bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes after adjuvant chemotherapy in the treatment of high‐risk urothelial carcinoma of the upper urinary tract (UUT‐UC)
Authors: Vassilakopoulou Maria , de la Motte Rouge Thibault , Colin Pierre , Ouzzane Adil , Khayat David , Dimopoulos Meletios‐Athanasios , Papadimitriou Christos A. , Bamias Aristotle , Pignot Géraldine , Nouhaud François Xavier , Hurel Sophie , Guy Laurent , Bigot Pierre , Roumiguié Mathieu , Rouprêt Morgan ,   for the French collaborative national database on UUT‐UCC
Published: June 2011

BACKGROUND:

Urothelial carcinoma of the upper urinary tract (UUT‐UC) was a rare, aggressive urologic cancer with a propensity for multifocality, local recurrence, and metastasis. High‐risk patients had poor outcomes. Because of the rarity of these tumors, randomized clinical trials and data regarding adjuvant chemotherapy in locally advanced tumors are currently unavailable. Our objective was to assess the effect of adjuvant chemotherapy and the impact of potential prognostic factors on survival in high‐risk, postsurgical UUT‐UC patients.

METHODS:

Using a multi‐institutional, international retrospective database, identified were 627 patients with high risk UUT‐UCs (pT3N0, pT4N0 and/or N+ and/or M+) who underwent surgical removal. Only patients who received adjuvant chemotherapy were included.

RESULTS:

Overall, 140 patients (22.6%) with a median age of 67 years were included. The median follow‐up was 22.5 months. The 5‐year, overall survival for the entire cohort was 43%, the 5‐year recurrence‐free survival was 54%, and metastasis‐free survival was 53% at 5 years. Positive surgical margins were an independent prognostic factor for recurrence (P = .06), cancer‐specific mortality (P = .05), and overall mortality (P = .02) of any cause. Adjuvant chemotherapy was not linked with overall or cancer‐specific survival in patients with high risk disease (adjuvant chemotherapy [n = 140] vs no treatment [n = 487]) (P >.5).

CONCLUSIONS:

Adjuvant postoperative chemotherapy did not offer any significant benefit to overall survival in our population. Additional data were necessary, and studies enrolling patients at high risk in clinical trials investigating neoadjuvant chemotherapy in conjunction with chemotherapy should have been highly encouraged. Cancer 2011;. © 2011 American Cancer Society.
Prognostic impact of severe thrombocytopenia in low‐risk myelodysplastic syndrome
Authors: Gonzalez‐Porras Jose Ramon , Cordoba Iris , Such Esperanza , Nomdedeu Benet , Vallespi Teresa , Carbonell Felix , Luño Elisa , Ardanaz Maite , Ramos Fernando , Pedro Carme , Gomez Valle , de Paz Raquel , Sanchez‐Barba Mercedes , Sanz Guillermo F. , del Cañizo and Consuelo ,   on behalf of the Spanish Myelodysplastic Syndrome Registry
Published: June 2011

BACKGROUND:

Thrombocytopenia is very common in myelodysplastic syndrome (MDS); however, its clinical impact in low‐risk patients remains controversial.

METHODS:

The authors analyzed the incidence and prognostic significance of thrombocytopenia at diagnosis in 2565 de novo MDS patients included in the Spanish MDS Registry.

RESULTS:

Thrombocytopenia (platelet count <100 × 109/L) was identified in 842 patients (32.8%). Severe thrombocytopenia (platelet count <30 × 109/L) was observed in 7.1% of patients and was significantly associated with a higher‐risk World Health Organization subtype (P = .026) and intermediate‐2/high‐risk International Prognostic Scoring System (IPSS) score (P = .046). Severe thrombocytopenia was the most important prognostic factor and had negative effects on the low/intermediate‐1 risk group. Median overall survival of patients with a platelet count <30 and ≥30 × 109/L was 16 months and 71 months, respectively (hazard ratio, 4.66; 95% confidence interval, 2.74‐7.90; P < .0001). The negative effect of severe thrombocytopenia in low/intermediate‐1 risk patients was caused by increased risk of bleeding.

CONCLUSIONS:

MDS patients with low/intermediate‐1 IPSS risk score and severe thrombocytopenia should no longer be regarded as low risk, and must be considered for disease‐altering approaches at diagnosis. Cancer 2011;. © 2011 American Cancer Society.
2′‐5′ oligoadenylate synthetase 1 polymorphism is associated with prostate cancer
Authors: Mandal Sanjay , Abebe Fisseha , Chaudhary Jaideep
Published: June 2011

BACKGROUND:

The antiviral, proapoptotic, antiproliferative gene 2′‐5′ oligoadenylate synthetase (2‐5OAS1) converts adenosine triphosphate into a series of 2′‐5′ oligoadenylates (2‐5A). In turn, 2‐5A activates latent ribonuclease (RNaseL), a candidate hereditary prostate cancer gene. OAS1 polymorphism (reference single nucleotide polymorphism [SNP] 2660 [rs2660]) has been associated with increased susceptibility to infections and various diseases. In general, the low‐enzyme‐activity adenine‐adenine (AA) genotype promotes susceptibility, whereas the high‐enzyme‐activity guanosine‐guanosine (GG) genotype confers protection. In this study, the authors investigated the association of this functional OAS1 polymorphism (rs2660) with prostate cancer.

METHODS:

Sample size and power were calculated using a power calculation software program for case‐control genetic association analyses. Genomic DNA samples from a control group (n = 140) and from a case group of patients with prostate cancer (n = 164) were used for genotyping SNPs rs2660, rs1131454, and rs34137742 in all samples. Statistical analyses were performed using a logistic regression model.

