bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface signature of Mediterranean water eddies in the North-East Atlantic: effect of the upper ocean stratification
Authors: Bashmachnikov I. , Carton X.
Published: July 2012

Abstract. Meddies, intra-thermocline eddies of Mediterranean water, are often visible at the sea surface as positive sea-level anomalies. Here we study the surface signature of several meddies tracked with RAFOS floats and AVISO altimetry. Then, theoretical estimates of the surface signature of a meddy are derived, based on geostrophy and potential vorticity balance. The intensity of the surface signature is proportional to the meddy core radius and to the Coriolis parameter, and inversely proportional to the core depth and buoyancy frequency. This indicates that surface signature of a meddy may be strongly reduced by the upper ocean stratification. Estimates suggest that the southernmost limit for detection in altimetry of small meddies (with radii on the order of 15 km) should lie in the northern subtropics, while large meddies (with radii of 25–30 km) could be detected as far south as the northern tropics. During the initial period of meddy acceleration after meddy formation or a stagnation stage, a cyclonic signal also is generated at the sea-surface, but mostly the anticyclonic surface signal follows the meddy.
Trends in depression diagnosis and consumption of antidepressants in Lithuania in 2004–2009
Authors: KAVALIAUSKIENĖ Liubov , PEČIŪRA Rimantas , ADOMAITIENĖ Virginija
Published: July 2012

Background. One in five people affected by depression will not recover fully from a first episode, and in 70–80% of those achieving remission, depression will recur. The aim of this study was to evaluate the consumption of antidepressants during six years (2004–2009) in Lithuania, to analyze the trends in the diagnosis of depression and its compliance with the use of antidepressants for the future investigation of rationalizing medicamentous depression treatment costs in Lithuania opportunities.
Materials and methods. Data on the total sales of antidepressants were obtained from the IMS (Intercontinental Marketing Service) Health Incorporated. The data were calculated by the DDD (Defined Daily Dose) methodology and expressed in DDDs per 1.000 inhabitants per day. Data on depression diagnosis were obtained from the National Psychiatric Health Centre and expressed as the number of diagnoses in total and by depression types and gender.
Results. The total consumption of antidepressants increased from 10.17 DDD / 1000 inhabitants / day in 2004 to 15.0 DDD / 1000 inhabitants / day in 2009. The number of total depression diagnoses increased by 12%. The number of first time diagnosed depression increased not as significantly as relapsed depression diagnoses – by 27%. In 2009, women were diagnosed with depression 4.5 times more frequently than men. Moreover, depression relapse numbers grew up by 33% during the six study years among women.
Conclusions. During the study period, the consumption of antidepressants increased by 48%. Women were diagnosed with depression more frequently than men. The results of our study show that the number of depression diagnoses are growing because of depression relapse in women.

Keywords: antidepressants consumption, depression relapse, pharmacoeconomics
Changes in prostate cancer incidence in 50–75-year-old men in Lithuania 2006–2009: effect of early diagnosis program
Authors: ADOMAITIS Robertas , JANKEVICIUS Feliksas , SMAILYTE Giedre , LEVULIENE Ruta
Published: July 2012

Background. The Lithuanian Prostate Cancer Early Diagnosis Program (LPCEDP) was launched in 2006. Our study aimed to evaluate the PSA testing offered by general practicians for prostate cancer screening as its results may differ from those reported in randomised screening studies.
Materials and methods. In the LPCEDP, GPs offered a PSA (prostate-specific antigen) test for informed men aged 50–75 years. A PSA > 3 ng/ml was a cut-off limit for referral to urologist. The study group comprised men aged 50–75 years, diagnosed with prostate cancer in 2006–2009. The Lithuanian Cancer Registry data: age at diagnosis, date of diagnosis, clinical stage. The state Patient Fund data: dates of PSA testing in the LPCEDP. The distribution of clinical stages of prostate cancer was analysed in the following age groups: 50–54, 55–59, 60–64, 65–69, 70–75 years. The incidence rate was expressed as cases per 100000 men per year. The logistic regression model was used to assess the effect of the LPCEDP.
Results. In 2006–2009, early prostate cancer accounted for 60.9% of incidence in
the study group. The LPCEDP resulted in a sharp rise of the incidence of prostate
cancer in 2007, followed by a gradual decline. Major changes in stage II and III tumour incidence resulted in stage migration. The peaks of total prostate cancer incidence and stage II cancer incidence among men aged 65–75 years coincided. In all age groups except 50–54 years, the incidence of stage III prostate cancer followed a downward trend since 2006. The logistic regression model showed that using the LPCEDP significantly increased the chances of men to be diagnosed with prostate cancer at an early stage.
Conclusions. The LPCEDP has resulted in a high incidence of prostate cancer (especially of stage II) in men aged 65–75 years. A steady decline of stage III prostate cancer incidence was observed. Men aged 50–54 years cannot benefit from the LPCEDP as they seldom come to GPs. In the current situation, overdiagnosis and overtreatment in men aged over 65 years may overshadow the benefits of timely PSA testing in younger men.

