Recent trends in hormone therapy utilization and breast cancer incidence rates in the high incidence population of Marin County, California

<p>Abstract</p> <p>Background</p> <p>Recent declines in invasive breast cancer have been reported in the US, with many studies linking these declines to reductions in the use of combination estrogen/progestin hormone therapy (EPHT). We evaluated the changing use of postmenopausal hormone therapy, mammography screening rates, and the decline in breast cancer incidence specifically for Marin County, California, a population with historically elevated breast cancer incidence rates.</p> <p>Methods</p> <p>The Marin Women's Study (MWS) is a community-based, prospective cohort study launched in 2006 to monitor changes in breast cancer, breast density, and personal and biologic risk factors among women living in Marin County. The MWS enrolled 1,833 women following routine screening mammography between October 2006 and July 2007. Participants completed a self-administered questionnaire that included items regarding historical hormone therapy regimen (estrogen only, progesterone only, EPHT), age of first and last use, total years of use, and reason(s) for stopping, as well as information regarding complementary hormone use. Questionnaire items were analyzed for 1,083 non-Hispanic white participants ages 50 and over. Breast cancer incidence rates were assessed overall and by tumor histology and estrogen receptor (ER) status for the years 1990-2007 using data from the Northern California Surveillance, Epidemiology and End Results (SEER) cancer registry.</p> <p>Results</p> <p>Prevalence of EPHT use among non-Hispanic white women ages 50 and over declined sharply from 21.2% in 1998 to 6.7% by 2006-07. Estrogen only use declined from 26.9% in 1998 to 22.4% by 2006-07. Invasive breast cancer incidence rates declined 33.4% between 2001 and 2004, with drops most pronounced for ER+ cancers. These rate reductions corresponded to declines of about 50 cases per year, consistent with population attributable fraction estimates for EPHT-related breast cancer. Self-reported screening mammography rates did not change during this period. Use of alternative or complementary agents did not differ significantly between ever and never hormone users. Of women who reported stopping EPHT in the past 5 years, 60% cited "health risks" or "news reports" as their primary reasons for quitting.</p> <p>Conclusion</p> <p>A dramatic reduction in EPHT use was followed temporally by a significant reduction in invasive and ER+ breast cancer rates among women living in Marin County, California.</p

Bovine Tuberculosis in Free-Ranging Carnivores from Michigan

During a survey of carnivores and omnivores for bovine tuberculosis conducted in Michigan (USA) since 1996, Mycobacterium bovis was cultured from lymph nodes pooled from six coyotes (Canis latrans) (four adult female, two adult male), two adult male raccoons (Procyon lotor), one adult male red fox (Vulpes vulpes), and one 1.5-yr-old male black bear (Ursus americanus). One adult, male bobcat (Felis rufus) with histologic lesions suggestive of tuberculosis was negative on culture but positive for organisms belonging to the Mycobacterium tuberculosis complex when tested by polymerase chain reaction. All the tuberculous animals were taken from three adjoining counties where M. bovis is known to be endemic in the free-ranging white-tailed deer (Odocoileus virginianus) population. There were two coyotes, one raccoon, one red fox, and one bobcat infected in Alpena county. Montmorency County had two coyotes and one raccoon with M. bovis. Two coyotes and a bear were infected from Alcona County. These free-ranging carnivores/omnivores probably became infected with M. bovis through consumption of tuberculous deer. Other species included in the survey were opossum (Didelphis virginiana), gray fox (Urocyon cinereoargenteus), and badger (Taxidea taxus); these were negative for M. bovis

Overall and cancer related mortality among patients with ocular inflammation treated with immunosuppressive drugs: retrospective cohort study

Context Whether immunosuppressive treatment adversely affects survival is unclear

The quality of different types of child care at 10 and 18 months. A comparison between types and factors related to quality.

The quality of care offered in four different types of non-parental child care to 307 infants at 10 months old and 331 infants at 18 months old was compared and factors associated with higher quality were identified. Observed quality was lowest in nurseries at each age point, except that at 18 months they offered more learning activities. There were few differences in the observed quality of care by child-minders, grandparents and nannies, although grandparents had somewhat lower safety and health scores and offered children fewer activities. Cost was largely unrelated to quality of care except in child-minding, where higher cost was associated with higher quality. Observed ratios of children to adults had a significant impact on quality of nursery care; the more infants or toddlers each adult had to care for, the lower the quality of the care she gave them. Mothers' overall satisfaction with their child's care was positively associated with its quality for home-based care but not for nursery settings

Light Curves and Colors of the Ejecta from Dimorphos after the DART Impact

On 26 September 2022 the Double Asteroid Redirection Test (DART) spacecraft impacted Dimorphos, a satellite of the asteroid 65803 Didymos. Because it is a binary system, it is possible to determine how much the orbit of the satellite changed, as part of a test of what is necessary to deflect an asteroid that might threaten Earth with an impact. In nominal cases, pre-impact predictions of the orbital period reduction ranged from ~8.8 - 17.2 minutes. Here we report optical observations of Dimorphos before, during and after the impact, from a network of citizen science telescopes across the world. We find a maximum brightening of 2.29 $\pm$ 0.14 mag upon impact. Didymos fades back to its pre-impact brightness over the course of 23.7 $\pm$ 0.7 days. We estimate lower limits on the mass contained in the ejecta, which was 0.3 - 0.5% Dimorphos' mass depending on the dust size. We also observe a reddening of the ejecta upon impact.Comment: Accepted by Natur

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Analysis of cancer risk and BRCA1 and BRCA2 mutation prevalence in the kConFab familial breast cancer resource

INTRODUCTION: The Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab) is a multidisciplinary, collaborative framework for the investigation of familial breast cancer. Based in Australia, the primary aim of kConFab is to facilitate high-quality research by amassing a large and comprehensive resource of epidemiological and clinical data with biospecimens from individuals at high risk of breast and/or ovarian cancer, and from their close relatives. METHODS: Epidemiological, family history and lifestyle data, as well as biospecimens, are collected from multiple-case breast cancer families ascertained through family cancer clinics in Australia and New Zealand. We used the Tyrer-Cuzick algorithms to assess the prospective risk of breast cancer in women in the kConFab cohort who were unaffected with breast cancer at the time of enrolment in the study. RESULTS: Of kConFab's first 822 families, 518 families had multiple cases of female breast cancer alone, 239 had cases of female breast and ovarian cancer, 37 had cases of female and male breast cancer, and 14 had both ovarian cancer as well as male and female breast cancer. Data are currently held for 11,422 people and germline DNAs for 7,389. Among the 812 families with at least one germline sample collected, the mean number of germline DNA samples collected per family is nine. Of the 747 families that have undergone some form of mutation screening, 229 (31%) carry a pathogenic or splice-site mutation in BRCA1 or BRCA2. Germline DNAs and data are stored from 773 proven carriers of BRCA1 or BRCA1 mutations. kConFab's fresh tissue bank includes 253 specimens of breast or ovarian tissue – both normal and malignant – including 126 from carriers of BRCA1 or BRCA2 mutations. CONCLUSION: These kConFab resources are available to researchers anywhere in the world, who may apply to kConFab for biospecimens and data for use in ethically approved, peer-reviewed projects. A high calculated risk from the Tyrer-Cuzick algorithms correlated closely with the subsequent occurrence of breast cancer in BRCA1 and BRCA2 mutation positive families, but this was less evident in families in which no pathogenic BRCA1 or BRCA2 mutation has been detected

Structure-Guided Evolution of Potent and Selective CHK1 Inhibitors through Scaffold Morphing

Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK2 were previously identified by fragment-based screening. The optimization of the pyrazolopyridines to a series of potent and CHK1-selective isoquinolines demonstrates how fragment-growing and scaffold morphing strategies arising from a structure-based understanding of CHK1 inhibitor binding can be combined to successfully progress fragment-derived hit matter to compounds with activity in vivo. The challenges of improving CHK1 potency and selectivity, addressing synthetic tractability, and achieving novelty in the crowded kinase inhibitor chemical space were tackled by multiple scaffold morphing steps, which progressed through tricyclic pyrimido[2,3-b]azaindoles to N-(pyrazin-2-yl)pyrimidin-4-amines and ultimately to imidazo[4,5-c]pyridines and isoquinolines. A potent and highly selective isoquinoline CHK1 inhibitor (SAR-020106) was identified, which potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts in nude mice

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements