bluuebunny/crossref_metadata_2025 huggingface dataset:
High resolution spiral CT for determining the malignant potential of solitary pulmonary nodules: refining and testing the test
Authors: Harders Stefan Walbom , Madsen Hans Henrik , Rasmussen Torben Riis , Hager Henrik , Rasmussen Finn
Published: April 2011

Background

A solitary pulmonary nodule (SPN) may represent early stage lung cancer. Lung cancer is a devastating disease with an overall 5-year mortality rate of approximately 84% but with early detection and surgery as low as 47%. Currently a contrast-enhanced multiple-row detector CT (MDCT) scan is the first examination when evaluating patients with suspected lung cancer.

Purpose

To apply an additional high resolution CT (HRCT) to SPNs to test whether certain morphological characteristics are associated with malignancy, to assess the diagnostic accuracy of HRCT in the characterization of SPNs, and to address the reproducibility of all measures.

Material and Method

Two hundred and thirteen participants with SPNs were included in a follow-up study. Blinded HRCT images were assessed with regard to margin risk categories (MRCs), calcification patterns and certain other characteristics and overall malignancy potential ratings (MPRs) were given. Morphological characteristics were tested against reference standard and ROC methodology was applied to assess diagnostic accuracy. Reproducibility was measured with Kappa statistics and 95% confidence intervals were computed for all results. Histopathology (90%) and CT follow-up (10%) were used as reference standard.

Results

MRCs ( P < 0.001), calcification patterns ( P = 0.003), and pleural retraction ( P < 0.001) were all statistically significantly associated to malignancy. Reproducibility was moderate to substantial. Sensitivity, specificity, and overall diagnostic accuracy of HRCT were 98%, 23% and 87%, respectively. Reproducibility was substantial.

Conclusion

Statistically significant associations between SPN MRCs, calcification patterns, pleural retraction and malignancy were found. HRCT yielded a very high sensitivity and a somewhat lower specificity for malignancy. Reproducibility was high.
Baseline incidence and severity of renal insufficiency evaluated by estimated glomerular filtration rates in patients scheduled for contrast-enhanced CT
Authors: Utsunomiya Daisuke , Yanaga Yumi , Awai Kazuo , Oda Seitaro , Funama Yoshinori , Namimoto Tomohiro , Yamashita Yasuyuki
Published: April 2011

Background

Although pre-existing renal insufficiency (RI) is the most important risk factor for contrast-induced nephropathy (CIN), the background distribution of baseline renal function has not been investigated thoroughly in patients scheduled for contrast-enhanced CT.

Purpose

To investigate the incidence and severity of baseline RI evaluated by estimated glomerular filtration rates (eGFR) in patients who underwent contrast-enhanced CT at an academic center.

Material and Methods

A total of 6586 patients (3630 men and 2956 women; mean age 57.0 ± 11.9 years) who underwent contrast-enhanced CT between January and December 2008 were retrospectively studied. Of these, 829 had cardiovascular diseases (CVD), 5116 had oncologic diseases, 178 had diabetes mellitus (DM), and 1572 had chronic liver disease (CLD). The eGFR (mL/min/1.73 m2) was calculated from their serum creatinine level. Mild, moderate-a, moderate-b, and severe RI were recorded at 60 < =eGFR < 90, 45 < =eGFR < 60, 30 < =eGFR < 45 and eGFR < 30, respectively.

Results

Of the 6586 patients, 1.6%, 3.7%, 13.7%, and 54.2% were judged to present with severe, moderate-b, moderate-a, and mild RI, respectively. While moderate-b-to-severe RI was recorded in 133 (3.2%) of 4161 patients aged 70 years or less, it was observed in 218 (9.0%) of the 2425 patients who were 71 years or older. Among the 829 CVD patients, 9.9% manifested moderate-b-to-severe- and 73.0% mild-to-moderate-a RI. The corresponding rates were 4.4% and 68.9% for oncologic disease, 16.9% and 61.2% for DM, and 4.8% and 71.5% for CLD patients. By univariate analysis, there was a significant association between moderate-b-to-severe RI and the advanced age, CVD, DM, and non-oncologic disease. Multivariate analysis showed that the advanced age, DM, and non-oncologic disease were statistically associated with moderate-b-to-severe RI.

Conclusion

The incidence of RI of eGFR < 45mL/min/1.73 m2 at baseline was high in patients with advanced age, CVD and DM and in patients without oncologic disease.
Clinical and radiological features of pandemic H1N1 2009 influenza virus infection manifesting as acute febrile respiratory illness at their initial presentations: comparison with contemporaneous non-H1N1 patients
Authors: Yun Tae Jin , Park Chang Min , Kwon Gu Jin , Woo Sung Koo , Park Seung Hoon , Choi Seung Hong , Lee Hyun Ju , Goo Jin Mo
Published: April 2011

Background

Since the first outbreak caused by the pandemic H1N1 2009 influenza in Mexico, the virus has spread widely across the world with meaningful morbidity and mortality. However, there are few data on the comparative investigations to assess the clinical and radiological features between the H1N1 patient and non-H1N1 patients.

Purpose

To assess the clinical and radiological features of patients infected by the pandemic H1N1 2009 flu virus at their initial presentation and to compare them with contemporaneous non-H1N1 patients with acute febrile respiratory illness.

