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Young adult involvement in sexual behavior typically occurs within a relationship context, but we know little about the ways in which specific features of romantic relationships influence sexual decision-making. Prior work on sexual risk taking focuses attention on health issues rather than relationship dynamics. We draw on data from the Toledo Adolescent Relationships Study (TARS) (n = 475) to examine the association between qualities and dynamics of current/most recent romantic relationships such as communication and emotional processes, conflict, demographic asymmetries, and duration and the management of sexual risk. We conceptualize 'risk management' as encompassing multiple domains, including (1) questioning the partner about previous sexual behaviors/risks, (2) using condoms consistently, and (3) maintaining sexual exclusivity within the relationship. We identify distinct patterns of risk management among dating young adults and find that specific qualities and dynamics of these relationships are linked to variations in risk management. Results from this paper suggest the need to consider relational dynamics in efforts to target and influence young adult sexual risk-taking and reduce STIs, including HIV.

Objectives: To determine the molecular basis in a Greek child suspected of having HbH disease and β-thalassemia trait., Methods:   Standard hematology, Hb electrophoresis, and HPLC. Multiplex ligation-dependent probe amplification (MLPA), direct sequencing, and breakpoint characterization by NimbleGen fine-tiling array analysis., Results: The index patient showed a moderate microcytic hypochromic anemia with normal ZPP and elevated HbA(2) , indicative for β-thalassemia trait. However, the moderate microcytic hypochromic anemia along with the observation of HbH inclusions in occasional red blood cells suggested a coexisting α-thalassemia. Molecular analysis indicated that the propositus inherited the β(+) -thalassemia mutation IVS2-745 (c>g) and a novel α(0) -thalassemia deletion from the mother, and the common non-deletion α-thalassemia allele α(2) (-5nt)α from the father. The α(0) -thalassemia deletion, named - -(BGS) , is approximately 131.6 kb in length. It removes the major regulatory elements along with the functional α-globin genes but leaves the theta-gene intact., Conclusions: The compound interaction of a β-thalassemia defect along with a single functional α-globin gene is quite rare. Although patients with HbH/β-thal and simple HbH disease have comparable levels of Hb, the absence of free β-globin chains and thus detectable non-functional HbH means that in HbH/β-thal, the levels of functional Hb are higher, resulting in a better compensated functional anemia. Rare large deletions as the one described here remain undetected by gap-PCR in routine molecular screening. The introduction of MLPA as a diagnostic screening tool may improve laboratory diagnostics for these defects. The use of NimbleGen fine-tiling arrays may give additional information about the precise location of breakpoints., (© 2011 John Wiley & Sons A/S.)

Although DNA analysis is needed for characterization of the mutations that cause β-thalassaemia, measurement of the Hb A(2) is essential for the routine identification of people who are carriers of β-thalassaemia. The methods of quantitating Hb A(2) are described together with pitfalls in undertaking these laboratory tests with particular emphasis on automated high-performance liquid chromatography and capillary electrophoresis., (© 2011 Blackwell Publishing Ltd.)

Measurement of the Haemoglobin F in red cell haemolysates is important in the diagnosis of δβ thalassaemia, hereditary persistence of fetal haemoglobin (HPFH) and in the diagnosis and management of sickle cell disease. The distribution of Hb F in red cells is useful in the diagnosis of HPFH and in the assessment of feto-maternal haemorrhage. The methods of quantifying Hb F are described together with pitfalls in undertaking these laboratory tests with particular emphasis on automated high-performance liquid chromatography and capillary electrophoresis., (© 2011 Blackwell Publishing Ltd.)

The goal of this study was to translate and adapt The Pain Disability Questionnaire (PDQ) to Brazilian Portuguese, as well as to assess its psychometric properties and practicability. The following methodological steps were followed: translation, synthesis, back-translation, expert committee assessment and pre-test. The psychometric properties were assessed through the application of a questionnaire to 119 patients with chronic musculoskeletal disorders. The results indicated the reliability of the instrument, with a Cronbach's alpha coefficient of 0.86, and high stability in the test-retest. A moderate correlation was found between the PDQ scores and the numerical pain scale. Negative correlations were found between the Spitzer Quality of Life Index and the functional condition, psychosocial component and total PDQ score. Construct validity demonstrated significant difference in PDQ scores between symptomatic and asymptomatic individuals. The PDQ revealed fast application and easy understanding. The results indicated a successful cultural adaptation and reliable psychometric properties.

Up to now, more than 200 different β-thalassemia (β-thal) mutations have been characterized. The majority are point mutations causing expression defects. Only approximately 10.0% of the defects are caused by large deletions involving the β-globin gene cluster causing β(0)-thal, (δβ)(0)-thal, (G)γ((A)γδβ)(0)-thal and other conditions with or without persistence of fetal hemoglobin (Hb). For the prevention of severe forms of β-thal intermedia and β-thal major, it is important to identify carriers of point mutations as well as carriers of deletions. β-Thalassemia and related disorders are most commonly present among populations from all Mediterranean countries as well as Southeast Asia, India, Africa, Central America and the Middle East. Twelve relatively frequently occurring deletion types have been described involving the β-globin gene cluster. These include the 105 bp β(0)-thal deletion, the 619 bp deletion, the 3.5 kb deletion, the Southeast Asian (SEA) deletion, the Filipino deletion, Hb Lepore, the Thai (δβ)(0)-thal, the Siriraj J (G)γ((A)γδβ)(0)-thal, the Chinese (G)γ((A)γδβ)(0)-thal, the Asian Indian deletion-inversion (G)γ((A)γδβ)(0)-thal as well as the (hereditary persistence of fetal hemoglobin) HPFH-6 and HPFH-7 deletions. To improve the rapid detection of the eight common β-globin cluster deletions in Southeast Asian countries, a simple molecular technique based on a single-tube multiplex gap-polymerase chain reaction (PCR) has been developed in this study. This technique provides a fast, simple and cost effective diagnostic test for deletion types of β-thal that can be applied in every molecular diagnostic laboratory having standard PCR equipment.

