bluuebunny/crossref_metadata_2025 huggingface dataset:
The use of erlotinib in daily practice: a study on adherence and patients' experiences
Authors: Timmers Lonneke , Boons Christel CLM , Mangnus Dirk , Moes Josee E , Swart Eleonora L , Boven Epie , Smit Egbert F , Hugtenburg Jacqueline G
Published: July 2011

Background

Adherence to pharmacological therapy is a complex and multi-factorial issue that can substantially alter the outcome of treatment. It has been shown that cancer patients, especially when using long-term medication, have similar adherence rates to those of patients with other diseases. The consequences of poor adherence are poor health outcomes and increased health care costs. Only few studies have focused on the use of oral anticancer agents in daily practice. Information about the reasons for non-adherence is essential for the development of interventions that may increase adherence. This paper presents the CAPER-erlotinib protocol, which is designed to study the relationship between adherence to erlotinib and both the plasma concentration and side-effects in patients with NSCLC. Further, the relationships between patient characteristics, disease characteristics, side-effects, quality of life, patient beliefs and attitude towards disease and medication, dose adjustments, reasons for discontinuation and plasma concentration of erlotinib will be explored.

Methods/Design

In this prospective observational cohort study 65 NSCLC patients of 18 years or older starting treatment with erlotinib will be followed for a period up to 16 weeks. The main study parameters are adherence, the plasma concentration of erlotinib and the number and grade of side-effects. At baseline and on erlotinib treatment in weeks 3-4, 8-9, 12 and 15-16, patients will be asked to fill out a questionnaire. In weeks 3-4, 8-9 and 15-16 blood samples are collected, which will be analysed for plasma concentration of erlotinib. Adherence will be measured using a medication event monitoring system.

Discussion

The present study aims to get more insight into patients' experiences with the use of erlotinib in daily practice and the various aspects that govern adherence. We hypothesize that side-effects play an important role in the way patients use erlotinib. We expect that the present study will provide valuable knowledge which will be useful for health care professionals to develop interventions to support patients. This approach will improve the adherence and persistence with the use of erlotinib in order to derive optimal benefit from the medication.

Trial Registration

NTR1830
Experiences of guided Internet-based cognitive-behavioural treatment for depression: A qualitative study
Authors: Bendelin Nina , Hesser Hugo , Dahl Johan , Carlbring Per , Nelson Karin Zetterqvist , Andersson Gerhard
Published: July 2011

Background

Internet-based self-help treatment with minimal therapist contact has been shown to have an effect in treating various conditions. The objective of this study was to explore participants' views of Internet administrated guided self-help treatment for depression.

Methods

In-depth interviews were conducted with 12 strategically selected participants and qualitative methods with components of both thematic analysis and grounded theory were used in the analyses.

Results

Three distinct change processes relating to how participants worked with the treatment material emerged which were categorized as (a) Readers, (b) Strivers, and (c) Doers. These processes dealt with attitudes towards treatment, views on motivational aspects of the treatment, and perceptions of consequences of the treatment.

Conclusions

We conclude that the findings correspond with existing theoretical models of face-to-face psychotherapy within qualitative process research. Persons who take responsibility for the treatment and also attribute success to themselves appear to benefit more. Motivation is a crucial aspect of guided self-help in the treatment of depression.
Zoledronic acid inhibits vasculogenic mimicry in murine osteosarcoma cell line in vitro
Authors: Fu Dehao , He Xianfeng , Yang Shuhua , Xu Weihua , Lin Tao , Feng Xiaobo
Published: July 2011

Background

To study the effects of zoledronic acid (ZA) on the vasculogenic mimicry of osteosarcoma cells in vitro.

Methods

A Three-dimensional culture of LM8 osteosarcoma cells on a type I collagen matrix was used to investigate whether osteosarcoma cells can develop vasculogenic mimicry, and to determine the effects of ZA on this process. In addition, the cellular ultrastructural changes were observed using scanning electron microscopy and laser confocal microscopy. The effects of ZA on the translocation of RhoA protein from the cytosol to the membrane in LM8 cells were measured via immunoblotting.

Results

ZA inhibited the development of vasculogenic mimicry by the LM8 osteosarcoma cells, decreased microvilli formation on the cell surface, and disrupted the F-actin cytoskeleton. ZA prevented translocation of RhoA protein from the cytosol to the membrane in LM8 cells.

Conclusions

ZA can impair RhoA membrane localization in LM8 cells, causing obvious changes in the ultrastructure of osteosarcoma cells and induce cell apoptosis, which may be one of the underlying mechanisms by which the agent inhibits the development of vasculogenic mimicry by the LM8 cells.
Detection and characterization of spontaneous internal deletion mutants of Beet Necrotic yellow vein virus RNA3 from systemic host Nicotiana benthamiana
Authors: Wang Ying , Fan Huiyan , Wang Xian-Bing , Li Min , Han Chenggui , Li Dawei , Yu Jialin
Published: July 2011

Background

Beet Necrotic Yellow Vein virus (BNYVV) is a member of the genus Benyvirus causing a worldwide sugar beet disease rhizomania. BNYVV contains four or five plus-sense single stranded RNAs. In altered selective conditions, multipartite RNA viruses of plant are prone to undergoing internal deletions, thus turning into Defective RNAs (D RNAs). Although several D RNAs have been reported in BNYVV infection, the spontaneous internal deletion mutants responsible for severe symptom in systemic host Nicotiana benthamiana (N. benthamiana) are not described so far.