Material and Methods

This retrospective study was approved by the ethics committee of the Armed Forces Medical Command, South Korea. From August to September 2009, 337 consecutive patients presented with an acute febrile respiratory illness in a tertiary military hospital. Reverse-transcriptase polymerase-chain-reaction tests were performed in 62 of these patients under the impression of H1N1 infection. Clinical and radiological features at their initial presentation were described for the H1N1 group ( n = 35) and non-H1N1 group ( n = 27) and compared between the two groups.

Results

Increased C-reactive protein level (97%) without leukocytosis (9%) or increased erythrocyte sedimentation rate (0%) was common in the H1N1 group at their initial presentation. On chest radiographs, 12 of 35 (34%) H1N1 patients had abnormal findings; nodules in 10 patients (83%) and consolidations in two (17%). Of the 28 H1N1 patients who underwent thin-section CT 16 patients (57%) showed abnormal findings; ground-glass opacities (GGOs) in 15 (94%), and nodules in 13 (81%). However, there were no significant differences between the H1N1 group and non-H1N1 group in terms of symptoms, laboratory results, or radiological findings ( P > 0.05).

Conclusion

Patients with H1N1 infection show consistent clinical and radiological features at their initial presentation, however, clinical and radiological features of the H1N1 group are not significantly different from those of the non-H1N1 group.
Posterior fossa dural arteriovenous fistulas: diagnosis and follow-up with time-resolved imaging of contrast kinetics (TRICKS) at 1.5T
Authors: Pekkola Johanna , Kangasniemi Marko
Published: April 2011

Background

Time-of-flight MR angiography (TOF MRA) is currently the most widely used non-invasive imaging tool to diagnose dural arteriovenous fistula (DAVF). It is, however, not as sensitive as invasive digital subtraction angiography (DSA) for detecting the arteriovenous shunting inherent in DAVF. Dynamic contrast-enhanced MR angiography allows separation of arterial and venous phases of contrast passage though the brain and can thus demonstrate early venous filling through the arteriovenous shunt.

Purpose

To compare the diagnostic value of TOF MRA and a commercially available dynamic contrast-enhanced MR angiography sequence (TRICKS) at 1.5T in detecting posterior fossa DAVF.

Material and Methods

We retrospectively collected image data for 19 patients who underwent TOF MRA, TRICKS, and DSA either for primary diagnosis or for follow-up of posterior fossa DAVF and assessed the performance of TOF MRA and TRICKS in demonstrating the arteriovenous shunt, with DSA as the reference standard.

Results

TRICKS detected early arterial filling at 94.4% sensitivity and 83.3% specificity. TOF MRA detected high flow-related signal within venous structures at 64.7% sensitivity and 80% specificity.

Conclusion

The commercially available dynamic MR angiography sequence TRICKS with fully automatic vendor postprocessing at 1.5T is more sensitive than TOF MRA in detecting the arteriovenous shunt in posterior fossa DAVF.
Intravascular papillary endothelial hyperplasia: report of two cases
Authors: Paunipagar Bhawan K , Rasalkar Darshana D , Ng Alex , Griffith James F , Bagaria Vaibhav
Published: April 2011

Intravascular papillary endothelial hyperplasia is a rare benign vascular proliferative process as a result of papillary proliferation of the endothelial cells within the vascular lumen. We report two cases of intravascular papillary endothelial hyperplasia affecting the extremities. The characteristic sonological and MR imaging features are discussed, with updated review of literature. Imaging features are helpful in achieving a definitive diagnosis of the intravascular papillary endothelial hyperplasia.
Uterine artery embolization for emergent management of postpartum hemorrhage associated with placenta accreta
Authors: Jung Hye Na , Shin Sung Wook , Choi Suk-Joo , Cho Sung Ki , Park Kwang Bo , Park Hong Suk , Kang Minho , Choo Sung Wook , Do Young Soo , Choo In-wook
Published: April 2011

Background

Although uterine artery embolization (UAE) is a well-recognized alternative treatment for postpartum hemorrhage (PPH) with a high clinical efficacy, the reported success rate of UAE for PPH associated with placenta accreta (PA) is lower. Recently, with advances in techniques and expertise, a few studies have reported favorable results of UAE in controlling PPH in the setting of PA.

Purpose

To evaluate the efficacy of UAE in the emergent management of intractable PPH associated with PA.

Material and Methods

Seventeen consecutive patients who underwent emergent UAE for the management of PPH associated with PA were included in this retrospective study. Medical records were reviewed regarding the delivery and UAE procedure. Follow-up gynecologic outcomes after UAE were obtained by telephone interview.

Results

UAE successfully controlled PPH in 14 patients (82.4%). Three patients underwent hysterectomy after UAE failed to stop the bleeding. All hysterectomy cases were accompanied by uterine atony or total placenta previa. Relevant gynecologic findings were obtained from 10 patients; three patients were breastfeeding and seven patients resumed normal menstruation, including one pregnancy.

Conclusion

UAE appears to be a safe and effective means by which to control PPH associated with PA. PA complicated by uterine atony or placenta previa may be at increased risk of UAE failure.
Superficial thrombophlebitis in varicose vein disease: the particular role of methylenetetrahydrofolate reductase
Authors: Wilmanns C , Casey A , Schinzel H , Walter P K
Published: April 2011

Background

The purpose of this study was to compare the genetic background of superficial (SVT) and deep vein thrombosis (DVT).