RESULTS:

A significant association was observed between the rs2660 genotype (A/G) and prostate cancer. Genotype AA increased the risk, whereas genotype GG decreased the risk of prostate cancer. The GG genotype was not observed in the African American samples. The AA genotype also increased the risk of prostate cancer with age.

CONCLUSIONS:

The OAS1 SNP rs2660 AA genotype was associated significantly with prostate cancer, whereas the GG genotype protected against prostate cancer. OAS1 rs2660 may be a prostate cancer susceptibility polymorphism, which is a significant observation, especially in a context of the OAS1‐RNaseL pathway. Thus, a functional defect in OAS1 because of the rs2660 SNP not only can attenuate RNaseL function but also can alter cell growth and apoptosis independent of RNaseL. Cancer 2011;. © 2011 American Cancer Society.
No effect of lysis solutions on absolute CD19+ lymphocytes count and CD45 index in chronic lymphocytic leukemia
Authors: Mekouar Hassan , Mullier François , Dinon Quentin , Bailly Nicolas , Cornet Yvan , Chatelain Bernard
Published: June 2011

The absolute CD19+ lymphocytes count is essential for chronic lymphocytic leukemia (CLL) management. At the present time, no standardized flow cytometry (FCM) protocol to measure B‐lymphocytes counts is established. The aims of the present study were first to evaluate the effect of different lysis solutions and of red blood cell lysis per se on CLL lymphocytes count and B‐lymphocytes CD45 expression and second to compare absolute B‐lymphocytes counts obtained by single (SP) and dual platforms (DP). Absolute CD19+ B‐lymphocytes counts and CD45 expression in 35 whole‐blood CLL samples were determined by FCM using either different lysis solutions or using a no wash no lyse (NWNL) protocol. Single platform using microbeads was also evaluated for absolute quantification. The absolute CD19+ B‐lymphocytes counts using different red blood cell lysis solutions correlated with NWNL method without any effect on CD45 expression. Bland and Altman plot showed homogenous distribution of bias; mean bias was less than 1% for all lysing solutions. Moreover, no statistically significant difference between SP and DP was observed. The type of lysis solution influences neither the CD19+ B‐lymphocytes count nor the CD45 expression. The two systems, SP and DP, yield comparable values with excellent agreement. However, the tendency of slightly lower results with SP showed the requirement of larger studies before standardization of B‐lymphocytes count in CLL patients. © 2011 International Clinical Cytometry Society
Management of a hemophilia patient in renal replacement therapy
Authors: Barbosa Silva Patrícia Aparecida , Soares Sônia Maria , Fráguas Gisele , de Oliveira Vaz Fada Marina , José da Silva Maria , Gabriel da Silva José
Published: June 2011

We describe the case of a male hypertensive patient with severe hemophilia A. In August 1999 he was admitted to our nephrology department, with hemarthrosis, severe hypertension, dyspnea with minimal efforts, increasing blood urea nitrogen, anemia, uremic symptoms, reduced urine volume, mild edema of the lower limbs, and no hyperkalemia. Imaging confirmed the diagnosis of end‐stage renal disease. A Tenckhoff peritoneal dialysis catheter was inserted, and he began continuous ambulatory peritoneal dialysis. In August 2005 he evolved to peritoneal failure (peritoneal equilibration test showing ultrafiltration disorder I) and was transferred to hemodialysis. A permanent catheter was inserted into the right subclavian vein. Hemodialysis sessions lasted 4 hours, three times a week, and gradually resulted in hemodynamic stabilization. In September 2005, an arteriovenous fistula was placed in the right forearm between the cephalic vein and the radial artery. In January 2007 the patient was admitted with abdominal and epigastric pain, double‐lumen catheter infection, peritoneal catheter infection, globoid tympanic abdomen, and mild pain on palpation. Preliminary studies showed a large preperitoneal hematoma with bowel compression. Due to the catheter infection, we decided to puncture the fistula using a 17‐G needle. Apart from some bleeding during and after the beginning of hemodialysis, there were no other fistula complications. The patient had progressive worsening of clinical symptoms and died in February 2007. In summary, an individualized treatment plan, mainly adequate hemostatic monitoring, care of the dialysis access, and multiprofessional and family involvement, may help in the management of hemophilia patients undergoing dialysis. Dial. Transplant. © 2011 Wiley Periodicals, Inc.
Combined therapy with sodium thiosulfate and parathyroidectomy in a patient with calciphylaxis
Authors: Castro Hector , Cabeza‐Rivera Franco , Green Dollie
Published: June 2011

Calciphylaxis is a serious form of vascular calcification that leads to skin necrosis with ulceration. It usually occurs in dialysis patients and carries very high morbidity and mortality rates. We present the case of a dialysis patient with biopsy‐proven calciphylaxis of the lower extremity and severe secondary hyperparathyroidism, who had been receiving outpatient sodium thiosulfate, with no improvement. For management of the severe hyperparathyroidism, the patient underwent surgical excision of the parathyroid glands, leading to rapid correction of parathyroid hormone (PTH) levels and the concomitant calcium and phosphorus abnormalities. Subsequently, she was continued on outpatient sodium thiosulfate on dialysis days, and follow‐up demonstrated progressive resolution of the skin lesion. We believe that in dialysis patients with significant secondary hyperparathyroidism and calciphylaxis, the combination of sodium thiosulfate with medical or surgical correction of the metabolic disorder should be considered as the first‐line management approach along with pain control and optimal wound care.
Bericht über die 69. Sitzung des Technischen Lenkungsausschusses der Europäischen Organisation für Technische Zulassungen
Authors: Springborn Matthias
Published: June 2011

Am 16. und 17. Februar 2011 fand die 69. Sitzung des Technischen Lenkungsausschusses der Europäischen Organisation für Technische Zulassungen (EOTA) in Brüssel statt. Im Folgenden werden die wesentlichen Beratungsinhalte kurz wiedergegeben.
Transcriptional response to foraging experience in the honey bee mushroom bodies
Authors: Lutz Claudia C. , Rodriguez‐Zas Sandra L. , Fahrbach Susan E. , Robinson Gene E.
Published: June 2011

Enriched environmental conditions induce neuroanatomical plasticity in a variety of vertebrate and invertebrate species. We explored the molecular processes associated with experience‐induced plasticity, using naturally occurring foraging behavior in adult worker honey bees (Apis mellifera). In honey bees, the mushroom bodies exhibit neuroanatomical plasticity that is dependent on accumulated foraging experience. To investigate molecular processes associated with foraging experience, we performed a time‐course microarray study to examine gene expression changes in the mushroom bodies as a function of days foraged. We found almost 500 genes that were regulated by duration of foraging experience. Bioinformatic analyses of these genes suggest that foraging experience is associated with multiple molecular processes in the mushroom bodies, including some that may contribute directly to neuropil growth, and others that could potentially protect the brain from the effects of aging and physiological stress. © 2011 Wiley Periodicals, Inc. Develop Neurobiol 72: 153–166, 2012
Process analytical sensors and image‐based techniques for single‐use bioreactors
Authors: Bluma Arne , Höpfner Tim , Prediger Andreas , Glindkamp Anne , Beutel Sascha , Scheper Thomas
Published: June 2011

In the field of biotechnology, the estimation of relevant process parameters is still a challenge. Particularly with regard to efficient control of processes with high product yields, a real‐time and reliable documentation with process analytical sensors is essential. Moreover, stricter regulations of the US Food and Drug Administration for the pharmaceutical industry concerning process documentation, imposed by the Process and Analytical Technology Initiative, have increased the demand for sensors that are able to very accurately monitor and document the production process. For the monitoring and control of bioprocesses, a huge variety of sensors is used. Most systems are based on optical or electrochemical sensors. Furthermore, the market demand for disposable sensor systems increases rapidly as the application of disposable bioreactors represents the biggest technical advance in modern biotechnology. These presterilized plastic bags significantly reduce the cost/income ratio and build a meaningful concept for the design and implementation of standardized peripheral bioproduction. Simple and flexible adaptation of sensors is a bottleneck and high‐production requirements of the sensor components have to be met. This contribution gives an overview on concepts of sensor systems and image‐based techniques that allow the online estimation of relevant process parameters used in single‐use bioreactor systems.
Seismic design and evaluation of steel moment‐resisting frames with compressed elastomer dampers
Authors: Karavasilis Theodore L. , Sause Richard , Ricles James M.
Published: June 2011

This paper evaluates the hysteretic behavior of an innovative compressed elastomer structural damper and its applicability to seismic‐resistant design of steel moment‐resisting frames (MRFs). The damper is constructed by precompressing a high‐damping elastomeric material into steel tubes. This innovative construction results in viscous‐like damping under small strains and friction‐like damping under large strains. A rate‐dependent hysteretic model for the compressed elastomer damper, formed from a parallel combination of a modified Bouc–Wen model and a non‐linear dashpot is presented. The model is calibrated using test data obtained under sinusoidal loading at different amplitudes and frequencies. This model is incorporated in the OpenSees [17] computer program for use in seismic response analyses of steel MRF buildings with compressed elastomer dampers. A simplified design procedure was used to design seven different systems of steel MRFs combined with compressed elastomer dampers in which the properties of the MRFs and dampers were varied. The combined systems are designed to achieve performance, which is similar to or better than the performance of conventional steel MRFs designed according to current seismic codes. Based on the results of nonlinear seismic response analyses, under both the design basis earthquake and the maximum considered earthquake, target properties for a new generation of compressed elastomer dampers are defined. Copyright © 2011 John Wiley & Sons, Ltd.
Can We Predict Exchange Rate Movements at Short Horizons?
Authors: Cheong Chongcheul , Kim Young‐Jae , Yoon Seong‐Min
Published: June 2011

This paper explains the unpredictability of exchange rate movements at short horizons and provides a plausible answer on the exchange rate disconnect puzzle. By generalizing Chaboud and Wright's (Journal of International Economics 2005; 66: 349–362) work, it is shown that exchange rates follow a martingale process at short horizons but over long horizons may contain some predictable structure. The empirical results applied to several major currencies of the US dollar support our hypothesis. This evidence is not coincided with the explanation of the inefficient market hypothesis under which exchange rate movements can be predictable in both short and long horizons. Copyright © 2011 John Wiley & Sons, Ltd.
Knockdown of RARB2 identifies a dual role in cancer
Authors: Pappas Jane J. , Toulouse André , Basik Mark , Lévesque Luc , Bradley W.E.C.
Published: June 2011

