News Article | October 2, 2017
Michigan’s Newborn Screening Technical Advisory Committee (TAC) voted unanimously Sept. 28 to move GAMT Deficiency forward to the Michigan Quality Assurance Advisory Committee (QAAC). The QAAC will review GAMT Deficiency for addition to the Michigan Newborn Screening Program and return their recommendation Nov. 13. Andy Rohrwasser, Newborn Screening Director for Utah’s Public Health Laboratory commented, “Michigan would be the second state to add GAMT to their newborn screening panel. Utah began screening for GAMT in 2015. The addition of GAMT to our panel was straightforward and easy. Screening for GAMT makes sense; early treatment can change a child’s life.” GAMT (Guanidinoacetate Methyltransferase) Deficiency is a deficiency of creatine synthesis that primarily affects the brain and muscles. Children with GAMT Deficiency experience physical and intellectual disabilities if not diagnosed and treated early in life. Symptoms often include global developmental delay, autism, and seizures, and some children have been incorrectly diagnosed with cerebral palsy. Early treatment with safe and inexpensive dietary supplements is of critical importance for these children. Laura Martin, genetic counselor and mother of a child with GAMT Deficiency, was present for the TAC vote. She remarked, “The Michigan Newborn Screening Technical Advisory Committee is composed of knowledgeable, thorough and compassionate professionals. It is obvious that they want to do the right thing for the children of Michigan, and I feel honored to have been present for this very important vote.” About ACD: The Association for Creatine Deficiencies’ mission is to eliminate the challenges of Cerebral Creatine Deficiency Syndromes (CCDS). ACD is committed to providing patient, family, and public education to advocate for early intervention through newborn screening, and to promote and fund medical research for treatments and cures for CCDS. For more information regarding ACD, please visit http://www.creatineinfo.org.
Chandrasekaran A.,Mission Research
Pediatrics and Neonatology | Year: 2017
Background: Neonatal tumors are different from tumors of the older children and knowledge gained from treating older children can not be extrapolated to neonates. Neonates have immature physiology and their haematopoietic and immune systems are not fully developed and the response to therapy is unpredictable. Hence it is imperative to study these tumors as separate entity.The aim of this study is to analyse this rare set of tumors in terms of their incidence, clinical features and management. Materials and methods: All babies admitted in our hospital with tumors from January, 2011 to January 2016 were studied. Tumor-like conditions like haemangioma, lymphangioma and hamartomas were included. The age, sex distribution, type of tumor and management were studied. Results: A total of 51 cases were registered out of which, 29 cases were haemangiomas and lymphangiomas. Of remaining 20 cases, 5 were benign ovarian cysts, 3 were neuroblastomas, 3 were congenital fibrosarcomas, 3 were sacrococcygeal teratomas. Wilm's tumor, congenital mesoblastic nephroma, haemangioendothelioma of liver and others formed the remaining six cases. Conclusion: Our study insists that the neonatal tumors are distinct subset of pediatric tumors, requiring careful selection of treatment modalities and most of the solid tumors can be successfully managed if diagnosed and treated early. Neonatal tumors are defined as tumors which are diagnosed before the first month of life. Some of them can be congenital (present at birth). Neonatal tumors are different from tumors in older children in terms of etiopathogenesis, behavior and response to therapy as well as long-term outcomes. © 2017.
Li E.,California Institute of Technology |
Materna S.C.,Mission Research |
Davidson E.H.,California Institute of Technology
Developmental Biology | Year: 2013
The sea urchin oral ectoderm gene regulatory network (GRN) model has increased in complexity as additional genes are added to it, revealing its multiple spatial regulatory state domains. The formation of the oral ectoderm begins with an oral-aboral redox gradient, which is interpreted by the cis-regulatory system of the nodal gene to cause its expression on the oral side of the embryo. Nodal signaling drives cohorts of regulatory genes within the oral ectoderm and its derived subdomains. Activation of these genes occurs sequentially, spanning the entire blastula stage. During this process the stomodeal subdomain emerges inside of the oral ectoderm, and bilateral subdomains defining the lateral portions of the future ciliary band emerge adjacent to the central oral ectoderm. Here we examine two regulatory genes encoding repressors, sip1 and ets4, which selectively prevent transcription of oral ectoderm genes until their expression is cleared from the oral ectoderm as an indirect consequence of Nodal signaling. We show that the timing of transcriptional de-repression of sip1 and ets4 targets which occurs upon their clearance explains the dynamics of oral ectoderm gene expression. In addition two other repressors, the direct Nodal target not, and the feed forward Nodal target goosecoid, repress expression of regulatory genes in the central animal oral ectoderm thereby confining their expression to the lateral domains of the animal ectoderm. These results have permitted construction of an enhanced animal ectoderm GRN model highlighting the repressive interactions providing precise temporal and spatial control of regulatory gene expression. © 2013 Elsevier Inc.
Settipane R.A.,Brown University |
Schwindt C.,Mission Research
American Journal of Rhinology and Allergy | Year: 2013
Allergic rhinitis affects 60 million of the U.S. population, 1.4 billion of the global population, and its prevalence appears to be increasing. The duration and severity of allergic rhinitis symptoms place a substantial burden on patient's quality of life, sleep, work productivity, and activity. The health impact of allergic rhinitis is compounded by associated complications and comorbidities including asthma, otitis media, sinusitis, and nasal polyps. Allergic rhinitis symptoms result from a complex, allergen-driven mucosal inflammatory process, modulated by immunoglobulin E (IgE), and caused by interplay between resident and infiltrating inflammatory cells and a number of vasoactive and proinflammatory mediators, including cytokines. This allergic response may be characterized as three phases: IgE sensitization, allergen challenge, and elicitation of symptoms. A thorough allergic history is the best tool for the diagnosis of allergic rhinitis, the establishment of which is achieved by correlating the patient's history and physical exam with an assessment for the presence of specific IgE antibodies to relevant aeroallergens determined by skin testing or by in vitro assay. Management of allergic rhinitis includes modifying environmental exposures, implementing pharmacotherapy, and, in select cases, administering allergen-specific immunotherapy. Intranasal therapeutic options include antihistamines, anticholinergic agents, corticosteroids (aqueous or aerosol), mast cell stabilizers, saline, and brief courses of decongestants. Selection of pharmacotherapy is based on the severity and chronicity of symptoms with the most effective medications being intranasal corticosteroids and intranasal antihistamines, which can be used in combination (separately or in fixed dose) for more difficult to control allergic rhinitis. Copyright © 2013, OceanSide Publications, Inc.
Carr W.W.,Mission Research
Pediatric Drugs | Year: 2013
Atopic dermatitis (AD) is an inflammatory skin disease commonly affecting children and managed by pediatricians, primary care physicians, allergists, and dermatologists alike. For many years, the only available topical pharmacological treatment was topical corticosteroids. This changed in 2000-2001, when topical formulations of two calcineurin inhibitors (tacrolimus and pimecrolimus) were approved for short-term or chronic intermittent treatment of AD in patients ≥2 years of age, in whom other treatments have been ineffective or contraindicated. These topical calcineurin inhibitors (TCIs) quickly became a popular treatment option due at least in part to concerns over adverse events associated with prolonged topical corticosteroid use, especially in children. However, based on theoretical concerns about a possible risk of lymphoma associated with TCI use, a Boxed Warning was placed on both products in 2006. Since then, despite an extensive body of evidence, no causal relationship has been demonstrated between TCI use and an increased risk of lymphoma; however, the US FDA has concluded that a link cannot be ruled out. In fact, based on post-marketing surveillance of spontaneous, literature, and solicited reports, we report here that the lymphoma incidence in the topical pimecrolimus-exposed population is up to approximately 54-fold less than that seen in the general US population. This review summarizes the mechanism of action of TCIs, the factors that prompted the Boxed Warning, and recent TCI safety and efficacy data. Based on these data, both topical corticosteroids and TCIs should have defined roles in AD management, with TCIs favored for sensitive skin areas (e.g., face) and instances where topical corticosteroids have proven ineffective, thereby minimizing the risk of adverse effects with both drug classes. © 2013 The Author(s).
