bluuebunny/crossref_metadata_2025 huggingface dataset:
Dextromethorphan Abuse: A Literature Review
Authors: Gershman Jennifer A , Fass Andrea D
Published: September 2013

Objective:

To review dextromethorphan abuse patterns from 2002–2012 and emphasize the pharmacist's role in prevention, education, and sales surveillance.

Data Sources:

A literature search was conducted through PubMed (2002-November 2012), EMBASE (2002-November 2012), and International Pharmaceutical Abstracts (2002-November 2012), using the search term dextromethorphan abuse. The Drug Enforcement Administration and National Association of Boards of Pharmacy websites were searched for dextromethorphan abuse and legislative updates. The search was limited to a 10-year period to identify the most current case reports and studies.

Study Selection and Data Extraction:

The limits used were studies/case reports evaluating humans and published in the English language. Only studies and case reports that assessed dextromethorphan abuse were included in the review. Eight studies and 9 case reports met the inclusion criteria.

Data Synthesis:

Case reports and studies demonstrate that there are patterns associated with dextromethor phan abuse. A study using data reported to the National Poison Data System identified Coricidin as the most (65.5%) commonly abused dextromethorphan product until 2006; its abuse has decreased since that time (p < 0.0001). The most common abuse effects and toxicities cited in studies and case reports include agitation, confusion, central nervous system depression, tachycardia, hypertension, lethargy, psychosis, hallucinations, mydriasis, dizziness, and cardiotoxicity. One study identified that 96% of samples tested positive for other substances in addition to dextromethorphan. Coingestion of other substances is also common among dextromethorphan abusers.

Conclusions:

Case reports and studies demonstrate that there are patterns associated with dextromethorphan abuse. It is difficult to identify dextromethorphan as the causative agent of abuse effects because of coingestion of other substances. Studies should examine the pharmacist's role and the association between dextromethorphan sales restrictions and abuse patterns.
Iron Supplementation and Epoetin Alfa in a Jehovah's Witness with Severe Iron Deficiency Anemia
Authors: Dunn Rebecca L , Blevins Steve M
Published: September 2013

Objective:

To report a case of severe iron deficiency anemia (IDA) in a Jehovah's Witness, successfully treated with iron supplementation and epoetin alfa.

Case Summary:

A 69-year-old African man, a Jehovah's Witness, presented with severe IDA of unknown cause and was admitted to the general medicine service. He was treated with oral and intravenous iron and subcutaneous epoetin alfa. His serum hemoglobin concentration steadily improved. He was discharged to home on epoetin alfa and iron supplementation. His hemoglobin concentration was stable 1 month later.

Discussion:

Iron is a critical factor in hemoglobin synthesis and erythropoiesis, and iron deficiency is a common cause of anemia. Jehovah's Witnesses with severe anemia pose a challenge to providers because of their refusal to accept blood products. Alternative treatment regimens are few, and little evidence exists to guide treatment decisions. Recombinant human erythropoietin (rHuEpo) may play a role, but little is known about its use in IDA. Most studies on rHuEpo focus on its use in the setting of surgery, burns, trauma, pregnancy, and severe gastrointestinal bleeding.

Conclusions:

This case demonstrates that rHuEpo plus iron supplementation may be an acceptable alternative to blood transfusion in a Jehovah's Witness patient with severe IDA.
Phenazopyridine-Induced Toxicity in an Elderly Patient Receiving a Prolonged Regimen of Therapeutic Doses
Authors: Ronald Katie E , Demissie Asmeret
Published: September 2013

Objective:

To report a case of yellow skin pigmentation, acute renal failure, methemoglobinemia, and hemolytic anemia in a patient receiving a prolonged regimen of therapeutic doses of phenazopyridine.

Case Summary:

A 74-year-old female was admitted to the hospital with respiratory distress and acute renal failure, admission serum creatinine of 4.5 mg/dL (reference range 0.7–1.4 mg/dL), and blood urea nitrogen of 80 mg/dL (6–22 mg/dL). Upon admission, she had yellow skin pigmentation, methemoglobinemia with a methemoglobin level of 18.8% (0–3%), and hemolytic anemia with hemoglobin of 6.9 g/dL (12–16 g/dL), reticulocyte count of 5.1% (0.5–2%), and peripheral blood smear revealing Heinz body hemolysis. She had been taking phenazopyridine 200 mg 3 times per day for the 3 weeks prior to admission. Phenazopyridine was discontinued, and the patient was treated with intravenous methylene blue for methemoglobinemia and supportive care for acute renal failure, yellow skin discoloration, and hemolytic anemia. After 5 days in the hospital, the patient was discharged with baseline laboratory values and baseline respiratory status. An objective causality assessment revealed that acute renal failure was possibly and methemoglobinemia and hemolytic anemia were probably associated with phenazopyridine.

Discussion:

Phenazopyridine toxicity may occur with acute overdose or chronic administration of therapeutic doses. Severe toxicity with phenazopyridine is relatively uncommon, but when it does occur it may present as a serious clinical picture, with adverse drug reactions (ADRs) such as methemoglobinemia, hemolytic anemia, acute renal failure, and hepatitis. Removal of phenazopyridine and provision of supportive treatment for the ADRs usually results in reversal of the complications and return to baseline function. Severe cases of methemoglobinemia may need to be treated with intravenous methylene blue in addition to supportive care. This case presents the importance of understanding the risks with long-term use of therapeutic doses of phenazopyridine, especially in geriatric patients.