Two chemoprevention trials have shown that retinoic acid (RA) may be harmful in patients at risk for lung cancer, and RA administration to this high‐risk group results in RARB2 reactivation. Although RARB2 is thought to possess tumor suppressive activity, its expression has recently been correlated with poorer prognosis in patients with nonsmall cell lung cancer. We hypothesized that RARB2 expression is necessary for the growth and maintenance of the oncogenic phenotype in lung cancer cells in which RARB2 has not been inactivated. We tested various antisense oligodeoxynucleotides (ASO) against RARB2 in multiple lung cancer cell lines and used microarray technology to compare the patterns of gene expression following ASO treatment versus RA treatment in the A‐549 lung cancer cell line. We show that ASO treatment reduces proliferation and causes apoptosis in 3 RARB2‐expressing lung cancer cell lines but has no apparent effect in at least two other lung cancer cells lines having lost RARB2 expression or one normal lung RARB2‐expressing cell line; we demonstrate a correlation between resulting RARB2 expression levels and cell growth; and identify transcriptional effects related to both RA and RARB2 signaling. In particular, five genes known to contribute to carcinogenesis or chemotherapeutic resistance are down‐regulated following ASO treatment: three of these are up‐regulated following RA treatment. This work demonstrates a dual role for RARB2 (tumor suppression and tumor promotion) and identifies a challenge with respect to using RARB2 as a target for treatment or prevention strategies. © 2011 Wiley‐Liss, Inc.
CBFB and MYH11 in inv(16)(p13q22) of acute myeloid leukemia displaying close spatial proximity in interphase nuclei of human hematopoietic stem cells
Authors: Weckerle Allison B. , Santra Madhumita , Ng Maggie C.Y. , Koty Patrick P. , Wang Yuh‐Hwa
Published: June 2011

To gain a better understanding of the mechanism of chromosomal translocations in cancer, we investigated the spatial proximity between CBFB and MYH11 genes involved in inv(16)(p13q22) found in patients with acute myeloid leukemia. Previous studies have demonstrated a role for spatial genome organization in the formation of tumorigenic abnormalities. The nonrandom localization of chromosomes and, more specifically, of genes appears to play a role in the mechanism of chromosomal translocations. Here, two‐color fluorescence in situ hybridization and confocal microscopy were used to measure the interphase distance between CBFB and MYH11 in hematopoietic stem cells (HSCs), where inv(16)(p13q22) is believed to occur, leading to leukemia development. The measured distances in HSCs were compared with mesenchymal stem cells, peripheral blood lymphocytes, and fibroblasts, as spatial genome organization is determined to be cell‐type specific. Results indicate that CBFB and MYH11 are significantly closer in HSCs compared with all other cell types examined. Furthermore, the CBFB‐MYH11 distance is significantly reduced compared with CBFB and a control locus in HSCs, although separation between CBFB and the control is ∼70% of that between CBFB and MYH11 on metaphase chromosomes. HSCs were also treated with fragile site‐inducing chemicals because both the genes contain translocation breakpoints within these regions. However, treatment with fragile site‐inducing chemicals did not significantly affect the interphase distance. Consistent with previous studies, our results suggest that gene proximity may play a role in the formation of cancer‐causing rearrangements, providing insight into the mechanism of chromosomal abnormalities in human tumors. © 2011 Wiley‐Liss, Inc.
Experience of tunnel construction in weak ground / Erfahrungen beim Bau von Tunneln in schlechtem Baugrund
Authors: Schubert Wulf
Published: June 2011

A whole range of problems are generally associated with the construction of tunnels in weak ground and under high overburden. Among those are large displacements, wide variation of stresses and strains, and sudden water ingress, to name just a few. A wide variety of behaviours can be experienced, depending on the ground conditions and the influencing factors. The contribution deals with experience from the construction of several Alpine tunnels in faulted rock masses. Specific characteristics of each project are highlighted, and the lessons learned described.

Eine ganze Reihe von Problemen ist mit Planung und Bau eines Tunnels in Baugrund mit schlechten Eigenschaften und hoher Überlagerung verbunden. Unter anderem sind dies große und stark anisotrope Verformungen oder plötzliche Wassereinbrüche, um nur einige wenige zu nennen. In Abhängigkeit von den Baugrundverhältnissen und den äußeren Einflüssen kann eine ganze Reihe unterschiedlicher Verhalten beobachtet werden. Der Beitrag fasst Erfahrungen zusammen, die beim Bau alpiner Tunnel im gestörten Gebirge gemacht wurden. Spezielle Charakteristika jedes Projekts werden aufgezeigt und die Lehren aus den Erfahrungen mitgeteilt.
A matching method for improving covariate balance in cost‐effectiveness analyses
Authors: Sekhon Jasjeet Singh , Grieve Richard D.
Published: June 2011

In cost‐effectiveness analyses (CEA) that use randomized controlled trials (RCTs), covariates of prognostic importance may be imbalanced and warrant adjustment. In CEA that use non‐randomized studies (NRS), the selection on observables assumption must hold for regression and matching methods to be unbiased. Even in restricted circumstances when this assumption is plausible, a key concern is how to adjust for imbalances in observed confounders. If the propensity score is misspecified, the covariates in the matched sample will be imbalanced, which can lead to conditional bias. To address covariate imbalance in CEA based on RCTs and NRS, this paper considers Genetic Matching. This matching method uses a search algorithm to directly maximize covariate balance.

We compare Genetic and propensity score matching in Monte Carlo simulations and two case studies, CEA of pulmonary artery catheterization, based on an RCT and an NRS. The simulations show that Genetic Matching reduces the conditional bias and root mean squared error compared with propensity score matching. Genetic Matching achieves better covariate balance than the unadjusted analyses of the RCT data. In the NRS, Genetic Matching improves on the balance obtained from propensity score matching and gives substantively different estimates of incremental cost‐effectiveness.

