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Background Patients at high-risk for breast cancer with genetic mutations are recommended to receive annual breast MRI in adjunct to annual mammography. Despite 15 years of clinical guidelines, uptake of annual breast MRI remains low. Further, little is known about screening patterns across genetic test results in patients tested for hereditary cancer susceptibility as part of usual care. Methods We conducted a retrospective cohort study in an integrated health system among women aged ≥18 years old, without prior breast cancer who had genetic testing for high penetrance hereditary cancer susceptibility genes between January 1, 2010 and December 31, 2018. Genetic test orders and results (pathogenic or likely pathogenic (P/LP) variant(s), negative, or variant of uncertain significance (VUS)) were obtained from health system administrative and laboratory data. Mammogram and breast MRI use data were extracted from electronic health records and claims data. To characterize screening patterns, we calculated average proportion of time covered (PTC) as the number of days covered by mammography and/or breast MRI divided by the number of days from screening eligibility until the earliest censoring event: end of observation period, reached age 75 years, breast cancer diagnosis, death, bilateral mastectomy, or disenrollment in the health system. Per National Comprehensive Cancer Network (NCCN) guidelines, women with P/LP variants in BRCA1/2, TP53, PALB2, CHEK2, ATM, and NF1 became eligible for screening on either the day they received their genetic test result or reached age eligibility and received one year of covered time for each mammogram or MRI imaging procedure received. Per Healthcare Effectiveness Data and Information Set (HEDIS) performance measures, all other women became eligible for screening at age 50 years and received two years of covered time for each mammogram received. Average PTC was calculated overall, by genetic test results, and by screening type. Poisson regression was used to determine the association between average PTC and patient-level factors (age at test, race/ethnicity, and genetic mutations) and guideline factors (recommended screening age state). Results Of 1,167 women meeting the inclusion criteria, 140 (12%) had P/LP in high penetrance breast cancer susceptibility genes (Table 1). Average PTC for individuals with a high penetrance susceptibility gene was 34.4% for MRI, 47.6% for mammogram, 63.2% for either MRI or mammogram, and 19.0% for both screening tests. The average PTC for those who tested negative, had VUS only, and had P/LP variants in genes unrelated to breast cancer was 50.3%, 44.4%, and 40.6%, respectively. Poisson regression model showed that among those with P/LP variants in high penetrance breast cancer genes, average PTC for annual MRI was positively associated with recommended screening initiation age ≥40 years (incident rate ratio [IRR]=2.07, 95% confidence interval [CI]: 1.94-2.20), higher absolute lifetime risk of breast cancer (IRR=1.38, 95% CI: 1.31-1.49), being 40-59 years old at genetic testing (IRR=1.04, 95% CI: 1.01-1.06), and non-Hispanic White race/ethnicity (IRR=1.10, 95% CI: 1.06-1.14). Conclusions Use of breast screening in women who had a P/LP variant(s) in high penetrance breast cancer susceptibility genes was low and not consistent with clinical guidelines, but comparable to the use of screening in women with negative and VUS results. Our findings suggest the need to improve screening in high-risk women with known genetic mutations and women at average risk. Table 1. Average PTC by NCCN and HEDIS recommendation. Citation Format: Boya Guo, Sarah Knerr, Karen Wernli, Kathleen Mittendorf, Heather Feigelson, Marian Gilmore, Gail Jarvik, Tia Kauffman, Erin Keast, Beth Liles, Frances Lynch, Kristin Muessig, Sonia Sasaki, David Veenstra, Jamilyn Zepp, Ben Wilfond, Katrina Goddard, Beth Devine. Screening Patterns of Mammography and Breast Magnetic Resonance Imaging Following Cancer Genetic Testing in an Integrated Health Care System [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-04-01.

The aim of this research was to examine predictors and characterize causes of suicide death in people with traumatic brain injury (TBI) and conduct sensitivity analyses with and without people whose first diagnosis of TBI occurred within 3 days of their suicide death.This case-control study examined suicide risk for people with TBI in eight Mental Health Research Network-affiliated healthcare systems. Sample 1 included 61 persons with TBI who died by suicide and their 75 matched controls with TBI who did not die by suicide between January 1, 2000, and December 31, 2013. Sample 2 excluded the 34 persons with TBI whose first TBI diagnosis occurred within 3 days of their suicide death and their 46 matched controls. Descriptive statistics characterized the sample stratified by cases and controls, while conditional logistic regression models estimated the adjusted odds of suicide.Over half of suicide deaths occurred within 3 days of a person's first diagnosis of TBI in the larger sample. After excluding these persons, people with TBI were 2.84 (95% confidence interval [CI]: 2.15-2.73) times more likely to die by suicide than were people without TBI. Among those with TBI, men were 16.39 times (95% CI: 1.89-142.15) more likely to die by suicide than were women.Accounting for TBI as a potential consequence of suicide attenuates the association between TBI and suicide, but a robust association persists-especially among men. Ultimately, all people with TBI should be carefully screened and monitored for suicide risk.HIGHLIGHTSPeople with traumatic brain injury (TBI) were at considerably elevated risk for suicide deathMen with TBI had significantly increased risk of suicide death compared to women with TBITBI timing suggests confusion of risk factors for and consequences of suicide.

This study aimed to evaluate the laboratory-related outcomes of participants who were offered genomic testing based on cancer family history risk assessment tools.Patients from clinics that serve populations with access barriers, who are screened at risk for a hereditary cancer syndrome based on adapted family history collection tools (the Breast Cancer Genetics Referral Screening Tool and PREMMOf all the participants, 87% successfully returned a saliva kit. Overall, 5% had a pathogenic/likely pathogenic cancer risk variant and 1% had a secondary finding. Almost all (14/15, 93%) participants completed recommended consultations with nongenetics providers after an average of 17 months. The recommended actions (eg, breast magnetic resonance imaging) were completed by 17 of 25 participants. Participant personal history of cancer and PREMMThis accessible model of hereditary cancer risk assessment and genetic testing yielded results that were often acted upon by patients and physicians.

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine.

This paper examines survey findings of tourist interest in Mi’kmaw cultural tourism in Nova Scotia. The results indicate a high interest in Mi’kmaw cultural tourism activities even though most tourists had not participated in Aboriginal tourism before. Further results indicate that tourists’ age, education and place of origin influence their level of interest in particular Mi’kmaw cultural tourism activities. Older tourists had lower interest in activities that required more time and physical activity whereas more-educated tourists had higher interest in participating in particular Mi’kmaw cultural tourism activities. Also, international tourists had the greatest interest in Mi’kmaw cultural tourism, especially activities that involved greater contact with the Mi’kmaw hosts.

This study assessed tourists' motivations and satisfaction in participating in authentic Mi'kmaw tourism activities in Nova Scotia, Canada, as well as the ideas, perceptions and components of sustainable cultural tourism development from the Mi'kmaw perspective. To solicit the tourists' perspective, surveys were administered to tourists visiting the existing Mi'kmaw cultural tourism sites in Nova Scotia, while the Mi'kmaw perspective was obtained through key informant interviews. The results of the survey suggest that tourists visiting the Mi'kmaw cultural tourism sites were highly educated and deeply interested in learning about culture and participating in authentic cultural experiences. Tourists were also highly satisfied with their experience and were interested in participating in aboriginal tourism again. Findings regarding the Mi'kmaw perspective indicate a focus on cultural tourism's ability to educate both tourists and the Mi'kmaw people on the Mi'kmaw culture as well as provide economic opportun...

