The Risk of Paradoxical Embolism (RoPE) Study: initial description of the completed database

BACKGROUND: Detecting a benefit from closure of patent foramen ovale in patients with cryptogenic stroke is hampered by low rates of stroke recurrence and uncertainty about the causal role of patent foramen ovale in the index event. A method to predict patent foramen ovale-attributable recurrence risk is needed. However, individual databases generally have too few stroke recurrences to support risk modeling. Prior studies of this population have been limited by low statistical power for examining factors related to recurrence. AIMS: The aim of this study was to develop a database to support modeling of patent foramen ovale-attributable recurrence risk by combining extant data sets. METHODS: We identified investigators with extant databases including subjects with cryptogenic stroke investigated for patent foramen ovale, determined the availability and characteristics of data in each database, collaboratively specified the variables to be included in the Risk of Paradoxical Embolism database, harmonized the variables across databases, and collected new primary data when necessary and feasible. RESULTS: The Risk of Paradoxical Embolism database has individual clinical, radiologic, and echocardiographic data from 12 component databases, including subjects with cryptogenic stroke both with (n = 1925) and without (n = 1749) patent foramen ovale. In the patent foramen ovale subjects, a total of 381 outcomes (stroke, transient ischemic attack, death) occurred (median follow-up 2·2 years). While there were substantial variations in data collection between studies, there was sufficient overlap to define a common set of variables suitable for risk modeling. CONCLUSION: While individual studies are inadequate for modeling patent foramen ovale-attributable recurrence risk, collaboration between investigators has yielded a database with sufficient power to identify those patients at highest risk for a patent foramen ovale-related stroke recurrence who may have the greatest potential benefit from patent foramen ovale closure.

Insights into the timing of repeated testing after treatment for Chlamydia trachomatis: data and modelling study

The objective of this study was to determine the optimal time interval for a repeated Chlamydia trachomatis (chlamydia) test.

The Bucknell Community College Scholarship Program: a Documentary as a Performative Social Science

Reviews Bucknell participation with the Jack Kent Cooke Foundation (a non-profit foundation with a mission to “help under-resourced students of exceptional promise reach their full potential through education".

Perceptions of Social Mobility in Community College Scholars at Bucknell University

While national leaders have joined the discussion more recently, scholars in the fields of education, psychology, and sociology, have been exploring the ways in which students? socioeconomic background affects the outcomes they experience as a result of their education (Lareau, Unequal Childhoods: Class, Race, and Family Life, 2003).Furthermore, the role played by the education system in creating or diminishing socioeconomic disparity has also been studied in depth (Bourdieu, 1977; Boudon, 1977). However, the journeys of students from low-income families that begin their education at community colleges and continue it, through careful planning or chance, at elite four-year institutions, has not been the subject of much attention. This thesis explores these students? perceptions of social mobility as they have been shaped by their experiences so far in life. This includes the exploration of changes in their perceptions as the contexts for their lives have been changed. Quantitative analysis of survey results and qualitative analysis of participant interviews serve as the data set for this study. The implications ofthe findings for student affairs practitioners are also explored.

Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease

Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.

Romany Families in Romania: Intelligence and Personality of Children Cross-cultural and Specific Problems of Development

Psychogenetic research has emphasised the influence of social factors on a child's intellectual development. In her work, Ms. Dumitrascu examines two such factors; family size and order of birth. However, since these formal parameters tend to be unstable, other more informal factors should be taken into consideration. Of these, perhaps the most interesting is the "style" of parental education, which Ms. Dumitrascu regards as an expression of national traditions at the family level. This educational style is culture dependent. Only a comparative, cross-cultural study can reveal the real mechanism through which educational style influences the development of a child's intellect and personality. Ms. Dumitrascu conducted an experimental cross-cultural study aimed at examining the effects of the family environment on a child's intellectual development. Three distinct populations were involved in her investigation, each having quite a distinct status in their geographical area; Romanians, Romanies (Gypsies) from Romania, and Russians from the Republic of Moldova. She presented her research in the form of a series of articles written in English totalling 85 pages, and also on disc. A significant difference was revealed between the intelligence of a child living in a large family, and that of a child with no brothers or sisters. In the case of Romany children, the gap is remarkably large. Ms. Dumitrascu concludes that the simultaneous action of several negative factors (low socio-economic status, large family size, socio-cultural isolation of a population) may delay child development. Subjected to such a precarious environment, Romany children do not seek self-realisation, but rather struggle to survive the hardship. Most of them remain out of civilisation. Unfortunately, adult Romanies seldom express any concern regarding their children's successful social integration. The school as main socialisation tool has no value for most parents. Ms. Dumitrascu argues the need for a major effort aimed at helping Romany's social integration. She hopes this project will be of some help for psychologists, social workers, teachers, and all those who are interested in the integration into society of minority groups.

