bluuebunny/crossref_metadata_2025 huggingface dataset:
Inverse association of general joint hypermobility with hand and knee osteoarthritis and serum cartilage oligomeric matrix protein levels
Authors: Chen Hsiang‐Cheng , Shah Svati H. , Li Yi‐Ju , Stabler Thomas V. , Jordan Joanne M. , Kraus Virginia Byers
Published: November 2008

Objective

Extensive joint hypermobility, lower serum cartilage oligomeric matrix protein (COMP) levels, and early‐onset osteoarthritis (OA) are phenotypes of inherited pseudoachondroplasia and multiple epiphyseal dysplasia. However, few studies have evaluated the association between articular hypermobility and primary OA. We undertook the present study to evaluate this association and to test the hypothesis that COMP levels are associated with hypermobility in patients with OA and individuals without OA.

Methods

Two separate cohorts were available for analysis, the CARRIAGE (CARolinas Region Interaction of Aging Genes and Environment) extended family and a subset of the GOGO (Genetics of Generalized Osteoarthritis) sibpair cohort. In the CARRIAGE family, we performed hand and knee examinations and hypermobility evaluations (Beighton criteria) and obtained sera for measurement of COMP and hyaluronan (HA). Data on COMP and HA levels and extensive joint radiographic and hypermobility data were also available for the GOGO cohort.

Results

The prevalence of hypermobility was 13% in the CARRIAGE family and 5% in the GOGO cohort. In the CARRIAGE family, hypermobility was associated with a significantly reduced prevalence of hand (especially proximal interphalangeal joint) and knee OA and lower mean serum COMP levels, both in the total cohort and in non‐hand‐OA subgroups. These results were further validated in the GOGO subsets without radiographic OA, in which hypermobility was also associated with a significantly reduced mean serum COMP level (P < 0.0001 adjusted for age). Serum HA levels did not differ in relation to hypermobility in either cohort.

Conclusion

The present results indicate that there is an inverse relationship between hypermobility and hand and knee OA, and that hypermobility is associated with lower serum COMP levels. Genetic variations of the COMP gene may account for some subgroups of benign joint hypermobility.
A conserved DYW domain of the pentatricopeptide repeat protein possesses a novel endoribonuclease activity
Authors: Nakamura Takahiro , Sugita Mamoru
Published: November 2008

Many plant pentatricopeptide repeat (PPR) proteins are known to contain a highly conserved C‐terminal DYW domain whose function is unknown. Recently, the DYW domain has been proposed to play a role in RNA editing in plant organelles. To address this possibility, we prepared recombinant DYW proteins and tested their cytidine deaminase activity. However, we could not detect any activity in the assays we used. Instead, we found that the recombinant DYW domains possessed endoribonuclease activity and cleaved before adenosine residues in the RNA molecule. Some DYW‐containing PPR proteins may catalyze site‐specific cleavage of target RNA species.
Inhibition of membrane‐bound cytochrome c oxidase by zinc ions: High‐affinity Zn2+‐binding site at the P‐side of the membrane
Authors: Vygodina Tatiana V. , Zakirzianova Wiolanta , Konstantinov Alexander A.
Published: November 2008

In the presence of the uncoupler, external zinc ions inhibit rapidly turnover of cytochrome c oxidase reconstituted in phospholipid vesicles or bound to the membrane of intact mitochondria. The effect is promoted by electron leaks into the oxidase during preincubation with Zn2+. Inhibition of liposome‐bound bovine cytochrome oxidase by external Zn2+ titrates with a K
i
of 1 ± 0.3 μM. Presumably, the Zn2+‐binding group at the positively charged side is not reactive in the oxidized enzyme, but becomes accessible to the cation in some partially reduced state(s) of the oxidase; reduction of CuB is tentatively proposed to be responsible for the effect.
Effect of hyperoxidized guanine on DNA primer–template structures: Spiroiminodihydantoin leads to strand slippage
Authors: Fenn Dickson , Chi Lai Man , Lam Sik Lok
Published: November 2008

Oxidation of guanine in DNA can lead to mutagenic lesions such as 7‐hydro‐8‐oxoguanine (oG). Upon further oxidation, a more mutagenic lesion, spirominodihydantoin (Sp), can occur. In this study, nuclear magnetic resonance (NMR) investigations were performed to determine the structural features of DNA primer–template models with 5′‐GG, 5′‐G(oG), 5′‐G(Sp) and 5′‐T(Sp) templates, that mimic the situation in which the downstream G of the template has been oxidized to oG or hyperoxidized to Sp. Our results show that misalignment occurs only in the 5′‐G(Sp) and 5′‐T(Sp) templates, providing structural insights into the observed differences in mutagenicity of Sp and oG during DNA replication.
Comparison between ultrasound and genetic testing for the early diagnosis of polycystic kidney disease in Persian and Exotic Shorthair cats
Authors: Bonazzi Mattia , Volta Antonella , Gnudi Giacomo , Cozzi Maria C. , Strillacci Maria G. , Polli Michele , Longeri Maria , Manfredi Sabrina , Bertoni Giorgio
Published: November 2008

