Case Report: Familial Gastric Cancer and Chordoma in the Same Family

Gastric cancers are the second most common malignancy in the world and represent a major burden to all societies even though the incidence of disease is decreasing in the industrialized world. The aetiology of the disease is complex and is believed to be primarily due to environmental factors but a small proportion of cases are recognised as being associated with genetic factors. Two inherited forms of stomach cancer have been identified, one which is associated with familial clusterings of stomach cancer and the other being a subgroup of families that belong to hereditary non polyposis colorectal cancer (or Lynch syndrome). In this report we present a small nuclear family which is unusual in that there is a clustering of malignancy which includes stomach cancer, colorectal cancer and chordoma. Genetic analysis failed to reveal any causative mutation in genes associated with HNPCC or in E-cadherin. Together, the clinical picture in this family may indicate that other genetic factors are behind this family's clustering of malignancy

Neuropsychological Testing of Astronauts

The Spaceflight Cognitive Assessment Tool for Windows (WinSCAT) is a computer program that administers a battery of five timed neuro-cognitive tests. WinSCAT was developed to give astronauts an objective and automated means of assessing their cognitive functioning during space flight, as compared with their own baseline performances measured during similar prior testing on the ground. WinSCAT is also intended for use by flight surgeons to assess cognitive impairment after exposure of astronauts to such cognitive assaults as head trauma, decompression sickness, and exposure to toxic gas. The tests were selected from among a group of tests, denoted the Automated Neuropsychological Assessment Metrics, that were created by the United States Navy and Army for use in evaluating the cognitive impairment of military personnel who have been subjected to medication or are suspected to have sustained brain injuries. These tests have been validated in a variety of clinical settings and are now in the public domain. The tests are presented in a Microsoft Windows shell that facilitates administration and enables immediate reporting of test scores in numerical and graphical forms

PHARMACOVIGILANCE AND ADVERSE DRUG REACTION REPORTING PRACTICES AMONG GHANAIAN HEALTHCARE PROFESSIONALS

Background - Under-reporting of adverse drug reactions (ADRs) is a challenging medication safety problem globally. Even though ADRs are associated with significant morbidity and mortality, poor reporting among healthcare professionals (HCPs) persists, particularly in resource-limited settings. This study aimed to explore HCP experiences and factors influencing ADR reporting in the Ghanaian hospital setting. Methods - A concurrent mixed methods design was undertaken using face-to-face semi-structured qualitative interviews, focus groups and a survey. Nursing, pharmacy and medical staff were sampled using a stratified random sample from five hospitals in Tamale, Ghana coupled with purposive sampling for interviews. Survey data were analysed descriptively using SPSS and in-depth interviews and focus group discussions analysed using a six-stage thematic analysis using NVivo. Findings - 386 HCPs (86% response rate) participated in the survey. Pharmacovigilance (PV) knowledge was low (19%) with the majority being unaware of the national PV centre (68%) and basic information on reporting forms (65%). Pharmacy staff were however more knowledgeable compared to nursing and medical staff. Only 13% of HCPs reported to have observed an ADR at least once in a year and another 14% had completed a form. The majority (92%) of HCPs agreed that patient safety could improve if they reported ADRs and disagreed that litigation (82%) and lethargy (81%) were a hindrance. Pharmacists were perceived to have a key ADR reporting role. Use of verbal reporting was perceived to reduce ADR reporting formally along with complex interrelated system and human factors, such as lack of forms, inadequate infrastructure, stakeholder issues, uncertainty about reporting responsibilities, poor interpersonal relations, perceive patient attitudes, bureaucracies, fear of wrongdoing and blame. Conclusions – This study suggests that ADR reporting is low and often informal in the Ghanaian hospital setting but enhancing the role of pharmacists may be important in improving ADR reporting, as well as increasing HCP awareness through training – particularly for non-pharmacy staff - and logistical changes such as electronic ADR reporting

The Economic History of Denton County, Texas, 1900-1950

"In the first fifty years of the twentieth century, Denton County's chief asset was the fertility of its land. Today the county's main asset is still its land but for a different reason. As industry decentralizes, as the city populace searches for new areas of settlement, as the county's educational institutions expand, as investors look for new tracts of land, as builders construct large interstate highways, and as digging machines create lakes and recreational areas, the principal asset of the county becomes the non-agrarian utility of its land. Accompanying this land value shift has been an occupational change."-- leaf 103

