bluuebunny/crossref_metadata_2025 huggingface dataset:
Forord
Authors: Kvist Jon , Rostgaard Tine , Ejrnæs Anders , Paster Thomas
Published: February 2024

Dette særnummer af Samfundsøkonomen er et festskrift for professor Bent Greve, i anledning af hans 70-års fødselsdag. Bent er uddannet økonom og har i en årrække haft sit virke ved Institut for Samfund og Erhverv, Roskilde Universitet, som institutleder og forsker. Han blev i 1997 udnævnt til Jean Monnet Professor i Europæisk arbejdsmarkeds- og social politik, og i 2001 udnævnt til professor i velfærdsstatsanalyse. Bent har sikret uddannelsen af utallige studerende på forvaltning og senere social videnskab udi forståelsen af velfærdsstatens og dens mange modeller og facetter.
Objective and Subjective Measures of Child Poverty in Denmark
Authors: Hussain Azhar
Published: February 2024

The relative poverty line has been criticized for being arbitrary since it is defined by purely statistical measures without any theory linking objective income poverty to subjectively experienced poverty. The objective-subjective poverty nexus is explored empirically by comparing poverty measures for Danish children using EU-SILC data from 2019. The objective measure is based on the 50 % poverty line, while the subjective measures cover deprivation, financial coping, and accumulation of deprivations. Results shows a far from perfect overlap between objective and subjective poverty, but the subjective poverty risk is much higher for income poor children compared to non-poor children.
The Federal Tax Service and its territorial divisions as objects of public control in Russia
Authors: Goncharov Vitalii Viktorovich , Grishchenko Ol'ga Vladimirovna , Petrenko Elena Gennad'evna
Published: February 2024

The article is devoted to the analysis of the Federal Tax Service and its territorial divisions as objects of public control in the Russian Federation. The paper substantiates the role and place of the institution of public control in the system of legal guarantees for the implementation and protection of the constitutional principles of democracy and the participation of Russian citizens in the management of state affairs. The Federal Tax Service and its territorial divisions occupy a special place in the system of objects of public control in the Russian Federation. However, the organization and implementation of public control measures in relation to the above-mentioned objects are associated with numerous problems caused by: the lack of consolidation of this institution of civil society in the Constitution of Russia, as well as legislation regulating the activities of tax authorities; weak powers of subjects of public control, insufficient use of modern information and communication technologies; lack of development of special forms, methods and types of public control measures in relation to the above-mentioned objects; weak use of Soviet and foreign experience of civil society control over the government apparatus.  A number of scientific research methods are used in the work, in particular: comparative legal; historical legal; statistical; sociological; formal logical; method of analyzing specific practical situations. The authors have developed and substantiated a system of measures to resolve problems related to the organization and implementation of public control in relation to the Federal Tax Service of Russia and its territorial divisions by: incorporating the institute of public control into the Basic Law of the country, as well as legislation regulating the organization and activities of tax authorities; developing specific features of the implementation of this institution of civil society in relation to to the activities, acts and decisions of tax authorities in the scientific literature and subordinate normative legal acts on public control using positive Soviet and foreign experience in the functioning of civil society institutions; development and implementation of comprehensive Federal programs for the development of organizational, methodological and technological base of subjects of public control with simultaneous expansion of their powers.
The Effect of Compensation Policy and Work Discipline on Nurse Productivity at dr. H. Marzoeki Mahdi Mental Hospital Bogor in 2023
Authors: Febrianti Icha Tiara Devi , Andriani Helen
Published: February 2024

Health worker productivity problems due to suboptimal institutional management still often occur, including at the dr. H. Marzoeki Mahdi Mental Hospital (RSJMM). Nurses are the largest number of health workers in hospitals with a high level of patient intervention; if there is inappropriate treatment, they risk decreasing work productivity. The aim of this research is to analyze the effect of financial compensation, non-financial compensation, and work discipline on nurse productivity at RSJMM. The research study used a quantitative approach by distributing questionnaires to 205 nurses. The results showed partially (1) financial compensation has no significant effect on nurse productivity (Sig. value 0.953 > 0.05, β=0.002); (2) Non-financial compensation has a positive and significant effect on nurse productivity (Sig. value 0.016 < 0.05, β=0.073); (3) Work discipline has a positive and significant effect on nurse productivity (Sig. value 0.000 < 0.05, β=0.293). The work discipline variable (0.293) most dominantly affects nurse productivity. Simultaneously, the three variables have a moderate effect on nurse productivity of 0.576 or 57.6%, while other variables influenced the remaining 42.4% was influenced by other variables. These results have limitations that are based on respondent's perceptions. It is suggested that hospitals need to optimize nurse productivity by improving hospital facilities, training, educational opportunities, transparency and fairness of compensation systems, recognition and feedback for employee performance, and compliance with work discipline.
Downregulation of Let-7 miRNA promotes Tc17 differentiation and emphysema via de-repression of RORγt
Authors: Erice Phillip A. , Huang Xinyan , Seasock Matthew J. , Robertson Matthew J. , Tung Hui-Ying , Perez-Negron Melissa A. , Lotlikar Shivani L. , Corry David B , Kheradmand Farrah , Rodriguez Antony
Published: February 2024