Sonographic Assessment of the Umbilical Cord

The umbilical cord is not an inert structure, suspended between the fetus and placenta, but it plays an active role and it is involved in several processes afflicting the feto-placental unit. Its study has to be regarding not only its morphology and morphometry, and the impendance of blood flow by Doppler waveform analysis, but it includes also an analysis of the coiling type and the amount of the Wharton Jelly. The umbilical cord has been considered like an important and huge source of informations, useful to assess the well-being of the fetus and the outcome of pregnancy. The standardization of ultrasound techniques is the first step to speak the same language and make the study of this structure a fundamental part of well-being fetus assessment. This article is carefully focused on morphologic, morphometric and functional ultrasound examination of umbilical cord and suggests that any anomaly detected should provide an indication for an intense fetal follow-up, useful for early helpful therapy, preventing serious complication for the pregnancy.

Late-onset manifestation of antenatal Bartter syndrome as a result of residual function of the mutated renal Na+-K+-2Cl- co-transporter

Genetic defects of the Na+-K+-2Cl- (NKCC2) sodium potassium chloride co-transporter result in severe, prenatal-onset renal salt wasting accompanied by polyhydramnios, prematurity, and life-threatening hypovolemia of the neonate (antenatal Bartter syndrome or hyperprostaglandin E syndrome). Herein are described two brothers who presented with hyperuricemia, mild metabolic alkalosis, low serum potassium levels, and bilateral medullary nephrocalcinosis at the ages of 13 and 15 yr. Impaired function of sodium chloride reabsorption along the thick ascending limb of Henle's loop was deduced from a reduced increase in diuresis and urinary chloride excretion upon application of furosemide. Molecular genetic analysis revealed that the brothers were compound heterozygotes for mutations in the SLC12A1 gene coding for the NKCC2 co-transporter. Functional analysis of the mutated rat NKCC2 protein by tracer-flux assays after heterologous expression in Xenopus oocytes revealed significant residual transport activity of the NKCC2 p.F177Y mutant construct in contrast to no activity of the NKCC2-D918fs frameshift mutant construct. However, coexpression of the two mutants was not significantly different from that of NKCC2-F177Y alone or wild type. Membrane expression of NKCC2-F177Y as determined by luminometric surface quantification was not significantly different from wild-type protein, pointing to an intrinsic partial transport defect caused by the p.F177Y mutation. The partial function of NKCC2-F177Y, which is not negatively affected by NKCC2-D918fs, therefore explains a mild and late-onset phenotype and for the first time establishes a mild phenotype-associated SLC12A1 gene mutation.

Becker muscular dystrophy with marked divergence between clinical and molecular genetic findings: case series

Both Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are caused by mutations of the X-linked dystrophin gene. BMD patients are less affected clinically than DMD patients. We present five patients with a diagnosis of BMD. First, two identical twins, with a deletion of exon 48 of the dystrophin gene, who experienced prominent muscle cramps from the age of three. The histopathological examination of muscle biopsies of these two twins revealed only very slight muscle fiber alterations. Second, two brothers who displayed marked, unusual intrafamilial variability of the clinical picture as well as showing a new point mutation in the dystrophin gene. And finally, a fifth boy who displayed a new point mutation in the dystrophin gene. Although he was clinically asymptomatic at the age of 15 and muscle biopsy only showed very minor myopathic signs, serum Creatine Kinase (CK) levels had been considerably elevated for years. Taken together, these cases add to the spectrum of marked discrepancies in clinical, histopathological and molecular genetic findings in BMD.

Mitochondrial neurogastrointestinal encephalomyopathy in three siblings: clinical, genetic and neuroradiological features

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder in which a nuclear mutation of the thymidine phosphorylase (TP) gene causes mitochondrial genomic dysfunction. Patients suffer from gastrointestinal dysmotility, cachexia, ptosis, external ophthalmoparesis, myopathy and polyneuropathy. Magnetic resonance imaging (MRI) shows leukoencephalopathy. We describe clinical, genetic and neuroradiological features of three brothers affected with MNGIE. Clinical examination, laboratory analyses, MRI and magnetic resonance spectroscopy (MRS) of the brain, and genetic analysis have been performed in all six members of the family with the three patients with MNGIE. Two of them are monozygous twins. They all suffered from gastrointestinal dysmotility, cachexia, ophthalmoplegia, muscular atrophies, and polyneuropathy. Urinary thymidine was elevated in the patients related to the severity of clinical disease, and urinary thymidine (normally not detectable) was also found in a heterozygous carrier. Brain MRI showed leukoencephalopathy in all patients; however, their cognitive functioning was normal. Brain MRS demonstrated reduced N-acetylaspartate and choline in severely affected areas. MRI of heterozygous carriers was normal. A new mutation (T92N) in the TP gene was identified. Urinary thymidine is for the first time reported to be detectable in a heterozygous carrier. MRS findings indicate loss of neurons, axons, and glial cells in patients with MNGIE, but not in heterozygous carriers.