A History of the Upper Guinea Coast, 1545-1800

This thesis is concerned with the relatively small sectionof the West African coast between the Gambia and Cape Mount, It seeks to reconstruct a picture of that society in the mid-sixteenth century, while it was still free of profound European influence. Such a picture provides the indispensable basis for analysing the impact of external forces on the narrow coastal strip, being used to embrace not only the Europeans but also influences from the hinterland and adjacent coastal areas.In 1545 Sierra Leone (the southern portion of the UpperGuinea Coast) was subjected to invasions from Africans who werecalled 'Manes’. This is the starting point of the study of theexternal forces (Ch.Il), and the purely African influences aretreated once more in Ch. IX. However, it is the presence of thePortuguese (Ch.IIl) and other European traders, which is the external factor most in evidence; and the European association with the Upper Guinea Coast was based largely on the development of the Atlantic slave trade. This latter topic is treated in Chs. IV and X, while Ch. VI; deals with African products other than slaves. European rivalries as such constitute a very minor theme (as treated in Ch. V), for the aim has been to portray European activity in this region only in relationship to the African rulers, African peoples and African polities. Owing to the great differences in European and African culture, and owing to the potency and viciousness of the Atlantic slave trade, the Afro European relationship incorporated violent contradictions, which resolved themselves to the detriment of the society of the Upper Guinea Coast, By 1800, the littoral society was overwhelmed both from the landward and the seaward side by forces set in motion by the Atlantic slave trade

Selecting and Testing Cryptogam Species for Use in Wetland Delineation in Alaska

To support the determination of hydrophytic vegetation in wetland delineations in Alaska, USA, a series of tests were conducted to develop a group of “test positive” species to be used in a “cryptogam indicator.” In 2004, non-vascular cryptogam species (bryophytes, lichens, and fungi) from Interior and South-Central Alaska in the vicinities of Fairbanks and Anchorage were collected at a series of ten 50 × 50 cm plots along two 30 m transects in each of six upland and five wetland sites. Nineteen moss and liverwort species were selected from 86 species surveyed to test for wetland fidelity. In 2005, a plot-based analysis of frequency and cover data yielded a revised list of 17 bryophyte species that were specific to wetland communities dominated by black spruce, Picea mariana (P. Mill.) B.S.P. Fungi and lichens were found to be inadequate wetland indicators in the sampled locations because the lichen species were sparsely distributed and the fungi were too ephemeral. The cryptogam indicator was thus restricted to bryophytes. Also in 2005, bryophytes were analyzed for their presence on microtopographic positions within the landscape, including tops of hummocks and hollows at the bases of hummocks. Upland bryophyte species were found on hummock tops inside the wetland boundary, but were not abundant in the hollows (p < 0.05). The fidelity of the species selected for use in the cryptogam indicator was tested. It was determined that if more than 50% of all bryophyte cover present in hollows is composed of one or more of the 17 wetland bryophytes tested in 2005, then vascular vegetation can be considered to be hydrophytic (p < 0.001).Afin d’étayer la présence de végétation hydrophytique dans les délimitations de zones humides de l’Alaska, aux États-Unis, une série de tests a été effectuée dans le but d’aboutir à un groupe d’espèces « de test positives » à utiliser avec un « indicateur de sporophyte ». En 2004, des espèces de sporophytes non vasculaires (bryophytes, lichens et champignons) de l’intérieur et du centre-sud de l’Alaska, aux environs de Fairbanks et d’Anchorage, ont été recueillies à une série de dix parcelles de 50 sur 50 cm le long de deux transects de 30 m dans chacun de six sites montagnards et de cinq sites humides. Dix-neuf espèces de mousse et d’hépatiques ont été choisies à partir de 86 espèces prélevées dans le but d’en déterminer la fidélité aux zones humides. En 2005, une analyse de fréquence de parcelles et des données de couverture ont permis d’obtenir la liste révisée de 17 espèces de bryophytes propres aux zones humides dominées par l’épinette noire, Picea mariana (P. Mill.) B.S.P. Nous avons constaté que les champignons et les lichens étaient des indicateurs de zones humides inadéquats aux sites échantillonnés parce que les espèces de lichen étaient réparties maigrement et que les champignons étaient trop éphémères. Par conséquent, l’indicateur de sporophytes a été restreint aux bryophytes. Également en 2005, nous avons analysé les bryophytes afin d’en déterminer la présence à des positions microtopographiques du paysage, ce qui comprenait le sommet de hummocks et les creux à la base de hummocks. Des espèces de bryophytes montagnardes ont été décelées aux sommets de hummocks à l’intérieur de la limite des zones humides, mais celles-ci n’abondaient pas dans les creux (p < 0.05). La fidélité des espèces choisies afin d’être utilisées dans l’indicateur de sporophytes a été testée. Nous avons déterminé que si plus de 50 % de toute la couverture de bryophyte présente dans les creux est composée de l’une ou plusieurs des 17 bryophytes de zones humides testées en 2005, la végétation vasculaire peut alors être considérée comme hydrophytique (p < 0,001)