Conclusions:

The geriatric population and patients with renal insufficiency are at increased risk of phenazopyridine toxicity because of decreased renal clearance of phenazopyridine and its metabolites.
The Potential Effects of Dicloxacillin on Warfarin Management
Authors: Clarke Christina A , Patel Anita D
Published: September 2013

Objective:

To illustrate the effect that dicloxacillin may have on the anticoagulant properties of warfarin.

Case Summary:

A 69-year-old white male presented to the emergency department following a motor vehicle accident. He had been receiving a stable dose of warfarin of approximately 35–37.5 mg/wk for more than 2 years for atrial fibrillation. Computed tomography and magnetic resonance imaging revealed a 1 × 1.3 cm lesion in the anterior aspect of the pancreatic body. During a subsequent hospital stay for a distal pancreatectomy and splenectomy, the patient began a 6-week course of dicloxacillin to treat osteomyelitis of the elbow. During the course of treatment, the patient's warfarin dose was increased by 114% to reach a therapeutic international normalized ratio (INR) approximately 11 days after the antibiotic was discontinued.

Discussion:

Compared with previously published cases documenting the interaction between dicloxacillin and warfarin, to our knowledge, this is the first case to comprehensively assess and document other factors that potentially influenced the patient's INR. At every clinic visit, the patient was assessed for several factors that could have contributed to fluctuations in INR, none of which proved to have a significant effect.

Conclusions:

The addition of dicloxacillin to our patient's stable warfarin regimen resulted in a significant interaction that placed the patient at risk for thromboembolic complications. Careful monitoring of INR from the start of dicloxacillin therapy until 2 weeks after its discontinuation should be considered in patients who are taking warfarin and require dicloxacillin therapy.
Risperidone for Night Terrors and Sleepwalking in an Adult: A Case Report
Authors: Detweiler Mark B
Published: September 2013

Objective:

To report the successful treatment of a case of night terrors and sleepwalking in an adult using low-dose risperidone.

Case Summary:

A 30-year-old female with a history of nightmares as a teen, but with no prior psychiatric history, presented with new-onset night terrors and sleepwalking related to psychosocial stressors. She recalled images of being chased by monsters and of people trying to hurt her. Sleepwalking sometimes involved self-injurious behavior, as she ran through the house screaming. Intake diagnoses included general anxiety disorder (GAD), obsessive-compulsive disorder (OCD) and obsessive-compulsive personality disorder (OCPD). She reported compulsive counting since childhood and episodes of compulsive eating. Risperidone 1 mg was started and eventually titrated to 2 mg at night for night terror and sleepwalking suppression. For GAD, OCD, and OCPD, paroxetine 10 mg was started and titrated to 50 mg. Temazepam 30 mg was added to prolong sleep and cyproheptadine 4 mg was prescribed for anorgasmia. Symptoms were well controlled with the medications for about 8 months. The patient chose to stop the paroxetine and temazepam on day 655, but continued to take risperidone 2 mg for approximately 45 days. When she discontinued the risperidone, the night terrors and sleepwalking returned within 3 days.

Discussion:

Low-dose risperidone has been shown to modulate combat posttraumatic stress disorder nightmares. Its effectiveness for night terrors and sleepwalking has not been reported. In this case, risperidone was the sole medication suppressing night terrors and sleepwalking for a month and a half. As found in previous studies, 2 mg of risperidone seemed to be the optimal dose.

Conclusions:

Risperidone dosed at 1–2 mg at night may be a pharmacologic alternative for the symptoms of sleep terrors with sleepwalking.
Compliance with Antibiotic Dosing Guidelines in Critically Ill Patients Receiving Renal Replacement Therapy
Authors: Udani Suneel , Chen Ling-Xin , Daley Mitchell , Lat Ishaq , Koyner Jay L
Published: September 2013

Background:

Compliance with antibiotic dosing guidelines and achievement of target serum concentrations in patients with infection who are on renal replacement therapy (RRT) is complex, essential for supportive care, and not well studied.

Objective:

To determine adherence rates to antibiotic dosing guidelines in the setting of RRT in the intensive care unit (ICU).

Methods:

We conducted a retrospective, single-center, cohort study evaluating antibiotic dosing in all patients in the ICU receiving RRT between July 2007 and June 2009. Appropriate dosing was determined by comparing dose administered with established guidelines. Dosing was denoted as accurate if adjustment occurred prior to the third administered dose or, if appropriate dosing is every 12 hours or more, within 24 hours. We compared rates according to modality of RRT (intermittent hemodialysis [IHD] vs continuous veno-venous hemodialysis [CVVHD]), indication for RRT (acute kidney injury [AKI] vs end-stage renal disease [ESRD]), and presence of a clinical pharmacist on rounds.

Results:

Adherence rates of 546 patients receiving RRT, with 1761 individual antibiotic prescriptions, were analyzed. Dosing errors were more common in the group receiving CVVHD than in the IHD group (58.1% vs 49.5%; p < 0.001). Frequency of dosing errors did not differ significantly between patients receiving RRT for AKI versus those with ESRD (55.4% vs 51.3%; p = 0.24) or in ICUs with or without a pharmacist on rounds (53.0% vs 54.6%; p = 0.67). Underdosing occurred less frequently with a clinical pharmacist on rounds (18.7% vs 31.3%; p < 0.001). However, in-hospital mortality was not significantly different in underdosed individuals compared with the rest of the cohort (52.3% vs 51.6%; p = 0.92).