Environmental air irritants including nanosized carbon black (nCB) can drive systemic inflammation, promoting chronic obstructive pulmonary disease (COPD) and emphysema development. The
let-7
family of miRNAs is associated with IL-17-driven T cell inflammation, a canonical signature of lung inflammation. Recent evidence suggests the
let-7
family is downregulated in patients with COPD, however, how they cause emphysema remains unclear. Here we show that overall expression of the
let-7
miRNA clusters,
let-7b/let-7c2
and
let-7a1/let-7f1/let-7d
, are reduced in the lungs and T cells of smokers with emphysema as well as in mice with cigarette smoke (CS)- or nCB-elicited emphysema. We demonstrate that loss of the
let-7b/let-7c2-
cluster in T cells predisposed mice to exaggerated CS- or nCB-elicited emphysema. Furthermore, ablation of the
let-7b/let-7c2-cluster
enhanced CD8
+
IL17a
+
T cells (Tc17) formation in emphysema development in mice. Additionally, transgenic mice overexpressing
let-7
in T cells were resistant to Tc17 and CD4
+
T cells (Th17) development when exposed to nCB. Mechanistically, our findings reveal the master regulator of Tc17/Th17 differentiation, RAR-related orphan receptor gamma t (RORγt), as a direct target of
let-7
miRNA in T cells. Overall, our findings shed light on the
let-7
/RORγt axis as a braking and driving regulatory circuit in the generation of Tc17 cells and suggests a novel therapeutic approach for tempering the augmented IL-17-mediated response in emphysema.
A chemically-induced attenuated strain of Candida albicans generates robust protective immune response and prevents systemic candidiasis development
Authors: Bose Swagata , Sahu Satya Ranjan , Dutta Abinash , Acharya Narottam
Published: February 2024

Despite current antifungal therapy, invasive candidiasis causes >40% mortality in immunocompromised individuals. Therefore, developing an antifungal vaccine has a priority. Here, we could for the first time successfully attenuate the virulence of
Candida albicans
by treating it with a fungistatic dosage of EDTA and demonstrate it to be a potential live-whole cell vaccine by using murine models of systemic candidiasis. EDTA inhibited the growth and biofilm formation of
C. albicans
. RNA-seq analyses of EDTA-treated cells (CAET) revealed that genes mostly involved in metal homeostasis and ribosome biogenesis were up- and down-regulated, respectively. Consequently, a bulky cell-wall with elevated levels of mannan and β-glucan, and reduced levels of total monosomes and polysomes were observed. CAET was eliminated faster than the untreated strain (
Ca
) as found by differential fungal burden in the vital organs of the mice. Higher monocytes, granulocytes, and platelet counts were detected in
Ca-vs
CAET-challenged mice. While hyper-inflammation caused the killing of
Ca
-challenged mice, a critical balance of pro- and anti-inflammatory cytokines are the likely reasons for the protective immunity in CAET-infected mice.
Life by the Lake: Lubana Region and Its People in History and Present
Authors:   Institute of Philosophy and Sociology, University of Latvia, Krumina-Konkova Solveiga , Konkovs Karlis Aleksandrs ,   University of Latvia
Published: February 2024

This article is about the coexistence of people and the lake, about the consequences and responsibility of people interfering with the natural processes of nature. Part of the framework of this research was the governance process of surface water resources in Latvia, particularly public lakes, which was studied using a three-dimensional governance framing model of complementary dimensions of governance stakeholders, governance content, and governance instruments in order to determine how the lake is governed, and how it affects local culture and what role does culture have in the lake and public water governance. Lake Lubans was selected for this research, as it is Latvia’s largest lake, and its area contains an important Natura 2000 protected site – the Lubana Wetland complex, in addition to the fact that the region has been inhabited since the Neolithic era. Lake Lubans was discovered to be governed by several national institutions, led by the Nature Conservation Agency, as the lake is located in a protected area, with the Ministry of Agriculture being responsible for the governance of the lake dam system and control of farmland around the lake. The territory of the Lake Lubans wetlands was one of the first campgrounds of ancient people in Europe after the glaciers’ retreat, which also determines its importance in the history and culture of Latvia and Europe. Lake governance is almost only focused on nature and environmental protection, with economic and social aspects needing to be considered, and residents and other stakeholders needing to be sufficiently involved in governance. Currently, their interests have yet to be considered. Altogether, lake governance also needs to be improved from its perspective. Lake Lubans and the Lubana Wetland complex have not had a mandatory governance plan since 2009, but the first is in development, again missing all governance dimensions mentioned above. It was also found that nature communication and nature tourism are not only just potential lake/nature governance sectors but, if properly developed, would be valuable lake governance instruments, keeping stakeholders’ participation while supporting national organisations.
Impact of COVID-19 Pandemic on Tuberculosis Treatment Outcomes at a Tuberculosis Unit in Southern India: A Retrospective Observational Study
Authors: Shivalingaiah Anwith Huluvadi , Ayyappan Pranav , Kiruffi Divyarajan Vinitha , Muralidhar Madhusudan
Published: February 2024