Results

Systemic host N. benthamiana was inoculated by Chinese BNYVV isolates. RT-PCR and Northern blot showed that the D RNAs forms of BNYVV RNA3 were present in the systemic infection of the N. benthamiana. Three distinct D-RNA3s, named as D-RNA 3α, D-RNA 3β and D-RNA 3γ, were made into infectious clones. When inoculated on the N. benthamiana, the in vitro transcripts of D forms exhibited more stable than that of wild-type RNA3 in systemic movement. Among the detected mutant, the p25 protein frame-shift mutant (D-RNA3α) induced obvious necrotic lesions on Tetragonia.expansa (T. expansa) and pronounced systemic symptom on the N. benthamiana. The D-RNA3α was further mutated artificially to pre-terminate the downstream N protein, leading to the abolishment of the pathogenicity, indicating the N protein was responsible for the necrotic symptom.

Conclusion

Our studies demonstrated the internal deletion mutants of BNYVV-RNA3 were spontaneously generated in the systemic infection on N. benthamiana. The internal deletions didn't affect the efficient replication of D-RNA3s, instead by improving the stability and pathogenicity of RNA3 in the systemic host N. benthamiana. Besides, our results also suggested the downstream N protein of RNA3, but not the upstream p25 protein, may play an important role in the systemic infection on N. benthamiana.
Characterisation of five candidate genes within the ETEC F4ab/ac candidate region in pigs
Authors: Jacobsen Mette , Cirera Susanna , Joller David , Esteso Gloria , Kracht Steffen S , Edfors Inger , Bendixen Christian , Archibald Alan L , Vogeli Peter , Neuenschwander Stefan , Bertschinger Hans U , Rampoldi Antonio , Andersson Leif , Fredholm Merete , Jørgensen Claus B
Published: July 2011

Background

Enterotoxigenic Escherichia coli (ETEC) that express the F4ab and F4ac fimbriae is a major contributor to diarrhoea outbreaks in the pig breeding industry, infecting both newborn and weaned piglets. Some pigs are resistant to this infection, and susceptibility is inherited as a simple dominant Mendelian trait. Indentifying the genetics behind this trait will greatly benefit pig welfare as well as the pig breeding industry by providing an opportunity to select against genetically susceptible animals, thereby reducing the number of diarrhoea outbreaks. The trait has recently been mapped by haplotype sharing to a 2.5 Mb region on pig chromosome 13, a region containing 18 annotated genes.

Findings

The coding regions of five candidate genes for susceptibility to ETEC F4ab/ac infection (TFRC, ACK1, MUC20, MUC4 and KIAA0226), all located in the 2.5 Mb region, were investigated for the presence of possible causative mutations. A total of 34 polymorphisms were identified in either coding regions or their flanking introns. The genotyping data for two of those were found to perfectly match the genotypes at the ETEC F4ab/ac locus, a G to C polymorphism in intron 11 of TFRC and a C to T silent polymorphism in exon 22 of KIAA0226. Transcriptional profiles of the five genes were investigated in a porcine tissue panel including various intestinal tissues. All five genes were expressed in intestinal tissues at different levels but none of the genes were found differentially expressed between ETEC F4ab/ac resistant and ETEC F4ab/ac susceptible animals in any of the tested tissues.

Conclusions

None of the identified polymorphisms are obvious causative mutations for ETEC F4ab/ac susceptibility, as they have no impact on the level of the overall mRNA expression nor predicted to influence the composition of the amino acids composition. However, we cannot exclude that the five tested genes are bona fide candidate genes for susceptibility to ETEC F4ab/ac infection since the identified polymorphism might affect the translational apparatus, alternative splice forms may exist and post translational mechanisms might contribute to disease susceptibility.
The Cytosolic Chaperone Hsc70 Promotes Traffic to the Cell Surface of Intracellular Retained Melanocortin-4 Receptor Mutants
Authors: Meimaridou Eirini , Gooljar Sakina B. , Ramnarace Nalini , Anthonypillai Lucia , Clark Adrian J. L. , Chapple J. Paul
Published: July 2011

Inherited modifications in protein structure frequently cause a loss-of-function by interfering with protein synthesis, transport, or stability. For the obesity-linked melanocortin-4 receptor (MC4R) and other G protein-coupled receptors, many mutants are intracellular retained. The biogenesis and trafficking of G protein-coupled receptors are regulated by multiple factors, including molecular chaperone networks. Here, we have investigated the ability of the cytosolic cognate 70-kDa heat-shock protein (Hsc70) chaperone system to modulate cell surface expression of MC4R. Clinically occurring MC4R mutants S58C, P78L, and D90N were demonstrated to have reduced trafficking to the plasma membrane and to be retained at the endoplasmic reticulum (ER). Analyses by fluorescence recovery after photobleaching revealed that the mobility of MC4R mutant protein at the ER was reduced, implying protein misfolding. In cells expressing MC4R, overexpression of Hsc70 resulted in increased levels of wild-type and mutant receptors at the cell surface. MC4R and Hsc70 coimmunoprecipitated, and fluorescence recovery after photobleaching analyses showed that increasing cellular levels of Hsc70 promoted the mobility of ER retained MC4R. Moreover, expression of HSJ1b, a cochaperone that enhances degradation of Hsc70 clients, reduced cellular levels of MC4R. Hsp70 and Hsp90 chaperone systems collaborate in the cellular processing of clients. For MC4R, inhibition of endogenous Hsp90 by geldanamycin reduced receptor levels. By contrast, expression of the Hsp90 cochaperone Aha1 (activator of Hsp90 ATPase) increased cellular levels of MC4R. Finally, we demonstrate that signaling of intracellular retained MC4R mutants is increased in cells overexpressing Hsc70. These data indicate that cytosolic chaperone systems can facilitate rescue of intracellular retained MC4R by improving folding. They also support proteostasis networks as a potential target for MC4R-linked obesity.
Chiral Discrimination of Drugs by DNA Tetranucleotides under Electrospray Ionisation Conditions
Authors: Sivaleela Tallagadda , Nagaveni Voleti , Prabhakar Sripadi , Vairamani Mariappanadar
Published: July 2011

