154 research outputs found

    Bypass and embolization for a vertebral artery aneurysm in a patient with Marfan syndrome

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    Extracranial vertebral artery aneurysms represent an uncommon presentation of collagen vascular disease. We performed staged proximal embolization of large left vertebral artery aneurysm after distal common carotid-to-vertebral bypass at C2 in a young adult patient with Marfan syndrome and a hypoplastic contralateral vertebral artery. Dilation of the autogenous saphenous vein graft occurred at 1 year with proximal graft stenosis requiring operative revision. Subsequent dilation of the basilar artery led to symptoms of pontine compression at 18 months that have resolved at 31 months of follow-up

    Anomalous Aortic Origin of a Coronary Artery With an Interarterial Course Should Family Screening Be Routine?

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    ObjectivesWe sought to present cases of familial occurrence of anomalous aortic origin of a coronary artery with an interarterial course (AAOCA) to determine if it would alter our current screening and management recommendations.BackgroundAnomalous aortic origin of a coronary artery with an interarterial course is a rare congenital anomaly that carries an increased risk of sudden death in children and young adults. There are no reports in the literature of familial AAOCA in the pediatric population.MethodsIn preparation for a multi-institutional prospective study evaluating patient management and surgical outcomes in children and young adults with AAOCA, a questionnaire was sent to multiple pediatric institutions in North and South America. Several respondents indicated caring for families with more than 1 member with AAOCA. These patients were identified and charts were retrospectively reviewed.ResultsWe identified 5 families in which a child was diagnosed with AAOCA and another family member was subsequently identified through screening with echocardiography. The odds of this occurring are significantly greater than what would be expected by chance. All identified by screening were asymptomatic and had anomalous right coronary artery despite 2 of the 5 index cases having anomalous left coronary artery.ConclusionsIt is possible that there is a genetic link for AAOCA. Future research into this is warranted. Due to the potential risk of myocardial ischemia and sudden death associated with AAOCA, screening first-degree relatives for AAOCA using transthoracic echocardiography would be the prudent approach to potentially prevent a sudden catastrophic event

    Synthesis of a boronic acid anhydride based ligand and its application in beryllium coordination

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    The synthesis of a boronic acid anhydride‐based ligand containing one three‐ and one four‐coordinated boron atom is presented. This ligand was successfully employed as a tridentate ÎșÂčN,ÎșÂČO‐ligand in the coordination of beryllium chloride and both the ligand and the resulting complex have been structurally characterized. While the boron‐element separations are within the typical range of related homo‐nuclear compounds, the corresponding beryllium‐element distances are rather long, suggesting unexpectedly high electron density at the beryllium center. Incorporation of a beryllium atom in a six‐membered ring causes no more distortion than the corresponding boron atom, suggesting that analogous ligand systems could be used in boron and beryllium coordination chemistry. The generated hetero‐tri‐nuclear complex enables the direct comparison of bond lengths and angles at beryllium and boron atoms in similar coordination environments and can act as a monomolecular model for beryllium borates

    The chemistry and metallurgy of beryllium

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    Beryllium (Be), the first of the group 2 alkali-earth ele­ments, is a silver-gray metal possessing an unmatched combination of physical and mechanical properties, which are vital for a variety of applications that offer tre­mendous benefits to society. It is the lightest workable metal, only two-thirds the weight of aluminium, yet it has six times the stiffness of steel, making it an ideal mate­rial for stiffness-dependent and weight-limited applica­tions. The chart in Fig. 1 illustrates how much beryllium outclasses other engineering materials with respect to thermal conductivity and dimensional stability (ability of a material to retain its uniformity under stress measured as the Young's modulus to density ratio). These unique properties of beryllium translate into performance en­hancement in the end product, for instance the James Webb Space Telescope (JWST: see Fig. 2). The next gen­eration James Webb Space Telescope, scheduled to be launched in 2018 as NASA's replacement for the Hubble telescope, will utilise a 6.5 meter wide beryllium mirror to reveal images of distant galaxies 200 times beyond what has ever been sighted

    Predicting performance using background characteristics of international medical graduates in an inner-city university-affiliated Internal Medicine residency training program

