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<title>Stephen P. Baker</title>
<copyright>Copyright (c) 2011  All rights reserved.</copyright>
<link>http://works.bepress.com/stephen_baker</link>
<description>Recent documents in Stephen P. Baker</description>
<language>en-us</language>
<lastBuildDate>Thu, 04 Aug 2011 01:47:30 PDT</lastBuildDate>
<ttl>3600</ttl>


	
		
	

	
		
	

	
		
	

	
		
	







<item>
<title>Prevention of Alzheimer&apos;s disease in high risk groups: statin therapy in subjects with PSEN1 mutations or heterozygosity for apolipoprotein E epsilon 4</title>
<link>http://works.bepress.com/stephen_baker/99</link>
<guid isPermaLink="true">http://works.bepress.com/stephen_baker/99</guid>
<pubDate>Tue, 02 Aug 2011 08:11:04 PDT</pubDate>
<description>
	<![CDATA[
	<p>Because cerebrospinal fluid (CSF) abnormalities in presymptomatic subjects with <em>PSEN1 </em>(presenilin  1) mutations may be observed 4 to 12 years prior to the estimated age  at onset, it is possible to test putative therapies on the CSF analytes  that correlate with neurodegeneration during this presymptomatic window  of clinical opportunity. It is also possible to test the same therapy on  a comparison group with increased risk status conferred by both  hyperlipidemia and heterozygosity for apolipoprotein Eε4. To our  knowledge, the only putative therapy thus far tested in such a common  design has been statin therapy. The results of these tests show  increases in soluble amyloid precursor protein (sAPP)α correlating with  statin-induced decreases in serum cholesterol levels in the non-<em>PSEN1 </em>subjects.  This result could be one functional correlate for part of the  substantial risk reduction for late onset Alzheimer's disease recently  reported in the Rotterdam study, a large, long-term prospective statin  trial. Statin therapy significantly decreased both sAPPα and sAPPβ in  presymptomatic <em>PSEN1 </em>subjects. Initially, elevated phospho-tau levels in <em>PSEN1 </em>subjects  did not further increase during the 2 to 3 years of statin therapy,  possibly indicative of a prophylactic effect. These results suggest that  large and longer term trials of statin therapy correlating changes in  CSF biomarker levels with clinical course may be warranted in both  presymptomatic <em>PSEN1 </em>and non-<em>PSEN1 </em>subjects.</p>

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</description>

<author>Daniel A. Pollen et al.</author>


<category>Cerebrospinal Fluid</category>

<category>Presenilin-1</category>

<category>Alzheimer Disease</category>

<category>Apolipoprotein E4</category>

<category>Hydroxymethylglutaryl-CoA Reductase Inhibitors</category>

</item>






<item>
<title>Hospital Mortality, Length of Stay, and Preventable Complications Among Critically Ill Patients Before and After Tele-ICU Reengineering of Critical Care Processes</title>
<link>http://works.bepress.com/stephen_baker/98</link>
<guid isPermaLink="true">http://works.bepress.com/stephen_baker/98</guid>
<pubDate>Tue, 02 Aug 2011 08:10:55 PDT</pubDate>
<description>
	<![CDATA[
	<p><p id="x-x-x-p-1"><strong>Context:</strong> The association of an adult tele-intensive care unit (ICU) intervention with hospital mortality, length of stay, best practice                      adherence, and preventable complications for an academic medical center has not been reported.  <p id="x-x-x-p-2"><strong>Objective</strong>: To quantify the association of a tele-ICU intervention with hospital mortality, length of stay, and complications that are                      preventable by adherence to best practices.  <p id="x-x-x-p-3"><strong>Design, Setting, and Patients:</strong> Prospective stepped-wedge clinical practice study of 6290 adults  admitted to any of 7 ICUs (3 medical, 3 surgical, and 1                      mixed cardiovascular) on 2 campuses of an 834-bed  academic medical center that was performed from April 26, 2005, through                      September 30, 2007. Electronically supported and  monitored processes for best practice adherence, care plan creation, and                      clinician response times to alarms were evaluated.  <p id="x-x-x-p-4"><strong>Main Outcome Measures</strong>: Case-mix and severity-adjusted hospital mortality. Other outcomes included hospital and ICU length of stay, best practice                      adherence, and complication rates.  <p id="x-x-x-p-5"><strong>Results:</strong> The hospital  mortality rate was 13.6% (95% confidence interval [CI], 11.9%-15.4%)  during the preintervention period compared                      with 11.8% (95% CI, 10.9%-12.8%) during the  tele-ICU intervention period (adjusted odds ratio [OR], 0.40 [95% CI,  0.31-0.52]).                      The tele-ICU intervention period compared with the  preintervention period was associated with higher rates of best clinical                      practice adherence for the prevention of deep vein  thrombosis (99% vs 85%, respectively; OR, 15.4 [95% CI, 11.3-21.1]) and                      prevention of stress ulcers (96% vs 83%,  respectively; OR, 4.57 [95% CI, 3.91-5.77], best practice adherence for  cardiovascular                      protection (99% vs 80%, respectively; OR, 30.7 [95%  CI, 19.3-49.2]), prevention of ventilator-associated pneumonia (52% vs                      33%, respectively; OR, 2.20 [95% CI, 1.79-2.70]),  lower rates of preventable complications (1.6% vs 13%, respectively, for                      ventilator-associated pneumonia [OR, 0.15; 95% CI,  0.09-0.23] and 0.6% vs 1.0%, respectively, for catheter-related  bloodstream                      infection [OR, 0.50; 95% CI, 0.27-0.93]), and  shorter hospital length of stay (9.8 vs 13.3 days, respectively; hazard  ratio                      for discharge, 1.44 [95% CI, 1.33-1.56]). The  results for medical, surgical, and cardiovascular ICUs were similar.  <p id="x-x-x-p-6"><strong>Conclusion:</strong> In a single  academic medical center study, implementation of a tele-ICU intervention  was associated with reduced adjusted                      odds of mortality and reduced hospital length of  stay, as well as with changes in best practice adherence and lower rates                      of preventable complications.</p>