Few data have evaluated Zn balance in young children after the first year of life. The objective of the present study was to study the relationships among Zn intake, absorption, endogenous faecal excretion, and retention in a group of healthy children. Thirty children, aged 15–48 months, were studied on a diet representative of their usual daily mineral intake. Zn absorption was assessed using a dual-tracer stable-isotope technique. Endogenous Zn faecal excretion and Cu absorption were determined in a subset of children. We found that Zn intake from the in-patient weighed dietary record (5·0 (sd 2·1) mg/d) was significantly greater than the current estimated average requirement (EAR; 2·5 mg/d; P r2 P>0·4, for all). Absolute Zn absorption was significantly related to Zn intake (r2 0·696; P r2 0·506; P sd 10·8) %) despite the high Zn intake. The EAR for Zn based on this dataset would appear to be between 4·2 and 4·7 mg/d to allow for a net average retention of 120 μg/d consistent with growth needs. We concluded that at relatively high Zn intakes there was little evidence of down regulation of absorption or up regulation of urinary or endogenous faecal Zn excretion across the intake range studied. Zn retention was positively correlated with intake. A Zn intake between 4·2 and 4·7 mg/d should meet the requirement for normal growth for this age group.

Few calcium balance data are available from young children on which to base dietary recommendations.The objective of the study was to evaluate the relation between calcium intake and balance in healthy children aged 1-4 y consuming typical American diets.Subjects were assigned to a diet with nutrient intakes similar to those of their usual diet. Calcium absorption was assessed by using a dual-tracer stable-isotope technique. Endogenous fecal excretion was measured in a subset of children, and net calcium balance was calculated.Mean calcium intake was 551 mg/d (range: 124-983 mg/d), and mean (+/-SEM) calcium retention was 161 +/- 17 mg/d. Both linear and nonlinear modeling of balance data showed that a calcium intake of approximately 470 mg/d led to calcium retention of 140 mg/d, which is the amount that meets expected bone growth needs in children of this age. No evidence was found that calcium intakes of 800 to 900 mg/d reached the threshold intake beyond which no additional increase in calcium retention would occur.Bone growth needs in 1-4-y-old children following American diets are met by a daily calcium intake of approximately 470 mg/d, which suggests that the current Adequate Intake of 500 mg/d is close to the actual Estimated Average Requirement. The benefits and risks of higher calcium intakes consistent with threshold values should be evaluated in a controlled trial before those intakes could be used as a basis for dietary recommendations.

In adults, adaptation to changes in magnesium intake is largely due to changes in fractional magnesium absorption and urinary magnesium excretion. We sought to examine whether these homeostatic mechanism also occurred in young children.Children, 12-48 m old were studied (n=30). They were adapted to a home diet representative of their usual magnesium intake for 7 d then admitted for a stable isotope study. Children received 5 mg Mg-25 intravenously, and 10 mg Mg-26 orally (5 mg with breakfast and 5 mg with lunch). Magnesium absorption was calculated from the relative fractional excretion of the oral and intravenous isotopes in the urine samples. Endogenous fecal magnesium absorption was calculated in a subgroup from the fecal and urinary excretion of the intravenous tracer.Magnesium intake (mean +/- SD; 106 +/- 25 mg/d) was significantly greater than the Estimated Average Requirement (EAR) described by the Institute of Medicine in the US (65 mg/d, p0.0001). Across the range of intake studied, fractional magnesium absorption was significantly (P = 0.0383) but weakly (r(2) = 0.144) related to magnesium intake. Absolute magnesium absorption (the product of fractional absorption and intake) significantly increased as intake increased (r(2) = 0.566, P0.0001). Urinary magnesium excretion was unrelated to magnesium intake (r(2) = 0.036, P = 0.31). Endogenous fecal magnesium excretion tended to increase as magnesium intake increased (r(2) = 0.312, P = 0.12). Magnesium retention (absolute absorption minus urinary and fecal losses) was positive in 26 of the 30 subjects studied, and was linearly related to magnesium intake (r(2) = 0.157, P = 0.0304). A magnesium intake of 52-78 mg/d would appear to be required to meet the needs for absorbed magnesium for half the children at this age range, suggesting that the current EAR is broadly appropriate.In young children, consuming magnesium intakes typical of the US population, fractional magnesium absorption is a major site of magnesium homeostasis, but magnesium retention increased linearly across the intake range studied. Our results support at EAR for magnesium of 55-80 mg/d and an RDA of 70-100 mg/d.

