Neovascularization is a critical component in the progression of malignant melanoma. The objective of this study was to determine whether alpha(nu)beta(3)-targeted paramagnetic nanoparticles can ...detect and characterize sparse alpha(nu)beta integrin expression on neovasculature induced by nascent melanoma xenografts ( approximately 30 mm(3)) at 1.5T. Athymic nude mice bearing human melanoma tumors were intravenously injected with alpha(v)beta(3)-integrin-targeted paramagnetic nanoparticles, nontargeted paramagnetic nanoparticles, or alpha(v)beta(3)-targeted-nonparamagnetic nanoparticles 2 hr before they were injected with alpha(v)beta(3)-integrin-targeted paramagnetic nanoparticles (i.e., in vivo competitive blockade) and imaged with MRI. Contrast enhancement of neovascularity in animals that received alpha(nu)beta(3)-targeted paramagnetic nanoparticles increased 173% by 120 min. Signal contrast with nontargeted paramagnetic nanoparticles was approximately 50% less than that in the targeted group (P < 0.05). Molecular MRI results were corroborated by histology. In a competitive cell adhesion assay, incubation of alpha(nu)beta(3)-expressing cells with targeted nanoparticles significantly inhibited binding to a vitronectin-coated surface, confirming the bioactivity of the targeted nanoparticles. The present study lowers the limit previously reported for detecting sparse biomarkers with molecular MRI in vivo. This technique may be employed to noninvasively detect very small regions of angiogenesis associated with nascent melanoma tumors, and to phenotype and stage early melanoma in a clinical setting.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Neovascularization is a critical component in the progression of malignant melanoma. The objective of this study was to determine whether alpha sub( nu ) beta sub(3)-targeted paramagnetic ...nanoparticles can detect and characterize sparse alpha sub( nu ) beta integrin expression on neovasculature induced by nascent melanoma xenografts ( similar to 30 mm super(3)) at 1.5T. Athymic nude mice bearing human melanoma tumors were intravenously injected with alpha sub( nu ) beta sub(3)-integrin-targeted paramagnetic nanoparticles, nontargeted paramagnetic nanoparticles, or alpha sub( nu ) beta sub(3)-targeted-nonparamagnetic nanoparticles 2 hr before they were injected with alpha sub( nu ) beta sub(3)-integrin-targeted paramagnetic nanoparticles (i.e., in vivo competitive blockade) and imaged with MRI. Contrast enhancement of neovascularity in animals that received alpha sub( nu ) beta sub(3)-targeted paramagnetic nanoparticles increased 173% by 120 min. Signal contrast with nontargeted paramagnetic nanoparticles was approximately 50% less than that in the targeted group (P < 0.05). Molecular MRI results were corroborated by histology. In a competitive cell adhesion assay, incubation of alpha sub( nu ) beta sub(3)-expressing cells with targeted nanoparticles significantly inhibited binding to a vitronectin-coated surface, confirming the bioactivity of the targeted nanoparticles. The present study lowers the limit previously reported for detecting sparse biomarkers with molecular MRI in vivo. This technique may be employed to noninvasively detect very small regions of angiogenesis associated with nascent melanoma tumors, and to phenotype and stage early melanoma in a clinical setting.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A physical map of the mouse genome is an essential tool for both positional cloning and genomic sequencing in this key model system for biomedical research. Indeed, the construction of a mouse ...physical map with markers spaced at an average interval of 300 kb is one of the stated goals of the Human Genome Project. Here we report the results of a project at the Whitehead Institute/MIT Center for Genome Research to construct such a physical map of the mouse. We built the map by screening sequenced-tagged sites (STSs) against a large-insert yeast artificial chromosome (YAC) library and then integrating the STS-content information with a dense genetic map. The integrated map shows the location of 9,787 loci, providing landmarks with an average spacing of approximately 300 kb and affording YAC coverage of approximately 92% of the mouse genome. We also report the results of a project at the MRC UK Mouse Genome Centre targeted at chromosome X. The project produced a YAC-based map containing 619 loci (with 121 loci in common with the Whitehead map and 498 additional loci), providing especially dense coverage of this sex chromosome. The YAC-based physical map directly facilitates positional cloning of mouse mutations by providing ready access to most of the genome. More generally, use of this map in addition to a newly constructed radiation hybrid (RH) map provides a comprehensive framework for mouse genomic studies.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background: The relationship between illness severity and neuroanatomical abnormalities in schizophrenia remains unclear. The purpose of this study was to test whether the pattern and extent of brain ...volume abnormalities differed between two patient groups, distinguished by their overall severity and clinical course of schizophrenia.