Introduction: The Coronavirus Disease-2019 (COVID-19) pandemic significantly affected both existing and undiagnosed Tuberculosis (TB) patients worldwide. The impact of the pandemic on the treatment outcomes of these patients in India remains unclear. Aim: To assess the difference in TB treatment outcomes before and during the COVID-19 pandemic in an economically disadvantaged urban area in Southern India. Materials and Methods: A retrospective observational study was conducted at a TB Unit in South Bangalore, Southern India, serving a population of 2,50,000 from January 2022 to December 2022. Purposive sampling was employed to select 516 patients who had registered for TB treatment during the years 2019 and 2020. The socio-demographic details and TB profiles of the patients were collected and tabulated. Treatment outcomes were classified according to World Health Organisation (WHO) definitions after a case record analysis. Data were entered into Microsoft Excel 2018 and analysed using Open Epi software. Descriptive statistics, such as mean and standard deviation, were used to report socio-demographic profiles, and the Chisquare test was utilised to evaluate the differences in treatment outcomes. A p-value <0.05 was considered statistically significant. Results: The study included a total of 516 subjects. There were fewer cases registered in 2020 (n=202), especially after the first quarter, compared to the number registered in 2019 (n=314). The majority of the cases during both years were new instances of microbiologically confirmed pulmonary TB with no co-morbidities. Treatment success rates were 85.35% in 2019 and 88.61% in 2020, which was not statistically significant. Conclusion: There was a noticeable reduction in the number of cases registered during 2020, indicating that the COVID19 pandemic had a definite effect on TB case notification. However, treatment success rates increased during the COVID19 pandemic. This increase in the treatment success rate from 85.35% to 88.61% could be attributed to the decrease in the number of registered cases during the pandemic. The study thus found no significant impact on TB treatment success rate due to the COVID-19 pandemic.
The Influence of Marketing Relationship and Service Quality on Customer Loyalty of Sharia Savings Products (Case Study of BMT Mekah Mekar Barokah Bojonegoro)
Authors: Emiarti Endah , Yasdi
Published: February 2024

This study aims to improve and strengthen customer loyalty towards Sharia savings products at BMT Mekah Mekar Barokah Bojonegoro. Therefore, the purpose of this study is to determine the influence of marketing relationship and service quality on member loyalty of Sharia savings products at BMT Mekah Mekar Barokah Bojonegoro. This research uses purposive sampling with 45 respondents who are members of sharia savings products from 2020 to 2022. This type of research is descriptive-quantitative through correlational analysis or looking for the influence between independent variables on the dependent variable using statistical calculations. From the results of this test it can be concluded that marketing relationship has a direct effect on member loyalty by 30.2%. Service quality has a direct effect on member loyalty by 25.4%. And marketing relationship on service quality is 10.8%.
Customer Churn Prediction using Machine Learning Models
Authors: Sam Glory , Asuquo Philip , Stephen Bliss
Published: February 2024

Customer churn is a critical concern for the telecommunication industry. Understanding and predicting customer churn can lead to more effective retention strategies and an increase in profitability. Predicting customer churn allows telecommunication companies to identify potentially dissatisfied customers early on and take proactive measures to retain them. Due to a large client base, the telecom industry generates a large volume of data on a daily basis. Decision makers and business analysts stressed that acquiring new customers is more expensive than retaining existing ones. Business analysts and customer relationship management (CRM) analysts must understand the reasons for customer churn as well as behaviour patterns from existing churn data. This paper proposes a churn prediction model that uses classication and clustering techniques to identify churn customers and provides the factors that contribute to customer churning in the telecom sector. The results presented shows that XBoost and Random Forest achieved higher prediction accuracy when compared to K- Nearest Neighbours, Support Vector Machines and Decision Trees in terms of accuracy, precision, F1-Score and recall.
Assessment of Stream Flow of Hidkal Dam Catchment Area in Krishna Basin of India Using SIMHYD Model
Authors: Rao I. Bhaskara , Nemichandrappa M. , Rao K. V. , Polisgowdar B. S. , Reddy G. V. Srinivasa , Sreenivas A. G. , Ajayakumar M. Y.
Published: February 2024

A study was conducted to predict the stream flow from a catchment area of Hidkal dam situated in Krishna basin of India. The SimHYD model was selected to setup the stream flow model under limited data conditions. Daily rainfall, potential evapotranspiration (PET) and observed discharges were used as input data to setup the model.  Sensitivity analysis was carried out to identify the more sensitive parameter and fixed final parameter values. A genetic algorithm was used for calibration and validation of the model with object function of Nash -Sutcliffe Equation (NSE). The performance of model during calibration and validation with monthly stream flow (m3/s) was found to be very good in terms of NSE, R2. The NSE and correlation coefficient were found to be 0.77 and 0.93 during calibration period and 0.90 and 0.95 during validation period respectively. The was a very good agreement between monthly observed and simulated stream flows of catchment area of Hidkal Dam. The NSE value of model during calibration period with daily runoff was found to be satisfactory at 0.51. It was observed that good agreement between observed and simulated daily runoff (in mm) with a correlation coefficient is 0.74. NSE and correlation coefficient during validation period using daily data are found to be 0.80 and 0.9 respectively. This study concluded that the SimHYD model can be used for assessment of stream flow with limited data.
A dysmorphic boy with 4qter deletion and 4q32.3‐34.3 duplication: Clinical, cytogenetic, and molecular findings
Authors: Van Buggenhout Griet , Maas Nicole M.C. , Fryns Jean‐Pierre , Vermeesch Joris R.
Published: November 2004