Autosomal-dominant polycystic kidney disease (AD-PKD) is common in Persians and Persians-related breeds. The aims of this study were to evaluate the sensitivity and specificity of early ultrasound examination and to compare ultrasound and genetic testing for early diagnosis. Sixty-three Persians and seven Exotic Shorthairs were considered. All underwent ultrasonographic and genetic testing (polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) assay) between 2.5 and 3.5 months of age (10–14 weeks). With ultrasound, 41.4% showed renal cysts, while 37.1% were PKD positive by genetic testing and DNA sequencing. Six cats with at least one renal cyst were negative by genetic testing, while only one cat negative at ultrasound resulted positive at genetic test. DNA sequencing of three polycystic cats, negative by genetic test, revealed they were heterozygous for the mutation. Agreement was described by Cohen's kappa that resulted 0.85, considering genetic test and DNA sequencing. Sensitivity and specificity of ultrasound were 96.2% and 91%, respectively. Sensitivity was higher and specificity lower than reported previously. The higher sensitivity could be due to improved technical capabilities of ultrasound machines and transducers. Other causes of PKD could explain the lower specificity. In conclusion, ultrasound resulted in a reliable diagnostic method for feline AD-PKD1 at early age and it should always be used with genetic testing, in order to reach a complete screening programme and eventually to identify other genetic mutations.
Scale dependence of subgrid-scale model coefficients: An a priori study
Authors: Bou-Zeid Elie , Vercauteren Nikki , Parlange Marc B. , Meneveau Charles
Published: November 2008

Dynamic subgrid-scale models require an a priori assumption about the variation in the model coefficients with filter scale. The standard dynamic model assumes independence of scale while the scale dependent model assumes power-law dependence. In this paper, we use field experimental data to investigate the dependence of model coefficients on filter scale for the Smagorinsky and the nonlinear models. The results indicate that the assumption of a power-law dependence, which is often used in scale dependent dynamic models, holds very well for the Smagorinsky model. For the nonlinear model, the power-law assumption seems less robust but still adequate.
Surface plasmon excitation of Au and Ag in scanning probe energy loss spectroscopy
Authors: Pulisciano A. , Park S. J. , Palmer R. E.
Published: November 2008

We explore the incident energy dependence of the electronic excitation spectra of Au and Ag films in scanning probe energy loss spectroscopy (SPELS) and also high resolution electron energy loss spectroscopy. We show that the spectra obtained in SPELS depend strongly on the incident electron beam energy. In the case of Au, interband transitions mask the surface plasmon unless the field emission voltage is reduced to ∼100 V, whereas there is a clear surface plasmon peak above 300 V for Ag.
Finite size effects on the electromagnetic field enhancement from low-dimensional silver nanoshell dimer arrays
Authors: Song Youlin , Zhao Ke , Jia Yu , Hu Xing , Zhang Zhenyu
Published: November 2008

Finite size effects on the optical properties of one-dimensional (1D) and two-dimensional (2D) nanoshell dimer arrays are investigated using generalized Mie theory and coupled dipole approximation within the context of surface-enhanced Raman spectroscopy (SERS). It is shown that the huge enhancement in the electromagnetic (EM) field at the center of a given dimer oscillates with the length of the 1D array. For an array of fixed length, the EM enhancement also oscillates along the array, but with a different period. Both types of oscillations can be attributed to the interference of the dynamic dipole fields from different dimers in the array. When generalized to 2D arrays, EM enhancement higher than that of the 1D arrays can be gained with a constant magnitude, a salient feature advantageous to experimental realization of single-molecule SERS.
Site-specific fragmentation caused by core-level photoionization in F3SiCH2CH2Si(CH3)3 vapor: Comparison between Si:1s and 2p photoionizations by means of photoelectron-photoion-photoion triple-coincidence spectroscopy
Authors: Nagaoka Shin-ichi , Takemoto Mai , Prümper Georg , Fukuzawa Hironobu , Tamenori Yusuke , Suzuki Isao H. , Ueda Kiyoshi
Published: November 2008

Site-specific fragmentation caused by Si:1s and 2p core-level photoionizations in F3SiCH2CH2Si(CH3)3 vapor was studied by energy-selected-photoelectron photoion-photoion triple-coincidence spectroscopy. The difference between the chemical shifts of the two Si sites is larger for the 1s ionization than for the 2p (2s) ionization. The fragmentation caused by the Si:1s ionization is more violent than that caused by the Si:2p ionization. The ions and ion pairs showing high site specificity for the Si:1s ionization belong to small fragments compared to those in the Si:2p ionization. Criteria for high site-specificity in fragmentation are discussed in conjunction with the present results.
Synthesis of soft/hard magnetic FePt-based glassy alloys with supercooled liquid region
Authors: Makino Akihiro , Kazahari Akihiro , Zhang Wei , Yubuta Kunio , Kubota Takeshi , Inoue Akihisa
Published: November 2008

