Ecological Health: Ethics as the Starting Place.

When considering the health and flourishing of humans and human communities, we cannot ignore that we are constitutively bound to the health of ecosystems of which we are a part. As such, global climate change is a central concern for health care and bioethics. Addressing the complex and interrelated realities bound up with global climate change requires a multifaceted and integrated approach from diverse academic and professional disciplines and perspectives.

Taxonomy of Middle Miocene foraminifera from the northern Namibian continental shelf.

Middle Miocene foraminifera from the northern Namibian outer continental shelf are indicators of a period prior to the initiation of the Benguela Upwelling System (BUS). This study provides an update to the occurrence and taxonomy of Miocene foraminifera from the continental margin of Namibia. The taxonomy of 51 benthic and 12 planktic foraminiferal species from the northern Namibian shelf are discussed, their stratigraphic significance given, and their ecological preferences and regional distribution summarised within this study.

A systematic review of peer-reviewed literature authored by medical professionals regarding US biomedicine's role in responding to climate change.

Extant literature illustrates a substantive impact on human health because of climate change. Despite this, discussions of the ethical and policymaking role of US health care's response to this problem are underdeveloped within peer-reviewed literature indexed in core medical databases. We conducted a systematic literature review in August 2017 at Vanderbilt University Medical Center of the following medical, business and policy databases to examine the state of inquiry on this topic: PubMed, CINAHL, PsychINFO, JAMA Network, Health Affairs, Business Source Complete, Greylit.

Variation in palaeo-shorelines explains contemporary population genetic patterns of rocky shore species.

Processes driving and maintaining disjunct genetic populations in marine systems are poorly understood, owing to a lack of evidence of hard barriers that could have shaped patterns of extant population structure. Here, we map two genetically divergent lineages of an obligate rocky shore fish, Clinus cottoides, and model sea-level change during the last 110 000 years to provide the first evidence of a vicariant event along the southern coastline of Africa. Results reveal that lowered sea levels during glacial periods drastically reduced rocky intertidal habitat, which may have isolated populations in two refugia for at least 40 000 years.

Comparative analysis of IRF6 variants in families with Van der Woude syndrome and popliteal pterygium syndrome using public whole-exome databases.

Purpose: Mutations in the transcription factor IRF6 cause allelic autosomal dominant clefting syndromes, Van der Woude syndrome, and popliteal pterygium syndrome. We compared the distribution of IRF6 coding and splice-site mutations from 549 families with Van der Woude syndrome or popliteal pterygium syndrome with that of variants from the 1000 Genomes and National Heart, Lung, and Blood Institute Exome Sequencing Projects.

Methods: We compiled all published pathogenic IRF6 mutations and performed direct sequencing of IRF6 in families with Van der Woude syndrome or popliteal pterygium syndrome.

Exon-level array CGH in a large clinical cohort demonstrates increased sensitivity of diagnostic testing for Mendelian disorders.

Purpose: Mendelian disorders are most commonly caused by mutations identifiable by DNA sequencing. Exonic deletions and duplications can go undetected by sequencing, and their frequency in most Mendelian disorders is unknown.

Methods: We designed an array comparative genomic hybridization (CGH) test with probes in exonic regions of 589 genes.

An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities.

Purpose: Copy number variants have emerged as a major cause of human disease such as autism and intellectual disabilities. Because copy number variants are common in normal individuals, determining the functional and clinical significance of rare copy number variants in patients remains challenging. The adoption of whole-genome chromosomal microarray analysis as a first-tier diagnostic test for individuals with unexplained developmental disabilities provides a unique opportunity to obtain large copy number variant datasets generated through routine patient care.

Prevalence and nonrandom distribution of exonic mutations in interferon regulatory factor 6 in 307 families with Van der Woude syndrome and 37 families with popliteal pterygium syndrome.

Purpose: Interferon regulatory factor 6 encodes a member of the IRF family of transcription factors. Mutations in interferon regulatory factor 6 cause Van der Woude and popliteal pterygium syndrome, two related orofacial clefting disorders. Here, we compared and contrasted the frequency and distribution of exonic mutations in interferon regulatory factor 6 between two large geographically distinct collections of families with Van der Woude and between one collection of families with popliteal pterygium syndrome.

Oligonucleotide array CGH studies in myeloproliferative neoplasms: comparison with JAK2V617F mutational status and conventional chromosome analysis.

Comparative genomic hybridization (CGH), using oligo arrays with either 44,000 or 105,000 oligonucleotides, was performed on granulocyte-derived DNA from 71 patients with BCR-ABL-negative classic myeloproliferative neoplasms (MPNs): 32 primary myelofibrosis (PMF), 26 polycythemia vera (PV) and 13 essential thrombocythemia (ET). Copy number changes (CNCs) were detected in 44%, 35%, and 15% of the cases with PMF, PV and ET, respectively. In ET and PMF, CNCs were more frequently detected in the presence of JAK2V617F (50% vs.

Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis.

Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects approximately 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated.

Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris.

Ichthyosis vulgaris (OMIM 146700) is the most common inherited disorder of keratinization and one of the most frequent single-gene disorders in humans. The most widely cited incidence figure is 1 in 250 based on a survey of 6,051 healthy English schoolchildren. We have identified homozygous or compound heterozygous mutations R501X and 2282del4 in the gene encoding filaggrin (FLG) as the cause of moderate or severe ichthyosis vulgaris in 15 kindreds.

Genetic heterogeneity in erythrokeratodermia variabilis: novel mutations in the connexin gene GJB4 (Cx30.3) and genotype-phenotype correlations.

Erythrokeratodermia variabilis is an autosomal dominant genodermatosis characterized by persistent plaque-like or generalized hyperkeratosis and transient red patches of variable size, shape, and location. The disorder maps to a cluster of connexin genes on chromosome 1p34-p35.1 and, in a subset of families, results from mutations in the gene GJB3 encoding the gap junction protein connexin-31 (Cx31).

Mapping of the associated phenotype of an absent granular layer in ichthyosis vulgaris to the epidermal differentiation complex on chromosome 1.

Ichthyosis vulgaris (IV) is a mild to severe scaling disorder of uncertain etiology estimated to affect as many as 1 : 250 in the population. Family studies have shown that in many cases IV follows an autosomal dominant inheritance pattern, but gene mapping studies have not been reported. To investigate the genetic basis for inherited IV, we have performed gene linkage studies in two multigenerational families where affected individuals have clinical features of IV but distinct histological features.

Two cases of primarily palmoplantar keratoderma associated with novel mutations in keratin 1.

Mutations in keratin 1 were initially described in the classical form of bullous congenital ichthyosiform erythroderma (also known as epidermolytic hyperkeratosis). More recently the range of phenotypes associated with mutations in this gene has been extended to include annular ichthyosiform erythroderma and mild epidermolytic palmoplantar keratoderma. Here we present two novel mutations in the keratin 1 gene (KRT1): a 5' donor splice site mutation in exon 1 (591 + 2T > A) that predicts a 22 amino acid in-frame deletion in the keratin 1 1A domain; and an in-frame deletion in exon 7 (1376del24) that predicts a foreshortened 2B coiled-coil domain of keratin 1.