The DNA tetranucleotides, extended versions of GCA at the 3′-end or 5′-end, were used as chiral selectors for the chiral discrimination of atenolol, DOPA, tamsulosin, valacyclovir and zolmitriptan. Chiral discrimination was achieved by investigating the collision-induced dissociation spectra of the [X + Y – 2H]2– ion generated by electrospraying a solution mixture of tetranucleotide (X) and R- or S-analyte drug (Y). The relative abundances of the precursor ion and the product ion, resulting from the loss of drug, were considered for measuring the degree of chiral discrimination. Among all the tetranucleotides studied, AGCA showed the highest chiral discrimination. The present study emphasised the position of an adenine base in the tetranucleotide in chiral discrimination. The suitability of the method for the measurement of optical purity was also demonstrated in the case of zolmitriptan.
Investigation of Coordination of Mg(II) Cations to 2-Pyrimidinyloxy-N-Arylbenzylamines by Electrospray Mass Spectrometry: Insights for Mg(II) Catalyzed Smiles Rearrangement Reactions
Authors: Wang Haoyang , Xu Chu , Zhang Li , Tang Qinghong , Guo Yinlong , Lu Long
Published: July 2011

The CH3OH solutions of pyrimidinyloxy- N-arylbenzylamines (1–5) in the presence of Mg(II)X2 salts (X = Cl or ClO4) were investigated by electrospray ionization mass spectrometry and tandem mass spectrometry (MS/MS) subsequently, showing that the cationic Mg(II) complexes1–5·MgX+ were important active complexes or intermediates for initiating interesting Smiles rearrangement reactions in both the gas- and solution phases. By using different MgX2 salts and selecting a set of reactants with different substitutes, the role of the counter-ion (X−) and the structure effect of the reactants on the Mg(II) catalyzed Smiles rearrangement reactions were studied. Moreover, the solvent effect on Mg(II) catalyzed Smiles rearrangement reactions was revealed by studying the CH3OH adduct complexes of1–5·MgCl+, which showed that the coordination of CH3OH to the Mg(II) center in the complexes decreased the reaction tendency. The mechanisms involved in the gas-phase Mg(II) catalyzed Smiles rearrangement reactions were proposed on the basis of MS/MS experiments and theoretical computations, showing some unique chemistries initiated by introducing Mg(II) into the template molecules.
Targeted and Non-Targeted Boron Complex Formation followed by Electrospray Fourier Transform Ion Cyclotron Mass Spectrometry: A Novel Approach for Identifying Boron Esters with Natural Organic Matter
Authors: Gaspar Andras , Lucio Marianna , Harir Mourad , Schmitt-Kopplin Philippe
Published: July 2011

The formation of boron esters was investigated in peat-soluble humified materials with a detailed molecular-level description of boron–organic interactions. Thousands of individually baseline separated signals were obtained from the analysis of natural organic matter of peat samples, using Fourier transform ion cyclotron resonance mass spectrometry. This technique offers unsurpassed isotope-specific mass resolution that can lead to precise molecular formula assignments by means of mathematical data analysis and visualisation techniques, such as mass defect (Kendrick) or elemental ratio (van Krevelen) plots. The analysis of potential boron binding structures within the sample of natural organic matter was described based on prior results. Herein, we describe an algorithm that can be used to effectively distinguish and filter complexes through data obtained from boron-enriched systems with highly intricate mass spectra, such as natural organic matter.
Photoionization Study of L-Valine in the Gas Phase by Vacuum Ultraviolet Synchrotron Radiation
Authors: Zhou Shaohui , Chu Genbai , Cao Lanlan , Shan Xiaobin , Liu Fuyi , Han Ju-Guang , Sheng Liusi
Published: July 2011

The photoionization and photodissociation of L-valine are studied by tunable synchrotron vacuum ultraviolet photoionization mass spectrometry at the photon energy of 13 eV. The ionization energy of L-valine and the appearance energies of major fragments are measured by the photoionization efficiency spectrum in the photon energy range of 8–11 eV. Possible formation pathways of the major fragments, NH2CHC(OH)2+ ( m/z = 75), NH2(CH3)2(CH)2+ ( m/z = 72) and NH2CHCO+ ( m/z = 57), are discussed in detail with the theoretical calculations at the B3LYP/6-31++G (d, p) level. Hydrogen migration is considered as the key way for the formation of NH2CHC(OH)2+ ( m/z = 75) and NH2CHCO+ ( m/z = 57). Further more, other fragments, NH2CHCOOH+ ( m/z = 74), (C H3)2(C H)2+ ( m/z = 56), C4H7+ ( m/z = 55), NH2CHOH+ ( m/z = 46), NH2CH2+ ( m/z = 30) and m/z = 18, species are also briefly described.
Some Thoughts on Electrospray Ionization Mechanisms
Authors: Crotti Sara , Seraglia Roberta , Traldi Pietro
Published: July 2011

