The Amplifier - v. 7, no. 9

In this issue...Newman Club, Conoco, Petroleum Engineering, Marriage Lectures, Magma, Manuel Galup, Butte Mines, Glen Welch, Mountain View Church

Domestic Violence

Since the 1960s, there has been growing awareness regarding the issue of domestic violence as a form of violence against women, which has been largely influenced by the work of feminist activist and scholars in North America and Europe (Dobash and Dobash 1992). Other terms have been used to describe the same phenomenon, including domestic abuse, spousal abuse, wife battering, marital violence, intimate partner violence. Though there is no doubt that this problem has existed for much more than five decades, the tendency to label it as ‘private matters’ or ‘marital disagreements’ has obscured the reality of women living with abuse in their home. At a general level, domestic violence can be defined as the means used by a man in order to assert his control and domination over his intimate partner, whether they are married or not (Mullender 1996). It can involve incidents of physical and sexual violence, as well as verbal, psychological and financial abuse. Though some of its manifestations may be associated with particular cultural or religious groups – e.g. forced marriage and honour killing in South-Asian communities – domestic violence affects women from all classes and backgrounds.

Life partnerships in childhood cancer survivors, their siblings, and the general population

Background: Life partnerships other than marriage are rarely studied in childhood cancer survivors (CCS). We aimed (1) to describe life partnership and marriage in CCS and compare them to life partnerships in siblings and the general population; and (2) to identify socio-demographic and cancer-related factors associated with life partnership and marriage. Methods: As part of the Swiss Childhood Cancer Survivor Study (SCCSS), a questionnaire was sent to all CCS (aged 20–40 years) registered in the Swiss Childhood Cancer Registry (SCCR), aged <16 years at diagnosis, who had survived ≥5 years. The proportion with life partner or married was compared between CSS and siblings and participants in the Swiss Health Survey (SHS). Multivariable logistic regression was used to identify factors associated with life partnership or marriage. Results: We included 1,096 CCS of the SCCSS, 500 siblings and 5,593 participants of the SHS. Fewer CCS (47%) than siblings (61%, P < 0.001) had life partners, and fewer CCS were married (16%) than among the SHS population (26%, P > 0.001). Older (OR = 1.14, P < 0.001) and female CCS (OR = 1.85, <0.001) were more likely to have life partners. CCS who had undergone radiotherapy, bone marrow transplants (global PTreatment = 0.018) or who had a CNS diagnosis (global PDiagnosis < 0.001) were less likely to have life partners. Conclusion: CCS are less likely to have life partners than their peers. Most CCS with a life partner were not married. Future research should focus on the effect of these disparities on the quality of life of CCS.

Phenotypic variability in familial combined pituitary hormone deficiency caused by a PROP1 gene mutation resulting in the substitution of Arg-->Cys at codon 120 (R120C).

As pituitary function depends on the integrity of the hypothalamic-pituitary axis, any defect in the development and organogenesis of this gland may account for a form of combined pituitary hormone deficiency (CPHD). A mutation in a novel, tissue-specific, paired-like homeodomain transcription factor, termed Prophet of Pit-1 (PROP1), has been identified as causing the Ames dwarf (df) mouse phenotype, and thereafter, different PROP1 gene alterations have been found in humans with CPHD. We report on the follow-up of two consanguineous families (n = 12), with five subjects affected with CPHD (three males and two females) caused by the same nucleotide C to T transition, resulting in the substitution of Arg-->Cys in PROP1 at codon 120. Importantly, there is a variability of phenotype, even among patients with the same mutation. The age at diagnosis was dependent on the severity of symptoms, ranging from 9 months to 8 yr. Although in one patient TSH deficiency was the first symptom of the disorder, all patients became symptomatic by exhibiting severe growth retardation and failure to thrive, which was mainly caused by GH deficiency (n = 4). The secretion of the pituitary-derived hormones (GH, PRL, TSH, LH, and FSH) declined gradually with age, following a different pattern in each individual; therefore, the deficiencies developed over a variable period of time. All of the subjects entered puberty spontaneously, and the two females also experienced menarche and periods before a replacement therapy was necessary.