Since the glassy alloys have structural homogeneity on a nanoscopic scale and wide supercooled liquid region, ΔTx (temperature interval between glass transition and crystallization), these materials are recognized as promising micro/nano-materials for nanomachines or micro electro-mechanical systems (MEMS). As one of the micro/nano components, the hard magnetic one is immensely desired. We systematically investigated the effect of metalloids composition in Fe-Pt-metalloids alloys on the glass-forming ability, and developed Fe55Pt25Si16B2P2, Fe55Pt25Si15B3P2 and (Fe0.55Pt0.25Si0.16B0.02P0.02)96Zr4 (at%) glassy alloys with ΔTx of 37 K and 48 K, respectively. With structural change from the glassy phase to a nano-composite structure consisting of L10 FePt phase, the coercivity significantly increases from 15 A/m to 170 kA/m for the former one. There is possibility for making the hard magnetic components by the fabrication in ΔTx followed by annealing for the crystallization of the FePt–based glassy alloys. Considering the high magnetocrystalline anisotropy of the L10 phase, which should lead to room-temperature ferromagnetic stability for component sizes as small as nm-order, these Fe-Pt-based glassy alloys have great potential for fabrication of hard magnetic micro/nano structures.
Structure of bottle-brush polymers in solution: A Monte Carlo test of models for the scattering function
Authors: Hsu Hsiao-Ping , Paul Wolfgang , Binder Kurt
Published: November 2008

Extensive Monte Carlo results are presented for the structure of a bottle-brush polymer under good solvent or theta solvent conditions. Varying the side chain length, backbone length, and the grafting density for a rigid straight backbone, both radial density profiles of monomers and side chain ends are obtained as well as structure factors describing the scattering from a single side chain and from the total bottle-brush polymer. To describe the structure in the interior of a very long bottle brush, a periodic boundary condition in the direction along the backbone is used, and to describe effects due to the finiteness of the backbone length, a second set of simulations with free ends of the backbone is performed. In the latter case, the inhomogeneity of the structure in the direction along the backbone is carefully investigated. We use these results to test various phenomenological models that have been proposed to interpret experimental scattering data for bottle-brush macromolecules. These models aim to extract information on the radial density profile of a bottle brush from the total scattering via suitable convolution approximations. Limitations of this approach and the optimal way to perform the analysis of the scattering data within this approach are discussed.
Ultrafast energy redistribution in C60 fullerenes: A real time study by two-color femtosecond spectroscopy
Authors: Shchatsinin Ihar , Laarmann Tim , Zhavoronkov Nick , Schulz Claus Peter , Hertel Ingolf V.
Published: November 2008

Strong-field excitation and energy redistribution dynamics of C60 fullerenes are studied by means of time-resolved mass spectrometry in a two-color femtosecond pump-probe setup. Resonant pre-excitation of the electronic system via the first dipole-allowed HOMO→LUMO+1(t1g) (HOMO denotes highest occupied molecular orbital and LUMO denotes lowest unoccupied molecular orbital) transition with ultrashort 25 fs pulses at 399 nm of some 1012Wcm−2 results in a highly nonequilibrium distribution of excited electrons and vibrational modes in the neutral species. The subsequent coupling among the electronic and nuclear degrees of freedom is monitored by probing the system with time-delayed 27 fs pulses at 797 nm of some 1013Wcm−2. Direct information on the characteristic relaxation time is derived from the analysis of transient singly and multiply charged parent and fragment ion signals as a function of pump-probe delay and laser pulse intensity. The observed relaxation times τel≃60–400fs are attributed to different microcanonical ensembles prepared in the pre-excitation process and correspond to different total energy contents and energy sharing between electronic and vibrational degrees. The characteristic differences and trends allow one to extract a consistent picture for the formation dynamics of ions in different charge states and their fullerenelike fragments and give evidence to collective effects in multiple ionization such as plasmon-enhanced energy deposition.
Implementation of the full explicitly correlated coupled-cluster singles and doubles model CCSD-F12 with optimally reduced auxiliary basis dependence
Authors: Köhn Andreas , Richings Gareth W. , Tew David P.
Published: November 2008

An implementation of the full explicitly correlated coupled-cluster singles and doubles model CCSD-F12 using a single Slater-type geminal has been obtained with the aid of automated term generation and evaluation techniques. In contrast to a previously reported computer code [T. Shiozaki et al., J. Chem. Phys. 129, 071101 (2008)], our implementation features a reduced dependence on the auxiliary basis set due to the use of a reformulated evaluation of the so-called Z-intermediate rather than straight forward insertion of an auxiliary basis expansion, which allows an unambiguous comparison to more approximate CCSD-F12 models. First benchmark results for total correlation energies and reaction energies indicate an excellent performance of the much cheaper CCSD(F12) model.
Semispectral measures as convolutions and their moment operators
Authors: Kiukas Jukka , Lahti Pekka , Ylinen Kari
Published: November 2008

The moment operators of a semispectral measure having the structure of the convolution of a positive measure and a semispectral measure are studied, paying attention to the natural domains of these unbounded operators. The results are then applied to conveniently determine the moment operators of the Cartesian margins of the phase space observables.
Effect of a periodic electrostatic potential on magnetized particle transport
Authors: Ordonez C. A.
Published: November 2008

A classical trajectory Monte Carlo study is reported regarding the motion of a charged particle that is caused to drift across a magnetic field toward an artificially structured boundary, which produces a spatially periodic electrostatic potential. It is found that, for the system studied, the drift toward the boundary is inhibited if the particle’s speed associated with motion parallel to the magnetic field is much larger than the particle’s speed associated with cyclotron motion. The results are not dependent on the particle’s sign of charge. Possible implications for magnetic confinement of beams or plasmas are discussed.
Terahertz wave generation via optical rectification from multiferroic BiFeO3
Authors: Talbayev D. , Lee Seongsu , Cheong S.-W. , Taylor A. J.
Published: November 2008

We detected broadband coherent terahertz emission from multiferroic BiFeO3 after illuminating a high-quality bulk single ferroelectric domain crystal with an ∼100 fs optical pulse. The dependence of the emitted terahertz waveform on the energy and polarization of the optical pulse is consistent with the optical rectification mechanism of terahertz emission. We also report room-temperature terahertz optical constants of BiFeO3.
Nanowire field-effect transistor with Bi1.5Zn1.0Nb1.5O7 dielectric
Authors: Fu Wangyang , Xu Zhi , Liu Kaihui , Wang Wenlong , Bai Xuedong , Wang Enge
Published: November 2008

In this letter, amorphous Bi1.5Zn1.0Nb1.5O7 films with large permittivity (∼70) are prepared as the gate dielectric for ZnO nanowire field-effect transistors by using low-temperature (∼100°C) pulsed laser deposition. The transistors exhibit a low operation gate voltage (<3V), a high carrier mobility (∼42cm2∕Vs), and a steep subthreshold swing up to 240mV/decade. These results combined with near-room-temperature processing technique suggest that the nanowire transistor with Bi1.5Zn1.0Nb1.5O7 dielectric is a promising candidate for high-performance flexible electronics.
Electrical and reliability characteristics of copper-doped carbon (CuC) based resistive switching devices for nonvolatile memory applications
Authors: Pyun Myeongbum , Choi Hyejung , Park Ju-Bong , Lee Dongsoo , Hasan Musarrat , Dong Rui , Jung Seung-Jae , Lee Joonmyoung , Seong Dong-jun , Yoon Jaesik , Hwang Hyunsang
Published: November 2008

We have investigated copper-doped carbon (CuC) as a new solid-state electrolyte material for resistive switching devices. Compared with CuS electrolytes, CuC devices demonstrate good memory characteristics such as a high resistance ratio of over two orders, higher operation voltage, and high temperature retention characteristics. Using 1000 cell array devices, we have also confirmed uniform distributions of resistance and switching voltages. Both high and low resistance states showed negligible degradation of resistance for over 104 s at 85 °C, confirming good retention characteristics.
Gene–disease relationship discovery based on model-driven data integration and database view definition
Authors: Yilmaz S. , Jonveaux P. , Bicep C. , Pierron L. , Smaïl-Tabbone M. , Devignes M.D.
Published: November 2008

Motivation: Computational methods are widely used to discover gene–disease relationships hidden in vast masses of available genomic and post-genomic data. In most current methods, a similarity measure is calculated between gene annotations and known disease genes or disease descriptions. However, more explicit gene–disease relationships are required for better insights into the molecular bases of diseases, especially for complex multi-gene diseases.

Results: Explicit relationships between genes and diseases are formulated as candidate gene definitions that may include intermediary genes, e.g. orthologous or interacting genes. These definitions guide data modelling in our database approach for gene–disease relationship discovery and are expressed as views which ultimately lead to the retrieval of documented sets of candidate genes. A system called ACGR (Approach for Candidate Gene Retrieval) has been implemented and tested with three case studies including a rare orphan gene disease.

Availability: The ACGR sources are freely available at http://bioinfo.loria.fr/projects/acgr/acgr-software/. See especially the file ‘disease_description’ and the folders ‘Xcollect_scenarios’ and ‘ACGR_views’.

Contact:  devignes@loria.fr

Supplementary information:  Supplementary data are available at Bioinformatics online.
Tactical reproductive parasitism via larval cannibalism in Peruvian poison frogs
Authors: Brown Jason L , Morales Victor , Summers Kyle
Published: November 2008

We report an unusual example of reproductive parasitism in amphibians.
Dendrobates variabilis
, an Amazonian poison frog, oviposits at the surface of the water in small pools in plants and deposits tadpoles within the pools. Tadpoles are highly cannibalistic and consume young tadpoles if they are accessible. Deposition of embryos and tadpoles in the same pool is common. Genetic analyses indicate that tadpoles are frequently unrelated to embryos in the same pool. A pool choice experiment in the field demonstrated that males carrying tadpoles prefer to place them in pools with embryos, facilitating reproductive parasitism via cannibalism.
A biological sub-micron thickness optical broadband reflector characterized using both light and microwaves
Authors: Vukusic P , Kelly R , Hooper I
Published: November 2008

Broadband optical reflectors generally function through coherent scattering from systems comprising one of three designs: overlapped; chirped; or chaotic multilayer reflectors. For each, the requirement to scatter a broad band of wavelengths is met through the presence of a variation in nanostructural periodicity running perpendicular to the systems' outer surfaces. Consequently, the requisite total thickness of the multilayer can often be in excess of 50 μm. Here, we report the discovery and the microwave-assisted characterization of a natural system that achieves excellent optical broadband reflectivity but that is less than 1 μm thick. This system, found on the wing scales of the butterflyArgyrophorus argenteus, comprises a distinctive variation in periodicity that runs parallel to the reflecting surface, rather than perpendicular to it. In this way, the requirement for an extensively thick system is removed.
The Rockwool Group: delivering business growth through culture change
Authors: Geisler Hansen Per , Soerensen Jakob
Published: November 2008

Purpose

The purpose of this article is to show how The Rockwool Group has undergone an impressive change journey in recent years. Under the leadership of its president and chief executive officer, Eelco van Heel, the business has successfully redefined its strategic objectives, clarified its vision and mission and positively changed its culture to one that focuses firmly on people and values. The aim of this article is to examine the strategic role that HR has played in helping the organization meet its goals.