Electrospray ionization (ESI) mechanisms are highly complex, due to a series of physical and chemical phenomena taking place on a complex system, as a solution is. In fact, even if the solution of an analyte in a protic medium can be considered at first sight to be a two-component system, the presence of solvent dissociation equilibria and the possible interactions solvent–solvent dissociation products, solvent dissociation products–analyte make this system highly complex, also for the presence of possible ionic compounds (for example, Na+, K+) which strongly affect the above equilibria. A high number of research articles have been published, mainly devoted to charged droplet production and to gas-phase ion generation. They all show the high complexity of the processes affecting electrospray measurements related to either the chemical equilibria present in the condensed phase and to electrolysis processes at the emitter tip or to the processes occurring in the sprayed droplets. As a result, the chemical composition inside the small droplets from which the analyte ions are generated can be significantly different from those in sprayed solution. In this review, after a short survey of the proposed ESI mechanisms, some experiments are described. They were performed to examine if ion mobility in solution, before the formation of the sprayed charged droplets, can affect the ESI results. The data, obtained by studying both inorganic and organic analytes, indicate that the ESI spectra are dependent on the analyte dimension and charge state which, as a consequence, affect their ion mobility in solution.
Salmonella typhimurium in the hip: look before a SLE patient leaps
Authors: Anil Kumar V , Krishna Sushma , Thilak Jai , Dinesh Kavitha R , Karim Shamsul
Published: July 2011

Salmonellosis is a common infection in systemic lupus erythematosus patients. The present study reports on two such cases of Salmonella typhimurium septic arthritis among the 102 patients seen during a four-year period.
Clinical profile of children with kerosene aspiration
Authors: Venkatesh C , Sriram P , Adhisivam B , Mahadevan S
Published: July 2011

Accidental aspiration of kerosene is a common problem among children in developing countries. This descriptive study involved the retrospective analysis of children admitted with kerosene aspiration in a tertiary care hospital in South India for a year. Kerosene aspiration contributed to 60.4% of poisoning cases. Boys aged less than three years and from a rural background formed a significant proportion. Tachypnoea, cough and crepitations were the predominant clinical findings. Male gender and malnutrition (weight for age <80%) were significantly associated with prolonged hospital stay.
Investor Sentiment and Analysts' Earnings Forecast Errors
Authors: Hribar Paul , McInnis John
Published: July 2011

We correlate analysts' forecast errors with temporal variation in investor sentiment. We find that when sentiment is high, analysts' forecasts of one-year-ahead earnings and long-term earnings growth are relatively more optimistic for “uncertain” or “difficult-to-value” firms. Adding these forecast errors to a regression of stock returns on sentiment absorbs a sizable fraction of the explanatory power of sentiment for the cross section of future returns. This finding provides direct support for the notion that investor sentiment affects the earnings expectations of hard-to-value firms. Additional tests suggest that this bias in expectations is unlikely to be strategic in nature. Our results provide new insight into the mechanism through which investor sentiment affects returns.

This paper was accepted by Brad Barber, Teck Ho, and Terrance Odean, special issue editors.
Bubbles and Information: An Experiment
Authors: Sutter Matthias , Huber Jürgen , Kirchler Michael
Published: July 2011

A symmetric distribution of information, although omnipresent in real markets, is rarely considered in experimental economics. We study whether information about imminent future dividends can abate bubbles in experimental asset markets. We find that markets with asymmetrically informed traders have significantly smaller bubbles than markets with symmetrically informed or uninformed traders. Hence, fundamental values are better reflected in market prices—implying higher market efficiency—when some traders know more than others about future dividends. This suggests that bubbles are abated when traders know that a subset of them have an edge (in information) over others.

This paper was accepted by Brad Barber, Teck Ho, and Terrance Odean, special issue editors.
Systemic Risk: What Defaults Are Telling Us
Authors: Giesecke Kay , Kim Baeho
Published: July 2011

This paper develops dynamic measures of the systemic risk of the financial sector as a whole. It defines systemic risk as the conditional probability of failure of a sufficiently large fraction of the total population of financial institutions. This definition recognizes that the cause of systemic distress is the correlated failure of institutions to meet obligations to creditors, customers, and trading partners. The likelihood estimators of the failure probability are based on a dynamic hazard model of correlated failure timing that captures the influence on failure timing of time-varying macroeconomic and sector-specific risk factors, and of spillover effects. Tests indicate that our measures provide accurate out-of-sample forecasts of the term structure of systemic risk in the United States for the period from 1998 to 2009.