We conclude that Genetic Matching can improve balance on measured covariates in CEA that use RCTs and NRS, but with NRS, this will be insufficient to reduce bias; the selection on observables assumption must also hold. Copyright © 2011 John Wiley & Sons, Ltd.
The reduction of SIRT1 in livers of old mice leads to impaired body homeostasis and to inhibition of liver proliferation
Authors: Jin Jingling , Iakova Polina , Jiang Yanjun , Medrano Estela E. , Timchenko Nikolai A.
Published: June 2011

Age declines liver functions, leading to the development of age-associated diseases. A member of the sirtuins family, SIRT1, is involved in the control of glucose homeostasis and fat metabolism. Because aging livers have alterations in glucose and fat metabolism, we examined a possible role of SIRT1 in these alterations. We found that aged livers have a reduced expression of SIRT1 and have lost proper control of the regulation of SIRT1 after partial hepatectomy (PH). Down-regulation of SIRT1 in the liver of old mice is mediated by CCAAT/Enhancer Binding Protein/histone deacetylase 1 (C/EBPβ-HDAC1) complexes, which bind to and repress the SIRT1 promoter. In the livers of young mice, SIRT1 is activated after PH and supports high levels of glucose and triglycerides during liver regeneration. In old mice, however, C/EBPβ-HDAC1–mediated repression of the SIRT1 promoter blocks activation of SIRT1, leading to low levels of glucose and triglycerides during liver regeneration. Down-regulation of SIRT1 in the livers of young mice resulted in alterations similar to those observed in the livers of old mice, whereas the normalization of SIRT1 in the livers of old mice corrects the levels of glucose and triglycerides after PH. The normalization of SIRT1 in old mice also improves liver regeneration via the elimination of the C/EBPα-Brm complex. These studies showed a critical role of the reduction of SIRT1 in age-associated liver dysfunctions and provide a potential tool for the correction of liver functions in old patients after surgical resections. (HEPATOLOGY 2011;)
Clinical implications of acute myeloid leukemia presenting as myeloid sarcoma
Authors: Avni Batia , Rund Debora , Levin Moshe , Grisariu Sigal , Ben‐Yehuda Dina , Bar‐Cohen Sara , Paltiel Ora
Published: June 2011

In this retrospective study, we aim to analyze the characteristics, treatments, and overall survival of all patients presenting with isolated myeloid sarcoma (MS) or MS with concomitant acute myeloid leukemia (AML) compared with all patients with AML, treated during the same period. We identified patients with AML with or without MS at diagnosis, presenting to our medical center between the years 1990 and 2005. There was no statistically significant difference between the groups regarding gender, age, cytogenetic risk groups, rate of complete remission, number of cycles of chemotherapy needed to achieve complete remission, and rate of first relapse. The time to death in the MS group was not significantly different (p = 0.60) from the AML group, and radiotherapy did not affect the median time to death. Transplantation prolonged survival in both groups (p = 0.018 and p < 0.0001, respectively). Patients with MS at diagnosis might benefit from upfront aggressive treatment with hematopoietic stem cell transplantation. Copyright © 2011 John Wiley & Sons, Ltd.
Understanding the impact of conflict on health services in Iraq: information from 401 Iraqi refugee doctors in Jordan
Authors: Burnham Gilbert , Malik Sana , Dhari Al‐Shibli Ammar S. , Mahjoub Ali Rasheed , Baqer Alya'a Qays , Baqer Zainab Qays , Qaraghuli Faraj Al , Doocy Shannon
Published: June 2011

Objectives

This study aims to assess how conflict has affected the function of Iraqi health services and its doctors.

Methods

Interviews were conducted in person or by mobile phone with 401 Iraqi doctors entering Jordan since 2003, using respondent‐driven sampling methods.

Results

Of the Iraqi doctors interviewed in 2008, 94% came from Baghdad, although 25% had moved within Iraq in the past year. They reported a steady year‐by‐year decline in Iraqi health services from 2003 through 2006, with perhaps some improvement in 2007. By 2006, 67% of doctors said essential drugs were present less than half of the time (95% confidence interval [CI] 54–81), and 69% (95% CI 56–84) said essential equipment was available or working half the time or less. By 2006, 95% said their facilities lacked skilled health workers, and 90% noted reduced quality of care. Violent death rates among doctors in Baghdad reached 47.6/1000/yr (95% CI 42.0–53.7) in 2006. In the same year, migration rates for Baghdad doctors moving elsewhere in Iraq were 143.8/1000/yr (95% CI 134.0–154.1), and departure from Iraq was 299.5/1000/yr (95% CI 285.3–314.3).

Conclusions

Deterioration of health services quality, staffing levels and violence against doctors continued from 2003 through 2006, although these may have improved slightly in 2007. In 2009 and 2010, reports suggest that assassinations of doctors and out‐migration have continued. Few have returned. Copyright © 2011 John Wiley & Sons, Ltd.
Multicomponent synthesis of pyridazine and pyridazinoquinazoline derivatives in the presence of catalysts such as magnesium oxide (MgO) and 12‐tungstophosphoric acid (PW)
Authors: Sheibani Hassan , Esfandiarpoor Zeinab
Published: June 2011

A series of 3‐amino‐2,5‐dihydropyridazines and fused pyridazinoquinazolines have been prepared in a one‐step procedure from three‐component reactions of (arylhydrazono)‐propan‐2‐ones, aldehydes and malononitrile or ethyl cyanoacetate in the presence of magnesium oxide (MgO) and 12‐tungstophosphoric acid (PW) as highly effective heterogeneous catalysts. The salient features of these methods include high conversions, short reaction times, cleaner reaction profiles, and the use of inexpensive and readily available catalysts. J. Heterocyclic Chem., 48, 1122 (2011).
Feeding mechanics and dietary implications in the fossil sloth Neocnus (Mammalia: Xenarthra: Megalonychidae) from haiti
Authors: McAfee Robert K.
Published: June 2011

