bluuebunny/crossref_metadata_2025 huggingface dataset:
A SYMMETRIC HYPERBOLIC FORMULATION OF THE GENERAL RELATIVISTIC MOMENT EQUATIONS FOR MATTER AND RADIATION
Authors: BANACH ZBIGNIEW
Published: March 2007

For a fluid-radiation mixture, i.e. a relativistic gas consisting of material particles and photons, we derive a 14D causal evolution system of first-order symmetric hyperbolic form for a set of basic physical gas-state variables, which is defined relative to a network of observers with arbitrary 4-velocities. This system is obtained by taking moments of the relativistic Boltzmann equation (the so-called central moments) and by truncating and closing the resulting system of moment equations by means of an appropriate (5+9)-moment closure prescription. The material medium under consideration is assumed to be a nonbarotropic perfect gas described by a local Jüttner equilibrium distribution function. With regards to the photon gas, we employ the modified Grad-type approach, which begins by expanding the phase density (i.e. the number density of photons) about a local Planck equilibrium distribution and including the trace-free anisotropic pressure in the expansion. The main advantage of using the above (5+9)-moment closure prescription is that the matter fluid's peculiar velocity and the radiative heat flux are incorporated into the model in a non-perturbative manner, thereby allowing virtually arbitrarily large values for the individual components of these dynamical variables. Within the framework of a reduced 3 + 1 orthonormal frame formalism, we also explain how to choose the initially arbitrary 4-velocity vector field, as this is crucial for the determination of the full 38D causal matter-radiation-gravity system.
Clotrimazole-sensitive K+ currents regulate pacemaker activity in interstitial cells of Cajal
Authors: Zhu Yaohui , Ye Jing , Huizinga Jan D.
Published: March 2007

Interstitial cells of Cajal (ICC) are pacemaker cells for gut peristaltic motor activity. Compared with cardiac pacemaker cells, little is known about mechanisms that regulate ICC excitability. The objective of the present study was to investigate a potential role for clotrimazole (CTL)-sensitive K currents ( ICTL) in the regulation of ICC excitability and pacemaker activity. ICC were studied in situ and in short-term culture by using the whole cell patch-clamp configuration. In situ, ICC exhibited spontaneous transient inward currents followed by transient outward currents. CTL blocked outward currents, thereby increasing the net inward currents, and depolarized ICC, thereby establishing CTL-sensitive channels as regulators of ICC pacemaker activity. In short-term culture, a ICTL was identified that showed increased conductance when depolarized from the resting membrane potential to 0 mV and subsequent inward rectification at further depolarized potentials. The ICTL markedly increased with increasing intracellular calcium and was insensitive to the ether-à-go-go-related K channel blocker E-4031 and the large-conductance calcium-activated K channel blocker iberiotoxin. ICTL contributed 3–9 nS to the whole cell conductance at 0 mV membrane potential under physiological conditions; it was fast activating (τ = 88 ms), showed little time-dependent inactivation, and exhibited a deactivation time constant of 38 ms. The nitric oxide donor sodium nitroprusside (SNP) increased ICTL. Single-channel activity, activated by calcium and SNP, was inhibited by CTL, with a single-channel conductance of ∼38 pS. In summary, ICC generate a ICTL on depolarization through an intermediate-conductance calcium-activated K channel that regulates pacemaker activity and ICC excitability.
Hypertrophic and dilated cardiomyopathy mutations differentially affect the molecular force generation of mouse α-cardiac myosin in the laser trap assay
Authors: Debold Edward P. , Schmitt J. P. , Patlak J. B. , Beck S. E. , Moore J. R. , Seidman J. G. , Seidman C. , Warshaw D. M.
Published: March 2007

Point mutations in cardiac myosin, the heart's molecular motor, produce distinct clinical phenotypes: hypertrophic (HCM) and dilated (DCM) cardiomyopathy. Do mutations alter myosin's molecular mechanics in a manner that is predictive of the clinical outcome? We have directly characterized the maximal force-generating capacity (Fmax) of two HCM (R403Q, R453C) and two DCM (S532P, F764L) mutant myosins isolated from homozygous mouse models using a novel load-clamped laser trap assay. Fmaxwas 50% (R403Q) and 80% (R453C) greater for the HCM mutants compared with the wild type, whereas Fmaxwas severely depressed for one of the DCM mutants (65% S532P). Although Fmaxwas normal for the F764L DCM mutant, its actin-activated ATPase activity and actin filament velocity ( Vactin) in a motility assay were significantly reduced (Schmitt JP, Debold EP, Ahmad F, Armstrong A, Frederico A, Conner DA, Mende U, Lohse MJ, Warshaw D, Seidman CE, Seidman JG. Proc Natl Acad Sci USA 103: 14525–14530, 2006.). These Fmaxdata combined with previous Vactinmeasurements suggest that HCM and DCM result from alterations to one or more of myosin's fundamental mechanical properties, with HCM-causing mutations leading to enhanced but DCM-causing mutations leading to depressed function. These mutation-specific changes in mechanical properties must initiate distinct signaling cascades that ultimately lead to the disparate phenotypic responses observed in HCM and DCM.
An analysis of the DOCA-salt model of hypertension in HO-1−/− mice and the Gunn rat
Authors: Nath Karl A. , d'Uscio Livius V. , Juncos Julio P. , Croatt Anthony J. , Manriquez Melissa C. , Pittock Siobhan T. , Katusic Zvonimir S.
Published: March 2007