This paper was accepted by Wei Xiong, finance.
Generalized Differentiation with Positively Homogeneous Maps: Applications in Set-Valued Analysis and Metric Regularity
Authors: Pang C. H. Jeffrey
Published: July 2011

We propose a new concept of generalized differentiation of set-valued maps that captures first-order information. This concept encompasses the standard notions of Fréchet differentiability, strict differentiability, calmness and Lipschitz continuity in single-valued maps, and the Aubin property and Lipschitz continuity in set-valued maps. We present calculus rules, sharpen the relationship between the Aubin property and coderivatives, and study how metric regularity and open covering can be refined to have a directional property similar to our concept of generalized differentiation. Finally, we discuss the relationship between the robust form of generalized differentiation and its one-sided counterpart.
Flows and Decompositions of Games: Harmonic and Potential Games
Authors: Candogan Ozan , Menache Ishai , Ozdaglar Asuman , Parrilo Pablo A.
Published: July 2011

In this paper we introduce a novel flow representation for finite games in strategic form. This representation allows us to develop a canonical direct sum decomposition of an arbitrary game into three components, which we refer to as the potential, harmonic, and nonstrategic components. We analyze natural classes of games that are induced by this decomposition, and in particular, focus on games with no harmonic component and games with no potential component. We show that the first class corresponds to the well-known potential games. We refer to the second class of games as harmonic games, and demonstrate that this new class has interesting properties which contrast with properties of potential games. Exploiting the decomposition framework, we obtain explicit expressions for the projections of games onto the subspaces of potential and harmonic games. This enables an extension of the equilibrium properties of potential and harmonic games to “nearby” games.
Factors Associated With the Early Work Experiences of Adolescents With Severe Disabilities
Authors: Carter Erik W. , Austin Diane , Trainor Audrey A.
Published: July 2011

The early work experiences of a nationally representative sample of youth with severe disabilities (i.e., intellectual disabilities, autism, multiple disabilities) were examined. Using data from the National Longitudinal Transition Study-2, we explored the extent to which various student-, family-, school-, and community-level factors were associated with paid work experiences during high school. Findings highlight the elusiveness of early work experiences for many youth with severe disabilities and call attention to malleable factors that may play a role in shaping employment success during high school. Recommendations for research and practice are highlighted.
Choosing Employment: Factors That Impact Employment Decisions for Individuals With Intellectual Disability
Authors: Timmons Jaimie Ciulla , Hall Allison Cohen , Bose Jennifer , Wolfe Ashley , Winsor Jean
Published: July 2011

Little is known about the factors that shape the employment-related decisions of individuals with intellectual and/or developmental disabilities. Findings from qualitative interviews with individuals, their family members, and employment-support professionals from four community rehabilitation providers throughout Massachusetts were reported. Recognizing the value of participatory action research, we also included a co-researcher with intellectual disability who participated in all facets of the research process. Findings revealed a collection of people and factors considered influential in employment-related decision-making. The family in the formative years, school-based staff and early employment experiences, the culture of the community rehabilitation providers, the job developer, and personal preferences all influenced participants' decisions. Through understanding these persuasive elements, we offer recommendations to those in the intellectual and developmental disabilities field to optimize employment choices and outcomes.
Structure, dynamics, and mechanism of the lead-dependent ribozyme
Authors: Qi Xin , Xia Tianbing
Published: July 2011

Leadzyme is a small catalytic RNA that was identified by in vitro selection for Pb2+-dependent cleavage from a tRNA library. Leadzyme employs a unique two-step Pb2+-specific mechanism to cleave within its active site. NMR and crystal structures of the active site revealed different folding patterns, but neither features the in-line alignment for attack by the 2′-OH nucleophilic group. These experimentally determined structures most likely represent ground states and are catalytically inactive. There are significant dynamics of the active site and the motif samples multiple conformations at the ground states. Various metal ion binding sites have been identified, including one that may be occupied by a catalytic Pb2+. Based on functional group analysis, a computational model of the transition state has been proposed. This model features a unique base triple that is consistent with sequence and functional group requirements for catalysis. This structure is likely only populated transiently, but imposing appropriate conformational constraints may significantly stabilize this state thereby promoting catalysis. Other ions may inhibit the cleavage by competing for the Pb2+ binding site, or by stabilizing the ground state thereby suppressing its transition to the catalytically active conformation. Some rare earth ions can enhance the reaction via an unknown mechanism. Because of its unique chemistry and dynamic behavior, leadzyme can continue to serve as an excellent model system for teaching us RNA biology and chemistry.
Redundant role of the cytochrome c-mediated intrinsic apoptotic pathway in pancreatic β-cells
Authors: Choi Diana , Schroer Stephanie A , Lu Shun Yan , Cai Erica P , Hao Zhenyue , Woo Minna
Published: July 2011

Cytochromecis one of the central mediators of the mitochondrial or the intrinsic apoptotic pathway. Mice harboring a ‘knock-in’ mutation of cytochromec, impairing only its apoptotic function, have permitted studies on the essential role of cytochromec-mediated apoptosis in various tissue homeostasis. To this end, we examined the role of cytochromecin pancreatic β-cells under homeostatic conditions and in diabetes models, including those induced by streptozotocin (STZ) and c-Myc. Previous studies have shown that both STZ- and c-Myc-induced β-cell apoptosis is mediated through caspase-3 activation; however, the precise mechanism in these modes of cell death was not characterized. The results of our study show that lack of functional cytochromecdoes not affect glucose homeostasis or pancreatic β-cell mass under basal conditions. Moreover, the cytochromec-mediated intrinsic apoptotic pathway is required for neither STZ- nor c-Myc-induced β-cell death. We also observed that the extrinsic apoptotic pathway mediated through caspase-8 was not essential in c-Myc-induced β-cell destruction. These findings suggest that cytochromecis not required for STZ-induced β-cell apoptosis and, together with the caspase-8-mediated extrinsic pathway, plays a redundant role in c-Myc-induced β-cell apoptosis.
Diagnostic Tests in Neonatology: Evaluation and Interpretation Using Sepsis as an Example
Authors: Rajani Anand K. , Philip Alistair G. S.
Published: July 2011

Diagnostic clinical tests are becoming increasingly important in medicine. In the case of neonatal sepsis, a number of new clinical laboratory tests have emerged to aid in diagnosis. In this article, the example of neonatal sepsis is used to review preconditions for evaluating a diagnostic test, common measures of test performance (eg, sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios). Reference values of these measures for a good diagnostic test are also reviewed. The interpretation of receiver operating characteristic curves for comparing diagnostic tests, determining the optimal cut-off for quantitative tests and assessing diagnostic accuracy, is also examined.
Aiming for Zero: Preventing Invasive Candida Infections in Extremely Preterm Infants
Authors: Kaufman David A.
Published: July 2011

Strong evidence shows that prevention of invasive Candida infections (ICI) can be achieved by every neonatal intensive care unit (NICU). Due to the incidence of ICI and high infection-associated mortality and neurodevelopmental impairment, antifungal prophylaxis should be targeted to infants weighing less than 1,000 g or born at or before 27 weeks' gestation. Even in NICUs that have low rates of ICI, antifungal prophylaxis is crucial to improving survival and neurodevelopmental outcomes in this vulnerable population. Strong evidence supports the use of both fluconazole and nystatin for such prophylaxis. Fluconazole is preferred in high-risk preterm infants because intravenous (IV) fluconazole prophylaxis has greater efficacy compared with enteral nystatin prophylaxis, is effective in the most immature patients, is less expensive, requires fewer doses, and can be administered to infants who have gastrointestinal disease or hemodynamic instability. For infants weighing 1,000 to 1,500 g, either drug could be chosen for prophylaxis. Fluconazole prophylaxis administered at 3 mg/kg twice a week, starting after birth and requiring central or peripheral access, appears to be the safest and most effective schedule in preventing ICI while attenuating the emergence of fungal resistance.
Topics in Neonatal Informatics
Authors: Palma Jonathan P. , Sharek Paul J. , Classen David C. , Longhurst Christopher A.
Published: July 2011

Computerized physician order entry (CPOE) is the feature of electronic medical record (EMR) implementation that arguably offers the greatest quality and patient safety benefits. The gains are potentially greater for critically ill neonates, but the effect of CPOE on quality and safety is dependent upon local implementation decisions.
Bernard Palissy (1510–1590) and the French geologists: a critical reappraisal concerning the founding naturalist and his rustic ceramics
Authors: Plaziat Jean-Claude
Published: July 2011

Bernard Palissy benefited from two centuries (mid-18th - mid-20th c.) of a striking reputation – only partly justified – as a precursor of the European geologists and as a prolific producer of a new ceramic ware. During the last decades that appreciation was revealed to be overrated. His scientific and technological fame were respectively founded on misreadings by 18th c. rediscoverers (Jussieu, Réaumur, Fontenelle) and on erroneous attributions to a so-called “rustic Palissy’s ware style” of most of the pieces of China with animals in full relief referred to Palissy. The attributions to the Palissy’s workshop of pieces including fossil shell casts, by 19th c. romantic ceramic collectors, was confirmed by Alexandre Brongniart [1854], the pioneer decipherer, along with G. Cuvier, of the geology of the Paris basin, who identified Lutetian fossil shells. Munier-Chalmas [in Dupuy, 1894], noting that Palissy did not accept that inland fossils could belong to any marine assemblages, did not understand that this misinterpretation contradicts the current fame of Palissy as the discoverer of marine transgressions.

Modern geologists, following F. Ellenberger [1988], the first to point out this contradiction, undertook the rehabilitation of the true geological message of Palissy as a pluridisciplinary precursor in nature processes elucidation, at least equal to Leonardo da Vinci in accuracy. This contribution seeks also to solve the last major point of misunderstanding, which resulted in the mingling of the rare true rustic wares designed and produced in Palissy’s workshop at Saintes (according to the shells and vertebrates casts), with the more famous and numerous chinas, different in style, especially those with Tertiary fossil shells cast from nature, probably conceived more than a century after the rustiques figulines of Palissy, in a workshop set up in the northernmost Ile de France and not copied from them. The highest established merits of Palissy are acknowledged, that finally place him ahead of the world geologists.
Impact on Gaza aquifer from recharge with partially treated wastewater
Authors: Hamdan Sami M. , Nassar Abdelmajid , Troeger Uwe
Published: July 2011

The Gaza Strip suffers from high pressure imposed on its water resources. There is a deficit of about 50 mm3 every year, which has led to a declination of groundwater level and deterioration of groundwater quality. New water resources are sought to fulfil the water deficit; among them is the artificial recharge of treated wastewater to groundwater. The impact of recharging partially treated wastewater in Gaza was tested through a pilot project implemented east of the existing wastewater treatment plant. The daily application of about 10,000 m3 of effluent to infiltration basins had an effect on the aquifer, which was monitored through the surrounding operating water wells over five years from 2000 until 2005. Although the monitored wells are operated for irrigation by farmers, impacts were clearly noticed. Groundwater levels improved and an increase in some areas of 0.6 m within three years was observed. The nitrate ion concentration also decreased in the groundwater due to nitrification processes. However, chloride ion, which indicates salinity, increased because the effluent has high chloride concentration. Boron levels increased in some areas to 0.5 mg/l, which could affect sensitive crops grown in the area.
Nitrogen-removal efficiency in an upflow partially packed biological aerated filter (BAF) without backwashing process
Authors: Biplob Pramanik , Fatihah Suja , Shahrom Zain , Ahmed ElShafie
Published: July 2011