Keywords: prostate cancer, early diagnosis, PSA
Work experience and school workers’ health evaluated by salutogenic health indicators
Authors: ANDRUŠKIENĖ Jurgita , KIRVELIENĖ Deimantė , MARTINKĖNAS Arvydas , ANDERSSON Ingemar , EJLERTSSON Göran
Published: July 2012

Background. The aim of the study was to establish relations between work experience and health, evaluated by salutogenic health indicators, among school workers.
Materials and methods. Teachers (n = 180) and other school workers (n = 154) from randomly selected Panevėžys district schools were questioned using instruments developed by scientists of the Kristianstad University: the Work Experience Measurement Scale (WEMS) and Salutogenic Health Indicator Scale (SHIS). The questionnaire of personal data contained questions about sociodemographic and work-related characteristics. The differences among the mean values were tested by the independent samples t-test and one-way ANOVA. The Cronbach’s alpha coefficient was used to check the internal consistency. The significance level was accepted at p = 0.05.
Results. In the teachers’ group, 86.7% were females (75.3% among others), 20.4% were older than 55 years (30.7% in other goups), 18.9% held an executive position (8.5% among others). Teachers, as compared with other school workers, scored higher the domain of internal work experience, (76.9 vs. 62.8, respectively), while other school workers gave higher standardized scores for the time experience domain (71.9 vs. 63.7, p < 0.001 respectively). The SHIS scores among teachers varied from 54.7 (worst experience) to 78.0 (best experience), p < 0.001. In the group of other school workers, the SHIS mean scores varied from 51.9 to 80.0, p < 0.001.
Conclusions. Teachers more positively evaluated the domain of internal working experience, while other school workers were more satisfied with time experience at the workplace. The established strong correlation between work experience and health, measured by salutogenic health indicators, encouraged the idea to implement workrelated health promotion at school.

Keywords: work experience, health, school, salutogenic health indicators
Medication rationality in treating depression
Authors: KAVALIAUSKIENĖ Liubov , PEČIŪRA Rimantas , ADOMAITIENĖ Virginija
Published: July 2012

Background. The costs of depression treatment in Lithuania increase because of high depression relapse rates which indicate the necessity to evaluate first-time depression treatment rationality. The aim of this study was to evaluate the use of antidepressants according to the opinion of three groups of specialists (family doctors, psychiatrists and pharmacists) in order to assess the possibilities of a more rational use of depression treatment costs rationalizing opportunities.
Materials and methods. Data on depression diagnoses were obtained from the Republic Psychiatric Health Centre. In 2009, 361 Lithuanian pharmacist, 317 family doctors and 280 psychiatrists were interviewed. The data were processed using the Statistical Package for the Social Sciences program.
Results. In the study period (2004–2009), the volume of total depression diagnoses grew up by 12% and the number of relapsed depression diagnoses by 27%. Among family doctors, 13% still don’t launch depression treatment by themselves, and 62% of them refer patients to psychiatrists in cases of depression relapse. Those who prescribe a medicine all alone in most cases use sertraline, but even 38% of family doctors mention benzodiazepines. According to family doctors’ answers, 32% of them reevaluate the effect of medications in 4 weeks and 25% do not monitor it at all. More than 50% of pharmacists have noted that every day they are asked by patients for antidepressants without prescription.
Conclusions. The abundance of cases of recurrent depression, recorded by family doctors, encourage to revise the preparedness of family doctors to treat this disease. The specialists’ opinion makes us to reevaluate and question the quality of depression treatment and to rationalize the efficiency of depression treatment in Lithuania as regards its both economic and social aspects.

Keywords: depression treatment, antidepressants, depression relapse
Molecular analysis of multifocal prostate cancer cases
Authors: SABALIAUSKAITĖ Rasa , PETROŠKA Donatas , DASEVIČIUS Darius , LAURINAVIČIUS Arvydas , JANKEVIČIUS Feliksas , LAZUTKA Juozas R. , JARMALAITĖ Sonata
Published: July 2012

Background. Prostate cancer (PCa) is usually a multifocal disease with different foci displaying histological and molecular heterogeneity. Biopsy-based pathology diagnosis of PCa may not be representative of the entire tumour; thus, markers more precisely characterizing every focus of multifocal PCa are highly instrumental for a better testing of PCa.
Materials and Methods. Two distant foci of prostate adenocarcinoma were obtained from prostatectomy specimens of ten patients with pT2–pT3 stage PCa. The expression of TMPRSS2 : ERG, TMPRSS2 : ETV1, and TERT was assessed by means of reverse transcription PCR and quantified using the real-time-based approach. Ki-67, ERG, EMA, AMACR, p16, and p53 expression was evaluated by means of immunohistochemistry (IHC) on tissue microarrays (TMA).
Results. Two out of ten cases were identified with different Gleason scores in paired foci of PCa. The expression of most of the IHC markers was quite even between TMA cores of each PCa case, with p16 showing the highest level of heterogeneity (44%; 4/9); 80% (8/10) of multifocal PCa expressed different variants of the TMPRSS2 : ERG transcript or showed a varying status of fusion positivity in paired foci, and the expression levels of the transcript were also heterogeneous. Similarly, 90% (9/10) of PCa showed a different positivity for TERT expression in paired foci.
Conclusions. Measurement of TMPRSS2 : ERG and TERT expression offers a valuable tool for identifying most aggressive tumour foci and selecting a relevant treatment of PCa.

Keywords: prostate cancer, multifocality, TMPRSS2 : ERG, telomerase
MUDANÇAS DE PARADIGMAS NA GESTÃO DO PROFISSIONAL DE SECRETARIADO
Authors: Almeida Walkíria Gomes de , Rogel Geórgia T. S. , Shimoura Alzira da Silva
Published: July 2012

Neste mercado instável, com mudanças contínuas, torna-se necessário que os profissionais busquem, cada vez mais, qualificação e se preparem para uma competitividade avassaladora, buscando alternativas para o seu desenvolvimento. O profissional de secretariado evoluiu e se desenvolveu muito ao longo de uma trajetória de lutas e conquistas, incluindo a globalização e a revolução tecnológica. O perfil desse profissional mudou e, hoje, observa-se que ele atua como cogestor, empreendedor e consultor, trabalhando o operacional, mas com foco no resultado. A profissão conquistou muitas vitórias: promulgação das leis de regulamentação, código de ética, a criação da Federação Nacional das Secretárias e Secretários e Sindicatos de Classe no Brasil todo, entre outros. Mas, mesmo com toda essa evolução, ainda existem empresas e/ou gestores que não acreditam na mudança de paradigmas dessa profissão; julgam que o trabalho é o mesmo das décadas passadas. Assim, a presente pesquisa buscou investigar quais são as competências desejáveis a fim de que o profissional de secretariado contribua para a gestão de resultados da empresa.
A PRÁTICA DO CONHECIMENTO DO PROFISSIONAL DE SECRETARIADO EXECUTIVO NA ORGANIZAÇÃO DE ARQUIVOS: UM ESTUDO DE CASO
Authors: Lourenço Fernanda Maria Alves , Cantarotti Aline
Published: July 2012