Methods

Factor V (FV)-Leiden (G16891A)-, factor II(G20210A)-mutations, protein C- and S, as well as methylenetetrahydrofolate reductase (MTHFR) polymorphisms at C677T and A1298C, and serum homocysteine levels (hcy) were determined in 29 patients with SVT and 26 with DVT.

Findings

FV- and –II-mutations were less frequent in patients with SVT (2/3) compared with DVT (9/5), respectively ( P < 0.002 in case of FV). However, the frequency of the MTHFR C677T polymorphism was significantly higher in patients with SVT compared with DVT (CT 12 versus 10, and TT 7 versus 1, respectively, P << 0.001). The distribution of the MTHFR A1298C genotype and serum hcy levels was similar in both patient groups. Protein S-deficiency was recorded once (SVT).

Interpretation

These results suggest that the MTHFR C677T-mutant genetically predisposes its carriers to SVT which may contribute to hypercoagulation in pre-existing varicose vein disease.
Interpretation of duplex ultrasound in arteriovenous dialysis access: a review of pathologies
Authors: Cullen Nicola , Powell Steven
Published: April 2011

Dialysis access represents a lifeline for the patient with chronic kidney disease requiring renal replacement therapy. The gold standard is well recognized as the autogenous arterio-venous fistula. The surveillance and maintenance of access is therefore crucial to avoid access failure and subsequent morbidity, particularly through central venous catheterization.

Ultrasound examination should involve a review of the clinical history and both physical and sonographic assessment. The interpretation of the acquired information can lead to accurate diagnosis and instigate timely and appropriate treatment of malfunctioning access.

The purpose of this pictorial essay is to describe the complete evaluation of a dialysis access and review the findings associated with the most common pathologies.
An unusual case of a renal artery aneurysm mimicking a renal calculus
Authors: Shah Mushtaq , Sharp Catherine , Weston Michael
Published: April 2011

We report a case of a 55-year-old woman who presented with symptoms typical of renal colic. Ultrasonography demonstrated a calcific density in the region of the renal hilum that demonstrated features in keeping with a renal calculus. The patient underwent extracorporeal shockwave lithotripsy, but pain prompted further imaging that revealed that the calcification in the renal hilum was in fact a renal artery aneurysm. We conclude that to avoid such a diagnostic error, colour or power Doppler should be utilized.
A retrospective review of basilic and cephalic vein-based fistulas
Authors: Ramanathan Anantha K , Nader Nader D , Dryjski Maciej L , Dosluoglu Hasan H , Cherr Gregory S , Curl G Richard , Kuritzky Alan S , Harris Linda M
Published: April 2011

This study compares outcomes of basilic and cephalic vein fistulas for hemodialysis. A retrospective review of arteriovenous fistulas in a university hospital system was performed using charts and hemodialysis records. Patency and demographic data were assessed with life table analysis. One hundred fifty-six patients (88 males; 68 females) underwent creation of 172 autogenous fistulas (mean age 61 years; mean follow-up 78 weeks). There were 101 basilic vein transpositions and 71 cephalic vein fistulas. Primary patency did not differ significantly, while assisted primary patency was significantly better for basilic vein fistulas at one year (73% versus 53%: P = 0.024). Secondary patency was significantly better for basilic fistulas through three years (58% versus 52%; P = 0.027). Primary failure (thrombosis before access or failed maturation) was significantly higher for cephalic than basilic fistulas (28% versus 13%; P = 0.01). Maturation time, usage time and complications were not significantly significant. Thirty-three (33%) basilic vein-based fistulas and 12 (17%) cephalic vein fistulas required revision during follow-up. Basilic vein-based fistulas perform as well as or better than cephalic vein-based fistulas in terms of patency, maturation time, and usage time and complication rates, though requiring more re-interventions.
Outcome of lower extremity revascularization for peripheral artery occlusive disease: is there a difference between men and women?
Authors: Seymour Keri A , Sadowitz Benjamin , Amankwah Kwame S , Gahtan Vivian
Published: April 2011

The incidence of peripheral arterial occlusive disease (PAD) increases with age. Women represent a growing percentage of the elderly population who present with PAD. While speculation exists that gender affects outcome after revascularization procedures, the literature is confusing and often conflicting. This review compares outcomes by gender after open surgical and endovascular lower extremity revascularization (LER) procedures including: demographic differences, patency rates, limb salvage rates, long-term survival, perioperative complications and 30-day mortality. This review summarizes the existing data and discusses current influences on outcome after LER.
Interpretable Predictive Models for Knowledge Discovery from Home‐Care Electronic Health Records
Authors: Westra Bonnie L. , Dey Sanjoy , Fang Gang , Steinbach Michael , Kumar Vipin , Oancea Cristina , Savik Kay , Dierich Mary
Published: April 2011

The purpose of this methodological study was to compare methods of developing predictive rules that are parsimonious and clinically interpretable from electronic health record (EHR) home visit data, contrasting logistic regression with three data mining classification models. We address three problems commonly encountered in EHRs: the value of including clinically important variables with little variance, handling imbalanced datasets, and ease of interpretation of the resulting predictive models. Logistic regression and three classification models using Ripper, decision trees, and Support Vector Machines were applied to a case study for one outcome of improvement in oral medication management. Predictive rules for logistic regression, Ripper, and decision trees are reported and results compared using F‐measures for data mining models and area under the receiver‐operating characteristic curve for all models. The rules generated by the three classification models provide potentially novel insights into mining EHRs beyond those provided by standard logistic regression, and suggest steps for further study.
Tetrabenazine for the Treatment of Tardive Dyskinesia
Authors: Leung Jonathan G , Breden Ericka L
Published: April 2011

Objective:

To evaluate the safety and effectiveness of tetrabenazine for the treatment of tardive dyskinesia.