Association of Long Runs of Homozygosity With Alzheimer Disease Among African American Individuals

IMPORTANCE: Mutations in known causal Alzheimer disease (AD) genes account for only 1% to 3% of patients and almost all are dominantly inherited. Recessive inheritance of complex phenotypes can be linked to long (>1-megabase [Mb]) runs of homozygosity (ROHs) detectable by single-nucleotide polymorphism (SNP) arrays. OBJECTIVE: To evaluate the association between ROHs and AD in an African American population known to have a risk for AD up to 3 times higher than white individuals. DESIGN, SETTING, AND PARTICIPANTS: Case-control study of a large African American data set previously genotyped on different genome-wide SNP arrays conducted from December 2013 to January 2015. Global and locus-based ROH measurements were analyzed using raw or imputed genotype data. We studied the raw genotypes from 2 case-control subsets grouped based on SNP array: Alzheimer's Disease Genetics Consortium data set (871 cases and 1620 control individuals) and Chicago Health and Aging Project-Indianapolis Ibadan Dementia Study data set (279 cases and 1367 control individuals). We then examined the entire data set using imputed genotypes from 1917 cases and 3858 control individuals. MAIN OUTCOMES AND MEASURES: The ROHs larger than 1 Mb, 2 Mb, or 3 Mb were investigated separately for global burden evaluation, consensus regions, and gene-based analyses. RESULTS: The African American cohort had a low degree of inbreeding (F ~ 0.006). In the Alzheimer's Disease Genetics Consortium data set, we detected a significantly higher proportion of cases with ROHs greater than 2 Mb (P = .004) or greater than 3 Mb (P = .02), as well as a significant 114-kilobase consensus region on chr4q31.3 (empirical P value 2 = .04; ROHs >2 Mb). In the Chicago Health and Aging Project-Indianapolis Ibadan Dementia Study data set, we identified a significant 202-kilobase consensus region on Chr15q24.1 (empirical P value 2 = .02; ROHs >1 Mb) and a cluster of 13 significant genes on Chr3p21.31 (empirical P value 2 = .03; ROHs >3 Mb). A total of 43 of 49 nominally significant genes common for both data sets also mapped to Chr3p21.31. Analyses of imputed SNP data from the entire data set confirmed the association of AD with global ROH measurements (12.38 ROHs >1 Mb in cases vs 12.11 in controls; 2.986 Mb average size of ROHs >2 Mb in cases vs 2.889 Mb in controls; and 22% of cases with ROHs >3 Mb vs 19% of controls) and a gene-cluster on Chr3p21.31 (empirical P value 2 = .006-.04; ROHs >3 Mb). Also, we detected a significant association between AD and CLDN17 (empirical P value 2 = .01; ROHs >1 Mb), encoding a protein from the Claudin family, members of which were previously suggested as AD biomarkers. CONCLUSIONS AND RELEVANCE: To our knowledge, we discovered the first evidence of increased burden of ROHs among patients with AD from an outbred African American population, which could reflect either the cumulative effect of multiple ROHs to AD or the contribution of specific loci harboring recessive mutations and risk haplotypes in a subset of patients. Sequencing is required to uncover AD variants in these individuals