An infant boy presented with trigonocephaly, mild craniofacial features, a small VSD, open ductus Botalli (ODB), bilateral hip dysplasia, psychomotor retardation, and hypotonia. The karyotype was 46,XY,del(4)(q34). Unexpectedly, fluorescence in situ hybridization (FISH) studies revealed not only a deletion but also a duplication. The deletion extends from 4qter to 4q34.3 and the duplication from 4q32.3 to q34.3. This is the first description of a deletion inverted duplication 4q. Possible mechanisms we can envision by which this deletion/duplication arose could be a U‐type exchange causing end‐to‐end fusion or a two step event with a paracentric inversion and subsequent cross‐over in the inverted segment. This observation suggests that the karyotype of patients with a 4q deletion should be confirmed by molecular cytogenetics. © 2004 Wiley‐Liss, Inc.
Functional analysis of polymorphic variation within the promoter and 5′ untranslated region of the neurofibromatosis type 1 (NF1) gene
Authors: Horan Martin P. , Osborn Michael , Cooper David N. , Upadhyaya Meena
Published: November 2004

The regulatory regions of the neurofibromatosis type 1 (NF1) gene have scarcely been screened either for mutations of potential pathological importance or for functional polymorphisms. To address this question, a 987 bp sequence spanning the promoter and 5′ flanking sequence of the human NF1 gene was screened for sequence variants in 570 unrelated NF1 patients and 105 controls. Five novel sequence variants were identified, comprising a 14 bp deletion at −142 within the promoter region, three single nucleotide substitutions in the 5′UTR (C + 247T, C + 261G, G + 462C), and a substitution (C + 514T) at the 5′ end of the coding region that served to generate a Stop codon. The latter is likely to be of pathological significance since it is predicted to lead to the synthesis of a truncated protein. The functional significance of three of the other variants (14 bp del, C + 261G, G + 462C) was explored by luciferase reporter gene expression and electrophoretic mobility shift assays. The del14 variant demonstrated allele‐specific protein binding without altered reporter gene expression and the G + 462C allele showed slightly decreased reporter gene expression. © 2004 Wiley‐Liss, Inc.
Novel mutation in the tyrosine kinase domain of FGFR2 in a patient with Pfeiffer syndrome
Authors: Zankl Andreas , Jaeger Gudrun , Bonafé Luisa , Boltshauser Eugen , Superti‐Furga Andrea
Published: November 2004

Mutations in the fibroblast growth factor receptor 2 (FGFR2) cause a variety of craniosynostosis syndromes. The mutational spectrum tends to be narrow with the majority of mutations occurring in either exon IIIa or IIIc or in the intronic sequence preceding exon IIIc. Mutations outside of this hotspot are uncommon and the few identified mutations have demonstrated wide clinical variability, making it difficult to establish a clear‐cut genotype–phenotype correlation. To better delineate the clinical picture associated with these unusual mutations, we describe a severely affected patient with Pfeiffer syndrome and a missense mutation in the tyrosine kinase (TK) domain of FGFR2. © 2004 Wiley‐Liss, Inc.
Somatic mosaicism of chromosome 7 in a highly proliferating melanocytic congenital naevus in a ring chromosome 7 patient
Authors: Mehraein Yasmin , Ehlhardt Sandra , Wagner Arnold , Göttert Elisabeth , Tilgen Wolfgang , Zang Klaus D. , Dill‐Müller Dorothee
Published: November 2004

Ring chromosome 7 is a rare but well documented chromosomal aberration in man. So far at least 14 cases have been reported in the literature showing a variable but distinct pattern of phenotypic characteristics in affected individuals. Besides others, skin findings as pigmented naevi are especially frequent. Loss of chromosomal material from the terminal chromosome arms in the structurally abnormal ring chromosome 7 as well as somatic mosaicism with loss or gain of chromosome 7 has been suggested to be responsible for the clinical symptoms. We now report another case of a ring chromosome 7 in a 14‐year‐old boy with multiple remarkable congenital naevi, where we could demonstrate for the first time somatic mosaicism showing significant gain of chromosome 7 within a highly proliferating melanocytic congenital naevus (MCN). © 2004 Wiley‐Liss, Inc.
Subcutaneous neurofibromas are associated with mortality in neurofibromatosis 1: A cohort study of 703 patients
Authors: Khosrotehrani Kiarash , Bastuji‐Garin Sylvie , Riccardi Vincent M. , Birch Patricia , Friedman Jan M. , Wolkenstein Pierre
Published: November 2004

Neurofibromatosis 1 (NF1) is a common genetic disorder with an autosomal dominant mode of inheritance, an increased morbidity and mortality, and a shorter lifespan. Although the disease is fully penetrant by the age of 8, the variability in symptoms and complications is high, even among members of the same family. The aim of this study was to identify easily recognizable clinical features that may be associated with mortality in a cohort of patients affected with NF1. We used prospectively collected data from the Neurofibromatosis Institute Database (NFID) and included in our analysis 703 patients who fulfilled the NIH diagnostic criteria for NF1. Clinical, especially dermatological features were tested as potential factors associated with mortality. Among the patients, 405 (57.6%) were children and 298 (42.4%) were adults. The mean follow‐up was 2.4 years (median = 0.98, range: 0–15.3 years). Forty patients died during follow‐up, mostly due to tumor development such as sarcoma (n = 18). In the adult population, subcutaneous neurofibromas (odds ratio [OR] = 3.6, 95% confidence interval (CI): [1.2–11.3], P = 0.02) and male gender (OR = 5.6, [1.5–20.9], P = 0.004) were independent predictors of mortality after adjustment for age. Among children, the presence of facial plexiform neurofibromas and pruritus were significantly associated with mortality in univariate analysis. Our study describes independent risk factors of mortality in a large cohort of adult and pediatric patients. Close follow‐up should be obtained for patients presenting with subcutaneous neurofibromas. © 2004 Wiley‐Liss, Inc.
Autosomal dominant flat umbilicus
Authors: Leung Alexander K.C. , McLeod D. Ross
Published: November 2004