Data Sources:

Literature was accessed through MEDLINE (1966-September 2010) and The Cochrane Library using the terms tetrabenazine, tardive dyskinesia, and movement disorders. In addition, references from publications identified were reviewed.

Study Selection and Data Extraction:

All English-language articles identified from the data sources were reviewed.

Data Synthesis:

Options available for the management of tardive dyskinesia are limited. Tetrabenazine is a central monoamine-depleting agent approved by the Food and Drug Administration (or chorea associated with Huntington's disease. Three prospective studies of tetrabenazine in the treatment of tardive dyskinesia were identified, as well as 8 additional trials, 1 case series, and 8 case reports. Tetrabenazine may provide benefit in managing symptoms of tardive dyskinesia unresponsive to other treatment modalities. Treatment of tardive dyskinesia with tetrabenazine may be limited by cost and clinically significant adverse effects such as depression, parkinsonism, and somnolence.

Conclusions:

Small trials indicate tetrabenazine may be effective for the treatment of tardive dyskinesia. However, larger, well-conducted trials are needed to confirm these findings. Currently, there is a lack of data coupled with the risk of significant adverse effects to recommend the routine use of tetrabenazine in the management of tardive dyskinesia. Before using tetrabenazine for (he management of tardive dyskinesia, all other options should be exhausted and careful monitoring employed.
Prospective Cohort Study on the Effects and Tolerability of Flutamide in Patients with Female Pattern Hair Loss
Authors: Paradisi Roberto , Porcu Eleonora , Fabbri Raffaella , Seracchioli Renato , Battaglia Cesare , Venturoli Stefano
Published: April 2011

Background

Flutamide has been rarely used (or the treatment of female pattern hair loss (FPHL). Flutamide treatment for FPHL has not been evaluated in long-term studies with sufficiently large numbers of women.

Objective:

To evaluate long-term effects, safety, and tolerability of flutamide in women with FPHL.

Methods:

A prospective cohort study was conducted in our tertiary care university hospital. The cohort included 101 women diagnosed with FPHL from January 1991 to January 2006. These women received yearly reducing doses (250, 125, and 62.5 mg/day) of flutamide for 4 years. The cohort included 33 patients treated with flutamide alone and 68 treated with flutamide combined with an oral contraceptive. Clinical and endocrine evaluations were assessed semiannually and annually, respectively, in the first 3 years of the study, and once in the following year. Liver function was evaluated quarterly.

Results:

Both groups showed a marked decrease in alopecia scores after 12 months of flutamide therapy, compared with baseline values. The maximum drug effect occurred after 2 years and was maintained during the following 2 years of treatment. Androgens were strongly suppressed. During the first year of treatment, 4% of patients abandoned the study due to hepatic disorders related to the drug. During the following years, with the lower treatment regimen, no patient abandoned the study because of hepatic alterations.

Conclusions:

Flutamide is a satisfactory therapeutic regimen for treatment of FPHL in the long run. Moreover, the use of very low doses (62.5 mg/day) of flutamide is associated with complete hepatic tolerability and high adherence.
Medication Assessments by Care Managers Reveal Potential Safety Issues in Homebound Older Adults
Authors: Golden Adam G , Qiu Dingxi , Roos Bernard A
Published: April 2011

Background

Over-the-counter (OTC) medications, benzodiazepines, and barbiturates are not covered under many Medicare drug benefit plans; hence, their use by homebound older adults is largely unreported. Furthermore, the tiered design of Medicare drug formularies may in fact promote the use of older but potentially inappropriate medications. Little is known about the use of these medications in the homebound older adult population.

Objective:

To determine the prevalence of the use by homebound older adults of OTC drugs, dietary supplements (vitamins, minerals, and herbal products), Part D-excluded medications (benzodiazepines and barbiturates), and potentially inappropriate medications (according to Beers criteria).

Methods:

Patients were enrollees in a home and community-based Medicaid waiver provider. All clients were older than 65 and were dually eligible for Medicare and Medicaid. All clients met Florida Medicaid's medical and financial criteria for nursing home placement. The medication list was obtained by geriatric care managers during a home assessment.

Results:

A total of 3911 older adults (mean [SD] age 83.6 [8.0] years) were taking an average of 9.9 [4.8] drugs. Of these individuals. 74.5% were using an OTC medication, 41.9% were using a dietary supplement, 29.6% were using a benzodiazepine or barbiturate, and 25.2% were using at least 1 potentially inappropriate medication.

Conclusions:

Based on data gathered by a geriatric care management assessment, we found that most of the homebound older adults enrolled in our study used medications not included in their Medicare drug benefit. The use of potentially inappropriate medications was also common in this population. Future drug safety initiatives involving the elderly will benefit from engaging care managers in identifying and addressing the potential hazards posed by commonly used prescribed and nonprescribed medications.
Analysis of Circulating MicroRNA: Preanalytical and Analytical Challenges
Authors: McDonald Jennifer S , Milosevic Dragana , Reddi Honey V , Grebe Stefan K , Algeciras-Schimnich Alicia
Published: April 2011

BACKGROUND

There is great interest in circulating microRNAs (miRNAs) as disease biomarkers. Translating promising miRNAs into validated clinical tests requires the characterization of many preanalytical and analytical parameters.