Conclusions:

Antibiotic underdosing is common. Increased awareness of dose adjustment guidelines for CVVHD and having a clinical pharmacist on rounds may improve rates of underdosing.
Patient Attitudes concerning Pharmacist Inquiry of Spirituality in a Community Pharmacy
Authors: Twigg Geoffrey , Johnson Mark S
Published: September 2013

Background:

Health care professionals, including physicians and nurses, are becoming more aware of the importance of addressing and incorporating spirituality into patient care. Less is known concerning pharmacist inquiry of patient spiritual beliefs.

Objective:

To observe patients' attitudes in having the pharmacist inquire about their spiritual beliefs in the community pharmacy setting and to determine patient characteristics that may be predictive of these attitudes.

Methods:

This study was conducted in an independent pharmacy on the Eastern Shore of Maryland over a 2-week period. Patients voluntarily filled out an 11-question survey assessing baseline religiosity, using the Duke University Religion Index (DUREL) and attitudes on inquiry by the pharmacist regarding spirituality. The results were analyzed to assess patient attitudes and correlations predictive of these attitudes.

Results:

A total of 105 participants completed the survey. Participants scored high on organizational, nonorganizational, and intrinsic religiosity as assessed by DUREL. Survey results revealed that most patients felt that it was appropriate for both physicians (69%) and pharmacists (57%) to inquire about spiritual beliefs, most (86%) patients believed that prayer was important in treatment, 57% of patients felt comfortable having their pharmacist offer prayer, and 93% felt that spiritual health positively impacts physical and mental health. Organizational religiosity proved to be the best baseline predictor of patient desire in having spirituality acknowledged in pharmacy care (OR 1.733; p = 0.002). Other strong predictors included intrinsic religiosity (OR 1.271; p = 0.004), the patient's desire to have physicians inquire about spirituality (OR 10.365; p = 0.001), and patient comfort level with pharmacist prayer (OR 3.729; p = 0.039).

Conclusions:

This pilot study provides initial evidence that patients are generally supportive of pharmacist inquiry concerning their spiritual and religious beliefs in the community pharmacy setting, with more frequent organized religious attendance being the best predictor. Further studies are needed to validate these results.
Adherence, Persistence, and Predictors Associated with Early Niacin Termination
Authors: Christian Jennifer Briley , Rabatin Vincent , Lowe Kimberly A
Published: September 2013

Background:

Niacin is the most effective therapy currently available to increase high-density lipoprotein cholesterol. However, adherence to niacin may be limited by a number of factors and it is important to characterize who is likely to discontinue the medicine.

Objective:

To measure adherence and persistence to niacin, estimate the influence of niacin dose on adherence, and identify factors associated with early termination of niacin.

Methods:

This retrospective study estimated adherence to niacin by calculating the medication possession ratio, persistence, number of refills, and termination proportion in a large, deidentified US health claims database consisting of 42,685 insurance-carrying adults who were new users of niacin.

Results:

We identified 29,801 new users of niacin who were not taking statins or fibric acid, 12,298 new users of niacin plus statin, 441 new users of niacin plus fibric acid, and 145 new users who initiated all 3 agents. Persistence was lowest among individuals taking less than 1 g/day and was highest among those taking niacin plus fibric acid plus statin (5.10 vs 7.17 months, respectively). However, lower niacin dose was associated with greater adherence, regardless of statin use. Termination of niacin within 1 year of initiation was significantly associated with being female or having 1 of the following conditions: peripheral vascular disease, chronic pulmonary disease, diabetes mellitus, rheumatic disease, or liver disease. Increased age, taking niacin in combination with a statin, or taking drugs from 2 or more concomitant prescription medication classes were significantly associated with a reduced likelihood of termination within 1 year.

Conclusions:

We observed relatively high adherence rates to niacin; however, most patients failed to persist with use of the drug beyond 7 months.
A Clinical Review of Statin-Associated Myopathy
Authors: Shannon Jennifer A. , John Samuel M. , Parihar Harish S. , Allen Shari N. , Ferrara Jenna J.
Published: September 2013

Objective: To review the epidemiology, clinical features, proposed mechanisms, risk factors, and management of statin-associated myopathy. Data Sources: Literature searches were conducted in PubMed (1948 to April 2013), TOXLINE, International Pharmaceutical Abstracts (1970 to April 2013), and Google Scholar using the terms statin, hydroxymethylglutaryl-coenzyme A reductase inhibitors, myopathy, myalgia, safety, and rhabdomyolysis. Results were limited to English publications. Study Selection and Data Extraction: All relevant original studies, guidelines, meta-analyses, and reviews of statin-associated myopathy and safety of statins were assessed for inclusion. References from selected articles were reviewed to identify additional citations. Data Synthesis: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors remain one of the most effective medications for reducing low-density-lipoprotein cholesterol. Statins are well tolerated by most patients; however, it is estimated that 10% to 15% of patients develop statin-related muscle adverse effects known as statin-associated myopathy. Although clinicians may be aware of statin-associated myopathy, they may not be aware of its clinical presentation. Providers should assess individual patient risk factors before choosing the appropriate statin. A variety of skeletal muscle aches that may not present as a danger to the patient, may affect patient adherence and quality of life. There are several steps that providers can take to properly treat and manage patients with myalgia complaints. Conclusions: Statin-associated myopathy is a clinical problem that contributes to statin therapy discontinuation. Patients who are statin intolerant may be treated with alternative treatment options such as low-dose statins, switching statins, using alternative dosing strategies in statins with longer half-lives, non-statin lipid-lowering agents, and complementary therapies.
Patient Perceptions Regarding Enrollment in Automatic Prescription Refill Programs
Authors: Grimm Maureen , Ford Heath , Grubbs Kimberly , Sarao Sukhmani
Published: September 2013

