ha; Hwang, Yong Il

2017-01-01

Few studies have examined the natural course of early COPD. The aim of this study was to observe the natural course of early COPD patients. We also aimed to analyze medical utilization and costs for early COPD during a 6-year period. Patients with early COPD were selected from Korean National Health and Nutrition Examination Survey (KNHANES) data. We linked the KNHANES data of patients with early COPD to National Health Insurance data. A total of 2,397 patients were enrolled between 2007 and 2012. The mean forced expiratory volume in 1 second (FEV 1 ) was 78.6%, and the EuroQol five dimensions questionnaire (EQ-5D) index value was 0.9. In total, 110 patients utilized health care for COPD in 2007, and this number increased to 179 in 2012. The total mean number of days used per person increased from 4.9 in 2007 to 7.8 in 2012. The total medical cost per person also increased from 248.8 US dollar (USD) in 2007 to 780.6 USD in 2013. A multiple linear regression revealed that age, lower body mass index, lower FEV 1 (%), and lower EQ-5D score were significantly associated with medical costs. Even in early COPD patients, some of them eventually progressed and utilized health care for COPD.

28 CFR 2.43 - Early termination.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 1 2012-07-01 2012-07-01 false Early termination. 2.43 Section 2.43..., YOUTH OFFENDERS, AND JUVENILE DELINQUENTS United States Code Prisoners and Parolees § 2.43 Early... shall also conduct a status review whenever the supervision officer recommends early termination of the...

28 CFR 2.43 - Early termination.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 1 2013-07-01 2013-07-01 false Early termination. 2.43 Section 2.43..., YOUTH OFFENDERS, AND JUVENILE DELINQUENTS United States Code Prisoners and Parolees § 2.43 Early... shall also conduct a status review whenever the supervision officer recommends early termination of the...

28 CFR 2.43 - Early termination.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Early termination. 2.43 Section 2.43..., YOUTH OFFENDERS, AND JUVENILE DELINQUENTS United States Code Prisoners and Parolees § 2.43 Early... shall also conduct a status review whenever the supervision officer recommends early termination of the...

28 CFR 2.43 - Early termination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Early termination. 2.43 Section 2.43..., YOUTH OFFENDERS, AND JUVENILE DELINQUENTS United States Code Prisoners and Parolees § 2.43 Early... shall also conduct a status review whenever the supervision officer recommends early termination of the...

28 CFR 2.43 - Early termination.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Early termination. 2.43 Section 2.43..., YOUTH OFFENDERS, AND JUVENILE DELINQUENTS United States Code Prisoners and Parolees § 2.43 Early... shall also conduct a status review whenever the supervision officer recommends early termination of the...

Equity Starts Early: Addressing Racial Inequities in Child Care and Early Education Policy

ERIC Educational Resources Information Center

Johnson-Staub, Christine

2017-01-01

Child care and early education policies are shaped by a history of systemic and structural racism. This has created major racial disparities in children's access to quality child care that meets their cultural and linguistic needs and enables their parents to work. Early care and education workers are overwhelmingly in low-quality jobs with…

NASA Early Career Fellowship Program

NASA Astrophysics Data System (ADS)

Smith, H. D.

2012-12-01

The Early Career Fellowship program was established in 2005 to facilitate the integration of outstanding early career planetary science researchers into established research funding programs by providing tools and experience useful to maintain a successful research program. Executing a successful research program requires a few key elements such as: successful proposal writing; adequate (paid) research time; management of a laboratory; collaboration and networking; frequent and high-quality publications; and adequate start-up equipment funds. These elements may be particularly critical for early career researchers searching for a tenure- track or equivalent position. The Early Career Fellowship program recognizes the importance of these skills and provides extra funding and resources to begin a successful research program. For consideration into The Early Career Fellowship program, the candidate needs to be the P. I. or Science P.I. of a funded research proposal from one of the participating R&A program areas, be within 7 years of earning a PhD, hold a non-tenure track position, and indicate the early career candidacy when submitting the research proposal. If the research proposal is funded and the discipline scientist nominates the candidate as an early career fellow, the candidate is then considered a Fellow and eligible to propose for Step 2. Upon obtaining a tenure-track equivalent position the Fellow submits a Step 2 proposal for up to one hundred thousand dollars in start-up funds. Start-up funds may be used for salary; undergraduate and/or graduate research assistants; supplies and instrument upgrades; travel to conferences, meetings, and advisory groups; time and travel for learning new skills; publication page charges; books and journal subscriptions; computer time and/or specialized software; and other justified research-specific needs. The early career fellowship program provides resources that a more established scientist would have acquired allowing

43 CFR 10010.9 - Apply NEPA early.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Apply NEPA early. 10010.9 Section 10010.9... Initiating the NEPA Process § 10010.9 Apply NEPA early. (a) The Commission will initiate early consultation... early with interested private parties and organizations, including when the Commission's own involvement...

WWC Review of the Report "Early College, Early Success: Early College High School Initiative Impact Study." What Works Clearinghouse Single Study Review

ERIC Educational Resources Information Center

What Works Clearinghouse, 2014

2014-01-01

Early College High Schools partner with colleges and universities to provide students with an opportunity to earn an Associate's degree or college credits toward a Bachelor's degree at no or low cost to students. In a recent study, researchers found that attending Early College High Schools improved some high school and postsecondary outcomes for…

Michigan Early Adolescent Survey: Final Report.

ERIC Educational Resources Information Center

Keith, Joanne; And Others

This document contains the final report from the Michigan Early Adolescent Survey, a study undertaken to: (1) develop a profile of Michigan early adolescents that focused on out-of-school time and included biological, psychological, and sociological information; (2) develop a profile of families which included early adolescents; (3) assess the…

Challenges and Limitations in Early Intervention

ERIC Educational Resources Information Center

Hadders-Algra, Mijna

2011-01-01

Research over the past three decades has shown that early intervention in infants biologically at risk of developmental disorders, irrespective of the presence of a brain lesion, is associated with improved cognitive development in early childhood without affecting motor development. However, at present it is unknown whether early intervention is…

7 CFR 1717.901 - Early approval.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 11 2011-01-01 2011-01-01 false Early approval. 1717.901 Section 1717.901 Agriculture... for Supplemental Financing Required by 7 CFR 1710.110 § 1717.901 Early approval. (a) Conditions. If... supplemental financing early in the process, before funding is available for the concurrent RUS insured loan...

Early Interventions: Keys to Successful Readers.

ERIC Educational Resources Information Center

Jeffreys, JoAnn; Spang, Joan

This action research outlines an early reading intervention project for improving students' reading skills and promoting the implementation of early reading intervention programs. The targeted population includes first and second grade students in one school located in the suburbs of a major city in Illinois. The problem of early reading…

Early Childhood Services in New Zealand.

ERIC Educational Resources Information Center

Oborn, Glennie

2002-01-01

Describes the types and characteristics of New Zealand early childhood education services. Specific areas addressed include: (1) Te Whaariki, the New Zealand early childhood curriculum; (2) great outdoors as a feature of early education; (3) education and care centers; (4) kindergartens and playcenters; and (5) Te Kohanga Reo, Maori language and…

Early- versus Late-Onset Dysthymia

PubMed Central

Sansone, Lori A.

2009-01-01

In the current Diagnostic and Statistical Manual of Mental Disorders, dysthymic disorder is categorized as either early-onset or late-onset, based upon the emergence of symptoms before or after the age of 21, respectively. Does this diagnostic distinction have any meaningful clinical implications? In this edition of The Interface, we present empirical studies that have, within a single study, compared individuals with early-versus late-onset dysthymia. In this review, we found that, compared to those with late-onset dysthymia, early-onset patients are more likely to harbor psychiatric comorbidity both on Axis I and II, exhibit less psychological resilience, and have more prominent family loadings for mood disorders. These findings suggest that this distinction is meaningful and that the early-onset subtype of dysthymia is more difficult to effectively treat. PMID:20049145

Effect of socioeconomic status disparity on child language and neural outcome: how early is early?

PubMed

Hurt, Hallam; Betancourt, Laura M

2016-01-01

It is not news that poverty adversely affects child outcome. The literature is replete with reports of deleterious effects on developmental outcome, cognitive function, and school performance in children and youth. Causative factors include poor nutrition, exposure to toxins, inadequate parenting, lack of cognitive stimulation, unstable social support, genetics, and toxic environments. Less is known regarding how early in life adverse effects may be detected. This review proposes to elucidate "how early is early" through discussion of seminal articles related to the effect of socioeconomic status on language outcome and a discussion of the emerging literature on effects of socioeconomic status disparity on brain structure in very young children. Given the young ages at which such outcomes are detected, the critical need for early targeted interventions for our youngest is underscored. Further, the fiscal reasonableness of initiating quality interventions supports these initiatives. As early life adversity produces lasting and deleterious effects on developmental outcome and brain structure, increased focus on programs and policies directed to reducing the impact of socioeconomic disparities is essential.

Predicting Readmission at Early Hospitalization Using Electronic Clinical Data: An Early Readmission Risk Score.

PubMed

Tabak, Ying P; Sun, Xiaowu; Nunez, Carlos M; Gupta, Vikas; Johannes, Richard S

2017-03-01

Identifying patients at high risk for readmission early during hospitalization may aid efforts in reducing readmissions. We sought to develop an early readmission risk predictive model using automated clinical data available at hospital admission. We developed an early readmission risk model using a derivation cohort and validated the model with a validation cohort. We used a published Acute Laboratory Risk of Mortality Score as an aggregated measure of clinical severity at admission and the number of hospital discharges in the previous 90 days as a measure of disease progression. We then evaluated the administrative data-enhanced model by adding principal and secondary diagnoses and other variables. We examined the c-statistic change when additional variables were added to the model. There were 1,195,640 adult discharges from 70 hospitals with 39.8% male and the median age of 63 years (first and third quartile: 43, 78). The 30-day readmission rate was 11.9% (n=142,211). The early readmission model yielded a graded relationship of readmission and the Acute Laboratory Risk of Mortality Score and the number of previous discharges within 90 days. The model c-statistic was 0.697 with good calibration. When administrative variables were added to the model, the c-statistic increased to 0.722. Automated clinical data can generate a readmission risk score early at hospitalization with fair discrimination. It may have applied value to aid early care transition. Adding administrative data increases predictive accuracy. The administrative data-enhanced model may be used for hospital comparison and outcome research.

Early College for All: Efforts to Scale up Early Colleges in Multiple Settings

ERIC Educational Resources Information Center

Edmunds, Julie A.

2016-01-01

Given the positive impacts of the small, stand-alone early college model and the desire to provide those benefits to more students, organizations have begun efforts to scale up the early college model in a variety of settings. These efforts have been supported by the federal government, particularly by the Investing in Innovation (i3) program.…

Children with Special Needs: Lessons for Early Childhood Professionals. Early Childhood Education Series.

ERIC Educational Resources Information Center

Kostelnik, Marjorie J.; Onaga, Esther; Rohde, Barbara; Whiren, Alice

Bridging the gap between child development and strategies for inclusion, this book is intended to help early childhood practitioners and pre-service teachers feel better equipped to meet the needs of all the children in their early childhood setting. Each chapter of the book is a case study introducing a child (ages birth to 8 years) with one or…

Positioning and early mobilisation in stroke.

PubMed

Keating, Moira; Penney, Maree; Russell, Petra; Bailey, Emma

Stroke unit care, providing early rehabilitation, improves long-term outcomes for patients following a stroke. Early mobilisation and good positioning are recognised as key aspects of care in stroke units. Nurses working on stroke units have an important role because they are able to implement positioning and early mobilisation strategies 24 hours a day, reducing the risk of complications and improving functional recovery. Patients benefit if nurses work effectively with the therapy team in positioning and early mobilisation. Nurses also need appropriate training and expertise to make best use of specialist equipment.

Colorado Early Childhood Study.

ERIC Educational Resources Information Center

Colorado State Dept. of Education, Denver. Planning and Evaluation Unit.

The Colorado State Board of Education allocated Title IV-V funds in 1975 for a study of the status of early childhood education in Colorado. The purposes of the study were to: (1) gather data relevant to early childhood education on the status of all children from birth through age 5; (2) identify needs of children of this age within the state;…

Early College High Schools

ERIC Educational Resources Information Center

Dessoff, Alan

2011-01-01

For at-risk students who stand little chance of going to college, or even finishing high school, a growing number of districts have found a solution: Give them an early start in college while they still are in high school. The early college high school (ECHS) movement that began with funding from the Bill and Melinda Gates Foundation 10 years ago…

Time-Resolved and Spectroscopic Three-Dimensional Optical Breast Tomography

DTIC Science & Technology

2008-04-01

Appendix 1. Each raw image was then cropped to select out the information-rich region, and binned to enhance the signal-to-noise ratio. All the binned...component analysis, near infrared (NIR) imaging, optical mammography , optical imaging using independent component analysis (OPTICA). I. INTRODUCTION N EAR...merging 5 × 5 pixels into one to enhance the SNR, resulting in a total of 352 images of 54 × 55 pixels each. All the binned images corresponding to

Survival After Early and Normal Retirement

ERIC Educational Resources Information Center

Haynes, Suzanne G.; And Others

1978-01-01

Describes an epidemiological study of the patterns and correlates of survival after early (age 62 to 64) and normal retirement (age 65). Death rates were significantly elevated during the first, fourth, and fifth years after early retirement. Pre-retirement health status was the only significant predictor of survival after early retirement.…

Leadership in Early Childhood Special Education

ERIC Educational Resources Information Center

Arora, Samita Berry

2013-01-01

With the demands of high quality early childhood special education programs within public school settings, there is a need to place emphasis on research and training regarding early childhood leaders and managers in this complex and diverse field. The focus of this research is to examine what early childhood special education (ECSE) leadership…

29 CFR 553.225 - Early relief.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 3 2011-07-01 2011-07-01 false Early relief. 553.225 Section 553.225 Labor Regulations... Enforcement Employees of Public Agencies Tour of Duty and Compensable Hours of Work Rules § 553.225 Early... employees on the previous shift prior to the scheduled starting time. Such early relief time may occur...

29 CFR 553.225 - Early relief.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Early relief. 553.225 Section 553.225 Labor Regulations... Enforcement Employees of Public Agencies Tour of Duty and Compensable Hours of Work Rules § 553.225 Early... employees on the previous shift prior to the scheduled starting time. Such early relief time may occur...

Processes of early stroke care and hospital costs.

PubMed

Svendsen, Marie Louise; Ehlers, Lars H; Hundborg, Heidi H; Ingeman, Annette; Johnsen, Søren P

2014-08-01

The relationship between processes of early stroke care and hospital costs remains unclear. We therefore examined the association in a population based cohort study. We identified 5909 stroke patients who were admitted to stroke units in a Danish county between 2005 and 2010.The examined recommended processes of care included early admission to a stroke unit, early initiation of antiplatelet or anticoagulant therapy, early computed tomography/magnetic resonance imaging (CT/MRI) scan, early physiotherapy and occupational therapy, early assessment of nutritional risk, constipation risk and of swallowing function, early mobilization,early catheterization, and early thromboembolism prophylaxis.Hospital costs were assessed for each patient based on the number of days spent in different in-hospital facilities using local hospital charges. The mean costs of hospitalization were $23 352 (standard deviation 27 827). The relationship between receiving more relevant processes of early stroke care and lower hospital costs followed a dose–response relationship. The adjusted costs were $24 566 (95% confidence interval 19 364–29 769) lower for patients who received 75–100% of the relevant processes of care compared with patients receiving 0–24%. All processes of care were associated with potential cost savings, except for early catheterization and early thromboembolism prophylaxis. Early care in agreement with key guidelines recommendations for the management of patients with stroke may be associated with hospital savings.

[Autism: An early neurodevelopmental disorder].

PubMed

Bonnet-Brilhault, F

2017-04-01

With approximately 67 million individuals affected worldwide, autism spectrum disorder (ASD) is the fastest growing neurodevelopmental disorder (United Nations, 2011), with a prevalence estimated to be 1/100. In France ASD affects approximately 600,000 individuals (from childhood to adulthood, half of whom are also mentally retarded), who thus have a major handicap in communication and in adapting to daily life, which leads autism to be recognized as a national public health priority. ASD is a neurodevelopmental disorder that affects several domains (i.e., socio-emotional, language, sensori-motor, executive functioning). These disorders are expressed early in life with an age of onset around 18 months. Despite evidence suggesting a strong genetic link with ASD, the genetic determinant remains unclear. The clinical picture is characterized by impairments in social interaction and communication and the presence of restrictive and repetitive behaviors (DSM-5, ICD-10). However, in addition to these two main dimensions there is significant comorbidity between ASD and other neurodevelopmental disorders such as attention deficit hyperactivity disorder or with genetic and medical conditions. One of the diagnostic features of ASD is its early emergence: symptoms must begin in early childhood for a diagnosis to be given. Due to brain plasticity, early interventions are essential to facilitate clinical improvement. Therefore, general practitioners and pediatricians are on the front line to detect early signs of ASD and to guide both medical explorations and early rehabilitation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Evaluating and Supporting Early Childhood Teachers

ERIC Educational Resources Information Center

Passe, Angèle Sancho

2015-01-01

There's a lot of conversation in the early childhood community on evaluating teachers to improve their performance. Raising the quality of early care and education is a priority for policymakers and practitioners on local, state, and federal levels. As a result, much attention is being focused on early childhood educators to ensure that they do a…

Early Detection | Division of Cancer Prevention

Cancer.gov

[[{"fid":"171","view_mode":"default","fields":{"format":"default","field_file_image_alt_text[und][0][value]":"Early Detection Research Group Homepage Logo","field_file_image_title_text[und][0][value]":"Early Detection Research Group Homepage Logo","field_folder[und]":"15"},"type":"media","field_deltas":{"1":{"format":"default","field_file_image_alt_text[und][0][value]":"Early

37 CFR 1.219 - Early publication.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Early publication. 1.219... Applications § 1.219 Early publication. Applications that will be published under § 1.211 may be published earlier than as set forth in § 1.211(a) at the request of the applicant. Any request for early publication...

37 CFR 1.219 - Early publication.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 37 Patents, Trademarks, and Copyrights 1 2011-07-01 2011-07-01 false Early publication. 1.219... Applications § 1.219 Early publication. Applications that will be published under § 1.211 may be published earlier than as set forth in § 1.211(a) at the request of the applicant. Any request for early publication...

