Healthcare system priorities for successful integration of genomics: An Australian focus

This paper examines key considerations for the successful integration of genomic technologies into healthcare systems. All healthcare systems strive to introduce new technologies that are effective and affordable, but genomics offers particular challenges, given the rapid evolution of the technology. In this context we frame internationally relevant discussion points relating to effective and sustainable implementation of genomic testing within the strategic priority areas of the recently endorsed Australian National Health Genomics Policy Framework. The priority areas are services, data, workforce, finances, and person-centred care. In addition, we outline recommendations from a government perspective through the lens of the Australian health system, and argue that resources should be allocated not to just genomic testing alone, but across the five strategic priority areas for full effectiveness

Stationary solutions of the one-dimensional nonlinear Schroedinger equation: I. Case of repulsive nonlinearity

All stationary solutions to the one-dimensional nonlinear Schroedinger equation under box and periodic boundary conditions are presented in analytic form. We consider the case of repulsive nonlinearity; in a companion paper we treat the attractive case. Our solutions take the form of stationary trains of dark or grey density-notch solitons. Real stationary states are in one-to-one correspondence with those of the linear Schr\"odinger equation. Complex stationary states are uniquely nonlinear, nodeless, and symmetry-breaking. Our solutions apply to many physical contexts, including the Bose-Einstein condensate and optical pulses in fibers.Comment: 11 pages, 7 figures -- revised versio

Documenting the Establishment, Spread, and Severity of Phyllachora maydis on Corn, in the United States

Tar spot on corn, caused by the fungus (Phyllachora maydis Maubl. [Phyllachorales: Phyllachoraceae]), is an emerging disease in the United States. In 2018 and 2019, significant but localized epidemics of tar spot occurred across the major corn producing region of the Midwest. After being first detected in 2015, tar spot was detected in 135 and 139 counties where the disease was not previously detected in 2018 and 2019, respectively, and is now established across 310 counties across the United Sates. Foliage with signs (stromata) of P. maydis and symptoms of tar spot were collected from 128 fields in 2018 and 191 fields in 2019, across seven states. Samples were assessed for severity of fungal stromata (percent leaf area covered with stromata) on foliage and the incidence of fisheye lesions (proportion of lesions with fisheye symptoms) associated with fungal stromata. Stromatal severity on samples in 2018 ranged from 0.5 to 67% and incidence of fisheye lesions ranged from 0 to 12%, whereas in 2019, stromatal severity ranged from 0.1 to 35% and incidence of fisheye lesions ranged from 0 to 80%, with 95% of samples presenting less than 6% incidence of fisheye lesions. Tar spot has spread substantially from where it was first reported in the United States. Collaborative efforts to monitor the spread and educate clientele on management are essential as this disease spreads into new areas

Clinical and epidemiological features of acute zika virus infections in León, Nicaragua

The American Zika virus (ZIKV) epidemic has highlighted the need to gain a better understanding of this emerging virus. The goal of this study was to describe the clinical symptoms, laboratory findings, and risk factors for symptomatic ZIKV infection in an area with ongoing transmission of other arboviral infections. We recruited patients at least 2 years of age seeking care at public health centers in León, Nicaragua, between January 2016 and August 2017, for fever, maculopapular rash, and/or nonsuppurative conjunctivitis with a duration of less than 1 week. A laboratory diagnosis of ZIKV was established using a combination of molecular and serological tests. Clinical and laboratory findings and potential risk factors were compared between participants with and without acute ZIKV infection. Fifty-eight (26%) of the 225 participants included in the analysis were found to have acute ZIKV infection. Pregnancy and reports of previous arboviral infection were associated with a higher risk of ZIKV infection. Rash, conjunctivitis, sore throat, and lower absolute neutrophil counts were associated with acute ZIKV infection. The clinical characteristics and risk factors identified were consistent with those identified by previous studies; however, we found sore throat to be a feature of ZIKV infection. We also found that neutrophil counts were lower in ZIKV-infected subjects. These clinical symptoms and laboratory data may help clinicians suspect ZIKV infection during future outbreaks