O secretariado executivo é uma profissão polivalente, que agrega funções múltiplas. A seguinte pesquisa trata de uma dessas funções: a organização de arquivos, com enfoque na área contábil, fruto do estágio realizado em um escritório especializado, no qual se constatou um problema em relação ao seu atual modelo de arquivo. A relevância desta pesquisa se dá pelo fato de que, quando uma organização de arquivos é feita de maneira incorreta, ela pode interferir na situação da empresa e acarretar atraso ou até perda negócios. A partir de então, foi possível alcançar o objetivo geral da pesquisa, que era o de analisar os arquivos da empresa, em seu modelo atual e, na sequência, apresentar sugestão de melhoria para o sistema de arquivamento da empresa.
OS MANUAIS DE CORRESPONDÊNCIAS COMERCIAIS (1950-2000): UMA INTERPRETAÇÃO À LUZ DA HISTORIOGRAFIA LINGUÍSTICA
Authors: Zanon Marilena
Published: July 2012

Este trabalho nasceu de inquietações profissionais, no que tange à linguagem rebuscada e artificial, utilizada nas comunicações escritas, das empresas, principalmente, naquelas onde trabalhei. Buscava sempre a resposta para o meu questionamento, em situações normais de trabalho e, até mesmo, em situações conflitantes em que a correspondência apresentava tratamento exageradamente cortês e artificial. Com o objetivo de circunscrever essa linguagem, analisamos esses aspectos em Manuais de Cartas Comerciais produzidos no Brasil - no eixo Rio-São Paulo - no período de 1950 a 2000 (um de cada década). Por seu ineditismo, consideramos apropriado o tema escolhido, Estudo dos Manuais de Correspondências Comercias (1950-2000): Uma interpretação à luz da Historiografia Lingüística, para a finalidade desta pesquisa, no nível de doutoramento. Tivemos como ponto de partida, o objetivo geral: verificar em que medida os Manuais de Correspondências Comerciais influenciaram os profissionais e contribuíram para a elaboração de textos específicos, no âmbito empresarial, no período compreendido entre 1950-2000. Concluímos que os Manuais analisados, reproduziram a norma-padrão da Língua Portuguesa, foram muito úteis a inúmeros profissionais dos mais diferentes segmentos da sociedade, apesar da ausência de procedimentos metodológicos e explicações consistentes sobre a apresentação do modelo, bem como de bibliografia que desse fundamentação e transparência à obra.
ENSINO DE LÍNGUA ESTRANGEIRA NO CURSO DE SECRETARIADO EXECUTIVO BILÍNGUE: BUSCANDO UM CAMINHO PARA AS ANÁLISES DE NECESSIDADES ESPECÍFICAS
Authors: De Sanctis Ricardo José Orsi , Abib Ivani Vecina
Published: July 2012

O presente trabalho tem o objetivo de estabelecer uma abordagem para novos planos de ensino em língua estrangeira que leve em conta as necessidades dos alunos do Curso de Secretariado Executivo Bilíngue. Esse estudo foi realizado em uma grande universidade particular do sudeste do Brasil. Os métodos de pesquisa utilizados foram a análise dos relatos de experiência, a observação sistemática de planos de ensino de docentes de língua estrangeira e um trabalho de campo com entrevistas com profissionais da área de Secretariado Executivo Bilíngue. Para suporte à realização de uma revisão bibliográfica tivemos como referencial teórico autores que discutem o ensino de língua estrangeira pesquisando as características, análises de necessidades de aprendizagem de língua para fins específicos, no caso em pauta, as necessidades do atuante na área de Secretariado Executivo. Como principais resultados tivemos discussões ideológicas que foram da prática docente ao trabalho docente numa perspectiva marxista. Tais discussões podem ser consideradas o embrião de uma pesquisa-ação que ainda está em andamento e que poderá suscitar inúmeros questionamentos ao longo dos replanejamentos com base na análise dos dados estudados pelos docentes envolvidos. Adicionalmente, pudemos observar que para que o trabalho docente garanta aos alunos acesso ao que não é reiterativo na vida social, devemos por em cheque os conceitos desenvolvidos por estudiosos de língua estrangeira com relação à necessidade subjetiva e objetiva, uma vez que a homogeneidade de necessidades é algo muito discutível, pois não se consegue prever qual será modelo de gestão da empresa onde esse aluno trabalhará, bem como a prática social que dita a produção de textos e o âmbito de sua atuação.
A Bayesian approach to robust process identification with ARX models
Authors: Khatibisepehr Shima , Huang Biao
Published: July 2012

In the context of process industries, outlying observations mostly represent a large random error resulting from irregular process disturbances, instrument failures, or transmission problems. Statistical analysis of process data contaminated with outliers may lead to biased parameter estimation and plant‐model mismatch. The problem of process identification in the presence of outliers has received great attention and a wide variety of outlier identification approaches have been proposed. However, there is a great need to seek for more general solutions and a robust framework to deal with different types of outliers. The main objective of this work is to formulate and solve the robust process identification problem under a Bayesian framework. The proposed solution strategy not only yields maximum a posteriori estimates of model parameters but also provides hyperparameters that determine data quality as well as prior distribution of model parameters. Identification of a simulated continuous fermentation reactor is considered to show the effectiveness and robustness of the proposed Bayesian framework. The advantages of the method are further illustrated through an experimental case study of a pilot‐scale continuous stirred tank heater. © 2012 American Institute of Chemical Engineers AIChE J, 59: 845–859, 2013
Highly resolved simulations of solids suspension in a small mixing tank
Authors: Derksen J.J.
Published: July 2012