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</description>

<author>Craig M. Lilly et al.</author>


<category>Academic Medical Centers</category>

<category>Critical Care</category>

<category>Telemedicine</category>

<category>Intensive Care</category>

<category>Intensive Care Units</category>

<category>Outcome and Process Assessment (Health Care)</category>

<category>Hospital Mortality</category>

<category>Length of Stay</category>

</item>






<item>
<title>A preclinical 188Re tumor therapeutic investigation using MORF/cMORF pretargeting and an antiTAG-72 antibody CC49</title>
<link>http://works.bepress.com/stephen_baker/97</link>
<guid isPermaLink="true">http://works.bepress.com/stephen_baker/97</guid>
<pubDate>Tue, 02 Aug 2011 08:10:47 PDT</pubDate>
<description>
	<![CDATA[
	<p>The utility of MORF/cMORF pretargeting for the radiotherapy of cancer requires further validation in tumored mice before clinical trials. We now report on a therapeutic study in mice pretargeted with MORF-CC49 (an anti-TAG-72 antibody CC49 conjugated with MORF, a phosphorodiamidate morpholino oligomer) and then targeted by 188Re-cMORF (a 188Re labeled complementary MORF). Before the dose-escalating therapeutic study, a pretargeting study in LS174T tumored mice was performed at tracer levels. By both necropsy and imaging, the tracer study showed that the whole body radioactivity was largely restricted to tumor in the mice pretargeted 48 h earlier with MORF-CC49 and the tumor radioactivity was retained over 90 h. After decay correction, a best-fit to the biodistribution provided the areas under the radioactivity curves (AUCs) used for the radiation dose estimates. The tumor to normal organ AUC ratios in all cases were greater than unity and ranged from 3 (kidneys) to 48 (muscle). Tumor growth was inhibited in the therapy study. At the highest 188Re dose of 1.40 mCi, a complete but temporary tumor remission was evident in 3 out of the 5 animals. Histological examination of tissues from these animals showed no evidence of cytotoxicity to normal tissues but obvious radiation damage to tumor. In conclusion, effective radiotherapy was achieved in a mouse model by MORF/cMORF pretargeting using 188Re as the therapeutic radionuclide and CC49 as the pretargeting antibody.</p>

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</description>

<author>Guozheng Liu et al.</author>


<category>Colonic Neoplasms</category>

<category>Radioisotopes</category>

<category>Radiopharmaceuticals</category>

<category>Xenograft Model Antitumor Assays</category>

</item>






<item>
<title>Gender-Specific Reduction of Estrogen-Sensitive Small RNA, miR-30b, in Subjects With Schizophrenia</title>
<link>http://works.bepress.com/stephen_baker/96</link>
<guid isPermaLink="true">http://works.bepress.com/stephen_baker/96</guid>
<pubDate>Tue, 02 Aug 2011 08:10:40 PDT</pubDate>
<description>
	<![CDATA[
	<p>Estrogen signaling pathways affect cortical function and metabolism, are thought to play a role in the pathophysiology of schizophrenia, and exert neuroprotective effects in female subjects at risk. However, the molecular signatures of estrogen signaling in normal and diseased cerebral cortex remain largely unexplored. Expression of the estrogen-sensitive small RNA, microRNA-30b (miR-30b), was studied in 30 controls and 30 matched samples from subjects diagnosed with schizophrenia from prefrontal cortex (PFC), as well as in 23 samples from parietal cortex (12 controls and 11 schizophrenia cases). The majority of case and control samples were genotyped for an estrogen receptor alpha (Esr1) sequence variant (rs2234693) previously associated with genetic risk, and a subset of them were subjected to further analysis to determine expression of mature and precursor forms of miR-30b (pre/pri-miR-30b). Gender-dimorphic expression was also explored in mouse frontal cortex and hippocampus. A significant interaction between gender and diagnosis was discovered for changes in mature miR-30b levels, so that miR-30b expression was significantly reduced in the cerebral cortex of female but not male subjects with schizophrenia. In addition, disease-related changes in miR-30b expression in a subset of female subjects were further modulated by Esr1 genotype. Changes after antipsychotic drug exposure remained insignificant. These preliminary findings point to the possibility that disease-related changes in the expression of small noncoding RNAs such as miR-30b in schizophrenia could be influenced by gender and potentially regulated by estrogen signaling.</p>

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</description>

<author>Nikolaos Mellios et al.</author>


<category>MicroRNAs</category>

<category>Estrogens</category>

<category>Schizophrenia</category>

</item>






<item>
<title>Response to Comment on &quot;Reassessment of the Role of Mut S Homolog 5 in Ig Class Switch Recombination Shows Lack of Involvement in cis- and trans-Switching&quot;</title>
<link>http://works.bepress.com/stephen_baker/95</link>
<guid isPermaLink="true">http://works.bepress.com/stephen_baker/95</guid>
<pubDate>Thu, 25 Mar 2010 11:11:21 PDT</pubDate>
<description>
	<![CDATA[
	<p>Response to: Reassessment of the role of Mut S homolog 5 in Ig class switch recombination shows lack of involvement in cis- and trans-switching. Guikema JE, Schrader CE, Leus NG, Ucher A, Linehan EK, Werling U, Edelmann W, Stavnezer J. J Immunol. 2008 Dec 15;181(12):8450-9.PMID: 19050263.</p>