Congenital factor XIII deficiency in Pakistan: characterization of seven families and identification of four novel mutations

Deficiency of coagulation factor XIII (FXIII) belongs to the rare bleeding disorders and its incidence is higher in populations with consanguineous marriages. The aims of this study were to characterize patients and relatives from seven families with suspected FXIII deficiency from Pakistan and to identify the underlying mutations. As a first indicator of FXIII deficiency, a 5M urea clot solubility test was used. Plasma FXIII A- and B-subunit antigen levels were determined by ELISA. FXIII activity was measured with an incorporation assay. Sequencing of all exons and intron/exon boundaries of F13A was performed, and a novel splice site defect was confirmed by RT-PCR analysis. Genetic analysis revealed six different mutations in the F13A gene. Two splice site mutations were detected, a novel c.1460+1G>A mutation in the first nucleotide of intron 11 and a previously reported c.2045G>A mutation in the last nucleotide of exon 14. Neither of them was expressed at protein level. A novel nonsense mutation in exon 4, c.567T>A, p.Cys188X, was identified, leading in homozygous form to severe FXIII deficiency. Two novel missense mutations were found in exons 8 and 9, c.1040C>A, p.Ala346Asp and c.1126T>C, p.Trp375Arg, and a previously reported missense mutation in exon 10, c.1241C>T, p.Ser413Leu. All patients homozygous for these missense mutations presented with severe FXIII deficiency. We have analysed a cohort of 27 individuals and reported four novel mutations leading to congenital FXIII deficiency.

The relationship between rheumatoid arthritis and reproductive function

There is growing support for the theory that an interaction between the immune and reproductive/endocrine systems underlies the pathogenesis of autoimmune rheumatic diseases. Most of the recent evidence derives from studies of sex hormones and pregnancy in women with systemic lupus. Other than an ameliorative effect of pregnancy, little is known about reproductive factors in relation to rheumatoid arthritis. To elucidate the relationship, a population-based retrospective study was undertaken. Included were 378 female residents of Olmsted County, Minnesota diagnosed with rheumatoid arthritis between 1950 and 1982 (cases) and 325 arthritis-free, married female controls matched to the 324 married cases on birth-year, age at first marriage, and duration of Olmsted County residency. Information of reproductive factors was extracted from the medical records system maintained by the Mayo Clinic.^ Cases had lower fertility rates compared with the female population of Minnesota (rate ratio = 0.86, 95% confidence interval (CI)= 0.80-0.92). Fertility was significantly reduced even prior to the onset of rheumatoid factor positive arthritis. Restricting the comparison to married Olmsted County residents did not alter the results. Further adjustments for time not at risk of conception using survival analysis and proportional hazards modeling only intensified the fertility reduction in the married cases compared with controls. Nulligravidity was more common among cases than controls (odds ratio = 3.16, CI = 1.61-6.20). Independent of fertility, pregnancy had a protective effect against rheumatoid arthritis (odds ratio = 0.31, CI = 0.11-0.89), which was dramatically reversed in the 12 months postpartum (odds ratio = 4.67, CI = 1.50-14.47). Cases were younger at menopause than controls (p $<$ 0.01).^ Small but statistically insignificant associations were observed between rheumatoid arthritis and the following factors: increased frequency of complaints to a physician of infertility; increased frequency of spontaneous abortion, premature birth, and congenital malformations following arthritis onset; and increased prevalence of menopause at arthritis onset. Cases did not differ from controls on age at menarche, duration of pregnancy, or birth weight.^ The findings provide further support for the involvement of the reproductive/endocrine systems in the pathogenesis of autoimmune rheumatic disease. The search for biological mechanisms should be intensified. ^

Characterization of a novel CYP19A1 (aromatase) R192H mutation causing virilization of a 46,XX newborn, undervirilization of the 46,XY brother, but no virilization of the mother during pregnancies.

BACKGROUND P450 aromatase (CYP19A1) is essential for the biosynthesis of estrogens from androgen precursors. Mutations in the coding region of CYP19A1 lead to autosomal recessive aromatase deficiency. To date over 20 subjects have been reported with aromatase deficiency which may manifest during fetal life with maternal virilization and virilization of the external genitalia of a female fetus due to low aromatase activity in the steroid metabolizing fetal-placental unit and thus high androgen levels. During infancy, girls often have ovarian cysts and thereafter fail to enter puberty showing signs of variable degree of androgen excess. Moreover, impact on growth, skeletal maturation and other metabolic parameters is seen in both sexes. OBJECTIVE AND HYPOTHESIS We found a novel homozygous CYP19A1 mutation in a 46,XX girl who was born at term to consanguineous parents. Although the mother did not virilize during pregnancy, the baby was found to have a complex genital anomaly at birth (enlarged genital tubercle, fusion of labioscrotal folds) with elevated androgens at birth, normalizing thereafter. Presence of 46,XX karyotype and female internal genital organs (uterus, vagina) together with biochemical findings and follow-up showing regression of clitoral hypertrophy, as well as elevated FSH suggested aromatase deficiency. Interestingly, her older brother presented with mild hypospadias and bilateral cryptorchidism and was found to carry the same homozygous CYP19A1 mutation. To confirm the clinical diagnosis, genetic, functional and computational studies were performed. METHODS AND RESULTS Genetic analysis revealed a homozygous R192H mutation in the CYP19A1 gene. This novel mutation was characterized for its enzymatic activity (Km, Vmax) in a cell model and found to have markedly reduced catalytic activity when compared to wild-type aromatase; thus explaining the phenotype. Computational studies suggest that R192H disrupts the substrate access channel in CYP19A1 that may affect binding of substrates and exit of catalytic products. CONCLUSION R192H is a novel CYP19A1 mutation which causes a severe phenotype of aromatase deficiency in a 46,XX newborn and maybe hypospadias and cryptorchidism in a 46,XY, but no maternal androgen excess during pregnancy.

Polonofilizm i polskość wśród czeskich emancypantek w drugiej połowie XIX wieku: przykład Karoliny Světlej

The awakening of national consciousness went hand in hand in Bohemia with an anxiety about national disappearance. In this context, the recourse to Pan-Slavism was for the Czechs a way to encourage themselves through the idea of belonging to a great Slavic world, while the Slavic Congress organized in Prague in 1848 was an attempt to realize this ideal. The Congress was a failure from the political point of view, but it did have some socio-cultural repercussions: notably, it served as a pretext for the advancement of women's issues in Bohemia. It is indeed in the wake of the Congress that Honorata z Wiśniowskich Zapová, a Polish women settled in Prague after her marriage to a Czech intellectual, founded, under the guise of collaboration between all Slavic women, the first women's association, as well as a (very short-lived) Czech-Polish institute, where Czech, as well as Polish girls, could get a quality education in their mother tongue. Honorata was undoubtedly the source of the polonophilia wind that seemed to blow over the Czech emancipation movement in the second half of the nineteenth century. In particular, Karolina Světlá showed in her Memoirs a great recognition for Honorata's efforts in matters of emancipation and education, and explicitly took up the challenge launched by the latter in founding another women's association and in inaugurating a school for underprivileged girls. But the tribute Světlá paid to Honorata is even more evident in her literary work, where Poland and the Polish woman (who often wears Honorata's features) play a significant role (see for example her short novel Sisters or her story A Few Days in the Life of a Prague Dandy). Světlá was probably the Czech feminist writer who, in her activities and in her work, relied most strongly on the Polish woman as a model for the Czech woman. However, she wasn't alone. In general, it was a characteristic of the Czech feminist movement of the second half of the nineteenth century to have recourse to the Polish woman and to Poland as a landmark for comparison and as a goal to be achieved.

Patterns of psychological adaptation to divorce

Despite the increase in divorces after a long relationship, this trend remains a neglected research topic. The present contribution seeks to identify patterns of psychological adaptation to divorce after a long-term marriage. Data from a questionnaire study with 308 persons aged 45–65 years, who divorced after having been married for an average of 25 years, are presented. Exploratory latent profile analysis with various well-being outcomes revealed five groups: one with average adapted, one with resilients, and three small groups with seriously affected individuals. Discriminant variables between the groups were personality, time since separation, a new relationship, and financial situation. Age, gender, and length of marriage played a marginal role; satisfaction with the former marriage and initiator status were not relevant.