Domenech C.,Free University of Berlin |
Wehr T.,Mission Research
IEEE Transactions on Geoscience and Remote Sensing | Year: 2011
The Earth Clouds, Aerosols, and Radiation Explorer (EarthCARE) mission responds to the need to improve the understanding of the interactions between cloud, aerosol, and radiation processes. The fundamental mission objective is to constrain retrievals of cloud and aerosol properties such that their impact on top-of-atmosphere (TOA) radiative fluxes can be determined with an accuracy of 10 W · m -2. However, TOA fluxes cannot be measured instantaneously from a satellite. For the EarthCARE mission, fluxes will be estimated from the observed solar and thermal radiances measured by the Broadband Radiometer (BBR). This paper describes an approach to obtain shortwave (SW) fluxes from BBR radiance measurements. The retrieval algorithms are developed relying on the angular distribution models (ADMs) employed by Clouds and the Earth's Radiant Energy System (CERES) instrument. The solar radiance-to-flux conversion for the BBR is performed by simulating the Terra CERES ADMs using a backpropagation artificial neural network (ANN) technique. The ANN performance is optimized by testing different architectures, namely, feedforward, cascade forward, and a customized-forward network. A large data set of CERES measurements used to resemble the forthcoming BBR acquisitions has been collected. The CERES BBR-like database is sorted by their surface type, sky conditions, and scene type and then stratified by four input variables (solar zenith angle and BBR SW radiances) to construct three different training data sets. Then, the neural networks are analyzed, and the adequate ADM classification scheme is selected. The results of the BBR ANN-based ADMs show SW flux retrievals compliant with the CERES flux estimates. © 2011 IEEE.
Rao P.S.,Mission Research
The Indian journal of medical research | Year: 2013
Disability-adjusted life years (DALYs) have been accepted as a useful method to estimate the burden of disease, and can be adapted to determine the number of productive years lost due to the disability. DALY has been reported for many studies but not for leprosy. Hence this study was carried out in three States of India. In view of the fact that in this study, productive working years are used, the term is modified as DAWLY. A representative random sample of 150 leprosy affected persons, 50 from each States of Uttar Pradesh, West Bengal and Chhattisgarh, was chosen, and data were collected on detailed work-life history, occupation, time when leprosy was discovered, reported and treatment started, break of job/loss of income due to leprosy. The loss of wages and durations were used to compute the life-years lost due to leprosy, and summarized over the average total duration of 42 years of productive work-life from 18 to 60 years. The percentage losses were determined and differences tested for statistical significance. The overall mean (± SE) disability adjusted working life years was 28.6 (±0.67), a reduction of 13.4 yr from the ideal productive working life period of 42 yr. The youngest patients with disability had a reduction of 41.4 per cent, as compared to the oldest patients. There was a significant increase in loss based on year for those whose disability started earlier (P=0.0024). On an average, 30 per cent of the leprosy affected person's work life is lost due to disability.
Shenoy U.,Mission Research |
Paul J.,Mission Research |
Antony D.,Mission Research
Paediatric Anaesthesia | Year: 2014
A 3-year-old child was successfully resuscitated following bupivacaine cardiotoxicity with 20% intravenous lipid emulsion (ILE). Large volume of ILE was used targeting clinically adequate perfusion. Subsequently, there were features of ventilation/perfusion (V/P) mismatch. © 2013 John Wiley & Sons Ltd.
Morris J.K.,University of Kansas Medical Center |
Burns J.M.,University of Kansas Medical Center |
Burns J.M.,Mission Research
Current Neurology and Neuroscience Reports | Year: 2012
Accumulating evidence indicates a role for metabolic dysfunction in the pathogenesis of Alzheimer's disease (AD). It is widely reported that Type 2 diabetes (T2D) increases the risk of developing AD, and several postmortem analyses have found evidence of insulin resistance in the AD brain. Thus, insulin-based therapies have emerged as potential strategies to slow cognitive decline in AD. The main methods for targeting insulin to date have been intravenous insulin infusion, intranasal insulin administration, and use of insulin sensitizers. These methods have elicited variable results regarding improvement in cognitive function. This review will discuss the rationale for targeting insulin signaling to improve cognitive function in AD, the results of clinical studies that have targeted insulin signaling, and what these results mean for future studies of the role of insulin-based therapies for AD. © Springer Science+Business Media, LLC 2012.