Providing the Missing Link: the Exposure Science Ontology ExO

Environmental health information resources lack exposure data required to translate molecular insights, elucidate environmental contributions to diseases, and assess human health and ecological risks. We report development of an Exposure Ontology, ExO, designed to address this information gap by facilitating centralization and integration of exposure data. Major concepts were defined and the ontology drafted and evaluated by a working group of exposure scientists and other ontology and database experts. The resulting major concepts forming the basis for the ontology are exposure stressor , exposure receptor , exposure event , and exposure outcome . Although design of the first version of ExO focused on human exposure to chemicals, we anticipate expansion by the scientific community to address exposures of human and ecological receptors to the full suite of environmental stressors. Like other widely used ontologies, ExO is intended to link exposure science and diverse environmental health disciplines including toxicology, epidemiology, disease surveillance, and epigenetics

Casting a wider net: Immunosurveillance by nonclassical MHC molecules

Most studies of T lymphocytes focus on recognition of classical major histocompatibility complex (MHC) class I or II molecules presenting oligopeptides, yet there are numerous variations and exceptions of biological significance based on recognition of a wide variety of nonclassical MHC molecules. These include αβ and γδ T cells that recognize different class Ib molecules (CD1, MR-1, HLA-E, G, F, et al.) that are nearly monomorphic within a given species. Collectively, these T cells can be considered “unconventional,” in part because they recognize lipids, metabolites, and modified peptides. Unlike classical MHC-specific cells, unconventional T cells generally exhibit limited T-cell antigen receptor (TCR) repertoires and often produce innate immune cell-like rapid effector responses. Exploiting this system in new generation vaccines for human immunodeficiency virus (HIV), tuberculosis (TB), other infectious agents, and cancer was the focus of a recent workshop, “Immune Surveillance by Non-classical MHC Molecules: Improving Diversity for Antigens,” sponsored by the National Institute of Allergy and Infectious Diseases. Here, we summarize salient points presented regarding the basic immunobiology of unconventional T cells, recent advances in methodologies to measure unconventional T-cell activity in diseases, and approaches to harness their considerable clinical potential

Longitudinal study of vascular remodeling in coronary arteries after heart transplantation

Cross-sectional studies by intravascular ultrasound (IVUS) in heart transplant recipients have suggested that vascular remodeling occurs in coronary arteries years after transplant. However, no reports describe vascular remodeling in the same cohort of patients studied prospectively using morphometric analysis (10 evenly spaced images obtained from a slow pullback from the left anterior descending coronary artery). Morphometric analysis better reflects total vessel anatomy compared with previously reported site (2 to 3 images) analysis. We reviewed 20 patients studied by IVUS at 2 months, 1 year, 2 years, and 3 years after heart transplant.Over time, the coronary artery luminal area decreased from baseline level of 12.0 mm(2) to a 3-year mark of 9.7 mm(2) (p = 0.02). Vessel shrinkage was seen in 16/20 patients. After an initial rise in intimal parameters (maximal intimal thickness, intimal index, and plaque area) from baseline to 1 year, we found a significant decrease in intimal parameters between Year 1 and Year 3 after transplant. For example, plaque area decreased from 2.05 mm(2) at 1 year post-transplant to 1.48 mm(2) by 3 years post-transplant (p = 0.05). In a majority of heart transplant patients, early intimal thickening in the first year post-transplant is accompanied by constrictive remodeling. Over the subsequent 2 years, further constrictive remodeling is seen despite a decrease in intimal area

Oral High-Dose Atorvastatin Treatment in Relapsing-Remitting Multiple Sclerosis

BACKGROUND:Recent data from animal models of multiple sclerosis (MS) and from a pilot study indicated a possible beneficial impact of statins on MS. METHODOLOGY/PRINCIPAL FINDINGS:Safety, tolerability and effects on disease activity of atorvastatin given alone or in combination with interferon-beta (IFN-beta) were assessed in a phase II open-label baseline-to-treatment trial in relapsing-remitting MS (RRMS). Patients with at least one gadolinium-enhancing lesion (CEL) at screening by magnetic resonance imaging (MRI) were eligible for the study. After a baseline period of 3 monthly MRI scans (months -2 to 0), patients followed a 9-month treatment period on 80 mg atorvastatin daily. The number of CEL in treatment months 6 to 9 compared to baseline served as the primary endpoint. Other MRI-based parameters as well as changes in clinical scores and immune responses served as secondary endpoints. Of 80 RRMS patients screened, 41 were included, among them 16 with IFN-beta comedication. The high dose of 80 mg atorvastatin was well tolerated in the majority of patients, regardless of IFN-beta comedication. Atorvastatin treatment led to a substantial reduction in the number and volume of CEL in two-sided multivariate analysis (p = 0.003 and p = 0.008). A trend towards a significant decrease in number and volume of CEL was also detected in patients with IFN-beta comedication (p = 0.060 and p = 0.062), in contrast to patients without IFN-beta comedication (p = 0.170 and p = 0.140). Immunological investigations showed no suppression in T cell response but a significant increase in IL-10 production. CONCLUSIONS/SIGNIFICANCE:Our data suggest that high-dose atorvastatin treatment in RRMS is safe and well tolerated. Moreover, MRI analysis indicates a possible beneficial effect of atorvastatin, alone or in combination with IFN-beta, on the development of new CEL. Thus, our findings provide a rationale for phase II/III trials, including combination of atorvastatin with already approved immunomodulatory therapy regimens. TRIAL REGISTRATION:ClinicalTrials.gov NCT00616187