Design/methodology/approach

The case study discusses how managers across the global Rockwool business have been empowered to take on the mantle of change and adapt their own behavior for the good of the wider business. It examines the leadership approach taken to launching the change program and identifies how challenges were overcome in gaining buy‐in from across the organization.

Findings

Through the “Leading People & Brands” program, which encourages managers to mobilize their people to undertake positive change, the Rockwool Group has successfully cascaded responsibility for change throughout the organization.

Originality/value

This case study demonstrates the importance of going beyond simply communicating a new vision to gaining buy‐in from employees. This was achieved at Rockwool by listening and responding to feedback and adapting the launch program so that its message was simpler, understood by all, easy to translate into action and involved managers in its implementation.
Direct marketing and relationships
Authors: Harridge‐March Sally
Published: November 2008

Purpose

The purpose of this paper is to discuss the complementary effect of relationship marketing and direct marketing and outline the foundations of direct marketing that can be enhanced by relationship marketing principles.

Design/methodology/approach

This is a personal viewpoint based on many years of working in, teaching and research of direct and relationship marketing.

Findings

The paper finds that both disciplines of direct marketing and relationship marketing have something of value to the other. The combination of the two strategies can only be of value and benefit to both customers and organisations.

Originality/value

The value of this paper is that it outlines the symbiotic strength of direct marketing and relationship marketing that allows contemporary marketers to utilise the best of both disciplines to establish and maintain strong relationships with their customers
Mapping the profiles of franchisees
Authors: Huang Yu‐an , Phau Ian
Published: November 2008

Purpose

The purpose of this paper is to investigate franchisees' perception of the value of quality service in the franchise system.

Design/methodology/approach

Two dimensions, perceived importance and perceived gaps of the quality of the franchise system, form the anchors of a proposed 2 × 2 franchise system quality (FSQ) matrix. This is empirically tested with 200 Australian franchisees.

Findings

The results reflected a strong evidence of four distinct profiles of franchisees as conceptualized. These results also showed that the more cooperative the franchisees, the better their performance and satisfaction levels with the system. In contrast to existing literature, franchisees who fall in the high‐perceived importance cells of the FSQ matrix have a stronger desire for autonomy.

Practical implications

Cooperation between franchisees and franchisors are fundamental to achieve success. It is important to provide resources and assistance to franchisees and these are considered as key success factors. Further, determining the profile of the franchisees allows franchisors to determine the potential Best Buddy who are considered an asset in the franchise system.

Research limitations/implications

A larger sample size should be implored that focuses on specific industries or service sectors. The research can be replicated in other non‐Western contexts to formulate different insights. Cross‐national studies could be conducted to investigate differences between cultures.

Originality/value

The paper addresses the gap in literature by examining franchisees' perception of the value of services provided in a franchise system. The FSQ Matrix is also conceptualized and empirically tested on an Australian sample.
A biomechanical basis for tears of the human acetabular labrum
Authors: Smith C D , Masouros S , Hill A M , Amis A A , Bull A M J
Published: November 2008

Objective:

Acetabular labral tears predominantly affect young patients and are a source of hip pain in the athlete. Four causes of the initiation of labral tears have been proposed; trauma, hypolaxity of the anterior capsule, dysplasia and bony impingement. A further cause could be reduced biomechanical properties in the area most susceptible to tears. However, no work has defined these properties.

Design:

32 compressive and 32 tensile test samples were harvested from fresh-frozen cadaveric acetabula. The labrum was divided into eight areas to allow comparison around its circumference. Semiconfined compressive testing and tensile testing were performed at a displacement rate of 10 mm/min in a controlled environment of 100% humidity at 37 (SD 1)°C.

Setting:

Cadaveric study.

Results:

The mean compressive stiffness was 31.75 (SD 16.7) MPa, and the mean tensile elastic modulus was 24.7 (SD 10.8) MPa. The anterosuperior region had a significantly lower compressive elastic modulus than either of the posterior quadrants (p<0.05) and a significantly lower tensile modulus to the anterioinferior area (p<0.05).

Conclusions:

The biomechanical properties in the anterosuperior region may be a contributing factor to the initiation of labral tears.
Therapy for Specific Problems: Youth Tobacco Cessation
Authors: Curry Susan J. , Mermelstein Robin J. , Sporer Amy K.
Published: November 2008

Cigarette smoking is the leading cause of premature morbidity and mortality in the United States. The majority of children smoke their first cigarette in early adolescence, and many older teens have well-established dependence on nicotine. Efforts to promote and support smoking cessation among these youth smokers are critical. The available experimental studies of youth cessation interventions find that behavioral interventions increase the chances of youth smokers achieving successful cessation. Currently there is insufficient evidence for the effectiveness of pharmacological treatments with youth smokers. Many innovative studies have been compromised by challenges in recruiting sufficient numbers of youth, obtaining approval for waivers of parental consent, and high attrition in longitudinal studies. Key areas for future work include bridging the fields of adolescent development and treatment design, matching treatments to developmental trajectories of smoking behavior, better understanding treatment processes and treatment moderators, and building demand for evidence-based cessation treatments.
Workplace Victimization: Aggression from the Target's Perspective
Authors: Aquino Karl , Thau Stefan
Published: November 2008