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</description>

<author>Jeroen E. J. Guikema et al.</author>


<category>Cell Cycle Proteins</category>

<category>DNA-Binding Proteins</category>

<category>Immunoglobulin Class Switching</category>

<category>Recombination, Genetic</category>

</item>






<item>
<title>Interleukin 18 binding protein (IL18-BP) inhibits neointimal hyperplasia after balloon injury in an atherosclerotic rabbit model</title>
<link>http://works.bepress.com/stephen_baker/94</link>
<guid isPermaLink="true">http://works.bepress.com/stephen_baker/94</guid>
<pubDate>Thu, 25 Mar 2010 11:11:19 PDT</pubDate>
<description>
	<![CDATA[
	<p>OBJECTIVES: Interleukin 18 (IL18) is an interferon (IFN)-gamma-inducing factor and a proinflammatory and proatherogenic cytokine. IL18 binding protein (IL18-BP) functions as an IL18 inhibitor. This study was designed to investigate whether systemic administration of IL18-BP could inhibit neointimal hyperplasia and arterial lipid deposition.</p>
<p>METHODS: New Zealand white, male rabbits were fed with a 21% fat, 0.15% cholesterol diet. The left superficial femoral artery (SFA) was de-endotheliazed with a 2F arterial embolectomy catheter. IL18-BP (5 microg, 10 microg, or 25 microg), or 0.9% saline (control) was administered by i.v. bolus during surgery. Rabbits were followed-up at 2 and 4 weeks. Intima-media (I/M) and lumen-whole artery (L/A) area ratios, and luminal areas were measured. Serum lipid levels, liver enzymes, and kidney function were evaluated. Inflammatory cells were quantified and further verified with immunohistofluorescence staining. The extent of lipid deposition in the artery wall was quantified with Oil Red O (ORO) staining employing Zeiss AxioVision 4.6.3. Image analysis software. Lipid laden cells including macrophages were evaluated by transmission electron microscopy (TEM).</p>
<p>RESULTS: Intravenous IL18-BP 5 microg, 10 microg, and 25 microg significantly reduced I/M ratios compared with the control group at both 2 and 4 weeks. There was no significant difference between the 5 microg and 10 microg dose groups. However, at 10 microg, IL18-BP significantly increased L/A ratio more than either the 5 microg IL18-BP or control groups. The high fat diet caused significant elevation of serum lipids at 4 and 6 weeks. IL18-BP had no effect on blood lipid levels. Lipid deposit in the thoracic aorta of the control group at 6 weeks was more than at 4 weeks (P = .025). Administration of IL18-BP inhibited the lipid deposition at 4 weeks (not significant) and 6 weeks (P = .012 to .008) compared with its control group. Lipid laden macrophages (foam cells), as well as endothelial cells and smooth muscle cells were seen in the descending thoracic aorta after 6 weeks of a high fat diet by ORO, immunohistofluorescence staining, and TEM. The lipid laden cells were not seen in either of IL18-BP groups. IL18-BP 10 microg significantly inhibited mono/macro adherence and infiltration in the SFA after balloon-injury at 2 weeks after surgery.</p>
<p>CONCLUSION: A single intravenous dose of IL18-BP significantly decreased arterial neointimal hyperplasia, improved lumen to artery ratio after balloon-injury and also prevented arteriosclerosis progression.</p>
<p>CLINICAL RELEVANCE: A single intravenous dose of IL18BP decreased neointimal hyperplasia and improved arterial L/A ratios in an atherosclerotic balloon-injury animal model. These preliminary results suggest that IL18BP may be a promising molecular approach to inhibit neointimal hyperplasia and arteriosclerosis progression following coronary and peripheral angioplasty.</p>

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</description>

<author>Jian-ming Li et al.</author>


<category>Angioplasty, Balloon</category>

<category>Animals</category>

<category>Atherosclerosis</category>

<category>Dietary Fats</category>

<category>Disease Models, Animal</category>

<category>Disease Progression</category>

<category>Dose-Response Relationship, Drug</category>

<category>Femoral Artery</category>

<category>Hyperplasia</category>

<category>Inflammation</category>

<category>Injections, Intravenous</category>

<category>Intercellular Signaling Peptides and Proteins</category>

<category>Kidney Function Tests</category>

<category>Lipid Metabolism</category>

<category>Lipids</category>

<category>Liver Function Tests</category>

<category>Male</category>

<category>Mice</category>

<category>Rabbits</category>

<category>Recombinant Proteins</category>

<category>Time Factors</category>

<category>Tunica Intima</category>

<category>Tunica Media</category>

</item>






<item>
<title>Inhibition of neutrophil apoptosis after severe trauma is NFkappabeta dependent</title>
<link>http://works.bepress.com/stephen_baker/93</link>
<guid isPermaLink="true">http://works.bepress.com/stephen_baker/93</guid>
<pubDate>Thu, 25 Mar 2010 11:11:18 PDT</pubDate>
<description>
	<![CDATA[
	<p>BACKGROUND: Systemic inflammation may inhibit neutrophil (PMN) apoptosis and promote multiple organ dysfunction syndrome. We hypothesize that severe trauma causes dysregulation of PMN apoptosis.</p>
<p>METHODS: Neutrophils were isolated from trauma patients (24-72 hours after injury; n = 16) and controls (healthy volunteers) and incubated for 18 hours. In separate experiments, control cells were treated +/- the nuclear factor kappa beta (NFkappabeta) inhibitor pyrrolidinithiocarbamate then incubated with 25% patient or control plasma. Apoptosis was quantified by enzyme-linked immunosorbent assay for histone-associated DNA and annexin V fluorescence-activated cell sorter. NFkappabeta activation was determined by Western blot for phosphorylated I kappabeta.</p>
<p>RESULTS: Apoptosis was inhibited in trauma patient PMN. Neutrophil apoptosis correlated with multiple organ dysfunction syndrome score, Acute Physiology and Chronic Health Evaluation II, and platelet count. Patient plasma inhibited apoptosis and induced phosphorylation of I kappabeta in control cells. Inhibition of PMN apoptosis by patient plasma was blocked by pretreatment with pyrrolidinithiocarbamate.</p>
<p>CONCLUSION: NFkappabeta-dependent inhibition of neutrophil apoptosis occurs after trauma. Early inhibition of PMN apoptosis is dependent on the magnitude of injury.</p>