We describe a Chinese family among whom five members in three generations had a flat umbilicus with vertical and male to male transmission indicative of autosomal dominant inheritance. Except the proband, who also had Tetralogy of Fallot, other affected members had a flat umbilicus as an isolated anomaly. Autosomal dominant transmission of isolated flat umbilicus has not been reported previously. © 2004 Wiley‐Liss, Inc.
Antioxidant treatment improves in vivo cardiac and skeletal muscle bioenergetics in patients with Friedreich's ataxia
Authors: Lodi Raffaele , Hart Paul E. , Rajagopalan Bheeshma , Taylor Doris J. , Crilley Jenifer G. , Bradley Jane L. , Blamire Andrew M. , Manners David , Styles Peter , Schapira Anthony H.V. , Cooper J. Mark
Published: November 2004

Friedreich's ataxia (FA) is the most common form of autosomal recessive spinocerebellar ataxia and is often associated with a cardiomyopathy. The disease is caused by an expanded intronic GAA repeat, which results in deficiency of a mitochondrial protein called frataxin. In the yeast YFH1 knockout model of the disease there is evidence that frataxin deficiency leads to a severe defect of mitochondrial respiration, intramitochondrial iron accumulation, and associated production of oxygen free radicals. Recently, the analysis of FA cardiac and skeletal muscle samples and in vivo phosphorus magnetic resonance spectroscopy (31P‐MRS) has confirmed the deficits of respiratory chain complexes in these tissues. The role of oxidative stress in FA is further supported by the accumulation of iron and decreased aconitase activities in cardiac muscle. We used 31P‐MRS to evaluate the effect of 6 months of antioxidant treatment (Coenzyme Q10 400 mg/day, vitamin E 2,100 IU/day) on cardiac and calf muscle energy metabolism in 10 FA patients. After only 3 months of treatment, the cardiac phosphocreatine to ATP ratio showed a mean relative increase to 178% (p = 0.03) and the maximum rate of skeletal muscle mitochondrial ATP production increased to 139% (p = 0.01) of their respective baseline values in the FA patients. These improvements, greater in prehypertrophic hearts and in the muscle of patients with longer GAA repeats, were sustained after 6 months of therapy. The neurological and echocardiographic evaluations did not show any consistent benefits of the therapy after 6 months. This study demonstrates partial reversal of a surrogate biochemical marker in FA with antioxidant therapy and supports the evaluation of such therapy as a disease‐modifying strategy in this neurodegenerative disorder.
Superoxide stress identifies neurons at risk in a model of ataxia‐telangiectasia
Authors: Quick Kevin L. , Dugan Laura L.
Published: November 2004

Ataxia‐telangiectasia (A‐T) is an autosomal recessive disorder caused by mutations in the ATM gene. A‐T children demonstrate sensitivity to ionizing radiation, predisposition to hematological malignancies, and telangiectasias. However, the hallmark of A‐T is fulminant degeneration of cerebellar Purkinje cells accompanied by a progressive ataxia with features of both cerebellar and basal ganglia dysfunction. Although the ATM gene product (ATM) is known to be involved in DNA repair, the mechanisms that link loss of ATM with neurodegeneration remain unknown. Recently, it has been suggested that abnormalities in redox status contribute to the A‐T phenotype. To address this question in the nervous system, we measured reactive oxygen species (ROS) in brain regions and specific neuronal populations in ATM−/− mice. We found increased ROS levels in cerebellum and striatum but not cortex of ATM−/− mice compared to ATM+/+ mice. Confocal microscopic examination revealed elevated superoxide levels in cerebellar Purkinje cells and nigral dopaminergic neurons but not cortical neurons, thus mapping increased superoxide levels onto the neuronal populations selectively affected in A‐T. These data are the first demonstration of elevated levels of ROS in neurons at risk in any genetic neurodegenerative disorder and, furthermore, suggest that ATM acts as a pro‐survival signal in post‐mitotic Purkinje cells and dopaminergic neurons by modifying superoxide radical handling in these selectively vulnerable neurons.
How long do new‐onset seizures in children last?
Authors: Shinnar Shlomo , Berg Anne T. , Moshe Solomon L. , Shinnar Reuel
Published: November 2004

Although there are data on the duration of seizures in patients with refractory epilepsy, little is known about the duration of seizures in nonrefractory epilepsy populations. In a prospective study, seizure duration was determined in 407 children with a first unprovoked seizure using a structured interview and review of medical and ambulance records. Analysis focused on the distribution of seizure duration and on the conditional probability that a seizure would stop once it had already lasted for a specified time. Seizures lasted ≥5 minutes in 50% of cases, ≥10 minutes in 29%, ≥20 minutes in 16%, and ≥30 minutes in 12%. Seizure duration data were best fit as the sum of two exponential distributions, one with a mean of 3.6 minutes accounting for 76% of cases and the other with a mean of 31 minutes accounting for 24% of cases. The longer a seizure lasted, the less likely it was to stop within the next few minutes. In the 182 children with 2 or more seizures, the durations of the first and second seizures were highly correlated (r = 0.395, p < 0.0001). We conclude that the distribution of seizure duration in children with a first unprovoked seizure differs markedly from that observed in patients with refractory epilepsy. A subgroup of patients are predisposed to prolonged seizures. The data suggest that, once a seizure lasts for more than 5–10 minutes, it is unlikely to stop spontaneously within the next few minutes, and intervention is therefore indicated. These findings also support the continued use of the current definition of status epilepticus as a seizure lasting for 30 minutes or longer for epidemiologic studies.
Neuropeptides and neurotrophins in neonatal blood of children with autism or mental retardation
Authors: Nelson Karin B. , Grether Judith K. , Croen Lisa A. , Dambrosia James M. , Dickens Benjamin F. , Jelliffe Laura L. , Hansen Robin L. , Phillips Terry M.
Published: November 2004