METHODS

miRNAs were extracted from serum and plasma samples of healthy volunteers, and miRNAs known to be present in serum and plasma (miR-15b, miR-16, miR-24, and miR-122) were amplified by reverse-transcription quantitative PCR. Stability and the effects of hemolysis were determined. Assay variation and its components, including the effect of adding control miRNA, were assessed by nested ANOVA.

RESULTS

miRNA concentrations were higher in plasma than in serum. Processing of plasma to remove subcellular/cellular components reduced miRNA concentrations to those of serum. The miRNAs analyzed were stable refrigerated or frozen for up to 72 h and were stable at room temperature for 24 h. Hemolysis increased the apparent concentration of 3 of the miRNAs. The total variability of replicate miRNA concentrations was <2.0-fold, with most of the variability attributable to the extraction process and interassay imprecision. Normalizing results to those of spiked exogenous control miRNAs did not improve this variability.

CONCLUSIONS

Detailed validation of the preanalytical steps affecting miRNA detection and quantification is critical when considering the use of individual miRNAs as clinical biomarkers. Unless these causes of imprecision are considered and mitigated, only miRNAs that are extremely up- or downregulated will be suitable as clinical biomarkers.
Power Assigning Method for Increasing the Number of Users in Time-spreading Optical CDMA Systems
Authors: Salehi Mohammad Reza , Abiri Ebrahim , Kazemi Keyvan , Dezfouli Mehran
Published: April 2011

In this paper, a method for increasing the number of supportable users in a time-spreading Optical code division multiple access (OCDMA) system is proposed. In the presented technique, a unique codeword is assigned to a couple of users instead of just one. Different optical powers are employed for such users in order to distinguish them from each other. Other methods use the frequency or the polarization of the optical signals as an additional coding dimension to increase the number of codewords and hence the number of users in the network. It is proposed to employ nonlinear optical regenerators for separating optical pulses with different powers. A comprehensive design algorithm for such regenerators is presented. In order to evaluate the performance of the designed regenerators a TS-OCDMA system is simulated using OptiSystem software. Results indicate an error free transmission in the system employing the proposed technique.
Information Processing with Length Intervals of Stationary Random Point Processes
Authors: Bendjaballah Cherif
Published: April 2011

For some typical noiseless binary channels operating with signals at low power level, the limits of the information transmission are computed. This is performed for random point processes on a subset of size and on the semi line . The calculations are compared using two length intervals processors, depending on whether the processor starts with a point of the process (type I processor) or with an arbitrary point (type II processor).
Neuregulin-1 Signals from the Periphery Regulate AMPA Receptor Sensitivity and Expression in GABAergic Interneurons in Developing Neocortex
Authors: Abe Yuichi , Namba Hisaaki , Kato Taisuke , Iwakura Yuriko , Nawa Hiroyuki
Published: April 2011

Neuregulin-1 (NRG1) signaling is thought to contribute to both neuronal development and schizophrenia neuropathology. Here, we describe the developmental effects of excessive peripheral NRG1 signals on synaptic activity and AMPA receptor expression of GABAergic interneurons in postnatal rodent neocortex. A core peptide common to all NRG1 variants (eNRG1) was subcutaneously administered to mouse pups. Injected eNRG1 penetrated the blood–brain barrier and activated ErbB4 NRG1 receptors in the neocortex, in which ErbB4 mRNA is predominantly expressed by parvalbumin-positive GABAergic interneurons. We prepared neocortical slices from juvenile mice that were receiving eNRG1 subchronically and recorded inhibitory synaptic activity from layer V pyramidal neurons. Postnatal eNRG1 treatment significantly enhanced polysynaptic IPSCs, although monosynaptic IPSCs were not affected. Examination of excitatory inputs to parvalbumin-containing GABAergic interneurons revealed that eNRG1 treatment significantly increased AMPA-triggered inward currents and the amplitudes and frequencies of miniature EPSCs (mEPSCs). Similar effects on mEPSCs were observed in mice treated with a soluble, full-length form of NRG1 type I. Consistent with the electrophysiologic data, expression of the AMPA receptor GluA1 (i.e., GluR1, GluRA) was upregulated in the postsynaptic density/cytoskeletal fraction prepared from eNRG1-treated mouse neocortices. Cortical GABAergic neurons cultured with eNRG1 exhibited a significant increase in surface GluA1 immunoreactivity at putative synaptic sites on their dendrites. These results indicate that NRG1 circulating in the periphery influences postnatal development of synaptic AMPA receptor expression in cortical GABAergic interneurons and may play a role in conditions characterized by GABA-associated neuropathologic processes.
The Type 3 Adenylyl Cyclase Is Required for Novel Object Learning and Extinction of Contextual Memory: Role of cAMP Signaling in Primary Cilia
Authors: Wang Zhenshan , Phan Trongha , Storm Daniel R.
Published: April 2011