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</description>

<author>Brian Nolan et al.</author>


<category>Apoptosis</category>

<category>Cells, Cultured</category>

<category>Enzyme-Linked Immunosorbent Assay</category>

<category>Histones</category>

<category>Humans</category>

<category>Multiple Organ Failure</category>

<category>NF-kappa B</category>

<category>Neutrophils</category>

<category>Phosphorylation</category>

<category>Pyrrolidines</category>

<category>Thiocarbamates</category>

<category>Wounds and Injuries</category>

</item>






<item>
<title>Molecular determinants of dysregulated GABAergic gene expression in the prefrontal cortex of subjects with schizophrenia</title>
<link>http://works.bepress.com/stephen_baker/92</link>
<guid isPermaLink="true">http://works.bepress.com/stephen_baker/92</guid>
<pubDate>Thu, 25 Mar 2010 11:11:16 PDT</pubDate>
<description>
	<![CDATA[
	<p>BACKGROUND: Prefrontal deficits in gamma-aminobutyric acid (GABA)ergic gene expression, including neuropeptide Y (NPY), somatostatin (SST), and parvalbumin (PV) messenger RNAs (mRNAs), have been reported for multiple schizophrenia cohorts. Preclinical models suggest that a subset of these GABAergic markers (NPY/SST) is regulated by brain-derived neurotrophic factor (BDNF), which in turn is under the inhibitory influence of small noncoding RNAs. However, it remains unclear if these mechanisms are important determinants for dysregulated NPY and SST expression in prefrontal cortex (PFC) of subjects with schizophrenia.</p>
<p>METHODS: Using a postmortem case-control design, the association between BDNF protein, NPY/SST/PV mRNAs, and two BDNF-regulating microRNAs (miR-195 and miR-30a-5p) was determined in samples from the PFC of 20 schizophrenia and 20 control subjects. Complementary studies were conducted in cerebral cortex of mice subjected to antipsychotic treatment or a brain-specific ablation of the Bdnf gene.</p>
<p>RESULTS: Subjects with schizophrenia showed deficits in NPY and PV mRNAs. Within-pair differences in BDNF protein levels showed strong positive correlations with NPY and SST and a robust inverse association with miR-195 levels, which in turn were not affected by antipsychotic treatment or genetic ablation of Bdnf.</p>
<p>CONCLUSIONS: Taken together, these results suggest that prefrontal deficits in a subset of GABAergic mRNAs, including NPY, are dependent on the regional supply of BDNF, which in turn is fine-tuned through a microRNA (miRNA)-mediated mechanism.</p>

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</description>

<author>Nikolaos Mellios et al.</author>


<category>Adult</category>

<category>Aged</category>

<category>Aged, 80 and over</category>

<category>Animals</category>

<category>Brain-Derived Neurotrophic Factor</category>

<category>Case-Control Studies</category>

<category>Chromatin</category>

<category>Gene Expression Regulation</category>

<category>Genotype</category>

<category>Humans</category>

<category>Immunoassay</category>

<category>Immunoprecipitation</category>

<category>Male</category>

<category>Mice</category>

<category>Mice, Inbred C57BL</category>

<category>Mice, Knockout</category>

<category>MicroRNAs</category>

<category>Middle Aged</category>

<category>Neuropeptide Y</category>

<category>Parvalbumins</category>

<category>Prefrontal Cortex</category>

<category>RNA</category>

<category>Schizophrenia</category>

<category>Somatostatin</category>

<category>Young Adult</category>

<category>gamma-Aminobutyric Acid</category>

</item>






<item>
<title>Cell polarity protein Lgl2 is lost or aberrantly localized in gastric dysplasia and adenocarcinoma: an immunohistochemical study</title>
<link>http://works.bepress.com/stephen_baker/91</link>
<guid isPermaLink="true">http://works.bepress.com/stephen_baker/91</guid>
<pubDate>Thu, 25 Mar 2010 11:11:14 PDT</pubDate>
<description>
	<![CDATA[
	<p>The diagnosis of gastric epithelial dysplasia, a precursor lesion of gastric adenocarcinoma, is hindered by interobserver variability and by its resemblance to regenerative changes. Loss of cell polarity, a histological feature of gastric epithelial dysplasia, may be difficult to ascertain, especially in the setting of inflammation or injury. A biomarker of cell polarity could be useful in diagnosis of dysplasia, but has not been reported. The Lethal giant larvae (lgl) gene controls apical-basal polarity of epithelial cells in Drosophila, and has properties of a tumor-suppressor gene. Two homologs, lgl1 and lgl2, are present in mammals and lgl2 mRNA is highly expressed in the stomach. The goal of our study was to test the hypothesis that Lgl2 protein expression and/or localization are disrupted in gastric epithelial dysplasia and adenocarcinoma. Routinely processed pathology specimens including 94 benign mucosae of digestive organs, in addition to 36 reactive gastropathy, 57 gastric epithelial dysplasia, and 77 gastric adenocarcinomas, were immunostained for Lgl2 protein. All normal, reactive, and chronically inflamed gastric epithelia showed basolateral Lgl2 staining. Normal esophageal, duodenal, colonic, biliary, and pancreatic duct mucosae, as well as gastric intestinal metaplasia, did not express Lgl2. All but one case each of gastric epithelial dysplasia and adenocarcinoma showed either complete loss of anti-Lgl2 immunoreactivity or diffuse, mostly weak, cytoplasmic staining. Complete loss of immunoreactivity was significantly more often observed in diffuse-type than in intestinal-type adenocarcinomas (79 vs 48%, respectively). Our data suggest that Lgl2 expression is either aberrantly localized or lost in gastric epithelial dysplasia and adenocarcinoma, whereas it is maintained in reactive gastric mucosa. We propose that Lgl2 may be a potential marker to rule out gastric epithelial dysplasia and adenocarcinoma in diagnostic specimens. However, the consistently negative anti-Lgl2 immunoreactivity seen in intestinal metaplasia does not allow differentiation of dysplasia from intestinal metaplasia with reactive change.</p>