Heme oxygenase-1 (HO-1) is induced in the vasculature in the DOCA-salt model of hypertension in rats. Whereas the HO system and its products may exert vasodilator effects, recent studies have suggested that the HO system may predispose to hypertension. The present study examined the effects of selected components of the HO system, specifically, the HO-1 isozyme and the product bilirubin in the DOCA-salt model of systemic hypertension; the experimental approach employed mutant rodent models, namely, the HO-1−/− mouse and the hyperbilirubinemic Gunn rat. DOCA-salt induced HO-1 protein in the aorta in HO-1+/+ mice and provoked a significant rise in systolic arterial pressure in HO-1−/− mice but not in HO-1+/+ mice; this effect could not be ascribed to impaired urinary sodium excretion or impaired glomerular filtration rate in the DOCA-salt-treated HO-1−/− mice. The administration of DOCA salt to uninephrectomized rats significantly increased systolic arterial pressure in wild-type rats, an effect that was attenuated in the mutant Gunn rat; this reduction in systemic hypertension in the DOCA-salt-treated Gunn rat was not due to a greater induction of HO-1 in the vasculature or to a more avid urinary sodium excretion. DOCA-salt impaired endothelium-dependent and endothelium-independent vasorelaxation in wild-type rats but not in Gunn rats; prior exposure to bilirubin repaired the defect in endothelium-dependent vasorelaxation in aortic rings in DOCA-salt-treated rats. DOCA salt stimulated vascular production of superoxide anion in wild-type but not in Gunn rats. We suggest that HO-1 and the product bilirubin may exert a countervailing effect in the DOCA-salt model of systemic hypertension.
Cardiovascular dysfunction in Zucker obese and Zucker diabetic fatty rats: role of hydronephrosis
Authors: Marsh Susan A. , Powell Pamela C. , Agarwal Anupam , Dell'Italia Louis J. , Chatham John C.
Published: March 2007

Recent studies in our laboratory using the Zucker obese (ZO) and Zucker diabetic fatty (ZDF) rat models resulted in unexpectedly high mortality rates in all genotypes including healthy homozygous lean Zucker rats, possibly because of renal dysfunction. Therefore, we evaluated left ventricular (LV) and kidney morphology and function in young ZO, Zucker diabetic fatty obese (ZDFO), homozygous Zucker/ZDF lean (ZL), and Sprague-Dawley (SD) rats. Hydronephrosis was evident in ZL, ZO, and ZDFO but not SD kidneys. ZDFO rats exhibited impaired LV shortening and relaxation with increased arterial stiffness. LV wall thickness was lower and LV end-systolic wall stress was higher in ZDFO compared with SD rats. Plasma ANG II was lower in ZO and ZDFO rats, which may be a result of reduced renal parenchyma with hydronephrosis; norepinephrine was higher in ZDFO rats than SD controls. Covariate analysis indicated that LV end-systolic wall stress was associated with renal dysfunction. The presence of hydronephrosis and its association with LV dysfunction potentially limits the ZDF model for study of the effects of diabetes on renal and cardiovascular function.
Stroke and Vascular Cognitive Impairment
Authors: Hachinski Vladimir
Published: March 2007

Advances in stroke are occurring at an unprecedented pace, but often in disciplinary isolation and without optimal mechanisms for systematically translating, integrating and applying the findings.

Knowledge accrues in pieces, but is understood in patterns. To optimize knowledge acquisition and application, infrastructures and systems need to be set up along with appealing incentives. The approach needs to be
transdisciplinary
, going beyond the bounds of any given discipline, reciprocally
translational
, and
transactional
, meaning that the interchanges have to yield previously agreed benefits to the parties (
The Triple T Approach
). A new breed of leaders needs to be developed and nurtured to catalyze the process.

Opportunities abound. Stroke and most brain diseases share the same pathophysiological fundamental mechanisms. An integrated, systematic approach to these processes could yield not only greater understanding but new, common therapeutic targets for several diseases.
Biphasic clinical trials
could combine the best features of pragmatic and explanatory, randomized clinical trials. The greatest opportunity of all may be the largely under-explored and under-exploited borderlands between cerebrovascular and Alzheimer disease. One in three of us will have a stroke, become demented, or both. For each person who has a stroke or Alzheimer disease, two have some cognitive impairment short of dementia, often subclinical cerebrovascular disease on a substrate of Alzheimer changes. The fact that cerebrovascular and Alzheimer disease share the same risk factors, provide a great opportunity for prevention, if implemented at the
“brain at risk”
stage.

Systematically integrating what we know and evaluating what we do
could spur progress. Research is not only an activity but an attitude. Making evaluation and incentives to excel part of the funding of all stroke activities would yield far ranging cumulative improvements in all aspects of stroke.

No system can replace the individual initiative, creativity and insights that lead to the great discoveries, but progress is not made by breakthroughs alone. No one’s work is so exalted that it cannot be improved, nor so humble that it has no value. We can all make a difference.
Activity Level and Subjective Knee Function 15 Years after Anterior Cruciate Ligament Injury
Authors: Kostogiannis Ioannis , Ageberg Eva , Neuman Paul , Dahlberg Leif , Friden Thomas , Roos Harald
Published: March 2007

Background

The activity level and subjective knee function after an anterior cruciate ligament (ACL) injury treated without reconstruction have not been well elucidated.

Hypothesis

Patients with ACL injury can achieve good knee function and satisfactory long-term activity level when treated by early activity modification combined with rehabilitation.

Study Design

Cohort study (prognosis); Level of evidence, 2.

Materials and Methods

One hundred patients with an acute total ACL injury were observed for 15 years. All patients initially underwent arthroscopic surgery and a rehabilitation program. They were advised to modify their activity level, especially by avoiding contact sports. Patients with recurrent giving-way episodes and/or secondary meniscal injuries that required fixation (n = 6) were subsequently excluded and underwent reconstruction (n = 22). Sixty-seven patients with unilateral nonreconstructed ACL injury remained at the 15-year follow-up. The Lysholm knee score, Tegner activity level, and a visual analog score for global knee function were recorded at regular intervals. At the final follow-up, patients were further evaluated with the Knee injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) subjective knee evaluation form.

Results

Forty patients resumed their preinjury activity level or higher within 3 years. The median activity level 15 years after injury had decreased from 7 to 4 according to Tegner activity scale (P < .001). The mean Lysholm knee score was 96 and 95, 1 and 3 years after injury, respectively, but declined to 86 after 15 years (P < .001). Forty-nine patients had good/excellent results, and 14 had fair (n = 6) or poor function (n = 8) at 15 years. Patients injured in contact sports scored lower in the quality of life sub-scale of KOOS than those injured in noncontact sports (P < .05). Thirteen of the 67 patients (19%) were reoperated with an arthroscopic procedure because of knee symptoms.

Conclusion

Early activity modification and neuromuscular rehabilitation resulted in a good knee function and an acceptable activity level in the majority of the nonreconstructed patients. The decline in activity level of patients engaged in contact sports at the time of injury affected their subjective quality of life more than patients involved in noncontact sports.
EGO, a novel, noncoding RNA gene, regulates eosinophil granule protein transcript expression
Authors: Wagner Lori A. , Christensen Clarissa J. , Dunn Diane M. , Spangrude Gerald J. , Georgelas Ann , Kelley Linda , Esplin M. Sean , Weiss Robert B. , Gleich Gerald J.
Published: March 2007

Gene expression profiling of early eosinophil development shows increased transcript levels of proinflammatory cytokines, chemokines, transcription factors, and a novel gene, EGO (eosinophil granule ontogeny). EGO is nested within an intron of the inositol triphosphate receptor type 1 (ITPR1) gene and is conserved at the nucleotide level; however, the largest open reading frame (ORF) is 86 amino acids. Sucrose density gradients show that EGO is not associated with ribosomes and therefore is a noncoding RNA (ncRNA). EGO transcript levels rapidly increase following interleukin-5 (IL-5) stimulation of CD34+ hematopoietic progenitors. EGO RNA also is highly expressed in human bone marrow and in mature eosinophils. RNA silencing of EGO results in decreased major basic protein (MBP) and eosinophil derived neurotoxin (EDN) mRNA expression in developing CD34+ hematopoietic progenitors in vitro and in a CD34+ cell line model. Therefore, EGO is a novel ncRNA gene expressed during eosinophil development and is necessary for normal MBP and EDN transcript expression.
Case-control and family-based association studies of candidate genes in autistic disorder and its endophenotypes: TPH2 and GLO1
Authors: Sacco Roberto , Papaleo Veruska , Hager Jorg , Rousseau Francis , Moessner Rainald , Militerni Roberto , Bravaccio Carmela , Trillo Simona , Schneider Cindy , Melmed Raun , Elia Maurizio , Curatolo Paolo , Manzi Barbara , Pascucci Tiziana , Puglisi-Allegra Stefano , Reichelt Karl-Ludvig , Persico Antonio M
Published: March 2007

Background

The TPH2 gene encodes the enzyme responsible for serotonin (5-HT) synthesis in the Central Nervous System (CNS). Stereotypic and repetitive behaviors are influenced by 5-HT, and initial studies report an association of TPH2 alleles with childhood-onset obsessive-compulsive disorder (OCD) and with autism. GLO1 encodes glyoxalase I, the enzyme which detoxifies α-oxoaldehydes such as methylglyoxal in all living cells. The A111E GLO1 protein variant, encoded by SNP C419A, was identifed in autopsied autistic brains and proposed to act as an autism susceptibility factor. Hyperserotoninemia, macrocephaly, and peptiduria represent some of the best-characterized endophenotypes in autism research.

Methods

Family-based and case-control association studies were performed on clinical samples drawn from 312 simplex and 29 multiplex families including 371 non-syndromic autistic patients and 156 unaffected siblings, as well as on 171 controls. TPH2 SNPs rs4570625 and rs4565946 were genotyped using the TaqMan assay; GLO1 SNP C419A was genotyped by PCR and allele-specific restriction digest. Family-based association analyses were performed by TDT and FBAT, case-control by χ2, endophenotypic analyses for 5-HT blood levels, cranial circumference and urinary peptide excretion rates by ANOVA and FBAT.

Results

TPH2 alleles and haplotypes are not significantly associated in our sample with autism (rs4570625: TDT P = 0.27, and FBAT P = 0.35; rs4565946: TDT P = 0.45, and FBAT P = 0.55; haplotype P = 0.84), with any endophenotype, or with the presence/absence of prominent repetitive and stereotyped behaviors (motor stereotypies: P = 0.81 and 0.84, verbal stereotypies: P = 0.38 and 0.73 for rs4570625 and rs4565946, respectively). Also GLO1 alleles display no association with autism (191 patients vs 171 controls, P = 0.36; TDT P = 0.79, and FBAT P = 0.37), but unaffected siblings seemingly carry a protective gene variant marked by the A419 allele (TDT P < 0.05; patients vs unaffected siblings TDT and FBAT P < 0.00001).

Conclusion

TPH2 gene variants are unlikely to contribute to autism or to the presence/absence of prominent repetitive behaviors in our sample, although an influence on the intensity of these behaviors in autism cannot be excluded. GLO1 gene variants do not confer autism vulnerability in this sample, but allele A419 apparently carries a protective effect, spurring interest into functional correlates of the C419A SNP.
Evaluation of the structural quality of modeled proteins by using globularity criteria
Authors: Costantini Susan , Facchiano Angelo M , Colonna Giovanni
Published: March 2007

Background

The knowledge of the three-dimensional structure of globular proteins is fundamental for a detailed investigation of their functional properties. Experimental methods are too slow for structure investigation on a large scale, while computational prediction methods offer alternatives that are continuously being improved. The international Comparative Assessment of Structure Prediction (CASP), an "a posteriori" evaluation of the quality of theoretical models when the experimental structure becomes available, demonstrates that predictions can be successful as well as unsuccessful, and this suggests the necessity for evaluations able to discard "a priori" the wrong models.

Results

We analyzed different structural properties of globular proteins for experimentally solved proteins belonging to the four different structural classes: "mainly alpha", "mainly beta", "alpha/beta" and "alpha+beta". The properties were found to be linearly correlated to protein molecular weight, but with some differences among the four classes. These results were applied to develop an evaluation test of theoretical models based on the expected globular properties of proteins. To verify the success of our test, we applied it to several protein models submitted to the sixth edition of CASP. The best theoretical models, as judged by CASP assessors, were in agreement with the expected properties, while most of the low-quality models had not passed our evaluations.

Conclusion

This study supports the need for careful checks to avoid the diffusion of incorrect structural models. Our test allows the evaluation of models in the absence of experimental reference structures, thereby preventing the diffusion of incorrect structural models and the formulation of incorrect functional hypotheses. It can be used to check the globularity of predicted models, and to supplement other methods already used to evaluate their quality.
Can cancer patients assess the influence of pain on functions? A randomised, controlled study of the pain interference items in the Brief Pain Inventory
Authors: Stenseth Guri , Bjørnnes Marit , Kaasa Stein , Klepstad Pål
Published: March 2007

Background

The Brief Pain Inventory (BPI) is recommended as a pain measurement tool by the Expert Working Group of the European Association of Palliative Care. The BPI is designed to assess both pain severity and interference with functions caused by pain. The purpose of this study was to investigate if pain interference items are influenced by other factors than pain.

Methods

We asked adult cancer patients to complete the original and a revised BPI on two study days. In the original version of the BPI the patients were asked how, during the last 24 hours, pain has interfered with functions. In the revised BPI this question was changed to how, during the last 24 hours, these functions are affected in general. Heath related quality of life was assessed at both study days applying the European Organization for Research and Treatment of Cancer quality of life questionnaire.

Results

Forty-eight of the 55 included patients completed both assessments. The BPI pain intensities scores and the health related quality of life scores were similar at the two study days. Except for mood this study observed no significant distinctions between the patients' BPI interference items scores in the original (pain influence on function) and the revised BPI (function in general). Seventeen patients reported higher influence from pain on functions than the total influence on function from all causes.

Conclusion

We observed similar scores in the original BPI interference scores (pain influence on function) compared with the revised BPI interference scores (decreased function in general). This finding might imply that the BPI interference scale measures are partly responded to as more of a global interference measure.
Adipocytokines and the Regulation of Lipid Metabolism in Growth Hormone Transgenic and Calorie-Restricted Mice
Authors: Wang Zhihui , Masternak Michal M. , Al-Regaiey Khalid A. , Bartke Andrzej
Published: March 2007

Chronic elevation of GH induces resistance to insulin and hyperinsulinemia in both humans and animals, whereas calorie restriction (CR) improves peripheral insulin sensitivity in many species. To investigate the mechanisms that lead to insulin resistance in animals with high levels of GH as well as the mechanisms that might improve insulin sensitivity, we fed GH-overexpressing transgenic mice ad libitum or subjected them to 30% CR. We then assayed the plasma adipocytokines levels related to insulin sensitivity, plasma lipid levels, and tissue triglycerides accumulation and examined adipocyte morphology. Furthermore, we evaluated mRNA expression and protein levels of enzymes or regulators involved in regulating hepatic lipid metabolism. Our results suggest that decreased plasma adiponectin, increased plasma resistin and cholesterol, and elevated levels of TNF-α and IL-6 in adipocytes may all contribute to the insulin resistance observed in GH-Tg mice. Increased accumulation of triglycerides and impaired adipocytes differentiation in GH-transgenic mice provide plausible mechanisms for the alterations of adipocytokines. Hepatic and muscle insulin resistance in these mice is probably related to excessive accumulation of fatty acids and their metabolites. An increase in plasma adiponectin and decrease in plasma IL-6, triglycerides, and cholesterol levels in response to CR may improve insulin sensitivity.
Structural Behaviour of Mortar-Less Interlocking Masonry System under Eccentric Compressive Loads
Authors: Thanoon Waleed A. , Jaafar M.S. , Noorzaei J. , Kadir M. Razali A. , Fares S.
Published: March 2007

Interlocking masonry wall as a structural load-bearing element is still unexplored simply because its basic behaviour and complete response to failure is not known. In addition, there is no design code available to provide necessary guidance for a safe design of interlocking walls. This paper provides an attempt to ascertain the structural response of interlocking masonry walls compared to conventional bonded walls. Individual block units, prisms and full-scale wall specimens were tested under the action of concentric and eccentric compressive loads. The effect of different patterns of reinforced concrete stiffeners has also been investigated. The test results were discussed in terms of wall efficiency, strength capacity, deflection, strain distribution, cracking patterns and failure modes. The results indicate a promising future use of the interlocking masonry system in construction.
Database Consistency Using Update-Ordering in Distributed Databases
Authors: Shuhadah W. N. , Deris M. Mat , Noraziah A. , Saman M.Y. , Rabiei M.
Published: March 2007

Database consistency is one of the major issues in replicated database in distributed database systems. The logical design for the replicated nodes and the transaction management mechanism are two aspects that give a serious impact to the performance and the consistency of replicated databases. This paper proposes a new model that combines the Neighbor Replication on Grid (NRG), where the data is replicated to the neighbors of the grid with the Update Ordering approach. The performance comparison shows that the proposed mechanism greatly improves the performance of the replicated database up to two orders of magnitude while preserving the data consistency.
Non-Overlapping Domain Decomposition Algorithm for the Hermite Radial Basis Function Meshless Collocation Approach: Applications to Convection Diffusion Problems
Authors: Rosales A. Hernandez , Power H.
Published: March 2007

In the particular case of solving large-scale boundary value problems, the computational cost derived as a result of the application of any numerical scheme represent a determinant factor in the determination of its computational efficiency. The present work studies the influence of the non-overlapping domain decomposition and higher order interpolation functions on the Hermite radial basis collocation method, as a way to improve its efficiency under high demanding numerical conditions. A series of high Péclet convection diffusion and multi-zone problems are tested. Comparison between the numerical results and its analytical solution is carried out for each of them.
Sex Differences in Heritability of Neck Pain
Authors: Fejer René , Hartvigsen Jan , Kyvik Kirsten Ohm
Published: March 2007

Experimental studies have suggested biological factors as a possible explanation for gender disparities in perception of pain. Recently, heritability of liability to neck pain (NP) has been found to be statistically significantly larger in women compared to men. However, no studies have been conducted to determine whether the sex differences in heritability of NP are due to sex-specific genetic factors. Data on lifetime prevalence of NP from a populationbased cross-sectional survey of 33,794 Danish twins were collected and age-stratified univariate biometrical modeling using sex-limitation models was performed based on 10,605 dizygotic (DZ) twins of opposite sex to estimate the qualitative sex differences. In a full sex-limitation model the genetic component in females were higher than in males, but the genetic and the shared environmental correlations were equal to what is normally assumed between same-sex DZ twins. A ‘no-sex-effects’ model showed the overall best model fit which confirms absence of sex-related gene interaction. The age-stratified sex-limitation models showed similar results. Thus, there is no evidence for a sex-specific genetic influence in the liability of heritability of NP.
Heritability of the Second to Fourth Digit Ratio (2d:4d): A Twin Study
Authors: Paul Simon N. , Kato Bernet S. , Cherkas Lynn F. , Andrew Toby , Spector Tim D.
Published: March 2007

The second to fourth finger length ratio (2d:4d) has been the subject of much recent work and is thought to be related to diverse gender and hormone-related traits including sports ability, disease susceptibility, attractiveness and sexuality. It is established in utero and remains constant in adulthood. Familial clustering has been thought to contribute to the development of 2d:4d from early studies but no twin studies exploring heritability have been reported to date. In this study, a sample of 456 female twin pairs (148 monozygotic [MZ], 308 dizygotic [DZ]) aged 18 to 79 years was used to estimate the heritability of 2d:4d for the right and left hands. Finger lengths were derived from hand xrays. Variance components analysis was used to estimate and contrast genetic and environmental effects on this phenotype. The mean 2d:4d was 0.92 (SD = 0.001) for both hands. The MZ intraclass correlation was higher than in DZ (.66 vs. .35 for right 2d:4d, and .71 vs. .37 for left 2d:4d). The best fit model included additive polygenic and unique environmental effects (‘AE’ model), with no significant common environmental effects detected. Heritability was estimated to be approximately 66% for 2d:4d (95% confidence interval 0.5–0.78). These results suggest a substantial genetic contribution to the determination of this hormonally related skeletal ratio in women, which could be more influential than the effects of common prenatal environmental factors. However the current study design does not preclude the possibility of confounding between heritability estimates and unobserved prenatal effects.
Efficacy of Retrospective Recall of Attention-Deficit Hyperactivity Disorder Symptoms: A Twin Study
Authors: Schultz Mark R. , Rabi Keren , Faraone Stephen V. , Kremen William , Lyons Michael J.
Published: March 2007

Attention-deficit hyperactivity disorder (ADHD) is currently recognized as a neurobiological, genetically based disorder in both children and adults. In this article we examine whether, by using a sample of middle-aged male twin veterans, the phenotypic characterization, prevalence, heritability and the longitudinal course of the illness is comparable to results observed in samples of children and adolescents. We evaluated the utility of adult reports of lifetime ADHD symptoms by examining the heritability of retrospectively reported childhood symptoms, using both symptom-based and discrete classification- based approaches, as well as examining the persistence of ADHD symptoms into adulthood for that subsample of individuals who were judged to possibly have ADHD as children. Our results showed prevalence rates that were approximately similar to those observed in other studies, demonstrable familiality, similar item endorsement patterns, a strong genetic association between hyperactive and inattentive subtypes, and a longitudinal decline in symptom severity. We concluded that while assessing ADHD in adult probands may be less accurate than with children or adolescents, since it demonstrates several characteristics in common with other assessment techniques it remains a viable diagnostic and research strategy, even with population samples.
Linguistic Features of Japanese Twins at 3 or 4 Years of Age Evaluated by Illinois Test of Psycholinguistic Abilities
Authors: Kobayashi Yoko , Hayakawa Kazuo , Hattori Rituko , Ito Mikiko , Kato Kenji , Hayashi Chisato , Mikami Hiroshi
Published: March 2007

In general, twins have delayed language development early in childhood compared with singletons. The purpose of this study was to clarify the overall linguistic features of twins. A Japanese version of the Illinois Test of Psycholinguistic Abilities (ITPA) was administered in 24 twin pairs (aged 3 to 4 years) at their own homes. The overall language abilities of the twins were in the normal range (based on ITPA normative data: mean scale score 36.0 ± 6.0 points), and for the ITPA subtests only, Auditory Reception fell within the range of language disorder (mean scale score 24.9 ± 5.1 points). The findings suggest that in 3- to 4-year-old Japanese twins, overall language abilities are not delayed. However, there may be specific difficulties with auditory reception skills.
A Note on the Asymptotic Distribution of Likelihood Ratio Tests to Test Variance Components
Authors: Visscher Peter M.
Published: March 2007

When using maximum likelihood methods to estimate genetic and environmental components of (co)variance, it is common to test hypotheses using likelihood ratio tests, since such tests have desirable asymptotic properties. In particular, the standard likelihood ratio test statistic is assumed asymptotically to follow a χ2distribution with degrees of freedom equal to the number of parameters tested. Using the relationship between least squares and maximum likelihood estimators for balanced designs, it is shown why the asymptotic distribution of the likelihood ratio test for variance components does not follow a χ2distribution with degrees of freedom equal to the number of parameters tested when the null hypothesis is true. Instead, the distribution of the likelihood ratio test is a mixture of χ2distributions with different degrees of freedom. Implications for testing variance components in twin designs and for quantitative trait loci mapping are discussed. The appropriate distribution of the likelihood ratio test statistic should be used in hypothesis testing and model selection.
High Microsatellite and SNP Genotyping Success Rates Established in a Large Number of Genomic DNA Samples Extracted From Mouth Swabs and Genotypes
Authors: Min Josine L. , Lakenberg Nico , Bakker-Verweij Margreet , Suchiman Eka , Boomsma Dorret I. , Slagboom P. Eline , Meulenbelt Ingrid
Published: March 2007

In this article, we present the genomic DNA yield and the microsatellite and single nucleotide polymorphism (SNP) genotyping success rates of genomic DNA extracted from a large number of mouth swab samples. In total, the median yield and quality was determined in 714 individuals and the success rates in 378,480 genotypings of 915 individuals. The median yield of genomic DNA per mouth swab was 4.1 μg (range 0.1–42.2 μg) and was not reduced when mouth swabs were stored for at least 21 months prior to extraction. A maximum of 20 mouth swabs is collected per participant. Mouth swab samples showed in, respectively, 89% for 390 microsatellites and 99% for 24 SNPs a genotyping success rate higher than 75%. A very low success rate of genotyping (0%–10%) was obtained for 3.2% of the 915 mouth swab samples using microsatellite markers. Only 0.005% of the mouth swab samples showed a geno-typing success rate lower than 75% (range 58%–71%) using SNPs. Our results show that mouth swabs can be easily collected, stored by our conditions for months prior to DNA extraction and result in high yield and high-quality DNA appropriate for genotyping with high success rate including whole genome searches using microsatellites or SNPs.
Familial Risks for Diseases of Myoneural Junction and Muscle in Siblings Based on Hospitalizations and Deaths in Sweden
Authors: Hemminki Kari , Li Xinjun , Sundquist Kristina
Published: March 2007

Diseases of the myoneural junction and muscle are disabling and some are life-threatening. Recent successes in the identification of the underlying genetic mechanisms have had profound implication for their diagnostics, treatment and classification. We define familial risks for siblings who were hospitalized for or deceased from diseases of the myoneural junction and muscle. A nationwide database on diseases of the myoneural junction and muscle was constructed by linking the Multigeneration Register on 0- to 69-year-old siblings to the Hospital Discharge Register and the Causes of Death Register from years 1987 to 2001. Standardized risk ratios (SIRs) were calculated for affected sibling pairs by comparing to those whose siblings had no diseases of myoneural junction and muscle. Among a total of 2307 patients, myasthenia gravis, muscular dystrophy and myotonic disorders were commonest diagnoses. The sibling risks for these disease were 22, 190 and 198, respectively, when a sibling was diagnosed with any disease of the myoneural junction and muscle. The concordant SIRs, both siblings presenting the same disease, were 42 for myasthenia gravis, 737 for muscular dystrophy, 2000 for congenital myopathy, 1211 for myotonic disorder, 909 for periodic paralysis and 209 for unspecified myopathy. Only a few discordant sibling pairs were noted. The very high overall SIRs for the diseases of the myoneural junction and muscle imply that the sporadic forms of these diseases are relatively rare and these diseases are overwhelmingly heritable.
Genetic Influences on Free and Cued Recall in Long-Term Memory Tasks
Authors: Volk Heather E. , McDermott Kathleen B. , Roediger Henry L. , Todd Richard D.
Published: March 2007

Long-term memory (LTM) problems are associated with many psychiatric and neurological illnesses and are commonly measured using free and cued recall tasks. Although LTM has been linked with biologic mechanisms, the etiology of distinct LTM tasks is unknown. We studied LTM in 95 healthy female twin pairs identified through birth records in the state of Missouri. Performance on tasks of free recall of unrelated words, free and cued recall of categorized words, and the vocabulary section of the Wechsler Adult Intelligence Scale (WAIS-R) were examined using structural equation modeling. Additive genetic and unique environmental factors influenced LTM and intelligence. Free recall of unrelated and categorized words, and cued recall of categorized words, were moderately heritable (55%, 38%, and 37%). WAIS-R vocabulary score was highly heritable (77%). Controlling for verbal intelligence in multivariate analyses of recall, two components of genetic influence on LTM were found; one for all three recall scores and one for free and cued categorized word recall. Recall of unrelated and categorized words is influenced by different genetic and environmental factors indicating heterogeneity in LTM. Verbal intelligence is etiologically different from LTM indicating that these two abilities utilize different brain functions.
Sex Differences in Symptoms of Depression in Unrelated Individuals and Opposite-Sex Twin and Sibling Pairs
Authors: Middeldorp Christel M. , Wray Naomi R. , Andrews Gavin , Martin Nicholas G. , Boomsma Dorret I.
Published: March 2007

Diagnosis of a major depressive episode by theDiagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Associationrequires 5 out of 9 symptoms to be present. Therefore, individuals may differ in the specific symptoms they experience and reach a diagnosis of depression via different pathways. It has been suggested that depressed women more often report symptoms of sleep disturbance, appetite or weight disturbance, fatigue, feelings of guilt/worthlessness and psychomotor retardation than depressed men. In the current study, we investigate whether depressed men and women differ in the symptoms they report. Two samples were selected from a sample of Dutch and Australian twins and siblings. First, Dutch and Australian unrelated depressed individuals were selected. Second, a matched epidemiological sample was created consisting of opposite-sex twin and sibling pairs in which both members were depressed. No sex differences in prevalence rates for symptoms were found, with the exception of decreased weight in women in the sample of unrelated individuals. In general, the similarities in symptoms seem to far outweigh the differences in symptoms between men and women. This signifies that men and women are alike in their symptom profiles for major depression and genes for depression are probably expressed in the same way in the two sexes.
Stillbirths in Multiple Births: Test of Independence
Authors: Fellman Johan , Eriksson Aldur W.
Published: March 2007

The stillbirth rate in twins is a more sensitive indicator of environmental hazards than the stillbirth rate in singletons. Medical care or other socioeconomic factors may be more influential for perinatal survival in twin than in single deliveries. Studies have indicated that stillbirths among children in a set of multiple maternities are not independent. Models were considered assuming independent outcomes within a set of multiple maternities. Analyses of the stillbirth rates confirm that the risk of stillbirth among males is almost constantly higher than among females. Any model introduced should assume different stillbirth rates for males and females. The models were tested with both maximum likelihood and minimum χ2 methods. Data was analyzed from Sweden, the Åland Islands, Saxony, England and Wales, and significant discrepancies obtained from the independence models. The same-sexed twin data contain both monozygotic and dizygotic twin sets with apparently different stillbirth rates. Consequently, for same-sexed twins the proposed model could be considered too simple. After improvement by splitting the same-sexed data into monozygotic and dizygotic twin sets, the dependence still remains. The proportion of both same-sexed and opposite-sexed twin pairs that contain two stillborn is greater than what the stillbirth rates and the independence should indicate. Consequently, stillbirth rate estimates based on the relative frequency of twin sets with two stillborn children have a positive bias. When the stillbirth rate decreases, the number of sets with two stillborn children decreases more slowly than would be indicated by independence.
HealthTwiSt: The Berlin Twin Registry
Authors: Busjahn Andreas
Published: March 2007

The Berlin Twin Registry began as a short-term local project and developed into a resource that now serves partners throughout Germany and Europe. A twin registry as a private company is a different approach with pros and cons. Compared to academic institutions, there are greater flexibilities in collaborations, as well as acquisition and use of research funds. Recruitment is based on invitation in the context of the mass media coverage of scientific results. Phenotyping in normal twin subjects is concentrated on intermediate phenotypes that can bear on common diseases. These phenotypes include proteomic approaches and gene expression. Some results are briefly described to give an impression of the range of research topics and related opportunities for retrospective and prospective collaborative research.
CoSMoS and TwinPaW: Initial Report on Two New German Twin Studies
Authors: Spinath Frank M. , Wolf Heike
Published: March 2007

After briefly recapitulating two earlier German twin studies (BiLSAT and GOSAT), we present two new German twin studies with a longitudinal perspective: CoSMoS and TwinPaW. The twin study on Cognitive ability, Self-reported Motivation and School performance (CoSMoS) aims to investigate predictors and influences of school performance in a genetically sensitive design, beginning with children in late elementary school. The Twin study on Personality And Wellbeing (TwinPaW) focuses on adult personality and its relation to physical health as well as health-related behavior in an adult sample of twins. Both studies are characterized by an effort to recruit new large twin samples through a novel recruitment procedure aimed at reducing self-selective sampling. In two German federal states, contact information on persons born on the same day and with the same name was retrieved from record sections. From the resulting pool of more than 36,000 addresses we contacted approximately 2000 parents of twins aged 9 and 10 for CoSMoS, as well as 2000 adult twin pairs for TwinPaW by telephone and mail. Personal contact by telephone proved to be more efficient with agreement rates of 63% in the children sample and 65% in the adult sample. In this article we briefly describe the rationale and the study aims of CoSMoS and TwinPaW as well as the characteristics of the sample we have recruited so far.
The Osaka University Aged Twin Registry: Epigenetics and Identical Twins Discordant for Aging-Dependent Diseases
Authors: Hayakawa Kazuo , Kato Kenji , Onoi Miyuki , Yang-Ping Cai , Kanamori Masao , Doi Syuichi , Hayashi Chisato , Kikuchi Hiroyuki , Nishihara Reiko , Kadota Kensuke
Published: March 2007

The Osaka University Aged Twin Registry (OUATR) is the largest adult twin registry in Japan. Since its establishment in 1974, the OUATR has conducted a number of studies with particular focus on the environmental contribution to physical–cognitive–mental aging, longevity and aging-dependent diseases in later adulthood. The registry consists of 12,000 pairs of Japanese twins born between 1900 and 1935. Two hundred and fifty pairs of twins have undergone comprehensive medical examination to date. Follow-up questionnaires have been mailed out on a regular basis, for the purpose of checking current vital statuses, health conditions, and so forth. The main objective of this longitudinal twin study is to contribute to the prevention of lifestyle-related diseases and the promotion of successful aging.
Twin Database of the Secondary School Attached to the Faculty of Education of the University of Tokyo
Authors: Ooki Syuichi , Asaka Akio
Published: March 2007

This article profiles the historical twin databases of the secondary education school attached to the Faculty of Education at the University of Tokyo. The school was established in 1948. Every year, about 50 pairs of twins of all sex and zygosity combinations and aged 11 to 12 years take an examination, and about 10 to 20 pairs are admitted based on the results. Three independent datasets exist: one for applicants (11–12 years), one for students (12–18 years), and one for graduates (18–72 years). These three historical databases and research perspectives are introduced herein.
Population-Based Database of Multiples in Childhood of Ishikawa Prefecture, Japan
Authors: Ooki Syuichi
Published: March 2007

A new type of population-based database of multiples in childhood at the prefecture level was initiated in 2004 in Ishikawa Prefecture, Japan. We conducted an exhaustive search for demographic information concerning families with multiples, family support provided by governmental and medical institutions by mailed questionnaire, and at the same time tried to organize a human network to support such families. This registry aims not only to aid research on human genetics and maternal and child health, but also to contribute to the development of welfare programs for families with multiples.
Update on the NAS-NRC Twin Registry
Authors: Page William F.
Published: March 2007

The National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry is one of the oldest, national population-based twin registries in the United States. It consists of 15,924 white male twin pairs born in the years 1917 to 1927 (inclusive), both of whom served in the armed forces, mostly during World War II. This article updates activity in this registry since the earlier 2002 article in Twin Research. The results of clinically based studies on dementia, Parkinson's disease, age-related macular degeneration, and primary osteoarthritis were published, as well as articles based on previously collected questionnaire data on chronic fatigue syndrome, functional limitations, and healthy aging. In addition, risk factor studies are being planned to merge clinical data with earlier collected risk factor data from questionnaires. Examination data from the subset of National Heart, Lung, and Blood Institute (NHLBI) twins resulted in a number of articles, including the relationship of endogenous sex hormones to coronary heart disease and morphological changes in aging brain structures. The NEO Five-Factor Personality Inventory (a paper-and-pencil self-administered questionnaire) has been fielded for the first time. A push to consolidate the various data holdings of the registry is being made.