Early Restoration | NOAA Gulf Spill Restoration

Science.gov Websites

Early Restoration Plan. On April 20, 2011 we reached an agreement with BP to start restoration planning draft plan for the third phase of early restoration in December 2013. We are considering your comments : All Phase III information and documents Phase II Useful Links: Phase II Early Restoration Plan &

Sprites and Early ionospheric VLF perturbations

NASA Astrophysics Data System (ADS)

Haldoupis, Christos; Amvrosiadi, Nino; Cotts, Ben; van der Velde, Oscar; Chanrion, Olivier; Neubert, Torsten

2010-05-01

Past studies have shown a correlation between sprites and early VLF perturbations, but the reported correlation varies widely from ~ 50% to 100%. The present study resolves these large discrepancies by analyzing several case studies of sprite and narrowband VLF observations, in which multiple transmitter-receiver VLF links with great circle paths (GCPs) passing near a sprite-producing thunderstorm were available. In this setup, the multiple links act in a complementary way that makes the detection of early VLF perturbations much more probable compared to a single VLF link that can miss several of them, a fact that was overlooked in past studies. The evidence shows that sprites are accompanied by early VLF perturbations in a one-to-one correspondence. This implies that the sprite generation mechanism may cause also sub-ionospheric conductivity disturbances that produce early VLF events. However, the one-to-one "sprite to early" event relationship, if viewed conversely as "early to sprite", appears not to be always reciprocal. This is because the number of early events detected in some cases was considerably larger than the number of sprites. Since the great majority of the early events not accompanied by sprites was caused by positive cloud to ground (+CG) lightning discharges, it is possible that sprites or sprite halos were concurrently present in these events as well but were missed by the sprite-watch detection system. In order for this option to be resolved we need more studies using highly sensitive optical systems capable of detecting weaker sprites, sprite halos and elves.

Early recognition of growth abnormalities permitting early intervention

USDA-ARS?s Scientific Manuscript database

Normal growth is a sign of good health. Monitoring for growth disturbances is fundamental to children's health care. Early detection and diagnosis of the causes of short stature allows management of underlying medical conditions, optimizing attainment of good health and normal adult height. This rev...

Integrating Computer Technology in Early Childhood Education Environments: Issues Raised by Early Childhood Educators

ERIC Educational Resources Information Center

Wood, Eileen; Specht, Jacqueline; Willoughby, Teena; Mueller, Julie

2008-01-01

The purpose of this study was to assess the educators' perspectives on the introduction of computer technology in the early childhood education environment. Fifty early childhood educators completed a survey and participated in focus groups. Parallels existed between the individually completed survey data and the focus group discussions. The…

Integrating partner professionals. The Early Explorers project: Peers Early Education Partnership and the health visiting service.

PubMed

Barlow, J; Coe, C

2013-01-01

  A range of voluntary sector organizations are involved in the delivery of services to children, particularly within the Early Year's sector and children's centres. Peers Early Education Partnership (PEEP) Early Explorers project is one example of the way in which explicit partnerships are being forged across statutory and voluntary sectors with the aim of improving outcomes for children and families. This paper reports an exploration of stakeholder views and experiences of two Early Explorer clinics located in areas of high deprivation.   Semi-structured interviews were conducted with a purposive sample of stakeholders (n= 25) from children's centres, PEEP, the health visiting service and service users. Data were fully transcribed and analysed using a thematic approach.   The data suggest that the two key groups of stakeholders providing Early Explorer clinics (i.e. health visitors and PEEP practitioners) had quite different objectives in terms of their early goals for the clinic, but that despite these differences good progress was achieved in terms of working together effectively. All stakeholders including service users referred to the presence of PEEP as having improved the quality of the clinic environment, and participating mothers identified a wide range of benefits from the enhanced service. However, somewhat restricted views about the role of practitioners within the clinics were identified by users, and the findings suggest that although the early goals for the clinic had been exceeded, these may have been limited in terms of true 'partnership' working.   Early Explorer clinics appeared to have enhanced the service provided within traditional child health clinics and to have provided practitioners with access to hard-to-reach families and parents with access to services that are consistent with the broader policy aims of improving parent-infant interaction. However, questions remain as to whether the benefit of 'partnership' working was fully

Early anthropometric indices predict short stature and overweight status in a cohort of Peruvians in early adolescence

PubMed Central

Sterling, Robie; Miranda, J Jaime; Gilman, Robert H; Cabrera, Lilia; Sterling, Charles R; Bern, Caryn; Checkley, William

2014-01-01

While childhood malnutrition is associated with increased morbidity and mortality, less well understood is how early childhood growth influences height and body composition later in life. We revisited 152 Peruvian children who participated in a birth cohort study between 1995 and 1998, and obtained anthropometric and bioimpedance measurements 11 to 14 years later. We used multivariable regression models to study the effects of childhood anthropometric indices on height and body composition in early adolescence. Each standard deviation decrease in length-for-age at birth was associated with a decrease in adolescent height-for-age of 0.7 SD in both boys and girls (all p<0.001) and 9.7 greater odds of stunting (95% CI 3.3 to 28.6). Each SD decrease in length-for-age in the first 30 months of life was associated with a decrease in adolescent height-for-age of 0.4 in boys and 0.6 standard deviation in girls (all p<0.001) and with 5.8 greater odds of stunting (95% CI 2.6 to 13.5). The effect of weight gain during early childhood on weight in early adolescence was more complex to understand. Weight-for-length at birth and rate of change in weight-for-length in early childhood were positively associated with age- and sex-adjusted body mass index and a greater risk of being overweight in early adolescence. Linear growth retardation in early childhood is a strong determinant of adolescent stature, indicating that, in developing countries, growth failure in height during early childhood persists through early adolescence. Interventions addressing linear growth retardation in childhood are likely to improve adolescent stature and related-health outcomes in adulthood. PMID:22552904

Early anthropometric indices predict short stature and overweight status in a cohort of Peruvians in early adolescence.

PubMed

Sterling, Robie; Miranda, J Jaime; Gilman, Robert H; Cabrera, Lilia; Sterling, Charles R; Bern, Caryn; Checkley, William

2012-07-01

While childhood malnutrition is associated with increased morbidity and mortality, less well understood is how early childhood growth influences height and body composition later in life. We revisited 152 Peruvian children who participated in a birth cohort study between 1995 and 1998, and obtained anthropometric and bioimpedance measurements 11-14 years later. We used multivariable regression models to study the effects of childhood anthropometric indices on height and body composition in early adolescence. Each standard deviation decrease in length-for-age at birth was associated with a decrease in adolescent height-for-age of 0.7 SD in both boys and girls (all P < 0.001) and 9.7 greater odds of stunting (95% CI 3.3-28.6). Each SD decrease in length-for-age in the first 30 months of life was associated with a decrease in adolescent height-for-age of 0.4 in boys and 0.6 standard deviation in girls (all P < 0.001) and with 5.8 greater odds of stunting (95% CI 2.6-13.5). The effect of weight gain during early childhood on weight in early adolescence was more complex to understand. Weight-for-length at birth and rate of change in weight-for-length in early childhood were positively associated with age- and sex-adjusted body mass index and a greater risk of being overweight in early adolescence. Linear growth retardation in early childhood is a strong determinant of adolescent stature, indicating that, in developing countries, growth failure in height during early childhood persists through early adolescence. Interventions addressing linear growth retardation in childhood are likely to improve adolescent stature and related-health outcomes in adulthood. Copyright © 2012 Wiley Periodicals, Inc.

[Early flat colorectal cancer].

PubMed

Castelletto, R H; Chiarenza, C; Ottino, A; Garay, M L

1991-01-01

We report three cases of flat early colorectal carcinoma which were detected during the examination of 51 surgical specimens of colorectal resection. Two of them were endoscopically diagnosed, but the smallest one was not seen in the luminal instrumental examination. From the bibliographic analysis and our own experience we deduce the importance of flat lesions in the development of early colorectal carcinoma, either originated from pre-existent adenoma or de novo. Flat variants of adenoma, and presumably flush or depressed ones, must be considered as important factors in the early sequence adenoma-cancer. An appropriate endoscopic equipment with employment of additional staining techniques (such as carmine indigo and methylene blue) and the correct investigation during inflation-deflation procedures facilitates the identification of small lesions, their eradication and prevention from advanced forms of colorectal carcinoma.

[The early pregnancy factor (EPF) as an early marker of disorders in pregnancy].

PubMed

Straube, W; Römer, T; Zeenni, L; Loh, M

1995-01-01

The early pregnancy factor (EPF) seems to be very helpful in clinical applications such as early detection of pregnancy, differential diagnosis of failure of fertilization or implementation and prognosis of a fertilized ovum. Our purpose was to investigate the diagnostic value of single and serial measurement of EPF, especially in the differential diagnosis of abortion and extrauterine pregnancy. Women with a history of 6-16 weeks amenorrhoea with/without vaginal bleeding were included in the prospective study. The EPF-test system was carried out by means of the rosette inhibition method. EPF proved to be always positive in normal pregnant women and always negative in nonpregnant controls. In case of threatened abortion the prognosis was good, when the EPF values were positive, and poor when they became negative. Patients suffering from spontaneous and missed abortion mostly showed negative EPF-values. This was also true in ectopic pregnancies. The sensitivity and specificity of EPF-test system were 83%. The positive predictive value was observed to be 54% and the negative predictive value 95%. The EPF as an early embryonic signal may be a suitable parameter for the clinical use detecting pregnancy disturbances very early.

Marital conflict and early adolescents' self-evaluation: the role of parenting quality and early adolescents' appraisals.

PubMed

Siffert, Andrea; Schwarz, Beate; Stutz, Melanie

2012-06-01

Cognitive appraisals and family dynamics have been identified as mediators of the relationship between marital conflict and children's adjustment. Surprisingly little research has investigated both meditational processes in the same study. Guided by the cognitive-contextual framework and the spillover hypothesis, the present study integrated factors from both theories early adolescents' appraisals of threat and self-blame, as well as perceived parenting quality as mediators of the link between early adolescents' perception of marital conflict and their self-evaluations (self-esteem and scholastic competence). Analyses were based on the first two waves of an ongoing longitudinal study. Participants were 176 two-parent families, and their early adolescents (50.5% girls) whose mean age was 10.61 years at Time 1 (SD =0.40) and 11.63 years at Time 2 (SD=0.39). Structural equation modeling analyses indicated that parenting quality and early adolescents' perceived threat provided indirect pathways between marital conflict and early adolescents' self-esteem 1 year later when controlling for their initial level of self-esteem. With respect to scholastic competence, only fathers' parenting was an indirect link. Self-blame did not play a role. Implications for understanding the mechanisms by which exposure to marital conflict predicts early adolescents' maladjustment are discussed.

Capturing early signs of deterioration: the dutch-early-nurse-worry-indicator-score and its value in the Rapid Response System.

PubMed

Douw, Gooske; Huisman-de Waal, Getty; van Zanten, Arthur R H; van der Hoeven, Johannes G; Schoonhoven, Lisette

2017-09-01

To determine the predictive value of individual and combined dutch-early-nurse-worry-indicator-score indicators at various Early Warning Score levels, differentiating between Early Warning Scores reaching the trigger threshold to call a rapid response team and Early Warning Score levels not reaching this point. Dutch-early-nurse-worry-indicator-score comprises nine indicators underlying nurses' 'worry' about a patient's condition. All indicators independently show significant association with unplanned intensive care/high dependency unit admission or unexpected mortality. Prediction of this outcome improved by adding the dutch-early-nurse-worry-indicator-score indicators to an Early Warning Score based on vital signs. An observational cohort study was conducted on three surgical wards in a tertiary university-affiliated teaching hospital. Included were surgical, native-speaking, adult patients. Nurses scored presence of 'worry' and/or dutch-early-nurse-worry-indicator-score indicators every shift or when worried. Vital signs were measured according to the prevailing protocol. Unplanned intensive care/high dependency unit admission or unexpected mortality was the composite endpoint. Percentages of 'worry' and dutch-early-nurse-worry-indicator-score indicators were calculated at various Early Warning Score levels in control and event groups. Entering all dutch-early-nurse-worry-indicator-score indicators in a multiple logistic regression analysis, we calculated a weighted score and calculated sensitivity, specificity, positive predicted value and negative predicted value for each possible total score. In 3522 patients, 102 (2·9%) had an unplanned intensive care/high dependency unit admissions (n = 97) or unexpected mortality (n = 5). Patients with such events and only slightly changed vital signs had significantly higher percentages of 'worry' and dutch-early-nurse-worry-indicator-score indicators expressed than patients in the control group. Increasing number

Early Rockets

NASA Image and Video Library

2004-04-15

In addition to Dr. Robert Goddard's pioneering work, American experimentation in rocketry prior to World War II grew, primarily in technical societies. This is an early rocket motor designed and developed by the American Rocket Society in 1932.

Telomere length and early severe social deprivation: linking early adversity and cellular aging

PubMed Central

Drury, SS; Theall, K; Gleason, MM; Smyke, AT; De Vivo, I; Wong, JYY; Fox, NA; Zeanah, CH; Nelson, CA

2012-01-01

Accelerated telomere length attrition has been associated with psychological stress and early adversity in adults; however, no studies have examined whether telomere length in childhood is associated with early experiences. The Bucharest Early Intervention Project is a unique randomized controlled trial of foster care placement compared with continued care in institutions. As a result of the study design, participants were exposed to a quantified range of time in institutional care, and represented an ideal population in which to examine the association between a specific early adversity, institutional care and telomere length. We examined the association between average relative telomere length, telomere repeat copy number to single gene copy number (T/S) ratio and exposure to institutional care quantified as the percent of time at baseline (mean age 22 months) and at 54 months of age that each child lived in the institution. A significant negative correlation between T/S ratio and percentage of time was observed. Children with greater exposure to institutional care had significantly shorter relative telomere length in middle childhood. Gender modified this main effect. The percentage of time in institutional care at baseline significantly predicted telomere length in females, whereas the percentage of institutional care at 54 months was strongly predictive of telomere length in males. This is the first study to demonstrate an association between telomere length and institutionalization, the first study to find an association between adversity and telomere length in children, and contributes to the growing literature linking telomere length and early adversity. PMID:21577215

Unlocking the Future: Early Literacy.

ERIC Educational Resources Information Center

Blair, Leslie Asher, Ed.

1999-01-01

This newsletter of the Southwest Educational Development Laboratory (SEDL)contains a collection of articles which discuss various aspects of early literacy. Articles in the newsletter are: "Introduction: Reading Instruction, a Key to the Future"; "Ensuring Early Literacy through Coherent Instruction" (Leslie Blair);…

Early extubation after cardiac surgery: emotional status in the early postoperative period.

PubMed

Silbert, B S; Santamaria, J D; Kelly, W J; O'brien, J L; Blyth, C M; Wong, M Y; Allen, N B

2001-08-01

To compare the emotional state during the first 3 days after coronary artery surgery of patients who had undergone early versus conventional extubation. A prospective, randomized, controlled trial. University hospital, single center. Eligible patients (n = 100) presenting for elective coronary artery surgery, randomized to an early extubation group or a conventional extubation group. Emotional status was measured by the Hospital Anxiety and Depression Scale (HAD), the Self Assessment Manikin (SAM), and the Multiple Affect Adjective Check List-Revised (MAACL-R). Tests were administered preoperatively and on the 1st and 3rd days postoperatively. Of patients in the conventional extubation group, 30% showed moderate-to-severe depressive symptoms (HAD score >10) on day 3 postoperatively compared with 8% of patients in the early extubation group (p = 0.02). There was a clinically insignificant increase in MAACL-R depression score on the 1st postoperative day within both groups but no other differences within or between groups in SAM or MAACL-R scores. Early extubation results in fewer patients displaying depressive symptoms on the 3rd postoperative day but appears to have little effect on other measurements of emotional status. Anesthetic management during coronary artery bypass graft surgery may play an important role in the overall well-being of the patient by decreasing the incidence of postoperative depression. Copyright 2001 by W.B. Saunders Company.

Couple Therapy with Veterans: Early Improvements and Predictors of Early Dropout.

PubMed

Fischer, Melanie S; Bhatia, Vickie; Baddeley, Jenna L; Al-Jabari, Rawya; Libet, Julian

2017-07-28

Family services within Veterans Affairs Medical Centers fulfill an important role in addressing relationship distress among Veterans, which is highly prevalent and comorbid with psychopathology. However, even for evidence-based couple therapies, effectiveness is weaker compared to controlled studies, maybe because many Veteran couples drop out early and do not reach the "active" treatment stage after the 3-4 session assessment. In order to improve outcomes, it is critical to identify couples at high risk for early dropout, and understand whether couples may benefit from the assessment as an intervention. The current study examined (a) demographics, treatment delivery mode, relationship satisfaction, and psychological symptoms as predictors of dropout during and immediately following the assessment phase, and (b) changes in relationship satisfaction during assessment. 174 couples completed questionnaires during routine intake procedures. The main analyses focused on 140 male Veterans and their female civilian partners; 36.43% dropped out during the assessment phase and 24.74% of the remaining couples immediately following the first treatment session. More severe depressive symptoms in non-Veteran partners were associated with dropout during assessment. Relationship satisfaction improved significantly during the assessment phase for couples who did not drop out, with larger gains for non-Veteran partners. No demographics or treatment delivery mode were associated with dropout. Although more research is needed on engaging couples at risk for early dropout and maximizing early benefits, the findings suggest that clinicians should attend to the civilian partner's and Veteran's depressive symptoms at intake and consider the assessment part of active treatment. © 2017 Family Process Institute.

Early Education and Care, and Reconceptualizing Play. Advances in Early Education and Day Care.

ERIC Educational Resources Information Center

Reifel, Stuart, Ed.; Brown, Mac H., Ed.

Providing a forum for current thought about the field of early education and care, this book reviews efforts worldwide to educate young children. The book examines child care quality, presents a cultural feminist perspective on caregiving, discusses curricular issues, and considers the role of play in early childhood practice. The chapters are:…

Explaining Why Early-Maturing Girls Are More Exposed to Sexual Harassment in Early Adolescence

ERIC Educational Resources Information Center

Skoog, Therése; Bayram Özdemir, Sevgi

2016-01-01

In this study, we tested two competing explanations of the previously established link between early female puberty and sexual harassment in early adolescence. The sample included 680 seventh-grade Swedish girls (M[subscript age] = 13.40, SD = 0.53). Findings revealed that looking more sexually mature and being sexually active mediated the link…

Sophisticated digestive systems in early arthropods.

PubMed

Vannier, Jean; Liu, Jianni; Lerosey-Aubril, Rudy; Vinther, Jakob; Daley, Allison C

2014-05-02

Understanding the way in which animals diversified and radiated during their early evolutionary history remains one of the most captivating of scientific challenges. Integral to this is the 'Cambrian explosion', which records the rapid emergence of most animal phyla, and for which the triggering and accelerating factors, whether environmental or biological, are still unclear. Here we describe exceptionally well-preserved complex digestive organs in early arthropods from the early Cambrian of China and Greenland with functional similarities to certain modern crustaceans and trace these structures through the early evolutionary lineage of fossil arthropods. These digestive structures are assumed to have allowed for more efficient digestion and metabolism, promoting carnivory and macrophagy in early arthropods via predation or scavenging. This key innovation may have been of critical importance in the radiation and ecological success of Arthropoda, which has been the most diverse and abundant invertebrate phylum since the Cambrian.

Challenges facing early career academic cardiologists.

PubMed

Tong, Carl W; Ahmad, Tariq; Brittain, Evan L; Bunch, T Jared; Damp, Julie B; Dardas, Todd; Hijar, Amalea; Hill, Joseph A; Hilliard, Anthony A; Houser, Steven R; Jahangir, Eiman; Kates, Andrew M; Kim, Darlene; Lindman, Brian R; Ryan, John J; Rzeszut, Anne K; Sivaram, Chittur A; Valente, Anne Marie; Freeman, Andrew M

2014-06-03

Early career academic cardiologists currently face unprecedented challenges that threaten a highly valued career path. A team consisting of early career professionals and senior leadership members of American College of Cardiology completed this white paper to inform the cardiovascular medicine profession regarding the plight of early career cardiologists and to suggest possible solutions. This paper includes: 1) definition of categories of early career academic cardiologists; 2) general challenges to all categories and specific challenges to each category; 3) obstacles as identified by a survey of current early career members of the American College of Cardiology; 4) major reasons for the failure of physician-scientists to receive funding from National Institute of Health/National Heart Lung and Blood Institute career development grants; 5) potential solutions; and 6) a call to action with specific recommendations. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Children’s early helping in action: Piagetian developmental theory and early prosocial behavior

PubMed Central

Hammond, Stuart I.

2014-01-01

After a brief overview of recent research on early helping, outlining some central problems, and issues, this paper examines children’s early helping through the lens of Piagetian moral and developmental theory, drawing on Piaget’s “Moral Judgment of the Child” (Piaget, 1932/1997), “Play, Dreams, and Imitation in Childhood” (Piaget, 1945/1951), and the “Grasp of Consciousness” (Piaget, 1976). Piaget refers to a level of moral development in action that precedes heteronomous and autonomous moral reasoning. This action level allows children to begin to interact with people and objects. In his later work, Piaget explores the gradual construction of understanding from this activity level. Taken together, these elements of Piagetian theory provide a promising conceptual framework for understanding the development of early helping. PMID:25101027

Morphogenesis of early stage melanoma

NASA Astrophysics Data System (ADS)

Chatelain, Clément; Amar, Martine Ben

2015-08-01

Melanoma early detection is possible by simple skin examination and can insure a high survival probability when successful. However it requires efficient methods for identifying malignant lesions from common moles. This paper provides an overview first of the biological and physical mechanisms controlling melanoma early evolution, and then of the clinical tools available today for detecting melanoma in vivo at an early stage. It highlights the lack of diagnosis methods rationally linking macroscopic observables to the microscopic properties of the tissue, which define the malignancy of the tumor. The possible inputs of multiscale models for improving these methods are shortly discussed.

Analysis of Early Military Attrition Behavior.

DTIC Science & Technology

1984-06-01

military separation. Although hizh school graduation status is the primary single factor affecting attrition, age and previous employment stability...assignment like individual suitability and satisfaction do not significantly influence early attrition; the early attrition rate of nonhigh- school ...a recruit with a single previous employer. I I V IS BLANK vi * Various indicators of military job match had no significant impact on early attrition

[Early mobilization. Competencies, responsibilities, milestones].

PubMed

Nydahl, P; Dewes, M; Dubb, R; Filipovic, S; Hermes, C; Jüttner, F; Kaltwasser, A; Klarmann, S; Klas, K; Mende, H; Rothaug, O; Schuchhardt, D

2016-03-01

Early mobilization is an evident, interprofessional concept to improve the outcome of intensive care patients. It reduces psychocognitive deficits and delirium and attenuates a general deconditioning, including atrophy of the respiratory pump and skeletal muscles. In this regard the interdisciplinary approach of early mobilization, taking into account different levels of mobilization, appears to be beneficial. The purpose of this study was to explore opinions on collaboration and tasks between different professional groups. During the 25th Bremen Conference on Intensive Medicine and Nursing on 20 February 2015, a questionnaire survey was carried out among the 120 participants of the German Early Mobilization Network meeting. In all, 102 questionnaires were analyzed. Most participants reported on the interdisciplinarity of the approach, but none of the tasks and responsibilities concerning early mobilization can be assigned to a single professional group. The practical implementation of mobilizing orally intubated patients may require two registered nurses as well as a physical therapist. Implementation in daily practice seems to be heterogeneous. There is no consensus regarding collaboration, competencies, and responsibilities with respect to early mobilization of intensive care patients. The approach to date has been characterized by a lack of interprofessional communication, which may lead to an inefficient use of the broad and varied base of knowledge and experienceof the different professions.

Telomere lengthening early in development.

PubMed

Liu, Lin; Bailey, Susan M; Okuka, Maja; Muñoz, Purificación; Li, Chao; Zhou, Lingjun; Wu, Chao; Czerwiec, Eva; Sandler, Laurel; Seyfang, Andreas; Blasco, Maria A; Keefe, David L

2007-12-01

Stem cells and cancer cells maintain telomere length mostly through telomerase. Telomerase activity is high in male germ line and stem cells, but is low or absent in mature oocytes and cleavage stage embryos, and then high again in blastocysts. How early embryos reset telomere length remains poorly understood. Here, we show that oocytes actually have shorter telomeres than somatic cells, but their telomeres lengthen remarkably during early cleavage development. Moreover, parthenogenetically activated oocytes also lengthen their telomeres, thus the capacity to elongate telomeres must reside within oocytes themselves. Notably, telomeres also elongate in the early cleavage embryos of telomerase-null mice, demonstrating that telomerase is unlikely to be responsible for the abrupt lengthening of telomeres in these cells. Coincident with telomere lengthening, extensive telomere sister-chromatid exchange (T-SCE) and colocalization of the DNA recombination proteins Rad50 and TRF1 were observed in early cleavage embryos. Both T-SCE and DNA recombination proteins decrease in blastocyst stage embryos, whereas telomerase activity increases and telomeres elongate only slowly. We suggest that telomeres lengthen during the early cleavage cycles following fertilization through a recombination-based mechanism, and that from the blastocyst stage onwards, telomerase only maintains the telomere length established by this alternative mechanism.

Early Identification of Autism

PubMed Central

Webb, Sara Jane; Jones, Emily J.H.

2016-01-01

In the first year of life, infants who later go on to develop autistic spectrum disorders (ASD) may exhibit subtle disruptions in social interest and attention, communication, temperament, and head circumference growth that occur prior to the onset of clinical symptoms. These disruptions may reflect the early course of ASD development and may also contribute to the later development of clinical symptoms through alterations in the child’s experience of his or her environment. By age 2, developmental precursors of autism symptoms can be used to diagnose children reliably, and by age 3, the diagnosis is thought to be relatively stable. The downward extension of the autism diagnosis poses important questions for therapists in designing interventions that are applicable for infants who demonstrate early risk factors. We review current knowledge of the early signs of ASD in the infancy period (0–12 months) and the manifestation of symptoms in toddlerhood (12– 36 months), noting the importance of considering the variability in onset and trajectory of ASD. Finally, we consider the implications of this emerging research for those who work or interact with young children, including the importance of early monitoring and the development and evaluation of age-appropriate interventions. PMID:28090148

Early Intervention in Psychosis

PubMed Central

McGorry, Patrick D.

2015-01-01

Abstract Early intervention for potentially serious disorder is a fundamental feature of healthcare across the spectrum of physical illness. It has been a major factor in the reductions in morbidity and mortality that have been achieved in some of the non-communicable diseases, notably cancer and cardiovascular disease. Over the past two decades, an international collaborative effort has been mounted to build the evidence and the capacity for early intervention in the psychotic disorders, notably schizophrenia, where for so long deep pessimism had reigned. The origins and rapid development of early intervention in psychosis are described from a personal and Australian perspective. This uniquely evidence-informed, evidence-building and cost-effective reform provides a blueprint and launch pad to radically change the wider landscape of mental health care and dissolve many of the barriers that have constrained progress for so long. PMID:25919380

Early intervention for psychosis

PubMed Central

Marshall, Max; Rathbone, John

2014-01-01

Background Proponents of early intervention have argued that outcomes might be improved if more therapeutic efforts were focused on the early stages of schizophrenia or on people with prodromal symptoms. Early intervention in schizophrenia has two elements that are distinct from standard care: early detection, and phase-specific treatment (phase-specific treatment is a psychological, social or physical treatment developed, or modified, specifically for use with people at an early stage of the illness). Early detection and phase-specific treatment may both be offered as supplements to standard care, or may be provided through a specialised early intervention team. Early intervention is now well established as a therapeutic approach in America, Europe and Australasia. Objectives To evaluate the effects of: (a) early detection; (b) phase-specific treatments; and (c) specialised early intervention teams in the treatment of people with prodromal symptoms or first-episode psychosis. Search methods We searched the Cochrane Schizophrenia Group Trials Register (March 2009), inspected reference lists of all identified trials and reviews and contacted experts in the field. Selection criteria We included all randomised controlled trials (RCTs) designed to prevent progression to psychosis in people showing prodromal symptoms, or to improve outcome for people with first-episode psychosis. Eligible interventions, alone and in combination, included: early detection, phase-specific treatments, and care from specialised early intervention teams. We accepted cluster-randomised trials but excluded non-randomised trials. Data collection and analysis We reliably selected studies, quality rated them and extracted data. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) and used intention-to-treat analysis (ITT). Main results Studies were diverse, mostly small

Early identification systems for emerging foodborne hazards.

PubMed

Marvin, H J P; Kleter, G A; Prandini, A; Dekkers, S; Bolton, D J

2009-05-01

This paper provides a non-exhausting overview of early warning systems for emerging foodborne hazards that are operating in the various places in the world. Special attention is given to endpoint-focussed early warning systems (i.e. ECDC, ISIS and GPHIN) and hazard-focussed early warning systems (i.e. FVO, RASFF and OIE) and their merit to successfully identify a food safety problem in an early stage is discussed. Besides these early warning systems which are based on monitoring of either disease symptoms or hazards, also early warning systems and/or activities that intend to predict the occurrence of a food safety hazard in its very beginning of development or before that are described. Examples are trend analysis, horizon scanning, early warning systems for mycotoxins in maize and/or wheat and information exchange networks (e.g. OIE and GIEWS). Furthermore, recent initiatives that aim to develop predictive early warning systems based on the holistic principle are discussed. The assumption of the researchers applying this principle is that developments outside the food production chain that are either directly or indirectly related to the development of a particular food safety hazard may also provide valuable information to predict the development of this hazard.

75 FR 20830 - Early Learning

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-21

... meetings and written submissions, is seeking input from State agencies responsible for early learning and... intervention service providers and other providers of services to young children), students, technical... receive all written submissions of comments on the four early learning topics on or before 5 p.m...

Enhanced influence of early-spring tropical Indian Ocean SST on the following early-summer precipitation over Northeast China

NASA Astrophysics Data System (ADS)

Han, Tingting; He, Shengping; Wang, Huijun; Hao, Xin

2017-04-01

The relationship between the tropical Indian Ocean (TIO) and East Asian summer monsoon/precipitation has been documented in many studies. However, the precursor signals of summer precipitation in the TIO sea surface temperature (SST), which is important for climate prediction, have drawn little attention. This study identified a strong relationship between early-spring TIO SST and subsequent early-summer precipitation in Northeast China (NEC) since the late 1980s. For 1961-1986, the correlations between early-spring TIO SST and early-summer NEC precipitation were statistically insignificant; for 1989-2014, they were positively significant. Since the late 1980s, the early-spring positive TIO SST anomaly was generally followed by a significant anomalous anticyclone over Japan; that facilitated anomalous southerly winds over NEC, conveying more moisture from the North Pacific. Further analysis indicated that an early TIO SST anomaly showed robust persistence into early summer. However, the early-summer TIO SST anomaly displayed a more significant influence on simultaneous atmospheric circulation and further affected NEC precipitation since the late 1980s. In 1989-2014, the early-summer Hadley and Ferrell cell anomalies associated with simultaneous TIO SST anomaly were much more significant and extended further north to mid-latitudes, which provided a dynamic foundation for the TIO-mid-latitude connection. Correspondingly, the TIO SST anomaly could lead to significant divergence anomalies over the Mediterranean. The advections of vorticity by the divergent component of the flow effectively acted as a Rossby wave source. Thus, an apparent Rossby wave originated from the Mediterranean and propagated east to East Asia; that further influenced the NEC precipitation through modulation to the atmospheric circulation (e.g., surface wind, moisture, vertical motion).

Early Diagnosis of Breast Cancer.

PubMed

Wang, Lulu

2017-07-05

Early-stage cancer detection could reduce breast cancer death rates significantly in the long-term. The most critical point for best prognosis is to identify early-stage cancer cells. Investigators have studied many breast diagnostic approaches, including mammography, magnetic resonance imaging, ultrasound, computerized tomography, positron emission tomography and biopsy. However, these techniques have some limitations such as being expensive, time consuming and not suitable for young women. Developing a high-sensitive and rapid early-stage breast cancer diagnostic method is urgent. In recent years, investigators have paid their attention in the development of biosensors to detect breast cancer using different biomarkers. Apart from biosensors and biomarkers, microwave imaging techniques have also been intensely studied as a promising diagnostic tool for rapid and cost-effective early-stage breast cancer detection. This paper aims to provide an overview on recent important achievements in breast screening methods (particularly on microwave imaging) and breast biomarkers along with biosensors for rapidly diagnosing breast cancer.

77 FR 16551 - Early Retiree Reinsurance Program

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-21

...] Early Retiree Reinsurance Program AGENCY: Centers for Medicare & Medicaid Services (CMS), HHS. ACTION: Notice. SUMMARY: This notice establishes a timeframe by which plan sponsors participating in the Early... Early Retiree Reinsurance Program (ERRP) which provides reimbursement to eligible sponsors of employment...

Early Rockets

NASA Image and Video Library

2004-04-15

In the 19th Century, experiments in America, Europe, and elsewhere attempted to build postal rockets to deliver mail from one location to another. The idea was more novel than successful. Many stamps used in these early postal rockets have become collector's items.

40 CFR 63.78 - Early reduction demonstration evaluation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Early reduction demonstration... Regulations Governing Compliance Extensions for Early Reductions of Hazardous Air Pollutants § 63.78 Early reduction demonstration evaluation. (a) The permitting authority will evaluate an early reduction...

40 CFR 63.78 - Early reduction demonstration evaluation.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 9 2011-07-01 2011-07-01 false Early reduction demonstration... Regulations Governing Compliance Extensions for Early Reductions of Hazardous Air Pollutants § 63.78 Early reduction demonstration evaluation. (a) The permitting authority will evaluate an early reduction...

Early Childhood Education in Taiwan.

ERIC Educational Resources Information Center

Barclay, Lisa K.

1989-01-01

Describes early childhood education in Taiwan, focusing on living patterns and child care arrangements, the position of the individual within the family and community, and the application of cultural norms to early childhood education. Compares the behavior of Chinese preschool children to that of American preschool children. (RJC)

Early caregiving and physiological stress responses.

PubMed

Luecken, Linda J; Lemery, Kathryn S

2004-05-01

Inadequate early caregiving has been associated with risks of stress-related psychological and physical illness over the life span. Dysregulated physiological stress responses may represent a mechanism linking early caregiving to health outcomes. This paper reviews evidence linking early caregiving to physiological responses that can increase vulnerability to stress-related illness. A number of high-risk family characteristics, including high conflict, divorce, abuse, and parental psychopathology, are considered in the development of stress vulnerability. Three theoretical pathways linking caregiving to physiological stress responses are outlined: genetic, psychosocial, and cognitive-affective. Exciting preliminary evidence suggests that early caregiving can impact long-term physiological stress responses. Directions for future research in this area are suggested.

An Electron-Beam Controlled Semiconductor Switch

DTIC Science & Technology

1989-11-01

of the Seventeenth Power Modulator Symposium, Seattle, WA, pp. 214-218. 1986. 21. Bovino , L., ’ioumans,R., Weiner, H., Burke, T . , "Optica lly... Bovino , R. Youmans, M. Weiner, and T. Burke, ’ ’Optically Co ntrolled Semiconducto r Switch for ~lulti-~legawatt Rep-Rated Pulse r s ," Conf. Record...p. 615. (II 1 W. N. Carr, IEEE Trans. Electron Devices, vol. ED-12, p. 531 , 1965. (121 T. Burke, M. Weiner. L. Bovino , and R. Youmans, in Proc

Laboratory for X-Ray Optics

DTIC Science & Technology

1993-04-29

Kearney, "El uso de las pelfculas delgadas en la optica de rayos - x ," Proc. Symposium on the Physics of Superlattices, May 1991, in press. 6. J.M...Bolling Air Force Base ELEMENT NO. NO. NO ACCESSION NO Washin ton, D.C. 20332- //( ~ ~ C 11. TITLE (Incluft Security Claw ffation) [ TLaboratory for X ...three years under contract AFOSR-90-O 140, "Laboratory for X -Ray O.ptics. Duig thspro we concenrae our effrt in two areas: 1) grwth of epitaxial

Race to the Top--Early Learning Challenge: An Analysis of Impact on IDEIA, Part C Early Intervention Programs

ERIC Educational Resources Information Center

Bohjanen, Sharon L.

2016-01-01

Infants and toddlers who live in poverty are more likely to experience developmental delays or disabilities and less likely to access early intervention (EI) services. The federal initiative Race to the Top--Early Learning Challenge (RTT-ELC) was designed to increase access to high quality early learning programs for children at risk for…

Building Community Systems for Young Children: Early Childhood Education. Building State Early Childhood Comprehensive Systems Series, Number 11

ERIC Educational Resources Information Center

Bassok, Daphna; Stipek, Deborah; Inkelas, Moira; Kuo, Alice

2005-01-01

This report examines the importance and funding sources of early child care and education (ECE), and the ways in which the State Early Childhood Comprehensive Systems (SECCS) Initiative improves early childhood outcomes. Section I presents what is known about the importance of ECE, quality and access. Section II describes the current funding…

Examining the Challenges Early Childhood Teacher Candidates Face in Figuring Their Roles as Early Educators

ERIC Educational Resources Information Center

Brown, Christopher P.; Feger, Beth Smith

2010-01-01

Federal, state, and local policy makers' high-stakes standards-based accountability reforms are transforming the early childhood teacher education process. These reforms affect how early education teacher candidates figure their role as teachers. By employing Holland, Lachicotte, Skinner, and Cain's conception of figured worlds to analyze the…

Early Detection of Sporadic Pancreatic Cancer

PubMed Central

Chari, Suresh T.; Kelly, Kimberly; Hollingsworth, Michael A.; Thayer, Sarah P.; Ahlquist, David A.; Andersen, Dana K.; Batra, Surinder K.; Brentnall, Teresa A.; Canto, Marcia; Cleeter, Deborah F.; Firpo, Matthew A.; Gambhir, Sanjiv Sam; Go, Vay Liang W.; Hines, O. Joe; Kenner, Barbara J.; Klimstra, David S.; Lerch, Markus M.; Levy, Michael J.; Maitra, Anirban; Mulvihill, Sean J.; Petersen, Gloria M.; Rhim, Andrew D.; Simeone, Diane M.; Srivastava, Sudhir; Tanaka, Masao; Vinik, Aaron I.; Wong, David

2015-01-01

Abstract Pancreatic cancer (PC) is estimated to become the second leading cause of cancer death in the United States by 2020. Early detection is the key to improving survival in PC. Addressing this urgent need, the Kenner Family Research Fund conducted the inaugural Early Detection of Sporadic Pancreatic Cancer Summit Conference in 2014 in conjunction with the 45th Anniversary Meeting of the American Pancreatic Association and Japan Pancreas Society. This seminal convening of international representatives from science, practice, and clinical research was designed to facilitate challenging interdisciplinary conversations to generate innovative ideas leading to the creation of a defined collaborative strategic pathway for the future of the field. An in-depth summary of current efforts in the field, analysis of gaps in specific areas of expertise, and challenges that exist in early detection is presented within distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. In addition, an overview of efforts in familial PC is presented in an addendum to this article. It is clear from the summit deliberations that only strategically designed collaboration among investigators, institutions, and funders will lead to significant progress in early detection of sporadic PC. PMID:25931254

Text-Bullying among Early Adolescents

ERIC Educational Resources Information Center

Raskauskas, Juliana

2007-01-01

Increased availability of cell-phones has provided new avenues through which adolescents can bully their peers. Text-bullying is an emerging form of bullying which may threaten the emotional well-being of early adolescents. In this study 565 early adolescents (10-13 years old) completed questionnaires regarding their experiences with bullying…

Wyoming Early Childhood Readiness Standards.

ERIC Educational Resources Information Center

Wyoming State Dept. of Education, Cheyenne.

Because children entering kindergarten come with a variety of preschool and home experiences, and accordingly, with varying levels of school readiness, the Wyoming Early Childhood Readiness Standards have been developed to provide a more consistent definition of school readiness. The goal for the Standards is to provide early childhood educators…

Early Childhood Inclusion in Spain

ERIC Educational Resources Information Center

Giné, Climent; Balcells-Balcells, Anna; Cañadas, Margarita; Paniagua, Gema

2016-01-01

This article describes early childhood inclusion in educational settings in Spain. First, we address the legislative framework of preschool education in Spain and offer a brief analysis of some relevant issues, including the current situation of early childhood education and inclusion at this stage. Second, current policies and practices relating…

Teachers in Early Childhood Policy

ERIC Educational Resources Information Center

Kilderry, Anna

2014-01-01

This paper examines teacher accountability and authority in early childhood policy. It reports on data from a study that investigated the influences affecting early childhood teacher decision-making at the preschool level in Victoria, Australia. Using a question raised by Ball "Where are the teachers in all this [policy]?" provided a…

Missouri: Early Head Start Initiative

ERIC Educational Resources Information Center

Center for Law and Social Policy, Inc. (CLASP), 2012

2012-01-01

Missouri's Early Head Start/Child Care Partnership Project expands access to Early Head Start (EHS) services for children birth to age 3 by developing partnerships between federal Head Start, EHS contractors, and child care providers. Head Start and EHS contractors that participate in the initiative provide services through community child care…

Early dynamics of transversally thermalized matter

NASA Astrophysics Data System (ADS)

Bialas, A.; Chojnacki, M.; Florkowski, W.

2008-10-01

We argue that the idea that the parton system created in relativistic heavy-ion collisions is formed in a state with transverse momenta close to thermodynamic equilibrium and its subsequent dynamics at early times is dominated by pure transverse hydrodynamics of the perfect fluid is compatible with the data collected at RHIC. This scenario of early parton dynamics may help to solve the problem of early equilibration. Quark Matter 2008, Jaipur, India, February 2008.

34 CFR 300.226 - Early intervening services.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 2 2011-07-01 2010-07-01 true Early intervening services. 300.226 Section 300.226... CHILDREN WITH DISABILITIES Local Educational Agency Eligibility § 300.226 Early intervening services. (a... coordinated, early intervening services, which may include interagency financing structures, for students in...

Actionable Intelligence about Early Childhood Risks in Philadelphia

ERIC Educational Resources Information Center

LeBoeuf, Whitney A.; Barghaus, Katherine; Fantuzzo, John; Coe, Kristen; Brumley, Benjamin

2016-01-01

"Early childhood risks" are markers of early childhood experiences that extensive research has shown to be detrimental to later academic and behavioral outcomes. In Philadelphia, evidence indicates that seven early childhood risks tracked by public agencies have negative effects on early school outcomes. These risks include low…

Early Childhood Review: Papers from GAEC, 1996-1997.

ERIC Educational Resources Information Center

Cartwright, Penny, Ed.; Kelly, Clare, Ed.; McLean, Kathy, Ed.; Mellor, Nikki, Ed.; Pidgeon, Sue, Ed.; Stevens, Judith, Ed.; Stables, Kay, Ed.

1996-01-01

This periodical, from Goldsmiths Association for Early Childhood (GAEC), addresses a variety of issues related to early childhood education in Great Britain. Articles included in the Spring 1996 issue are: (1) "Traditional Story Telling in the Early Years" (Fiona Collins); (2) "International Focus--Early Childhood Education…

Early Childhood Intervention and Early Childhood Special Education in Turkey within the Scope of the Developmental System Approach

ERIC Educational Resources Information Center

Diken, Ibrahim H.; Bayhan, Pinar; Turan, Figen; Sipal, R. Firat; Sucuoglu, Bulbin; Ceber-Bakkaloglu, Hatice; Gunel, Mintaze Kerem; Kara, Ozgun Kaya

2012-01-01

The purpose of this article was to provide an overview of early childhood intervention and early childhood special education (ECI/ECSE) services and practices in Turkey by using the Developmental System Approach (M. J. Guralnick, 2001). After pointing out the history of early childhood and ECI/ECSE services and current legislations with regard to…

Bioecological Theory, Early Child Development and the Validation of the Population-Level Early Development Instrument

ERIC Educational Resources Information Center

Guhn, Martin; Goelman, Hillel

2011-01-01

The Early Development Instrument (EDI; Janus and Offord in "Canadian Journal of Behavioural Science" 39:1-22, 2007) project is a Canadian population-level, longitudinal research project, in which teacher ratings of Kindergarten children's early development and wellbeing are linked to health and academic achievement variables at the…

39 CFR 775.7 - Planning and early coordination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 39 Postal Service 1 2010-07-01 2010-07-01 false Planning and early coordination. 775.7 Section 775... POLICY ACT PROCEDURES § 775.7 Planning and early coordination. Early planning and coordination among... to the proposed action. Operational and facility personnel must cooperate in the early concept stages...

39 CFR 775.7 - Planning and early coordination.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 39 Postal Service 1 2011-07-01 2011-07-01 false Planning and early coordination. 775.7 Section 775... POLICY ACT PROCEDURES § 775.7 Planning and early coordination. Early planning and coordination among... to the proposed action. Operational and facility personnel must cooperate in the early concept stages...

Oaklahoma: Early Head Start Initiative

ERIC Educational Resources Information Center

Center for Law and Social Policy, Inc. (CLASP), 2012

2012-01-01

The Oklahoma Early Childhood Program uses public and private funds to enhance and expand high quality early care and education opportunities for children birth through age 3. The George Kaiser Family Foundation initiated the pilot in 2006 by matching state general revenue with private donations. Since that time, other private funders and providers…

Nebraska: Early Head Start Initiative

ERIC Educational Resources Information Center

Center for Law and Social Policy, Inc. (CLASP), 2012

2012-01-01

Since 1999, Nebraska's Early Head Start Infant/Toddler Quality Initiative has supported Early Head Start (EHS) and community child care partnerships to improve the quality and professionalism of infant and toddler care. EHS programs apply to receive funding to establish partnerships with center-based or home-based child care.The initiative has…

Teaching and Testing Early Reading. Focus On

ERIC Educational Resources Information Center

Mraz, Maryann; Kissel, Brian

2007-01-01

This issue of "Focus On" provides an overview of several key early literacy components: phonemic awareness, alphabet knowledge, concepts of print, oral language development, writing, family literacy, and reading aloud. Suggestions for assessing early literacy development are provided, and examples of implementation of effective early literacy…

Early bioenergetic evolution

PubMed Central

Sousa, Filipa L.; Thiergart, Thorsten; Landan, Giddy; Nelson-Sathi, Shijulal; Pereira, Inês A. C.; Allen, John F.; Lane, Nick; Martin, William F.

2013-01-01

Life is the harnessing of chemical energy in such a way that the energy-harnessing device makes a copy of itself. This paper outlines an energetically feasible path from a particular inorganic setting for the origin of life to the first free-living cells. The sources of energy available to early organic synthesis, early evolving systems and early cells stand in the foreground, as do the possible mechanisms of their conversion into harnessable chemical energy for synthetic reactions. With regard to the possible temporal sequence of events, we focus on: (i) alkaline hydrothermal vents as the far-from-equilibrium setting, (ii) the Wood–Ljungdahl (acetyl-CoA) pathway as the route that could have underpinned carbon assimilation for these processes, (iii) biochemical divergence, within the naturally formed inorganic compartments at a hydrothermal mound, of geochemically confined replicating entities with a complexity below that of free-living prokaryotes, and (iv) acetogenesis and methanogenesis as the ancestral forms of carbon and energy metabolism in the first free-living ancestors of the eubacteria and archaebacteria, respectively. In terms of the main evolutionary transitions in early bioenergetic evolution, we focus on: (i) thioester-dependent substrate-level phosphorylations, (ii) harnessing of naturally existing proton gradients at the vent–ocean interface via the ATP synthase, (iii) harnessing of Na+ gradients generated by H+/Na+ antiporters, (iv) flavin-based bifurcation-dependent gradient generation, and finally (v) quinone-based (and Q-cycle-dependent) proton gradient generation. Of those five transitions, the first four are posited to have taken place at the vent. Ultimately, all of these bioenergetic processes depend, even today, upon CO2 reduction with low-potential ferredoxin (Fd), generated either chemosynthetically or photosynthetically, suggesting a reaction of the type ‘reduced iron → reduced carbon’ at the beginning of bioenergetic evolution

Bipolar Disorder and Early Affective Trauma.

PubMed

de Codt, Aloise; Monhonval, Pauline; Bongaerts, Xavier; Belkacemi, Ikram; Tecco, Juan Martin

2016-09-01

Bipolar disorder is a chronic psychiatric disease with a high prevalence and is a major psychosocial and medical burden. The exact etiological pathways of bipolar disorder are not fully understood. Genetic factors are known to play an important role in the etiology of bipolar disorder. However, high rates of discordance among identical twins and a growing body of evidence that environmental factors such as early stress can influence the onset and course of psychiatric diseases underline the importance of additional etiological mechanisms of bipolar disorders. There has been little investigation about early trauma in bipolar disorder. The aim of this study was to review the literature on the association between early traumatic interactions like child neglect, mistreatment, abuse or early parental separation and the occurrence of bipolar disorder in adulthood or impact on the course of the disease. Studies investigating associations between child neglect, mistreatment, abuse or early parental separation and occurrence of bipolar disorder in adulthood or impact on the course of the disease were searched in the Pubmed database. More than 700 articles were sorted independently by two of the authors using predefined criteria. Only research articles, reviews and meta-analyses were selected for this review. 53 articles met the inclusion criteria. To date, four systematic reviews partially addressed our research question. Early trauma is more frequently found in the past of bipolar patients than in the general population. Studies support a harmful effect of childhood trauma on the course of bipolar disease, with more anxious, depressive or psychotic symptoms, an early age of onset and a worse prognosis. Early trauma is more often found in the past of bipolar adult patients than the general population and studies support a harmful effect of childhood trauma on the course of bipolar disease, with more anxious, depressive or psychotic symptoms, an early age of onset and a

New Directions in Intercultural Early Education in Australia

ERIC Educational Resources Information Center

Miller, Melinda; Petriwskyj, Anne

2013-01-01

Early education in Australia encompasses both early education and care (ECEC) and the early years of school. Educational approaches to cultural and linguistic diversity have varied not only by sector but also by jurisdiction based on distinct curriculum frameworks and policies. In Australian early education, provision for cultural and linguistic…

Family Income Dynamics, Early Childhood Education and Care, and Early Child Behavior Problems in Norway

ERIC Educational Resources Information Center

Zachrisson, Henrik D.; Dearing, Eric

2015-01-01

The sociopolitical context of Norway includes low poverty rates and universal access to subsidized and regulated Early Childhood Education and Care (ECEC). In this context, the association between family income dynamics and changes in early child behavior problems was investigated, as well as whether high-quality ECEC buffers children from the…

Validation of the Early Functional Abilities scale: An assessment of four dimensions in early recovery after traumatic brain injury.

PubMed

Poulsen, Ingrid; Kreiner, Svend; Engberg, Aase W

2018-02-13

The Early Functional Abilities scale assesses the restoration of brain function after brain injury, based on 4 dimensions. The primary objective of this study was to evaluate the validity, objectivity, reliability and measurement precision of the Early Functional Abilities scale by Rasch model item analysis. A secondary objective was to examine the relationship between the Early Functional Abilities scale and the Functional Independence Measurement™, in order to establish the criterion validity of the Early Functional Abilities scale and to compare the sensitivity of measurements using the 2 instruments. The Rasch analysis was based on the assessment of 408 adult patients at admission to sub-acute rehabilitation in Copenhagen, Denmark after traumatic brain injury. The Early Functional Abilities scale provides valid and objective measurement of vegetative (autonomic), facio-oral, sensorimotor and communicative/cognitive functions. Removal of one item from the sensorimotor scale confirmed unidimensionality for each of the 4 subscales, but not for the entire scale. The Early Functional Abilities subscales are sensitive to differences between patients in ranges in which the Functional Independence Measurement™ has a floor effect. The Early Functional Abilities scale assesses the early recovery of important aspects of brain function after traumatic brain injury, but is not unidimensional. We recommend removal of the "standing" item and calculation of summary subscales for the separate dimensions.

Fossil evidence for a herbaceous diversification of early eudicot angiosperms during the Early Cretaceous

PubMed Central

Jud, Nathan A.

2015-01-01

Eudicot flowering plants comprise roughly 70% of land plant species diversity today, but their early evolution is not well understood. Fossil evidence has been largely restricted to their distinctive tricolpate pollen grains and this has limited our understanding of the ecological strategies that characterized their primary radiation. I describe megafossils of an Early Cretaceous eudicot from the Potomac Group in Maryland and Virginia, USA that are complete enough to allow reconstruction of important life-history traits. I draw on quantitative and qualitative analysis of functional traits, phylogenetic analysis and sedimentological evidence to reconstruct the biology of this extinct species. These plants were small and locally rare but widespread, fast-growing herbs. They had complex leaves and they were colonizers of bright, wet, disturbance-prone habitats. Other early eudicot megafossils appear to be herbaceous rather than woody, suggesting that this habit was characteristic of their primary radiation. A mostly herbaceous initial diversification of eudicots could simultaneously explain the heretofore sparse megafossil record as well as their rapid diversification during the Early Cretaceous because the angiosperm capacity for fast reproduction and fast evolution is best expressed in herbs. PMID:26336172

Fossil evidence for a herbaceous diversification of early eudicot angiosperms during the Early Cretaceous.

PubMed

Jud, Nathan A

2015-09-07

Eudicot flowering plants comprise roughly 70% of land plant species diversity today, but their early evolution is not well understood. Fossil evidence has been largely restricted to their distinctive tricolpate pollen grains and this has limited our understanding of the ecological strategies that characterized their primary radiation. I describe megafossils of an Early Cretaceous eudicot from the Potomac Group in Maryland and Virginia, USA that are complete enough to allow reconstruction of important life-history traits. I draw on quantitative and qualitative analysis of functional traits, phylogenetic analysis and sedimentological evidence to reconstruct the biology of this extinct species. These plants were small and locally rare but widespread, fast-growing herbs. They had complex leaves and they were colonizers of bright, wet, disturbance-prone habitats. Other early eudicot megafossils appear to be herbaceous rather than woody, suggesting that this habit was characteristic of their primary radiation. A mostly herbaceous initial diversification of eudicots could simultaneously explain the heretofore sparse megafossil record as well as their rapid diversification during the Early Cretaceous because the angiosperm capacity for fast reproduction and fast evolution is best expressed in herbs. © 2015 The Author(s).

Early Childhood Inclusion in the United Kingdom

ERIC Educational Resources Information Center

Blackburn, Carolyn

2016-01-01

A policy-to-practice paper is presented of early childhood inclusion in England. The article aims to report the benefits of early intervention services and early childhood inclusion for children with special educational needs and disabilities (SEND), document the chronology of policy development, and discuss research evidence about…

34 CFR 300.711 - Early intervening services.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 2 2011-07-01 2010-07-01 true Early intervening services. 300.711 Section 300.711... Secretary of the Interior § 300.711 Early intervening services. (a) The Secretary of the Interior may allow... funds), to develop and implement coordinated, early intervening services, which may include interagency...

34 CFR 300.226 - Early intervening services.

Code of Federal Regulations, 2010 CFR

2010-07-01

... CHILDREN WITH DISABILITIES Local Educational Agency Eligibility § 300.226 Early intervening services. (a... annually report to the SEA on— (1) The number of children served under this section who received early intervening services; and (2) The number of children served under this section who received early intervening...

34 CFR 303.11 - Early intervention program.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 2 2010-07-01 2010-07-01 false Early intervention program. 303.11 Section 303.11... AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION EARLY INTERVENTION PROGRAM FOR INFANTS AND... intervention program. As used in this part, early intervention program means the total effort in a State that...

34 CFR 303.11 - Early intervention program.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 2 2011-07-01 2010-07-01 true Early intervention program. 303.11 Section 303.11... AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION EARLY INTERVENTION PROGRAM FOR INFANTS AND... intervention program. As used in this part, early intervention program means the total effort in a State that...

Depressive Symptomatology among Very Early Maturing Girls.

ERIC Educational Resources Information Center

Rierdan, Jill; Koff, Elissa

1991-01-01

The relationship between very early menarche and depression was studied in a sample of 488 girls (336 sixth graders and 152 seventh graders), less than 10 percent of whom were very early maturers. Very early menarche was associated with higher levels of depression than was more normative development. (SLD)

Arizona Early Childhood Education Standards.

ERIC Educational Resources Information Center

Arizona State Dept. of Education, Phoenix.

In an effort to provide a sound basis for educational accountability for preschool programs, the Arizona Early Childhood Education (ECE) Standards were developed as a framework for literacy-based programs for 3- and 4-year-olds and to provide parents with a basic understanding of indicators of early learning. These standards, to be adopted by…

An early Cambrian greenhouse climate.

PubMed

Hearing, Thomas W; Harvey, Thomas H P; Williams, Mark; Leng, Melanie J; Lamb, Angela L; Wilby, Philip R; Gabbott, Sarah E; Pohl, Alexandre; Donnadieu, Yannick

2018-05-01

The oceans of the early Cambrian (~541 to 509 million years ago) were the setting for a marked diversification of animal life. However, sea temperatures-a key component of the early Cambrian marine environment-remain unconstrained, in part because of a substantial time gap in the stable oxygen isotope (δ 18 O) record before the evolution of euconodonts. We show that previously overlooked sources of fossil biogenic phosphate have the potential to fill this gap. Pristine phosphatic microfossils from the Comley Limestones, UK, yield a robust δ 18 O signature, suggesting sea surface temperatures of 20° to 25°C at high southern paleolatitudes (~65°S to 70°S) between ~514 and 509 million years ago. These sea temperatures are consistent with the distribution of coeval evaporite and calcrete deposits, peak continental weathering rates, and also our climate model simulations for this interval. Our results support an early Cambrian greenhouse climate comparable to those of the late Mesozoic and early Cenozoic, offering a framework for exploring the interplay between biotic and environmental controls on Cambrian animal diversification.

Anti-early pregnancy by PDT

NASA Astrophysics Data System (ADS)

Ding, Ai-Hua; Chen, Hui-Ling

1993-03-01

The effect of laser on anti-early pregnancy in rabbits showed that laser in combination with HPD could induce necrosis of blastocysts and complete absorption. The anti-fertility efficiency of the combined treatment was more effective than that of the He-Ne laser or the HPD treatment alone. The fluorescence spectrum of HPD determined by PNQ3 showed that its affinity to embryonic tissue was about 4 times greater than that to uterine tissue. This may underlie the mechanisms of anti-early pregnancy of the laser. The operation of artificial abortion is a routine method to terminate early pregnancy. Though it is simple and easy, its syndrome and complications can not be absolutely avoided. Many antifertility drugs have been reported, however, they often bring in general reaction. Our present work is to explore a new way of anti-early pregnancy in rabbits by means of the light inhibitory and light sensitive effects of laser. It is a quite safe and painless treatment without expanding and scraping of the uterus.

Effectiveness of early adalimumab therapy in psoriatic arthritis patients from Reuma.pt - EARLY PsA.

PubMed

Santos, Helena; Eusébio, Mónica; Borges, Joana; Gonçalves, Diana; Ávila-Ribeiro, Pedro; Faria, Daniela Santos; Lopes, Carina; Rovisco, João; Águeda, Ana; Nero, Patrícia; Valente, Paula; Cravo, Ana Rita; Santos, Maria José

2017-01-01

Objective To compare outcomes in psoriatic arthritis (PsA) patients initiating adalimumab (ADA), with short- and long-term disease duration and to evaluate the potential effect of concomitant conventional synthetic disease-modifying antirheumatic drugs (csDMARD) or glucocorticoids. Methods Analyses included adult PsA patients registered in the Rheumatic Diseases Portuguese Register (Reuma.pt) between June 2008-June 2016 who received ADA for ≥3 months. Psoriatic Arthritis Response Criteria (PsARC) response, tender and swollen joint count, inflammatory parameters, patient (PtGA) and physician global assessment (PhGA), Disease Activity Score-28 joints (DAS28), and Health Assessment Questionnaire Disability Index (HAQ-DI) were compared between patients with <5 years of disease (early PsA) and those with ≥5 years of disease duration (late PsA). Time to achieving PsARC response was estimated using the Kaplan-Meier method. Results Of 135 PsA patients treated with ADA, 126 had information on disease duration (earlyPsA, n=41). PsARC response was achieved by 72.9% of the patients (88.0% early PsA vs 62.2% late PsA; P=0.022) after 3 months and by 85.4% after 24 months (100% early PsA vs 75.9% late PsA; P=0.044). Early PsA patients achieved significantly less painful joints (2.7 vs 6.7, p=0.006), lower mean C-reactive protein (0.5 mg/dL vs 1.3 mg/dL; P=0.011), and PhGA (18.3 vs 28.1; P=0.020) at 3 months. In the long term, early PsA patients also had fewer swollen joints (0.3 vs 1.7; P=0.030) and lower PhGA (6.3 vs 21.9; P<0.001), C-reactive protein (0.4 mg/dL vs 1.0 mg/dL; P=0.026), and DAS28 (2.2 vs 3.2; P=0.030). HAQ-DI decreased in both groups reaching a mean value at 24 months of 0.4 and 0.8 (P=ns) in early and late PsA, respectively. Early PsA patients obtained PsARC response more rapidly than late PsA (3.8 and 7.4 months, respectively; P=0.008). Concomitant csDMARDs showed clinical benefit (2-year PsARC response, 88.3% vs 60.0%; P=0.044). Concomitant glucocorticoids

Early traumatic events in psychopaths.

PubMed

Borja, Karina; Ostrosky, Feggy

2013-07-01

The relationship between diverse early traumatic events and psychopathy was studied in 194 male inmates. Criminal history transcripts were revised, and clinical interviews were conducted to determine the level of psychopathy using the Psychopathy Checklist-Revised (PCL-R) Form, and the Early Trauma Inventory was applied to assess the incidence of abuse before 18 years of age. Psychopathic inmates presented a higher victimization level and were more exposed to certain types of intended abuse than sociopathic inmates, while the sum of events and emotional abuse were associated with the PCL-R score. Our studies support the influence of early adverse events in the development of psychopathic offenders. © 2013 American Academy of Forensic Sciences.

Music as therapy in early history.

PubMed

Thaut, Michael H

2015-01-01

The notion of music as therapy is based on ancient cross-cultural beliefs that music can have a "healing" effect on mind and body. Explanations for the therapeutic mechanisms in music have almost always included cultural and social science-based causalities about the uses and functions of music in society. However, it is also important to note that the view of music as "therapy" was also always strongly influenced by the view and understanding of the concepts and causes of disease. Magical/mystical concepts of illness and "rational" medicine probably lived side by side for thousands of years. Not until the late-nineteenth and early-twentieth centuries were the scientific foundations of medicine established, which allowed the foundations of music in therapy to progress from no science to soft science and most recently to actual brain science. Evidence for "early music therapy" will be discussed in four broad historical-cultural divisions: preliterate cultures; early civilizations in Mesopotamia, Egypt, Israel; Greek Antiquity; Middle Ages, Renaissance, and Baroque. In reviewing "early music therapy" practice, from mostly unknown periods of early history (using preliterate cultures as a window) to increasingly better documented times, including preserved notation samples of actual "healing" music, five theories and applications of early music therapy can be differentiated. © 2015 Elsevier B.V. All rights reserved.

Are female orphans at risk for early marriage, early sexual debut, and teen pregnancy? Evidence from sub-Saharan Africa.

PubMed

Palermo, Tia; Peterman, Amber

2009-06-01

Female orphans are widely cited as being at risk for early marriage, early childbearing, and risky sexual behavior; however, to date no studies have examined these linkages using population-level data across multiple countries. This study draws from recent Demographic and Health Surveys from ten sub-Saharan African countries to examine the relationship between orphanhood status and measures of early marriage, early sexual debut, and teen pregnancy among adolescent girls aged 15 to 17. Results indicate that, overall, little association is found between orphanhood and early marriage or teen pregnancy, whereas evidence from seven countries supports associations between orphanhood and early sexual debut. Findings are sensitive to the use of multivariate models, type of orphan, and country setting. Orphanhood status alone may not be a sufficient targeting mechanism for addressing these outcomes in many countries; a broader, multidimensional targeting scheme including orphan type, schooling, and poverty measures would be more robust in identifying and aiding young women at risk.

Teaching Early College High School at LaGuardia Community College. Early College High School Initiative

ERIC Educational Resources Information Center

Glick, Marcia

2006-01-01

The Bill & Melinda Gates Foundation, along with Carnegie Corporation of New York, the Ford Foundation, and the W.K. Kellogg Foundation, is funding the Early College High School Initiative. The 13 partner organizations are creating or redesigning more than 250 pioneering small high schools. Jobs for the Future coordinates the Early College High…

Perceived Stress and Canadian Early Childcare Educators

ERIC Educational Resources Information Center

Wagner, Shannon L.; Forer, Barry; Cepeda, Ivan L.; Goelman, Hillel; Maggi, Stefania; D'Angiulli, Amedeo; Wessel, Julie; Hertzman, Clyde; Grunau, Ruth E.

2013-01-01

Background: Occupational stress for early childcare educators is an area of apparent understudy in the literature. The present study attempted to address this gap and provide some updated data regarding the experiences of this occupational group. Methods: Early childhood workers across a variety of early childhood education settings (N = 69)…

43 CFR 10010.9 - Apply NEPA early.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Apply NEPA early. 10010.9 Section 10010.9... Initiating the NEPA Process § 10010.9 Apply NEPA early. (a) The Commission will initiate early consultation and coordination with other Federal agencies having jurisdiction by law or special expertise with...

43 CFR 10010.9 - Apply NEPA early.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Apply NEPA early. 10010.9 Section 10010.9... Initiating the NEPA Process § 10010.9 Apply NEPA early. (a) The Commission will initiate early consultation and coordination with other Federal agencies having jurisdiction by law or special expertise with...

43 CFR 10010.9 - Apply NEPA early.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Apply NEPA early. 10010.9 Section 10010.9... Initiating the NEPA Process § 10010.9 Apply NEPA early. (a) The Commission will initiate early consultation and coordination with other Federal agencies having jurisdiction by law or special expertise with...

Early Learning and Educational Technology Policy Brief

ERIC Educational Resources Information Center

Lee, Joan

2016-01-01

Recognizing the growth of technology use in early learning settings, the U.S. Department of Education and U.S. Department of Health and Human Services collaborated in the development of the "Early Learning and Educational Technology Policy Brief" to promote developmentally appropriate use of technology in homes and early learning…

Early Childhood Education: A Workbook for Administrators.

ERIC Educational Resources Information Center

Hewes, Dorothy; Hartman, Barbara

Business management theory and principles as applied to the administration of early childhood programs are presented in this workbook. Following a brief survey of the historical background of early childhood education and current early childhood programs, information and guidance to help plan, operate, and evaluate program facilities are provided.…

Dispersing Waves: Innovation in Early Childhood Education

ERIC Educational Resources Information Center

Meade, Anne, Ed.

2010-01-01

Early childhood education Centres of Innovation (COI) were established in 2002 as part of the 10-year plan for early childhood education, "Pathways to the Future/Nga Huarahi Arataki." In COI projects, innovative early childhood teaching teams reflect on and investigate their practices through action research, and share their findings…

Adverse Housing Conditions and Early-Onset Delinquency.

PubMed

Jackson, Dylan B; Newsome, Jamie; Lynch, Kellie R

2017-09-01

Housing constitutes an important health resource for children. Research has revealed that, when housing conditions are unfavorable, they can interfere with child health, academic performance, and cognition. Little to no research, however, has considered whether adverse housing conditions and early-onset delinquency are significantly associated with one another. This study explores the associations between structural and non-structural housing conditions and delinquent involvement during childhood. Data from the Fragile Families and Child Wellbeing Study (FFCWS) were employed in this study. Each adverse housing condition was significantly associated with early-onset delinquency. Even so, disarray and deterioration were only significantly linked to early delinquent involvement in the presence of health/safety hazards. The predicted probability of early-onset delinquency among children exposed to housing risks in the presence of health/safety hazards was nearly three times as large as the predicted probability of early-onset delinquency among children exposed only to disarray and/or deterioration, and nearly four times as large as the predicted probability of early-onset delinquency among children exposed to none of the adverse housing conditions. The findings suggest that minimizing housing-related health/safety hazards among at-risk subsets of the population may help to alleviate other important public health concerns-particularly early-onset delinquency. Addressing household health/safety hazards may represent a fruitful avenue for public health programs aimed at the prevention of early-onset delinquency. © Society for Community Research and Action 2017.

Effects of a Computer-Based Early Reading Program on the Early Reading and Oral Language Skills of At-Risk Preschool Children

ERIC Educational Resources Information Center

Huffstetter, Mary; King, James R.; Onwuegbuzie, Anthony J.; Schneider, Jenifer J.; Powell-Smith, Kelly A.

2010-01-01

This study examined the effects of a computer-based early reading program (Headsprout Early Reading) on the oral language and early reading skills of at-risk preschool children. In a pretest-posttest control group design, 62 children were randomly assigned to receive supplemental instruction with Headsprout Early Reading (experimental group) or…

Promoting Health in Early Childhood

ERIC Educational Resources Information Center

Rossin-Slater, Maya

2015-01-01

Children who are healthy early in life--from conception to age five--not only grow up to be healthier adults, they are also better educated, earn more, and contribute more to the economy. The United States lags behind other advanced countries in early childhood health, threatening both the health of future generations and the nation's long-term…

Invest in Early Childhood Education

ERIC Educational Resources Information Center

Kagan, Sharon Lynn; Reid, Jeanne L.

2009-01-01

The history of American early education is one of changing roles and goals. As federal engagement in early childhood has shifted in response to social, political, and economic needs, few policy efforts have focused on long-term planning or coordination. The authors identify the appropriate roles of federal, state, and local governments and make 13…

The late early Miocene Sabine River

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manning, E.

Work on a new late early Miocene vertebrate fossil site, in a paleochannel deposit of the upper Carnahan Bayou Member of the lower Fleming Formation, has revealed unexpected data on the course and nature of the Sabine River of that time. Screen washing for smaller vertebrate remains at the site, just west of the Sabine River in Newton County, central eastern Texas, has resulted in the recovery of early Permian, Early Cretaceous, Late Cretaceous (Maestrichtian), Paleocene/Eocene, late Eocene, and Oligocene/Miocene fossils, in addition to the main early Miocene fauna. The reworked fossils, as well as distinctive mineral grains, show thatmore » the late early Miocene Sabine River was connected to the Texas/Oklahoma/Arkansas boundary section of the Red River, as well as to rivers draining the southern Ouachita Mountains. These rivers must have joined the Texas/Louisiana boundary section of the Sabine River somewhere in northwest Louisiana at that time. This suggests that the Louisiana section of the present Red River pirated the Texas/Oklahoma/Arkansas boundary section of the river some time after the early Miocene. The preservation of recognizable fossils transported hundreds of miles in a large river itself requires explanation. It is speculated here that the late early Miocene Sabine River incorporated a large amount of the then recently deposited volcanic ash from the Trans-Pecos Volcanic Field. Montmorillonite clay from the altered volcanic ash would have made the river very turbid, which could have allowed coarse sand-sized particles to be carried in the suspended load of the river, rather than in its bed load (where they would have been destroyed by the rolling chert gravel). Additional evidence for such long-distance fossil transport in the late early Miocene rivers of the western Gulf Coastal Plain comes from the abundant Cretaceous fossils of the upper Oakville Formation of southeast Texas and the Siphonina davisi zone of the southeast Texas subsurface.« less

The development of functional network organization in early childhood and early adolescence: A resting-state fNIRS study.

PubMed

Cai, Lin; Dong, Qi; Niu, Haijing

2018-04-01

Early childhood (7-8 years old) and early adolescence (11-12 years old) constitute two landmark developmental stages that comprise considerable changes in neural cognition. However, very limited information from functional neuroimaging studies exists on the functional topological configuration of the human brain during specific developmental periods. In the present study, we utilized continuous resting-state functional near-infrared spectroscopy (rs-fNIRS) imaging data to examine topological changes in network organization during development from early childhood and early adolescence to adulthood. Our results showed that the properties of small-worldness and modularity were not significantly different across development, demonstrating the developmental maturity of important functional brain organization in early childhood. Intriguingly, young children had a significantly lower global efficiency than early adolescents and adults, which revealed that the integration of the distributed networks strengthens across the developmental stages underlying cognitive development. Moreover, local efficiency of young children and adolescents was significantly lower than that of adults, while there was no difference between these two younger groups. This finding demonstrated that functional segregation remained relatively steady from early childhood to early adolescence, and the brain in these developmental periods possesses no optimal network configuration. Furthermore, we found heterogeneous developmental patterns in the regional nodal properties in various brain regions, such as linear increased nodal properties in the frontal cortex, indicating increasing cognitive capacity over development. Collectively, our results demonstrated that significant topological changes in functional network organization occurred during these two critical developmental stages, and provided a novel insight into elucidating subtle changes in brain functional networks across development. Copyright �

Early markers of adult obesity: a review

PubMed Central

Brisbois, T D; Farmer, A P; McCargar, L J

2012-01-01

Summary The purpose of this review was to evaluate factors in early childhood (≤5 years of age) that are the most significant predictors of the development of obesity in adulthood. Factors of interest included exposures/insults in the prenatal period, infancy and early childhood, as well as other socio-demographic variables such as socioeconomic status (SES) or birth place that could impact all three time periods. An extensive electronic and systematic search initially resulted in 8,880 citations, after duplicates were removed. Specific inclusion and exclusion criteria were set, and following two screening processes, 135 studies were retained for detailed abstraction and analysis. A total of 42 variables were associated with obesity in adulthood; however, of these, only seven variables may be considered as potential early markers of obesity based on the reported associations. Possible early markers of obesity included maternal smoking and maternal weight gain during pregnancy. Probable early markers of obesity included maternal body mass index, childhood growth patterns (early rapid growth and early adiposity rebound), childhood obesity and father's employment (a proxy measure for SES in many studies). Health promotion programmes/agencies should consider these factors as reasonable targets to reduce the risk of adult obesity. PMID:22171945

Kentucky's Statewide Early Childhood Professional Development System

ERIC Educational Resources Information Center

Rous, Beth; Grove, Jaime; Townley, Kim

2007-01-01

Public school systems have recently become major players in providing services for children in their early years. In addition, a number of other services are available to young children including child care, Head Start, and Early Head Start programs. The link between program quality and professional development of early care and education…

Early Childhood Care and Education in Kenya

ERIC Educational Resources Information Center

Mbugua, Tata J.

2004-01-01

Recent years have seen a global endeavor to prioritize early childhood care and education as a foundation for later learning and development, as evidenced by the Global Guidelines for Early Childhood Education and Care in the 21st Century (Association for Childhood Education International/World Organization for Early Childhood, 1999). Such efforts…

Management of Early Carcinoma of the Ovary

PubMed Central

Chapman, George W.

1988-01-01

Ovarian cancer represents a formidable challenge to physicians. Early symptoms are nonspecific, and are usually attributed to disorders of the upper gastrointestinal tract. Especially important is suspicion of this neoplasm in its early stage. This article discusses the epidemiology, clinical features, evaluation, and treatment of early carcinomas of the ovary. PMID:3071612

Early intervention for post-traumatic stress disorder.

PubMed

Bryant, Richard A

2007-02-01

The potentially debilitating effect of posttraumatic stress disorder (PTSD) has created much interest in early intervention strategies that can reduce PTSD. This review critiques the evidence for psychological debriefing approaches and alternate early intervention strategies. The review critiques the randomized controlled trials of psychological debriefing, and early provision of cognitive behavior therapy. The latter approach involves therapy attention on acutely traumatized individuals who are high risk for PTSD development, and particularly in people with acute stress disorder (ASD). Psychological debriefing does not prevent PTSD. Cognitive behaviour therapy strategies have proven efficacy in reducing subsequent PTSD in ASD populations. Despite the promising evidence for early provision of CBT, many people do not benefit from CBT. This review concludes with consideration of major challenges facing early intervention approaches in the context of terrorist attacks and mass disasters.

An outcomes evaluation of an emergency department early pregnancy assessment service and early pregnancy assessment protocol

PubMed Central

Wendt, Kim; Crilly, Julia; May, Chris; Bates, Kym; Saxena, Rakhee

2014-01-01

Background Complications in early pregnancy, such as threatened or actual miscarriage is a common occurrence resulting in many women presenting to the emergency department (ED). Early pregnancy service delivery models described in the literature vary in terms of approach, setting and outcomes. Our objective was to determine outcomes of women who presented to an Australian regional ED with diagnoses consistent with early pregnancy complications following the implementation of an early pregnancy assessment service (EPAS) and early pregnancy assessment protocol (EPAP) in July 2011. Methods A descriptive, comparative (6 months before and after) study was undertaken. Data were extracted from the hospital ED information system and medical healthcare records. Outcome measures included: time to see a clinician, ED length of stay, admission rate, re-presentation rate, hospital admission and types of pathology tests ordered. Results Over the 12 -month period, 584 ED presentations were made to the ED with complications of early pregnancy (268 PRE and 316 POST EPAS–EPAP). Outcomes that improved statistically and clinically following implementation included: time to see a clinician (decreased by 6 min from 35 to 29 min), admission rate (decreased 6% from 14.5% to 8.5%), increase in β-human chorionic gonadotrophin ordering by 10% (up to 80% POST), increase in ultrasound (USS) performed by 10% (up to 73% POST) and increase in pain score documentation by 23% (up to 36% POST). Conclusions The results indicate that patient and service delivery improvements can be achieved following the implementation of targeted service delivery models such as EPAS and EPAP in the ED. PMID:24136123

Association Between Early Menarche and School Bullying.

PubMed

Su, Qiru; Chen, Zhengyang; Li, Ruili; Elgar, Frank J; Liu, Zhihao; Lian, Qiguo

2018-04-25

Early pubertal onset may relate to more involvement in bullying in adolescent girls, both as a target and as a perpetrator. However, the few studies of the association between early menarche and school bullying have shown mixed findings. The present study examined whether early menarche is associated with bullying victimization and perpetration. We obtained survey data on adolescent girls from the 2001-2002, 2005-2006, and 2009-2010 cycles of the Health Behaviour in School-aged Children study in 35 European and North American countries. We identified school bullying in the past 2 months using the Revised Olweus Bully/Victim Questionnaire. We defined early menarche as a reported onset of menarche before 11 years and tested the associations between early menarche and bullying victimization and perpetration using three-level logistic regression models. The sample included 227,443 adolescent girls with a mean age of 13.64 (standard deviation [SD] 1.63) years, of which 10,172 (4.47%) were early matured; 62,528 (28.33%) and 56,582 (25.67%) were occasional victims and perpetrators, respectively; and 21,985 (9.96%) and 14,115 (6.40%) were frequent victims and perpetrators, respectively. Early menarche related to occasional victimization (adjusted odds ratio [OR] [95% confidence interval [CI] = 1.21 [1.12-1.31]) and perpetration (aOR [95% CI] = 1.19 [1.11-1.27]) and to frequent victimization (aOR [95% CI] = 1.35 [1.22-1.50]) and perpetration (aOR [95% CI] = 1.46 [1.31-1.63]). Early menarche in European and North American adolescent girls positively relates to bullying victimization and perpetration. Early-maturing girls should not be neglected in antibullying programs. Copyright © 2018 The Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

43 CFR 46.200 - Applying NEPA early.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 false Applying NEPA early. 46.200 Section 46.200... ENVIRONMENTAL POLICY ACT OF 1969 Initiating the NEPA Process § 46.200 Applying NEPA early. (a) For any... environmental impacts, bureaus must coordinate, as early as feasible, with: (1) Any other bureaus or Federal...

43 CFR 46.200 - Applying NEPA early.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 false Applying NEPA early. 46.200 Section 46.200... ENVIRONMENTAL POLICY ACT OF 1969 Initiating the NEPA Process § 46.200 Applying NEPA early. (a) For any... environmental impacts, bureaus must coordinate, as early as feasible, with: (1) Any other bureaus or Federal...

43 CFR 46.200 - Applying NEPA early.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true Applying NEPA early. 46.200 Section 46.200... ENVIRONMENTAL POLICY ACT OF 1969 Initiating the NEPA Process § 46.200 Applying NEPA early. (a) For any... environmental impacts, bureaus must coordinate, as early as feasible, with: (1) Any other bureaus or Federal...

43 CFR 46.200 - Applying NEPA early.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false Applying NEPA early. 46.200 Section 46.200... ENVIRONMENTAL POLICY ACT OF 1969 Initiating the NEPA Process § 46.200 Applying NEPA early. (a) For any... environmental impacts, bureaus must coordinate, as early as feasible, with: (1) Any other bureaus or Federal...

Early Math.

ERIC Educational Resources Information Center

Van Nuys, Ute Elisabeth

1986-01-01

Presents reviews of the following mathematics software designed to teach young children counting, number recognition, visual discrimination, matching, addition, and subtraction skills; Stickybear Numbers, Learning with Leeper, Getting Ready to Read and Add, Counting Parade, Early Games for Young Children, Charlie Brown's 1,2,3's, Let's Go Fishing,…

Early Childhood.

ERIC Educational Resources Information Center

Peters, Donald L.; Willis, Sherry L.

This book summarizes theory and discusses major issues pertaining to child development in the early childhood years. Chapter I provides an introduction to the conceptual framework and major theories of child development. Chapter II deals with motor, sensory, and perceptual development. Chapter III focuses on the cognitive-developmental theory of…

Determinacion de Caracteristicas Opticas del Telescopio OAN150

NASA Astrophysics Data System (ADS)

Galan, M. J.; Cobos, F. J.

1987-05-01

En el Observatorio de Calar Alto, en Almería, España, está ubicado un telescopio de 15O-cms de diámetro -construído por REOSC- perteneciente al Observatorio Astronómico Nacional, con sede en Madrid, España. La infraestructura técnica del OAN ha sido tradicionalmente débil y actualmente se está haciendo un esfuerzo por fortalecerla. Existe una información muy limitada del telescopio en general; de su óptica en particular se conocían los valores de los parámetros principales pero sin saber si éstos corresponden a valores teóricos ó de construcción. Por ello se consideró necesario iniciar una investigación para conocer en detalle los valores reales de las componentes ópticas del telescopio, obteniéndose algunos resultados de interés. El primario del telescopio OANl5O es aproximadamente F/3 y el siste ma en su conjunto es F/8.2, con su sistema corrector de campo. En términos generales, la imagen es satisfactoria en todo el campo y, sin sistema corrector, la imagen axial también es buena. En un futuro muy cercano se piensa diseñar instrumentación adicional para este telescopio. Conocer con mayor precisión sus características puede ser de gran utilidad para tal fin, pues se efectúan los cálculos considerando conjuntamente al telescopio y al instrumento.

Examining Text Complexity in the Early Grades

ERIC Educational Resources Information Center

Fitzgerald, Jill; Elmore, Jeff; Hiebert, Elfrieda H.; Koons, Heather H.; Bowen, Kimberly; Sanford-Moore, Eleanor E.; Stenner, A. Jackson

2016-01-01

The Common Core raises the stature of texts to new heights, creating a hubbub. The fuss is especially messy at the early grades, where children are expected to read more complex texts than in the past. But early-grades teachers have been given little actionable guidance about text complexity. The authors recently examined early-grades texts to…

Global Trends in Early Childhood Education: 2009

ERIC Educational Resources Information Center

Neugebauer, Roger; Goodeve, Emily

2009-01-01

As early childhood professionals from 78 countries prepare to travel to Belfast for the 2009 World Forum on Early Care and Education, these authors surveyed a sampling of those who will be attending on the current trends in early childhood education in their country. Delegates from over 40 countries responded, and in reviewing the reports from…

Infliximab in active early rheumatoid arthritis

PubMed Central

Breedveld, F; Emery, P; Keystone, E; Patel, K; Furst, D; Kalden, J; St, C; Weisman, M; Smolen, J; Lipsky, P; Maini, R

2004-01-01

Objective: To examine the impact of the combination of infliximab plus methotrexate (MTX) on the progression of structural damage in patients with early rheumatoid arthritis (RA). Methods: Subanalyses were carried out on data for patients with early RA in the Anti-TNF Therapy in RA with Concomitant Therapy (ATTRACT) study, in which 428 patients with active RA despite MTX therapy received placebo with MTX (MTX-only) or infliximab 3 mg/kg or 10 mg/kg every (q) 4 or 8 weeks with MTX (infliximab plus MTX) for 102 weeks. Early RA was defined as disease duration of 3 years or less; 82 of the 428 patients (19%) met this definition. Structural damage was assessed with the modified van der Heijde-Sharp score. The changes from baseline to week 102 in total modified van der Heijde-Sharp score were compared between the infliximab plus MTX groups and the MTX-only group. Results: The erosion and joint space narrowing scores from baseline to week 102 in the cohort of patients with early RA decreased significantly in each infliximab dose regimen compared with the MTX-only regimen. Consistent benefit was seen in the joints of both hands and feet. Conclusions: Infliximab combined with MTX inhibited the progression of structural damage in patients with early RA during the 2 year period of treatment. Early intervention with infliximab in patients with active RA despite MTX therapy may provide long term benefits by preventing radiographic progression and preserving joint integrity. PMID:14722203

Early Mother-Child Separation, Parenting, and Child Well-Being in Early Head Start Families

PubMed Central

Howard, Kimberly; Martin, Anne; Berlin, Lisa J.; Brooks-Gunn, Jeanne

2011-01-01

Drawing on theories of attachment and family instability, this study examined associations between early mother-child separation and subsequent maternal parenting behaviors and children’s outcomes in a sample of 2080 families who participated in the Early Head Start Research and Evaluation Project, the vast majority of whom were poor. Multiple regression models revealed that, controlling for baseline family and maternal characteristics and indicators of family instability, the occurrence of a mother-child separation of a week or longer within the first two years of life was related to higher levels of child negativity (at age 3) and aggression (at ages 3 and 5). The effect of separation on child aggression at age 5 was mediated by aggression at age 3, suggesting that the effects of separation on children’s aggressive behavior are early and persistent. PMID:21240692

Low-Cost Space Structure (LCSS) Experiment. Volume I of II.

DTIC Science & Technology

1996-06-01

Cell Multiline laser - 2 100 Hold spots at BSM2 (tilts optica Tilt spots fixed offset path of (1/segment) w.r.t. 1 segment only) each other with off...Piston/Fine Piston Sensor Multiline Laser 3 Piston 1 BSM2 (pistons LEC segment w.r.t. optical path of other to 1 segment only) increase sharpness 7 LGSS...independent steering and pistoning of one beamline with respect to the other with the fixed mirror M2 and tilt/piston mirror BSM2 pair. The telescope

Early retirement and income loss in patients with early and advanced Parkinson's disease.

PubMed

Johnson, Scott; Davis, Matthew; Kaltenboeck, Anna; Birnbaum, Howard; Grubb, Elizabeth; Tarrants, Marcy; Siderowf, Andrew

2011-11-01

The indirect costs of Parkinson's disease (PD) may be larger than direct healthcare costs, and the largest component of indirect costs is income loss related to early retirement. No recent retrospective analysis details PD-related early retirement and income loss in the US. We used an observational, matched cohort to study wages and labour force participation over 4 years and to simulate lifetime income losses conditional on being newly diagnosed with PD (naive) or having evidence of increasing disability. Actively employed primary beneficiaries of private insurance policies aged 18-64 years with more than two PD diagnoses (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]: 332.x) or one diagnosis and a prescription of an antiparkinsonian drug were selected from a privately insured claims database. Continuous health coverage during analysis periods was required. Naive patients were defined as having no claims history indicative of PD during the year prior to first diagnosis or prescription use. A PD with ambulatory assistance devices (PDAAD) cohort was also followed from the date of first evidence of a wheelchair or walker. Controls without PD were matched on age, sex and region. Survival analysis and Wilcoxon rank sum tests were used to compare rates of early retirement and income loss. A simulation of projected economic loss was conducted for PD cohorts diagnosed at different ages using Bureau of Labor Statistics labour force participation and income data. Naive PD patients (n = 278) and PDAAD patients (n = 28) were on average aged 53 years and had significantly higher rates of co-morbidities at baseline versus controls. Conditional on being employed, there was no statistical difference in earnings. However, the hazard of early retirement associated with PD was 2.08 (p < 0.001) for the naive cohort and 5.01 (p < 0.001) for the PDAAD cohort. From age 40 to 79 years, earnings losses in year 2009 values were

Cognitive load effects on early visual perceptual processing.

PubMed

Liu, Ping; Forte, Jason; Sewell, David; Carter, Olivia

2018-05-01

Contrast-based early visual processing has largely been considered to involve autonomous processes that do not need the support of cognitive resources. However, as spatial attention is known to modulate early visual perceptual processing, we explored whether cognitive load could similarly impact contrast-based perception. We used a dual-task paradigm to assess the impact of a concurrent working memory task on the performance of three different early visual tasks. The results from Experiment 1 suggest that cognitive load can modulate early visual processing. No effects of cognitive load were seen in Experiments 2 or 3. Together, the findings provide evidence that under some circumstances cognitive load effects can penetrate the early stages of visual processing and that higher cognitive function and early perceptual processing may not be as independent as was once thought.

The Early Communication Indicator for Infants and Toddlers: Early Head Start Growth Norms from Two States

ERIC Educational Resources Information Center

Greenwood, Charles R.; Walker, Dale; Buzhardt, Jay

2010-01-01

The Early Communication Indicator (ECI) is a measure relevant to intervention decision making and progress monitoring for infants and toddlers. With increasing recognition of the importance of quality early childhood education and intervention for all children, measurement plays an important role in documenting children's progress and outcomes of…

50 CFR 402.11 - Early consultation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Consultation Procedures § 402.11 Early consultation. (a) Purpose. Early consultation is designed to reduce the likelihood of conflicts between listed species or critical...

50 CFR 402.11 - Early consultation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Consultation Procedures § 402.11 Early consultation. (a) Purpose. Early consultation is designed to reduce the likelihood of conflicts between listed species or critical...

50 CFR 402.11 - Early consultation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Consultation Procedures § 402.11 Early consultation. (a) Purpose. Early consultation is designed to reduce the likelihood of conflicts between listed species or critical...

50 CFR 402.11 - Early consultation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Consultation Procedures § 402.11 Early consultation. (a) Purpose. Early consultation is designed to reduce the likelihood of conflicts between listed species or critical...

50 CFR 402.11 - Early consultation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Consultation Procedures § 402.11 Early consultation. (a) Purpose. Early consultation is designed to reduce the likelihood of conflicts between listed species or critical...

Early Adversity, Psychopathology, and Latent Class Profiles of Global Physical Health From Preschool Through Early Adolescence.

PubMed

Whalen, Diana J; Belden, Andy C; Tillman, Rebecca; Barch, Deanna M; Luby, Joan L

The purpose of the present report was to describe the longitudinal trajectories of physical health beginning during preschool and continuing into early adolescence; explore whether these trajectories were predicted by psychosocial adversity, family income-to-needs ratio, and psychiatric disorders occurring during the preschool period; and determine whether psychiatric disorders mediated these relations. Participants included 296 children participating in a longitudinal study of early-onset psychopathology spanning 10 years. Semistructured clinical interviews were conducted with caregivers to determine children's psychiatric diagnoses between ages 3 and 6 years. Caregivers also completed annual assessments of their child's physical health problems (ages 3-13) and reported on the family's income and indicators of psychosocial adversity. Growth mixture modeling revealed 2 trajectories of physical health problems: a stable, low group (n = 199) and a high, increasing group (n = 57) indicating linear increases in physical health problems from ages 3 to 13. Preschool psychiatric diagnoses (Estimate [Est] = 0.05, p < .001), family income-to-needs ratio (Est = -0.01, p = .012), and psychosocial adversity (Est = 0.02, p = .015) predicted membership in the high, increasing trajectory of physical health problems. Early-onset psychopathology mediated relations between psychosocial adversity and physical health problems (αβ = 0.31, p = .050) and between income-to-needs ratio and physical health problems (αβ = -0.29, p < .021). These findings indicate the importance of early indicators of risk: low income-to-needs ratios, high psychosocial adversity, and psychiatric disorders occurring during the preschool period for contributing to increasing physical health problems from preschool through early adolescence. Early-onset psychiatric disorders also mediated relations between psychosocial adversity, income-to-needs ratio, and physical health problems.

Early Rockets

NASA Image and Video Library

1950-01-01

Test firing of a Redstone Missile at Redstone Test Stand in the early 1950's. The Redstone was a high-accuracy, liquid-propelled, surface-to-surface missile developed by the von Braun Team under the management of the U.S. Army. The Redstone was the first major rocket development program in the United States.

Early Rockets

NASA Image and Video Library

2004-04-15

During the early introduction of rockets to Europe, they were used only as weapons. Enemy troops in India repulsed the British with rockets. Later, in Britain, Sir William Congreve developed a rocket that could fire to about 9,000 feet. The British fired Congreve rockets against the United States in the War of 1812.

[Early diagnosis of autism: Phenotype-endophenotype].

PubMed

Kotsopoulos, S

2015-01-01

Autism Spectrum Disorders have for some time been the focus of intense interest for clinicians and researchers because of the high prevalence of the disorders among children in the community (approximately 1%), their severity and pervasiveness. Particular attention has been paid to the early diagnosis of the disorder and to the intensive therapeutic intervention. Currently the best prognosis for autism lays in the early diagnosis and intervention. Postponing the diagnosis and the intervention beyond infancy is considered loss of precious time. The diagnosis of autism, which begins early in life, was until recently considered that could be reliability made at the age of 3 years. Recent follow up studies however on children at risk for autism (children who had an older sibling with autism) have shown that the clinical signs of autism emerge at the end of the first year and become distinct by the end of the second year when the diagnosis can reliably be made. From a clinical perspective it is noted that the early clinical signs of risk for autism are related to social communication (e.g. limited or absent response when calling his/her name and to joint attention), stereotype behaviours and body movements or unusual handling of objects (e.g. intensive observation of objects and stereotype movements of hands and tapping or spinning), incongruent regulation of emotions (reduced positive and increased negative emotion). There is also delay in developmental characteristics such as the language (both receptive and expressive) and motor (particularly in postural control - characteristic is the drop of the head backwards when the infant is held in horizontal position). Studies on various aspects of the endophenotype of certain clinical signs among infants at risk for Autism Spectrum Disorders, such as avoidance of eye contact, delay in verbal communication and increase of the head circumference, may provide useful information and may assist the clinician on follow up in the

New Early Cycladic Figurine At Nea Styra

NASA Astrophysics Data System (ADS)

Kosma, M.

The existence of an Early Bronze Age coastal site in the district of Nea Styra has been known since the end of the 19th century when three marble figurines of early Cycladic type had been found in the area. During the 20th century survey investigations conducted by Greek and foreign archaeologists offered new evidence which demonstrated the significance of the site during the Early and Middle Helladic periods. A new figurine of early Cycladic type, which recently came to light at Nea Styra due to the control of building permits by the 11th Ephorate of Prehistoric and Classical Antiquities, reaffirms the identification of the area as one of the three most important sites on Euboea during the Early Helladic II period. This paper focuses on a newly discovered figurine and its typological character. The new find is compared to the figurines that had been found in the 19th century at Nea Styra. We hope that the scheduled excavations on the private land plot where the new figurine was found will offer new data leading to a better understanding of the character of the Early Helladic settlement in this part of southern Euboea.

Early Childhood Educator and Administrator Surveys on the Use of Assessments and Standards in Early Childhood Settings. REL 2014-019

ERIC Educational Resources Information Center

Irwin, Clare W.; O'Dwyer, Laura; Cook, Kyle DeMeo

2014-01-01

The Early Childhood Educator Survey and the Early Childhood Administrator Survey allow users to collect consistent data on the use of child assessments and learning standards in early childhood learning settings. Each survey includes modules on educator/administrator background information, assessment use, and learning standards implementation.…

The Timing of Middle-Childhood Peer Rejection and Friendship: Linking Early Behavior to Early-Adolescent Adjustment

ERIC Educational Resources Information Center

Pedersen, Sara; Vitaro, Frank; Barker, Edward D.; Borge, Anne I. H.

2007-01-01

This study used a sample of 551 children surveyed yearly from ages 6 to 13 to examine the longitudinal associations among early behavior, middle-childhood peer rejection and friendedness, and early-adolescent depressive symptoms, loneliness, and delinquency. The study tested a sequential mediation hypothesis in which (a) behavior problems in the…

From Early Starters to Late Finishers? A Longitudinal Study of Early Foreign Language Learning in School

ERIC Educational Resources Information Center

Jaekel, Nils; Schurig, Michael; Florian, Merle; Ritter, Markus

2017-01-01

Foreign language education has now been implemented at the elementary school level across Europe, and early foreign language education has gained traction following language policies set by the European Commission. The long-term effects of an early start, however, have not received ample scientific scrutiny. The present study assessed early…

Conditions on Early Mars Might Have Fostered Rapid and Early Development of Life

NASA Technical Reports Server (NTRS)

Gibson, Everett K.; McKay, David S.; Thomas-Keprta, Kathie L.; Clemett, Simon J.; Wentworth, Susan J.

2007-01-01

The exploration of Mars during the past decades has begun to unveil the history of the planet. The combinations of remote sensing, in situ geochemical compositional measurements and photographic observations from both above and on the surface have shown Mars to have a dynamic and active geologic evolution. Mars geologic evolution clearly had conditions that were suitable for supporting life. For a planet to be able to be habitable, it must have water, carbon sources, energy sources and a dynamic geologic past. Mars meets all of these requirements. The first 600 My of Martian history were ripe for life to develop because of the abundance of (i) Water-carved canyons and oceans or lakes with the early presence of near surface water shown by precipitated carbonates in ALH84001 well-dated at approx.3.9 Gy., (ii) Energy from the original accretional processes, a molten core which generated a strong magnetic field leaving a permanent record in the early crust, early active volcanism continuing throughout Martian history, and, and continuing impact processes, (iii) Carbon and water from possibly extensive volcanic outgassing (i.e. H2O, CO2, CH4, CO, O2, N2, H2S, SO2, etc.) and (iv) some crustal tectonics as revealed by faulting and possible plate movement reflected by the magnetic pattern in the crust. The question arises: "Why would life not evolve from these favorable conditions on early Mars in its first 600 My?" During this period, it seems likely that environmental near-surface conditions on Mars were more favorable to life than at any later time. Standing bodies of water, precipitation and flowing surface water, and possibly abundant hydrothermal energy would all favor the formation of early life. Even if life developed elsewhere (on Earth, Venus, or on other solar systems) and was transported to Mars, the surface conditions were likely very hospitable for that introduced life to multiply and evolve.

AOSSM Early Sport Specialization Consensus Statement.

PubMed

LaPrade, Robert F; Agel, Julie; Baker, Joseph; Brenner, Joel S; Cordasco, Frank A; Côté, Jean; Engebretsen, Lars; Feeley, Brian T; Gould, Daniel; Hainline, Brian; Hewett, Timothy; Jayanthi, Neeru; Kocher, Mininder S; Myer, Gregory D; Nissen, Carl W; Philippon, Marc J; Provencher, Matthew T

2016-04-01

Early sport specialization is not a requirement for success at the highest levels of competition and is believed to be unhealthy physically and mentally for young athletes. It also discourages unstructured free play, which has many benefits. To review the available evidence on early sports specialization and identify areas where scientific data are lacking. Think tank, roundtable discussion. The primary outcome of this think tank was that there is no evidence that young children will benefit from early sport specialization in the majority of sports. They are subject to overuse injury and burnout from concentrated activity. Early multisport participation will not deter young athletes from long-term competitive athletic success. Youth advocates, parents, clinicians, and coaches need to work together with the sport governing bodies to ensure healthy environments for play and competition that do not create long-term health issues yet support athletic competition at the highest level desired.

Scoping the evidence for EarlyBird and EarlyBird Plus, two United Kingdom-developed parent education training programmes for autism spectrum disorder.

PubMed

Dawson-Squibb, John-Joe; Davids, Eugene Lee; de Vries, Petrus J

2018-03-01

EarlyBird and EarlyBird Plus are parent education and training programmes designed by the UK National Autistic Society in 1997 and 2003, having been delivered to more than 27,000 families in 14 countries. These group-based programmes aim to (1) support parents immediately after diagnosis of autism spectrum disorder, (2) empower parents, encouraging a positive perception of their child's autism spectrum disorder and (3) help parents establish good practice. In the absence of any previous comprehensive review, we performed a scoping review of all peer-reviewed publications on EarlyBird/EarlyBird Plus. A search was conducted between February and June 2016 using EbscoHost, Sabinet, SAGE Journals, Directory of Open Access Journals, BioMed Central, Scopus, ScienceDirect and grey literature. Two reviewers independently screened titles and abstracts for inclusion. In total, 18 articles were identified: 16 from the United Kingdom and 2 from New Zealand. We reviewed the context, study populations, design, outcome measures, whether focus was on parental perception, parental change or child changes and programme feasibility. Strong parental support for the acceptability but lower level evidence of efficacy of EarlyBird/EarlyBird Plus was found. Future research should consider randomised controlled trials. There is no research on EarlyBird/EarlyBird Plus in low-resource settings; therefore, we recommend broader feasibility evaluation of EarlyBird/EarlyBird Plus including accessibility, cultural appropriateness and scalability.

Developments in early intervention for psychosis in Hong Kong.

PubMed

Wong, G H Y; Hui, C L M; Wong, D Y; Tang, J Y M; Chang, W C; Chan, S K W; Lee, E H M; Xu, J Q; Lin, J J X; Lai, D C; Tam, W; Kok, J; Chung, D W S; Hung, S F; Chen, E Y H

2012-09-01

The year 2011 marked the 10-year milestone of early intervention for psychosis in Hong Kong. Since 2001, the landscape of early psychosis services has changed markedly in Hong Kong. Substantial progress has been made in the areas of early intervention service implementation, knowledge generation, and public awareness promotion. Favourable outcomes attributable to the early intervention service are supported by solid evidence from local clinical research studies; early intervention service users showed improved functioning, ameliorated symptoms, and decreased hospitalisation and suicide rates. Continued development of early intervention in Hong Kong over the decade includes the introduction and maturation of several key platforms, such as the Hospital Authority Early Assessment Service for Young People with Psychosis programme, the Psychosis Studies and Intervention Unit by the University of Hong Kong, the Hong Kong Early Psychosis Intervention Society, the Jockey Club Early Psychosis Project, and the postgraduate Psychological Medicine (Psychosis Studies) programme. In this paper, we reviewed some of the major milestones in local service development with reference to features of the Hong Kong mental health system. We describe chronologically the implementation and consolidation of public early intervention services as well as recent progresses in public awareness work that are tied in with knowledge generation and transfer, and outline the prospects for early intervention in the next decade and those that follow.

Coaching in Early Mathematics.

PubMed

Germeroth, Carrie; Sarama, Julie

2017-01-01

Falling scores in math have prompted a renewed interest in math instruction at early ages. By their own admission, early childhood educators are generally underprepared and not always comfortable teaching math. Professional development (PD) in early mathematics is widely considered a main way to increase teachers' skills and efficacy (e.g., Guskey, 2000; Hyson & Woods, 2014; Munby, Russell, & Martin, 2001; Piasta, Logan, Pelatti, Capps, & Petrill, 2015; Richardson & Placier, 2001; Sarama, Clements, Wolfe, & Spitler, 2016; Sarama & DiBiase, 2004; Zaslow, 2014). However, it has been documented that stand-alone PD is not as effective in changing practice (e.g., Biancarosa & Bryk, 2011; Garet et al., 2008; Guskey, 2000; Hyson & Woods, 2014; Institute of Medicine and National Research Council, 2015; Joyce & Showers, 2002; Zaslow, 2014). Site-embedded ongoing support in the form of coaching or mentoring has been shown to be critical for successful implementation (Neuman & Cunningham, 2009; Powell, Diamond, Burchinal, & Koehler, 2010). In this chapter, we describe coaching models and abstract characteristics of effective coaching from the research. With this background, we provide an in-depth view of the coaching aspect of two large empirical studies in early mathematics. We introduce the theoretical framework from which the coaching models for these projects were developed and describe the research on which they were based. We then summarize how the planned models were instantiated and challenges to their implementation within each project. In the final section, we summarize what we have learned and described implications and challenges for the field. © 2017 Elsevier Inc. All rights reserved.

Early appendectomy shortens antibiotic course and hospital stay in children with early perforated appendicitis.

PubMed

Tsai, Hsin-Yu; Chao, Hsun-Chin; Yu, Wan-Ju

2017-10-01

The optimal management of perforated appendicitis in the pediatric population has been controversial. This study aimed to compare the therapeutic efficacy between conservative treatment (CS) and early appendectomy (EA) in pediatric perforated appendicitis, and to determine whether surgical intervention is an optimal treatment modality for early perforated appendicitis in children. Patients treated between January 2012 and April 2014, aged 0-18 years, with an imaging-based diagnosis of perforated appendicitis were retrospectively reviewed. Patients were classified into nonabscess and abscess groups by image findings, and were further categorized into CS and EA groups by treatment modality. Early perforated appendicitis was defined as having duration of symptoms≤7 days, C-reactive protein level≤200 mg/L, maximum abscess diameter≤5 cm, and absence of general peritonitis, and unstable vital signs. The clinical features and therapeutic outcomes were compared between CS and EA in each group. A total of 326 patients had confirmed appendicitis, including 116 patients with an image diagnosis of perforation. The CS group had a significantly longer duration of symptoms, larger abscesses, and higher serum C-reactive protein levels at presentation (all p<0.05). Patients in the EA group had a shorter antibiotic course and length of hospitalization, and a lower rate of antibiotic escalation than those in the CS group (p<0.001, p<0.001, and p<0.05, respectively). In patients with early perforated appendicitis, the CS and EA groups showed no difference in baseline disease severity. Patients in the EA group also had a shorter antibiotic course and length of hospitalization than those in the CS group (p<0.001 and p<0.001, respectively). Compared with CS, EA shortens the antibiotic course and hospital stay in pediatric early perforated appendicitis, even in the presence of small abscesses. Copyright © 2017. Published by Elsevier B.V.

Where Are the Early Years of School in Contemporary Early Childhood Education Reforms? An Historical Perspective

ERIC Educational Resources Information Center

Krieg, Susan; Whitehead, Kay

2015-01-01

Although international definitions of early childhood repeatedly refer to a birth-8 age span, there are complex, institutional divides within this age range. This paper explores the divide between pre-compulsory and compulsory early childhood institutions. In countries such as Finland this divide is not such an issue because children do not begin…

Conceptions of and Early Childhood Educators' Experiences in Early Childhood Professional Development Programs: A Qualitative Metasynthesis

ERIC Educational Resources Information Center

Brown, Christopher P.; Englehardt, Joanna

2016-01-01

Policy makers and early childhood stakeholders across the United States continue to seek policy solutions that improve early educators' instruction of young children. A primary vehicle for attaining this goal is professional development. This has led to an influx of empirical studies that seek to develop a set of best practices for professional…

Early Lung Cancer Diagnosis by Biosensors

PubMed Central

Zhang, Yuqian; Yang, Dongliang; Weng, Lixing; Wang, Lianhui

2013-01-01

Lung cancer causes an extreme threat to human health, and the mortality rate due to lung cancer has not decreased during the last decade. Prognosis or early diagnosis could help reduce the mortality rate. If microRNA and tumor-associated antigens (TAAs), as well as the corresponding autoantibodies, can be detected prior to clinical diagnosis, such high sensitivity of biosensors makes the early diagnosis and prognosis of cancer realizable. This review provides an overview of tumor-associated biomarker identifying methods and the biosensor technology available today. Laboratorial researches utilizing biosensors for early lung cancer diagnosis will be highlighted. PMID:23892596

[Early Intervention and Cognitive Development: A Longitudinal Study with Psychologically Stressed Mother-Child-Dyad during Early Childhood].

PubMed

Zwönitzer, Annabel; Ziegenhain, Ute; Bovenschen, Ina; Pillhofer, Melanie; Spangler, Gottfried; Gerlach, Jennifer; Gabler, Sandra; Kindler, Heinz; Fegert, Jörg M; Künster, Anne Katrin

2016-01-01

Early intervention programs aiming at developing parents’ relationship and parenting skills and supporting young families have become increasingly established in Germany throughout the last decade. The present longitudinal study analyzed 53 children and their mothers receiving early intervention due to their psychosocially highly challenging life situations and personal circumstances. The children were examined at birth and at an age of twelve months as well as between ages two and four. The results revealed that the child’s cognitive development could be predicted by both maternal sensitivity and mother’s psychosocial stress. However, the amount, type, and intensity of early intervention did not have any effect on the child’s development. In terms of the effectiveness of early interventions the results implicate that interventions seems to be offered in an unspecific manner and does not contribute to an improvement of the child’s developmental status.

Early dissemination seeds metastasis in breast cancer

PubMed Central

Hosseini, Hedayatollah; Obradović, Milan M.S.; Hoffmann, Martin; Harper, Kathryn; Sosa, Maria Soledad; Werner-Klein, Melanie; Nanduri, Lahiri Kanth; Werno, Christian; Ehrl, Carolin; Maneck, Matthias; Patwary, Nina; Haunschild, Gundula; Gužvić, Miodrag; Reimelt, Christian; Grauvogl, Michael; Eichner, Norbert; Weber, Florian; Hartkopf, Andreas; Taran, Florin-Andrei; Brucker, Sara Y.; Fehm, Tanja; Rack, Brigitte; Buchholz, Stefan; Spang, Rainer; Meister, Gunter; Aguirre-Ghiso, Julio A.; Klein, Christoph A.

2016-01-01

Accumulating data suggest that metastatic dissemination often occurs early during tumour formation but the mechanisms of early metastatic spread have not yet been addressed. Here, we studied metastasis in a HER2-driven mouse breast cancer model and found that progesterone-induced signalling triggered migration of cancer cells from early lesions shortly after HER2 activation, but promoted proliferation in advanced primary tumour cells. The switch from migration to proliferation was regulated by elevated HER2 expression and increased tumour cell density involving miRNA-mediated progesterone receptor (PGR) down-regulation and was reversible. Cells from early, low-density lesions displayed more stemness features than cells from dense, advanced tumours, migrated more and founded more metastases. Strikingly, we found that at least 80% of metastases were derived from early disseminated cancer cells (DCC). Karyotypic and phenotypic analysis of human disseminated cancer cells and primary tumours corroborated the relevance of these findings for human metastatic dissemination. PMID:27974799

Mid-childhood fruit and vegetable consumption: The roles of early liking, early consumption, and maternal consumption.