Educational development between faculty and administration

This essay employs Identity Theory to explore the professional identities of educational developers, arguing that it is important to pay attention to the different saliences, or weights, that developers attach to the faculty and administrative sides of their identities

Fifteen years of research on oral–facial–digital syndromes: from 1 to 16 causal genes

Oral–facial–digital syndromes (OFDS) gather rare genetic disorders characterised by facial, oral and digital abnormalities associated with a wide range of additional features (polycystic kidney disease, cerebral malformations and several others) to delineate a growing list of OFDS subtypes. The most frequent, OFD type I, is caused by a heterozygous mutation in the OFD1 gene encoding a centrosomal protein. The wide clinical heterogeneity of OFDS suggests the involvement of other ciliary genes. For 15 years, we have aimed to identify the molecular bases of OFDS. This effort has been greatly helped by the recent development of whole-exome sequencing (WES). Here, we present all our published and unpublished results for WES in 24 cases with OFDS. We identified causal variants in five new genes (C2CD3, TMEM107, INTU, KIAA0753 and IFT57) and related the clinical spectrum of four genes in other ciliopathies (C5orf42, TMEM138, TMEM231 and WDPCP) to OFDS. Mutations were also detected in two genes previously implicated in OFDS. Functional studies revealed the involvement of centriole elongation, transition zone and intraflagellar transport defects in OFDS, thus characterising three ciliary protein modules: the complex KIAA0753-FOPNL-OFD1, a regulator of centriole elongation; the Meckel-Gruber syndrome module, a major component of the transition zone; and the CPLANE complex necessary for IFT-A assembly. OFDS now appear to be a distinct subgroup of ciliopathies with wide heterogeneity, which makes the initial classification obsolete. A clinical classification restricted to the three frequent/well-delineated subtypes could be proposed, and for patients who do not fit one of these three main subtypes, a further classification could be based on the genotype

Life Patterns, Personality Style and Self-Esteem in Gifted Family-Oriented and Career-Committed Women, 1969-1970

The data were collected during 1969 and 1970. The sample consisted of 81 intellectually gifted women, including 29 homemakers, 25 married professionals with children, and 27 single professionals. The homemakers were women who had graduated with distinction from a high-ranking, large midwestern state university between 1945 and 1955. Both groups of professional women were on the faculty of the university the homemakers had attended. The data collection instrument was a 41-page mailed, self-administered questionnaire. It included nine projective cues as well as numerous precoded and open-ended items addressing the following topics: early experiences; activities; attitudes; values; occupation; job satisfaction and difficulties; perceived future life satisfactions; and the effects of marriage, children, career, and menopause on a woman's life. The Murray Research Archive holds all numeric file da ta, and original record paper data from the study

Life Patterns, Personality Style And Self-esteem In Gifted Family Oriented And Career Committed Women.

Ph.D.Clinical psychologyPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/127332/2/7123698.pd

The rise of Nazism before World War II : Memories of Germany /

The memoir is a transcript of an interview with Hilde Birnbaum from June to August of 1999, conducted by Judith Bendor in Seattle, Washington. Description of the Frankfurt Jewish community, where Hilde’s father was the leader of the Gemeinde. Hilde had private lessons in Hebrew with the rabbi Caesar Seligmann. Hilde reflects on the time leading up to the rise of Nazism in Germany. She was a law student and was already very aware of the dangers of National Socialism prior to 1933 due to her frequent travels abroad. In 1931 she worked in an internship at a law firm in London. After the overwhelming success of the Nazis at the elections she decided not to return to Germany, since she did not see a future for herself as a woman and a Jew. Her father convinced her to finish her studies in Germany. Continuation of studies in Freiburg and encounter with Nazi student groups as a member of the social-democratic student faction. Graduation and Referendar position in Limburg in 1932. In March of 1933 she left Germany with her sister Edith for England, being warned by colleagues at court of the anti-Jewish boycot. They crossed the Dutch border and waited for invitations from relatives in London in order to get an entry permit for England. They were warmly received by the Heim family and settled in London. Difficulties of finding work. Hilde was introduced to influential British journalists and politicians, who disregarded her concerns of the possible dangers of Nazi Germany.The following years she travelled frequently to Germany to convince her parents and friends to leave the country, until she was declared an enemy of the Reich and lost her German citizenship. Her mother started preparations to leave without the knowledge of her husband. Observations about life in Nazi Germany. Trip to Palestine in 1936. In 1938, only weeks before “Kristallnacht”, Hilde’s parents joined her in London, before they went to the United States. Her sister Edith had already left with her husband for Seattle in 1936. Preperations for Hilde’s emigration to the United States. She arrived in Seattle in the winter of 1938.The lawyer Hilde Birnbaum, nee Merzbach, was born in 1909 in Frankfurt am Main, Germany. Her family was a well-known family who lived in Frankfurt for several generations and owned the established Merzbach bank. Her father, a veteran of World War One, was a prominent lawyer and head of the Jewish community in Frankfurt. Law studies in Freiburg and member of the Social Democrats. In March of 1933 Hilde left Germany for England together with her sister Edith. She emigrated to the United States via Paris in 1938.Himmler, Heinrich, 1900-1945Levy, HildeSchirach, Balduir von, 1907-1974Education, higher, 1918-1933Education, Jewish, 1918-1933Professions and occupations, bank owner