This article reviews research on workplace victimization, which we define as acts of aggression perpetrated by one or more members of an organization that cause psychological, emotional, or physical harm to their intended target. We compare several types of victimizing behaviors that have been introduced into the organizational psychology literature to illustrate differences and similarities among them. We then review studies looking at who is likely to become a victim of aggression. Predictors include personality, demographic, behavioral, structural, and organizational variables. We also review research on coping strategies for victimization, which include problem-focused and emotion-focused strategies. We conclude with a summary of challenges for victimization research. These include addressing the proliferation of constructs and terms into the literature, attempting to clarify inconclusive findings, and using theory to guide the selection of study variables.
Genetic Screening: Programs, Principles, and Research – Thirty Years Later
Authors: Simopoulos A.P.
Published: November 2008

Screening programs for genetic diseases and characteristics have multiplied in the last 50 years. ‘Genetic Screening: Programs, Principles, and Research’ is the report of the Committee for the Study of Inborn Errors of Metabolism (SIEM Committee) commissioned by the Division of Medical Sciences of the National Research Council at the National Academy of Sciences in Washington, DC, published in 1975. The report is considered a classic in the field worldwide, therefore it was thought appropriate 30 years later to present the Committee’s modus operandi and bring the Committee’s recommendations to the attention of those involved in genetics, including organizational, educational, legal, and research aspects of genetic screening. The Committee’s report anticipated many of the legal, ethical, economic, social, medical, and policy aspects of genetic screening. The recommendations are current, and future committees should be familiar with them. In 1975 the Committee stated: ‘As new screening tests are devised, they should be carefully reviewed. If the experimental rate of discovery of new genetic characteristics means an accelerating rate of appearance of new screening tests, now is the time to develop the medical and social apparatus to accommodate what later on may otherwise turn out to be unmanageable growth.’ What a prophetic statement that was. If the Committee’s recommendations had been implemented on time, there would be today a federal agency in existence, responsive and responsible to carry out the programs and support research on various aspects of genetic screening, including implementation of a federal law that protects consumers from discrimination by their employers and the insurance industry on the basis of genetic information.
The Cost Effectiveness of Screening Newborns for Congenital Adrenal Hyperplasia
Authors: Yoo B.K. , Grosse S.D.
Published: November 2008

Objective: To assess the cost effectiveness of newborn screening for congenital adrenal hyperplasia (CAH) in the U.S. newborn population. Methods: We constructed a decision model to estimate the incremental cost-effectiveness ratio (ICER) of CAH screening compared to a strategy of no screening. Two types of cost effectiveness analyses (CEA) were conducted to measure ICER as net cost per life year (LY): (1) traditional CEA with sensitivity and scenario analyses, and (2) probabilistic CEA. Results: ICERs for (1) base-case analysis in traditional CEA and (2) probabilistic CEA were USD 292,000 and USD 255,700 per LY saved in 2005 USD, respectively. ICERs were particularly sensitive to assumptions regarding the mortality rate for the salt wasting type of CAH, in a range from 2 to 9%. The ICERs for best-case and worst-case scenarios were USD 30,900 and USD 2.9 million per LY saved, respectively. Conclusions: Using common benchmarks for cost effectiveness, our results indicate that CAH screening would be unlikely to be considered cost effective unless assumptions favorable to screening were adopted, although it could meet economic criteria used to assess U.S. regulatory policies. A limitation is that the analysis excludes outcomes such as correct assignment of gender and quality of life.
Immune Dysregulation and Chronic Stress among Older Adults: A Review
Authors: Gouin Jean-Philippe , Hantsoo Liisa , Kiecolt-Glaser Janice K.
Published: November 2008

Aging is associated with a natural dysregulation in immune functioning which may be amplified when it occurs in the context of chronic stress. Family dementia caregiving provides an excellent model to study the impact of chronic stress on immune functioning among older individuals. Empirical data suggest that the stress of caregiving dysregulates multiple components of innate and adaptive immunity. Elderly caregivers have poorer responses to vaccines, impaired control of latent viruses, exaggerated production of inflammatory mediators and accelerated cellular aging, compared to noncaregiving older adults. The chronic stress-induced immune dysregulation observed among older caregivers appears to be of sufficient magnitude to impact health. Furthermore, evidence suggests that chronic stress leads to premature aging of the immune system.
Sympathetic Nervous System and Lymphocyte Proliferation in the Fischer 344 Rat Spleen: A Longitudinal Study
Authors: Bellinger Denise L. , Silva Dorian , Millar Ashley Brooke , Molinaro Christine , Ghamsary Mark , Carter Jeff , Perez Sam , Lorton Dianne , Lubahn Cheri , Araujoa Gerson , Thyagarajan Srinivasan
Published: November 2008