Lynch Frances. La France, la Grande-Bretagne et le problème du dollar, 1945-1950. Une profonde mésentente. In: Matériaux pour l'histoire de notre temps, n°18, 1990. La mésentente cordiale : les relations franco-britanniques, 1945-1957, sous la direction de René Girault . pp. 12-19.

Few studies have evaluated iron absorption in small children after the first year of life. Our objectives were to examine the relations among iron intake, iron absorption, and iron status in a group of healthy children. We studied 28 children, ages 12 to 48 mo, after a 7-d home adaptation to a diet representative of their usual daily mineral intake. A multi-tracer stable isotope study was performed to assess iron absorption both from a meal ((58)Fe) and from a reference iron dose ((57)Fe) given with ascorbic acid without a meal. Iron intake was 6.9 +/- 2.4 mg, approximately the 35th percentile of typical U.S. intakes. Absorption of (58)Fe was related to serum ferritin (r(2) = 0.319, P = 0.0018) and more so to reference dose iron absorption (r(2) = 0.653, P0.0001). Iron absorption was negatively correlated with zinc intake (r(2) = 0.090, P = 0.0049) but was not correlated with iron intake (P = 0.20). However, zinc intake was not correlated with measures of iron status, including reference dose iron absorption and serum ferritin (r(2)0.1, P0.25). Total absorbed iron was similar to needs estimated by the Institute of Medicine. We conclude that iron absorption in young children is more closely related to iron status than to iron intake. Reference dose iron absorption may be superior to serum ferritin as a surrogate measure for iron status in this age group. Although zinc intake may affect iron absorption from a meal, it does not appear to have a detectable effect on overall iron status in otherwise well-nourished children.

To test a collaborative-care, cognitive-behavioral therapy (CBT) program adjunctive to selective serotonin reuptake inhibitor (SSRI) treatment in HMO pediatric primary care.A randomized effectiveness trial comparing a treatment-as-usual (TAU) control condition consisting primarily of SSRI medication delivered outside the experimental protocol (n = 75) versus TAU SSRI plus brief CBT (n = 77). Participants were identified by a recent dispense of SSRI medication followed by telephone screening. Adolescents with a diagnosis of major depressive disorder (n = 152) were enrolled. The CBT program employed cognitive restructuring and/or behavioral activation training. Therapists consulted with prescribing pediatricians to improve medication adherence.Through 1-year follow-up, the authors found CBT advantages on the Short Form-12 Mental Component Scale (p = .04), reductions in TAU outpatient visits (p = .02), and days' supply of all medications (p = .01). No effects were detected for major depressive disorder episodes; a nonsignificant trend favoring CBT was detected on the Center for Epidemiology Depression Scale (p = .07).The authors detected a weak CBT effect, possibly rendered less significant by the small sample and likely attenuated by the unexpected reduction in SSRI pharmacotherapy in the CBT condition. Small, incremental improvements over monotherapy, such as observed in this study, most likely represent the new norm in adolescent depression treatment research.

(2013). A Corridor through Time: The Archaeology of the A55 Anglesey Road Scheme. Edited by Richard Cuttler, Andrew Davidson and Gwilym Hughes. Archaeological Journal: Vol. 170, No. 1, pp. 325-325.

The first two authors report on the excavation of a series of cairns in the Aline Valley, Morvern: Acharn (NM 702504, NM 697507), Claggan (NM 697493) and Kinlochaline (NM 692474). The latter two sites belong to the kerb-cairn class of monument, and a discussion of kerb-cairns in Argyll, Perthshire, Aberdeenshire and N Wales is provided by Lynch and Ritchie. Charcoal associated with central cremation burials at Claggan gave radiocarbon dates centred on c 1000 bc. D N Marshall reports on the excavation of an allied monument at Portavadie, Cowal (NR 933691). An appendix records mesolithic sites with microburins and microliths at Acharn, Morvern (NM 697504). AR