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    <p>Abstract</p> <p>Background</p> <p>IMGs constitute about a third of the United States (US) internal medicine graduates. US residency training programs face challenges in selection of IMGs with varied background features. However data on this topic is limited. We analyzed whether any pre-selection characteristics of IMG residents in our internal medicine program are associated with selected outcomes, namely competency based evaluation, examination performance and success in acquiring fellowship positions after graduation.</p> <p>Methods</p> <p>We conducted a retrospective study of 51 IMGs at our ACGME accredited teaching institution between 2004 and 2007. Background resident features namely age, gender, self-reported ethnicity, time between medical school graduation to residency (pre-hire time), USMLE step I & II clinical skills scores, pre-GME clinical experience, US externship and interest in pursuing fellowship after graduation expressed in their personal statements were noted. Data on competency-based evaluations, in-service exam scores, research presentation and publications, fellowship pursuance were collected. There were no fellowships offered in our hospital in this study period. Background features were compared between resident groups according to following outcomes: (a) annual aggregate graduate PGY-level specific competency-based evaluation (CBE) score above versus below the median score within our program (scoring scale of 1 – 10), (b) US graduate PGY-level specific resident in-training exam (ITE) score higher versus lower than the median score, and (c) those who succeeded to secure a fellowship within the study period. Using appropriate statistical tests & adjusted regression analysis, odds ratio with 95% confidence intervals were calculated.</p> <p>Results</p> <p>94% of the study sample were IMGs; median age was 35 years (Inter-Quartile range 25th – 75th percentile (IQR): 33–37 years); 43% women and 59% were Asian physicians. The median pre-hire time was 5 years (IQR: 4–7 years) and USMLE step I & step II clinical skills scores were 85 (IQR: 80–88) & 82 (IQR: 79–87) respectively. The median aggregate CBE scores during training were: PG1 5.8 (IQR: 5.6–6.3); PG2 6.3 (IQR 6–6.8) & PG3 6.7 (IQR: 6.7 – 7.1). 25% of our residents scored consistently above US national median ITE scores in all 3 years of training and 16% pursued a fellowship.</p> <p>Younger residents had higher aggregate annual CBE score than the program median (p < 0.05). Higher USMLE scores were associated with higher than US median ITE scores, reflecting exam-taking skills. Success in acquiring a fellowship was associated with consistent fellowship interest (p < 0.05) and research publications or presentations (p <0.05). None of the other characteristics including visa status were associated with the outcomes.</p> <p>Conclusion</p> <p>Background IMG features namely, age and USMLE scores predict performance evaluation and in-training examination scores during residency training. In addition enhanced research activities during residency training could facilitate fellowship goals among interested IMGs.</p

    CLICK-A: Optical Communication Experiments From a CubeSat Downlink Terminal

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    The CubeSat Laser Infrared CrosslinK (CLICK) mission is a technology demonstration of low size, weight, and power (SWaP) CubeSat optical communication terminals for downlink and crosslinks. The mission is broken into two phases: CLICK-A, which consists of a downlink terminal hosted in a 3U CubeSat, and CLICK-B/C, which consists of a pair of crosslink terminals each hosted in their own 3U CubeSat. This work focuses on the CLICK-A 1.2U downlink terminal, whose goal was to establish a 10 Mbps link to a low-cost portable 28 cm optical ground station called PorTeL. The terminal communicates with M-ary pulse position modulation (PPM) at 1550 nm using a 200 mW Erbium-doped fiber amplifier (EDFA) with a 1.3 mrad FWHM beam divergence. CLICK-A ultimately serves as a risk reduction phase for the CLICK-B/C terminals, with many components first being demonstrated on CLICK-A. CLICK-A was launched to the International Space Station on July 15th, 2022 and was deployed by Nanoracks on September 6th, 2022 into a 51.6° 414 km orbit. We present the results of experiments performed by the mission with the optical ground station located at MIT Wallace Astrophysical Observatory in Westford, MA. Successful acquisition of an Earth to space 5 mrad FWHM (5 Watts at 976 nm) pointing beacon was demonstrated by the terminal on the second experiment on November 2nd, 2022. First light on the optical ground station tracking camera was established on the third experiment on November 10th, 2022. The optical ground station showed sufficient open, coarse, and fine tracking performance to support links with the terminal with a closed-loop RMS tracking error of 0.053 mrad. Results of three optical downlink experiments that produced beacon tracking results are discussed. These experiments demonstrated that the internal microelectromechanical system (MEMS) fine steering mirror (FSM) corrected for an average blind spacecraft pointing error of 8.494 mrad and maintained an average RMS pointing error of 0.175 mrad after initial blind pointing error correction. With these results, the terminal demonstrated the ability to achieve sufficient fine pointing of the 1.3 mrad FWHM optical communication beam without pointing feedback from the terminal to improve the nominal spacecraft pointing. Spacecraft drag reduction maneuvers were used to extend mission life and inform the mission operations of the CLICK-B/C phase of the mission. Results from the spacecraft drag maneuvers are also presented