Methods: Subjects were 56 severely ill, chronically hospitalized schizophrenic men from Napa State Hospital (SH-SZ), 44 moderately ill, acutely hospitalized schizophrenic men from the Palo Alto Veterans Administration Health Care System (VA-SZ), and 52 healthy male control subjects. Temporolimbic, ventricular, and frontoparietal volumes, quantified from 3-mm coronal spin-echo magnetic resonance images and adjusted for cerebral volume and age, were compared using analysis of variance.
Results: Compared to control subjects, both SZ groups had smaller (
p < .05) temporal lobe and frontoparietal gray matter volumes and larger ventricles and temporal sulci. Whereas SH-SZ had more pronounced cerebrospinal fluid and frontoparietal abnormalities relative to VA-SZ; VA-SZ had greater temporal lobe gray matter deficits. Neither patient group had hippocampal or cerebral volume deficits relative to control subjects. There were no differences between diagnostic subtypes.
Conclusions: The magnitude of volume abnormalities in schizophrenia varies with respect to disease severity and to brain region, but disease severity is not associated with anatomically distinct subgroups.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
SciPy is an open source scientific computing library for the Python programming language. SciPy 1.0 was released in late 2017, about 16 years after the original version 0.1 release. SciPy has become ...a de facto standard for leveraging scientific algorithms in the Python programming language, with more than 600 unique code contributors, thousands of dependent packages, over 100,000 dependent repositories, and millions of downloads per year. This includes usage of SciPy in almost half of all machine learning projects on GitHub, and usage by high profile projects including LIGO gravitational wave analysis and creation of the first-ever image of a black hole (M87). The library includes functionality spanning clustering, Fourier transforms, integration, interpolation, file I/O, linear algebra, image processing, orthogonal distance regression, minimization algorithms, signal processing, sparse matrix handling, computational geometry, and statistics. In this work, we provide an overview of the capabilities and development practices of the SciPy library and highlight some recent technical developments.
The Cardiff Sib-Pair Study Farmer, Anne; Redman, Kate; Harris, Tanya ...
Crisis : the journal of crisis intervention and suicide prevention,
2001, Volume:
22, Issue:
2
Journal Article
Peer reviewed
Depression is associated with high rates of suicidal ideation, which varies in intensity from transient thoughts of wishing to be dead to the making of plans and, finally, to attempts to kill ...oneself. There is limited evidence from family, twin, and adoption studies that completed suicide is familial and has a genetic etiological component. However, it is unclear whether suicidal ideation is also familial. The familiality of suicidal ideation has been examined in the subjects who participated in the Cardiff Depression Study, namely, 108 depressed probands, their nearest-aged siblings, and 105 healthy control subjects and their siblings. The study showed that 66% of depressed subjects had experienced suicidal ideation in the week prior to the interview, and that this was significantly associated with recurrent illness. Suicidal ideation was not shown to be familial. However, somewhat surprisingly, 6% of healthy, never-depressed subjects admitted to having had transient suicidal thoughts. Suicidal ideation was significantly associated with high neuroticism and psychoticism scores and severe threatening life events.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
478.
Case 36-2003 Singh, Ajay K; Colvin, Robert B
The New England journal of medicine,
11/2003, Volume:
349, Issue:
21
Journal Article
Peer reviewed
A 68-year old woman was admitted to the hospital because of impaired renal function. The differential diagnosis is discussed by Singh, who presents the diagnostic possibilities according to a ...paradigm based on prerenal, intrinsic renal, and postrenal factors.
Presentation of Case
A 68-year-old woman was admitted to the hospital because of impaired renal function. One month earlier, she had had difficulty breathing and had felt as though she had a fever; she went to another hospital, where nebulizers were prescribed, and her dyspnea improved. Two weeks later, malaise and a sensation of chilliness developed, with diffuse pains in the arms and legs, which prompted her to take two or three tablets of ibuprofen every four to five hours for two weeks, although the medication was only minimally effective. Ten days before admission, pruritus developed. She consulted a physician, . . .
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