Although primary cilia are found on neurons throughout the brain, their physiological function remains elusive. Human ciliopathies are associated with cognition defects, and transgenic mice lacking proteins expressed in primary cilia exhibit defects in learning and memory. Recently, it was reported that mice lacking the G-protein-coupling receptor somatostatin receptor-3 (SSTR3), a protein expressed predominately in the primary cilia of neurons, have defective memory for novel object recognition and lower cAMP levels in the brain. Since SSTR3 is coupled to regulation of adenylyl cyclase, this suggests that adenylyl cyclase activity in primary cilia of CNS neurons may be critical for some forms of learning and memory. Because the type 3 adenylyl cyclase (AC3) is expressed in primary cilia of hippocampal neurons, we examined AC3−/−mice for several forms of learning and memory. Here, we report that AC3−/−mice show no short-term memory for novel objects and fail to exhibit extinction of contextual fear conditioning. They also show impaired learning and memory for temporally dissociative passive avoidance. Since AC3 is exclusively expressed in primary cilia, we conclude that cAMP signals generated within primary cilia contribute to some forms of learning and memory, including extinction of contextual fear conditioning.
Reduced BACE1 Activity Enhances Clearance of Myelin Debris and Regeneration of Axons in the Injured Peripheral Nervous System
Authors: Farah Mohamed H. , Pan Bao Han , Hoffman Paul N. , Ferraris Dana , Tsukamoto Takashi , Nguyen Thien , Wong Philip C. , Price Donald L. , Slusher Barbara S. , Griffin John W.
Published: April 2011

β-Site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is an aspartyl protease best known for its role in generating the amyloid-β peptides that are present in plaques of Alzheimer's disease. BACE1 has been an attractive target for drug development. In cultured embryonic neurons, BACE1-cleaved N-terminal APP is further processed to generate a fragment that can trigger axonal degeneration, suggesting a vital role for BACE1 in axonal health. In addition, BACE1 cleaves neuregulin 1 type III, a protein critical for myelination of peripheral axons by Schwann cells during development. Here, we asked whether axonal degeneration or axonal regeneration in adult nerves might be affected by inhibition or elimination of BACE1. We report that BACE1 knock-out and wild-type nerves degenerated at a similar rate after axotomy and to a similar extent in the experimental neuropathies produced by administration of paclitaxel and acrylamide. These data indicate N-APP is not the sole culprit in axonal degeneration in adult nerves. Unexpectedly, however, we observed that BACE1 knock-out mice had markedly enhanced clearance of axonal and myelin debris from degenerated fibers, accelerated axonal regeneration, and earlier reinnervation of neuromuscular junctions, compared with littermate controls. These observations were reproduced in part by pharmacological inhibition of BACE1. These data suggest BACE1 inhibition as a therapeutic approach to accelerate regeneration and recovery after peripheral nerve damage.
Evaluation of Two Siblings With Papillon‐Lefèvre Syndrome 5 Years After Treatment of Periodontitis in Primary and Mixed Dentition
Authors: Nickles Katrin , Schacher Beate , Schuster Gabriele , Valesky Eva , Eickholz Peter
Published: April 2011

Background: This case report describes the clinical and microbiologic long‐term outcome 5 years after periodontal therapy of two siblings diagnosed with Papillon‐Lefèvre syndrome (PLS) and tinea capitis.

Methods: In 2005, two brothers diagnosed with PLS and tinea capitis began periodontal treatment. Both of them showed premature mobility of the primary dentition, markedly increased probing depths, and subgingival Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans; Aa). Initial therapy consisted of scaling and root planing based on the concept of full‐mouth disinfection, extraction of periodontally hopeless deciduous teeth, and systemic antibiotics. Reevaluation of clinical parameters revealed a dramatic improvement. After that, the patients were enrolled in a stringent maintenance program. Microbiologic monitoring was performed 1 and 5 years after treatment.

Results: Five years after initial treatment, the periodontal situation was stable in both patients. Residual deciduous teeth, with the exception of one tooth, could be retained and no further teeth were lost. Further disease progression on the previously involved teeth was controlled, and development of periodontitis on erupting teeth was prevented for a period of 5 years.

Conclusions: Even periodontally affected deciduous teeth can be treated successfully in patients with PLS. Suppression of Aa and a stringent maintenance program are of high importance.
Altered Cell Motility and Attachment With Titanium Surface Modifications
Authors: Palaiologou Archontia , Stoute Diana , Fan Yuwei , Lallier Thomas E.
Published: April 2011

Background: Titanium implants are widely used in dentistry to replace lost teeth. Various surface modifications have been used to improve implant retention and osseointegration. This study is designed to compare the ability of three titanium surfaces to promote cell attachment and cell motility of cells relevant to periodontal tissues.

Methods: Three clinically relevant surfaces were tested: 1) machined titanium; 2) a titanium surface roughened through acid etching (dual thermal‐etched titanium [DTET]); and 3) a titanium surface roughened with nanometer‐scale calcium phosphate deposition (nanoscale calcium phosphate–impregnated titanium [NCPIT]). Cell attachment and migration were examined for four cell types: rat osteosarcoma cells, human osteoblasts, and gingival and periodontal ligament (PDL) fibroblasts.

Results: All four cell types attached to each of the three titanium surfaces equally by 2 hours, and the PDL and gingival fibroblasts generally displayed less attachment than the osteosarcoma cells and osteoblasts. The cells displayed differential motility and long‐term attachment to each of the titanium surfaces. Osteosarcoma cells displayed preferential motility on NCPIT, whereas PDL fibroblasts were more motile on machined titanium, and gingival fibroblasts moved more rapidly on both DTET and NCPIT. Osteoblasts displayed little motility on any of the titanium surfaces and lost viability on NCPIT after 24 hours. Gingival fibroblasts lost attachment to machined titanium.