An upflow, partially packed biological aerated filter (BAF) reactor was used to remove nitrogen in the form of ammonia ions by a nitrification process that involves physical, chemical and biological phenomena governed by a variety of parameters such as dissolved oxygen concentration, pH and alkalinity. Dissolved oxygen (DO) and pH were shown to have effects on the nitrification process in this study. Three C:N ratios i.e., 10, 4 and 1 were compared during this study by varying the nitrogen loading while the carbon loading was kept constant at 0.405 ± 0.015 kg chemical oxygen demand m−3 d−1. The removal efficiencies of ammonia linearly increase with a rise of the initial concentration of ammonia-nitrogen. The results of the 115 days' operation of the BAF system showed that its overall NH3-N performance was good, where a removal efficiency of 87.0 ± 2.9%, 89.2 ± 1.38% and 91.1 ± 0.7% and COD removal of 87.6 ± 2.9%, 86.4 ± 2.1% and 89.5 ± 2.6% were achieved for the C:N ratios of 10, 4 and 1, respectively on average, over 6 h hydraulic retention time (HRT). No clogging occurred throughout the period although backwashing was eliminated. It was concluded that the BAF system proposed in this study removed nitrogen by the nitrification process extremely well.
Building computers in Serbia: The first half of the digital century
Authors: Protic Jelica , Ristanovic Dejan
Published: July 2011

In this paper, we describe the early development of CER-10, the first digital
computer built in Serbia, honor its inventors, and follow the professional
path of its chief designers, prof. Rajko Tomovic and prof. Tihomir Aleksic,
who became the first university professor of computer engineering in Serbia.
We also give a short overview of CER family of computers that were developed
after the CER-10 till midseventies. In the early eighties, computer
revolution continued with personal computers, so we show the early attempts
to produce this kind of computers in Serbia, from "build it yourself"
campaigns to the industrial production, and we analyze implications of these
attempts to the development of user community and evolution to the
information society.
Mechanical properties and surface characterization of translucent composite wire following topical fluoride treatment
Authors: Hammad Shaza M. , Al-Wakeel Essam E. , Gad El-Sayed
Published: July 2011

Objective:

To determine the effects of a fluoride prophylactic agent on the mechanical properties and surface quality of a preformed round translucent composite archwire while comparing it with nickel-titanium (Ni-Ti) and multistranded stainless steel wires.

Materials and Methods:

The wires were immersed in an acidulated phosphate fluoride solution (APF) or in distilled water (control) for 1.5 hours at 37°C. Flexural modulus of elasticity (E) and yield strength (YS) of the wires were measured using a three-point bending test in a universal testing machine. The springback ratio (YS/E) was calculated for each wire. The influence of fluoride treatment on properties of the wires was statistically analyzed using Student's t-test at α  =  .05. Surface changes were observed with a scanning electron microscope.

Results:

Fluoride treatment produced a statistically significant reduction in E, YS, and YS/E of the composite wire (P < .05). In addition, a significant decrease in E of Ni-Ti wire was found after exposure to fluoride, upon comparison with distilled water control treatment. On the other hand, no significant effect of fluoride treatment was found on YS and YS/E of Ni-Ti wire and on studied properties of the multistranded stainless steel wire (P > .05). Corrosive changes in surface topography were observed after exposure to the fluoride agent and were more pronounced with the composite wire.

Conclusions:

These results suggest that using a topical fluoride agent with translucent composite wire could decrease the mechanical properties and might damage the surface of the wire, potentially contributing to prolonged orthodontic treatment.
A comparative evaluation of lingual retainer failure bonded with or without liquid resin
Authors: Bazargani Farhan , Jacobson Sven , Lennartsson Bertil
Published: July 2011

Objective:

To prospectively evaluate and compare the effect of liquid resin on lingual retainer failure after a 2-year follow-up.

Materials and Methods:

Fifty-two patients (26 males, 26 females) with a mean age of 18.3 ± 1.3 years at follow-up, were randomized into two groups: the resin group and the nonresin group. The lingual retainers in the resin group were bonded to the enamel surfaces with two-step bonding resin, Optibond FL, and Tetric EvoFlow. The nonresin group followed the same procedure of bonding retainers but without applying the Optibond FL. Retainer failure, calculus accumulation, and discoloration of composite pads adjacent to the retainers during the 2-year observation period were registered, compared, and statistically analyzed with a Fisher's exact test and chi-square test.

Results:

In the resin group, the incidence of retainer failure was 4% and occurred at the composite-wire interface; in the nonresin group, the incidence was 27% and occurred at the enamel-composite interface. The difference between the groups was statistically significant (P  =  .049). The incidences of calculus accumulation and discoloration adjacent to the composite pads were 27% and 69% (P  =  .003 and P < .001) higher in the nonresin group, respectively.

Conclusion:

Application of resin in bonding of lingual retainers appears to reduce the incidence of retainer failure as well as the incidence of calculus accumulation and discoloration adjacent to the composite pads.
Diagnosis of presumed acute ischemic stroke and associated seizure management in a Congo African grey parrot
Authors: Beaufrère Hugues , Nevarez Javier , Gaschen Lorrie , Ryan Kirk , Schnellbacher Rodney , Tully Thomas
Published: July 2011

Case Description—A 14-year-old Congo African grey parrot (Psittacus erithacus erithacus) was evaluated for an acute onset of falling off of its perch and tonic-clonic movements.