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</description>

<author>Mikhail Lisovsky et al.</author>


<category>Adenocarcinoma</category>

<category>Adenoma</category>

<category>Adolescent</category>

<category>Adult</category>

<category>Aged</category>

<category>Aged, 80 and over</category>

<category>Cell Polarity</category>

<category>Cytoskeletal Proteins</category>

<category>Female</category>

<category>Fluorescent Antibody Technique, Direct</category>

<category>Gastric Mucosa</category>

<category>Humans</category>

<category>Immunoenzyme Techniques</category>

<category>Male</category>

<category>Middle Aged</category>

<category>Precancerous Conditions</category>

<category>Stomach Neoplasms</category>

<category>Tumor Markers, Biological</category>

<category>Young Adult</category>

</item>






<item>
<title>Long-term statin therapy and CSF cholesterol levels: implications for Alzheimer&apos;s disease</title>
<link>http://works.bepress.com/stephen_baker/90</link>
<guid isPermaLink="true">http://works.bepress.com/stephen_baker/90</guid>
<pubDate>Thu, 25 Mar 2010 11:11:13 PDT</pubDate>
<description>
	<![CDATA[
	<p>BACKGROUND/AIMS: It is not yet established whether statins (lipophilic or hydrophilic) reduce the risk of Alzheimer's disease and, if so, by differentially modifying brain lipid levels. Our aim was to assess changes in brain cholesterol metabolism as reflected in the cerebrospinal fluid (CSF) before and after treatment with either atorvastatin or simvastatin.</p>
<p>METHODS: We carried out a longitudinal analysis of CSF cholesterol, lathosterol and 24(S)-hydroxycholesterol before and after treatment with maximum doses of statins in 10 asymptomatic subjects, 8 of whom were heterozygous for apolipoprotein E epsilon4, and in 6 presymptomatic PS1 subjects.</p>
<p>RESULTS: Statins initially reduced CSF lathosterol cholesterol and 24(S)-hydroxycholesterol in both PS1 and non-PS1 subjects reaching a nadir at 6-7 months, followed by a return to baseline at 15 months with an overshoot at 2 years, tending to return to baseline thereafter.</p>
<p>CONCLUSIONS: Possible long-term protective effects of statins are not likely largely related to the temporally-dependent biphasic effects of statin therapy upon the magnitude and direction of changes in CSF lipid levels and their subsequent return to baseline levels.</p>

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</description>

<author>Barbara A. Evans et al.</author>


<category>Adult</category>

<category>Aged</category>

<category>Alzheimer Disease</category>

<category>Apolipoproteins E</category>

<category>Cholesterol</category>

<category>Female</category>

<category>Heptanoic Acids</category>

<category>Heterozygote</category>

<category>Humans</category>

<category>Hydroxycholesterols</category>

<category>Hydroxymethylglutaryl-CoA Reductase Inhibitors</category>

<category>Male</category>

<category>Middle Aged</category>

<category>Mutation</category>

<category>Pilot Projects</category>

<category>Presenilin-1</category>

<category>Pyrroles</category>

<category>Simvastatin</category>

</item>






<item>
<title>Statins differentially affect amyloid precursor protein metabolism in presymptomatic PS1 and non-PS1 subjects</title>
<link>http://works.bepress.com/stephen_baker/89</link>
<guid isPermaLink="true">http://works.bepress.com/stephen_baker/89</guid>
<pubDate>Thu, 25 Mar 2010 11:11:12 PDT</pubDate>
<description>
	<![CDATA[
	
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</description>

<author>Douglas A. Hinerfeld et al.</author>


<category>Adult</category>

<category>Aged</category>

<category>Alzheimer Disease</category>

<category>Amyloid beta-Protein</category>

<category>Amyloid beta-Protein Precursor</category>

<category>Apolipoprotein E4</category>

<category>Female</category>

<category>Humans</category>

<category>Hydroxymethylglutaryl-CoA Reductase Inhibitors</category>

<category>Male</category>

<category>Middle Aged</category>

<category>Mutation</category>

<category>Peptide Fragments</category>

<category>Presenilin-1</category>

<category>Time Factors</category>

</item>






<item>
<title>Midline anterior repair alone vs anterior repair plus vaginal paravaginal repair: a comparison of anatomic and quality of life outcomes</title>
<link>http://works.bepress.com/stephen_baker/88</link>
<guid isPermaLink="true">http://works.bepress.com/stephen_baker/88</guid>
<pubDate>Thu, 25 Mar 2010 11:11:11 PDT</pubDate>
<description>
	<![CDATA[
	<p>Our aim was to study the anatomic recurrence rates and quality of life outcomes of patients who had undergone either anterior colporrhaphy (AC) or anterior colporrhaphy and vaginal paravaginal repair (AC + VPVR) as part of surgery for pelvic organ prolapse. Chart reviews were used to identify anatomic prolapse recurrence. Phone interviews assessed quality of life outcomes [Urogenital Distress Inventory (UDI) and the Incontinence Impact Questionnaire (IIQ)] outcomes. There was a trend towards longer time to anatomic recurrence (any compartment > or =grade 2) in the AC group compared with the AC + VPVR group (median 24 vs 13 months, p=0.069). If only patients who had undergone previous surgery were compared, time to anatomic recurrence appeared significantly longer in the AC group (median 41 vs 12 months, p=0.022). There were 55% of women in the AC group and 46% of women in the AC + VPVR group who reported significant bladder or bulge symptoms based on responses to the phone-administered UDI and IIQ (p=0.89). Our retrospective study did not suggest that adding VPVR was superior in terms of anatomic or quality of life outcomes. Prospective assessment of the role of VPVR in the treatment of pelvic organ prolapse is needed.</p>

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</description>

<author>Abraham N. Morse et al.</author>


<category>Aged</category>

<category>Female</category>

<category>Gynecologic Surgical Procedures</category>

<category>Humans</category>

<category>Middle Aged</category>

<category>Parity</category>

<category>Pregnancy</category>

<category> *Quality of Life</category>

<category>Recurrence</category>

<category>Retrospective Studies</category>

<category>Treatment Outcome</category>

<category>Uterine Prolapse</category>

<category>Vagina</category>

</item>






<item>
<title>Ammonia and carbon dioxide concentrations in disposable and reusable static mouse cages</title>
<link>http://works.bepress.com/stephen_baker/87</link>
<guid isPermaLink="true">http://works.bepress.com/stephen_baker/87</guid>
<pubDate>Thu, 25 Mar 2010 11:11:09 PDT</pubDate>
<description>
	<![CDATA[
	<p>The value of a static mouse cage is partially determined by the cage's ability to dissipate carbon dioxide and ammonia. The authors compared the concentrations of ammonia and carbon dioxide produced by mice housed in two types of static isolator cages: a newly introduced disposable cage and a conventional reusable cage. Female mice were housed in three disposable and three reusable cages (n = 5 per cage). After 7 d, groups that were housed in disposable cages were rehoused in fresh reusable cages and vice versa. Intracage carbon dioxide, ammonia, temperature and relative humidity were measured daily. Overall, there were no significant differences in carbon dioxide or ammonia concentrations between the cage types. Within 30 min of placing mice in cages, carbon dioxide concentrations rose to more than 10,000 ppm in both cage types and rarely dropped below 8,000 ppm during both phases of the study. Ammonia concentrations rose slowly until day 4 and then began to rise rapidly. The maximum average ammonia concentration was 710 ppm. There was a highly significant relationship between increasing levels of humidity and ammonia production in the disposable cages (r = 0.88). For the reusable cages, the correlation was not as strong (r = 0.68). Both cage types were similar in their ability to dissipate carbon dioxide and ammonia. The suggested frequency of cage changing can only be estimated; on the basis of existing literature, it seems prudent to change cages when the ammonia concentration reaches 50 ppm.</p>

	]]>
</description>

<author>Jerald Silverman et al.</author>


<category>Ammonia</category>

<category>Animals</category>

<category> *Animals, Laboratory</category>

<category>Carbon Dioxide</category>

<category>Disposable Equipment</category>

<category>Female</category>

<category>Housing, Animal</category>

<category>Humidity</category>

<category>Mice</category>

<category>Mice, Inbred ICR</category>

<category>Temperature</category>

</item>






<item>
<title>MDCT of 220 consecutive patients with suspected acute pulmonary embolism: incidence of pulmonary embolism and of other acute or non-acute thoracic findings</title>
<link>http://works.bepress.com/stephen_baker/86</link>
<guid isPermaLink="true">http://works.bepress.com/stephen_baker/86</guid>
<pubDate>Thu, 25 Mar 2010 11:11:08 PDT</pubDate>
<description>
	<![CDATA[
	<p>PURPOSE: This study was undertaken to evaluate the incidence of pulmonary embolism (PE) and other clinically relevant thoracic findings discovered on contrast-enhanced multidetector computed tomography (MDCT) examination in patients with a suspicion of acute PE.</p>
<p>MATERIALS AND METHODS: We retrospectively reviewed 220 reports of 40-row MDCT exams in consecutive patients (101 men, 119 women; mean age 55 years+/-18) suspected for acute PE. Presenting symptoms and risk factors were recorded. Image quality and incidence of PE and other clinically relevant thoracic findings were evaluated.</p>
<p>RESULTS: MDCT were diagnostic in 96.8% of patients. Nineteen patients (8.6%) were positive for PE. Signs and symptoms were present in 82.7% (182) and risk factors in 38.2% (84) of the population. Clinically relevant thoracic findings were detected in 45.9% (101) of the patients. Ten patients had PE and other thoracic findings. Half of the patients (110) had neither PE nor other clinically relevant thoracic findings.</p>
<p>CONCLUSIONS: Chest MDCT, with an excellent overall image quality, provided an explanation for the clinical presentation in about 50% of emergency department patients studied and was useful in detecting PE and other thoracic diseases with symptoms mimicking PE. However, half of the exams were negative.</p>

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</description>

<author>Silvia Tresoldi et al.</author>


<category>Adolescent</category>

<category>Adult</category>

<category>Aged</category>

<category>Aged, 80 and over</category>

<category>Female</category>

<category>Humans</category>

<category>Incidence</category>

<category>Italy</category>

<category>Lung Diseases</category>

<category>Male</category>

<category>Middle Aged</category>

<category>Predictive Value of Tests</category>

<category>Pulmonary Embolism</category>

<category>Radiographic Image Enhancement</category>

<category>Retrospective Studies</category>

<category>Sensitivity and Specificity</category>

<category>Tomography, Spiral Computed</category>

</item>






<item>
<title>Independent predictors of morbidity and mortality in blunt colon trauma</title>
<link>http://works.bepress.com/stephen_baker/85</link>
<guid isPermaLink="true">http://works.bepress.com/stephen_baker/85</guid>
<pubDate>Thu, 25 Feb 2010 07:57:17 PST</pubDate>
<description>
	<![CDATA[
	<p>We sought to determine the impact of (1) grade of the colon injury, (2) the formation of an ostomy, and (3) associated injuries on outcomes such as morbidity and mortality after blunt colon injuries. We retrospectively reviewed 16,814 cases of blunt abdominal trauma. Patients with colonic injuries were selected and charts reviewed for demographic, clinical, and outcomes data. Injuries were grouped by the Colon Injury Scale (grades I-V). Independent risk factors of morbidity included spine and lung injuries, as well as increased age. A higher grade of colon injury trended toward a significant association with intra-abdominal complications. Independent risk factors of mortality included liver, heart, and lung injuries, as well as intracerebral blood and female gender. The grade of colon injury, the formation of an ostomy, and management of the colon trauma did not independently predict increased intra-abdominal complications, morbidity, or mortality. These results indicate that patients afflicted with blunt colon trauma experience a high rate of morbidity and mortality from associated injuries and or increased age. Treatment regimens directed at these factors will be most helpful in reducing the high morbidity and mortality after blunt colon trauma. Factors such as ostomy formation and management strategy are not associated with increased morbidity or mortality after blunt colon trauma.</p>

