Ethical bearings in an Inter-generational Auto/biography: writing in my mother's voice.

"Beatrice Speaking" is an account of three years of my mother’s life (from 1945 to 1948). The narrative is written in the first-person voice of Beatrice, my mother (not, of course, her real name), and is framed by a prologue and epilogue in the first-person voice of one of her children (myself) in the present. I have struggled to find a name for the hybrid offspring that I have produced; intergenerational auto/biography is much closer than any of the alternatives. I want to explain the reason for my difficult decision to tell this story in the first-person narrating voice of Beatrice. To write in my mother’s voice raises ethical problems about appropriation and authenticity; more immediately, for years this was simply an impossibly presumptuous thing for me to do. Using the third-person ‘she’ was the only way to balance my role as writer and creator of the character Beatrice against my sense of intrusion into my mother’s private life. All the writing I did about her earlier life ("Inventing Beatrice") was done in this third-person voice. But when I came to the 1945–1948 period, I became stuck. I had writer’s block. During six months I slowly realised that I had only two choices: I could either use Beatrice’s own first-person voice (being honest and faithful to her letters) or else I would fall silent altogether. I chose the first option, to let Beatrice speak for herself, and started writing again. The biggest leap that this entailed was putting myself into her (Beatrice’s/my mother’s) moral space, living within it and accepting it at the same time as I profoundly rejected at least some of it for myself

Perturbation of the Developmental Potential of Preimplantation Mouse Embryos by Hydroxyurea

Women are advised not to attempt pregnancy while on hydroxyurea (HU) due to the teratogenic effects of this agent, based on results obtained from animal studies. Several case reports suggest that HU may have minimal or no teratogenic effects on the developing human fetus. Fourteen cases of HU therapy in pregnant patients diagnosed with acute or chronic myelogenous leukemia, primary thrombocythemia, or sickle cell disease (SCD) have been reported. Three pregnancies were terminated by elective abortion; 1 woman developed eclampsia and delivered a phenotypically normal stillborn infant. All other patients delivered live, healthy infants without congenital anomalies. We contend that case studies such as these have too few patients and cannot effectively address the adverse effect of HU on preimplantation embryo or fetuses. The objective of this study was to assess the risks associated with a clinically relevant dose of HU used for the treatment of SCD, on ovulation rate and embryo development, using adult C57BL/6J female mice as a model. In Experiment 1, adult female mice were randomly assigned to a treatment or a control group (N = 20/group). Treatment consisted of oral HU (30 mg/kg) for 28 days; while control mice received saline (HU vehicle). Five days to the cessation of HU dosing, all mice were subjected to folliculogenesis induction with pregnant mare serum gonadotropin (PMSG). Five mice/group were anesthetized at 48 hours post PMSG to facilitate blood collection via cardiac puncture for estradiol-17β (E2) measurement by RIA. Ovulation was induced in the remaining mice at 48 hours post PMSG with human chorionic gonadotropin (hCG) and immediately caged with adult males for mating. Five plugged female mice/group were sacrificed for the determination of ovulation rate. The remaining mated mice were sacrificed about 26 hours post hCG, ovaries excised and weighed and embryos harvested and cultured in Whitten’s medium (WM) supplemented with CZBt. In Experiments 2 and 3, (N = 10/Experiment) folliculogenesis and ovulation were induced in untreated mice followed by mating. Recovered embryos were either exposed continuously (Experiment 2) or intermittently (Experiment 3) to bioavailable HU (18 μg HU/mL of WM + CZBt) or WM + CZBt only (control). Treated mice sustained decreased ovarian wt, ovulation rate and circulating E2 compared with controls (P < 0.05). Fewer embryos retrieved from HU-treated mice developed to blastocyst stage (32%) compared with those from controls (60%; P < 0.05). Furthermore, continuous or intermittent in vitro exposures of embryos to HU also resulted in reduced development to blastocyst stage (continuous HU, 9 vs. control, 63%; P < 0.05; intermittent HU, 20 vs. control, 62%; P < 0.05) with embryos exposed continuously to HU in vitro fairing worse. Even though HU is well tolerated, our data suggest that it compromises folliculogenesis and the ability of generated embryos to develop. Therefore, designed studies with larger numbers of patients receiving HU during pregnancy, with longer follow-up of exposed children and more careful assessment of embryo/fetotoxic effects, are required before this agent can be promoted as safe in pregnancy

