Arterial Anomalies Pertaining to the Aortic Arches and the Branches Arising From Them

For a number of years I have been interested in the arterial variations which have been encountered in my dissecting rooms. Notes have been made of these abnormalities and the literature describing similar conditions has been gradually collected. The more recent textbooks in anatomy devote little space to the subject of arterial variations and the classic works which have reviewed the field are no longer readily consulted; then, too, new facts have been added to our knowledge of arterial development since the most recent of the latter were published. In view of these facts it has seemed worth while to assemble the cases I have collected from the various sources and classify them according to our present knowledge of development. I wish to take this opportunity to express my thanks to Doctor W. F. Whitney, curator of the anatomical museum at Harvard Medical School, for placing the splendid collection of the Warren Museum at my disposal for study. In the later pages I have used the results of my study freely, referring to the various anomalies as from the Warren Museum. The following does not purport to be the entire list of all cases reported, for it was not possible with the library facilities and time I had at my disposal to consult all the works that might contain a record of such variations, but I believe a sufficient number have been collected on which to base reliable conclusions of the scope and possibly relative frequency of such abnormalities. The bibliography at the end of this study includes not only the cases referred to in the body of the work but, in addition, many titles which I was unable to consult but which came to me on good authority. I have included the latter believing that a full bibliography on any subject has a distinct value of its own. In this study I have confined the observations to those anomalies directly related to the aortic arches and the ventral aorta. In many cases the factor which has produced these variations seems to have influenced the development of the heart; since, however, no constant relationship could be discovered between the heart anomalies and those of the arches, I will reserve the study of the heart for a future paper. All cases which might be considered to be the result of known pathological processes have been excluded. Arterial variation is but one of many irregularities encountered in the human body and in order to appreciate it fully we must consider the subject of variation as a whole, otherwise we may be inclined to think that arterial variations have a significance and perhaps an importance greater than any other anomalies encountered

Tumor-specific HMG-CoA reductase expression in primary premenopausal breast cancer predicts response to tamoxifen

ABSTRACT: INTRODUCTION: We previously reported an association between tumor-specific 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) expression and a good prognosis in breast cancer. Here, the predictive value of HMG-CoAR expression in relation to tamoxifen response was examined. METHODS: HMG-CoAR protein and RNA expression was analyzed in a cell line model of tamoxifen resistance using western blotting and PCR. HMG-CoAR mRNA expression was examined in 155 tamoxifen-treated breast tumors obtained from a previously published gene expression study (Cohort I). HMG-CoAR protein expression was examined in 422 stage II premenopausal breast cancer patients, who had previously participated in a randomized control trial comparing 2 years of tamoxifen with no systemic adjuvant treatment (Cohort II). Kaplan-Meier analysis and Cox proportional hazards modeling were used to estimate the risk of recurrence-free survival (RFS) and the effect of HMG-CoAR expression on tamoxifen response. RESULTS: HMG-CoAR protein and RNA expression were decreased in tamoxifen-resistant MCF7-LCC9 cells compared with their tamoxifen-sensitive parental cell line. HMG-CoAR mRNA expression was decreased in tumors that recurred following tamoxifen treatment (P < 0.001) and was an independent predictor of RFS in Cohort I (hazard ratio = 0.63, P = 0.009). In Cohort II, adjuvant tamoxifen increased RFS in HMG-CoAR-positive tumors (P = 0.008). Multivariate Cox regression analysis demonstrated that HMG-CoAR was an independent predictor of improved RFS in Cohort II (hazard ratio = 0.67, P = 0.010), and subset analysis revealed that this was maintained in estrogen receptor (ER)-positive patients (hazard ratio = 0.65, P = 0.029). Multivariate interaction analysis demonstrated a difference in tamoxifen efficacy relative to HMG-CoAR expression (P = 0.05). Analysis of tamoxifen response revealed that patients with ER-positive/HMG-CoAR tumors had a significant response to tamoxifen (P = 0.010) as well as patients with ER-positive or HMG-CoAR-positive tumors (P = 0.035). Stratification according to ER and HMG-CoAR status demonstrated that ER-positive/HMG-CoAR-positive tumors had an improved RFS compared with ER-positive/HMG-CoAR-negative tumors in the treatment arm (P = 0.033); this effect was lost in the control arm (P = 0.138), however, suggesting that HMG-CoAR predicts tamoxifen response. CONCLUSIONS: HMG-CoAR expression is a predictor of response to tamoxifen in both ER-positive and ER-negative disease. Premenopausal patients with tumors that express ER or HMG-CoAR respond to adjuvant tamoxifen

Terrigenous plant wax inputs to the Arabian Sea : implications for the reconstruction of winds associated with the Indian Monsoon

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Elsevier B. V. for personal use, not for redistribution. The definitive version was published in Geochimica et Cosmochimica Acta 69 (2005): 2547-2558, doi:10.1016/j.gca.2005.01.001.We have determined the accumulation rates and carbon isotopic compositions (δ13C) of long-chain (C24–C32) terrigenous plant wax fatty acids in 19 surface sediment samples geographically distributed throughout the Arabian Sea in order to assess the relationship between plant wax inputs and the surrounding monsoon wind systems. Both the accumulation rate data and the δ13C data show that there are three primary eolian sources of plant waxes to the Arabian Sea: Africa, Asia, and the Arabian Peninsula. These sources correspond to the three major wind systems in this region: the summer (Southwest) monsoon, the winter (Northeast) monsoon, and the summer northwesterlies that blow over the Arabian Peninsula. In addition, plant waxes are fluvially supplied to the Gulf of Oman and the Eastern African margin by nearby rivers. Plant wax δ13C values reflect the vegetation types of the continental source regions. Greater than 75% of the waxes from Africa and Asia are derived from C4 plants. Waxes delivered by northwesterly winds reflect a greater influence (25–40%) of C3 vegetation, likely derived from the Mesopotamian region. These data agree well with previously published studies of eolian dust deposition, particularly of dolomite derived from the Arabian Peninsula and the Mesopotamian region, in surface sediments of the Arabian Sea. The west-to-east gradient of plant wax δ13C and dolomite accumulation rates are separately useful indicators of the relationship between the northwesterly winds and the winds of the Southwest monsoon. Combined, however, these two proxies could provide a powerful tool for the reconstruction of both southwest monsoon strength as well as Mesopotamian aridity.This work was supported by a SGER grant from the National Science Foundation to D.O. and a Schlanger Ocean Drilling Fellowship to K.D

Long-term functional health status and exercise test variables for patients with pulmonary atresia with intact ventricular septum: A Congenital Heart Surgeons Society study

Background: A bias favoring biventricular (BV) repair exists regarding choice of repair pathway for patients with pulmonary atresia with intact ventricular septum (PAIVS). We sought to determine the implications of moving borderline candidates down a BV route in terms of late functional health status (FHS) and exercise capacity (EC). Methods: Between 1987 and 1997, 448 neonates with PAIVS were enrolled in a multi-institutional study. Late EC and FHS were assessed following repair (mean 14 years) using standardized exercise testing and 3 validated FHS instruments. Relationships between FHS, EC, morphology, and 3 end states (ie, BV, univentricular [UV], or 1.5-ventricle repair [1.5V]) were evaluated. Results: One hundred two of 271 end state survivors participated (63 BV, 25 UV, and 14 1.5V). Participants had lower FHS scores in domains of physical functioning (P<.001) compared with age- and sex-matched normal controls, but scored significantly higher in nearly all psychosocial domains. EC was higher in 1.5V-repair patients (P ¼ .02), whereas discrete FHS measures were higher in BV-repair patients. Peak oxygen consumption was low across all groups, and was positively correlated with larger initial tricuspid valve z-score (P<.001), with an enhanced effect within the BV-repair group. Conclusions: Late patient-perceived physical FHS and measured EC are reduced, regardless of PAIVS repair pathway, with an important dichotomy whereby patients with PAIVS believe they are doing well despite important physical impediments. For those with smaller initial tricuspid valve z-score, achievement of survival with BV repair may be at a cost of late deficits in exercise capacity, emphasizing that better outcomes may be achieved for borderline patients with a 1.5V- or UV-repair strategy. (J Thorac Cardiovasc Surg 2013;145:1018-27

Do Changes in the Pace of Events Affect One-Off Judgments of Duration?

Five experiments examined whether changes in the pace of external events influence people’s judgments of duration. In Experiments 1a–1c, participants heard pieces of music whose tempo accelerated, decelerated, or remained constant. In Experiment 2, participants completed a visuo-motor task in which the rate of stimulus presentation accelerated, decelerated, or remained constant. In Experiment 3, participants completed a reading task in which facts appeared on-screen at accelerating, decelerating, or constant rates. In all experiments, the physical duration of the to-be-judged interval was the same across conditions. We found no significant effects of temporal structure on duration judgments in any of the experiments, either when participants knew that a time estimate would be required (prospective judgments) or when they did not (retrospective judgments). These results provide a starting point for the investigation of how temporal structure affects one-off judgments of duration like those typically made in natural settings

The Nitric Oxide Pathway Provides Innate Antiviral Protection in Conjunction with the Type I Interferon Pathway in Fibroblasts