Background: Research has shown that medication adherence is strongly associated with improved patient outcomes and lower health care costs. Although adherence strategies, including automatic prescription refill programs, improve medication adherence to varying degrees, no report to date has examined patient perceptions of and barriers to enrollment in automatic refill programs. This study analyzes patient perceptions of and predictors of enrollment in automatic prescription refill programs through a cross-sectional analysis of patients at a grocer-based community pharmacy. Objectives: To determine patient perceptions regarding automatic prescription refill programs and identify potential barriers to enrollment. Methods: Patient perceptions regarding an automatic refill program were gathered through a survey and assessed using exploratory factor analysis and binary logistic regression techniques for significant predictors of program enrollment. A convenience sample of pharmacy patrons 18 years of age and older was identified at a grocer-based community pharmacy. Results: A total of 110 surveys were evaluated. Hypertension and mental health conditions were the most commonly reported disorders (29.1% and 26.4%, respectively). Enrollment in the program more than doubled during the study period, and all participants enrolled at baseline chose to remain in the program. Eight different perceptions were identified that accounted for approximately 79.14% of data variance. Of the perceptions identified, patients’ sense of satisfaction, in terms of receiving timely, convenient medication refills and not running out of medications, significantly predicted enrollment in the automatic refill program ( P = .0036). Conclusions: Automatic prescription refill programs are known to support patient adherence to medications. Promoting a refill program as a timely and convenient means of safeguarding against running out of medications or medication refills may increase program enrollment and, consequently, medication adherence.
Strength improving mechanism of laser arc hybrid welding of wrought AA 2219 aluminium alloy using AlMg5 wire
Authors: Zhang C , Gao M , Li G , Chen C , Zeng X Y
Published: September 2013

Laser arc hybrid welding of wrought AA 2219 aluminium alloy was studied. The cross-weld tensile strength of the joint using AlMg5 wire was 20% higher than that using AlCu7 wire. The reasons for strength improvement were analysed by microstructure observations via scanning electron microscopy, transmission electron microscopy and electron backscattering patterns. The results showed the strength improvement of the joint using AlMg5 wire depended on two reasons. One is the formation of large amount of fine S–Al2CuMg precipitates. The other is the preformed pinning effect of the precipitates on the dislocations. Finally, the formation of the fine S–Al2CuMg precipitates of the joint using AlMg5 wire was discussed by thermodynamic calculation, and the formation of the preformed dislocation pining effect was discussed by the collision theory of adjacent dendrites during solidification.
A randomized, controlled trial to evaluate the effect of an anti-interleukin-9 monoclonal antibody in adults with uncontrolled asthma
Authors: Oh Chad K , Leigh Richard , McLaurin Kimmie K , Kim Keunpyo , Hultquist Micki , Molfino Nestor A
Published: September 2013

Background

Preclinical studies suggest that interleukin-9 may be a central mediator in the development and maintenance of airway inflammation in asthma. The aim of this study was therefore to evaluate the effects of MEDI-528, an anti-interleukin-9 monoclonal antibody, in adults with confirmed uncontrolled moderate-to-severe asthma.

Methods

In this prospective double-blind, multicenter, parallel-group study, 329 subjects were randomized (1:1:1:1) to subcutaneous placebo or MEDI-528 (30, 100, 300 mg) every 2 weeks for 24 weeks, in addition to their usual asthma medications. The primary endpoint was change in mean Asthma Control Questionnaire-6 (ACQ-6) score at week 13. Secondary endpoints included weighted asthma exacerbation rates and pre-bronchodilator forced expiratory volume in 1 second (FEV1) at weeks 13 and 25, as well as Asthma Quality of Life Questionnaire scores at weeks 12 and 25 and the safety of MEDI-528 throughout the study period. The primary endpoint was analyzed using analysis of covariance.

Results

The study population (n = 327) was predominantly female (69%) with a mean age of 43 years (range 18–65). The mean (SD) baseline ACQ-6 score for placebo (n = 82) and combined MEDI-528 (n = 245) was 2.8 (0.7) and 2.8 (0.8); FEV1 % predicted was 70.7% (15.9) and 71.5% (16.7). Mean (SD) change from baseline to week 13 in ACQ-6 scores for placebo vs combined MEDI-528 groups was −1.2 (1.0) vs −1.2 (1.1) (p = 0.86). Asthma exacerbation rates (95% CI) at week 25 for placebo vs MEDI-528 were 0.58 (0.36–0.88) vs 0.49 (0.37–0.64) exacerbations/subject/year (p = 0.52). No significant improvements in FEV1 % predicted were observed between the placebo and MEDI-528 groups. Adverse events were comparable for placebo (82.9%) and MEDI-528 groups (30 mg, 76.5%; 100 mg, 81.9%; 300 mg, 85.2%). The most frequent were asthma (placebo vs MEDI-528, 30.5% vs 33.5%), upper respiratory tract infection (14.6% vs 17.1%), and headache (9.8% vs 9.8%).