Pseudodominant Inheritance of Goitrous Congenital Hypothyroidism Caused by TPO Mutations: Molecular and in Silico Studies

Context and Objective: Most cases of goitrous congenital hypothyroidism (CH) from thyroid dyshormonogenesis 1) follow a recessive mode of inheritance and 2) are due to mutations in the thyroid peroxidase gene (TPO). We report the genetic mechanism underlying the apparently dominant inheritance of goitrous CH in a nonconsanguineous family of French Canadian origin. Design, Setting, and Participants: Two brothers identified by newborn TSH screening had severe hypothyroidism and a goiter with increased (99m)Tc uptake. The mother was euthyroid, but the father and two paternal uncles had also been diagnosed with goitrous CH. After having excluded PAX8 gene mutations, we hypothesized that the underlying defect could be TPO mutations. Results: Both compound heterozygous siblings had inherited a mutant TPO allele carried by their mother (c.1496delC; p.Pro499Argfs2X), and from their father, one brother had inherited a missense mutation (c.1978C-->G; p.Gln660Glu) and the other an insertion (c.1955insT; p.Phe653Valfs15X). The thyroid gland of one uncle who is a compound heterozygote for TPO mutations (p.Phe653Valfs15X/p.Gln660Glu) was removed because of concurrent multiple endocrine neoplasia type 2A. Immunohistochemistry revealed normal TPO staining, implying that Gln660Glu TPO is expressed properly. Modeling of this mutant in silico suggests that its three-dimensional structure is conserved, whereas the electrostatic binding energy between the Gln660Glu TPO and its heme group becomes repulsive. Conclusion: We report a pedigree presenting with pseudodominant goitrous CH due to segregation of three different TPO mutations. Although goitrous CH generally follows a recessive mode of inheritance, the high frequency of TPO mutations carriers may lead to pseudodominant inheritance.

"Brethren upon the same level" : membership and class in Calumet's Masonic Lodge

The Keweenaw Peninsula of Upper Michigan was a ethnic conglomerate of cultures and ideas, with people attracted to the area by the mineral wealth found along the Copper Range. The center of copper mining from the mid 1860s to 1968 was in the vicinity of Calumet Township, home to the world-famous Calumet and Hecla Mining Company. The township depended on the mines and the company’s president Agassiz’s strove to make the area a “model community,” that included groups such as the Free and Accepted Masons. Men from myriad backgrounds arrived in Calumet from the British Isles, Germany, Finland, Eastern and Southern Europe and the Eastern United States. As in other communities from the time period these men formed common interest groups like Masonic Lodge 271, which received its charter in 1870. Gentlemen joined with merchants and craftsmen. They became “brethren upon the same level,” and were elevated to the status of Master Mason. This symbolic transformation within the Lodge removed the men from the “profane world” outside the sanctity of Masonry, and in the ritualistic transformation of the meeting they were reborn into Masonry’s sacred mysteries. Masonry acted as a means of moral guidance to men and gave them access to a larger social and economic community through a common connection of brotherhood. As the candidates moved through the three Blue Lodge degrees of Entered Apprentice, Fellowcraft, and Master Mason they saw each other as “brethren upon the same level” – all economic classes equal within the Masonic Lodge. To examine equality within Lodge 271, this study sorted workers into classes to allow a comparison of Lodge 271’s membership. Possibly a comparison between other lodges can be drawn from the membership. The Union Building in Calumet, MI will be examined for its role in the ritualistic transformation of Masonry as it housed Masonic activities and transformations. This transformation brought men into the lodge of brothers. While Masonry professed equality between members however, to what extent did the membership of the lodge reflect this between the brethren? To what extent did economic class determine who was made “brethren upon the same level? 1 Arthur Thurner, Calumet Copper and People: History of a Michigan Mining Community, 1864-1970 (Hancock, MI: Book Concern, 1974), 122.

Electrolytic Recovery of Copper and Zinc from Brass.

The reclamation of metals from scrap is becoming increasingly important in the metallurgical industry. Copper, because it does not corrode readily and is electronegative to most common metals, is peculiarly adapted to reclamation.

The Acropolitan - v. 3, no. 3

In this issue...Anderson Carlisle Club, Mines Smoker, Rotary and Exchange Club, Kiwanis Club, Forestry policies, Elbert Hubbard, Rosenstein Brothers