Clinical Findings—Clinical signs were consistent with partial seizures. Findings on whole-body radiography, CBC, and plasma biochemical analysis were unremarkable. Plasma magnesium, ionized calcium, and bile acids concentrations were within reference limits. A magnetic resonance imaging (MRI) examination of the head revealed the presence of a focal hyperintensity at the central to left side of the optic chiasm and a hyperintense focus in the right side of the midbrain area in T2-weighted and FLAIR pulse sequence images. These findings were most consistent with an acute ischemic stroke with 2 brain infarcts.

Treatment and Outcome—Seizures were initially managed with potassium bromide and phenobarbital administration. On the basis of poor results and difficulties to reach therapeutic blood concentrations, the treatment plan was changed to levetiracetam and zonisamide administration. Blood concentrations were monitored for both drugs, and the frequency of seizures substantially decreased thereafter. A follow-up MRI examination 2 months later revealed resolution of the hyperintense signals. During the 20-month follow-up period, subsequent clusters of seizures were managed by adjusting levetiracetam and zonisamide dosages and adding clonazepam and gabapentin administration to the treatment plan. Regression of intraparenchymal hyperintense lesions and improvement of clinical signs made a diagnosis of acute ischemic stroke most likely.

Clinical Relevance—Findings for this Congo African grey parrot indicated that an antemortem diagnosis of an acute ischemic stroke followed by long-term seizure management may be possible in affected psittacines.
Relationship of in vitro minimum inhibitory concentrations of tilmicosin against Mannheimia haemolytica and Pasteurella multocida and in vivo tilmicosin treatment outcome among calves with signs of bovine respiratory disease
Authors: McClary David G. , Loneragan Guy H. , Shryock Thomas R. , Carter Brandon L. , Guthrie Carl A. , Corbin Marilyn J. , Mechor Gerald D.
Published: July 2011

Objective—To determine associations between in vitro minimum inhibitory concentrations (MICs) of tilmicosin against Mannheimia haemolytica and Pasteurella multocida and in vivo tilmicosin treatment outcome among calves with clinical signs of bovine respiratory disease (BRD).

Design—Observational, retrospective, cohort study.

Animals—976 feeder calves with clinical signs of BRD enrolled in 16 randomized clinical trials.

Procedures—Records of clinical trials from October 26, 1996, to November 15, 2004, were searched to identify calves with BRD from which a single isolate of M haemolytica or P multocida was identified via culture of deep nasal swab samples prior to treatment with tilmicosin (10 mg/kg [4.5 mg/lb], SC) and for which MICs of tilmicosin against the isolate were determined. The MICs of tilmicosin against recovered isolates and response to tilmicosin treatment were evaluated.

Results—Tilmicosin resistance among M haemolytica and P multocida isolates was uncommon (6/745 [0.8%] and 16/231 [6.9%], respectively). Treatment outcome, defined as success or failure after tilmicosin treatment, did not vary with the MIC of tilmicosin against recovered isolates. The proportion of treatment failures attributed to M haemolytica isolates categorized as resistant (MIC of tilmicosin, ≥ 32 μg/mL) or not susceptible (MIC of tilmicosin, ≥ 16 μg/mL), was 0.2% and 0.5%, respectively.

Conclusions and Clinical Relevance—Recovery of tilmicosin-resistant M haemolytica or P multocida isolates was rare, and no association was detected between MIC of tilmicosin and treatment response.
Evaluation of the sedative and cardiovascular effects of intramuscular administration of dexmedetomidine with and without concurrent atropine administration in dogs
Authors: Congdon Jonathan M. , Marquez Megan , Niyom Sirirat , Boscan Pedro
Published: July 2011

Objective—To evaluate degree of sedation and cardiovascular, respiratory, acid-base excess, and electrolyte variables in response to IM administration of dexmedetomidine or dexmedetomidine with atropine.

Design—Randomized crossover study.

Animals—5 healthy 1- to 2-year-old sexually intact male Treeing Walker Coonhounds.

Procedures—Dogs were instrumented with catheters placed in the dorsal pedal artery and lateral saphenous vein. All dogs received dexmedetomidine (10 μg/kg [4.5 μg/lb], IM) or dexmedetomidine with atropine (0.02 mg/kg [0.009 mg/lb], IM). Variables were measured at baseline (time 0) and 5, 15, 30, and 60 minutes after drug administration.

Results—In all dogs, lithium dilution cardiac output decreased from a mean ± SD baseline value of 5.07 ± 1.0 L/min to 2.1 ± 0.9 L/min. Cardiac output was not different between dexmedetomidine group dogs and dexmedetomidine-atropine group dogs. Mean arterial pressure increased from baseline in both groups but was significantly higher in dexmedetomidine-atropine group dogs, compared with dexmedetomidine group dogs. Heart rate in dexmedetomidine group dogs decreased from 110 ± 14.2 beats/min to 49.4 ± 10.4 beats/min by 15 minutes. No differences were seen in blood gas values, electrolyte concentration, or hemoglobin values over time or between groups. Arrhythmias were detected in dexmedetomidine-atropine group dogs and included atrioventricular block, ventricular premature contractions, and ventricular bigeminy.

Conclusions and Clinical Relevance—Administration of atropine at 0.02 mg/kg, IM, with dexmedetomidine at 10 μg/kg, IM, resulted in an increase in mean arterial blood pressure and heart rate; deleterious cardiac arrhythmias were also observed. Use of atropine with dexmedetomidine is not recommended in dogs.