Conclusions

The addition of MEDI-528 to existing asthma controller medications was not associated with any improvement in ACQ-6 scores, asthma exacerbation rates, or FEV1 values, nor was it associated with any major safety concerns.

Trial registration

ClinicalTrials.gov: NCT00968669.
Feature ranking based on synergy networks to identify prognostic markers in DPT-1
Authors: Adl Amin Ahmadi , Qian Xiaoning , Xu Ping , Vehik Kendra , Krischer Jeffrey P
Published: September 2013

Interaction among different risk factors plays an important role in the development and progress of complex disease, such as diabetes. However, traditional epidemiological methods often focus on analyzing individual or a few ‘essential’ risk factors, hopefully to obtain some insights into the etiology of complex disease. In this paper, we propose a systematic framework for risk factor analysis based on a synergy network, which enables better identification of potential risk factors that may serve as prognostic markers for complex disease. A spectral approximate algorithm is derived to solve this network optimization problem, which leads to a new network-based feature ranking method that improves the traditional feature ranking by taking into account the pairwise synergistic interactions among risk factors in addition to their individual predictive power. We first evaluate the performance of our method based on simulated datasets, and then, we use our method to study immunologic and metabolic indices based on the Diabetes Prevention Trial-Type 1 (DPT-1) study that may provide prognostic and diagnostic information regarding the development of type 1 diabetes. The performance comparison based on both simulated and DPT-1 datasets demonstrates that our network-based ranking method provides prognostic markers with higher predictive power than traditional analysis based on individual factors.
Production of biodiesel from soybean and Jatropha Curcas oils with KSF and amberlyst 15 catalysts in the presence of co-solvents
Authors: Calgaroto Cleber , Calgaroto Selma , Mazutti Marcio A , de Oliveira Debora , Pergher Sibele , de Oliveira J Vladimir
Published: September 2013

Experimental conditions for the production of fatty acid methyl esters (FAME) from Jatropha curcas and soybean oils using two acid heterogeneous catalysts (Amberlyst15 and KSF) was optimized, in the presence of different co-solvents (THF, acetone, petroleum ether and n-hexane) in a batch reactor at fixed conditions: oil to methanol molar ratio (1:9), catalyst concentration (4.8 wt%), co-solvent mass ratio (1:1), 160°C and 6 hours. Results showed that the use of co-solvents led to a reduction in the FAME conversion. Higher conversions were obtained for Jatropha curcas compared to soybean oil. The Amberlyst15 presented an enhancement in the catalytic activity after regeneration, providing high biodiesel conversions compared to the fresh resin. The catalyst also presented stability after 5 cycles of reuse. Activity lost was observed for KSF after 2 successive batch experiments, probably due to a deactivation of acid sites.
Proteomic analysis of mismatch repair-mediated alkylating agent-induced DNA damage response
Authors: Chen Xi , Zhao Yong , Li Guo-Min , Guo Lin
Published: September 2013

Background

Mediating DNA damage-induced apoptosis is an important genome-maintenance function of the mismatch repair (MMR) system. Defects in MMR not only cause carcinogenesis, but also render cancer cells highly resistant to chemotherapeutics, including alkylating agents. To understand the mechanisms of MMR-mediated apoptosis and MMR-deficiency-caused drug resistance, we analyze a model alkylating agent (N-methyl-N’-nitro-N-nitrosoguanidine, MNNG)-induced changes in protein phosphorylation and abundance in two cell lines, the MMR-proficient TK6 and its derivative MMR-deficient MT1.

Results

Under an experimental condition that MNNG-induced apoptosis was only observed in MutSα-proficient (TK6), but not in MutSα-deficient (MT1) cells, quantitative analysis of the proteomic data revealed differential expression and phosphorylation of numerous individual proteins and clusters of protein kinase substrates, as well differential activation of response pathways/networks in MNNG-treated TK6 and MT1 cells. Many alterations in TK6 cells are in favor of turning on the apoptotic machinery, while many of those in MT1 cells are to promote cell proliferation and anti-apoptosis.

Conclusions

Our work provides novel molecular insights into the mechanism of MMR-mediated DNA damage-induced apoptosis.
GREM1, FRZB and DKK1 mRNA levels correlate with osteoarthritis and are regulated by osteoarthritis-associated factors
Authors: Leijten Jeroen CH , Bos Steffan D , Landman Ellie BM , Georgi Nicole , Jahr Holger , Meulenbelt Ingrid , Post Janine N , van Blitterswijk Clemens A , Karperien Marcel
Published: September 2013

Introduction

Osteoarthritis is, at least in a subset of patients, associated with hypertrophic differentiation of articular chondrocytes. Recently, we identified the bone morphogenetic protein (BMP) and wingless-type MMTV integration site (WNT) signaling antagonists Gremlin 1 (GREM1), frizzled-related protein (FRZB) and dickkopf 1 homolog (Xenopus laevis) (DKK1) as articular cartilage’s natural brakes of hypertrophic differentiation. In this study, we investigated whether factors implicated in osteoarthritis or regulation of chondrocyte hypertrophy influence GREM1, FRZB and DKK1 expression levels.