Aging is associated with reduced cellular immunity, which leads to increased rates of infectious disease, cancer and autoimmunity in the elderly. Previous findings from our laboratory revealed an age-related decline in sympathetic innervation of immune organs that affects immunity. These studies suggested potential sympathetic nervous system involvement in age-induced immune dysregulation. Objectives: The purpose of this study was to longitudinally characterize the effects of age on sympathetic neurotransmission in the spleen and net sympathetic activity/tone in male Fischer 344 rats. Methods: Splenic sympathetic neurotransmission was evaluated between 8 and 24 months of age by (1) splenic norepinephrine (NE) concentration and turnover, (2) β-adrenergic receptor (β-AR) expression and (3) β-AR-stimulated splenocyte cAMP production. Measures of sympathetic neurotransmission were correlated with age-related changes in Concanavalin A (Con A)-stimulated splenocyte proliferation. Results: Splenic NE turnover increased during middle age, then subsequently declined by 18 months of age compared with 8-month-old controls (young). Splenic NE concentration increased at 10 months and decreased at 18–24 months, compared with young rats; however, plasma NE levels were not affected by age. Plasma epinephrine levels were decreased at 24 months. NE synthesis blockade increased and decreased the rate of plasma catecholamine depletion in middle and old age, respectively. β-AR-stimulated cAMP production increased in splenocytes by 15 months. An age-related decrease in Con A-induced splenocyte proliferation was apparent by 10 months and persisted through 24 months. The decline in Con A-induced splenocyte proliferation correlated with the age-related increase in cAMP production. Conclusions: Aging alters sympathetic nervous system metabolism in the spleen to affect β-AR signaling to splenocytes, suggesting that altered sympathetic-immune modulation changes are evident by early middle age.
Influence of f-MLP, ACTH(1–24) and CRH on in vitro Chemotaxis of Monocytes from Centenarians
Authors: Genedani Susanna , Filaferro Monica , Carone Chiara , Ostan Rita , Bucci Laura , Cevenini Elisa , Franceschi Claudio , Monti Daniela
Published: November 2008

Objective: The lifelong exposure to a variety of stressors activates a plethora of defense mechanisms, including the hypothalamic-pituitary-adrenal axis which releases neuropeptides affecting the immune responses. Here, we report data on the capability of monocytes from young subjects and centenarians to migrate towards chemotactic stimuli (formyl-methionyl-leucyl-phenylalanine, f-MLP; adrenocorticotropic hormone, ACTH, and corticotrophin-releasing hormone, CRH). Plasma levels of ACTH, CRH and cortisol were measured as an index of ongoing stress response. Methods: Monocyte chemotaxis towards f-MLP (10–8M), ACTH(1–24) (10–14 and 10–8M) and CRH (10–14 and 10–8M) was evaluated in vitro in young subjects (n = 8, age range 25–35 years) and centenarians (n = 9, age >100 years) and expressed as chemotactic index. In 9 young subjects and 6 centenarians, plasma levels of cortisol, ACTH and CRH were measured. Results: Monocyte chemotaxis towards f-MLP, ACTH(1–24) and CRH (10–8M) was well preserved in centenarians, except when the lowest concentration of CRH was used. CRH, ACTH and cortisol plasma levels were significantly higher in centenarians than in young subjects. Conclusions: The capability of monocytes from centenarians to respond to chemotactic neuropeptides is well preserved. The decreased responsiveness to the lowest concentration of CRH might be due to downregulation of CRH receptors or to defects in the intracellular signal transduction pathway. The high plasma levels of cortisol, CRH and ACTH in centenarians indicate an activation of the entire stress axis, likely counteracting the systemic inflammatory process occurring with age. This activation fits with the hypothesis that lifelong low-intensity stressors activate ancient, hormetic defense mechanisms, favoring healthy aging and longevity.
Age-Associated Remodeling of Thymopoiesis: Role for Gonadal Hormones and Catecholamines
Authors: Leposavić Gordana , Perišić Milica
Published: November 2008

The present review summarizes recent data on age-related thymic changes termed thymic involution, and highlights the putative role of perturbances in extrathymical and, possibly, intrathymical production of gonadal steroids and catecholamines in this process. Thymic involution has been envisaged as an extremely complex process involving multifactorial mechanisms along the bone marrow-thymic axis that accounts for the major manifestations of immunosenescence. These mechanisms include basic cell aging processes (for example, cell replication and programmed cell death) and processes unique to the immune system (such as generation of the T cell receptor repertoire and control of potentially autoreactive cells). Given that the onset of age-associated thymic involution coincides with the rise in gonadal steroid levels at puberty, a causal link between these events has been suggested. It has been shown that: (1) peripubertal gonadectomy causes substantial decrease in the level of noradrenaline in adult male and female thymus and (2) catecholamines, acting via α- and β-adrenoceptor, produce suppressive effects on the thymic cellularity and production of both effector and regulatory T cells. Furthermore, the possibility that gonadal steroids contribute to thymic involution is discussed in this paper. In light of recent data indicating that effects of gonadal hormone deprivation on the thymic cellularity and function are long lasting but transitory, a putative role for the intrathymic sex steroid/catecholamine production in assuring the organ involution, under conditions of their limited supply by extrathymic sources, is also considered.
Gender-Specific Neuroimmunoendocrine Aging in a Triple-Transgenic 3×Tg-AD Mouse Model for Alzheimer’s Disease and Its Relation with Longevity
Authors: Giménez-Llort Lydia , Arranz Lorena , Maté Ianire , De la Fuente Mónica
Published: November 2008