Conclusions: Periodontal cells displayed differential motility and long‐term attachment to titanium surfaces. Selective modification of titanium surface properties in various regions of an implant may be useful in guiding specific cell populations to specific locations where they might best aid in osseointegration and soft tissue remodeling.
Amelogenin Enhances the Proliferation of Cementoblast Lineage Cells
Authors: Kunimatsu Ryo , Tanimoto Kotaro , Tanne Yuki , Kamiya Takashi , Ohkuma Satoru , Huang Yu‐Ching , Yoshimi Yuki , Miyauchi Mutsumi , Takata Takashi , Tanne Kazuo
Published: April 2011

Background: It is well known that enamel matrix proteins play a crucial role in tooth root formation and amelogenesis. Because amelogenin is a major enamel matrix protein, it is assumed that amelogenin also affects the metabolism of cementum. However, the biologic functions of amelogenin in cementoblasts remain unclear. The purpose of this study is to examine the effect of recombinant human full‐length amelogenin (rh174) on the proliferation of cultured human cementoblast‐like (HCEM) and human periodontal ligament (HPDL) cells.

Methods: HCEM and HPDL cells were cultured and treated with 100 ng/mL rh174 in the presence or absence of an anti‐cluster of differentiation (CD) 63 blocking antibody. Cell proliferation was evaluated using a cell proliferation enzyme‐linked immunosorbent assay 5‐bromo‐2‐deoxyuridine kit and quantification of the cell number by 3‐(4, 5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2 H‐tetrazolium‐inner salt assay. The phosphorylation of extracellular signal‐regulated kinases (ERK) 1/2 was measured by enzyme‐linked immunosorbent assay and Western blot analysis.

Results: The proliferation of HCEM and HPDL cells was enhanced significantly (P <0.05) by treatment with rh174, and inhibited significantly (P <0.05) by the addition of anti‐CD63 blocking antibody. In addition, the ratio of phosphorylated ERK1/2 to total ERK1/2 became significantly larger (P <0.05) by treatment with rh174, and was reduced significantly by the addition of anti‐CD63 blocking antibody in both HCEM and HPDL cells.

Conclusion: The results show that rh174 interacts with CD63, and rh174/CD63 interaction activates the ERK1/2 signaling pathway, enhancing the proliferation activities of HCEM and HPDL cells.
Canadian Federal Support for Climate Change and Health Research Compared With the Risks Posed
Authors: Ford James D. , Smith Tanya R. , Berrang-Ford Lea
Published: April 2011

For emerging public health risks such as climate change, the Canadian federal government has a mandate to provide information and resources to protect citizens' health. Research is a key component of this mandate and is essential if Canada is to moderate the health effects of a changing climate.

We assessed whether federal support for climate change and health research is consistent with the risks posed. We audited projects receiving federal support between 1999 and 2009, representing an investment of Can$16 million in 105 projects.

Although funding has increased in recent years, it remains inadequate, with negligible focus on vulnerable populations, limited research on adaptation, and volatility in funding allocations. A federal strategy to guide research support is overdue.
Effect of Common Impurities on the Phase Behavior of Carbon-Dioxide-Rich Systems: Minimizing the Risk of Hydrate Formation and Two-Phase Flow
Authors: Chapoy Antonin , Burgass Rod , Tohidi Bahman , Austell J. Michael , Eickhoff Charles
Published: April 2011

Carbon dioxide (CO2) produced by carbon-capture processes is generally not pure and can contain impurities such as N2, H2, CO, H2 S, and water. The presence of these impurities could lead to challenging flow-assurance issues. The presence of water may result in ice or gas-hydrate formation and cause blockage. Reducing the water content is commonly required to reduce the potential for corrosion, but, for an offshore pipeline system, it is also used as a means of preventing gas-hydrate problems; however, there is little information on the dehydration requirements. Furthermore, the gaseous CO2-rich stream is generally compressed to be transported as liquid or dense-phase in order to avoid two-phase flow and increase in the density of the system. The presence of impurities will also change the system's bubblepoint pressure, hence affecting the compression requirement.

The aim of this study is to evaluate the risk of hydrate formation in a CO2-rich stream and to study the phase behavior of CO2 in the presence of common impurities. An experimental methodology was developed for measuring water content in a CO2-rich phase in equilibrium with hydrates. The water content in equilibrium with hydrates at simulated pipeline conditions (e.g., 4°C and up to 190 bar) as well as after simulated choke conditions (e.g., at -2°C and approximately 50 bar) was measured for pure CO2 and a mixture of 2 mol% H2 and 98 mol% CO2. Bubblepoint measurements were also taken for this binary mixture for temperatures ranging from -20 to 25°C.

A thermodynamic approach was employed to model the phase equilibria. The experimental data available in the literature on gas solubility in water in binary systems were used in tuning the binary interaction parameters (BIPs). The thermodynamic model was used to predict the phase behavior and the hydrate-dissociation conditions of various CO2-rich streams in the presence of free water and various levels of dehydration (250 and 500 ppm). The results are in good agreement with the available experimental data. The developed experimental methodology and thermodynamic model could provide the necessary data in determining the required dehydration level for CO2-rich systems, as well as minimum pipeline pressure required to avoid two-phase flow, hydrates, and water condensation.
Quantifying the Uncertainty in Estimates of Ultimately Recoverable World Conventional Oil Resources
Authors: Tien Chih-Ming , McVay Duane A.
Published: April 2011

Since Hubbert proposed the "peak oil" concept to forecast ultimate recovery of crude oil for the US and the world, there have been countless debates over the timing of peak world conventional oil production rate and ultimate recovery. Forecasts presented in the literature can be grouped into those that are like Hubbert's, with an imminent peak, and those that do not predict an imminent peak. Although both groups have bases for their positions, viewpoints from the two groups are polarized and the debate is often heated. A big reason for the large divide between the two groups is the failure of both to acknowledge the significant uncertainty in their estimates. Although some authors attempt to quantify uncertainty, most use deterministic methods and present single values, with no ranges.