Methods

GREM1, FRZB and DKK1 mRNA levels were studied in articular cartilage from healthy preadolescents and healthy adults as well as in preserved and degrading osteoarthritic cartilage from the same osteoarthritic joint by quantitative PCR. Subsequently, we exposed human articular chondrocytes to WNT, BMP, IL-1β, Indian hedgehog, parathyroid hormone-related peptide, mechanical loading, different medium tonicities or distinct oxygen levels and investigated GREM1, FRZB and DKK1 expression levels using a time-course analysis.

Results

GREM1, FRZB and DKK1 mRNA expression were strongly decreased in osteoarthritis. Moreover, this downregulation is stronger in degrading cartilage compared with macroscopically preserved cartilage from the same osteoarthritic joint. WNT, BMP, IL-1β signaling and mechanical loading regulated GREM1, FRZB and DKK1 mRNA levels. Indian hedgehog, parathyroid hormone-related peptide and tonicity influenced the mRNA levels of at least one antagonist, while oxygen levels did not demonstrate any statistically significant effect. Interestingly, BMP and WNT signaling upregulated the expression of each other’s antagonists.

Conclusions

Together, the current study demonstrates an inverse correlation between osteoarthritis and GREM1, FRZB and DKK1 gene expression in cartilage and provides insight into the underlying transcriptional regulation. Furthermore, we show that BMP and WNT signaling are linked in a negative feedback loop, which might prove essential in articular cartilage homeostasis by balancing BMP and WNT activity.
Hypophosphatemia during continuous veno-venous hemofiltration is associated with mortality in critically ill patients with acute kidney injury
Authors: Yang Yi , Zhang Ping , Cui Yu , Lang Xia Bing , Yuan Jing , Jiang Hua , Lei Wen Hua , Lv Rong , Zhu Yi Ling , Lai En Yin , Chen Jiang Hua
Published: September 2013

Introduction

The primary aim of this study was to determine whether hypophosphatemia during continuous veno-venous hemofiltration (CVVH) is associated with the global outcome of critically ill patients with acute kidney injury (AKI).

Methods

760 patients diagnosed with AKI and had received CVVH therapy were retrospectively recruited. Death during the 28-day period and survival at 28 days after initiation of CVVH were used as endpoints. Demographic and clinical data including serum phosphorus levels were recorded along with clinical outcome. Hypophosphatemia was defined according to the colorimetric method as serum phosphorus levels < 0.81 mmol/L (2.5 mg/dL), and severe hypophosphatemia was defined as serum phosphorus levels < 0.32 mmol/L (1 mg/dL). The ratio of CVVH therapy days with hypophosphatemia over total CVVH therapy days was calculated to reflect the persistence of hypophosphatemia.

Results

The Cox proportional hazard survival model analysis indicated that the incidence of hypophosphatemia or even severe hypophosphatemia was not associated with 28-day mortality independently (p = 0.700). Further analysis with the sub-cohort of patients who had developed hypophosphatemia during the CVVH therapy period indicated that the mean ratio of CVVH therapy days with hypophosphatemia over total CVVH therapy days was 0.58, and the ratio independently associated with the global outcome. Compared with the patients with low ratio (< 0.58), those with high ratio (≥ 0.58) conferred a 1.451-fold increase in 28-day mortality rate (95% CI 1.103–1.910, p = 0.008).

Conclusions

Hypophosphatemia during CVVH associated with the global clinical outcome of critically ill patients with AKI. The ratio of CVVH therapy days with hypophosphatemia over total CVVH therapy days was independently associated with the 28-day mortality, and high ratio conferred higher mortality rate.
Intraspecific variation of recombination rate in maize
Authors: Bauer Eva , Falque Matthieu , Walter Hildrun , Bauland Cyril , Camisan Christian , Campo Laura , Meyer Nina , Ranc Nicolas , Rincent Renaud , Schipprack Wolfgang , Altmann Thomas , Flament Pascal , Melchinger Albrecht E , Menz Monica , Moreno-González Jesús , Ouzunova Milena , Revilla Pedro , Charcosset Alain , Martin Olivier C , Schön Chris-Carolin
Published: September 2013

Background

In sexually reproducing organisms, meiotic crossovers ensure the proper segregation of chromosomes and contribute to genetic diversity by shuffling allelic combinations. Such genetic reassortment is exploited in breeding to combine favorable alleles, and in genetic research to identify genetic factors underlying traits of interest via linkage or association-based approaches. Crossover numbers and distributions along chromosomes vary between species, but little is known about their intraspecies variation.

Results

Here, we report on the variation of recombination rates between 22 European maize inbred lines that belong to the Dent and Flint gene pools. We genotype 23 doubled-haploid populations derived from crosses between these lines with a 50 k-SNP array and construct high-density genetic maps, showing good correspondence with the maize B73 genome sequence assembly. By aligning each genetic map to the B73 sequence, we obtain the recombination rates along chromosomes specific to each population. We identify significant differences in recombination rates at the genome-wide, chromosome, and intrachromosomal levels between populations, as well as significant variation for genome-wide recombination rates among maize lines. Crossover interference analysis using a two-pathway modeling framework reveals a negative association between recombination rate and interference strength.