    Two Distinct Pathways Leading to Nuclear Apoptosis

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    Apaf-1−/− or caspase-3−/− cells treated with a variety of apoptosis inducers manifest apoptosis-associated alterations including the translocation of apoptosis-inducing factor (AIF) from mitochondria to nuclei, large scale DNA fragmentation, and initial chromatin condensation (stage I). However, when compared with normal control cells, Apaf-1−/− or caspase-3−/− cells fail to exhibit oligonucleosomal chromatin digestion and a more advanced pattern of chromatin condensation (stage II). Microinjection of such cells with recombinant AIF only causes peripheral chromatin condensation (stage I), whereas microinjection with activated caspase-3 or its downstream target caspase-activated DNAse (CAD) causes a more pronounced type of chromatin condensation (stage II). Similarly, when added to purified HeLa nuclei, AIF causes stage I chromatin condensation and large-scale DNA fragmentation, whereas CAD induces stage II chromatin condensation and oligonucleosomal DNA degradation. Furthermore, in a cell-free system, concomitant neutralization of AIF and CAD is required to suppress the nuclear DNA loss caused by cytoplasmic extracts from apoptotic wild-type cells. In contrast, AIF depletion alone suffices to suppress the nuclear DNA loss contained in extracts from apoptotic Apaf-1−/− or caspase-3−/− cells. As a result, at least two redundant parallel pathways may lead to chromatin processing during apoptosis. One of these pathways involves Apaf-1 and caspases, as well as CAD, and leads to oligonucleosomal DNA fragmentation and advanced chromatin condensation. The other pathway, which is caspase-independent, involves AIF and leads to large-scale DNA fragmentation and peripheral chromatin condensation

    Effects of thromboxane synthetase inhibition on patency and anastomotic hyperplasia of vascular grafts

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    The efficacy of a thromboxane synthetase inhibitor (U-63,557A, Upjohn) in promoting early patency and inhibiting anastomotic intimal hyperplasia in ePTFE grafts was compared to that of acetylsalicylic acid (ASA) in a canine model. Animals were started on ASA 5 gr po qd (Group I, n = 12) or U-63,557A 10 mg/kg po bid (Group II, n = 12) 1 day before placement of bilateral 5-mm-i.d., 13- to 16.5-cm-long ePTFE aortoiliac grafts and continued on the medication for the 16-week study. Six dogs in each group received autologous endothelial cell-seeded grafts, while the other six received unseeded grafts. Patency was determined weekly by assessment of femoral pulses. At the conclusion of the study anastomotic intimal hyperplasia was measured on serial sections through the distal anastomosis using a computer-linked digitizer. In Group I the patencies of seeded and unseeded grafts were not significantly different, being 100 and 83%, respectively. Furthermore, luminal narrowing due to intimal hyperplasia was not significantly different being 9.1 +/- 7.6% (x +/- SD) in seeded grafts and 8.8 +/- 8.1% in unseeded grafts. On the other hand, in Group II the seeded grafts had significantly improved patency when compared to the unseeded grafts (83% vs 33%, P P P P &lt; 0.01).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27929/1/0000353.pd

    Loss of CIC promotes mitotic dysregulation and chromosome segregation defects

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    Background: CIC is a transcriptional repressor inactivated by loss-of-function mutations in several cancer types, including gliomas, lung cancers, and gastric adenocarcinomas. CIC alterations and/or loss of CIC activity have been associated with poorer outcomes and more aggressive phenotypes across cancer types, which is consistent with the notion that CIC functions as a tumour suppressor across a wide range of contexts. Results: Using mammalian cells lacking functional CIC, we found that CIC deficiency was associated with chromosome segregation (CS) defects, resulting in chromosomal instability and aneuploidy. These CS defects were associated with transcriptional dysregulation of spindle assembly checkpoint and cell cycle regulators. We also identified novel CIC interacting proteins, including core members of the SWI/SNF complex, and showed that they cooperatively regulated the expression of genes involved in cell cycle regulation. Finally, we showed that loss of CIC and ARID1A cooperatively increased CS defects and reduced cell viability. Conclusions: Our study ascribes a novel role to CIC as an important regulator of the cell cycle and demonstrates that loss of CIC can lead to chromosomal instability and aneuploidy in human and murine cells through defects in CS, providing insight into the underlying mechanisms of CIC's increasingly apparent role as a "pan-cancer" tumour suppressor
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