Traktaty pedagogiczne Honoraty z Wiśniowskich Zapovej i Klementyny z Tańskich Hoffmanowej – inspiracja czy przeróbka?

As is well know, the long-lasting influence in Poland of Hoffmanowa’s conservative pedagogical treatise « Keepsake of a Good Mother » (1819) was criticized by more progressive Polish women writers of the 19th century, such as Narcyza Żmichowska and Eliza Orzeszkowa. But the unexpected success of that book in other Slav countries later in the 19th century, especially in Bohemia, is less well known. Honorata z Wiśniowskich Zapová (1825-1856), a member of the Galician Polish szlachta who moved to Prague after her marriage in 1841 to the Czech writer K. V. Zap, has been recently exhumed as a Czech writer by Czech and Polish literary criticism: apart from her essays in Czech journals on her native country, much emphasis has been laid on the value of her most important work, Nezabudky, dar našim pannám (Forget-me-not: A Gift to Our Young Ladies, published in 1859), which was the first book of pedagogy dedicated to the instruction of young women in Bohemia. In her preface to this book, Zapová mentions Hoffmanowa as being one of her many sources of inspiration. Wishing to know more about what exactly Zapová owes to Hoffmanowa, in this article I compare Hoffmanowa’s book of pedagogy with Zapová’s. I am astonished to discover that Zapová’s book is in fact an almost literal translation from Polish to Czech of „Keepsake of a Good Mother” – in other words, that it is a plagiarism of Hoffmanowa’s book. The main question I ask here is : why did no one until now, either in 19th-century criticism or in our contemporary criticism, mention this literary fraud before?

Risk of late effects of treatment in children newly diagnosed with standard-risk acute lymphoblastic leukaemia: a report from the Childhood Cancer Survivor Study cohort

BACKGROUND Treatment of patients with paediatric acute lymphoblastic leukaemia has evolved such that the risk of late effects in survivors treated in accordance with contemporary protocols could be different from that noted in those treated decades ago. We aimed to estimate the risk of late effects in children with standard-risk acute lymphoblastic leukaemia treated with contemporary protocols. METHODS We used data from similarly treated members of the Childhood Cancer Survivor Study cohort. The Childhood Cancer Survivor Study is a multicentre, North American study of 5-year survivors of childhood cancer diagnosed between 1970 and 1986. We included cohort members if they were aged 1·0-9·9 years at the time of diagnosis of acute lymphoblastic leukaemia and had received treatment consistent with contemporary standard-risk protocols for acute lymphoblastic leukaemia. We calculated mortality rates and standardised mortality ratios, stratified by sex and survival time, after diagnosis of acute lymphoblastic leukaemia. We calculated standardised incidence ratios and absolute excess risk for subsequent neoplasms with age-specific, sex-specific, and calendar-year-specific rates from the Surveillance, Epidemiology and End Results Program. Outcomes were compared with a sibling cohort and the general US population. FINDINGS We included 556 (13%) of 4329 cohort members treated for acute lymphoblastic leukaemia. Median follow-up of the survivors from 5 years after diagnosis was 18·4 years (range 0·0-33·0). 28 (5%) of 556 participants had died (standardised mortality ratio 3·5, 95% CI 2·3-5·0). 16 (57%) deaths were due to causes other than recurrence of acute lymphoblastic leukaemia. Six (1%) survivors developed a subsequent malignant neoplasm (standardised incidence ratio 2·6, 95% CI 1·0-5·7). 107 participants (95% CI 81-193) in each group would need to be followed-up for 1 year to observe one extra chronic health disorder in the survivor group compared with the sibling group. 415 participants (376-939) in each group would need to be followed-up for 1 year to observe one extra severe, life-threatening, or fatal disorder in the group of survivors. Survivors did not differ from siblings in their educational attainment, rate of marriage, or independent living. INTERPRETATION The prevalence of adverse long-term outcomes in children treated for standard risk acute lymphoblastic leukaemia according to contemporary protocols is low, but regular care from a knowledgeable primary-care practitioner is warranted. FUNDING National Cancer Institute, American Lebanese-Syrian Associated Charities, Swiss Cancer Research.

Troublesome Issues: Current Debates on Tensions between Gender Equality and Cultural Diversity in Austria

This paper will first deal with the legal and social situation of Islam and Muslims in Austria and then turn to particular “troublesome issues” at the intersection of gender equality and ethnic/religious diversity. The public debate on Muslims particularly focuses on the notion “not willing to integrate” and in the assumption of “parallel societies”. Hierarchical gender relations and “harmful traditions” such as veiling, female genital cutting, forced marriage and honour based violence recently became the centre of attention. We will show that the Austrian debate on these issues is shaped by the idea of “dangerous cultural difference” as something coming from outside and being concentrated in segregated Muslim enclaves. Despite the public authorities’ rejection of the idea that Islam was responsible for “harmful traditions”, legal as well as political measures in Austria not only combat violence against women but also fuel “cultural anxieties” between different ethnic and religious groups.

Highly efficient ketone body treatment in multiple acyl-CoA dehydrogenase deficiency-related leukodystrophy.

BACKGROUND Multiple acyl-CoA dehydrogenase deficiency- (MADD-), also called glutaric aciduria type 2, associated leukodystrophy may be severe and progressive despite conventional treatment with protein- and fat-restricted diet, carnitine, riboflavin, and coenzyme Q10. Administration of ketone bodies was described as a promising adjunct, but has only been documented once. METHODS We describe a Portuguese boy of consanguineous parents who developed progressive muscle weakness at 2.5 y of age, followed by severe metabolic decompensation with hypoglycaemia and coma triggered by a viral infection. Magnetic resonance (MR) imaging showed diffuse leukodystrophy. MADD was diagnosed by biochemical and molecular analyses. Clinical deterioration continued despite conventional treatment. Enteral sodium D,L-3-hydroxybutyrate (NaHB) was progressively introduced and maintained at 600 mg/kg BW/d (≈3% caloric need). Follow up was 3 y and included regular clinical examinations, biochemical studies, and imaging. RESULTS During follow up, the initial GMFC-MLD (motor function classification system, 0 = normal, 6 = maximum impairment) level of 5-6 gradually improved to 1 after 5 mo. Social functioning and quality of life recovered remarkably. We found considerable improvement of MR imaging and spectroscopy during follow up, with a certain lag behind clinical recovery. There was some persistent residual developmental delay. CONCLUSION NaHB is a highly effective and safe treatment that needs further controlled studies.

Marital stability, satisfaction and well-being in old age: Variability and continuity in long-term continuously married older persons

Objectives: Recent research shows that the well-documented positive effects of marital stability on well-being and health outcomes are conditional upon the quality of marriage. To date, few studies have explored the relationship between marital satisfaction, well-being and health among very long-term married individuals. This study aims at identifying groups of long-term married persons with respect to marital satisfaction and comparing them longitudinally concerning their well-being outcomes, marital stressors, personality and socio-demographic variables. Method: Data are derived from a survey (data collection 2012 and 2014) with 374 continuously married individuals at wave 1 (mean age: 74.2 years, length of marriage: 49.2 years) and 252 at wave 2. Cluster analyses were performed comparing the clusters with regard to various well-being outcomes. The predictive power of cluster affiliation and various predictors at wave 1 on well-being outcomes at wave 2 was tested using regression analyses. Results: Two groups were identified, one happily the other unhappily married, with the happily married scoring higher on all well-being and health outcomes. Regression analyses revealed that group affiliation at wave 1 was not any longer predictive of health, emotional loneliness and hopelessness two years later, when taking into account socio-demographic variables, psychological resilience and marital strain, whereas it remained an important predictor of life satisfaction and social loneliness. Conclusion: Marital satisfaction is associated with health and well-being in older couples over time, whereas psychological resilience and marital strain are major predictors explaining the variance of these outcomes.