Mitigating oxygen stress enhances aged mouse hematopoietic stem cell numbers and function

Bone marrow (BM) hematopoietic stem cells (HSCs) become dysfunctional during aging (i.e., they are increased in number but have an overall reduction in long-term repopulation potential and increased myeloid differentiation) compared with young HSCs, suggesting limited use of old donor BM cells for hematopoietic cell transplantation (HCT). BM cells reside in an in vivo hypoxic environment yet are evaluated after collection and processing in ambient air. We detected an increase in the number of both young and aged mouse BM HSCs collected and processed in 3% O2 compared with the number of young BM HSCs collected and processed in ambient air (~21% O2). Aged BM collected and processed under hypoxic conditions demonstrated enhanced engraftment capability during competitive transplantation analysis and contained more functional HSCs as determined by limiting dilution analysis. Importantly, the myeloid-to-lymphoid differentiation ratio of aged BM collected in 3% O2 was similar to that detected in young BM collected in ambient air or hypoxic conditions, consistent with the increased number of common lymphoid progenitors following collection under hypoxia. Enhanced functional activity and differentiation of old BM collected and processed in hypoxia correlated with reduced “stress” associated with ambient air BM collection and suggests that aged BM may be better and more efficiently used for HCT if collected and processed under hypoxia so that it is never exposed to ambient air O2

Understanding the elevated suicide risk of female soldiers during deployments

Background The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) has found that the proportional elevation in the US Army enlisted soldier suicide rate during deployment (compared with the never-deployed or previously deployed) is significantly higher among women than men, raising the possibility of gender differences in the adverse psychological effects of deployment. Method Person-month survival models based on a consolidated administrative database for active duty enlisted Regular Army soldiers in 2004–2009 (n = 975 057) were used to characterize the gender × deployment interaction predicting suicide. Four explanatory hypotheses were explored involving the proportion of females in each soldier’s occupation, the proportion of same-gender soldiers in each soldier’s unit, whether the soldier reported sexual assault victimization in the previous 12 months, and the soldier’s pre-deployment history of treated mental/behavioral disorders. Results The suicide rate of currently deployed women (14.0/100 000 person-years) was 3.1–3.5 times the rates of other (i.e. never-deployed/previously deployed) women. The suicide rate of currently deployed men (22.6/100 000 person-years) was 0.9–1.2 times the rates of other men. The adjusted (for time trends, sociodemographics, and Army career variables) female:male odds ratio comparing the suicide rates of currently deployed v. other women v. men was 2.8 (95% confidence interval 1.1–6.8), became 2.4 after excluding soldiers with Direct Combat Arms occupations, and remained elevated (in the range 1.9–2.8) after adjusting for the hypothesized explanatory variables. Conclusions These results are valuable in excluding otherwise plausible hypotheses for the elevated suicide rate of deployed women and point to the importance of expanding future research on the psychological challenges of deployment for women.Psycholog

Germline MBD4-deficiency causes a multi-tumor predisposition syndrome

We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. We identified five individuals with bi-allelic MBD4 variants within four families and these individuals had a personal and/or family history of adenomatous colorectal polyposis, acute myeloid leukemia, and uveal melanoma. MBD4 encodes a glycosylase involved in repair of G:T mismatches resulting from deamination of 5′-methylcytosine. The colorectal adenomas from MBD4-deficient individuals showed a mutator phenotype attributable to mutational signature SBS1, consistent with the function of MBD4. MBD4-deficient polyps harbored somatic mutations in similar driver genes to sporadic colorectal tumors, although AMER1 mutations were more common and KRAS mutations less frequent. Our findings expand the role of BER deficiencies in tumor predisposition. Inclusion of MBD4 in genetic testing for polyposis and multi-tumor phenotypes is warranted to improve disease management

Sociodemographic and career history predictors of suicide mortality in the United States Army 2004–2009