Three siblings with Asperger syndrome: A family case study

Reports of multiple incidence of Asperger syndrome have suggested links between Asperger syndrome and autism. In this case study, we describe three siblings with Asperger syndrome based on the ICD-10 criteria. There was no family history of mental retardation or of autism. We propose that in some families, Asperger syndrome may occur as a distinct clinical entity and show no overlap with autism. Les publications sur l'incidence multiple du Syndrome d'Asperger ont suggéré des liens entre ce syndrome et l'autisme. Dans cette étude, nous décrivons 3 membres d'une même fratrie avec un Syndrome d'Asperger répondant aux critères d'l'ICD-10. Il n'yavait pas dans l'histoire familiale de retard mental ni d'autisme. Nous proposons que dans certaines familles le Syndrome d'Asperger peut survenir comme entité clinique distincte sand chevauchement avec l'autisme. Berichte über multiples Auftreten des Asperger-Syndroms haben Zusammenhänge zwischen dem Asperger-Syndrom und Autismus nahegelegt. In diesem Fallbericht beschreiben wir drei Geschwister mit einem Asperger-Syndrom (ICD-10-Kriterien). Die Familienanamnese im Hinblick auf geistige Behinderung oder Autismus war unauffällig. Wir schlagen vor, daß in einigen Familien das Asperger-Syndrom als eine eigenständige klinische Entität ohne Überlappung zum Autismus auftreten kann.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41755/1/787_2005_Article_BF02098829.pd

The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

Renal cell carcinoma(RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival

Genomic testing for human health and disease across the life cycle: Applications and ethical, legal, and social challenges

The expanding use of genomic technologies encompasses all phases of life, from the embryo to the elderly, and even the posthumous phase. In this paper, we present the spectrum of genomic healthcare applications, and describe their scope and challenges at different stages of the life cycle. The integration of genomic technology into healthcare presents unique ethical issues that challenge traditional aspects of healthcare delivery. These challenges include the different definitions of utility as applied to genomic information; the particular characteristics of genetic data that influence how it might be protected, used and shared; and the difficulties applying existing models of informed consent, and how new consent models might be needed

Interferon-gamma signaling inhibition ameliorates angiotensin II-induced cardiac damage

Angiotensin (Ang) II induces vascular injury in part by activating innate and adaptive immunity; however, the mechanisms are unclear. We investigated the role of interferon (IFN)-{gamma} and interleukin (IL)-23 signaling. We infused Ang II into IFN-{gamma} receptor (IFN-{gamma}R) knockout mice and wild-type controls, as well as into mice treated with neutralizing antibodies against IL-23 receptor and IL-17A. Ang II-treated IFN-{gamma}R knockout mice exhibited reduced cardiac hypertrophy, reduced cardiac macrophage and T-cell infiltration, less fibrosis, and less arrhythmogenic electric remodeling independent of blood pressure changes. In contrast, IL-23 receptor antibody treatment did not reduce cardiac hypertrophy, fibrosis, or electric remodeling despite mildly reduced inflammation. IL-17A antibody treatment behaved similarly. In the kidney, IFN-{gamma}R deficiency reduced inflammation and tubulointerstitial damage and improved glomerular filtration rate. Nonetheless, albuminuria was increased compared with Ang II-treated wild-type controls. The glomeruli of Ang II-treated IFN-{gamma}R knockout mice exhibited fewer podocytes, less nephrin and synaptopodin staining, and impaired podocyte autophagy. Thus, IFN-{gamma} blockade, but not IL-23 receptor antibody treatment, protects from Ang II-induced cardiac damage and electric remodeling. In the kidney, IFN-{gamma} signaling acts in a cell type-specific manner. Glomerular filtration rate is preserved in the absence of the IFN-{gamma}R, whereas podocytes may require the IFN-{gamma}R in the presence of Ang II for normal integrity and function