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</description>

<author>Rocco Ricciardi et al.</author>


<category>Adolescent</category>

<category>Adult</category>

<category>Cerebral Hemorrhage</category>

<category>Cohort Studies</category>

<category>Colon</category>

<category>Digestive System Surgical Procedures</category>

<category>Female</category>

<category>Heart Injuries</category>

<category>Humans</category>

<category>Liver</category>

<category>Lung</category>

<category>Male</category>

<category>Middle Aged</category>

<category>Multiple Trauma</category>

<category>Predictive Value of Tests</category>

<category>Rectum</category>

<category>Sex Factors</category>

<category>Wounds, Nonpenetrating</category>

</item>






<item>
<title>Tamoxifen and estrogen lower circulating lipoprotein(a) concentrations in healthy postmenopausal women</title>
<link>http://works.bepress.com/stephen_baker/84</link>
<guid isPermaLink="true">http://works.bepress.com/stephen_baker/84</guid>
<pubDate>Thu, 25 Feb 2010 07:57:16 PST</pubDate>
<description>
	<![CDATA[
	<p>Data in the literature suggest that circulating levels of lipoprotein(a) [Lp(a)] and insulinlike growth factor I (IGF-I) respond similarly to therapy with growth hormone, estrogen, or tamoxifen. To more clearly document these relations, we designed a randomized, double-blind, placebo-controlled study of the effects of tamoxifen and continuous estrogen on circulating levels of Lp(a), IGF-I, and IGF binding protein 3 (IGFBP-3) in healthy postmenopausal women. Both estrogen and tamoxifen decreased serum levels of IGF-I to 30% below baseline during the 3 months of treatment, while IGFBP-3 levels were unchanged. Plasma Lp(a) levels decreased to 24% below baseline after 1 month of treatment with either estrogen or tamoxifen (P < .05 for estrogen only); after 3 months Lp(a) decreased to 34% below baseline with tamoxifen therapy (P < .05) but returned to only 16% below baseline with estrogen. The correlation between Lp(a) and IGF-I was highly significant (P < .0001). We conclude that (1) tamoxifen lowers plasma Lp(a) levels in healthy postmenopausal women, (2) the suppressive effects of tamoxifen and estrogen on circulating Lp(a) concentration diverge after the first month of therapy, and (3) circulating levels of Lp(a) and IGF-I are strongly correlated with each other, an indication that they may share regulatory influences.</p>

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</description>

<author>David A. Shewmon et al.</author>


<category>Aged</category>

<category>Carrier Proteins</category>

<category>Cholesterol, LDL</category>

<category>Double-Blind Method</category>

<category>Estrogens</category>

<category>Female</category>

<category>Humans</category>

<category>Insulin-Like Growth Factor Binding Proteins</category>

<category>Insulin-Like Growth Factor I</category>

<category> Lipoprotein(a)</category>

<category>Middle Aged</category>

<category>Osmolar Concentration</category>

<category>Postmenopause</category>

<category>Reference Values</category>

<category>Somatomedins</category>

<category>Tamoxifen</category>

</item>






<item>
<title>The use of neuromuscular blocking agents in the emergency department to facilitate tracheal intubation in the trauma patient: help or hindrance</title>
<link>http://works.bepress.com/stephen_baker/83</link>
<guid isPermaLink="true">http://works.bepress.com/stephen_baker/83</guid>
<pubDate>Thu, 25 Feb 2010 07:57:15 PST</pubDate>
<description>
	<![CDATA[
	<p>PURPOSE: The purpose of this study is to examine the relationship between the occurrence of a difficult intubation and (1) the use of neuromuscular blocking agents (NMB) and (2) the presence of airway injuries. It is a retrospective analysis of data from a trauma registry.</p>
<p>MATERIALS AND METHODS: Registry records of patients (n = 160) who required emergent endotracheal intubation or establishment of a surgical airway over a 3.5-year period in the emergency department were reviewed. Risk factors for difficult intubations were identified and analyzed using multivariate logistic regression analysis.</p>
<p>RESULTS: NMB were used in 75% of patients requiring intubation. Fifteen percent of the intubations were considered difficult. No association was found between the presence of airway injuries and difficult intubations; however, the use of succinylcholine was associated with a lower risk of difficult intubations compared with intubations where a nondepolarizing NMB was used.</p>
<p>CONCLUSIONS: The use of succinylcholine may result in fewer difficult intubations in the trauma patient than when a nondepolarizing NMB is used. The presence of airway injuries did not appear to predispose to difficult intubations.</p>

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</description>

<author>Elamana Vijayakumar et al.</author>


<category>Adult</category>

<category> *Emergency Treatment</category>

<category> *Facial Injuries</category>

<category>Female</category>

<category>Humans</category>

<category> *Intubation, Intratracheal</category>

<category>Male</category>

<category>Neuromuscular Depolarizing Agents</category>

<category>Neuromuscular Nondepolarizing Agents</category>

<category>Registries</category>

<category>Respiratory System</category>

<category>Retrospective Studies</category>

<category>Succinylcholine</category>

<category>Vecuronium Bromide</category>

</item>






<item>
<title>Cathepsin B expression and its correlation with tumor-associated laminin and tumor progression in gastric cancer</title>
<link>http://works.bepress.com/stephen_baker/82</link>
<guid isPermaLink="true">http://works.bepress.com/stephen_baker/82</guid>
<pubDate>Thu, 25 Feb 2010 07:57:14 PST</pubDate>
<description>
	<![CDATA[
	<p>OBJECTIVE: Cathepsin B, a lysosomal cysteine proteinase, is associated with degradation of laminin. Its activity has been shown to be increased in gastric carcinomas. Laminin is one of the major components of basement membrane involved in cell-matrix interactions and tumor progression. The objectives of this study were to correlate cathepsin B expression in tumor cells with tumor-associated laminin and to further correlate the two with tumor progression.</p>
<p>DESIGN AND SETTING: Resected gastric carcinomas (n = 29) taken from the surgical pathology files of the University of Massachusetts Medical Center, Worcester, were immunostained with cathepsin B and laminin using the avidin-biotin complex technique. Statistical analysis was performed using the exact linear by linear association test and exact Kruskal-Wallis test. Kaplan-Meier curves were plotted, and survival analysis was performed using a nonparametric log-rank test.</p>
<p>RESULTS: Cathepsin B was expressed in 27 (93%) of 29 tumors (11 weak and 16 strong). Staining of tumor-associated laminin showed patterns ranging from almost continuous (n = 4) to moderately discontinuous (n = 11) and highly fragmented (n = 14). The degree of cathepsin B staining in tumor cells significantly correlated with the laminin distribution pattern (P = .0001). The association between increased cathepsin B, decreased laminin, and higher tumor stage was also significant.</p>
<p>CONCLUSIONS: Increased cathepsin B expression by tumor cells associated with decreased tumor-associated laminin may suggest a mechanism for local tumor progression and metastasis. Staining for cathepsin B and laminin may be of prognostic value in gastric carcinomas.</p>

	]]>
</description>

<author>Ashraf Khan et al.</author>


<category>Adenocarcinoma</category>

<category>Adult</category>

<category>Aged</category>

<category>Aged, 80 and over</category>

<category>Cathepsin B</category>

<category>Disease Progression</category>

<category>Female</category>

<category>Humans</category>

<category>Immunohistochemistry</category>

<category>Laminin</category>

<category>Lymphatic Metastasis</category>

<category>Male</category>

<category>Middle Aged</category>

<category>Stomach Neoplasms</category>

<category>Survival Rate</category>

</item>






<item>
<title>Association between gastric intramucosal pH and splanchnic endotoxin, antibody to endotoxin, and tumor necrosis factor-alpha concentrations in patients undergoing cardiopulmonary bypass</title>
<link>http://works.bepress.com/stephen_baker/81</link>
<guid isPermaLink="true">http://works.bepress.com/stephen_baker/81</guid>
<pubDate>Thu, 25 Feb 2010 07:57:12 PST</pubDate>
<description>
	<![CDATA[
	<p>OBJECTIVES: To determine the association between gastric intramucosal pH, a minimally invasive marker reflecting the adequacy of oxygen delivery to the gastrointestinal tract, and splanchnic endotoxin, antibody to endotoxin, and tumor necrosis factor (TNF)-alpha concentrations in patients undergoing cardiopulmonary bypass.</p>
<p>DESIGN: Single-arm, prospective study.</p>
<p>SETTING: University hospital.</p>
<p>PATIENTS: Adults (n = 10) free of hepatic, pulmonary, and renal disease undergoing nonemergent coronary artery bypass surgery.</p>
<p>INTERVENTIONS: After induction of general anesthesia and endotracheal intubation, a tonometer nasogastric tube was positioned in the stomach, and triple-lumen fiberoptic catheters were inserted into the hepatic vein and pulmonary artery. Hepatic venous and mixed venous blood samples were analyzed for endotoxin, antibody to endotoxin, and TNF-alpha at six times: 30 mins after induction of anesthesia (time 1); during vena caval cannulation (time 2); after 15 mins of hypothermic cardiopulmonary bypass (time 3); during spontaneous left ventricular ejection after release of the aortic cross-clamp, but before termination of cardiopulmonary bypass (time 4); 15 mins after termination of cardiopulmonary bypass (time 5); and 1 hr after termination of cardiopulmonary bypass (time 6). Gastric intramucosal pH, systemic oxygen delivery (DO2), mixed venous oxygen saturation, hepatic venous oxygen saturation, and hepatic venous lactate concentrations were recorded at these same times. Data for each variable were compared with baseline values (time 1) for statistical significance.</p>
<p>MEASUREMENTS AND MAIN RESULTS: Cardiopulmonary bypass was associated with an increase (p < .05) in systemic endotoxin concentrations from ventricular ejection until the end of the study. Virtually identical changes in the splanchnic circulation at this time approached, but did not reach, statistical significance, because hepatic venous endotoxin concentrations were higher than the mixed venous endotoxin concentrations at baseline (41.6 +/- 11.2 vs. 16.9 +/- 4.9 pg/mL). Gastric intramucosal pH was abnormal (< 7.35) at 15 mins (p > .05) and at 1 hr after termination of cardiopulmonary bypass (p > .05). The relationship between endotoxin and gastric intramucosal pH was not statistically significant (p = .15). The decrease in endotoxin antibody was small and statistically insignificant. TNF-alpha was not detected in any patient. Systemic DO2 decreased (p < .05) after 15 mins of hypothermic cardiopulmonary bypass, but returned to baseline values thereafter. There were no significant changes in mixed venous and hepatic venous oxygen saturation values. Splanchnic lactate concentrations increased at cannulation (p < .05), after 15 mins of hypothermic cardiopulmonary bypass (p < .05), and 15 mins after termination of cardiopulmonary bypass (p < .05).</p>
<p>CONCLUSIONS: These observations are consistent with the hypothesis that impaired gut-barrier function is responsible for endotoxemia occurring during cardiopulmonary bypass. It is unclear whether increased mucosal permeability and mucosal acidosis are causally related phenomena or simply independent markers of damage to gut epithelium.</p>

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</description>

<author>Lars W. Andersen et al.</author>


<category>Adult</category>

<category>Antibodies</category>

<category> *Cardiopulmonary Bypass</category>

<category>Endotoxins</category>

<category>Gastric Mucosa</category>

<category>Humans</category>

<category>Hydrogen-Ion Concentration</category>

<category>Intraoperative Period</category>

<category>Liver</category>

<category>Mesentery</category>

<category>Middle Aged</category>

<category>Oxygen</category>

<category>Tumor Necrosis Factor-alpha</category>

</item>






<item>
<title>Comparison of tomosynthesis methods used with digital mammography</title>
<link>http://works.bepress.com/stephen_baker/79</link>
<guid isPermaLink="true">http://works.bepress.com/stephen_baker/79</guid>
<pubDate>Thu, 25 Feb 2010 07:57:11 PST</pubDate>
<description>
	<![CDATA[
	<p>RATIONALE AND OBJECTIVES: The authors performed this study to investigate the potential applicability of tomosynthesis to digital mammography. Four methods of tomosynthesis-tuned aperture computed tomography (TACT)-backprojection, TACT-iterative restoration, iterative reconstruction with expectation maximization, and Bayesian smoothing-were compared to planar mammography and analyzed in terms of their contrast-detail characteristics. Specific comparisons between the tomosynthesis methods were not attempted in this study.</p>
<p>MATERIALS AND METHODS: A full-field, amorphous, silicon-based, flat-panel digital mammographic system was used to obtain planar and tomosynthesis projection images. A composite tomosynthesis phantom with a centrally located contrast-detail insert was used as the object of interest. The total exposure for multiple views with tomosynthesis was always equal to or less than that for the planar technique. Algorithms were used to reconstruct the object from the acquired projections.</p>
<p>RESULTS: Threshold contrast characteristics with all tomosynthesis reconstruction methods were significantly better than those with planar mammography, even when planar mammography was performed at more than twice the exposure level. Reduction of out-of-plane structural components was observed in all the tomosynthesis methods analyzed.</p>
<p>CONCLUSION: The contrast-detail trends of all the tomosynthesis methods analyzed in this study were better than those of planar mammography. Further optimization of the algorithms could lead to better image reconstruction, which would improve visualization of valuable diagnostic information.</p>

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</description>

<author>Sankararaman Suryanarayanan et al.</author>


<category>Breast Neoplasms</category>

<category>Mammography</category>

<category>Phantoms, Imaging</category>

<category> *Radiographic Image Enhancement</category>

<category> *Signal Processing, Computer-Assisted</category>

<category> *Tomography, X-Ray Computed</category>

</item>





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