bluuebunny/crossref_metadata_2025 huggingface dataset:
Amazon's Mechanical Turk
Authors: Buhrmester Michael , Kwang Tracy , Gosling Samuel D.
Published: February 2011

Amazon’s Mechanical Turk (MTurk) is a relatively new website that contains the major elements required to conduct research: an integrated participant compensation system; a large participant pool; and a streamlined process of study design, participant recruitment, and data collection. In this article, we describe and evaluate the potential contributions of MTurk to psychology and other social sciences. Findings indicate that (a) MTurk participants are slightly more demographically diverse than are standard Internet samples and are significantly more diverse than typical American college samples; (b) participation is affected by compensation rate and task length, but participants can still be recruited rapidly and inexpensively; (c) realistic compensation rates do not affect data quality; and (d) the data obtained are at least as reliable as those obtained via traditional methods. Overall, MTurk can be used to obtain high-quality data inexpensively and rapidly.
Increased HIV-specific CD8+ T-cell cytotoxic potential in HIV elite controllers is associated with T-bet expression
Authors: Hersperger Adam R. , Martin Jeffrey N. , Shin Lucy Y. , Sheth Prameet M. , Kovacs Colin M. , Cosma Gabriela L. , Makedonas George , Pereyra Florencia , Walker Bruce D. , Kaul Rupert , Deeks Steven G. , Betts Michael R.
Published: February 2011

Recent data suggest that CD8+ T-cell effector activity is an important component in the control of HIV replication in elite controllers (ECs). One critical element of CD8+ T-cell effector function and differentiation is the T-box transcription factor T-bet. In the present study, we assessed T-bet expression, together with the effector proteins perforin, granzyme A (Grz A), granzyme B (Grz B), and granulysin, in HIV-specific CD8+ T cells from ECs (n = 20), chronically infected progressors (CPs; n = 18), and highly active antiretroviral therapy (HAART)–suppressed individuals (n = 19). Compared with the other cohort groups, HIV-specific CD8+ T cells among ECs demonstrated a superior ability to express perforin and Grz B, but with no detectable difference in the levels of Grz A or granulysin. We also observed higher levels of T-bet in HIV-specific CD8+ T cells from ECs, with an ensuing positive correlation between T-bet and levels of both perforin and Grz B. Moreover, HIV-specific CD8+ T cells in ECs up-regulated T-bet to a greater extent than CPs after in vitro expansion, with concomitant up-regulation of perforin and Grz B. These results suggest that T-bet may play an important role in driving effector function, and its modulation may lead to enhanced effector activity against HIV.
Enhancer of Zeste Homolog 2 Overexpression Has a Role in the Development of Anaplastic Thyroid Carcinomas
Authors: Borbone Eleonora , Troncone Giancarlo , Ferraro Angelo , Jasencakova Zuzana , Stojic Lovorka , Esposito Francesco , Hornig Nadine , Fusco Alfredo , Orlando Valerio
Published: February 2011

Context:

Enhancer of zeste homolog 2 (EZH2) is a histone lysine methyltransferase belonging to the polycomb group protein family. Overexpression of EZH2 has been found in several human malignancies including hematological and solid tumors.

Objectives:

In this study we investigated the expression levels of EZH2 and its polycomb group protein partners in thyroid carcinoma tissues with different degrees of malignancy to identify potential new therapeutic targets for anaplastic thyroid carcinoma (ATC).

Results:

We show that high EZH2 expression levels are characteristic of undifferentiated ATC, whereas no significant changes were observed in well-differentiated papillary and follicular thyroid carcinomas as compared with normal thyroid. Knockdown of EZH2 in ATC cell lines results in cell growth inhibition, loss of anchorage-independent growth, migration, and invasion properties. Moreover, we demonstrate that EZH2 directly controls differentiation of ATC cells by silencing the thyroid specific transcription factor paired-box gene 8 (PAX8).

Conclusions:

EZH2 is specifically overexpressed in ATC, and it directly contributes to transcriptional silencing of PAX8 gene and ATC differentiation.
Inhibition of the Ras/Raf/MEK/ERK and RET Kinase Pathways with the Combination of the Multikinase Inhibitor Sorafenib and the Farnesyltransferase Inhibitor Tipifarnib in Medullary and Differentiated Thyroid Malignancies
Authors: Hong David S. , Cabanillas Maria E. , Wheler Jennifer , Naing Aung , Tsimberidou Apostolia M. , Ye Lei , Waguespack Steven G. , Hernandez Mike , El Naggar Alder K. , Bidyasar Savita , Wright John , Sherman Steven I. , Kurzrock Razelle
Published: February 2011

Purpose:

Ras/Raf/MAPK kinase/ERK and rearranged in transformation (RET) kinase pathways are important in thyroid cancer. We tested sorafenib, a B-Raf, RET, and vascular endothelial growth factor receptor kinase inhibitor, combined with tipifarnib, a farnesyltransferase inhibitor that inactivates Ras and other farnesylated proteins.

Patients and Methods:

We treated 35 patients with differentiated thyroid cancer (DTC) and medullary thyroid cancer (MTC) in a phase I trial. Sorafenib and tipifarnib were given for 21 d with 7 d rest in each 28-d cycle.