The innate host response to virus infection is largely dominated by the production of type I interferon and interferon stimulated genes. In particular, fibroblasts respond robustly to viral infection and to recognition of viral signatures such as dsRNA with the rapid production of type I interferon; subsequently, fibroblasts are a key cell type in antiviral protection. We recently found, however, that primary fibroblasts deficient for the production of interferon, interferon stimulated genes, and other cytokines and chemokines mount a robust antiviral response against both DNA and RNA viruses following stimulation with dsRNA. Nitric oxide is a chemical compound with pleiotropic functions; its production by phagocytes in response to interferon-γ is associated with antimicrobial activity. Here we show that in response to dsRNA, nitric oxide is rapidly produced in primary fibroblasts. In the presence of an intact interferon system, nitric oxide plays a minor but significant role in antiviral protection. However, in the absence of an interferon system, nitric oxide is critical for the protection against DNA viruses. In primary fibroblasts, NF-κB and interferon regulatory factor 1 participate in the induction of inducible nitric oxide synthase expression, which subsequently produces nitric oxide. As large DNA viruses encode multiple and diverse immune modulators to disable the interferon system, it appears that the nitric oxide pathway serves as a secondary strategy to protect the host against viral infection in key cell types, such as fibroblasts, that largely rely on the type I interferon system for antiviral protection

Common Variation in Vitamin D Pathway Genes Predicts Circulating 25-Hydroxyvitamin D Levels among African Americans

Vitamin D is implicated in a wide range of health outcomes, and although environmental predictors of vitamin D levels are known, the genetic drivers of vitamin D status remain to be clarified. African Americans are a group at particularly high risk for vitamin D insufficiency but to date have been virtually absent from studies of genetic predictors of circulating vitamin D levels. Within the Southern Community Cohort Study, we investigated the association between 94 single nucleotide polymorphisms (SNPs) in five vitamin D pathway genes (GC, VDR, CYP2R1, CYP24A1, CYP27B1) and serum 25-hydroxyvitamin D (25(OH)D) levels among 379 African American and 379 Caucasian participants. We found statistically significant associations with three SNPs (rs2298849 and rs2282679 in the GC gene, and rs10877012 in the CYP27B1 gene), although only for African Americans. A genotype score, representing the number of risk alleles across the three SNPs, alone accounted for 4.6% of the variation in serum vitamin D among African Americans. A genotype score of 5 (vs. 1) was also associated with a 7.1 ng/mL reduction in serum 25(OH)D levels and a six-fold risk of vitamin D insufficiency (<20 ng/mL) (odds ratio 6.0, p = 0.01) among African Americans. With African ancestry determined from a panel of 276 ancestry informative SNPs, we found that high risk genotypes did not cluster among those with higher African ancestry. This study is one of the first to investigate common genetic variation in relation to vitamin D levels in African Americans, and the first to evaluate how vitamin D-associated genotypes vary in relation to African ancestry. These results suggest that further evaluation of genetic contributors to vitamin D status among African Americans may help provide insights regarding racial health disparities or enable the identification of subgroups especially in need of vitamin D-related interventions

Arterial Anomalies Pertaining to the Aortic Arches and the Branches Arising From Them

For a number of years I have been interested in the arterial variations which have been encountered in my dissecting rooms. Notes have been made of these abnormalities and the literature describing similar conditions has been gradually collected. The more recent textbooks in anatomy devote little space to the subject of arterial variations and the classic works which have reviewed the field are no longer readily consulted; then, too, new facts have been added to our knowledge of arterial development since the most recent of the latter were published. In view of these facts it has seemed worth while to assemble the cases I have collected from the various sources and classify them according to our present knowledge of development. I wish to take this opportunity to express my thanks to Doctor W. F. Whitney, curator of the anatomical museum at Harvard Medical School, for placing the splendid collection of the Warren Museum at my disposal for study. In the later pages I have used the results of my study freely, referring to the various anomalies as from the Warren Museum. The following does not purport to be the entire list of all cases reported, for it was not possible with the library facilities and time I had at my disposal to consult all the works that might contain a record of such variations, but I believe a sufficient number have been collected on which to base reliable conclusions of the scope and possibly relative frequency of such abnormalities. The bibliography at the end of this study includes not only the cases referred to in the body of the work but, in addition, many titles which I was unable to consult but which came to me on good authority. I have included the latter believing that a full bibliography on any subject has a distinct value of its own. In this study I have confined the observations to those anomalies directly related to the aortic arches and the ventral aorta. In many cases the factor which has produced these variations seems to have influenced the development of the heart; since, however, no constant relationship could be discovered between the heart anomalies and those of the arches, I will reserve the study of the heart for a future paper. All cases which might be considered to be the result of known pathological processes have been excluded. Arterial variation is but one of many irregularities encountered in the human body and in order to appreciate it fully we must consider the subject of variation as a whole, otherwise we may be inclined to think that arterial variations have a significance and perhaps an importance greater than any other anomalies encountered