Simulations of solid–liquid flow in an agitated tank have been performed. The simulations fully resolve the mildly turbulent liquid flow (Re ≈ 2000) in the tank, and the spherical solid particles suspended in the liquid. Full resolution of the particles sets the grid spacing and thereby limits the tank size and the number of particles (up to 3600 in this article) that are computationally affordable. The solids volume fraction is some 8%. The lattice‐Boltzmann method has been used to solve the flow dynamics; the particles move under the influence of resolved hydrodynamic forces, unresolved lubrication forces, net gravity, and collisions (with other particles, the tank wall, and the impeller). We show the start‐up of the suspension process, demonstrate its dependency on a Shields number (that we interpret in terms of the Zwietering correlation) and show the impact of polydispersity on the suspension process. © 2012 American Institute of Chemical Engineers AIChE J, 58: 3266–3278, 2012
Mixing induced by buoyancy‐driven flows in porous media
Authors: Meybodi Hamid Emami , Hassanzadeh Hassan
Published: July 2012

A theoretical model for fluid mixing in steady and transient buoyancy‐driven flows induced by laminar natural convection in porous layers is presented. This problem follows a highly nonlinear dynamics and its accurate modeling poses numerical challenges. Based on the Taylor dispersion theory, a one‐dimensional analytical model is developed for steady and transient velocity fields. To investigate steady‐state mixing, a unicellular steady velocity field is established by maintaining a thermal gradient across a porous layer of finite thickness. A passive tracer is then introduced into the flow field and the mixing process is studied. In the case of transient flows, as the convective flow grows and decays with time the behavior of the dispersion coefficient is characterized by a four‐parameter Weibull function. The simple analytical model developed here can recover scaling relations that have been reported in the literature to characterize the mixing process in steady and transient buoyancy‐driven flows. © 2012 American Institute of Chemical Engineers AIChE J, 59: 1378–1389, 2013
Occupation and the prevalence of current depression and frequent mental distress, WA BRFSS 2006 and 2008
Authors: Fan Z. Joyce , Bonauto David K. , Foley Michael P. , Anderson Naomi J. , Yragui Nanette L. , Silverstein Barbara A.
Published: July 2012

Background

Workers with depression and frequent mental distress (FMD) have lost work productivity. Limited systematic comparisons exist for the prevalence of depression and FMD across occupational groups.

Methods

Using a state‐added question for occupation coupled to measures of depression and FMD on the Washington State (WA) 2006 and 2008 Behavioral Risk Factor Surveillance System survey, we estimated the prevalence and odds ratios (ORs) among the 20,560 WA workers.

Results

The prevalences of current depression and FMD were 5.2% and 7.5%, respectively. The prevalence varied considerably across occupations. Compared with Management occupation, Truck drivers had significantly increased odds for both current depression [OR = 6.18, 95% confidence interval (CI): 2.52–15.16] and FMD (OR = 1.85, 95% CI: 1.01–3.41). Cleaning/Building services (OR = 1.95, 95% CI: 1.11–3.40) and Protective services (OR = 1.97, 95% CI: 1.19–3.27) were associated with increased FMD.

Conclusions

These findings demonstrate the need for research on possible sources of the differences for current depression and FMD across occupations. Am. J. Ind. Med. 55:893–903, 2012. © 2012 Wiley Periodicals, Inc.
Growth in individuals with Majewski osteodysplastic primordial dwarfism type II caused by pericentrin mutations
Authors: Bober Michael B. , Niiler Tim , Duker Angela L. , Murray Jennie E. , Ketterer Tara , Harley Margaret E. , Alvi Sabah , Flora Christina , Rustad Cecilie , Bongers Ernie M.H.F. , Bicknell Louise S. , Wise Carol , Jackson Andrew P.
Published: July 2012

Microcephalic primordial dwarfism (MPD) is a class of disorders characterized by intrauterine growth restriction (IUGR), impaired postnatal growth and microcephaly. Majewski osteodysplastic primordial dwarfism type II (MOPD II) is one of the more common conditions within this group. MOPD II is caused by truncating mutations in pericentrin (PCNT) and is inherited in an autosomal recessive manner. Detailed growth curves for length, weight, and OFC are presented here and derived from retrospective data from 26 individuals with MOPD II confirmed by molecular or functional studies. Severe pre‐ and postnatal growth failure is evident in MOPD II patients. The length, weight, and OFC at term (when corrected for gestational age) were −7.0, −3.9, and −4.6 standard deviation (SD) below the population mean and equivalent to the 50th centile of a 28–29‐, 31–32‐, and 30–31‐week neonate, respectively. While at skeletal maturity, the height, weight, and OFC were −10.3, −14.3, and −8.5 SD below the population mean and equivalent to the size of 3‐year 10‐ to 11‐month‐old, a 5‐year 2‐ to 3‐month‐old, and 5‐ to 6‐month‐old, respectively. During childhood, MOPD II patients grow with slowed, but fairly constant growth velocities and show no evidence of any pubertal growth spurt. Treatment with human growth hormone (n = 11) did not lead to any significant improvement in final stature. The growth charts presented here will be of assistance with diagnosis and management of MOPD II, and should have particular utility in nutritional management of MOPD II during infancy. © 2012 Wiley Periodicals, Inc.
Identification of the mechanism underlying a human chimera by SNP array analysis
Authors: Shin So Youn , Yoo Han‐Wook , Lee Beom Hee , Kim Kun Suk , Seo Eul‐Ju
Published: July 2012