Results:

We enrolled 22 patients with metastatic DTC (16 papillary, five follicular, and one poorly differentiated) and 13 patients with MTC, of whom 15 with DTC and 10 with MTC reached first restaging. When tissue was available, eight of 15 DTC patients (53%) had B-Raf mutations; eight of 13 MTC (61.5%) patients had RET mutations. MTC partial response rate was 38% (five of 13) (duration = 9+, 12, 13, 16+, and 34+ months), stable disease of at least 6 months was 31% (four of 13). The DTC partial response rate was 4.5% (one of 22), and stable disease of at least 6 months was 36% (eight of 22). Median progression-free survival for all 35 patients was 18 months (95% confidence interval, 14.6 to not reached months). Median overall survival has not been reached, with a median follow-up of 24 months with 80% overall survival. Grade 1–2 toxicities were mainly rash, fatigue, and diarrhea. The most common grade 3–4 toxicities were rash, rise in amylase/lipase, and fatigue.

Conclusions:

Inhibiting the Ras/Raf/MAPK kinase/ERK and RET kinase pathways with sorafenib and tipifarnib is well tolerated and active against thyroid cancer.
1,25-Dihydroxyvitamin D3 Reduces TGF-β3-Induced Fibrosis-Related Gene Expression in Human Uterine Leiomyoma Cells
Authors: Halder Sunil K. , Goodwin J. Shawn , Al-Hendy Ayman
Published: February 2011

Background:

Uterine leiomyomas (fibroids) are the most common benign estrogen-dependent tumors of premenopausal women. TGF-β3 up-regulates the synthesis of many of extracellular matrix proteins that are associated with tissue fibrosis.

Objective:

To examine the effect of 1,25-dihydroxyvitamin D3 (vitamin D3) on TGF-β3-induced fibrosis-related protein expression in immortalized human uterine leiomyoma (HuLM) cells.

Methods:

HuLM cells were treated with TGF-β3 with or without vitamin D3. Western blot analyses were employed to test the effect of vitamin D3 on TGF-β3-induced protein expression of collagen type 1, fibronectin, and plasminogen activator inhibitor-1 proteins. Western blots as well as immunofluorescence analyses were used to verify the effect of vitamin D3 on TGF-β3-induced Smad activation involved in extracellular matrix protein synthesis and deposition, which ultimately lead to tissue fibrosis.

Results:

We observed that TGF-β3 induced fibronectin and collagen type 1 protein expression in HuLM cells, and that effect was suppressed by vitamin D3. TGF-β3 also induced protein expression of plasminogen activator inhibitor-1, an important TGF-β target, in HuLM cells, which was also inhibited by vitamin D3. Additionally, TGF-β3 induced phosphorylation of Smad2 as well as nuclear translocation of Smad2 and Smad3 in HuLM cells, whereas vitamin D significantly reduced all these TGF-β3-mediated effects. Therefore, our results suggest that vitamin D3 has consistently reduced TGF-β3 effects that are involved in the process of fibrosis in human leiomyoma cells.

Conclusion:

Vitamin D3 is an antifibrotic factor that might be potentially useful as a novel therapeutic for nonsurgical treatment of benign uterine fibroids.
Limited Value of Ovarian Function Markers following Orthotopic Transplantation of Ovarian Tissue after Gonadotoxic Treatment
Authors: Janse Femi , Donnez Jacques , Anckaert Ellen , de Jong Frank H. , Fauser Bart C. J. M. , Dolmans Marie-Madeleine
Published: February 2011

Context:

In young women, some treatments for cancer or other conditions (such as sickle cell anemia) may give rise to primary ovarian insufficiency. Ovarian transplantation is one of the available options for fertility preservation, with highly variable pregnancy rates.

Objective:

The objective of the study was to investigate markers of ovarian reserve and ovarian function in women up to 7 yr after orthotopic ovarian transplantation. Secondary objectives were to assess the relationship between markers of ovarian reserve and pregnancy rate along with the duration of ovarian function.

Design:

This was a prospective cohort study in 10 women, with a mean follow-up of 2.5 yr.

Setting:

The study was conducted at a university hospital in Brussels, Belgium.

Patients:

Patients included 10 women who were about to receive or had previously received gonadotoxic treatment. In seven women cryopreservation of ovarian tissue was performed before starting treatment. Subsequently autografts were orthotopically transplanted in these women. Three women, who had already developed primary ovarian insufficiency due to treatment, underwent orthotopic transplantation of ovarian allograft tissue originating from their human leukocyte antigen-compatible sisters.

Main Outcome Measures:

Serum concentrations of FSH, LH, estradiol, inhibin B, and anti-Müllerian hormone (AMH) were measured.

Results:

On average, first menses took place after 4.7 months. Duration of graft functioning varied from 2 to more than 60 months. FSH concentrations remained elevated, whereas estradiol levels normalized and AMH was low to undetectable. Inhibin B varied among women and was not associated with the duration of ovarian function (hazard ratio 0.966, 95% confidence interval 0.881–1.059). Two spontaneous pregnancies occurred. Endocrine characteristics were not significantly different in these women.

Conclusions:

Low AMH and inhibin B concentrations may suggest decreased ovarian reserve in women after ovarian transplantation. AMH and inhibin B levels may not be associated with the duration of ovarian graft function or probability to achieve a pregnancy.
Fertility and Ovarian Function in High-Dose Estrogen-Treated Tall Women
Authors: Hendriks A. E. J. , Laven J. S. E. , Valkenburg O. , Fong S. Lie , Fauser B. C. J. M. , de Ridder M. A. J. , de Jong F. H. , Visser J. A. , van Ginneken A. M. , Boot A. M. , Drop S. L. S.
Published: February 2011

Background/Objective:

High-dose estrogen treatment to reduce final height of tall girls has been shown to interfere with fertility. Ovarian function has not been studied. We therefore evaluated fertility and ovarian function in tall women who did or did not receive such treatment in adolescence.