There has been little exploration of major biologic regulators of cerebral development in autism. In archived neonatal blood of children with autistic spectrum disorders (n = 69), mental retardation without autism (n = 60), or cerebral palsy (CP, n = 63) and of control children (n = 54), we used recycling immunoaffinity chromatography to measure the neuropeptides substance P (SP), vasoactive intestinal peptide (VIP), pituitary adenylate cyclase–activating polypeptide (PACAP), calcitonin gene–related peptide (CGRP), and the neurotrophins nerve growth factor (NGF), brain‐derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4/5 (NT4/5). Neonatal concentrations of VIP, CGRP, BDNF, and NT4/5 were higher (ANOVA, all p values < 0.0001 by Scheffe test for pairwise differences) in children in the autistic spectrum and in those with mental retardation without autism than in control children. In 99% of children with autism and 97% with mental retardation, levels of at least one of these substances exceeded those of all control children. Concentrations were similar in subgroups of the autistic spectrum (core syndrome with or without mental retardation, other autistic spectrum disorders with or without mental retardation) and in the presence or absence of a history of regression. Among children with mental retardation, concentrations did not differ by severity or known cause (n = 11, including 4 with Down syndrome). Concentrations of measured substances were similar in children with CP as compared with control subjects. SP, PACAP, NGF, and NT3 were not different by diagnostic group. No measured analyte distinguished children with autism from children with mental retardation alone. In autism and in a heterogeneous group of disorders of cognitive function, overexpression of certain neuropeptides and neurotrophins was observed in peripheral blood drawn in the first days of life.
Placebo‐controlled clinical trials in multiple sclerosis: Ethical considerations
Authors: Lublin Fred D. , Reingold Stephen C. ,   National Multiple Sclerosis Society (USA) Task Force on Placebo‐Controlled Clinical Trials in MS
Published: November 2004

The availability of partially effective therapies for some forms of multiple sclerosis (MS) raises practical and ethical issues for future placebo‐controlled clinical trials. An international Task Force of clinicians, statisticians, ethicists and regulators was convened to discuss these issues and develop consensus. The Task Force concluded that placebo‐controlled clinical trials in forms of MS for which partially effective therapies exist were ethical, so long as study subjects were fully apprised of the availability of such therapies and were encouraged to pursue them outside of a clinical trial. Patients who decline to utilize available treatments, after proper education and counseling, or those that fail all therapies can be considered to have no treatment alternatives and thus may participate in a placebo‐controlled trial.
3‐hydroxy‐3‐methylglutaryl‐CoA lyase deficiency in an adult with leukoencephalopathy
Authors: Bischof Felix , Nägele Thomas , Wanders Ronald J. A. , Trefz Friedrich K. , Melms Arthur
Published: November 2004

3‐Hydroxy‐3‐methylglutaryl‐CoA lyase deficiency is a disorder of leucine metabolism that usually presents with recurrent episodes of life‐threatening hypoglycemia during early childhood. We report on a 36‐year‐old woman with seizures, recurrent metabolic disturbances, and severe leukoencephalopathy. The diagnosis was made by analysis of amino acids in urine and serum and was confirmed by demonstration of the deficient enzyme in cultured skin fibroblasts. The patient improved clinically on oral L‐carnitine substitution. This treatable condition can remain unrecognized in adults and should be considered a potential cause of leukoencephalopathy. Ann Neurol 2004;56:727–730
Investigation into etching mechanism of polyethylene terephthalate (PET) films treated in helium and oxygenated‐helium atmospheric plasmas
Authors: Matthews Suzanne R. , Hwang Yoon J. , McCord Marian G. , Bourham Mohamed A.
Published: November 2004

This research makes an investigation into the etching mechanism of atmospheric plasma conditions on the surface of polyethylene terephthalate (PET) films. Two types of untreated PET films (S/200 and S/500) were exposed to plasma for 0 to 5.0 min in 30‐s increments. The first set of each film type was treated in helium plasma, while the second was treated in oxygenated‐helium plasma. Differential Scanning Calorimetry (DSC) was used to characterize pre‐ and post‐exposure films. Weight changes and the degree of solubility were also determined. Based on peak area results, the percent crystallinity of PET S/200 increased by an average of 4.57% (helium treated) and 13.56% (oxygenated‐helium treated), while the S/500 showed only a small increase. There was no significant change in the melting or crystallization temperatures of either film type, indicating a decrease in amorphous content versus an increase in crystalline material. Weight loss analysis supports this theory. Solubility testing revealed a continual decrease in swelling as exposure time was increased. A model was developed to predict the change in the degree of solubility for polyphase surfaces considering the etching rate per phase. The model was applied to PET with good correlation between the model and experimental data. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2383–2389, 2004
Copolymeric photoinitiators containing in‐chain thioxanthone and coinitiator amine for photopolymerization
Authors: Jiang Xuesong , Yin Jie
Published: November 2004