PubMed

Kong, Kai Ling; Gillman, Matthew W; Rifas-Shiman, Sheryl L; Wen, Xiaozhong

2016-10-01

Previous studies have shown that early liking, early consumption, and maternal consumption of fruits and vegetables (F&V) each predict children's F&V consumption, but no one has examined the independent contributions of these three correlated factors. We aim to examine the extent to which each of these 3 factors is associated with F&V consumption in mid-childhood after accounting for the other 2 in the analysis. We analyzed data from 901 mother-child dyads from Project Viva, a prospective pre-birth cohort study. Mothers reported their child's early liking and consumption of F&V at age 2 years and later consumption at mid-childhood (median age 7.7 years). They also reported their own consumption of F&V at 6 months postpartum. We used multivariable linear regression models to examine the independent associations of these 3 factors with mid-childhood consumption, adjusting for socio-demographic, pregnancy, and child confounders. At 2 years, 53% of the mothers strongly agreed that their child liked fruit and 25% strongly agreed that their child liked vegetables. F&V consumption was 2.5 (1.3) and 1.8 (1.1) times/d at age 2 y and 1.5 (1.1) and 1.3 (0.8) times/d in mid-childhood. Maternal F&V consumption was 1.4 (1.1) and 1.5 (1.0) times/d, respectively. Children's early consumption played the most predominant role. For every 1 time/d increment in children's early consumption of F&V, mid-childhood consumption was higher by 0.25 (95% confidence interval [CI]: 0.19, 0.30) times/d for fruits and 0.21 (95% CI: 0.16, 0.26) times/d for vegetables, adjusted for confounders plus the other 2 exposures. In conclusion, children's early F&V consumption has the most significant influence on children's later consumption. Published by Elsevier Ltd.

Early adversity, psychopathology, and latent class profiles of global physical health from preschool through early adolescence

PubMed Central

Whalen, Diana J.; Belden, Andy C.; Tillman, Rebecca; Barch, Deanna M.; Luby, Joan L.

2016-01-01

Objective The purpose of the present report was to describe the longitudinal trajectories of physical health beginning during preschool and continuing into early adolescence, explore whether these trajectories were predicted by psychosocial adversity, family income-to-needs ratio, and psychiatric disorders occurring during the preschool period, and determine whether psychiatric disorders mediated these relations. Methods Participants included 296 children participating in a longitudinal study of early-onset psychopathology spanning ten years. Semi-structured clinical interviews were conducted with caregivers to determine children’s psychiatric diagnoses between ages 3–6. Caregivers also completed annual assessments of their child’s physical health problems (ages 3–13), as well as reported on the family’s income and indicators of psychosocial adversity. Results Growth mixture modeling revealed two trajectories of physical health problems: a stable, low group (n = 199) and a high, increasing group (n = 57) indicating linear increases in physical health problems from ages 3–13. Preschool psychiatric diagnoses (Est= 0.05, p<.001), family income-to-needs ratio (Est= −0.01, p=.012), and psychosocial adversity (Est=0.02, p=.015) predicted membership in the high, increasing trajectory of physical health problems. Early-onset psychopathology mediated relations between psychosocial adversity and physical health problems (αβ= 0.31, p=.050) and between income-to-needs ratio and physical health problems (αβ= −0.29, p<.021). Conclusions These findings indicate the importance of early indicators of risk: low income-to-needs ratios, high psychosocial adversity, and psychiatric disorders occurring during the preschool period for contributing to increasing physical health problems from preschool through early adolescence. Early-onset psychiatric disorders also mediated relations between psychosocial adversity, income-to-needs ratio, and physical health problems

Family and Peer Predictors of Substance Use From Early Adolescence to Early Adulthood: An 11-Year Prospective Analysis

PubMed Central

Van Ryzin, Mark J.; Fosco, Gregory M.; Dishion, Thomas J.

2012-01-01

The focus of this study was social (i.e., family and peer) influences on substance use from early adolescence to early adulthood. A large, ethnically diverse sample of early adolescents (N = 998) was followed from age 12 to age 23. We tested direct and indirect effects of parental monitoring, family relationship quality, and association with deviant peers on change in substance use across time. Outcomes for tobacco, alcohol, and marijuana use were analyzed as separate pathways within the same overall model. The results suggest that a significant shift in the nature of family influence occurred across adolescence and into early adulthood, but deviant peer influence was relatively consistent across this period. Specifically, parental monitoring and deviant peer association were predictive of substance use in early adolescence, but family relationship quality was a significant predictor across the transition to high school and generally continued to predict use into later adolescence, as did association with deviant peers. Deviant peers were the only significant predictor in early adulthood. Our results also suggested that parental monitoring and family relationship quality indirectly predicted later substance use by way of deviant peers, implying that an important aspect of the family context is its influence on choice of friends and peer group composition. Implications for family-based prevention and intervention are discussed. PMID:22958864

Louisiana Resource Trustees Early Restoration Public Meeting | NOAA Gulf

Science.gov Websites

Publications Press Releases Story Archive Home Louisiana Resource Trustees Early Restoration Public Meeting Louisiana Resource Trustees Early Restoration Public Meeting share Posted on June 14, 2011 | Assessment and Early Restoration Restoration Area Title: Louisiana Resource Trustees Early Restoration Public

Preschool Teachers' Constructions of Early Reading

ERIC Educational Resources Information Center

Walker, Karen E.

2015-01-01

Research concerning preschool teachers' constructions of early reading has potential to influence teachers' curricular decisions and classroom practice. Six preschool teachers in North Texas were interviewed in regard to what they think about early reading and how they develop these understandings or constructions. The systematic, inductive…

Early Years Students' Relationships with Mathematics

ERIC Educational Resources Information Center

Takeuchi, Miwa Aoki; Towers, Jo; Plosz, Jennifer

2016-01-01

Early years mathematics experiences have been shown to be a significant predictor for students' school readiness and future mathematics achievement. Previous research also indicates an important connection between emotion and mathematics learning. How do students in early years education in Alberta describe their emotional relationship with…

A Literature Review of Early Intervention.

ERIC Educational Resources Information Center

Panitch, Melanie

This review of the literature on early childhood intervention with special needs children provides a Canadian perspective on theory, models, program development, effects, and training. After an introductory chapter, the second chapter identifies theoretical influences on early childhood intervention, including the work of Piaget, Bronfenbrenner,…

Transactional relations between caregiving stress, executive functioning, and problem behavior from early childhood to early adolescence

PubMed Central

LaGasse, Linda L.; Conradt, Elisabeth; Karalunas, Sarah L.; Dansereau, Lynne M.; Butner, Jonathan E.; Shankaran, Seetha; Bada, Henrietta; Bauer, Charles R.; Whitaker, Toni M.; Lester, Barry M.

2016-01-01

Developmental psychopathologists face the difficult task of identifying the environmental conditions that may contribute to early childhood behavior problems. Highly stressed caregivers can exacerbate behavior problems, while children with behavior problems may make parenting more difficult and increase caregiver stress. Unknown is: (1) how these transactions originate, (2) whether they persist over time to contribute to the development of problem behavior and (3) what role resilience factors, such as child executive functioning, may play in mitigating the development of problem behavior. In the present study, transactional relations between caregiving stress, executive functioning, and behavior problems were examined in a sample of 1,388 children with prenatal drug exposures at three developmental time points: early childhood (birth-age 5), middle childhood (ages 6 to 9), and early adolescence (ages 10 to 13). Transactional relations differed between caregiving stress and internalizing versus externalizing behavior. Targeting executive functioning in evidence-based interventions for children with prenatal substance exposure who present with internalizing problems and treating caregiving psychopathology, depression, and parenting stress in early childhood may be particularly important for children presenting with internalizing behavior. PMID:27427803

Early Silurian Foraminifera from Gondwana - an early origin of the multichambered globothalamids?

NASA Astrophysics Data System (ADS)

Kaminski, Michael

2017-04-01

Early Silurian foraminifera until now have been regarded to consist of simple single-chambered monothalamids and two-chambered tubothalamids with an agglutinated wall. Although pseudo-multichambered agglutinated foraminifera first appeared in the mid-Ordovician (Kaminski et al. 2009), the origin of true multichambered forms was not believed to have taken place until the early or middle Devonian at the earliest (Holcová, 2002). New discoveries from the Lower Silurian Qusaiba Shale Member in Saudi Arabia point to an earlier origin of the multichambered globothalamid Foraminifera than the currently accepted estimate of 350 Ma (Pawlowski et al. 2003). The agglutinated foraminiferal genera Ammobaculites and Sculptobaculites have been recovered from dark graptolite-bearing claystones of Telychian age, from the transitional facies between the Qusaiba and Sharawa Members of the Qasim Formation at the type locality near Qusaiba town, Saudi Arabia. The multichambered lituolids occur as rare components in a foraminiferal assemblage consisting mostly of monothalamids. This new finding revises our understanding of the early evolution of the multichambered globothalamid foraminifera. The fossil record now shows that the globothalamids were already present in Gondwana by 435 m.y. Holcová, K. 2002. Silurian and Devonian foraminifers and other acid-resistant microfossils from the Barrandian area. Acta Musei Nationalis Pragae, Series B, Historia Naturalis, 58 (3-4), 83-140. Kaminski, M.A., Henderson, A.S., Cetean, C.G. & Waskowska-Oliwa, A. 2009. A new family of agglutinated foraminifera: the Ammolagenidae n.fam., and the evolution of multichambered tests. Micropaleontology, 55 (5), 487-494. Pawlowski, J., Holzmann, M., Berney, C., Fahrni, J.F., Gooday, Aj., Cedhagen, T., Habura, A., & Bowser, SS. 2003. The evolution of early Foraminifera. Proceedings of the National Academy of Sciences, 100 (20), 11494-11498

Investigating Early Childhood Teachers' Views on Science Teaching Practices: The Integration of Science with Visual Art in Early Childhood Settings

ERIC Educational Resources Information Center

Öztürk Yilmaztekin, Elif; Erden, Feyza Tantekin

2017-01-01

This study investigates early childhood teachers' views about science teaching practices in an early childhood settings. It was conducted in a preschool located in Ankara, Turkey. The data of the study were collected through multiple sources of information such as interviews with early childhood teachers and observations of their practices in the…

Feedback-induced bistability of an optically levitated nanoparticle: A Fokker-Planck treatment

NASA Astrophysics Data System (ADS)

Ge, Wenchao; Rodenburg, Brandon; Bhattacharya, M.

2016-08-01

Optically levitated nanoparticles have recently emerged as versatile platforms for investigating macroscopic quantum mechanics and enabling ultrasensitive metrology. In this paper we theoretically consider two damping regimes of an optically levitated nanoparticle cooled by cavityless parametric feedback. Our treatment is based on a generalized Fokker-Planck equation derived from the quantum master equation presented recently and shown to agree very well with experiment [B. Rodenburg, L. P. Neukirch, A. N. Vamivakas, and M. Bhattacharya, Quantum model of cooling and force sensing with an optically trapped nanoparticle, Optica 3, 318 (2016), 10.1364/OPTICA.3.000318]. For low damping, we find that the resulting Wigner function yields the single-peaked oscillator position distribution and recovers the appropriate energy distribution derived earlier using a classical theory and verified experimentally [J. Gieseler, R. Quidant, C. Dellago, and L. Novotny, Dynamic relaxation of a levitated nanoparticle from a non-equilibrium steady state, Nat. Nano. 9, 358 (2014), 10.1038/nnano.2014.40]. For high damping, in contrast, we predict a double-peaked position distribution, which we trace to an underlying bistability induced by feedback. Unlike in cavity-based optomechanics, stochastic processes play a major role in determining the bistable behavior. To support our conclusions, we present analytical expressions as well as numerical simulations using the truncated Wigner function approach. Our work opens up the prospect of developing bistability-based devices, characterization of phase-space dynamics, and investigation of the quantum-classical transition using levitated nanoparticles.

AOSSM Early Sport Specialization Consensus Statement

PubMed Central

LaPrade, Robert F.; Agel, Julie; Baker, Joseph; Brenner, Joel S.; Cordasco, Frank A.; Côté, Jean; Engebretsen, Lars; Feeley, Brian T.; Gould, Daniel; Hainline, Brian; Hewett, Timothy E.; Jayanthi, Neeru; Kocher, Mininder S.; Myer, Gregory D.; Nissen, Carl W.; Philippon, Marc J.; Provencher, Matthew T.

2016-01-01

Background: Early sport specialization is not a requirement for success at the highest levels of competition and is believed to be unhealthy physically and mentally for young athletes. It also discourages unstructured free play, which has many benefits. Purpose: To review the available evidence on early sports specialization and identify areas where scientific data are lacking. Study Design: Think tank, roundtable discussion. Results: The primary outcome of this think tank was that there is no evidence that young children will benefit from early sport specialization in the majority of sports. They are subject to overuse injury and burnout from concentrated activity. Early multisport participation will not deter young athletes from long-term competitive athletic success. Conclusion: Youth advocates, parents, clinicians, and coaches need to work together with the sport governing bodies to ensure healthy environments for play and competition that do not create long-term health issues yet support athletic competition at the highest level desired. PMID:27169132

Assessing Thai Early Childhood Teachers' Knowledge of Inclusive Education

ERIC Educational Resources Information Center

Agbenyega, Joseph S.; Klibthong, Sunanta

2014-01-01

An ever-increasing number of children with and without disabilities are attending early childhood programmes and learning together. Early childhood inclusion considers all children with and without disabilities, and their families as full members of the early childhood community. Although many early childhood teachers accept the educational rights…

28 CFR 2.96 - Order of early termination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Order of early termination. 2.96 Section 2.96 Judicial Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND RECOMMITMENT OF....96 Order of early termination. When the Commission orders early termination from supervision, the...

28 CFR 2.96 - Order of early termination.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Order of early termination. 2.96 Section 2.96 Judicial Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND RECOMMITMENT OF....96 Order of early termination. When the Commission orders early termination from supervision, the...

Evidence for early disease-modifying drugs in rheumatoid arthritis

PubMed Central

Scott, David L

2004-01-01

Some research evidence supports early aggressive treatment of rheumatoid arthritis (RA) using combination therapy with two or more disease modifying anti-rheumatic drugs (DMARDs) plus steroids, or even DMARDs plus an anti-TNF. By contrast, conservatively delayed DMARD monotherapy, given after non-steroidal anti-inflammatory drugs have failed, has been criticised. However, recent long-term studies highlight the complexities in evaluating whether to abandon pyramidal treatment in favour of early DMARDs. Although patients given early DMARD therapy show short-term benefits, longer-term results show no prolonged clinical advantages from early DMARDs. By 5 years patients receiving early DMARDs had similar disease activity and comparable health assessment questionnaire scores to patients who received DMARDs later in their disease course. X-ray progression was persistent and virtually identical in both groups. These negative findings do not invalidate the case for early DMARD therapy, as it is gives sustained reductions in disease activity in the early years of treatment without excessive risks from adverse effects. However, early DMARDs alone do not adequately control RA in the longer term. This may require starting with very aggressive therapy or treating patients more aggressively after early DMARD therapy has been initiated. PMID:14979927

Early anaerobic metabolisms

PubMed Central

Canfield, Don E; Rosing, Minik T; Bjerrum, Christian

2006-01-01

Before the advent of oxygenic photosynthesis, the biosphere was driven by anaerobic metabolisms. We catalogue and quantify the source strengths of the most probable electron donors and electron acceptors that would have been available to fuel early-Earth ecosystems. The most active ecosystems were probably driven by the cycling of H2 and Fe2+ through primary production conducted by anoxygenic phototrophs. Interesting and dynamic ecosystems would have also been driven by the microbial cycling of sulphur and nitrogen species, but their activity levels were probably not so great. Despite the diversity of potential early ecosystems, rates of primary production in the early-Earth anaerobic biosphere were probably well below those rates observed in the marine environment. We shift our attention to the Earth environment at 3.8 Gyr ago, where the earliest marine sediments are preserved. We calculate, consistent with the carbon isotope record and other considerations of the carbon cycle, that marine rates of primary production at this time were probably an order of magnitude (or more) less than today. We conclude that the flux of reduced species to the Earth surface at this time may have been sufficient to drive anaerobic ecosystems of sufficient activity to be consistent with the carbon isotope record. Conversely, an ecosystem based on oxygenic photosynthesis was also possible with complete removal of the oxygen by reaction with reduced species from the mantle. PMID:17008221

Early Life Stages

EPA Pesticide Factsheets

Childhood should be viewed as a sequence of lifestages, from birth through infancy and adolescence. When assessing early life risks, consideration is given to risks resulting from fetal exposure via the pregnant mother, as well as postnatal exposures.

Early Literacy and Very Young Children

ERIC Educational Resources Information Center

Parlakian, Rebecca

2004-01-01

For infants and toddlers, education and care are "two sides of the same coin." The author briefly reviews current research on the importance of relationships to cognitive development and early language and literacy. Instructional strategies that are most appropriate to the early years include "intentionality" and "scaffolding." Intentionality…

The EHDI and Early Intervention Connection

ERIC Educational Resources Information Center

Nelson, Lauri; Bradham, Tamala S.; Houston, K. Todd

2011-01-01

State coordinators of early hearing detection and intervention (EHDI) programs completed a strengths, weaknesses, opportunities, and threats, or SWOT, analysis that examined 12 areas within state EHDI programs. For the early intervention focus question, 48 coordinators listed 273 items, and themes were identified within each SWOT category. A…

Early Childhood Training Workbook [and Videos].

ERIC Educational Resources Information Center

Magna Systems, Inc., Barrington, IL.

This early childhood training workbook and three accompanying video series provide instruction for early childhood caregivers and teachers in the areas of guidance and discipline, math, and diversity. The video series "Guidance and Discipline" demonstrates the ways in which teachers help children become self disciplined. The three videos…

37 CFR 1.219 - Early publication.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Early publication. 1.219... COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES National Processing Provisions Publication of Applications § 1.219 Early publication. Applications that will be published under § 1.211 may be published...

37 CFR 1.219 - Early publication.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 37 Patents, Trademarks, and Copyrights 1 2014-07-01 2014-07-01 false Early publication. 1.219... COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES National Processing Provisions Publication of Applications § 1.219 Early publication. Applications that will be published under § 1.211 may be published...

37 CFR 1.219 - Early publication.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Early publication. 1.219... COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES National Processing Provisions Publication of Applications § 1.219 Early publication. Applications that will be published under § 1.211 may be published...

Publication Opportunities for Early Childhood Academics.

ERIC Educational Resources Information Center

Sumsion, Jennifer

Recognizing the increasing pressure for publication for early childhood academics and the lack of current information about journals' publication practices, this study surveyed editors of Australian and international journals. The journals were selected through a survey of 43 academic staff of an institute of early childhood education and through…

32 CFR 1656.16 - Early release-grounds and procedures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false Early release-grounds and procedures. 1656.16... ALTERNATIVE SERVICE § 1656.16 Early release—grounds and procedures. (a) General Rule of Service Completion. An... service unless granted an early release. (b) Reasons For Early Release. The Director may authorize the...

32 CFR 1656.16 - Early release-grounds and procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 6 2011-07-01 2011-07-01 false Early release-grounds and procedures. 1656.16... ALTERNATIVE SERVICE § 1656.16 Early release—grounds and procedures. (a) General Rule of Service Completion. An... service unless granted an early release. (b) Reasons For Early Release. The Director may authorize the...