Methods:

This was a retrospective cohort study of 413 tall women aged 23–48 yr, of whom 239 women had been treated. A separate group of 126 fertile, normoovulatory volunteers aged 22–47 yr served as controls.

Results:

Fertility was assessed in 285 tall women (157 treated, 128 untreated) who had attempted to conceive. After adjustment for age, treated women were at increased risk of experiencing subfertility [odds ratio (OR) 2.29, 95% confidence interval (CI) 1.38–3.81] and receiving infertility treatments (OR 3.44, 95% CI 1.76–6.73). Moreover, fecundity was notably affected because treated women had significantly reduced odds of achieving at least one live birth (OR 0.26, 95% CI 0.13–0.52). Remarkably, duration of treatment was correlated with time to pregnancy (r = 0.23, P = 0.008). Ovarian function was assessed in 174 tall women (119 treated, 55 untreated). Thirty-nine women (23%) exhibited a hypergonadotropic profile. After adjusting for age category, treated women had significantly higher odds of being diagnosed with imminent ovarian failure (OR 2.83, 95% CI 1.04–7.68). Serum FSH levels in these women were significantly increased, whereas antral follicle counts and serum anti-Müllerian hormone levels were decreased.

Conclusion:

High-dose estrogen-treated tall women are at risk of subfertility in later life. Their fecundity is significantly reduced. Treated women exhibit signs of accelerated ovarian aging with concomitant follicle pool depletion, which may be the basis of the observed subfertility.
Correlation of Plasma Copeptin and Vasopressin Concentrations in Hypo-, Iso-, and Hyperosmolar States
Authors: Balanescu Sandrina , Kopp Peter , Gaskill Mary Beth , Morgenthaler Nils G. , Schindler Christian , Rutishauser Jonas
Published: February 2011

Background:

Copeptin, the C-terminal moiety of provasopressin, is cosecreted with vasopressin. Copeptin may be a useful parameter to characterize disorders of water homeostasis and can be readily measured in plasma or serum. However, it is unknown to date how circulating copeptin and vasopressin levels correlate at different plasma osmolalites.

Objective:

To correlate plasma copeptin with plasma osmolality and vasopressin concentrations in healthy subjects during iso-, hypo-, and hyperosmolar states.

Methods:

Plasma osmolalities, copeptin, and vasopressin levels were measured in 20 volunteers at baseline, after an oral water load, and during and after iv infusion of 3% saline. Correlation coefficients were determined between plasma osmolalites and copeptin and vasopressin concentrations, as well as between vasopressin and copeptin concentrations.

Results:

Median plasma osmolalities decreased from 290 mOsm/kg (range, 284–302) at baseline to 281 (273–288) mOsm/kg after water load and rose to 301 (298–307) mOsm/kg after hypertonic saline. Median plasma copeptin concentrations decreased from 3.3 (1.1–36.4) pm at baseline to 2.0 (0.9–10.4) pm after water load and increased to 13.6 (3.7–43.3) pm after hypertonic saline. Vasopressin and copeptin concentrations correlated with plasma osmolality (Spearman's rank correlation coefficient 0.49 and 0.77, respectively). There was a close correlation of vasopressin and copeptin concentrations (Spearman's rank correlation coefficient 0.8).

Conclusion:

Plasma vasopressin and copeptin correlate strongly over a wide range of osmolalities in healthy individuals. Therefore, the measurement of copeptin, which remains stable for several days, is a useful alternative to vasopressin measurements and will likely facilitate the differential diagnosis of disorders of water metabolism.
Osteoporosis Medication and Reduced Mortality Risk in Elderly Women and Men
Authors: Center Jacqueline R. , Bliuc Dana , Nguyen Nguyen D. , Nguyen Tuan V. , Eisman John A.
Published: February 2011

Context:

Osteoporotic fractures are associated with premature mortality. Antiresorptive treatment reduces refracture but mortality reduction is unclear.

Objective:

The objective of the study was to examine the effect of osteoporosis treatment [bisphosphonates (BP), hormone therapy (HT), and calcium ± vitamin D only (CaD)] on mortality risk.

Design:

This was a prospective cohort study (April 1989 to May 2007).

Setting:

The study was conducted with community-dwelling elderly (aged 60+ yr) subjects in Dubbo, a semiurban city, Australia.

Subjects:

Subjects included 1223 and 819 women and men in the Dubbo Osteoporosis Epidemiology Study.

Main Outcome Measure:

Mortality according to treatment group was recorded.

Results:

There were 325 (BP, n = 106; HT, n = 77; CaD, n = 142) women and 37 men (BP, n = 15; CaD, n = 22) on treatment. In women, mortality rates were lower with BP 0.8/100 person-years (0.4, 1.4) and HT 1.2/100 person-years (0.7, 2.1) but not CaD 3.2/100 person-years (2.5, 4.1) vs. no treatment 3.5/100 person-years (3.1, 3.8). Accounting for age, fracture occurrence, comorbidities, quadriceps strength, and bone mineral density, mortality risk remained lower for women on BP [hazard ratio (HR) 0.3 (0.2, 0.6)] but not HT [HR 0.8 (0.4, 1.8)]. For 429 women with fractures, mortality risk was still reduced in the BP group [adjusted HR 0.3 (0.2, 0.7)], not accounted for by a reduction in subsequent fractures. In men, lower mortality rates were observed with BP but not CaD [BP 1.0/100 person-years (0.3, 3.9) and CaD 3.1/100 person-years (1.5, 6.6) vs. no treatment 4.3/100 person-years (3.9, 4.8)]. After adjustment, mortality was similar, although not significant [HR 0.5 (0.1, 2.0)].

Conclusions:

Osteoporosis therapy appears to reduce mortality risk in women and possibly men.
A Clock-and-Offer Auction Market for Grid Resources When Bidders Face Stochastic Computational Needs
Authors: Bapna Ravi , Das Sanjukta , Day Robert , Garfinkel Robert , Stallaert Jan
Published: February 2011

Although significant technical advances have been made in the commercial deployment of grid computing, the pricing and allocation of distributed computing resources remains understudied. We develop a customized clock auction that is able to allocate grid resources and discover separate prices for the different computing resources under the condition that buyers do not know with certainty how much of these resources they will need. The proposed clock auction facilitates the discovery of unit prices for the resources in each time period in a finite-horizon market. Our mechanism exploits the lopsided nature of the grid market where a small number of large-scale jobs are expected to be completed by a large number of heterogeneous, distributed machines. The traditional stopping rule used for clock auctions is not effective in our setting, and therefore we design several adaptations that can be implemented in real time, geared toward ending the auction process quickly while producing a close-to-efficient allocation. Our extensive computations show that our clock-and-offer auction outperforms the traditional clock auction in terms of computational tractability, social welfare, and expected bidder's utility. For large problems of practical interest, we develop a transportation-based heuristic for the NP-complete bid feasibility problem and demonstrate theoretically and computationally that it quickly produces high-quality solutions to the overall problem.
Exact Solution of Graph Coloring Problems via Constraint Programming and Column Generation
Authors: Gualandi Stefano , Malucelli Federico
Published: February 2011

We consider two approaches for solving the classical minimum vertex coloring problem—that is, the problem of coloring the vertices of a graph so that adjacent vertices have different colors and minimizing the number of used colors—namely, constraint programming and column generation. Constraint programming is able to solve very efficiently many of the benchmarks but suffers from a lack of effective bounding methods. On the contrary, column generation provides tight lower bounds by solving the fractional vertex coloring problem exploited in a branch-and-price algorithm, as already proposed in the literature. The column generation approach is here enhanced by using constraint programming to solve the pricing subproblem and to compute heuristic solutions. Moreover, new techniques are introduced to improve the performance of the column generation approach in solving both the linear relaxation and the integer problem. We report extensive computational results applied to the benchmark instances: we are able to prove optimality of 11 new instances and to improve the best-known lower bounds on 17 other instances. Moreover, we extend the solution approaches to a generalization of the problem known as the minimum vertex graph multicoloring problem, where a given number of colors has to be assigned to each vertex.
An Asymptotic Test of Optimality Conditions in Multiresponse Simulation Optimization
Authors: Angün Ebru , Kleijnen Jack
Published: February 2011

This paper derives a novel, asymptotic statistical test of the Karush–Kuhn–Tucker first-order necessary optimality conditions in random simulation models with multiple responses. This test combines a simple form of the delta method and a generalized version of Wald's statistic. The test is applied to both a toy problem and an (s, S) inventory-optimization problem with a service-level constraint; its numerical results are encouraging.
A Hybrid Heuristic for an Inventory Routing Problem
Authors: Archetti Claudia , Bertazzi Luca , Hertz Alain , Speranza M. Grazia
Published: February 2011

We consider an inventory routing problem in discrete time where a supplier has to serve a set of customers over a multiperiod horizon. A capacity constraint for the inventory is given for each customer, and the service cannot cause any stockout situation. Two different replenishment policies are considered: the order-up-to-level and the maximum-level policies. A single vehicle with a given capacity is available. The transportation cost is proportional to the distance traveled, whereas the inventory holding cost is proportional to the level of the inventory at the customers and at the supplier. The objective is the minimization of the sum of the inventory and transportation costs. We present a heuristic that combines a tabu search scheme with ad hoc designed mixed-integer programming models. The effectiveness of the heuristic is proved over a set of benchmark instances for which the optimal solution is known.
On Equivalence of Semidefinite Relaxations for Quadratic Matrix Programming
Authors: Ding Yichuan , Ge Dongdong , Wolkowicz Henry
Published: February 2011

We analyze two popular semidefinite programming relaxations for quadratically constrained quadratic programs with matrix variables. These relaxations are based on vector lifting and on matrix lifting; they are of different size and expense. We prove, under mild assumptions, that these two relaxations provide equivalent bounds. Thus, our results provide a theoretical guideline for how to choose a less expensive semidefinite programming relaxation and still obtain a strong bound. The main technique used to show the equivalence and that allows for the simplified constraints is the recognition of a class of nonchordal sparse patterns that admit a smaller representation of the positive semidefinite constraint.
Discounted Continuous-Time Markov Decision Processes with Constraints: Unbounded Transition and Loss Rates
Authors: Guo Xianping , Piunovskiy Alexei
Published: February 2011

This paper deals with denumerable continuous-time Markov decision processes (MDP) with constraints. The optimality criterion to be minimized is expected discounted loss, while several constraints of the same type are imposed. The transition rates may be unbounded, the loss rates are allowed to be unbounded as well (from above and from below), and the policies may be history-dependent and randomized. Based on Kolmogorov's forward equation and Dynkin's formula, we remind the reader about the Bellman equation, introduce and study occupation measures, reformulate the optimization problem as a (primary) linear program, provide the form of optimal policies for a constrained optimization problem here, and establish the duality between the convex analytic approach and dynamic programming. Finally, a series of examples is given to illustrate all of our results.
Average Optimality in Nonhomogeneous Infinite Horizon Markov Decision Processes
Authors: Wachs Allise O. , Schochetman Irwin E. , Smith Robert L.
Published: February 2011

We consider a nonhomogeneous stochastic infinite horizon optimization problem whose objective is to minimize the overall average cost per period of an infinite sequence of actions (average optimality). Optimal solutions to such problems will in general be nonstationary. Moreover, a solution that initially makes poor decisions, and then selects wisely thereafter, can be average optimal. However, we seek average optimal solutions with optimal short-term, as well as long-term, behavior. Our approach is to first transform our stochastic problem into one that is deterministic, using the standard device of formulating the problem as one of choosing a sequence of policies, as opposed to actions. Within this deterministic framework, states become probability distributions over the original stochastic states. Then, by weakening the notion of state reachability, and strengthening the notion of efficiency traditionally used in the deterministic framework, we prove that such efficient solutions exist and are average optimal, thus simultaneously exhibiting both optimal long- and short-run behavior. This deterministic view of the property of stochastic ergodicity offers the potential to relax the traditional conditions for average optimality that use coefficients of ergodicity, as well as the opportunity to strengthen the criterion of average optimality through the property of efficiency.
Near-Optimal Solutions and Large Integrality Gaps for Almost All Instances of Single-Machine Precedence-Constrained Scheduling
Authors: Schulz Andreas S. , Uhan Nelson A.
Published: February 2011

We consider the problem of minimizing the weighted sum of completion times on a single machine subject to bipartite precedence constraints in which all minimal jobs have unit processing time and zero weight, and all maximal jobs have zero processing time and unit weight. For various probability distributions over these instances—including the uniform distribution—we show several “almost all”-type results. First, we show that almost all instances are prime with respect to a well-studied decomposition for this scheduling problem. Second, we show that for almost all instances, every feasible schedule is arbitrarily close to optimal. Finally, for almost all instances, we give a lower bound on the integrality gap of various linear programming relaxations of this problem.
Examining the Function of Problem Behavior in Fragile X Syndrome: Preliminary Experimental Analysis
Authors: Langthorne Paul , McGill Peter , O'Reilly Mark F , Lang Russell , Machalicek Wendy , Chan Jeffrey Michael , Rispoli Mandy
Published: February 2011

Fragile X syndrome is the most common inherited cause of intellectual and developmental disability. The influence of environmental variables on behaviors associated with the syndrome has received only scant attention. The current study explored the function served by problem behavior in fragile X syndrome by using experimental functional analysis methodology with 8 children with fragile X. No child met criteria for attention-maintained problem behavior, 5 children met criteria for escape-maintained problem behavior, and 4 children met criteria for tangible-maintained problem behavior. Results are discussed and compared with previous findings on the function of problem behavior in fragile X syndrome, and implications for intervention are discussed. It is noted that the external validity of these findings is limited by the small sample size.
Marital Satisfaction and Parenting Experiences of Mothers and Fathers of Adolescents and Adults With Autism
Authors: Hartley Sigan L , Barker Erin T , Seltzer Marsha Mailick , Greenberg Jan S , Floyd Frank J
Published: February 2011

The association of marital satisfaction with parenting burden and quality of the parent–child relationship was examined in 91 married mothers and fathers of co-residing adolescents and adults with autism spectrum disorders. Within-couple differences between mothers and fathers in how child characteristics related to these parenting experiences were also evaluated. Multilevel modeling was used to control for the dependency in couple data. Marital satisfaction was an important predictor of parenting experiences, particularly for fathers. Mothers reported feeling closer to their son or daughter than did fathers. Fathers' parenting experiences were more strongly impacted by child characteristics than were mothers' parenting experiences. Results emphasized the connection between the marital relationship and parenting experiences and overlapping but unique experiences of mothers and fathers.
Evaluation of the iChem® Velocity™ Urine Chemistry Analyzer in a hospital routine laboratory
Authors: Hoffmann Peter , Hoffmann Christina , Ziebig Reinhard , Zimmermann Mathias
Published: February 2011

Background: The novel urine chemistry analyzer iChem Velocity (IRIS Diagnostics) offers improved urinalysis automation options through integration with the well-established iQ200 urine microscopy analyzer. In the course of optimizing the workflow in our hospital routine laboratory, we evaluated the performance of the iChem Velocity.

Methods: A total of 257 random urine samples were analyzed with the iChem Velocity, iQ200, Clinitek Atlas (Siemens Healthcare Diagnostics) and by manual microscopy.

Results: Depending on the parameter, 93% (hemoglobin) to 100% (urobilinogen), the iChem Velocity and Clinitek Atlas results agreed within the same rank or within one level of difference. The Clinitek Atlas featured a higher sensitivity for hemoglobin (area under the curve 0.86) and leukocyte esterase (area under the curve 0.85) compared with the iChem Velocity (area under the curve for hemoglobin 0.73, leukocytes 0.78). Imprecision was highest for hemoglobin and leukocytes in a pathological sample pool. While the precision of the Clinitek Atlas for hemoglobin measurements was superior, the iChem Velocity was more precise in analyzing protein and pH.

Conclusions: Through urinalysis automation with the iChem Velocity and iQ200, we achieved a reduction of hands-on time by 89%. The sensitivity of this new system should be further improved through ongoing development.
The ROMA (Risk of Ovarian Malignancy Algorithm) for estimating the risk of epithelial ovarian cancer in women presenting with pelvic mass: is it really useful?
Authors: Montagnana Martina , Danese Elisa , Ruzzenente Orazio , Bresciani Valentina , Nuzzo Teresita , Gelati Matteo , Salvagno Gian Luca , Franchi Massimo , Lippi Giuseppe , Guidi Gian Cesare
Published: February 2011

Background: The study is aimed at evaluating the performance of the predictive model ROMA (Risk of Ovarian Malignancy Algorithm), which utilizes the combination of human epididymis protein 4 (HE4) and CA125 values to assess the risk of epithelial ovarian cancer (EOC) in women with a pelvic mass.

Methods: One hundred and four women diagnosed with a pelvic mass (55 EOC and 49 benign cases) and scheduled to have surgery were enrolled, along with 49 healthy females. Preoperative serum concentrations of HE4 and CA125 were measured. Separate logistic regression algorithms ROMA for pre-menopausal and post-menopausal women were used to categorize patients into low- and high-risk groups for EOC. The area under the curve (AUC), sensitivity and specificity were calculated for HE4, CA125 and ROMA for the diagnosis of ovarian cancer using receiver operating characteristic (ROC) analysis.

Results: The median CA125 and HE4 serum concentrations were significantly higher among EOC patients than in healthy females (both p<0.05) and those with a benign mass (both p<0.05). The pre-menopausal group included 36 benign cases (29 of which were classified by ROMA as low-risk with a specificity of 80.6%; 95% CI: 64.0%–91.8%), and 15 EOC (eight of which were classified by ROMA as high-risk, with a sensitivity of 53.3%; 95% CI: 26.6%–78.7%). The post-menopausal group enclosed 13 benign cases (11 of which were classified by ROMA as low-risk with a specificity of 84.6%; 95% CI: 54.6%–98.0%), and 40 EOC (33 of which were classified by ROMA as high-risk with a sensitivity of 82.5%; 95% CI: 67.2%–92.7%). In the pre-menopausal group, the AUC was 0.64 (p=0.12, 95% CI: 0.44–0.83) for CA125, 0.77 (p=0.003, 95% CI: 0.62–0.92) for HE4 and 0.77 (p=0.002, 95% CI: 0.63–0.92) for ROMA. In the post-menopausal group, the AUC was 0.84 (p=0.0003, 95% CI: 0.73–0.94) for CA125, 0.94 (p<0.0001, 95% CI: 0.88–0.99) for HE4 and 0.92 (p<0.0001, 95% CI: 0.85–0.99) for ROMA.

Conclusions: The ROMA is a simple scoring system which shows excellent diagnostic performance for the detection of EOC in post-menopausal women, but not in pre-menopausal women. Moreover, the dual marker combination of HE4 and CA125 (ROMA) does not show better performance than HE4 alone.
Diagnostic, prognostic and therapeutic relevance of B-type natriuretic hormone and related peptides in children with congenital heart diseases
Authors: Cantinotti Massimiliano , Giovannini Stefania , Murzi Bruno , Clerico Aldo
Published: February 2011

The aim of this article is to review the diagnostic and prognostic relevance of measurement of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in pediatric patients with congenital cardiac diseases (CHD). A computerized literature search in the National Library of Medicine using the keywords “BNP assay” and “NT-proBNP assay”+neonate/s and newborn/s was performed. Next, we refined the analysis to include only the studies specifically designed to evaluate the clinical usefulness of BNP and NT-proBNP measurements in children with CHD. Several authors suggested that BNP/NT-proBNP is clinically helpful as a diagnostic and prognostic marker for children with suspected CHD. BNP values are age dependent, even in paediatric populations. Unfortunately, accurate reference values for BNP and NT-proBNP for neonatal ages have only recently become available. As a result, the lack of homogenous and accurate decisional levels in the neonatal period greatly limits the clinical impact of the BNP assay, and also contributed to the production of conflicting results. Regardless of age, there is great variability in BNP/NT-proBNP values among CHD characterized by different hemodynamic and clinical conditions. In particular, cardiac defects characterized by left ventricular volume and pressure overload usually show a higher BNP response than CHD which is characterized by right ventricular volume or pressure overload. BNP and NT-proBNP may be considered helpful markers in the integral clinical approach for patients with CHD. Measurement of BNP cannot replace cardiac imaging (including echocardiography, angiography and magnetic resonance), but provide independent, low cost and complementary information for the evaluation of cardiac function and clinical status.
Confirmation of congenital adrenal hyperplasia by adrenal steroid profiling of filter paper dried blood samples using ultra-performance liquid chromatography-tandem mass spectrometry
Authors: Rossi Claudia , Calton Lisa , Brown Heather A. , Gillingwater Scott , Wallace A. Michael , Petrucci Francesca , Ciavardelli Domenico , Urbani Andrea , Sacchetta Paolo , Morris Michael
Published: February 2011

Background: The specificity of screening for congenital adrenal hyperplasia by direct measurement of 17-hydroxyprogesterone in filter paper dried blood spot samples by immunoassay is low and has a high false-positive rate. In order to reduce the false-positive rate of this test, we developed a rapid, robust, specific confirmatory procedure in which cortisol, 4-androstene-3,17-dione and 17-hydroxyprogesterone were measured simultaneously by ultra-performance liquid chromatography-tandem mass spectrometry.

Methods: After extraction, samples were analysed by ultra-performance liquid chromatography-tandem mass spectrometry and 17-hydroxyprogesterone was quantified accurately. Other steroids were determined using stable deuterated internal standards. In total, 25 patient blood spot samples and 92 control samples were analysed.

Results: The assay was linear for 17-hydroxyprogesterone, with a coefficient of determination >0.997 and imprecision ≤6.5%. An upper limit of normal for 17-hydroxyprogester-one of 4.45 nmol/L was established by analysing a cohort of samples from unaffected newborns. In addition, a cut-off of 3.5 for the peak areas ratio (17-hydroxyprogesterone+4-androstene-3,17-dione)/cortisol, allows confirmation of the affected steroidogenic enzyme.