Conclusions

To our knowledge, the present work provides the most comprehensive study on intraspecific variation of recombination rates and crossover interference strength in eukaryotes. Differences found in recombination rates will allow for selection of high or low recombining lines in crossing programs. Our methodology should pave the way for precise identification of genes controlling recombination rates in maize and other organisms.
Binary Flutter as an Oscillating Windmill — Scaling & Linear Analysis
Authors: Farthing S. P.
Published: September 2013

Alternating pitch and heave of a foil can tap light wind or slow free water flow, as the design flow speed for an oscillating blade in any fluid is shown to be limited by its material's ratio of endurance stress to density. The free amplitude of flutter instability is inherently suited to reciprocating a pump whose stroke needs to vary to efficiently capture the changeable wind. Whereas the useful pumping work of multiblade rotary windpumps with their fixed stroke is only 10% of the ideal annual wind energy capture.

Stability algebra of a foil free in pitch and elastic in heave is analytically solved for the first time to prove the stability contours of all Theodorsen frequencies radiate from the same super node of total imbalance and pitch inertia the same as for a virtual mass confined to the 3/4 chord point. The flutter frequency only involves these totals and the trail of the center of pressure behind the pitch axis. Oscillation is damped in the low ratios of total to virtual typical of hydrofoils in water but heavier- than-air wings can be unstable. High intrinsic pitch inertia ratio and trail decrease the tailheavy imbalance ratio needed to force pitch by heave. Perturbing the equations for heave varying as semi-rotary roll, an unswept wing of low enough dynamic imbalance ratio can start to flutter in light wind but stop and feather in storms. The dynamic imbalance can be reduced at large scale and low design windspeed where the gravity effect of static imbalance more safely forces pitch. Between starting and stopping, the amplitude ratio of pitch to roll drops, containing the rise with windspeed of the bending moment amplitude.
Meeting Peak Load Demand by an Offshore Wind Farm in Brazil
Authors: de Oliveira Filho Oyama D. Q. , Araújo Alex M. , Asibor Aigbokhan I. , Rohatgi Janardan
Published: September 2013

The Itamaracá island close to the state of Pernambuco in Brazil receives thousands of visitors during the period of long summer vacations (3 months), increasing the peak demand by a factor of almost 200%. The purpose of this work is to demonstrate that the offshore wind turbines can meet peak energy demand and at the same time reduce impact on conventional energy generation during other months as well. The method involves a nautical wind map at a height of 10 m, and extrapolating it for the desired height by logarithmic law. The annual wind energy output employs Weibull probability density function. The wind turbine siting is chosen with the aid of the nautical chart. The results obtained demonstrate that three wind turbines would generate about 30,000 MWh per year, sufficient for meeting electricity demand in the island.
Bridge-Rail Interaction for Continuous Welded Rail on Cable-Stayed Bridge Due to Temperature Change
Authors: Wang Ping , Zhao Weihua , Chen Rong , Xiao Jieling
Published: September 2013

Continuous welded rail (CWR) has been used in high-speed railways in China. The bridge-rail interaction caused by temperature change when CWR is paved on cable-stayed bridges is studied in this paper. A bridge-rail interaction model is first established using the finite element method. Based on the formulated model, the variation pattern of the force and displacement of rail and bridge-rail relative displacement due to temperature change is studied. The additional temperature forces experienced by stay cables and main towers are obtained, and the influence of the stiffness and temperature change of stay cables and main towers on the additional temperature force of rail is studied. Two simplified algorithms are proposed to facilitate the analysis of bridge-rail interaction. Results show that the distribution patterns of the additional temperature force and displacement of rail on the cable-stayed bridge are the same as those on a common bridge, and the forces experienced by stay cables and main towers are within the safety limit of bridge components. The stiffness variation of stay cables has more influence on the bridge-rail interaction than that of main towers. The distribution patterns of the forces and displacements obtained by the simplified algorithms are similar with those obtained by the FEM. The simplified algorithms can be used for the design of CWR laid on cable-stayed bridges.
Earthquake Response Analysis with Travelling-Wave for a Long-Span Steel Truss-Arch Railway Bridge
Authors: Wang Ruolin , Xu Lin
Published: September 2013

In this paper, seismic response properties of a long-span steel truss-arch railway bridge are analyzed in consideration of the travelling-wave effect of multiple earthquake inputs. Vertical earthquake excitations are considered in the study. The internal forces and displacement responses at structurally critical sections under earthquake excitations at multiple supports are evaluated and compared with the emphasis on investigating the travelling-wave effect on the response properties of the bridge. Taft and El-Centro earthquake waves are adopted respectively to account for different earthquake-wave properties. The influence of wave velocity and earthquake property on the structural dynamic responses taking into account travelling-wave effect is discussed.
Structural Responses of Secondary Lining of High-Speed Railway Tunnel Excavated in Loess Ground
Authors: Zhang Dingli , Fang Qian , Li Pengfei , Wong Louis Ngai Yuen
Published: September 2013

