Clinical consultations and investigations before and after discontinuation of endocrine therapy in women with primary breast cancer

Objective: Although clinical trials recommend that women with hormone-dependent primary breast cancer remain on endocrine therapy for at least 5 years, up to 60% discontinue treatment early. We determined whether these women had consulted with clinicians or had investigations for cancer recurrence or metastasis around the time they discontinued endocrine therapy, and whether clinical contact continued after discontinuation. Methods: We performed case-control and cohort studies of women from the 45 and Up Study who were diagnosed with invasive primary breast cancer between January 2003 and December 2008, and who had ≥12 months of anastrozole, exemestane, letrozole or tamoxifen subsequently dispensed. Results: Women who consulted general practitioners and surgeons/oncologists, and women who had breast ultrasound/mammogram were just as likely to discontinue endocrine therapy within 30 days as those who did not consult these clinicians or have this investigation. In the 6 months after early discontinuation, women who discontinued endocrine therapy were less likely to consult general practitioners (adjusted risk ratio [RRadj] 0.80; 95% confidence interval [CI] 0.75, 0.86) and surgeons/oncologists (RRadj 0.62; 95% CI 0.54, 0.72) than those who remained on therapy. Conclusions: For most women, endocrine therapy discontinuation did not appear to follow consultation with doctors managing their breast cancer treatment or investigations for recurrence or metastasis. However, women who discontinued endocrine therapy were less likely to consult their general practitioner or surgeon/oncologist in the 6 months following discontinuation than those who remained on therapy. Of the clinician groups studied, general practitioners are best placed to engage and support women to continue pharmacotherapy. However, mechanisms are needed to prompt clinicians to do this at every visit

Risk Factors for Congenital Heart Disease: the Baby Hearts Study, a population-based case-control study

We investigated the role of maternal environmental factors in the aetiology of congenital heart disease (CHD). A population-based case-control study (242 CHD cases, 966 controls) was conducted using an iPad questionnaire for mother with linkage to maternity and first trimester prescription records. Risk of CHD was associated with low maternal education (OR adjusted for confounders 1.59; 95% confidence interval [CI], 1.02-2.49), pregestational diabetes (OR 4.04; 95% CI 1.00-16.28), self-reported maternal clotting disorders (adjOR 8.55, 95%CI 1.51-48.44), prescriptions for the anticlotting medication enoxaparin (adjOR 3.22, 95%CI 1.01-10.22) and self-reported vaginal infections (adjOR 1.69, 95%CI 1.01-2.80). There was no strong support for the hypothesis that periconceptional folic acid supplements have a protective effect, but there was a protective effect of frequent consumption of folate rich fruits (adjOR 0.64, 95%CI 0.47-0.89). Compared to the most common pre-pregnancy dietary pattern, CHD risk was associated with a poor diet low in fruit and vegetables (adjOR 1.56, 95%CI 1.05-2.34). Mothers of cases reported more pregnancy related stress (adjOR 1.69; 95% CI 1.22-2.34) and multiple stressors (adjOR 1.94, 95%CI 0.83-4.53). We found no supportive evidence for CHD risk being associated with obesity, smoking, depression or antidepressant use in this population. Our findings add to the previous evidence base to show potential for public health approaches to help prevent CHD in future by modifying environmental factors. Independent confirmation should be sought regarding elevated CHD risk associated with maternal blood clotting disorders and their treatment, since we are the first to report this

Conformal Robotic Stereolithography

Additive manufacturing by layerwise photopolymerization, commonly called stereolithography (SLA), is attractive due to its high resolution and diversity of materials chemistry. However, traditional SLA methods are restricted to planar substrates and planar layers that are perpendicular to a single-axis build direction. Here, we present a robotic system that is capable of maskless layerwise photopolymerization on curved surfaces, enabling production of large-area conformal patterns and the construction of conformal freeform objects. The system comprises an industrial six-axis robot and a custom-built maskless projector end effector. Use of the system involves creating a mesh representation of the freeform substrate, generation of a triangulated toolpath with curved layers that represents the target object to be printed, precision mounting of the substrate in the robot workspace, and robotic photopatterning of the target object by coordinated motion of the robot and substrate. We demonstrate printing of conformal photopatterns on spheres of various sizes, and construction of miniature three-dimensional objects on spheres without requiring support features. Improvement of the motion accuracy and development of freeform toolpaths would enable construction of polymer objects that surpass the size and support structure constraints imparted by traditional SLA systems.American Society for Engineering Education. National Defense Science and Engineering Graduate FellowshipNational Institute of Mental Health (U.S.) (University of Michigan Microfluidics in Biomedical Sciences Training Program. 5T32-EB005582)Singapore-MIT Alliance for Research and Technology (SMART

Frailty in older patients undergoing emergency laparotomy

Objective: This study aimed to document the prevalence of frailty in older adults undergoing emergency laparotomy and to explore relationships between frailty and postoperative morbidity and mortality. Summary Background Data: The majority of adults undergoing emergency laparotomy are older adults (≥65 y) that carry the highest mortality. Improved understanding is urgently needed to allow development of targeted interventions. Methods: An observational multicenter (n=49) UK study was performed (March–June 2017). All older adults undergoing emergency laparotomy were included. Preoperative frailty score was calculated using the progressive Clinical Frailty Score (CFS): 1 (very fit) to 7 (severely frail). Primary outcome measures were the prevalence of frailty (CFS 5–7) and its association to mortality at 90 days postoperative. Secondary outcomes included 30-day mortality and morbidity, length of critical care, and overall hospital stay. Results: A total of 937 older adults underwent emergency laparotomy: frailty was present in 20%. Ninety-day mortality was 19.5%. After age and sex adjustment, the risk of 90-day mortality was directly associated with frailty: CFS 5 adjusted odds ratio (aOR) 3.18 [95% confidence interval (CI), 1.24–8.14] and CFS 6/7 aOR 6·10 (95% CI, 2.26–16.45) compared with CFS 1. Similar associations were found for 30-day mortality. Increasing frailty was also associated with increased risk of complications, length of Intensive Care Unit, and overall hospital stay. Conclusions: A fifth of older adults undergoing emergency laparotomy are frail. The presence of frailty is associated with greater risks of postoperative mortality and morbidity and is independent of age. Frailty scoring should be integrated into acute surgical assessment practice to aid decision-making and development of novel postoperative strategies

Reactivity of neodymium carriers in deep sea sediments: Implications for boundary exchange and paleoceanography

The dissolved neodymium (Nd) isotopic distribution in the deep oceans is determined by continental weathering inputs, water mass advection, and boundary exchange between particulate and dissolved fractions. Reconstructions of past Nd isotopic variability may therefore provide evidence on temporal changes in continental weathering inputs and/or ocean circulation patterns over a range of timescales. However, such an approach is limited by uncertainty in the mechanisms and importance of the boundary exchange process, and the challenge in reliably recovering past seawater Nd isotopic composition (εNd) from deep sea sediments. This study addresses these questions by investigating the processes involved in particulate–solution interactions and their impact on Nd isotopes. A better understanding of boundary exchange also has wider implications for the oceanic cycling and budgets of other particle-reactive elements. Sequential acid-reductive leaching experiments at pH ∼2–5 on deep sea sediments from the western Indian Ocean enable us to investigate natural boundary exchange processes over a timescale appropriate to laboratory experiments. We provide evidence that both the dissolution of solid phases and exchange processes influence the εNd of leachates, which suggests that both processes may contribute to boundary exchange. We use major element and rare earth element (REE) data to investigate the pools of Nd that are accessed and demonstrate that sediment leachate εNd values cannot always be explained by admixture between an authigenic component and the bulk detrital component. For example, in core WIND 24B, acid-reductive leaching generates εNd values between −11 and −6 as a function of solution/solid ratios and leaching times, whereas the authigenic components have εNd ≈ −11 and the bulk detrital component has εNd ≈ −15. We infer that leaching in the Mascarene Basin accesses authigenic components and a minor radiogenic volcanic component that is more reactive than Madagascan-derived clays. The preferential mobilisation of such a minor component demonstrates that the Nd released by boundary exchange could often have a significantly different εNd composition than the bulk detrital sediment. These experiments further demonstrate certain limitations on the use of acid-reductive leaching to extract the εNd composition of the authigenic fraction of bulk deep sea sediments. For example, the detrital component may contain a reactive fraction which is also acid-extractible, while the incongruent nature of this dissolution suggests that it is often inappropriate to use the bulk detrital sediment elemental chemistry and/or εNd composition when assessing possible detrital contamination of leachates. Based on the highly systematic controls observed, and evidence from REE patterns on the phases extracted, we suggest two approaches that lead to the most reliable extraction of the authigenic εNd component and good agreement with foraminiferal-based approaches; either (i) leaching of sediments without a prior decarbonation step, or (ii) the use of short leaching times and low solution/solid ratios throughout

A sibling study of whether maternal exposure to different types of natural space is related to birth weight

Background: Birthweight is an important determinant of health across the life course. Maternal exposure to natural space has been linked to higher birthweight, but stronger evidence of a causal link is needed. We use a quasi-experimental sibling study design to investigate if change in the mother’s exposure to natural space between births was related to birthweight, in urban Scotland. Methods: Amount (% area) of total natural space, total accessible (public) natural space, parks, woodlands and open water within 100 m of the mother’s postcode was calculated for eligible births (n = 40 194; 1991–2010) in the Scottish Longitudinal Study (a semi-random 5.3% sample of the Scottish population). Associations between natural space and birthweight were estimated, using ordinary least squares and fixed effects models. Results: Birthweight was associated with the total amount of natural space around the mother’s home (+8.2 g for interquartile range increase), but was unrelated to specific types of natural space. This whole-sample relationship disappeared in the sibling analysis, indicating residual confounding. The sibling models showed effects for total natural space with births to women who already had children (+20.1 g), and to those with an intermediate level of education (+14.1 g). Conclusions: The importance of total natural space for birthweight suggests that benefits can be experienced near to as well as within natural space. Ensuring expectant mothers have good access to high quality neighbourhood natural space has the potential to improve the infant’s start in life, and consequently their health trajectory over the life course

LOFAR/H-ATLAS: The low-frequency radio luminosity - star-formation rate relation

This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society. © 2018 The Author(s). Published by Oxford University Press on behalf of the Royal Astronomical Society.Radio emission is a key indicator of star-formation activity in galaxies, but the radio luminosity-star formation relation has to date been studied almost exclusively at frequencies of 1.4 GHz or above. At lower radio frequencies the effects of thermal radio emission are greatly reduced, and so we would expect the radio emission observed to be completely dominated by synchrotron radiation from supernova-generated cosmic rays. As part of the LOFAR Surveys Key Science project, the Herschel-ATLAS NGP field has been surveyed with LOFAR at an effective frequency of 150 MHz. We select a sample from the MPA-JHU catalogue of SDSS galaxies in this area: the combination of Herschel, optical and mid-infrared data enable us to derive star-formation rates (SFRs) for our sources using spectral energy distribution fitting, allowing a detailed study of the low-frequency radio luminosity--star-formation relation in the nearby Universe. For those objects selected as star-forming galaxies (SFGs) using optical emission line diagnostics, we find a tight relationship between the 150 MHz radio luminosity ($L_{150}$) and SFR. Interestingly, we find that a single power-law relationship between $L_{150}$ and SFR is not a good description of all SFGs: a broken power law model provides a better fit. This may indicate an additional mechanism for the generation of radio-emitting cosmic rays. Also, at given SFR, the radio luminosity depends on the stellar mass of the galaxy. Objects which were not classified as SFGs have higher 150-MHz radio luminosity than would be expected given their SFR, implying an important role for low-level active galactic nucleus activity.Peer reviewedFinal Published versio

Claudin 4 Is Differentially Expressed between Ovarian Cancer Subtypes and Plays a Role in Spheroid Formation

Claudin 4 is a cellular adhesion molecule that is frequently overexpressed in ovarian cancer and other epithelial cancers. In this study, we sought to determine whether the expression of claudin 4 is associated with outcome in ovarian cancer patients and may be involved in tumor progression. We examined claudin 4 expression in ovarian cancer tissues and cell lines, as well as by immunohistochemical staining of tissue microarrays (TMAs; n = 500), spheroids present in patients’ ascites, and spheroids formed in vitro. Claudin 4 was expressed in nearly 70% of the ovarian cancer tissues examined and was differentially expressed across ovarian cancer subtypes, with the lowest expression in clear cell subtype. No association was found between claudin 4 expression and disease-specific survival in any subtype. Claudin 4 expression was also observed in multicellular spheroids obtained from patients’ ascites. Using an in vitro spheroid formation assay, we found that NIH:OVCAR5 cells treated with shRNA against claudin 4 required a longer time to form compact spheroids compared to control NIH:OVCAR5 cells that expressed high levels of claudin 4. The inability of the NIH:OVCAR5 cells treated with claudin 4 shRNA to form compact spheroids was verified by FITC-dextran exclusion. These results demonstrate a role for claudin 4 and tight junctions in spheroid formation and integrity