Haitian species of the extinct ground sloth genus Neocnus (Mammalia: Pilosa: Megalonychidae) have previously been hypothesized to have a much reduced jugal bone and a correspondingly reduced masseter musculature but a paucity of specimens has prevented further investigation of this hypothesis. Recent discovery of jugal bones belonging to Haitian specimens of Neocnus within the University of Florida Museum collections enables the element to be more accurately described. The discovery also makes it possible to explore mastication in these sloths. Osteological characters related to feeding were examined, along with comparative estimations of bite force with the extant tree sloths, Bradypus and Choloepus, and their known dietary habits as a means to infer aspects of the paleodiet of Neocnus. There is a significant difference in moment arm calculations for m. masseter between predicted and actual jugals, but the overall significance for bite force is lost and hampered by small sample size. Neocnus demonstrates a variety of characters that are similar to those of Bradypus and not to Choloepus, which is a close phylogenetic relative. The masticatory musculature of Neocnus enabled a chewing cycle emphasizing a grinding combination of mesiodistal and linguobuccal movements of the molariform dentition. The orientations of m. masseter and m. temporalis are estimated to produce relatively high bite force ratios that imply a masticatory system with stronger versus faster components. Because of the similarity of bite forces and jaw mechanics to those of Bradypus, in addition to a number of osteological adaptations indicative of herbivorous grazers (elevated mandibular condyle, large and complex masseter, and robust angular process), the Haitian forms of Neocnus are considered to have been selective feeders with a folivorous diet. J. Morphol. 2011. © 2011 Wiley‐Liss, Inc.
Characteristics and origins of common chemical noise ions in negative ESI LC–MS
Authors: Trötzmüller Martin , Guo Xinghua , Fauland Alexander , Köfeler Harald , Lankmayr Ernst
Published: June 2011

Ionic chemical background noise in LC–MS has been one of the major problems encountered in trace analysis. In this study, the typical negative background ions in ESI LC–MS are investigated exemplarily. It was carried out using tandem mass spectrometry to study the products and precursors of the major background ions to examine their structures and structure relationship. Various typical LC eluents with different compositions and additives such as ammonium formate/formic acid and ammonium acetate/acetic acid have been studied. Several types of negative noise ions are concluded, which include the cluster chemical background ions only from mobile phase components and additives. Furthermore, there are also abundant clusters resulting from the solvation of some typical individual contaminants (e.g. additives and degradation products from tubing, impurities in the mobile phase, etc.), accompanied by some minor contribution from contaminants. The elemental composition of some selected ions was confirmed using the FT‐ICR accurate mass measurement. This work provides us insight into information about the structures and types of common negative background ions and will help to understand their formation and origins. More importantly, it will guide us to prevent chemical noise interference in practice and also contribute to develop methods for noise reduction based on selective ion‐molecule reactions. Copyright © 2011 John Wiley & Sons, Ltd.
Thymine quintets and their higher order assemblies studied by electrospray ionization mass spectrometry and theoretical calculation
Authors: Qiu Bo , Qin Zhen , Liu Jia , Luo Hai
Published: June 2011

We previously reported that thymine molecules can specifically form a pentameric magic number cluster named as thymine quintet in the presence of K+, Rb+ and Cs+. Actually, thymine decamer and doubly charged thymine 15‐mer metaclusters can be observed along with thymine quintet in the ESI mass spectra of thymine with the addition of K+, Rb+ and Cs+. The product ion spectra of these metaclusters, especially the 15‐mer with hetero central ions, indicate that they are higher order assemblies of thymine quintets. The collision‐induced dissociation experiments show that the gas‐phase stabilities of these metaclusters depend on the size of the central ions, following the order Cs+ > Rb+ > K+, while K+ leads to the highest dissociation energy of a thymine quintet. The optimized structures of thymine quintet and decamer were provided by density functional theory calculations, which showed that thymine quintet is bowl‐shaped and its tilting angle increases with the size of the central ion. Furthermore, the chirality of thymine quintet was defined for the first time and the resulting different diastereoisomers of thymine decamers were also revealed by the calculation study. Copyright © 2011 John Wiley & Sons, Ltd.
Simultaneous analysis of acetaminophen, p‐aminophenol and aspirin metabolites by hydrophilic interaction and strong anion exchange capillary liquid chromatography coupled to amperometric detection
Authors: Zheng Minmin , Wu Yimin , Lu Lanxiang , Ding Kang , Tang Fengxiang , Lin Zian , Wu Xiaoping
Published: June 2011

A simple and sensitive method has been developed for the simultaneous determination of polar nonsteroidal pharmaceuticals and metabolites, including acetaminophen, p‐aminophenol and several aspirin metabolites (salicylic acid, gentisic acid, salicyluric acid and 2,3‐dihydroxybenzoic acid), by capillary liquid chromatography with amperometric detection. Using a capillary monolithic column with mixed mode stationary phases and a mobile phase composed of acetonitrile and Tris buffer, rapid separation of six polar analytes was achieved within 8 min, and a hydrophilic interaction and strong anion exchange separation mechanism were exhibited. Method detection limits of six analytes ranged from 10 to 50 ng/mL. In terms of precision, the intra‐ and interday relative standard deviation values in all analytes never exceeded 3.1% for migration time and 8.9% for peak areas, respectively. This method provided a simple, rapid and cost‐effective approach for the analysis of polar pharmaceuticals. The applicability of the method in pharmacokinetics was verified by spiking human serum samples with the compounds and analyzing the recoveries.
Development and validation of an HPLC method for the determination of ten sulfonamide residues in milk according to 2002/657/EC
Authors: Tolika Evanthia P. , Samanidou Victoria F. , Papadoyannis Ioannis N.
Published: June 2011