Conclusions: A high throughput method for the detection of steroids related to congenital adrenal hyperplasia has been developed, allowing the false-positive rate associated with screening for 17-hydroxyprogesterone by immunoassay to be determined.
Carotid restenosis is associated with plasma ADMA concentrations in carotid endarterectomy patients
Authors: Zinellu Angelo , Sotgia Salvatore , Porcu Paolo , Casu Maria Antonietta , Bivona Giulia , Chessa Roberto , Deiana Luca , Carru Ciriaco
Published: February 2011

Background: The aim of this work has been to study the association between plasma asymmetric dimethylarginine (ADMA) concentrations and carotid stenosis in a group of 64 patients undergoing carotid endarterectomy (CEA).

Methods: Arginine, ADMA and symmetric dimethylarginine (SDMA) were measured using capillary electrophoresis with UV detection. An evaluation of plasma concentrations of total cysteine (tCys) and total homocysteine (tHcy) was also performed.

Results: Pearson’s analysis show a positive correlation between ADMA and carotid stenosis (r=0.37, p=0.003), which is also confirmed after stepwise multiple linear regression analysis. ADMA plasma concentrations were significantly associated with tHcy (r=0.40, p=0.001) and to a lesser extent, even if not significantly, with tCys (r=0.23, p=0.07).

Conclusions: Our data suggest that plasma ADMA is involved in carotid narrowing after CEA intervention. This suggests that this molecule may have an important role in the events that lead to stenosis.
An increase in serum uric acid concentrations is associated with an increase in the Framingham risk score in Korean adults
Authors: Nam Ga-Eun , Lee Kyung-Shik , Park Yong-Gyu , Cho Kyung-Hwan , Lee Seung-Hwan , Ko Byung-Joon , Kim Do-Hoon
Published: February 2011

Background: Uric acid is a novel cardiovascular disease (CVD) factor, but its use as an independent risk factor for CVD remains controversial. Here, we examined the correlation between Framingham risk score (FRS) and serum uric acid concentrations in asymptomatic Korean adults.

Methods: This cross-sectional study was performed on 8035 Korean adults. Besides FRS, we measured body mass index, fasting blood glucose, homeostasis model assessment of insulin resistance, creatinine, γ-glutamyltransferase, the lipid profile, uric acid, high-sensitive C-reactive protein, and the white blood cell count. All subjects were placed into one of three risk groups according to their FRS.

Results: All CVD related factors were significantly different in the three FRS groups. The increments of uric acid in-creased significantly FRS from the 10-year risk 0%–9% group to the >10% group after adjusting for other CVD-related factors using ordinal logistic regression analysis. Analyses of the three age groups showed similar effects.

Conclusions: An increased uric acid concentration is associated with an increase in coronary heart disease risk calculated from the FRS, and doctors need to pay attention to this CVD risk in apparently healthy adults with hyperuricemia.
The effect of a one-year weight reduction program on serum uric acid in overweight/obese children and adolescents
Authors: Krzystek-Korpacka Malgorzata , Patryn Eliza , Kustrzeba-Wojcicka Irena , Chrzanowska Joanna , Gamian Andrzej , Noczynska Anna
Published: February 2011

Background:Hyperuricemia may underlie obesity and related disorders, but the impact of weight reduction and metformin on serum uric acid (sUA) in Caucasian children/adolescents is unknown.

Methods:One hundred and thirteen children/adolescents were enrolled (83 completed) into 1-year weight reduction program (diet+exercise) without or with metformin. Anthropometric and biochemical measurements were conducted at baseline and at the end of follow-up (13±3 months).

Results:sUA decreased in 86% females and 67% males. Significantly more patients substantially (≥10%) reduced their sUA than body mass index (BMI)%. In females, sUA decreased regardless of type of intervention, but more markedly in the metformin group, and ΔsUA correlated positively with ΔBMI%, ΔWHtR (waist-to-height ratio), Δinsulin, ΔHOMA (homeostasis model of assessment), and Δtriglycerides/high density lipoprotein (HDL), but correlated negatively with baseline sUA, HOMA, insulin, and triglycerides/HDL. Of these, metformin treatment, baseline sUA, and ΔBMI% were independent predictors of sUA reduction, explaining 77% of data variability. In males, sUA reduction was significant in the metformin group only, and negatively correlated with ΔWHR (waist-to-hip ratio), ΔWHtR, Δleptin, baseline sUA, and waist circumference. Of these, baseline sUA and ΔBMI% were independent predictors of sUA reduction, explaining 69% of data variability. Except for sUA, females reduced their BMI%, waist circumference, triglycerides, triglycerides/HDL and increased HDL, while males reduced total cholesterol.

Conclusions:A longitudinal weight reduction program encompassing diet/exercise with or without metformin was more efficient in reducing sUA than weight and its effect on sUA and other metabolic parameters differed between genders. Weight loss did not condition sUA reduction, which was strongly dependent on baseline levels. The sUA reducing effects of metformin may contribute to its effects on blood pressure-lowering and endothelial function-improving properties in females.
Genetic variability of the fructosamine 3-kinase gene in diabetic patients
Authors: Mosca Lorena , Penco Silvana , Patrosso Maria C. , Marocchi Alessandro , Lapolla Annunziata , Sartore Giovanni , Chilelli Nino C. , Paleari Renata , Mosca Andrea
Published: February 2011

Background: Nonenzymatic glycation appears to be an important factor in the pathogenesis of diabetic complications. Fructosamine 3-kinase (FN3K), initially identified in erythrocytes, appears to be responsible for the removal of fructosamine from proteins, suggesting a protective role in nonenzymatic glycation. Recently, genetic variants in the FN3K gene have been studied in diabetic patients. The aim of our study was the molecular characterization of the FN3K gene in a representative group of Italian patients with type 1 (T1DM) and 2 (T2DM) diabetes mellitus and in a cohort of healthy controls.

Methods: Seventy diabetic subjects (35 type 1 and 35 type 2) with stable glycemic control and 33 healthy control subjects were evaluated using PCR and direct sequencing of the FN3K gene. Denaturing high performance liquid chromatography (DHPLC) was used in controls for screening for the presence of the genetic variants previously found in diabetic patients.

Results: Seven different genetic variants were identified, five of them already reported and two new: the p.R187X and p.Y239C mutations identified in two females affected by T2DM. No significant association was found between certain polymorphisms and diabetes conditions. Preliminary haplotype studies are also reported. With respect to genotypes, we noted that some were not present in all the investigated cohort, and some were found related to higher glycated hemoglobin compared to others, although not at a significant level, probably because of the small number of subjects investigated.

Conclusions: In conclusion, this study identified two new mutations and additional variants within the FN3K gene. This is the first study on FN3K in Italy. Future work is needed to achieve a better understanding of the FN3K enzyme and its possible clinical utility in the management of diabetic patients.
Kick-Starting the Ratchet: The Fate of Mutators in an Asexual Population
Authors: Söderberg R Jonas , Berg Otto G
Published: February 2011

Muller's ratchet operates in asexual populations without intergenomic recombination. In this case, deleterious mutations will accumulate and population fitness will decline over time, possibly endangering the survival of the species. Mutator mutations, i.e., mutations that lead to an increased mutation rate, will play a special role for the behavior of the ratchet. First, they are part of the ratchet and can come to dominance through accumulation in the ratchet. Second, the fitness-loss rate of the ratchet is very sensitive to changes in the mutation rate and even a modest increase can easily set the ratchet in motion. In this article we simulate the interplay between fitness loss from Muller's ratchet and the evolution of the mutation rate from the fixation of mutator mutations. As long as the mutation rate is increased in sufficiently small steps, an accelerating ratchet and eventual extinction are inevitable. If this can be countered by antimutators, i.e., mutations that reduce the mutation rate, an equilibrium can be established for the mutation rate at some level that may allow survival. However, the presence of the ratchet amplifies fluctuations in the mutation rate and, even at equilibrium, these fluctuations can lead to dangerous bursts in the ratchet. We investigate the timescales of these processes and discuss the results with reference to the genome degradation of the aphid endosymbiont Buchnera aphidicola.
Genetic Analysis Implicates the Set3/Hos2 Histone Deacetylase in the Deposition and Remodeling of Nucleosomes Containing H2A.Z
Authors: Hang Mingda , Smith M Mitchell
Published: February 2011

Histone variants and histone modification complexes act to regulate the functions of chromatin. In Saccharomyces cerevisiae the histone variant H2A.Z is encoded by HTZ1. Htz1 is dispensable for viability in budding yeast, but htz1Δ is synthetic sick or lethal with the null alleles of about 200 nonessential genes. One of the strongest of these interactions is with the deletion of SET3, which encodes a subunit of the Set3/Hos2 histone deacetylase complex. Little is known about the functions of Set3, and interpreting these genetic interactions remains a highly challenging task. Here we report the results of a forward genetic screen to identify bypass suppressors of the synthetic slow-growth phenotype of htz1Δ  set3Δ. Among the identified loss-of-function suppressors are genes encoding subunits of the HDA1 deacetylase complex, the SWR1 complex, the H2B deubiquitination module of SAGA, the proteasome, Set1, and Sir3. This constellation of suppressor genes is uncommon among the global set of htz1Δ synthetic interactions. BDF1, AHC1, RMR1, and CYC8 were identified as high-copy suppressors. We also identified interactions with SLX5 and SLX8, encoding the sumoylation-targeted ubiquitin ligase complex. In the context of htz1Δ  set3Δ, suppressors in the SWR1 and the H2B deubiquitination complexes show strong functional similarity, as do suppressors in the silencing genes and the proteasome. Surprisingly, while both htz1Δ  set3Δ and swr1Δ  set3Δ have severe slow-growth phenotypes, the htz1Δ  swr1Δ  set3Δ triple mutant grows relatively well. We propose that Set3 has previously unrecognized functions in the dynamic deposition and remodeling of nucleosomes containing H2A.Z.
Functional Properties of Microbial Transglutaminase Modified Soybean Glycinin and ?-Conglycinin
Authors: Hu Xiaozhong , Xu Xuebing , Fan Jun-Feng , Cheng Yong-Qiang , Li Lite
Published: February 2011

Soybean ?-conglycinin and glycinin were polymerized by a microbial transglutaminase (MTGase), and some functional properties of these polymers, including solubility, heat stability and emulsifying, foaming, and gelling properties, were investigated. SDS-PAGE showed that the acidic subunits of glycinin and ?, ? subunits of ?-conglycinin were easily susceptible to MTGase than basic subunits and ?-subunits, respectively. Although MTGase treatment led to the decreases in solubility and emulsifying activity of ?-conglycinin and glycinin, the significant improvements in their gelling and heat stability were observed (p < 0.05). In addition, the MTGase polymerization also increased the foaming property and emulsifying stability of glycinin. These results show that MTGase treatment could improve some functional properties of ?-conglycinin and glycinin, which provides a new opportunity to obtain specific functional properties of soy proteins used in various food systems.