To systematically study the mechanical properties and structural responses of the secondary lining for high-speed railway tunnels excavated in loess ground, on-site monitoring was performed to measure the contact pressure between the primary lining and secondary lining. It is found that the contact pressure reaches its first peak value when the tunnel formwork carriage is removed. The load acting on secondary lining is in the form of deformation pressure, which is different from the loose pressure prescribed in the China Tunnel Design Standard. The results obtained from this study enhance our understanding towards the mechanical characteristics of secondary lining for high-speed railway tunnels and are also beneficial to secondary lining design.
Study on the Mechanical Behavior of Lining Structure for Underwater Shield Tunnel of High-Speed Railway
Authors: Feng Kun , He Chuan , Fang Yong , Jiang Yingchao
Published: September 2013

Referring to the Shiziyang Tunnel – the first underwater shield tunnel for high-speed railway (HSR) in China, model tests and field tests are carried out to study the mechanical properties of the single-layer and double-layer lining structures under hydrostatic water pressure and the interaction between the lining and the stratum. The impact of assembling modes, various ground conditions and water level change on the mechanical behavior of the single-layer lining structure, the influence of the secondary lining construction time, the interface working modes of the double-layer lining structure, and their failure characteristics are investigated and explored in this study. The rationality and reliability of using double-layer lining structure is also discussed.
A Generalized Numerical Simulation Method for Pressure Waves Generated by High-Speed Trains Passing through Tunnels
Authors: Mei Yuangui
Published: September 2013

When high-speed trains pass through tunnels, pressure waves are generated and propagate along the tunnel. Passengers may suffer aural discomfort. A generalized numerical simulation method based on one-dimensional, compressible, unsteady, and non-homentropic flow and the method of characteristics is introduced and validated. Various applications of the method are presented. Pressure waves generated by a single train passing through and two trains passing each other in a plain tunnel are considered. Other applications in non-plain tunnels with auxiliary structures such as airshafts, cross-passages, and perforated walls are also presented. As a result, the proposed generalized numerical simulation method can be applied in most tunnel configurations and particularly used as an analytical tool in the aerodynamic design of high-speed railway tunnels.
The Effects of Side Branches on Compression Waves Propagating in High-Speed Railway Tunnels
Authors: Li Yaozhen
Published: September 2013

According to the theory of finite amplitude sound waves, a one-dimensional compressible unsteady non-homentropic flow model, and the method of characteristics based on the average parameter method are applied to calculate the propagation of entry compression waves in a tunnel, in which the strength of the entry compression wave mainly affects the magnitude of the micro-pressure wave. In addition, acoustical principles are used to simulate the effect of side branches in the tunnel on the sound wave to elucidate the distortion of the waveform of the compression wave. A real-world comparison shows that the programs presented correctly reveal the distortion of the compression wave in the tunnel. After validation, the effects of the number, location, and depth of the side branches are studied in detail. The results show that any change in the parameters of a single side branch has almost no effect on the distortion of the waveform of the compression wave. An increase in the number of side branches, however, does make their effect more significant. This is due to an increase in streaming and reflections which substantially reduce the pressure gradient of the compression wave arriving at the exit portal of the tunnel.
Influence of Pile Cap Effect on Piled Embankment Supporting High-Speed Railway
Authors: Chen H.Y. , Ma J.L. , Qin X.G. , Aziz H.Y.
Published: September 2013

A field test was performed on a piled embankment of Beijing-Shanghai High-speed Railway to investigate the influence of pile cap effect on piled embankment supporting high-speed railway. The developments of pressures and settlements above pile cap and soil surface are obtained by hydrostatic levels and soil pressure cells. Test results indicate that both relative settlement and pressure ratio vary with filling when the height of embankment is less than 0.9 m. When the height of embankment is more than 0.9 m, the relative settlement tends to be stationary while pressure ratio keeps rising till the end of filling and becomes steady quickly in standing period. Furthermore, the numerical simulation is made using Plaxis 2D to analyze the influence of pile cap coverage ratio on settlement and pressure distribution in the single pile processing area. Results show that enlarging the diameter of pile cap can improve the settlement stability of soil between piles remarkably, while reducing pile spacing can reduce the settlement of soil effectively.
Structural Vibration Analysis under Fuzzy Excitations Due to Passing Heavy Vehicles
Authors: Wang B.S. , Yang Y.W.
Published: September 2013

This paper presents a new method to predict the dynamic response of buildings due to passing heavy vehicles in the context of multi-source fuzzy dynamic finite element analysis. The uncertain parameters considered as fuzzy variables include structural mass, stiffness, damping matrix and magnitude of excitation applied at the ground or base level. The implementation of the proposed method consists of the following steps: 1) acquisition of the ground acceleration data through in-situ measurements, 2) analysis of the one-third octave band power spectrum density of the measured data, 3) construction of the fuzzy source membership functions of favorite center frequencies of the one-third octave band, 4) construction of the fuzzy dynamic finite element model of the building structure, 5) analysis of the fuzzy membership function of model responses, and 6) calculation of the overall weighted root-mean-square acceleration in α-sublevel of fuzzy number by ISO2631 standards, from which the effect of ground excitation on building response is assessed. A case study is provided to demonstrate the evaluation of the fuzzy dynamic characteristics and frequency response function in terms of multi-source fuzzy numbers.