Implementation of multiplex ligation-dependent probe amplification (MLPA) for thalassemia causing deletions has lead to the detection of new rearrangements. Knowledge of the exact breakpoint sequences should give more insight into the molecular mechanisms underlying these rearrangements, and would facilitate the design of gap-PCRs. We have designed a custom fine-tiling array with oligonucleotides covering the complete globin gene clusters. We hybridized 27 DNA samples containing newly identified deletions and nine positive controls. We designed specific primers to amplify relatively short fragments containing the breakpoint sequence and analyzed these by direct sequencing. Results from nine positive controls showed that array comparative genomic hybridization (aCGH) is suitable to detect small and large rearrangements. We were able to locate all breakpoints to a region of approximately 2 kb. We designed breakpoint primers for 22 cases and amplification was successful in 19 cases. For 12 of these, the exact locations of the breakpoints were determined. Seven of these deletions have not been reported before. aCGH is a valuable tool for high-resolution breakpoint characterization. The combination of MLPA and aCGH has lead to relatively cheap and easy to perform PCR assays, which might be of use for laboratories as an alternative for MLPA in populations where only a limited number of specific deletions occur with high frequency., (© 2011 Wiley Periodicals, Inc.)

Defining the spectrum of specific thalassemia mutations is an important issue when planning prevention programs in large multi ethnic countries as is Indonesia. In a first attempt to define the prevalence of the common mutations in East Java we selected a cohort of 17 transfusion-dependent patients attending the Dr. Soetomo Hospital, Surabaya, Indonesia. After basic diagnostics we performed direct DNA sequencing for all β-globin genes. The results obtained on 34 independent chromosomes revealed the following prevalence rates: c.79 G>A p. Glu27Lys (Hb E) 47.0%; c.92+5G>C (IVS-I-5 G>C) 20.6%; c.109_110 delC p.Pro37Leu fs X7 [codon 35 (-C)] 17.6%; c.46del T p.Trp16Gly fsX4 [codon 15 (-T)] 5.9%; c.126_129delCTTT p. Phe42Leu fs X19 (codons 41/42) 2.9%; c.316-197 C>T [IVS-II-654 (C>T)] 2.9%; c*112 A>G (PolyA) 2.9%. Our preliminary results show that the distribution of the prevalent mutations in our cohort is quite homogeneous but with different forms than previously reported. This indicates that more studies on a larger scale and in different geographical areas are needed to refine our provisional results and to characterize the molecular background of the disease in the whole country.

Objective: To examine the feasibility of standardized hemoglobinopathy (HBP) carrier testing for pregnant women in The Netherlands in addition to the standard anemia screening., Methods: We assessed the prevalence of HBP in women at the time of the first pregnancy visit using both a prospective cohort (N = 703) and a retrospective series of women selected at random (N = 588). For the purpose of analysis, the population was divided into a high risk and a low risk group for HBP based on maternal ethnicity. Screening for HBP utilized standard screening tests for anemia, with additional high performance liquid chromatography (Variant II); molecular analysis was performed by Gap-polymerase chain reaction (Gap-PCR) and if necessary, direct sequencing and multiplex ligation-dependent probe amplification (MLPA). Family history was reported or collected from the medical records., Results: β-Globin defects were found in 3.9% of the total population (50/1291). The frequency in the high risk population was 5.6% (37/656), compared with 1.2% (6/501) in the low risk group. In the prospective study we found 30 HBP carriers, leading to testing of 16 partners and identification of two couples at risk. One affected child was born. Mean gestational age at the screening was 11.3 weeks with a standard deviation (SD) of 5.8., Conclusion: We found that the prevalence of HBP carriers is high enough in our population to warrant HBP testing for the entire multiethnic population in early pregnancy at the time of anemia screening. This is feasible as most women had their booking early in their first trimester., (Copyright © 2011 John Wiley & Sons, Ltd.)

A comparison between the classic Plackett-Burman design (PB) ANOVA analysis and a genetic algorithm (GA) approach to identify significant factors have been carried out. This comparison was made by applying both analyses to data obtained from the experimental results when optimizing both chemical and enzymatic hydrolysis of three lignocellulosic feedstocks (corn and wheat bran, and pine sawdust) by a PB experimental design. Depending on the kind of biomass and the hydrolysis being considered, different results were obtained. Interestingly, some interactions were found to be significant by the GA approach and allowed to identify significant factors, that otherwise, based only in the classic PB analysis, would have not been taken into account in a further optimization step. Improvements in the fitting of c.a. 80% were obtained when comparing the coefficient of determination (R2) computed for both methods., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A neighborhood's normative climate is linked to, but conceptually distinct from, its structural characteristics such as poverty and racial/ethnic composition. Given the deleterious consequences of early sexual activity for adolescent health and well-being, it is important to assess normative influences on youth behaviors such as sexual debut, number of sex partners, and involvement in casual sexual experiences. The current study moves beyond prior research by constructing a measure of normative climate that more fully captures neighborhood norms, and analyzing the influence of normative climate on behavior in a longitudinal framework. Using recently geo-coded data from the Toledo Adolescent Relationships Study (TARS), we analyze the effect of normative climate on adolescents' sexual behaviors. Results indicate that variation in neighborhood normative climates increases adolescents' odds of sexual debut and casual sex, and is associated with their number of sex partners, even after accounting for neighborhood structural disadvantage and demographic risk factors.