Our objective is to quantify the uncertainty in estimates of world conventional ultimately recoverable resources (URR) and time to peak oil rate. We use two different methodologies. First, we employ a mathematical modeling technique based on regression of historical production data using Hubbert's logistic model and a normal distribution model. However, we conduct the analyses probabilistically, considering errors in both the data and the model, which results in likelihood probability distributions for URR and time to peak rate. Second, we use a multiple-experts analysis to combine estimates from the multitude of papers presented in the literature, yielding an overall distribution for estimated world URR.

Both the mathematical modeling and the multiple-experts analysis indicate that there is considerable uncertainty in estimates of world conventional oil URR. Our best estimate is a P10–P90 range of 1.8–4.4 trillion bbl with a mean of 2.9 trillion bbl. Because of some conservative assumptions in our analysis, we believe the uncertainty is actually greater than indicated above, and the additional uncertainty is in the upside, resulting in larger P90 and mean values. In short, we do not have enough information at this time to say with reliability what the ultimate world conventional oil recovery will be. It could peak soon, somewhere in the distant future, or somewhere in between. It would be wise to consider all of these possible outcomes in planning and making decisions regarding capital investment and formulation of energy policy.
New Correlations of Acid-Fracture Conductivity at Low Closure Stress Based on the Spatial Distributions of Formation Properties
Authors: Mou Jianye , Zhu D.. , Hill A.D.. D.
Published: April 2011

Because of irregular fracture surfaces caused by heterogeneities such as variations in local mineralogy and variations in leakoff behavior, we use a correlation to calculate fracture conductivity in acid fracturing. An acid-fracture-conductivity correlation consists of two parts: conductivity at zero closure stress and the rate of conductivity change with closure stress. Existing correlations do not consider the effect of variations in formation properties and were developed on the basis of laboratory experiments that use core samples with dimensions of only a few inches. On the other hand, acid-fracture simulators have grid sizes of several feet to tens of feet. Therefore, correlations should be scaled up properly when used in a fracture simulator. This paper presents new correlations to obtain the conductivity at zero closure stress. This conductivity can then be incorporated in acid-fracture-conductivity models that consider the effect of closure stress.

In this study, an extensive numerical study was performed using an intermediate-scale acid-fracture model with total dimensions comparable to a gridblock size in an acid-fracturing simulator and grid sizes comparable to core-sample sizes used in laboratory acid-fracture-conductivity tests. In this model, the distributions of permeability and mineralogy along the fracture faces are geostatistically generated. The model generates fracture-surface-etching profiles as a function of acid contact time, from which we can obtain fracture-width distributions when the fracture surfaces have come in contact at low closure stress. We then calculate the fracture conductivity by solving for the flow rate through this irregular domain for a fixed ∆p across the domain. By analyzing the relationship between the fracture conductivity created and statistical properties of the permeability and mineralogy distributions, we developed new acid-fracture-conductivity correlations for low closure stress. These correlations can be used directly to better predict the primary coefficient in the widely used Nierode-Kruk (Nierode and Kruk 1973) correlation of acid-fracture conductivity. This work allows the Nierode-Kruk (N-K) correlation to be scaled up to the dimensions appropriate for use in an acid-fracturing simulator.
Light- and Heavy-Solvent Impacts on Solvent-Aided-SAGD Process: A Low-Pressure Experimental Study
Authors: Li Weiqiang , Mamora Daulat , Li Yamin
Published: April 2011

Coinjecting solvent with steam under steam-assisted gravity-drainage (SAGD) process to reduce the required steam amount for heavy-oil production has gained importance in recent years. The objective of this experimental study was to investigate the drainage mechanism of coinjecting light and heavy solvents to improve production performance.

A 2D cross-sectional low-pressure scaled physical model was constructed. The model represented a half-symmetry cross section of a typical SAGD drainage in the Athabasca formation. Using an infrared camera, we visualized and recorded expansion of the steam chamber and temperature distribution. The fluid injection rate, pressure, and temperature, and produced-liquid volumes were also recorded.

The results show that the relative condensation time of solvent and steam results in different production performances. Light solvent, delivered in the vapour phase to the entire fluid interface, reduces the bitumen viscosity along the whole vapour-chamber boundary, but it may build a thick gas blanket that may reduce the heat transfer from the high-temperature vapour chamber to the surrounding low-temperature bitumen. Coinjecting a suitable multicomponent-solvent mixture, including a heavy solvent, can enhance the production performance by altering the condensation dynamics of the light hydrocarbons.

The conclusions from this study can be used to design suitable solvent mixtures and coinjection strategies to deliver a higher production rate, higher recovery factor with lower cumulative steam required/oil ratio (CSOR), and lower cumulative energy required for oil production (CEOR) from SAGD performance.