In the present work, we briefly review the evidence on the key role played by the neuroimmunoendocrine network in the etiopathogenesis of Alzheimer’s disease (AD) and provide new behavioral, immune and endocrinological data obtained on old male and female triple-transgenic 3×Tg-AD mice harboring PS1M146V, APPSwe and tauP301L transgenes in contrast to wild-type animals. The results indicate that several aspects of the impairment of the neuroimmunoendocrine network that occurs with aging are more evident in the 3×Tg-AD mice, especially in males. This supports the hypothesis of a premature immunosenescence as a pathogenically relevant factor in AD which was found to be enhanced in the 3×Tg-AD males, suggesting that this could also be responsible for the increased morbidity and mortality of these subjects. Therefore, future research on strategies that could improve the immune system and the other regulatory systems, such as the nervous and the endocrine system, as well as their communication, could have preventive and/or therapeutical effects on that disease. The results also show the relevance of gender differences that should be taken into consideration in both basic and clinical research for assessing new strategies for the control of AD.
Antipituitary Antibodies in Dutch Patients with Idiopathic Hypopituitarism
Authors: de Graaff L.C.G. , De Bellis A. , Bellastella A. , Hokken-Koelega A.C.S.
Published: November 2008

Background: Despite extensive research, in the majority of patients with isolated growth hormone deficiency (IGHD) and multiple pituitary hormone deficiency (MPHD), the cause of their clinical picture remains unknown. Recent articles suggest that some cases of idiopathic growth hormone deficiency might be explained by a silent form of autoimmune hypophysitis based on the presence of antipituitary antibodies (APA) at high titers (>1:8). Methods: We collected clinical data and serum from 71 patients participating in the Dutch HYPOPIT study. APA screening in 40 IGHD patients and 31 MPHD patients was performed by an indirect immunofluorescence method. APA, when present, were related to clinical and morphological pituitary findings. Results: APA were present at high titers in 7 of 31 MPHD patients (23%) and 1 of 40 IGHD patients (2.5%). Among APA-positive MPHD patients, apart from growth hormone deficiency, all patients of pubertal age had gonadotroph defi- ciency, all had thyroid hormone deficiency and 50% had ACTH deficiency. Conclusion: The high frequency of APA in our idiopathic MPHD population indicates that, in 23% of the patients diagnosed with idiopathic MPHD, the hormone deficiencies might actually be caused by a silent form of autoimmune hypophysitis. Screening for APA should therefore be considered in all patients with ‘idiopathic’ MPHD.
Pamidronate Treatment of Children with Moderate-to-Severe Osteogenesis Imperfecta: A Note of Caution
Authors: Alharbi M. , Pinto G. , Finidori G. , Souberbielle J.C. , Guillou F. , Gaubicher S. , Le Merrer M. , Polak M.
Published: November 2008

Background/Aims: Bisphosphonates have been reported to decrease fractures related to osteogenesis imperfecta (OI). We assessed the efficacy and long-term safety of pamidronate therapy in patients with moderate-to-severe OI. Methods: We conducted an open-label uncontrolled study in 14 boys and 13 girls whose mean age was 6.8 years at baseline. Intravenous pamidronate, 1 mg/kg/day, was given for 3 consecutive days every 4 months for 2–6 years, with physical therapy and orthopedic surgery as appropriate. Mobility score, fracture rate, height, bone mineral density (BMD) and bone healing were evaluated throughout follow-up. Results: In 24 (89%) patients, the fracture rate decreased to ≤2/year and/or the mobility score improved. The remaining 3 (11%) patients continued to experience more than 2 fractures per year with mobility scores <2 despite significant BMD gains. Delayed radiographic fracture healing (>6 months) occurred in 8 (29.6%) patients; their BMD gains, baseline age and treatment duration were not significantly different from those in the other patients. Tolerance was good. Conclusion: Pamidronate with physiotherapy and orthopedic management improved outcomes without delaying fracture healing in 19 (70%) of 27 patients. Delayed fracture healing occurred in 8/27 patients. Pamidronate should be reserved for severe OI with multiple fractures and/or flattened vertebras.
European Multicentre Study in Children Born Small for Gestational Age with Persistent Short Stature: Comparison of Continuous and Discontinuous Growth Hormone Treatment Regimens
Authors: Phillip Moshe , Lebenthal Yael , Lebl Jan , Zuckerman-Levin Nehama , Korpal-Szczyrska Maria , Marques Jorge Sales , Steensberg Adam , Jons Kirsten , Kappelgaard Anne-Marie , Ibanez Lourdes
Published: November 2008

Background: The most effective growth hormone (GH) treatment regimen for increasing height in short children born small for gestational age (SGA) has not been well defined. Methods: Short SGA children (n = 151, age 3–8 years, height less than –2.5 standard deviation scores) were randomised to receive low-dose GH for 2 years (0.033/0.033 mg/kg/day, n = 51), high-dose GH for 1 year and then no treatment for 1 year (0.100/0 mg/kg/day, n = 51) or were untreated for 1 year then received mid-dose GH for 1 year (0/0.067 mg/kg/day, n = 47). Height, bone age and adverse events were determined at check-ups every 3 months. Results: The mean ± SD additional height gain with GH after 1 year, relative to untreated controls, was higher with discontinuous high-dose than with continuous low-dose GH (6.5 ± 0.2 vs. 3.3 ± 0.2 cm). After 2 years, the additional height gain was similar between high- and low-dose GH groups (between-group treatment difference = 0.2, 95% CI = –0.8 to 1.2 cm, p = 0.702). Patients treated exclusively in the last year had a similar height gain to those in the other treatment groups (p = 0.604). Conclusions: In short SGA children, continuous low-dose and discontinuous high-dose GH regimens were associated with similar height gain. Treatment with mid-dose GH for 1 year also led to a similar improvement in growth.