Recent research demonstrates that perceptions of gender mistrust are implicated in lower marriage rates among low-income populations. Yet few quantitative studies have examined the factors predicting gender mistrust during adolescence and whether it influences the quality of subsequent nonmarital romantic relationships. Analysis of three waves of data from the Toledo Adolescent Relationships Study (N = 1,106) indicates that in addition to neighborhood poverty rates, parents' own gender mistrust and parent-child relationship quality are related to adolescents' gender mistrust, suggesting that parents play an important role in influencing adolescents' developing feelings of gender mistrust. Perceptions of gender mistrust are not related to whether adolescents are involved in dating relationships, but are linked to higher levels of jealousy and verbal conflict in adolescents' subsequent romantic relationships, albeit only for male adolescents.

Purpose: Parenthood may play a pivotal role in the criminal desistance process, but few studies have examined the conditions under which becoming a mother or father is most likely to lead to reductions in criminal behavior., Methods: The current longitudinal study draws on four waves of adolescent and young adult interview data (N = 1,066) and HLM regression models to examine the impact of parenthood on criminal trajectories, as well as the degree to which the prosocial potential of parenthood is modified by socioeconomic factors, the nature of the relationship between the biological parents, and pregnancy wantedness. The analysis also draws on narrative life history accounts elicited from a subset of these respondents (N = 22)., Results: SES and the wantedness of the pregnancy condition the relationship between parenthood and criminal involvement, however some gender differences emerged. Status of the relationship (married or cohabiting and single) was in general not a strong predictor., Conclusions: Highly disadvantaged young men and women are not as likely as more advantaged young adults to evidence lower levels of criminal behavior after becoming parents, however wanted pregnancies may reduce female involvement in crime regardless of socioeconomic status. In-depth qualitative data further elucidate the conditional nature of the parenthood-crime relationship.

The idea of a sexual double standard emphasizes that men have more sexual freedom, whereas women are subject to social sanctions for the same behaviors. This research uses a sample of adolescent women to examine the social consequences of reporting a greater number of sex partners. The research explores whether there are broader social costs and feelings of low self-worth associated with a high number of sex partners, and also focuses on characteristics of the adolescents' close friends. The analyses of quantitative data (n = 600) provide support for the emphasis on the adolescents' immediate network of friends: Friends' attitudes and behaviors were significant predictors of respondents' own sexual experiences, while those reporting a higher number of sex partners did not report a lack of popularity, desire for more friends, or lower self-esteem. In-depth relationship history narratives collected from a subset of respondents (n = 46) provide additional context. Women often recognized the existence of a double standard on a societal or school level, but support or acceptance provided by the more immediate network of similarly situated friends serves as a buffer against such negative attributions. The findings suggest that programs targeting sexual behaviors should focus on how peer norms influence girls' sexual choices.

There is a long tradition of studying parent-child relationships and adolescent delinquency. However, the association between parent-child relationships and criminal offending during young adulthood is less well understood. Although the developmental tasks of young adulthood tend to focus on intimate relationships, employment, and family formation, the parent-child bond persists over the life course and likely continues to inform and shape behavior beyond adolescence. Using data from the Toledo Adolescent Relationships Study (TARS), the influence of parental involvement on patterns of offending among respondents interviewed first as adolescents (mean age of 15 years), and later as young adults (mean age of 20 years), is examined. The TARS sample used for our study (N = 1,007) is demographically diverse (49.5% female; 25.3% Black; 7.2% Hispanic) and includes youth beyond those enrolled in college. The influences of both early and later parenting factors such as support, monitoring and conflict on young adults' criminal behavior are examined. Results show that early monitoring and ongoing parental support are associated with lower offending in young adulthood. These effects persist net of peer influence and adolescent delinquency. This suggests the importance of examining multiple ways in which parental resources and support influence early adult behavior and well-being.

We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories. A total of 1,941 unique genetic variants in 37 genes, encoding globins and other erythroid proteins, are currently documented in these databases, with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants, leading to a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The principles established here will serve as a model for other systems and for the analysis of other common and/or complex human genetic diseases.

We describe a new nondeletional α-thalassemia (α-thal) determinant found in a Moroccan infant and in two members of his family. The new mutation generates an abnormal hemoglobin (Hb) as a consequence of a Pro→Ser amino acid substitution at codon 37 (old nomenclature) of the α2 gene. The new Hb variant is barely separable on high performance liquid chromatography (HPLC) but the expression of the α chain mutant measured on reversed phase chromatography is one-third of that expected from a stable α2 variant, which explains the mild α-thal phenotype observed in the carriers. As shown for other mutations described in our laboratory (i.e., Hb Gouda), this variant could also be common in the North African population, overlooked because of the mild phenotype and silent behavior on HPLC. Nevertheless, these silent variants could generate intermediate Hb H diseases in association with Mediterranean α(0)-thal deletion defect.

Objectives: To evaluate the relationship between FAST peak percentage by adapted Bio-Rad Vnbs analysis using the valley-to-valley integration and genotypes with the aim to improve differentiation between severe α-thalassaemia forms (HbH disease) and the milder disease types., Method: DNA analysis for α-thalassaemia was performed on 91 dried blood spot samples presenting normal and elevated FAST peak levels, selected during three years of Dutch national newborn screening., Results: Significant differences were found between samples with and without α-thalassaemia mutations, regardless of the genetic profiles. No significant difference was demonstrated between HPLC in -α/αα and -α/-α, between -α/-α and - -/αα and between - -/αα and - -/-α genotypes., Conclusion: This study confirms that the percentage HbBart's, as depicted by the FAST peak, is only a relative indication for the number of α genes affected in α-thalassaemia. Based on the data obtained using the modified Bio-Rad Vnbs software, we adopted a cut-off value of 22.5% to discriminate between possible severe α-thalassaemia or HbH disease and other α-thalassaemia phenotypes. Retrospectively, if this cut-off value was utilized during this initial three-year period of neonatal screening, the positive predictive value would have been 0.030 instead of 0.014.

Research links sex ratios with the likelihood of marriage and divorce. However, whether sex ratios similarly influence precursors to marriage-transitions in and out of dating or cohabiting relationships-is unknown. Utilizing data from the Toledo Adolescent Relationships Study (TARS) and the 2000 census, this study assesses whether sex ratios influence the formation and stability of emerging adults' romantic relationships. Findings show that relationship formation is unaffected by partner availability, yet the presence of partners increases women's odds of cohabiting, decreases men's odds of cohabiting, and increases number of dating partners and cheating among men. It appears that sex ratios influence not only transitions in and out of marriage, but also the process through which individuals search for and evaluate partners prior to marriage.

We know more about parent and peer influences than about the ways in which specific qualities of adolescent romantic relationships may influence sexual decision-making. Using data from the Toledo Adolescent Relationships Study, we focus on communication processes and emotional feelings, as well as more basic contours of adolescent romantic relationships, including power and influence dynamics. Controlling for traditional predictors and duration of the relationship, results suggest that subjectively experienced relationship qualities matter for understanding teens' sexual behavior choices. Further, findings indicate a similar effect of most relationship qualities on male and female reports of sexual behavior. However, influence and power dynamics within the relationship were not related to the likelihood that boys reported sexual intercourse in a focal relationship. In contrast, girls who perceived a more favorable power balance were less likely to report sexual intercourse than their female counterparts who perceived a less favorable power balance. Recognizing that the results capture reciprocal influence processes, longitudinal and qualitative data are used to further explore the complex nature of these associations.

Over half of young adults have cohabited, but relatively little is known about the role delinquency and substance use play in youths' odds of cohabiting as well as the implications of cohabitation for early adult offending and substance use. This study focuses on the reciprocal relationship between cohabitation during late adolescence and young adulthood and self-reported offending and substance use. Using longitudinal data, we find that net of traditional predictors delinquency involvement is associated with increased odds of cohabitation and cohabiting at younger ages while substance use is not related to cohabiting during early adulthood. Further analysis indicates that cohabitation is associated with lower reports of substance use. However, cohabitation is not associated with self-reported offending. The results help to unravel the connection between cohabitation experience, offending and substance use, and early adult outcomes.

Hirschi argued that delinquent youth tend to form relatively "cold and brittle" relationships with peers, depicting these youths as deficient in their attachments to others. The current analysis explores connections between delinquency and the character of adolescent romantic ties, drawing primarily on the first wave of the Toledo Adolescent Relationships Study, and focusing on 957 teens with dating experience. We examine multiple relationship qualities/dynamics in order to explore both the "cold" and "brittle" dimensions of Hirschi's hypothesis. Regarding the "cold" assumption, results suggest that delinquency is not related to perceived importance of the romantic relationship, level of intimate self-disclosure or feelings of romantic love, and more delinquent youth actually report more frequent contact with their romantic partners. Analyses focused on two dimensions tapping the "brittle" description indicate that while durations of a focal relationship do not differ according to level of respondent delinquency, more delinquent youths report higher levels of verbal conflict.

Studies of teen dating violence have focused heavily on family and peer influences, but little research has been conducted on the relationship contexts within which violence occurs. The present study explores specific features of adolescent romantic relationships associated with the perpetration of physical violence. Relying on personal interviews with a sample of 956 adolescents, results indicate that respondents who self-report violence perpetration are significantly more likely than their non-violent counterparts to report higher levels of other problematic relationship dynamics and behaviors such as jealousy, verbal conflict, and cheating. However, we find no significant differences in levels of love, intimate self-disclosure, or perceived partner caring, and violent relationships are, on average, characterized by longer duration, more frequent contact, sexual intimacy and higher scores on the provision and receipt of instrumental support. Finally, violence is associated with the perception of a relatively less favorable power balance, particularly among male respondents. These findings complicate traditional views of the dynamics within violent relationships, add to our understanding of risk factors, and may also shed light on why some adolescents remain in physically abusive relationships.

Objectives: To diagnose hemoglobinopathies in newborns by separating and measuring the Hb fractions on high throughput capillary electrophoresis. To test and validate the Capillarys Neonat Fast Hb device (Sebia) on fresh and dry blood samples., Design and Methods: The Hb fractions in 1.600 cord blood samples from the multi ethnic Dutch population were separated and measured. Further, the sensitivity, specificity and reproducibility of the device in detecting abnormalities and measuring the Hb fractions were estimated., Results: The apparatus separated all significant Hb fractions that should be detected during newborn screening (NBS) with 100% sensitivity. The reproducibility of the migrations guaranteed putative specificity for the few relevant frequent variants observed (HbS, C, and E). The estimation of the HbA and F fractions proved reliable using a well-designed integration mode., Discussion: Due to the limited number of samples no cases with sickle cell disease or β-thalassemia major were found in this cohort. However, the heterozygous state for the common variants associated with these diseases was clearly recognizable. The measurements were sufficiently precise to recognize sickle cell disease, β-thalassemia major and intermedia and to identify carriers including possible β-thalassemia. Therefore, Capillarys Neonat Fast Hb (Sebia) can be considered as a valid instrument for NBS of the Hemoglobinopathies on fresh and dry blood samples., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objectives: To estimate the prevalence of children with sickle cell disease (SCD) in The Netherlands. To estimate the annual number of children newly diagnosed as having SCD and the proportion with diagnoses through neonatal screening To estimate the proportion of children with SCD receiving paediatric care in a comprehensive care setting., Design: Data from two sources, a survey of paediatric practices (n=107) and a laboratory database (n=20), were analysed by the capture-recapture method., Participants: Children with SCD aged <18 years, either born before 2003 or newly diagnosed as having SCD between 2003 and 2007., Main Outcome Measures: Prevalence, annual number of children newly diagnosed as having SCD, proportion of children with diagnoses through neonatal screening, proportion of children receiving paediatric care., Results: The prevalence of SCD in children living in The Netherlands on 1 January 2003 was 1:5152 (95% CI 1:4513 to 1:6015). In the next 4 years, the annual incidence was 1:2011 (95% CI 1:1743 to 1:2376). Nearly one-third (27%) of the children newly diagnosed as having SCD immigrated to The Netherlands after birth and would, therefore, be missed by the neonatal screening programme. Approximately 60% of all children with SCD were not reported by paediatricians., Conclusion: The number of children with SCD in The Netherlands is much higher than previously estimated, and the majority of these children seem not to be reviewed regularly by a paediatrician. Children born abroad (27% of new cases) do not benefit from neonatal screening and are at high risk of life-threatening complications before SCD is diagnosed. As this introduces disparities in healthcare, the initiation of adequate measures should be considered.

Production of recombinant Oryza sativa non-symbiotic hemoglobin 1 (OsHb1) by Escherichia coli was maximized in shake-flask cultures in media containing tryptone, yeast extract, sodium chloride and byproduct glycerol from biodiesel production. Response surface methodology (RSM) and artificial neural networks (ANNs), followed by multiple response optimization through a desirability function were applied to evaluate the amount of OsHb1 produced. The results obtained by the application of ANNs were more reliable since better statistical parameters were obtained. The optimal conditions were (g L(-1)), tryptone, 42.69; yeast extract, 20.11; sodium chloride, 17.77; and byproduct glycerol, 0.33. A maximum recombinant protein concentration of 3.50 g L(-1) and a minimum biomass concentration of 18.48 g L(-1) were obtained under these conditions. Although the concentrations of tryptone, yeast extract and sodium chloride are relatively high, the increase in the yield with respect to biomass formed (Y(P/X)) overcomes this disadvantage., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Alpha-thalassemia is an inherited hemoglobin disorder characterized by a microcytic hypochromic anemia caused by a quantitative reduction of the alpha-globin chain. The majority of the alpha-thalassemias is caused by deletions in the alpha-globin gene cluster. A deletion in the alpha-globin gene cluster, which was found in a Dutch family, was characterized by MLPA, long-range PCR and direct sequencing. We describe the molecular characterization of a novel 8.2kb deletion (--(AW)), involving both alpha-globin genes in cis. The deletion is caused by a non-homologous recombination event between an Alu and an L1-repeat sequence. This deletion is the third example of a non-homologous recombination event involving an Alu and an L1 repeat, and the first described in the human alpha-globin gene cluster. Because of a 25% risk of Hb Bart's with hydrops foetalis in the offspring when in combination with another alpha(0)-thalassemia allele, it is important to diagnose this deletion., (2010 Elsevier Inc. All rights reserved.)

We present the hematological characteristics of five patients from Surinam and the bordering French Guyana, who are carriers of the rare beta-thalassemia (beta-thal) mutation HBB:c.315+1G>T. Analysis of the phenotype/genotype relationship shows that this allele is a beta(0)-thal variant and illustrates the modulating effect of the alpha-globin gene status on the beta-thal phenotype. The ethnic origin of the five probands, belonging to the so-called Bush Negroes Maroons of Surinam and French Guyana, strongly suggests that this beta-thal mutation has a West African origin and spread in this ethnic group because of a founder effect and/or genetic drift.

We report three examples of chronic anaemia involving complex combinations of alpha- and beta-globin gene defects. The first case had a potential Hb H disease caused by the classic SEA/RW deletions masked by Hb E [beta26(B8)Glu-->Lys] in the homozygous state. The second had an unusual Hb H disease caused by compound heterozygosity for two different alpha2 polyadenylation site mutations masked by a beta-thalassaemia heterozygosity. The third had an intermediate alpha-thalassaemia with considerable anaemia caused by an as yet unknown polyadenylation site (AATAAA>AATAAC) mutation in combination with a common RW deletion masked by a common Hb C [beta6(A3)Glu-->Lys] heterozygosity. Diagnostic methods, genotype/phenotype correlations and the chance of overlooking these combinations during risk assessment in a multiethnic society are discussed.

The number of immigrants in Western Australia from many different areas where hemoglobinopathies are endemic has increased dramatically since the 1970s. Therefore, many different thalassemia mutations have been introduced in the country, which add a technological diagnostic problem to the serious burden of hemoglobinopathy management and to public health care. Recently, we have developed a rapid and simple technique based on Multiplex Ligation-dependent Probe Amplification to detect deletions causing alpha-and beta-thalassemia, deltabeta-thalassemia and Hereditary Persistence of Fetal Hemoglobin. A screening for (unknown) deletions was performed in a cohort of patients of different ethnic backgrounds preselected for their thalassemia phenotype, in which common deletions and point mutations were excluded. Out of 37 cases suspected to carry a deletion, 27 were found to carry 17 different deletion types of which 6 causing alpha-thalassemia and 5 causing beta-thalassemia were novel. For 3 of the deletions, we have been able to characterize the exact breakpoint sequences by long-range PCR and direct sequencing. These results show that MLPA is a suitable technology to detect unknown and uncommon deletions. These could represent a diagnostic problem when offering prevention to couples at risk presenting with unclear phenotypes and might result in a serious fetal problem when the deletion involves embryonic genes., (2010 Elsevier Inc. All rights reserved.)