Two kinds of copolymeric macromolecular photoinitiator, PTXPM and PTXPC, were prepared by introducing methylacryloyl or cinnamoyl groups to the side chain of PTXP. The photopolymerizations of poly(propylene glycol)diacrylate (PPGDA) and trimethylolpropane triacrylate (TMPTA), using PTXPM and PTXPC as photoinitiators, were studied by photo‐DSC. PTXPM and PTXPC have UV–vis spectra similar to that of PTXP with blue‐shift absorption maxima. The photopolymerization behavior of TMPTA, initiated by three photoinitiators, appears similar to that of PPGDA. Compared with PTXP and PTXPC, PTXPM gives higher polymerization rate and final conversion, in photopolymerization of PPGDA and TMPTA, which shows that the introduction of methyl acrylate to the PTXP chain has a greater effect on photopolymerization of PPGDA and TMPTA than that of cinnamoyl acrylate. The polymerization rate and final conversion, for photopolymerization of PPDGA initiated by PTXP, can be more effectively increased by the introduction of methyl acrylate group to the PTXP chain, than are those for TMPTA. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2395–2400, 2004
Electron‐beam curing of bismaleimide‐reactive diluent resins
Authors: Li Yuntao , Morgan Roger J. , Tschen Francisco , Sue H.‐J. , Lopata Vince
Published: November 2004

Electron‐beam (E‐beam) curing of 4,4′‐bismaleimidodiphenylmethane (BMPM)/BMI‐1,3‐tolyl/o,o′‐diallylbisphenol A (DABPA)–based bismaleimide (BMI) systems and their mixing with various reactive diluents, such as N‐vinylpyrrolidone (NVP) and styrene, were investigated to elucidate how temperature, electron‐beam dosage, and diluent concentration affect the cure extent. The effect of free‐radical initiator on the cure reactions was also studied. It was found that low‐intensity E‐beam exposures cannot cause the polymerization of BMI. High‐intensity E‐beam exposures give high reaction conversion attributed to a high temperature increase, which induced thermal curing. It was shown that the dilution and activation of NVP in BMI cause a more complete BMI cure reaction under E‐beam radiation. BMI/NVP can be initiated easily by low‐intensity E‐beam without thermal curing. FTIR studies indicate that about 70% of the reaction is complete for BMI/NVP with 200 kGy dosage exposure at 10 kGy per pass. The sample temperature only reaches about 75°C. The free‐radical initiator, dicumyl peroxide, can accelerate the reaction rate at the beginning of E‐beam exposure, but does not affect the final reaction conversion. The increase of the concentration of NVP in the BMI/NVP systems increases the reactive conversions almost linearly. © 2004 Wiley Periodicals Inc. J Appl Polym Sci 94: 2407‐2416, 2004
Synthesis and biological evaluation of novel 2′, 3′, 4′‐triply branched carbocyclic nucleosides as potential antiviral agents
Authors: Ko Ok Hyun , Hong Joon Hee
Published: November 2004

Novel 2′, 3′, 4′‐triply branched carbocyclic nucleosides were synthesized in this study. The introduction of two methyl groups in the 2′‐ and 3′‐position was accomplished by a Horner‐Wadsworth‐Emmons reaction and isopropenyl magnesium bromide addition, respectively. The construction of the required 4′‐quaternary carbon was carried out using a [3, 3]‐sigmatropic rearrangement. Bis‐vinyls were successfully cyclized using a Grubbs' catalyst II. The natural bases (adenine, cytosine) were efficiently coupled using a Pd(0) catalyst. The antiviral activities of the synthesized compounds were evaluated against HIV‐1, HSV‐1, HSV‐2 and HCMV. Compound 30 displayed moderate anti‐HCMV activity (EC50 = 30.1 μg/mL), without exhibiting any cytotoxicity at up to 100 μM.
Archaeological prospection of the Dutch perimarine landscape by means of magnetic methods
Authors: Kattenberg A. E. , Aalbersberg G.
Published: November 2004

Fluxgate gradiometer surveys on two sites in the coastal plains of The Netherlands showed unexpected results. On the one hand, archaeological features, identified by coring or test trenching, were undetectable owing to a lack of sufficient magnetic contrast between the infill of the archaeological structures and the surrounding natural (salt marsh) sediments. This lack of contrast was shown to be caused by the iron mineralogy and not by iron deficiency of the soil. On the other hand, geological features, interpreted as anoxic shallow creek fills, showed with surprising clarity. Analysis of black‐stained deposits underlying the features identified pyrite and associated iron sulphide minerals as the cause for the magnetic anomalies. The complex iron sulphide/oxide mineralogy of salt marsh environments, coupled with geological history of the sites with multiple marine inundations, indicate that detection and interpretation of magnetic anomalies in the coastal zone of The Netherlands requires both thorough knowledge of the geology and further research into the geochemistry of these deposits. Copyright © 2004 John Wiley & Sons, Ltd.
Lectin‐like oxidized low‐density lipoprotein receptor 1 mediates matrix metalloproteinase 3 synthesis enhanced by oxidized low‐density lipoprotein in rheumatoid arthritis cartilage
Authors: Kakinuma Takumi , Yasuda Tadashi , Nakagawa Takefumi , Hiramitsu Teruko , Akiyoshi Miki , Akagi Masao , Sawamura Tatsuya , Nakamura Takashi
Published: November 2004

Objective

To investigate for the presence of oxidized low‐density lipoprotein (ox‐LDL) and lectin‐like oxidized LDL receptor 1 (LOX‐1) in cartilage specimens from rheumatoid arthritis (RA) joints and to determine whether the interaction of ox‐LDL with LOX‐1 can induce matrix metalloproteinase 3 (MMP‐3) in articular cartilage explant culture.