A HPLC method with diode‐array detection, at 265 nm, was developed and validated for the determination of ten sulfonamides (SAs): sulfadiazine (SDZ), sulfathiazine (STZ), sulfamethoxine (SMTH), sulfamethizole (SMZ), sulfamethoxypyridazine (SMPZ), sulfamonomethoxine (SMMX), sulfamethoxazole (SMXZ), sulfisoxazole (SIX), sulfadimethoxine (SDMX), and sulfaquinoxaline (SQX) in milk. A mixture of ethyl acetate, n‐hexane, and isopropanol was used for the extraction of target analytes from milk. The mobile phase, a mixture of 0.1% v/v formic acid, CH3CN, and CH3OH was delivered to the analytical column under a gradient program. The procedure was validated according to the European Union regulation 2002/657/EC in terms of selectivity, stability, decision limit, detection capability, accuracy, and precision. Mean recoveries of sulfonamides from milk samples spiked at three concentration levels (0.5×MRL, 1×MRL, and 1.5×MRL) (MRL, maximum residue level) were 93.9–115.9% for SDZ, 97.8–102.9% for STZ, 94.6–107.0% for SMTH, 98.3–111.5% for SMZ, 95.3–108.4% for SMPZ, 97.9–106.0% for SMMX, 97.6–111.3% for SMXZ, 94.3–104.6% for SIX, 96.4–109.1% for SDMX, and 98.2–111.2% for SQX. All RSD values were lower than 8.8%. The decision limits CCa calculated by spiking 20 blank milk samples at MRL (100 μg/kg) ranged from 101.61 to 106.84 μg/kg, whereas the detection capability CCb ranged from 105.64 to 119.01 μg/kg.
The importance of within‐year repeated counts and the influence of scale on long‐term monitoring of sage‐grouse
Authors: Fedy Bradley C. , Aldridge Cameron L.
Published: June 2011

Long‐term population monitoring is the cornerstone of animal conservation and management. The accuracy and precision of models developed using monitoring data can be influenced by the protocols guiding data collection. The greater sage‐grouse (Centrocercus urophasianus) is a species of concern that has been monitored over decades, primarily, by counting the number of males that attend lek (breeding) sites. These lek count data have been used to assess long‐term population trends and for multiple mechanistic studies. However, some studies have questioned the efficacy of lek counts to accurately identify population trends. In response, monitoring protocols were changed to have a goal of counting lek sites multiple times within a season. We assessed the influence of this change in monitoring protocols on model accuracy and precision applying generalized additive models to describe trends over time. We found that at large spatial scales including >50 leks, the absence of repeated counts within a year did not significantly alter population trend estimates or interpretation. Increasing sample size decreased the model confidence intervals. We developed a population trend model for Wyoming greater sage‐grouse from 1965 to 2008, identifying significant changes in the population indices and capturing the cyclic nature of this species. Most sage‐grouse declines in Wyoming occurred between 1965 and the 1990s and lek count numbers generally increased from the mid‐1990s to 2008. Our results validate the combination of monitoring data collected under different protocols in past and future studies—provided those studies are addressing large‐scale questions. We suggest that a larger sample of individual leks is preferable to multiple counts of a smaller sample of leks. © 2011 The Wildlife Society.
Hot topic in hepatitis C virus research: The type of immunosuppression does not matter
Authors: Berenguer Marina
Published: June 2011

Key Points

1. The natural history of recurrent hepatitis C virus (HCV) is highly variable. Old donor age is a factor that has consistently been shown to affect disease progression.

2. Overall, immunosuppression determines the progression of HCV-related disease; however, the type of immunosuppressive agent used for induction or maintenance is not a key factor.

3. Steroid boluses should be avoided; they are associated with increased viremia, fibrosis progression, and reduced survival.

4. Antiviral therapy, particularly if it is successful, is associated with improved outcomes for liver transplant recipients with HCV.

5. There are no convincing data for modifying the type of immunosuppression before antiviral therapy is started.
A within‐subject comparison of 6‐[18F]fluoro‐m‐tyrosine and 6‐[18F]fluoro‐L‐dopa in Parkinson's disease
Authors: Gallagher Catherine L. , Christian Bradley T. , Holden James E. , Dejesus Onofre T. , Nickles Robert J. , Buyan‐Dent Laura , Bendlin Barbara B. , Harding Sandra J. , Stone Charles K. , Mueller Barb , Johnson Sterling C.
Published: June 2011

Progression of Parkinson's disease symptoms is imperfectly correlated with positron emission tomography biomarkers for dopamine biosynthetic pathways. The radiopharmaceutical 6‐[18F]fluoro‐m‐tyrosine is not a substrate for catechol‐O‐methyltransferase and therefore has a more favorable uptake‐to‐background ratio than 6‐[18F]fluoro‐L‐dopa. The objective of this study was to evaluate 6‐[18F]fluoro‐m‐tyrosine relative to 6‐[18F]fluoro‐L‐dopa with partial catechol‐O‐methyltransferase inhibition as a biomarker for clinical status in Parkinson's disease. Twelve patients with early‐stage Parkinson's disease, off medication, underwent Unified Parkinson Disease Rating Scale scoring, brain magnetic resonance imaging, and 3‐dimensional dynamic positron emission tomography using equivalent doses of 6‐[18F]fluoro‐m‐tyrosine and 6‐[18F]fluoro‐L‐dopa with tolcapone, a catechol‐O‐methyltransferase inhibitor. Images were realigned within subject, after which the tissue‐derived uptake rate constant was generated for volumes of interest encompassing the caudate nucleus, putamen, and subregions of the putamen. We computed both bivariate (Pearson) and partial (covariate of age) correlations between clinical subscores and tissue‐derived uptake rate constant. Tissue‐derived uptake rate constant values were correlated between the radiopharmaceuticals (r = 0.8). Motor subscores were inversely correlated with the contralateral putamen 6‐[18F]fluoro‐m‐tyrosine tissue‐derived uptake rate constant (|r| > 0.72, P < .005) but not significantly with the 6‐[18F]fluoro‐L‐dopa tissue‐derived uptake rate constant. The uptake rate constants for both radiopharmaceuticals were also inversely correlated with activities of daily living subscores, but the magnitude of correlation coefficients was greater for 6‐[18F]fluoro‐m‐tyrosine. In this design, 6‐[18F]fluoro‐m‐tyrosine uptake better reflected clinical status than did 6‐[18F]fluoro‐L‐dopa uptake. We attribute this finding to 6‐[18F]fluoro‐m‐tyrosine's higher affinity for the target, L‐aromatic amino acid decarboxylase, and the absence of other major determinants of the uptake rate constant. These results also imply that L‐aromatic amino acid decarboxylase activity is a major determinant of clinical status. © 2011 Movement Disorder Society
Release of lipophilic molecules during in vitro digestion of soy protein‐stabilized emulsions
Authors: Nik Amir Malaki , Corredig Milena , Wright Amanda J.
Published: June 2011

Scope: Solubilization of lipophilic bioactives in gastrointestinal fluids contributes to their bioavailability, but a better understanding of the transfer processes involved and the impact of molecular structure is required.

Methods and results: The transfer of β‐carotene (BC), coenzyme Q10 (CoQ10), vitamin D3 (VitD3), and phytosterols (PSs) from soy protein isolate‐stabilized oil‐in‐water emulsions to the aqueous phase during in vitro digestion was investigated. In the absence of lipolysis, transfer was mainly governed by molecular structure and partitioning within the oil droplets. Less than 3% BC and CoQ10, versus 30.4±0.3% PSs and 24.7±0.4% VitD3, were transferred in this case. However, with lipolysis, PSs and VitD3 rapidly partitioned into the aqueous phase, while lag phases and slower transfer rates were observed for BC and CoQ10. Positive and linear correlations between lipolysis and transfer were observed for all systems. After 2 h exposure to simulated duodenal conditions, there were no differences between percent micellization, except for BC which was proportionally lower. VitD3 and PSs mutually enhanced each other's transfer, while no interactions were observed between VitD3 and BC.

Conclusion: Bioactive molecular structure and co‐administration influenced the transfer behaviour, with implications for foods designed to optimize health benefits.
Bacterial biofilms associated with food particles in the human large bowel
Authors: Van Wey Amy S. , Cookson Adrian L. , Roy Nicole C. , McNabb Warren C. , Soboleva Tanya K. , Shorten Paul R.
Published: June 2011

Bacteria within the gastro‐intestinal tract affect host function via production of short‐chain fatty acids and synthesis of vitamins. Additionally, the commensal enteric bacteria modulate the immune system and provide protection from potentially pathogenic bacteria. Only recently heterogeneous bacterial biofilms were found to be associated with food particles within the intestinal tract. There are a number of studies investigating the formation and function of pathogenic and single‐species biofilms, though few studies have investigated the dynamics of multispecies biofilms, especially with regard to food/microbial/host interactions. The scope of this review is to discuss the current knowledge of bacterial biofilms associated with food particles in the human large bowel, examine the established mathematical models depicting bacterial attachment, and elucidate key areas for further research.
Fast fat suppression RF pulse train with insensitivity to B1 inhomogeneity for body imaging
Authors: Abe Takayuki
Published: June 2011

In higher‐field magnetic resonance imaging scanners, a spectrally selective fat saturation radiofrequency (RF) pulse does not work well because B1 inhomogeneity increases. An adiabatic 180° pulse is used to improve nonuniform fat suppression, but requires inversion recovery time. Therefore, a new RF pulse that achieves flip angles near 90° and is B1 insensitive has been developed. The pulse consists of three sinc‐shaped RF pulses with different flip angles and with different time intervals between each RF pulse. Using the Bloch equations, we analyzed the optimal combination of flip angles. Experimental results demonstrated that Mz was maintained at less than 0.05 M0 for a B1 inhomogeneity of ±35%. The optimal net flip angles was adjusted to 95° by varying the time interval between RF pulses. The pulse duration was 77 ms, which is less than half of the 170‐ms inversion recovery time required for the adiabatic pulse. We demonstrated excellent fat suppression for body imaging. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
Correction and transformation of normative neurophysiological data: Is there added value in the diagnosis of distal symmetrical peripheral neuropathy?
Authors: Mchugh John C. , Connolly Sean
Published: June 2011

Introduction:

Despite theoretical advantages, the practical impact of mathematical correction of normative electrodiagnostic data is poorly quantified.

Methods:

One hundred five healthy volunteers had clinical and neurophysiological assessment. The effects of age, height, gender, weight, and body mass index were explored using stepwise regression modeling. Reference values were derived from raw and adjusted data, which were transformed to allow appropriate use of parametric statistics. The diagnostic accuracy of derived limits was tested in patients at risk of distal symmetric peripheral neuropathy (DSPN) from chemotherapy.

Results:

The variability of our normative data was reduced by up to 69% through the use of regression modeling, but the overall benefits of mathematical correction were marginal. The most accurate reference limits were established using the 2.5th and 97.5th percentiles of the raw data.

Conclusions:

Stepwise statistical regression and mathematical transformation improve the distribution of normative data, but their practical impact for diagnosis of distal symmetrical polyneuropathy is small. Muscle Nerve 2011