Human chimerism resulting from the fusion of two different zygotes is a rare phenomenon. Two mechanisms of chimerism have been hypothesized: dispermic fertilization of an oocyte and its second polar body and dispermic fertilization of two identical gametes from parthenogenetic activation, and these can be identified and discriminated using DNA polymorphism. In the present study we describe a patient with chimerism presenting as a true hermaphrodite and applied single nucleotide polymorphism array analysis to demonstrate dispermic fertilization of two identical gametes from parthenogenetic activation as the underlying mechanism at the whole chromosome level. We suggest that application of genotyping array analysis to the diagnostic process in patients with disorders of sex development will help identify more human chimera patients and increase our understanding of the underlying mechanisms. © 2012 Wiley Periodicals, Inc.
Chromosome 9p deletion syndrome and sex reversal: Novel findings and redefinition of the critically deleted regions
Authors: Onesimo Roberta , Orteschi Daniela , Scalzone Maria , Rossodivita Aurora , Nanni Lorenzo , Zannoni Gian Franco , Marrocco Giacinto , Battaglia Domenica , Fundarò Carlo , Neri Giovanni
Published: July 2012

Deletions of the short arm of chromosome 9 are associated with two distinct clinical entities. Small telomeric 9p24.3 deletions cause genital anomalies in male subjects, ranging from disorder of gonadal sex to genital differentiation anomalies, while large terminal or interstitial deletions result in 9p‐malformation syndrome phenotype. The critical region for non‐syndromic 46,XY sex reversal was assigned to a 1 Mb interval of chromosome 9p, extending from the telomere to theDMRTgenes cluster. The 9p‐syndrome was assigned to bands 9p22.3p24.1, but a phenotypic map has not been established for this condition, probably because of the lack of detailed molecular and/or phenotypic characterization, as well as frequent involvement of additional chromosome rearrangements. Here, we describe a unique patient with a small isolated 9p terminal deletion, characterized by array‐CGH and FISH, who shows a complex phenotype with multiple physical anomalies, resembling the 9p‐syndrome, disorder of sex development with gonadoblastoma, congenital heart defect and epilepsy. The observed deletion includes the 46,XY sex‐reversal critical region, excluding the region so far associated with the 9p‐syndrome. Genotype–phenotype correlations are tentatively established comparing our patient to seven other previously reported males with isolated terminal 9p deletions, finely defined at a molecular level. Our observations expand the 9p deletion clinical spectrum, and add significantly to the definition of a 9p‐syndrome critical region. © 2012 Wiley Periodicals, Inc.
Nail and phalangeal agenesis in a patient with 4pter and 9pter duplication
Authors: Rambaud Jérôme , Marey Isabelle , Dupont Céline , Perrin‐Sabourin Laurence , Capri Yline , Tabet Anne Claude , Benzacken Brigitte , Verloes Alain , Aboura Azzedine , Gérard Marion
Published: July 2012

We report on an 8‐month‐old girl with intra‐uterine growth retardation, microcephaly, incomplete cleft lip, axial hypotonia, failure to thrive, and brachydactyly type B (phalangeal agenesis and absence of nails). She carried a supernumerary marker chromosome derived from chromosomes 4 and 9, leading to 4pter‐q12 and 9pter‐p21.2 duplication. The marker was derived from the 3:1 segregation of a maternal balanced translocation 46,XX, t(4;9)(q12;p21.2). The proposita is the first reported individual with distal phalangeal agenesis and anonychia, and trisomy 4p and partial trisomy 9p due to 3:1 segregation of a maternal reciprocal translocation. © 2012 Wiley Periodicals, Inc.
Primary hyperoxaluria type 1 and brachydactyly mental retardation syndrome caused by a novel mutation in AGXT and a terminal deletion of chromosome 2
Authors: Tammachote Rachaneekorn , Kingsuwannapong Nelawat , Tongkobpetch Siraprapa , Srichomthong Chalurmpon , Yeetong Patra , Kingwatanakul Pornchai , Monico Carla G. , Suphapeetiporn Kanya , Shotelersuk Vorasuk
Published: July 2012

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder caused by mutations in the alanine:glyoxylate aminotransferase (AGXT) gene, located on chromosome 2q37. Mutant AGXT leads to excess production and excretion of oxalate, resulting in accumulation of calcium oxalate in the kidney, and progressive loss of renal function. Brachydactyly mental retardation syndrome (BDMR) is an autosomal dominant disorder, caused by haploinsufficiency of histone deacetylase 4 (HDAC4), also on chromosome 2q37. It is characterized by skeletal abnormalities and developmental delay. Here, we report on a girl who had phenotypes of both PH1 and BDMR. PCR‐sequencing of the coding regions of AGXT showed a novel missense mutation, c.32C>G (p.Pro11Arg) inherited from her mother. Functional analyses demonstrated that it reduced the enzymatic activity to 31% of the wild‐type and redirected some percentage of the enzyme away from the peroxisome. Microsatellite and array‐CGH analyses indicated that the proband had a paternal de novo telomeric deletion of chromosome 2q, which included HDAC4. To our knowledge, this is the first report of PH1 and BDMR, with a novel AGXT mutation and a de novo telomeric deletion of chromosome 2q. © 2012 Wiley Periodicals, Inc.
Germline mosaicism of PHOX2B mutation accounts for familial recurrence of congenital central hypoventilation syndrome (CCHS)
Authors: Rand Casey M. , Yu Min , Jennings Lawrence J. , Panesar Kelvin , Berry‐Kravis Elizabeth M. , Zhou Lili , Weese‐Mayer Debra E.
Published: July 2012

Congenital central hypoventilation syndrome (CCHS), a rare disorder characterized by alveolar hypoventilation and autonomic dysregulation, is caused by mutations in the PHOX2B gene. Most mutations occur de novo, but recent evidence suggests that up to 25% are inherited from asymptomatic parents with somatic mosaicism for these mutations. However, to date, germline mosaicism has not been reported. This report describes a family with recurrence of PHOX2B mutation‐confirmed CCHS due to germline mosaicism. The first occurrence was a baby girl, noted on day 2 of life to have multiple episodes of apnea, bradycardia, and cyanosis while breathing room air. PHOX2B gene testing confirmed the diagnosis of CCHS with a heterozygous polyalanine repeat expansion mutation (PARM); genotype 20/27 (normal 20/20). Both parents tested negative for this mutation using fragment analysis (limit of detection <1%). Upon subsequent pregnancy [paternity confirmed using short tandem repeat (STR) analysis], amniocentesis testing identified the PHOX2B 20/27 genotype, confirmed with repeat testing. Elective abortion was performed at 21.5 weeks gestation. Testing of abortus tissue confirmed amniocentesis testing. The PHOX2B 20/27 expansion was not observed in a paternal sperm sample. This case represents the first reported family with recurrence of PHOX2B mutation‐confirmed CCHS without detection of a parental carrier state or mosaicism, confirming the previously hypothesized possibility of germline mosaicism for PHOX2B mutations. This is an important finding for genetic counseling of CCHS families, suggesting that even if somatic mosaicism is not detected in parental samples, there is still reason for careful genetic counseling and consideration of prenatal testing during subsequent pregnancies. © 2012 Wiley Periodicals, Inc.
Outside‐binding site mutations modify the active site's shapes in neuraminidase from influenza A H1N1
Authors: Tolentino‐Lopez Luis , Segura‐Cabrera Aldo , Reyes‐Loyola Paola , Zimic Mirko , Quiliano Miguel , Briz Veronica , Muñoz‐Fernández Angeles , Rodríguez‐Pérez Mario , Ilizaliturri‐Flores Ian , Correa‐Basurto Jose
Published: July 2012

The recent occurrence of 2009 influenza A (H1N1) pandemic as well as others has raised concern of a far more dangerous outcome should this virus becomes resistant to current drug therapies. The number of clinical cases that are resistant to oseltamivir (Tamiflu®) is larger than the limited number of neuraminidase (NA) mutations (H275Y, N295S, and I223R) that have been identified at the active site and that are associated to oseltamivir resistance. In this study, we have performed a comparative analysis between a set of NAs that have the most representative mutations located outside the active site. The recently crystallized NA‐oseltamivir complex (PDB ID: 3NSS) was used as a wild‐type structure. After selecting the target NA sequences, their three‐dimensional (3D) structure was built using 3NSS as a template by homology modeling. The 3D NA models were refined by molecular dynamics (MD) simulations. The refined models were used to perform a docking study, using oseltamivir as a ligand. Furthermore, the docking results were refined by free‐energy analysis using the MM‐PBSA method. The analysis of the MD simulation results showed that the NA models reached convergence during the first 10 ns. Visual inspection and structural measures showed that the mutated NA active sites show structural variations. The docking and MM‐PBSA results from the complexes showed different binding modes and free energy values. These results suggest that distant mutations located outside the active site of NA affect its structure and could be considered to be a new source of resistance to oseltamivir, which agrees with reports in the clinical literature. © 2012 Wiley Periodicals, Inc.
Autotaxin/ENPP2 regulates oligodendrocyte differentiation in vivo in the developing zebrafish hindbrain
Authors: Yuelling Larra W. , Waggener Christopher T. , Afshari Fatemah S. , Lister James A. , Fuss Babette
Published: July 2012

During development, progenitors that are committed to differentiate into oligodendrocytes, the myelinating cells of the central nervous system (CNS), are generated within discrete regions of the neuroepithelium. More specifically, within the developing spinal cord and hindbrain ventrally located progenitor cells that are characterized by the expression of the transcription factor olig2 give temporally rise to first motor neurons and then oligodendrocyte progenitors. The regulation of this temporal neuron‐glial switch has been found complex and little is known about the extrinsic factors regulating it. Our studies described here identified a zebrafish ortholog to mammalian atx, which displays evolutionarily conserved expression pattern characteristics. Most interestingly, atx was found to be expressed by cells of the cephalic floor plate during a time period when ventrally‐derived oligodendrocyte progenitors arise in the developing hindbrain of the zebrafish. Knock‐down of atx expression resulted in a delay and/or inhibition of the timely appearance of oligodendrocyte progenitors and subsequent developmental stages of the oligodendrocyte lineage. This effect of atx knock‐down was not accompanied by changes in the number of olig2‐positive progenitor cells, the overall morphology of the axonal network or the number of somatic abducens motor neurons. Thus, our studies identified Atx as an extrinsic factor that is likely secreted by cells from the floor plate and that is involved in regulating specifically the progression of olig2‐positive progenitor cells into lineage committed oligodendrocyte progenitors. © 2012 Wiley Periodicals, Inc.
The role of insulin‐like growth factors signaling in merlin‐deficient human schwannomas
Authors: Ammoun Sylwia , Schmid M. Caroline , Ristic Natalia , Zhou Lu , Hilton David , Ercolano Emanuela , Carroll Camille , Hanemann C. Oliver
Published: July 2012

Loss of the tumor suppressor merlin causes development of the tumors of the nervous system, such as schwannomas, meningiomas, and ependymomas occurring spontaneously or as part of a hereditary disease Neurofibromatosis Type 2 (NF2). Current therapies, (radio) surgery, are not always effective. Therefore, there is a need for drug treatments for these tumors. Schwannomas are the most frequent of merlin‐deficient tumors and are hallmark for NF2. Using our in vitro human schwannoma model, we demonstrated that merlin‐deficiency leads to increased proliferation, cell–matrix adhesion, and survival. Increased proliferation due to strong activation of extracellular‐signal‐regulated kinase 1/2 (ERK1/2) is caused by overexpression/activation of platelet‐derived growth factor receptor‐β (PDGFR‐β) and ErbB2/3 which we successfully blocked with AZD6244, sorafenib, or lapatinib. Schwannoma basal proliferation is, however, only partly dependent on PDGFR‐β and is completely independent of ErbB2/3. Moreover, the mechanisms underlying pathological cell–matrix adhesion and survival of schwannoma cells are still not fully understood. Here, we demonstrate that insulin‐like growth factor‐I receptor (IGF‐IR) is strongly overexpressed and activated in human primary schwannoma cells. IGF‐I and ‐II are overexpressed and released from schwannoma cells. We show that ERK1/2 is relevant for IGF‐I‐mediated increase in proliferation and cell–matrix adhesion, c‐Jun N‐terminal kinases for increased proliferation and AKT for survival. We demonstrate new mechanisms involved in increased basal proliferation, cell–matrix adhesion, and survival of schwannoma cells. We identified therapeutic targets IGF‐IR and downstream PI3K for treatment of schwannoma and other merlin‐deficient tumors and show usefulness of small molecule inhibitors in our model. PI3K is relevant for both IGF‐IR and previously described PDGFR‐β signaling in schwannoma. © 2012 Wiley Periodicals, Inc.
Detecting the flow relationships between deep and shallow aquifers in an exploited groundwater system, using long‐term monitoring data and quantitative hydrogeology: the Acque Albule basin case (Rome, Italy)
Authors: La Vigna Francesco , Mazza Roberto , Capelli Giuseppe
Published: July 2012

Five years of hydrogeological monitoring and field activities performed in the complex hydrogeological system of the Acque Albule basin (AAB) were conducted to define the hydrogeological setting, the relationship between deep and shallow aquifers and a conceptual groundwater flow model of this exploited area using conventional quantitative techniques. The basin, which is located close to Rome (Italy) on the west side of the Apennine chain and just north of the Colli Albani volcano, subsided after development of a north–south fault system (about 115 000 y bp). The AAB experiences intense hydrothermal activity, which has produced a large travertine deposit (80‐m thick). The travertine deposit constitutes a fractured aquifer that is the final destination of more than 5 m3 s‐1 of water and is strongly dewatered by quarry activities.

The complex hydrogeology of this basin was investigated, revealing two main hydraulically connected aquifers, one thermalised and partly confined into the limestone bedrock and one unconfined in the travertine. The two aquifers are separated by a non‐continuous clayey aquiclude. The hydrogeological survey and geological characterisation contributed to the development of the groundwater flow conceptual model. Analysis and comparison of the monitored levels highlighted the pattern of flow between the deep and shallow parts of the flow system. Copyright © 2012 John Wiley & Sons, Ltd.
Type 1 IFN inhibits the growth factor deprived apoptosis of cultured human aortic endothelial cells and protects the cells from chemically induced oxidative cytotoxicity
Authors: Sano Emiko , Tashiro Shinnya , Tadakuma Hisashi , Takei Toshiaki , Ueda Takuya , Tsumoto Kouhei
Published: July 2012

It has been shown that the genesis of atherosclerotic lesions is resulted from the injury of vascular endothelial cells and the cell damage is triggered by oxygen radicals generated from various tissues. Human vascular endothelial cells can survive and proliferate depending on growth factors such as VEGF or basic FGF and are induced apoptosis by the deprivation of growth factor or serum. It was found that type 1 IFN inhibits the growth factor deprived cell death of human aortic endothelial cells (HAEC) and protects the cells from chemically induced oxidative cytotoxicity. The anti‐apoptotic effects of type 1 IFN were certified by flow cytometry using annexin‐V‐FITC/PI double staining and cell cycle analysis, fluorescence microscopy using Hoechst33342 and PI, colorimetric assay for caspase‐3 activity, p53 and bax mRNA expressions, and cell counts. It was considered that IFN‐β inhibits the executive late stage apoptosis from the results of annexin‐V‐FITC/PI double staining and the inhibition of caspase‐3 activity, and that the anti‐apoptotic effect might be owing to the direct inhibition of the apoptotic pathway mediated by p53 from the transient down‐regulation of bax mRNA expression. Whereas, type 1 IFN protected the cells from the oxidative cytotoxicity induced by tertiary butylhydroperoxide (TBH) under the presence of Ca2+. The effects of IFN‐β is more potent inhibitor of cell death than IFN‐α. These results indicate that type 1 IFN, especially IFN‐β may be useful for the diseases with vascular endothelium damage such as atherosclerosis or restenosis after angioplasty as a medical treatment or a prophylactic. J. Cell. Biochem. 113: 3823–3834, 2012. © 2012 Wiley Periodicals, Inc.
Analysis of blastocyst culture of discarded embryos and its significance for establishing human embryonic stem cell lines
Authors: Wang Fang , Kong Hui‐Juan , Kan Quan‐Cheng , Liang Ju‐Yan , Zhao Fang , Bai Ai‐Hong , Li Peng‐Fen , Sun Ying‐Pu
Published: July 2012

In recent years, applications of stem cells have already involved in all domains of life science and biomedicine. People try to establish human embryonic stem cell lines (hESCs) in order to carry out hESC‐related studies. In this study, we explored what embryos are conducive to the establishment of hESCs. The discarded embryos from in vitro fertilization–embryo transfer (IVF–ET) cycles were sequentially incubated into blastocysts, and then the inner cell mass (ICM) was isolated and incubated in the mixed feeder layer. The cell lines which underwent serial passage were identified. After a total of 1,725 discarded embryos from 754 patients were incubated, 448 blastocysts were formed with 123 high‐quality blastocysts. The blastulation rate was significantly higher in the discarded embryos with non‐pronucleus (0PN) or 1PN than in the discarded embryos with 2PN or ≥3PN. The blastulation rate of the D3 embryos with 7–9 blastomeres was higher. Among the originally incubated 389 ICMs, 22 hESCs with normal karyotype were established, and identified to be ESCs. Therefore, in establishing hESCs with discarded embryos, D3 0PN or 1PN embryos with 7–9 blastomeres should be first selected, because they can improve high‐quality blastulation rate which can increase the efficiency of hESC establishment. J. Cell. Biochem. 113: 3835–3842, 2012. © 2012 Wiley Periodicals, Inc.
MEK1‐induced physiological hypertrophy inhibits chronic post‐myocardial infarction remodeling in mice
Authors: Yeh Che‐Chung , Malhotra Deepak , Yang Yi‐Lin , Xu Yanchun , Fan Yanying , Li Hongzhe , Mann Michael J.
Published: July 2012

Although activation of MEK‐ERK signaling is known to be cardioprotective during acute reperfusion injury, the effect of MEK activation on chronic changes in ventricular structure and function during the more complex process of remodeling after myocardial infarction (MI) with or without reperfusion remains uncertain. Four weeks after permanent coronary ligation, LV fractional shorting, preload recruitable stroke work, and end‐systolic elastance were all preserved in transgenic mice with CM‐specific upregulation of the MEK1‐ERK1/2 signaling pathway (MEK1 Tg) compared to wildtype (WT) controls (5.8% decline vs. 17.3%, P < 0.01; 603 ± 98 mmHg vs. 335 ± 98, P < 0.05; 6.14 ± 0.57 mmHg/µl vs. 3.92 ± 0.60, P < 0.05, respectively). Despite similar initial infarct sizes, post‐MI remodeling was significantly reduced in MEK1 Tg, demonstrated by reductions in chronic infarct size (28.5 ± 3.1% vs. 47.8 ± 3.2%), myocardial fibrosis (3.98 ± 0.74% vs. 9.27 ± 1.97%) and apoptosis (0.66 ± 0.11% vs. 1.60 ± 0.34%). Higher phosphorylation (i.e., activation) of pro‐survival transcription factor STAT3, higher expression of anti‐apoptotic protein Bcl2, and higher phosphorylation (i.e., inactivation) of pro‐apoptotic BAD were observed in the post‐MI remote myocardium of MEK1 Tg. MMP2 activity was higher in MEK1 Tg, while expression of TIMP3 and MMP9 activity were lower in transgenic mice. Beyond any immediate cardioprotective effect, therapeutic activation of MEK1‐ERK1/2 signaling during the chronic post‐MI period may preserve LV function by increasing the expression of pro‐survival factors and by suppressing factors, such as the balance between matrix modulating proteins, that promote pathological remodeling in the remote myocardium. J. Cell. Biochem. 114: 47–55, 2012. © 2012 Wiley Periodicals, Inc.
PERCEPTIONS OF NEIGHBORHOOD PROBLEMS AND HEALTH‐RELATED QUALITY OF LIFE
Authors: Erin M. Hill , Shepherd Daniel , Welch David , Dirks Kim N. , McBride David
Published: July 2012

This article examines the association between perceptions of neighborhood problems and health‐related quality of life (HRQOL) in a sample of New Zealand residents (n = 692). A modified version of the Neighborhood Problems Scale (originally developed by Steptoe and Feldman, 2001) and the World Health Organization Quality of Life (WHOQOL‐BREF) were used to assess perceptions of neighborhood problems and HRQOL, respectively. Multiple linear regression analyses were conducted to assess the association between perceptions of neighborhood problems and each of the WHOQOL‐BREF domains: physical, psychological, social, and environmental HRQOL. Perceptions of neighborhood problems and gender interacted in the physical HRQOL regression; the negative association between perceived neighborhood problems and physical HRQOL was stronger for males compared with females. Neighborhood problems were also negatively predictive of psychological, social, and environmental HRQOL. Overall, our results suggest that the various aspects of well‐being may be influenced by perceptions of neighborhood problems.
Application of anaerobic membrane bioreactors for the treatment of protein‐containing wastewaters under saline conditions
Authors: Hemmelmann Alberto , Torres Alvaro , Vergara Christian , Azocar Laura , Jeison David
Published: July 2012

BACKGROUND: Anaerobic treatment of saline wastewaters may be hindered by problems related with biomass retention, since at high salt concentrations formation of biofilms and granules may not proceed well. This research studied the use of anaerobic membrane bioreactors (AnMBR) as a way to promote complete biomass retention. A lab scale AnMBR fitted with a ceramic tubular membrane was operated for 2 years.

RESULTS: Results showed that enhanced biomass retention produces conditions enabling anaerobic treatment of saline wastewaters. Despite the high resulting sludge retention time, no accumulation of a high proportion of dead cells was observed. Protein degradation and not methanogenesis was shown to be the rate limiting step for organic matter degradation, a fact that is relevant for protein‐containing wastewaters such as those from seafood processing industries. Only low levels of flux could be applied, in the region of 5 L m−2 h−1 due to reversible cake formation promoted by single cell growth.

CONCLUSION: Biomass retention provided by membrane filtration promotes conditions suitable for efficient treatment of saline wastewaters. However, operation may be restricted to low values of flux due to biomass development as single cells. © 2012 Society of Chemical Industry