Methods

Human articular cartilage specimens obtained from patients with RA, osteoarthritis (OA), and femoral neck fractures were examined for LOX‐1 and ox‐LDL by confocal fluorescence microscopy. The association between ox‐LDL and LOX‐1 was evaluated by immunofluorescence analysis. Articular cartilage specimens from patients with femoral neck fractures were incubated with ox‐LDL, with or without preincubation with neutralizing anti–LOX‐1 antibody. MMP‐3 synthesis by chondrocytes in explant cartilage was evaluated by immunofluorescence, and protein secretion into conditioned medium was monitored by immunoblotting and enzyme‐linked immunosorbent assay.

Results

The majority of the RA chondrocytes stained positively with both anti–LOX‐1 and anti–ox‐LDL antibodies; however, no positive cells were found in OA and normal cartilage specimens. Anti–LOX‐1 antibody suppressed the binding of DiI‐labeled ox‐LDL to chondrocytes in explant culture, suggesting that the interaction was mediated by LOX‐1. In contrast to native LDL, ox‐LDL induced MMP‐3 synthesis by articular chondrocytes in association with the induction of LOX‐1, which resulted in enhanced secretion of MMP‐3 into the culture medium. Anti–LOX‐1 antibody reversed ox‐LDL–stimulated MMP‐3 synthesis to control levels.

Conclusion

Ox‐LDL, principally mediated by LOX‐1, enhanced MMP‐3 production in articular chondrocytes. Increased accumulation of ox‐LDL with elevated expression of LOX‐1 in RA cartilage indicates a specific role of the receptor–ligand interaction in cartilage pathology in RA.
Prolonged bleeding time and lupus anticoagulant: A second paradox in the antiphospholipid syndrome
Authors: Urbanus R. T. , de Laat H. B. , de Groot P. G. , Derksen R. H. W. M.
Published: November 2004

Objective

Systemic lupus erythematosus and antiphospholipid syndrome (APS) often appear concomitantly. Lupus nephritis and antiphospholipid antibody–related ischemic nephropathy cannot be distinguished clinically, although their etiology and treatment differ greatly. Examination of a renal biopsy sample is therefore essential in order to provide the correct treatment. We have observed that patients with lupus anticoagulant (LAC), a serologic marker for APS, often have a prolonged bleeding time, which is a contraindication for performing a percutaneous renal biopsy. We undertook this study to evaluate systematically the bleeding time in 27 consecutive patients.

Methods

The bleeding time was measured in 27 patients who were persistently positive for LAC and who were not exposed to aspirin or nonsteroidal antiinflammatory drugs. Platelet function and von Willebrand factor (vWF) parameters were subsequently assessed in patients with a prolonged bleeding time.

Results

Twenty‐one of 27 patients (78%) had a prolonged bleeding time despite a normal platelet count in the majority of patients (81%). Platelet functioning and vWF parameters in these 21 patients were normal, except for those in 1 patient with a mild storage pool disease.

Conclusion

With this study, we introduce yet another paradox in the phenomenon of APS. Although a prolonged bleeding time is generally accepted to be a sign of defective primary hemostasis, LAC is associated with thrombosis. Further studies are needed to elucidate the mechanism behind this disturbance of primary hemostasis.
Rituximab improves peripheral B cell abnormalities in human systemic lupus erythematosus
Authors: Anolik Jennifer H. , Barnard Jennifer , Cappione Amedeo , Pugh‐Bernard Aimee E. , Felgar Raymond E. , Looney R. John , Sanz Iñaki
Published: November 2004

Objective

B lymphocyte depletion has recently emerged as a promising approach to the treatment of systemic lupus erythematosus (SLE). As part of a phase I/II dose‐ranging trial of rituximab in the treatment of SLE, we evaluated the fate of discrete B cell subsets in the setting of selective depletion by anti‐CD20 monoclonal antibody and during the B cell recovery phase.

Methods

B cell depletion and phenotype were examined by flow cytometry of peripheral blood mononuclear cells for CD19, CD20, CD27, IgD, and CD38 expression. Changes in autoreactive B lymphocytes and plasma cells were assessed by determination of serum autoantibody levels (anti–double‐stranded DNA and VH4.34) and by direct monitoring of a unique autoreactive B cell population bearing surface antibodies whose heavy chain is encoded by the VH4.34 gene segment.

Results

Compared with normal controls, SLE patients displayed several abnormalities in peripheral B cell homeostasis at baseline, including naive lymphopenia, expansion of a CD27−,IgD− (double negative) population, and expansion of circulating plasmablasts. Remarkably, these abnormalities resolved after effective B cell depletion with rituximab and immune reconstitution. The frequency of autoreactive VH4.34 memory B cells also decreased 1 year posttreatment, despite the presence of low levels of residual memory B cells at the point of maximal B cell depletion and persistently elevated serum autoantibody titers in most patients.

Conclusion

This study is the first to show evidence that in SLE, specific B cell depletion therapy with rituximab dramatically improves abnormalities in B cell homeostasis and tolerance that are characteristic of this disease. The persistence of elevated autoantibody titers may reflect the presence of low levels of residual autoreactive memory B cells and/or long‐lived autoreactive plasma cells.