We report two new point mutations of the alpha1-globin gene found in a Greek and a Burmese patient, both living in Western Australia. The patients were initially selected for their microcytic hypochromic parameters as belonging to a group suspected for uncommon (deletion) defects. Gap-polymerase chain reaction (gap-PCR) and multiplex ligation-dependent probe amplification (MLPA) technologies were applied, and in those cases not showing deletions, direct sequencing was performed. We have found 1) HBA1:c.86C>T, Hb Nedlands [alpha28(B9)Ala-->Val] which, based on the red cell indices and phenotype prediction scores, is presumed to be clinically silent, and 2) HBA1:c.98T>A, Hb Queens Park [alpha32(B13)Met-->Lys] which seems to be associated with a mild alpha-thalassemia (alpha-thal) phenotype. The phenotype/genotype correlation is briefly described.

We report a novel thalassemia determinant found in a Nigerian woman living in the Netherlands, resulting from a 2 bp insertion at codons 9/10 of the β-globin gene (HBBc.28&#95;29insTA p.Ser10LeufsX11). The novel defect causes a frameshift with a consequent premature TGA stop codon, located at 11 positions downstream from the mutated codon. The phenotype was typical of a β-thalassemia (β-thal), trait with high RBC counts and compensated mild microcytic anemia. However, the Hb A(2) level was reported to be normal due to the presence of the common Hb A(2)' or Hb B2 [δ16(A13)Gly→Arg, GGC>CGC] variant that was not taken into account. We also present the opposite but comparable situation found in an a Palestinian man living in the USA. He was a carrier of a common β-globin gene defect [codon 6 (-A), HBB:c.20delA] in combination with a novel δ-globin gene defect at codon 6 [HBD. c.19G>C, Glu6Gln] that we have named Hb A(2)-Ramallah. In both cases, the provisional diagnosis could have been compromised when based on the measurement of the normal Hb A(2) fraction only.

During a second pilot study, intended to explore the possibility of a country wide implementation of carrier diagnostics for hemoglobinopathies in The Netherlands, we observed a new abnormal hemoglobin (Hb) variant in three members of a family of Scandinavian origin living in the Dutch city of The Hague (Den Haag). The proband, a 34-year-old female presented with low Hb, packed cell volume (PCV) and red blood cell (RBC) values but was normocytic and normochromic. High performance liquid chromatography (HPLC) analysis revealed a partially separated fraction following Hb A. Molecular diagnostics disclosed a TTT>TAT transversion at HBB:c.137 causing a Phe-->Tyr single amino acid substitution at position 45 of the beta-globin gene. Previously described heterozygous mutations at the same position [Hb Cheverly (Phe-->Ser) and Hb Arta (Phe-->Cys)] were reported to be associated with mild chronic hemolysis similar to this case. We describe the hematological features of the six family members, the biochemical and molecular data and we discuss the possible consequences in combination with the common beta-thalassemia (beta-thal) trait.

Background: The birth prevalence of severe haemoglobinopathies such as sickle cell disease (SCD) in the Netherlands has been estimated to be at least 50 newborns per year. Neonatal screening for SCD was added to the Dutch screening programme in January 2007. We here evaluated three high performance liquid chromatography (HPLC) systems for application in neonatal screening for haemoglobinopathies, and present the results of a subsequent pilot screening programme., Methods: The Variant NewBorn Screening (Vnbs) HPLC system (Bio-Rad) was validated by analysing 131 blood samples and blood mixtures. Subsequently, the performance of the G7 (Tosoh BioScience) and Ultra (Primus Corporation) was compared with the Vnbs. The three HPLC analysers were tested in a pilot screening programme on 21,969 dried blood spot samples from the routine Dutch neonatal screening programme., Results: The pilot screening resulted in 188 abnormal patterns. The three HPLC devices presented comparable within- and between-run precision and detected the abnormal samples similarly. The high throughput, sampling systems, presentation of results, and integration of the chromatograms, however, were different., Conclusion: All three analysers detected the same abnormal haemoglobins satisfactorily, but integrated the chromatograms with variable imprecision. Comparison of the results suggested that the Bio-Rad Vnbs was the preferred system. However, software adjustments were required to improve the diagnostic potential of this device for screening for beta- and alpha-thalassaemia.

We report two novel alpha2-globin gene mutations found in the same Surinamese family. The proband, a newborn presenting during neonatal screening with 21.3% Hb Bart's (gamma4), proved to be a carrier of the common -alpha(3.7) deletion and a novel codon 32 (ATG>AGG) transversion that we named Hb Rotterdam. The father carried the same point mutation with borderline hemoglobin (Hb), MCV and low MCH values. The mother presented with a significant microcytic hypochromic anemia and also carried the -alpha(3.7) deletion and a second novel TAT>TAG transversion generating a stop codon at position 24. Shortly thereafter, Hb Rotterdam was again found in two unrelated adult females and in a Canadian newborn, all of African origin, suggesting that Hb Rotterdam could be a frequently occurring alpha(T) determinant in the Black population. Screening and characterization of the mutations, phenotype/genotype correlation and the issue of reporting newborn carriers of alpha-thalassemia (alpha-thal) are discussed.

Sickle cell disease is known to be very common in the Omani population, although data are limited concerning beta-thalassemia (beta-thal). We report the molecular background of 87 unrelated patients from the Sultanate of Oman, diagnosed with beta-thal major (beta-TM), beta-thal intermedia (beta-TI) or minor. Diagnosis was based on clinical and hematological data and confirmed by molecular analysis. We found 11 different beta-thal determinants in our cohort, which consists of subjects from different regions of Oman. Six of these mutations have not been previously reported in the Omani population. The prevalence of alpha-thal single gene deletions (-alpha(3.7) and -alpha(4.2)) in the same cohort was very high (58.3%). These data will contribute to the implementation of a country-wide service for early molecular detection of hemoglobinopathies and for providing genetic counseling following premarital screening.

We report two new abnormal hemoglobins (Hbs) caused by mutations on the α2 gene. One resulted into an Asn→His substitution at position 68, the other in a Leu→Gln substitution at position 125. The first mutation was observed in a 61-year-old North European Belgian male during Hb A(1c) analysis and subsequently in other members of his family. The variant was expressed at a normal level and caused no hematological abnormalities in the carriers. The second was found in a 27-year-old Turkish male living in The Hague, The Netherlands, who presented with microcytic hypochromic parameters without iron deficiency and was also carrier of the common α2 IVS-I (-5 nt) deletion.

Objective: To review prevention data for hemoglobinopathies from Latium, a large Italian region with a considerable immigrant population and with a well-established regional prevention program., Method: All data pertaining to population screening for hemoglobinopathies in the Latium region were reviewed for the period 1994-2007. Screening was performed universally in secondary schools and to pregnant couples at the time of prenatal care. We have examined the trends in positive screening results as well as the type of hemoglobinopathies detected during the study period, and we have correlated them to the type of population (immigrant vs indigenous)., Results: From 1994 to 2007, 167 235 individuals were examined for carrier status for hemoglobinopathies, and 10 353 of them (6.2%) were immigrants. We have registered a threefold increase in rates of screen-positive subjects who belonged to ethnic minorities during the study period (from 2.7% in 1994 to 9.8% in 2007). Over half of the screen-positive subjects (5397/10 353) presented no hematological anomalies, 24% (n = 2472) had iron deficiency, and 24% (n = 2484) was classified as putative carriers. Among the last group, 22.6% were carriers of beta-thalassemia, 48% were suspected alpha-thalassemia carriers, and the remainder had less common hemoglobinopathies. While the prevention program resulted in nearly zero births of autochthonous newborns affected by severe hemoglobinopathies, a rise in number of affected individuals was noted among immigrants. Screening of secondary school students was accepted by 67% of immigrant parents, resulting in 9737 pupils screened between 2002 and 2006., Conclusion: Existing preventive programs for severe hemoglobinopathies should adapt to changes in population ethnicities. Screening for hemoglobinopathies at school age is an efficient strategy.

Objectives: We present in a brief summary the basic aspects of the most rational technologies used for new born screening (NBS) of the hemoglobinopathies and we report the preliminary results for the identification of beta-thalassemia carriers at birth by measuring the expression of the HbA fraction., Design and Methods: Separation and measurement of the Hb fractions in 1.500 cord blood samples collected among the multi-ethnic Dutch population using different methods., Results: By using a cut of <15% HbA we have found 4 carriers of point mutations defects 3 of which among a group of 34 newborns of ethnic origin and one among 120 north Europeans., Discussion: All methods for NBS summarized in this paper provide identification at practically 100% sensitivity and high specificity. However, all methods should be followed by routine parent's analysis to confirm the provisional results. Taking into consideration the gestation age and the HbA expression, we believe that carriers of beta-thalassemia can be preselected at birth with a reasonable degree of sensitivity and be confirmed by parent analysis.

Objectives: This review emphasizes the need for adapted prevention strategies in areas where severe hemoglobin disorders are endemic and in non-endemic countries where large immigrant groups are living., Design and Methods: Screening versus carrier diagnostics upon medical versus ethnic indication, ethical issues associated with carrier screening, information to multiethnic carriers and practical aspects of laboratory diagnostics are discussed., Results and Discussion: School screening is a valid option but needs follow up until partner choice. Premarital carrier diagnostics upon ethnic indication needs motivated GP's and might implicate (female) stigmatization in particular cultures. Early pregnancy is the best moment regarding the motivation, but needs rapid molecular analysis when a couple at risk seeks prevention. Neonatal screening is feasible when the organization is already present for other diseases and may offer retrospective as well as prospective primary prevention when all carriers are reported. Problems to be expected while implementing neonatal screening are summarized.

This study draws on social control and social learning theories to examine the role of dating-specific attitudes and practices as predictors of adolescents' sexual initiation. We include attention to the adolescent's reaction to control attempts as a further means of assessing family dynamics (i.e., frequency of dating disagreements). The study uses longitudinal data from 697 adolescents who were not sexually active at the first interview as well as separate interviews with parents. In models that include all parenting variables, parental caring, parents' preferences that the child should delay sex, and the frequency of dating disagreements are significant predictors of initiation of teen sexual activity.

We have tested five haemoglobin (Hb) separation apparatuses, dedicated to haemoglobinopathy diagnostics. These are the four high performance liquid chromatography devices: VARIANT II, HA 8160, G7, Ultra(2) and the Capillary Electrophoresis apparatus from Sebia. In the first place, we focussed on the capacity of all apparatuses to detect the most common structural variants relevant for public health, these being HbS, HbC, HbE, HbD-Punjab and HbO-Arab. We then compared how the high HbA(2)beta-thalassaemia carriers were identified. All apparatuses were able to identify carriers of these traits with the expected sensitivity and specificity. With the primary goal of a high degree of conformity in basic diagnostics of haemoglobinopathies, we present the interpretation and the significance of the results on all apparatuses, and we comment on the unavoidable problems and solutions.

Context: Research on adolescent condom use often focuses on the influence of parents, peers and environmental factors. Although most sexually active teenagers have sex within dating relationships, little is known about associations between the characteristics of these relationships and consistency of condom use., Methods: Data on 269 participants in Wave 1 of the Toledo Adolescent Relationships Study who had had sex in their current or most recent dating relationship were analyzed in logistic regression models to examine how positive and negative relationship qualities are associated with consistent condom use., Results: Among teenagers who had had sex with their dating partner, both negative relationship dynamics (conflict, partner's controlling behavior, mistrust, jealousy, perceived partner inferiority) and positive qualities (love, enmeshment, salience, self-disclosure) were negatively associated with consistent condom use (odds ratios, 0.7-0.9). Asymmetries in partners' age, race and school were not related to consistent condom use. Relationship duration was negatively associated with consistency (0.98-0.99), but the association was explained by feelings of relationship importance. Findings for relationship qualities were similar for males and females, with the exception of conflict, which was positively associated with consistent condom use among females but not males., Conclusions: Although the relationship processes associated with consistent condom use are complex, such processes appeared to be more strongly associated with consistent condom use than were social and demographic characteristics. Programs should focus on relationship qualities and dynamics, recognizing that both negative and positive relationship features are associated with consistent condom use.

When the molecular background of couples requesting prevention is unclear, family analysis and tools to define rare mutations are essential. We report two novel deletion defects observed in an Italian and in a Turkish couple. The first proband presented with microcytic hypochromic parameters without iron deficiency, a normal HbA(2) and an elevated HbF (10.6%). His father presented with a similar phenotype and his wife was heterozygous for the common Mediterranean codon 39 (HBB:c.118C>T) mutation. Having excluded point mutations and common deletions, Multiplex Ligation-dependent Probe Amplification was performed revealing an unknown Ggamma(Agammadeltabeta)(0)-thalassemia defect spanning from the Agamma gene to downstream of the beta-globin gene provisionally named Leiden 69.5 kb deletion. In the second case, the wife presented with a mild thalassemic picture, normal HbA(2), elevated HbF (18.5%) and a beta/alpha globin chain synthesis ratio of 0.62, without iron deficiency or any known beta-thalassemia defect, while the husband was a simple carrier of the common Mediterranean IVS-I-110 (HBB:c.93-21 G>A) mutation. A new large deletion involving the beta-gene and part of the delta-gene was identified by Multiplex Ligation-dependent Probe Amplification provisionally named "Leiden 7.4 kb".

Prevention of Hemoglobinopathies has developed around the world based upon the experience done in pioneering endemic countries and is now facing a new phase in non-endemic areas with a recent immigration history. We describe two situations, taking Latium (central Italy) and The Netherlands as two models for endemic and non-endemic countries both confronted with a large multi-ethnic immigrant society. We present prevention results and discuss aspects such as local knowledge and organization. We illustrate the importance of issues like information, carrier diagnostics, screening, counseling and prenatal diagnosis in particular situation of contrasting interest an different ethical opinions. We conclude by underlining the importance of implementing primary prevention at the European level, based upon better information, diagnostics and counseling.

We investigate the social and behavioral characteristics of male adolescents who self-identify as players, focusing particularly on Anderson's claim that this social role is inextricably linked with poverty and minority status. Results indicate that African American respondents, those affiliated with liberal peers and young men who initially report a relatively high number of sexual partners are more likely to resonate with this identity label. Nevertheless, analyses reveal that a number of players within the sample are not disadvantaged African American youth, and there is considerable variability in their attitude and behavior profiles. Findings based on longitudinal analyses indicate that the player identity is a significant predictor of later variations in self-reported sexual behavior, net of traditional predictors, including prior behavior. Yet results of in-depth interviews conducted with a subset of the respondents complicate these quantitative findings, highlighting that young men's perceptions of this identity are not as uniformly positive as Anderson's depiction might lead us to expect.

Prior research has documented general associations between dating and delinquency, but little is known about the specific ways in which heterosexual experiences influence levels of delinquency involvement and substance use. In the current study, we hypothesize that an adolescent's level of effort and involvement in heterosexual relationships play a significant role in forming the types of friendship networks and views of self that influence the likelihood of delinquency involvement and substance use. Analyses based on a longitudinal sample of adolescent youth (n=1,090) show that high levels of dating effort and involvement with multiple partners significantly increases unstructured and delinquent peer contacts, and influences self-views as troublemaker. These broader peer contexts and related self-views, in turn, mediate the path between dating relationships, self-reported delinquency, and substance use. Findings also document moderation effects: among those youths who have developed a troublemaker identity and who associate with delinquent peers, dating heightens the risk for delinquent involvement. In contrast, among those individuals who have largely rejected the troublemaker identity and who do not associate with delinquent friends, dating relationships may confer a neutral or even protective benefit. The analyses further explore the role of gender and the delinquency of the romantic partner.

Adolescent networks include parents, friends, and romantic partners, but research on the social learning mechanisms related to delinquency has not typically examined the characteristics of all three domains simultaneously. Analyses draw on data from the Toledo Adolescent Relationships Study (n = 957), and our analytic sample contains 51% male and 49% female as well as 69% white, 24% African-American, and 7% Latino respondents. Parents,' peers,' and partners' deviance are each related to respondents' delinquency, and affiliation with a greater number of deviant networks is associated with higher self-reported involvement. Analyses that consider enmeshment type indicate that those with both above average romantic partner and friend delinquency report especially high levels of self-reported involvement. In all comparisons, adolescents with deviant romantic partners are more delinquent than those youths with more prosocial partners, regardless of friends' and parents' behavior. Findings highlight the importance of capturing the adolescent's entire network of affiliations, rather than viewing these in isolation, and suggest the need for additional research on romantic partner influences on delinquent behavior and other adolescent outcomes.