The US Army suicide rate has increased sharply in recent years. Identifying significant predictors of Army suicides in Army and Department of Defense (DoD) administrative records might help focus prevention efforts and guide intervention content. Previous studies of administrative data, although documenting significant predictors, were based on limited samples and models. A career history perspective is used here to develop more textured models. The analysis was carried out as part of the Historical Administrative Data Study (HADS) of the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). De-identified data were combined across numerous Army and DoD administrative data systems for all Regular Army soldiers on active duty in 2004–2009. Multivariate associations of sociodemographics and Army career variables with suicide were examined in subgroups defined by time in service, rank and deployment history. Several novel results were found that could have intervention implications. The most notable of these were significantly elevated suicide rates (69.6–80.0 suicides per 100 000 person-years compared with 18.5 suicides per 100 000 person-years in the total Army) among enlisted soldiers deployed either during their first year of service or with less than expected (based on time in service) junior enlisted rank; a substantially greater rise in suicide among women than men during deployment; and a protective effect of marriage against suicide only during deployment. A career history approach produces several actionable insights missed in less textured analyses of administrative data predictors. Expansion of analyses to a richer set of predictors might help refine understanding of intervention implications.Psycholog

Communication and marketing as tools to cultivate the public's health: a proposed "people and places" framework

<p>Abstract</p> <p>Background</p> <p>Communication and marketing are rapidly becoming recognized as core functions, or core competencies, in the field of public health. Although these disciplines have fostered considerable academic inquiry, a coherent sense of precisely how these disciplines can inform the practice of public health has been slower to emerge.</p> <p>Discussion</p> <p>In this article we propose a framework – based on contemporary ecological models of health – to explain how communication and marketing can be used to advance public health objectives. The framework identifies the attributes of people (as individuals, as social networks, and as communities or populations) and places that influence health behaviors and health. Communication, i.e., the provision of information, can be used in a variety of ways to foster beneficial change among both people (e.g., activating social support for smoking cessation among peers) and places (e.g., convincing city officials to ban smoking in public venues). Similarly, marketing, i.e., the development, distribution and promotion of products and services, can be used to foster beneficial change among both people (e.g., by making nicotine replacement therapy more accessible and affordable) and places (e.g., by providing city officials with model anti-tobacco legislation that can be adapted for use in their jurisdiction).</p> <p>Summary</p> <p>Public health agencies that use their communication and marketing resources effectively to support people in making healthful decisions and to foster health-promoting environments have considerable opportunity to advance the public's health, even within the constraints of their current resource base.</p

Occupational differences in US Army suicide rates

Background Civilian suicide rates vary by occupation in ways related to occupational stress exposure. Comparable military research finds suicide rates elevated in combat arms occupations. However, no research has evaluated variation in this pattern by deployment history, the indicator of occupation stress widely considered responsible for the recent rise in the military suicide rate. Method The joint associations of Army occupation and deployment history in predicting suicides were analysed in an administrative dataset for the 729 337 male enlisted Regular Army soldiers in the US Army between 2004 and 2009. Results There were 496 suicides over the study period (22.4/100 000 person-years). Only two occupational categories, both in combat arms, had significantly elevated suicide rates: infantrymen (37.2/100 000 person-years) and combat engineers (38.2/100 000 person-years). However, the suicide rates in these two categories were significantly lower when currently deployed (30.6/100 000 person-years) than never deployed or previously deployed (41.2–39.1/100 000 person-years), whereas the suicide rate of other soldiers was significantly higher when currently deployed and previously deployed (20.2–22.4/100 000 person-years) than never deployed (14.5/100 000 person-years), resulting in the adjusted suicide rate of infantrymen and combat engineers being most elevated when never deployed [odds ratio (OR) 2.9, 95% confidence interval (CI) 2.1–4.1], less so when previously deployed (OR 1.6, 95% CI 1.1–2.1), and not at all when currently deployed (OR 1.2, 95% CI 0.8–1.8). Adjustment for a differential ‘healthy warrior effect’ cannot explain this variation in the relative suicide rates of never-deployed infantrymen and combat engineers by deployment status. Conclusions Efforts are needed to elucidate the causal mechanisms underlying this interaction to guide preventive interventions for soldiers at high suicide risk.Psycholog

Bostonia: The Boston University Alumni Magazine. Volume 16

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value &lt; 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p &lt; 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression